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Sample records for human neurological disease

  1. Human endogenous retroviruses in neurologic disease.

    PubMed

    Christensen, Tove

    2016-01-01

    Endogenous retroviruses are pathogenic - in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic cause-effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV-associated dementia (HAD), indications are accumulating for involvement of the HERV-K family, and also HERV-H/F and/or HERV-W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV-directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential. PMID:26818266

  2. Human Pluripotent Stem Cells: Applications and Challenges in Neurological Diseases

    PubMed Central

    Hibaoui, Youssef; Feki, Anis

    2012-01-01

    The ability to generate human pluripotent stem cells (hPSCs) holds great promise for the understanding and the treatment of human neurological diseases in modern medicine. The hPSCs are considered for their in vitro use as research tools to provide relevant cellular model for human diseases, drug discovery, and toxicity assays and for their in vivo use in regenerative medicine applications. In this review, we highlight recent progress, promises, and challenges of hPSC applications in human neurological disease modeling and therapies. PMID:22934023

  3. Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases.

    PubMed

    Yuan, Hongjie; Low, Chian-Ming; Moody, Olivia A; Jenkins, Andrew; Traynelis, Stephen F

    2015-07-01

    The advent of whole exome/genome sequencing and the technology-driven reduction in the cost of next-generation sequencing as well as the introduction of diagnostic-targeted sequencing chips have resulted in an unprecedented volume of data directly linking patient genomic variability to disorders of the brain. This information has the potential to transform our understanding of neurologic disorders by improving diagnoses, illuminating the molecular heterogeneity underlying diseases, and identifying new targets for therapeutic treatment. There is a strong history of mutations in GABA receptor genes being involved in neurologic diseases, particularly the epilepsies. In addition, a substantial number of variants and mutations have been found in GABA receptor genes in patients with autism, schizophrenia, and addiction, suggesting potential links between the GABA receptors and these conditions. A new and unexpected outcome from sequencing efforts has been the surprising number of mutations found in glutamate receptor subunits, with the GRIN2A gene encoding the GluN2A N-methyl-d-aspartate receptor subunit being most often affected. These mutations are associated with multiple neurologic conditions, for which seizure disorders comprise the largest group. The GluN2A subunit appears to be a locus for epilepsy, which holds important therapeutic implications. Virtually all α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor mutations, most of which occur within GRIA3, are from patients with intellectual disabilities, suggesting a link to this condition. Similarly, the most common phenotype for kainate receptor variants is intellectual disability. Herein, we summarize the current understanding of disease-associated mutations in ionotropic GABA and glutamate receptor families, and discuss implications regarding the identification of human mutations and treatment of neurologic diseases. PMID:25904555

  4. Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases.

    PubMed

    Yuan, Hongjie; Low, Chian-Ming; Moody, Olivia A; Jenkins, Andrew; Traynelis, Stephen F

    2015-07-01

    The advent of whole exome/genome sequencing and the technology-driven reduction in the cost of next-generation sequencing as well as the introduction of diagnostic-targeted sequencing chips have resulted in an unprecedented volume of data directly linking patient genomic variability to disorders of the brain. This information has the potential to transform our understanding of neurologic disorders by improving diagnoses, illuminating the molecular heterogeneity underlying diseases, and identifying new targets for therapeutic treatment. There is a strong history of mutations in GABA receptor genes being involved in neurologic diseases, particularly the epilepsies. In addition, a substantial number of variants and mutations have been found in GABA receptor genes in patients with autism, schizophrenia, and addiction, suggesting potential links between the GABA receptors and these conditions. A new and unexpected outcome from sequencing efforts has been the surprising number of mutations found in glutamate receptor subunits, with the GRIN2A gene encoding the GluN2A N-methyl-d-aspartate receptor subunit being most often affected. These mutations are associated with multiple neurologic conditions, for which seizure disorders comprise the largest group. The GluN2A subunit appears to be a locus for epilepsy, which holds important therapeutic implications. Virtually all α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor mutations, most of which occur within GRIA3, are from patients with intellectual disabilities, suggesting a link to this condition. Similarly, the most common phenotype for kainate receptor variants is intellectual disability. Herein, we summarize the current understanding of disease-associated mutations in ionotropic GABA and glutamate receptor families, and discuss implications regarding the identification of human mutations and treatment of neurologic diseases.

  5. Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases

    PubMed Central

    Yuan, Hongjie; Low, Chian-Ming; Moody, Olivia A.; Jenkins, Andrew

    2015-01-01

    The advent of whole exome/genome sequencing and the technology-driven reduction in the cost of next-generation sequencing as well as the introduction of diagnostic-targeted sequencing chips have resulted in an unprecedented volume of data directly linking patient genomic variability to disorders of the brain. This information has the potential to transform our understanding of neurologic disorders by improving diagnoses, illuminating the molecular heterogeneity underlying diseases, and identifying new targets for therapeutic treatment. There is a strong history of mutations in GABA receptor genes being involved in neurologic diseases, particularly the epilepsies. In addition, a substantial number of variants and mutations have been found in GABA receptor genes in patients with autism, schizophrenia, and addiction, suggesting potential links between the GABA receptors and these conditions. A new and unexpected outcome from sequencing efforts has been the surprising number of mutations found in glutamate receptor subunits, with the GRIN2A gene encoding the GluN2A N-methyl-d-aspartate receptor subunit being most often affected. These mutations are associated with multiple neurologic conditions, for which seizure disorders comprise the largest group. The GluN2A subunit appears to be a locus for epilepsy, which holds important therapeutic implications. Virtually all α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor mutations, most of which occur within GRIA3, are from patients with intellectual disabilities, suggesting a link to this condition. Similarly, the most common phenotype for kainate receptor variants is intellectual disability. Herein, we summarize the current understanding of disease-associated mutations in ionotropic GABA and glutamate receptor families, and discuss implications regarding the identification of human mutations and treatment of neurologic diseases. PMID:25904555

  6. Neurologic Diseases

    MedlinePlus

    ... muscular dystrophy Problems with the way the nervous system develops, such as spina bifida Degenerative diseases, where nerve cells are damaged or die, such as Parkinson's disease and Alzheimer's disease Diseases of the blood vessels that supply ...

  7. Cytokine Therapies in Neurological Disease.

    PubMed

    Azodi, Shila; Jacobson, Steven

    2016-07-01

    Cytokines are a heterogeneous group of glycoproteins that coordinate physiological functions. Cytokine deregulation is observed in many neurological diseases. This article reviews current research focused on human clinical trials of cytokine and anticytokine therapies in the treatment of several neurological disease including stroke, neuromuscular diseases, neuroinfectious diseases, demyelinating diseases, and neurobehavioral diseases. This research suggests that cytokine therapy applications may play an important role in offering new strategies for disease modulation and treatment. Further, this research provides insights into the causal link between cytokine deregulation and neurological diseases. PMID:27388288

  8. Ion channel genes and human neurological disease: Recent progress, prospects, and challenges

    PubMed Central

    Cooper, Edward C.; Jan, Lily Yeh

    1999-01-01

    What do epilepsy, migraine headache, deafness, episodic ataxia, periodic paralysis, malignant hyperthermia, and generalized myotonia have in common? These human neurological disorders can be caused by mutations in genes for ion channels. Many of the channel diseases are “paroxysmal disorders” whose principal symptoms occur intermittently in individuals who otherwise may be healthy and active. Some of the ion channels that cause human neurological disease are old acquaintances previously cloned and extensively studied by channel specialists. In other cases, however, disease-gene hunts have led the way to the identification of new channel genes. Progress in the study of ion channels has made it possible to analyze the effects of human neurological disease-causing channel mutations at the level of the single channel, the subcellular domain, the neuronal network, and the behaving organism. PMID:10220366

  9. [Sleep and neurological diseases].

    PubMed

    Mayer, G

    2016-06-01

    Knowledge of the physiology of sleep-wake regulation can contribute to an understanding of the pathophysiology and symptoms of neurological diseases and is helpful for initiating specific therapies for sleep-wake cycle stabilization. Based on historically important observations on the close relationship between sleep and neurological diseases, new insights and developments in selected neurological entities are presented in this review article. PMID:27167889

  10. Measles, mumps, rubella, and human parvovirus B19 infections and neurologic disease.

    PubMed

    Bale, James F

    2014-01-01

    While the systemic disorders associated with measles, mumps, and rubella viruses and human parvovirus B19 tend to be mild, each virus can produce potentially life-threatening neurologic disease in human hosts, especially when these viruses infect young children. Two of the viruses, rubella and parvovirus B19, can be vertically transmitted to fetuses during maternal infection and cause congenital infection. Neurologic complications are common after intrauterine infection with the rubella virus, a condition known as the congenital rubella syndrome. Two, measles and rubella viruses, can induce "slow viral" infections, serious, disorders that can occur several years after the initial exposure to the virus and typically have fatal outcomes.

  11. PDE5 Exists in Human Neurons and is a Viable Therapeutic Target for Neurologic Disease

    PubMed Central

    Teich, Andrew F.; Sakurai, Mikako; Patel, Mitesh; Holman, Cameron; Saeed, Faisal; Fiorito, Jole; Arancio, Ottavio

    2016-01-01

    Phosphodiesterase 5 (PDE5) is a critical component of the cGMP-PKG axis of cellular signaling in neurons, and inhibition of PDE5 has been shown to be therapeutic in a wide range of neurologic conditions in animal models. However, enthusiasm for PDE5 inhibitors in humans is limited by data suggesting that PDE5 may not exist in human neurons. Here, we first show that past attempts to quantify PDE5 mRNA were flawed due to the use of incorrect primers, and that when correct primers are used, PDE5 mRNA is detectable in human brain tissue. We then show that PDE5 protein exists in human brain by western blot and ELISA. Most importantly, we performed immunohistochemistry and demonstrate that PDE5 is present in human neurons. We hope that this work will trigger a renewed interest in the development of PDE5 inhibitors for neurologic disease. PMID:26967220

  12. The Application of Human iPSCs in Neurological Diseases: From Bench to Bedside

    PubMed Central

    Xie, Nina; Tang, Beisha

    2016-01-01

    In principle, induced pluripotent stem cells (iPSCs) are generated from somatic cells by reprogramming and gaining the capacity to self-renew indefinitely as well as the ability to differentiate into cells of different lineages. Human iPSCs have absolute advantages over human embryonic stem cells (ESCs) and animal models in disease modeling, drug screening, and cell replacement therapy. Since Takahashi and Yamanaka first described in 2007 that iPSCs can be generated from human adult somatic cells by retroviral transduction of the four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc, disease specific iPSC lines have sprung up worldwide like bamboo shoots after a spring rain, making iPSC one of the hottest and fastest moving topics in modern science. The craze for iPSCs has spread throughout main branches of clinical medicine, covering neurology, hematology, cardiology, endocrinology, hepatology, ophthalmology, and so on. Here in this paper, we will focus on the clinical application of human iPSCs in disease modeling, drug screening, and cell replacement therapy for neurological diseases. PMID:26880979

  13. The Application of Human iPSCs in Neurological Diseases: From Bench to Bedside.

    PubMed

    Xie, Nina; Tang, Beisha

    2016-01-01

    In principle, induced pluripotent stem cells (iPSCs) are generated from somatic cells by reprogramming and gaining the capacity to self-renew indefinitely as well as the ability to differentiate into cells of different lineages. Human iPSCs have absolute advantages over human embryonic stem cells (ESCs) and animal models in disease modeling, drug screening, and cell replacement therapy. Since Takahashi and Yamanaka first described in 2007 that iPSCs can be generated from human adult somatic cells by retroviral transduction of the four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc, disease specific iPSC lines have sprung up worldwide like bamboo shoots after a spring rain, making iPSC one of the hottest and fastest moving topics in modern science. The craze for iPSCs has spread throughout main branches of clinical medicine, covering neurology, hematology, cardiology, endocrinology, hepatology, ophthalmology, and so on. Here in this paper, we will focus on the clinical application of human iPSCs in disease modeling, drug screening, and cell replacement therapy for neurological diseases.

  14. Neurological diseases and pain

    PubMed Central

    2012-01-01

    Chronic pain is a frequent component of many neurological disorders, affecting 20–40% of patients for many primary neurological diseases. These diseases result from a wide range of pathophysiologies including traumatic injury to the central nervous system, neurodegeneration and neuroinflammation, and exploring the aetiology of pain in these disorders is an opportunity to achieve new insight into pain processing. Whether pain originates in the central or peripheral nervous system, it frequently becomes centralized through maladaptive responses within the central nervous system that can profoundly alter brain systems and thereby behaviour (e.g. depression). Chronic pain should thus be considered a brain disease in which alterations in neural networks affect multiple aspects of brain function, structure and chemistry. The study and treatment of this disease is greatly complicated by the lack of objective measures for either the symptoms or the underlying mechanisms of chronic pain. In pain associated with neurological disease, it is sometimes difficult to obtain even a subjective evaluation of pain, as is the case for patients in a vegetative state or end-stage Alzheimer's disease. It is critical that neurologists become more involved in chronic pain treatment and research (already significant in the fields of migraine and peripheral neuropathies). To achieve this goal, greater efforts are needed to enhance training for neurologists in pain treatment and promote greater interest in the field. This review describes examples of pain in different neurological diseases including primary neurological pain conditions, discusses the therapeutic potential of brain-targeted therapies and highlights the need for objective measures of pain. PMID:22067541

  15. Insomnia in neurological diseases.

    PubMed

    Provini, Federica; Lombardi, Carolina; Lugaresi, Elio

    2005-03-01

    Insomnia is the most common sleep complaint. Insomnia is not a disease itself but mostly a clinical sign of an underlying disease. Degenerative and vascular diseases involving the central nervous system (CNS) may impair sleep either as a result of the brain lesion or because of illness-related discomfort (motor immobility, social and familial impairment, depression, drugs). Some neurological conditions characterized by movement disorders that start or persist during sleep hinder sleep onset and/or sleep continuity, causing a poor sleep complaint. CNS lesions and/or dysfunction in three specific neurological conditions (fatal familial insomnia, Morvan's chorea, and delirium tremens) impair the basic mechanisms of sleep generation inducing a syndrome in which the inability to sleep is consistently associated with motor and sympathergic overactivation. Agrypnia excitata is the term that aptly defines this generalized overactivation syndrome.

  16. A novel porcine model of ataxia telangiectasia reproduces neurological features and motor deficits of human disease.

    PubMed

    Beraldi, Rosanna; Chan, Chun-Hung; Rogers, Christopher S; Kovács, Attila D; Meyerholz, David K; Trantzas, Constantin; Lambertz, Allyn M; Darbro, Benjamin W; Weber, Krystal L; White, Katherine A M; Rheeden, Richard V; Kruer, Michael C; Dacken, Brian A; Wang, Xiao-Jun; Davis, Bryan T; Rohret, Judy A; Struzynski, Jason T; Rohret, Frank A; Weimer, Jill M; Pearce, David A

    2015-11-15

    Ataxia telangiectasia (AT) is a progressive multisystem disorder caused by mutations in the AT-mutated (ATM) gene. AT is a neurodegenerative disease primarily characterized by cerebellar degeneration in children leading to motor impairment. The disease progresses with other clinical manifestations including oculocutaneous telangiectasia, immune disorders, increased susceptibly to cancer and respiratory infections. Although genetic investigations and physiological models have established the linkage of ATM with AT onset, the mechanisms linking ATM to neurodegeneration remain undetermined, hindering therapeutic development. Several murine models of AT have been successfully generated showing some of the clinical manifestations of the disease, however they do not fully recapitulate the hallmark neurological phenotype, thus highlighting the need for a more suitable animal model. We engineered a novel porcine model of AT to better phenocopy the disease and bridge the gap between human and current animal models. The initial characterization of AT pigs revealed early cerebellar lesions including loss of Purkinje cells (PCs) and altered cytoarchitecture suggesting a developmental etiology for AT and could advocate for early therapies for AT patients. In addition, similar to patients, AT pigs show growth retardation and develop motor deficit phenotypes. By using the porcine system to model human AT, we established the first animal model showing PC loss and motor features of the human disease. The novel AT pig provides new opportunities to unmask functions and roles of ATM in AT disease and in physiological conditions.

  17. Neurological Disease Rises from Ocean to Bring Model for Human Epilepsy to Life

    PubMed Central

    Ramsdell, John S.

    2010-01-01

    Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had seizures and/or amnesia and four died; however, one survivor unexpectedly developed temporal lobe epilepsy (TLE) a year after the event. Nearly a decade later, several thousand sea lions have stranded on California beaches with neurological symptoms. Analysis of the animals stranded over an eight year period indicated five clusters of acute neurological poisoning; however, nearly a quarter have stranded individually outside these events with clinical signs of a chronic neurological syndrome similar to TLE. These poisonings are not limited to sea lions, which serve as readily observed sentinels for other marine animals that strand during domoic acid poisoning events, including several species of dolphin and whales. Acute domoic acid poisoning is five-times more prominent in adult female sea lions as a result of the proximity of their year-round breeding grounds to major domoic acid bloom events. The chronic neurological syndrome, on the other hand, is more prevalent in young animals, with many potentially poisoned in utero. The sea lion rookeries of the Channel Islands are at the crossroads of domoic acid producing harmful algal blooms and a huge industrial discharge site for dichlorodiphenyltrichloroethane (DDTs). Studies in experimental animals suggest that chronic poisoning observed in immature sea lions may result from a spatial and temporal coincidence of DDTs and domoic acid during early life stages. Emergence of an epilepsy syndrome from the ocean brings a human epilepsy model to life and provides unexpected insights into interaction with legacy contaminants and expression of disease at different life stages. PMID:22069654

  18. Happiness and neurological diseases.

    PubMed

    Barak, Yoram; Achiron, Anat

    2009-04-01

    Happiness is an emotional state reflecting positive feelings and satisfaction with life, which, as an outcome in disease states or as an end point in clinical trials, is a neglected concept in most therapeutic areas. In neurological disease, happiness is important as it can be diminished either as a direct result of damage to neuronal tissue or as a reaction to a poor prognosis. The monitoring and maintenance of happiness and wellbeing have historically been considered to be peripheral to medicine. However, as happiness interacts with the patient's physical health, it is an important parameter to assess alongside all aspects of any given disease. Happiness provides a reliable overview of the patient's general status over and above standard parameters for quality of life, and is more wide-ranging than the narrow measures of disease activity or treatment efficacy that are the focus of most clinical trials. In many studies, happiness has been associated with health and success in most areas of life, including performance at work, sporting achievement and social functioning. For approximately a decade, previously studied aspects of psychology have been grouped under the label of positive psychology (PoP). Principles of this discipline are now being used to guide some treatments in neurological and psychiatric diseases. PoP aims to define patient wellbeing in scientific terms and to increase understanding of happiness, meaning in life, resilience and character strengths, as well as to determine how this knowledge can be applied clinically to promote health. Some evidence has emerged recently suggesting that improvements in patient status can result from interventions to improve the patient's level of happiness in diseases, including epilepsy, Huntington's disease, multiple sclerosis, Parkinson's disease and stroke. Several effective approaches to increase happiness employ activities to engage and stimulate patients who might otherwise be unoccupied and isolated. In

  19. Modeling Neurological Disease by Rapid Conversion of Human Urine Cells into Functional Neurons.

    PubMed

    Zhang, Shu-Zhen; Ma, Li-Xiang; Qian, Wen-Jing; Li, Hong-Fu; Wang, Zhong-Feng; Wang, Hong-Xia; Wu, Zhi-Ying

    2016-01-01

    Somatic cells can be directly converted into functional neurons by ectopic expression of defined factors and/or microRNAs. Since the first report of conversion mouse embryonic fibroblasts into functional neurons, the postnatal mouse, and human fibroblasts, astroglia, hepatocytes, and pericyte-derived cells have been converted into functional dopaminergic and motor neurons both in vitro and in vivo. However, it is invasive to get all these materials. In the current study, we provide a noninvasive approach to obtain directly reprogrammed functional neurons by overexpression of the transcription factors Ascl1, Brn2, NeuroD, c-Myc, and Myt1l in human urine cells. These induced neuronal (iN) cells could express multiple neuron-specific proteins and generate action potentials. Moreover, urine cells from Wilson's disease (WD) patient could also be directly converted into neurons. In conclusion, generation of iN cells from nonneural lineages is a feasible and befitting approach for neurological disease modeling. PMID:26770203

  20. Neurological findings of Lyme disease.

    PubMed Central

    Pachner, A. R.; Steere, A. C.

    1984-01-01

    Neurologic involvement of Lyme disease typically consists of meningitis, cranial neuropathy, and radiculoneuritis, alone or in combination, lasting for months. From 1976 to 1983, we studied 38 patients with Lyme meningitis. Headache and mild neck stiffness, which fluctuated in intensity, and lymphocytic pleocytosis were the common findings. Half of the patients also had facial palsies, which were unilateral in 12 and bilateral in seven. In addition, 12 patients had motor and/or sensory radiculoneuropathies; asymmetric weakness of extremities was the most common finding. Although incomplete presentations of neurologic involvement of Lyme disease may be confused with other entities, the typical constellation of neurologic symptoms represents a unique clinical picture. PMID:6516450

  1. Neurology Case Studies: Cerebrovascular Disease.

    PubMed

    Farooq, Muhammad U; Gorelick, Philip B

    2016-08-01

    This article discusses interesting vascular neurology cases including the management of intracranial stenosis, migraine headache and stroke risk, retinal artery occlusions associated with impaired hearing, intracranial occlusive disease, a heritable cause of stroke and vascular cognitive impairment, and an interesting clinico-neuroradiologic disorder associated with eclampsia. PMID:27445238

  2. DNA Repair Deficiency and Neurological Disease

    PubMed Central

    McKinnon, Peter J.

    2011-01-01

    Preface Responding to genotoxic stress is a prerequisite for development of the nervous system. Mutations in a variety of DNA repair factors can lead to human diseases that are characterized by pronounced neuropathology. In many of these syndromes the neurological component is amongst the most deleterious aspects of the disease. The nervous system poses a particular challenge in terms of clinical intervention, as the neuropathology often arises during nervous system development, and can be fully penetrant by childhood. Understanding how DNA repair deficiency impacts the nervous system will provide a rationale basis for therapies targeted at ameliorating the neurological problems in these syndromes. PMID:19145234

  3. Genomic medicine and neurological disease

    PubMed Central

    Boone, Philip M.; Wiszniewski, Wojciech; Lupski, James R.

    2011-01-01

    “Genomic medicine” refers to the diagnosis, optimized management, and treatment of disease—as well as screening, counseling, and disease gene identification—in the context of information provided by an individual patient’s personal genome. Genomic medicine, to some extent synonymous with “personalized medicine,” has been made possible by recent advances in genome technologies. Genomic medicine represents a new approach to health care and disease management that attempts to optimize the care of a patient based upon information gleaned from his or her personal genome sequence. In this review, we describe recent progress in genomic medicine as it relates to neurological disease. Many neurological disorders either segregate as Mendelian phenotypes or occur sporadically in association with a new mutation in a single gene. Heritability also contributes to other neurological conditions that appear to exhibit more complex genetics. In addition to discussing current knowledge in this field, we offer suggestions for maximizing the utility of genomic information in clinical practice as the field of genomic medicine unfolds. PMID:21594611

  4. Somatic mutation, genomic variation, and neurological disease.

    PubMed

    Poduri, Annapurna; Evrony, Gilad D; Cai, Xuyu; Walsh, Christopher A

    2013-07-01

    Genetic mutations causing human disease are conventionally thought to be inherited through the germ line from one's parents and present in all somatic (body) cells, except for most cancer mutations, which arise somatically. Increasingly, somatic mutations are being identified in diseases other than cancer, including neurodevelopmental diseases. Somatic mutations can arise during the course of prenatal brain development and cause neurological disease-even when present at low levels of mosaicism, for example-resulting in brain malformations associated with epilepsy and intellectual disability. Novel, highly sensitive technologies will allow more accurate evaluation of somatic mutations in neurodevelopmental disorders and during normal brain development.

  5. Progressive neurologic and somatic disease in a novel mouse model of human mucopolysaccharidosis type IIIC.

    PubMed

    Marcó, Sara; Pujol, Anna; Roca, Carles; Motas, Sandra; Ribera, Albert; Garcia, Miguel; Molas, Maria; Villacampa, Pilar; Melia, Cristian S; Sánchez, Víctor; Sánchez, Xavier; Bertolin, Joan; Ruberte, Jesús; Haurigot, Virginia; Bosch, Fatima

    2016-09-01

    Mucopolysaccharidosis type IIIC (MPSIIIC) is a severe lysosomal storage disease caused by deficiency in activity of the transmembrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT) that catalyses the N-acetylation of α-glucosamine residues of heparan sulfate. Enzyme deficiency causes abnormal substrate accumulation in lysosomes, leading to progressive and severe neurodegeneration, somatic pathology and early death. There is no cure for MPSIIIC, and development of new therapies is challenging because of the unfeasibility of cross-correction. In this study, we generated a new mouse model of MPSIIIC by targeted disruption of the Hgsnat gene. Successful targeting left LacZ expression under control of the Hgsnat promoter, allowing investigation into sites of endogenous expression, which was particularly prominent in the CNS, but was also detectable in peripheral organs. Signs of CNS storage pathology, including glycosaminoglycan accumulation, lysosomal distension, lysosomal dysfunction and neuroinflammation were detected in 2-month-old animals and progressed with age. Glycosaminoglycan accumulation and ultrastructural changes were also observed in most somatic organs, but lysosomal pathology seemed most severe in liver. Furthermore, HGSNAT-deficient mice had altered locomotor and exploratory activity and shortened lifespan. Hence, this animal model recapitulates human MPSIIIC and provides a useful tool for the study of disease physiopathology and the development of new therapeutic approaches. PMID:27491071

  6. Progressive neurologic and somatic disease in a novel mouse model of human mucopolysaccharidosis type IIIC

    PubMed Central

    Marcó, Sara; Pujol, Anna; Roca, Carles; Motas, Sandra; Ribera, Albert; Garcia, Miguel; Molas, Maria; Villacampa, Pilar; Melia, Cristian S.; Sánchez, Víctor; Sánchez, Xavier; Bertolin, Joan; Ruberte, Jesús; Haurigot, Virginia

    2016-01-01

    ABSTRACT Mucopolysaccharidosis type IIIC (MPSIIIC) is a severe lysosomal storage disease caused by deficiency in activity of the transmembrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT) that catalyses the N-acetylation of α-glucosamine residues of heparan sulfate. Enzyme deficiency causes abnormal substrate accumulation in lysosomes, leading to progressive and severe neurodegeneration, somatic pathology and early death. There is no cure for MPSIIIC, and development of new therapies is challenging because of the unfeasibility of cross-correction. In this study, we generated a new mouse model of MPSIIIC by targeted disruption of the Hgsnat gene. Successful targeting left LacZ expression under control of the Hgsnat promoter, allowing investigation into sites of endogenous expression, which was particularly prominent in the CNS, but was also detectable in peripheral organs. Signs of CNS storage pathology, including glycosaminoglycan accumulation, lysosomal distension, lysosomal dysfunction and neuroinflammation were detected in 2-month-old animals and progressed with age. Glycosaminoglycan accumulation and ultrastructural changes were also observed in most somatic organs, but lysosomal pathology seemed most severe in liver. Furthermore, HGSNAT-deficient mice had altered locomotor and exploratory activity and shortened lifespan. Hence, this animal model recapitulates human MPSIIIC and provides a useful tool for the study of disease physiopathology and the development of new therapeutic approaches. PMID:27491071

  7. Neurologic Diseases in Special Care Patients.

    PubMed

    Robbins, Miriam R

    2016-07-01

    Neurologic diseases can have a major impact on functional capacity. Patients with neurologic disease require individualized management considerations depending on the extent of impairment and impact on functional capacity. This article reviews 4 of the more common and significant neurologic diseases (Alzheimer disease, cerebrovascular accident/stroke, multiple sclerosis, and Parkinson disease) that are likely to present to a dental office and provides suggestions on the dental management of patients with these conditions.

  8. Somatic Mutation, Genomic Variation, and Neurological Disease

    PubMed Central

    Poduri, Annapurna; Evrony, Gilad D.; Cai, Xuyu; Walsh, Christopher A.

    2014-01-01

    Genetic mutations causing human disease are conventionally thought to be inherited through the germ line from one’s parents and present in all somatic (body) cells, except for most cancer mutations, which arise somatically. Increasingly, somatic mutations are being identified in diseases other than cancer, including neurodevelopmental diseases. Somatic mutations can arise during the course of prenatal brain development and cause neurological disease—even when present at low levels of mosaicism, for example—resulting in brain malformations associated with epilepsy and intellectual disability. Novel, highly sensitive technologies will allow more accurate evaluation of somatic mutations in neurodevelopmental disorders and during normal brain development. PMID:23828942

  9. [Biopterin and child neurologic disease].

    PubMed

    Shintaku, Haruo

    2009-01-01

    Tetrahydrobiopterin (BH4) deficiencies are disorders affecting phenylalanine metabolism in the liver and neurotransmitter biosynthesis in the brain. BH4 is the essential cofactor in the enzymatic hydroxylation of 3 aromatic amino acids (phenylalanine, tyrosine, and tryptophan). BH4 is synthesized from guanosine triphosphate (GTP), catalyzed by GTP cyclohydrolase I (GTPCH), 6-pyruvoyl-tetrahydropterin synthase, and sepiapterin reductase (SR), and in aromatic amino acids, the hydoxylating system is regenerated by pterin-4a-carbinolamine dehydrolase and dihydropteridine reductase (DHPR). BH4 deficiency has been diagnosed in patients with hyperphenylalaninemia (HPA) by neonatal mass-screening based on BH4 oral-loading tests, analysis of urinary or serum pteridines, and measurement of DHPR activity in blood using a Guthrie card. BH4 deficiency without treatment causes combined symptoms of HPA and neurotransmitter (dopamine, norepinephrine, epinephrine, and serotonin) deficiency, such as red hair, psychomotor retardation, and progressive neurological deterioration. However, autosomal dominant GTPCH deficiency and autosomal recessive SR deficiency leads to BH4 and neurotransmitter deficiency without HPA and may not be detected by neonatal screening for phenylketonuria. The former is Segawa's disease, which is characterized by dopa-responsive dystonia with marked diurnal fluctuation and is caused by a defect of GTPCH, and the latter is SR deficiency, which is characterized by progressive psychomotor retardation, dystonia, and severe dopamine and serotonin deficiencies. Biochemical diagnosis is performed by the measurement of neopterin and biopterin levels, since both are low in Segawa disease, and the biopterin level is high in SR deficiency in cerebrospinal fluid. We must consider metabolic disorders of biopterin in child neurologic diseases with dystonia.

  10. Human Embryonic Stem Cells: A Model for the Study of Neural Development and Neurological Diseases

    PubMed Central

    Prajumwongs, Piya; Weeranantanapan, Oratai; Jaroonwitchawan, Thiranut; Noisa, Parinya

    2016-01-01

    Although the mechanism of neurogenesis has been well documented in other organisms, there might be fundamental differences between human and those species referring to species-specific context. Based on principles learned from other systems, it is found that the signaling pathways required for neural induction and specification of human embryonic stem cells (hESCs) recapitulated those in the early embryo development in vivo at certain degree. This underscores the usefulness of hESCs in understanding early human neural development and reinforces the need to integrate the principles of developmental biology and hESC biology for an efficient neural differentiation. PMID:27239201

  11. Human Neurological Development: Past, Present and Future

    NASA Technical Reports Server (NTRS)

    Pelligra, R. (Editor)

    1978-01-01

    Neurological development is considered as the major human potential. Vision, vestibular function, intelligence, and nutrition are discussed as well as the treatment of neurological disfunctions, coma, and convulsive seizures.

  12. Neurological and ocular fascioliasis in humans.

    PubMed

    Mas-Coma, Santiago; Agramunt, Verónica H; Valero, María Adela

    2014-01-01

    Fascioliasis is a food-borne parasitic disease caused by the trematode species Fasciola hepatica, distributed worldwide, and Fasciola gigantica, restricted to given regions of Africa and Asia. This disease in humans shows an increasing importance, which relies on its recent widespread emergence related to climate and global changes and also on its pathogenicity in the invasive, biliary, and advanced chronic phases in the human endemic areas, mainly of developing countries. In spite of the large neurological affection capacity of Fasciola, this important pathogenic aspect of the disease has been pronouncedly overlooked in the past decades and has not even appear within the numerous reviews on the parasitic diseases of the central nervous system. The aim of this wide retrospective review is an in-depth analysis of the characteristics of neurological and ocular fascioliasis caused by these two fasciolid species. The terms of neurofascioliasis and ophthalmofascioliasis are restricted to cases in which the direct affection of the central nervous system or the eye by a migrant ectopic fasciolid fluke is demonstrated by an aetiological diagnosis of recovered flukes after surgery or spontaneous moving-out of the fluke through the orbit. Cases in which the ectopic fluke is not recovered and the symptoms cannot be explained by an indirect affection at distance may also be included in these terms. Neurofascioliasis and ophthalmofascioliasis cases are reviewed and discussed. With regard to fascioliasis infection giving an indirect rise to neurological affection, the distribution and frequency of cases are analysed according to geography, sex, and age. Minor symptoms and major manifestations are discussed. Three main types of cases are distinguished depending on the characteristics of their manifestations: genuine neurological, meningeal, and psychiatric or neuropsychic. The impressive symptoms and signs appearing in each type of these cases are included. Brain examination

  13. Neurological Complications of Lyme Disease

    MedlinePlus

    ... may begin with flu-like symptoms such as fever, chills, swollen lymph nodes, headaches, fatigue, muscle aches, and joint pain. Neurological complications most often occur in the second stage ... such as fever, stiff neck, and severe headache. Other problems, which ...

  14. Molecular Imaging in Traditional Chinese Medicine Therapy for Neurological Diseases

    PubMed Central

    Wan, Haitong; Li, Jinhui; Zhang, Hong; Tian, Mei

    2013-01-01

    With the speeding tendency of aging society, human neurological disorders have posed an ever increasing threat to public health care. Human neurological diseases include ischemic brain injury, Alzheimer's disease, Parkinson's disease, and spinal cord injury, which are induced by impairment or specific degeneration of different types of neurons in central nervous system. Currently, there are no more effective treatments against these diseases. Traditional Chinese medicine (TCM) is focused on, which can provide new strategies for the therapy in neurological disorders. TCM, including Chinese herb medicine, acupuncture, and other nonmedication therapies, has its unique therapies in treating neurological diseases. In order to improve the treatment of these disorders by optimizing strategies using TCM and evaluate the therapeutic effects, we have summarized molecular imaging, a new promising technology, to assess noninvasively disease specific in cellular and molecular levels of living models in vivo, that was applied in TCM therapy for neurological diseases. In this review, we mainly focus on applying diverse molecular imaging methodologies in different TCM therapies and monitoring neurological disease, and unveiling the mysteries of TCM. PMID:24222911

  15. Roles of Circular RNAs in Neurologic Disease

    PubMed Central

    Shao, Yiye; Chen, Yinghui

    2016-01-01

    Circular RNAs (circRNAs) are a novel type of endogenous noncoding RNA receiving increasing attention. They have been shown to act as a natural microRNA sponges that repress the activity of corresponding miRNAs by binding with them, thus regulating target genes. Numerous studies have shown that miRNAs are involved in the pathogenesis of neurological diseases. Therefore, circRNAs may act as important regulatory factors in the occurrence and development processes of neurological disease. PMID:27147959

  16. Dysfunctional HCN ion channels in neurological diseases

    PubMed Central

    DiFrancesco, Jacopo C.; DiFrancesco, Dario

    2015-01-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed as four different isoforms (HCN1-4) in the heart and in the central and peripheral nervous systems. HCN channels are activated by membrane hyperpolarization at voltages close to resting membrane potentials and carry the hyperpolarization-activated current, dubbed If (funny current) in heart and Ih in neurons. HCN channels contribute in several ways to neuronal activity and are responsible for many important cellular functions, including cellular excitability, generation, and modulation of rhythmic activity, dendritic integration, transmission of synaptic potentials, and plasticity phenomena. Because of their role, defective HCN channels are natural candidates in the search for potential causes of neurological disorders in humans. Several data, including growing evidence that some forms of epilepsy are associated with HCN mutations, support the notion of an involvement of dysfunctional HCN channels in different experimental models of the disease. Additionally, some anti-epileptic drugs are known to modify the activity of the Ih current. HCN channels are widely expressed in the peripheral nervous system and recent evidence has highlighted the importance of the HCN2 isoform in the transmission of pain. HCN channels are also present in the midbrain system, where they finely regulate the activity of dopaminergic neurons, and a potential role of these channels in the pathogenesis of Parkinson’s disease has recently emerged. The function of HCN channels is regulated by specific accessory proteins, which control the correct expression and modulation of the neuronal Ih current. Alteration of these proteins can severely interfere with the physiological channel function, potentially predisposing to pathological conditions. In this review we address the present knowledge of the association between HCN dysfunctions and neurological diseases, including clinical, genetic, and physiopathological

  17. Need for palliative care for neurological diseases.

    PubMed

    Provinciali, Leandro; Carlini, Giulia; Tarquini, Daniela; Defanti, Carlo Alberto; Veronese, Simone; Pucci, Eugenio

    2016-10-01

    The new concept of palliative care supports the idea of palliation as an early approach to patients affected by disabling and life-limiting disease which focuses on the patient's quality of life along the entire course of disease. This model moves beyond the traditional concept of palliation as an approach restricted to the final stage of disease and widens the fields of intervention. There is a growing awareness of the importance of palliative care not only in oncological diseases but also in many other branches of medicine, and it appears particularly evident in the approach to many of the most frequent neurological diseases that are chronic, incurable and autonomy-impairing illnesses. The definition and implementation of palliative goals and procedures in neurology must take into account the specific features of these conditions in terms of the complexity and variability of symptoms, clinical course, disability and prognosis. The realization of an effective palliative approach to neurological diseases requires specific skills and expertise to adapt the concept of palliation to the peculiarities of these diseases; this approach should be realized through the cooperation of different services and the action of a multidisciplinary team in which the neurologist should play a central role to identify and face the patient's needs. In this view, it is paramount for the neurologist to be trained in these issues to promote the integration of palliative care in the care of neurological patients.

  18. Need for palliative care for neurological diseases.

    PubMed

    Provinciali, Leandro; Carlini, Giulia; Tarquini, Daniela; Defanti, Carlo Alberto; Veronese, Simone; Pucci, Eugenio

    2016-10-01

    The new concept of palliative care supports the idea of palliation as an early approach to patients affected by disabling and life-limiting disease which focuses on the patient's quality of life along the entire course of disease. This model moves beyond the traditional concept of palliation as an approach restricted to the final stage of disease and widens the fields of intervention. There is a growing awareness of the importance of palliative care not only in oncological diseases but also in many other branches of medicine, and it appears particularly evident in the approach to many of the most frequent neurological diseases that are chronic, incurable and autonomy-impairing illnesses. The definition and implementation of palliative goals and procedures in neurology must take into account the specific features of these conditions in terms of the complexity and variability of symptoms, clinical course, disability and prognosis. The realization of an effective palliative approach to neurological diseases requires specific skills and expertise to adapt the concept of palliation to the peculiarities of these diseases; this approach should be realized through the cooperation of different services and the action of a multidisciplinary team in which the neurologist should play a central role to identify and face the patient's needs. In this view, it is paramount for the neurologist to be trained in these issues to promote the integration of palliative care in the care of neurological patients. PMID:27299428

  19. Metabolic Disturbances in Diseases with Neurological Involvement

    PubMed Central

    Duarte, João M. N.; Schuck, Patrícia F.; Wenk, Gary L.; Ferreira, Gustavo C.

    2014-01-01

    Degeneration of specific neuronal populations and progressive nervous system dysfunction characterize neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. These findings are also reported in inherited diseases such as phenylketonuria and glutaric aciduria type I. The involvement of mitochondrial dysfunction in these diseases was reported, elicited by genetic alterations, exogenous toxins or buildup of toxic metabolites. In this review we shall discuss some metabolic alterations related to the pathophysiology of diseases with neurological involvement and aging process. These findings may help identifying early disease biomarkers and lead to more effective therapies to improve the quality of life of the patients affected by these devastating illnesses. PMID:25110608

  20. Mitochondrial Biology and Neurological Diseases

    PubMed Central

    Arun, Siddharth; Liu, Lei; Donmez, Gizem

    2016-01-01

    Mitochondria are extremely active organelles that perform a variety of roles in the cell including energy production, regulation of calcium homeostasis, apoptosis, and population maintenance through fission and fusion. Mitochondrial dysfunction in the form of oxidative stress and mutations can contribute to the pathogenesis of various neurodegenerative diseases such as Parkinson’s (PD), Alzheimer’s (AD), and Huntington’s diseases (HD). Abnormalities of Complex I function in the electron transport chain have been implicated in some neurodegenerative diseases, inhibiting ATP production and generating reactive oxygen species that can cause major damage to mitochondria Mutations in both nuclear and mitochondrial DNA can contribute to neurodegenerative disease, although the pathogenesis of these conditions tends to focus on nuclear mutations. In PD, nuclear genome mutations in the PINK1 and parkin genes have been implicated in neurodegeneration [1], while mutations in APP, PSEN1 and PSEN2 have been implicated in a variety of clinical symptoms of AD [5]. Mutant htt protein is known to cause HD [2]. Much progress has been made to determine some causes of these neurodegenerative diseases, though permanent treatments have yet to be developed. In this review, we discuss the roles of mitochondrial dysfunction in the pathogenesis of these diseases. PMID:26903445

  1. Recognition and treatment of neurologic Wilson's disease.

    PubMed

    Lorincz, Matthew T

    2012-11-01

    As Wilson's disease is both preventable and treatable, the diagnosis must not be missed. Despite this, it is usually misdiagnosed. Misdiagnosis and delay in treatment are clinically relevant because if left untreated, Wilson's disease progresses to hepatic failure or severe neurologic disability, and death. Those adequately treated have a normal life span. Wilson's disease is an autosomal recessive disease caused by mutations in the ATP7B gene. Mutations in ATP7B result in abnormal copper metabolism and subsequent toxic accumulation of copper. The clinical manifestations of neurologic Wilson's disease include variable combinations of dysarthria, dystonia, tremor, parkinsonism, ataxia, and choreoathetosis. Once the possibility of Wilson's disease is considered, diagnosis is straight forward. Currently available treatments, including zinc acetate and trientine, are generally well tolerated and effective.

  2. Neurologic manifestations of lyme disease.

    PubMed

    Halperin, John J

    2011-08-01

    Borrelia burgdorferi infection, the tick-borne spirochetosis known as Lyme disease or Lyme borreliosis, involves the nervous system (neuroborreliosis) in 10% to 15% of patients. Common manifestations include lymphocytic meningitis, cranial neuritis, mononeuropathy multiplex, and painful radiculoneuritis. Rare patients develop inflammation in the brain or spinal cord. Regardless of the form of involvement, neuroborreliosis can be microbiologically cured in virtually all patients using standard 2- to 4-week antimicrobial regimens. Oral regimens appear to be as effective as parenteral ones in most instances. Although patients ill with Lyme disease may have concomitant cognitive or memory difficulty, these symptoms are not specific to neuroborreliosis and, when present in isolation, should not be viewed as suggestive of this diagnosis. When present as part of Lyme disease, they do not require additional or different treatment.

  3. The Neurologic Manifestations of Mitochondrial Disease

    ERIC Educational Resources Information Center

    Parikh, Sumit

    2010-01-01

    The nervous system contains some of the body's most metabolically demanding cells that are highly dependent on ATP produced via mitochondrial oxidative phosphorylation. Thus, the neurological system is consistently involved in patients with mitochondrial disease. Symptoms differ depending on the part of the nervous system affected. Although almost…

  4. Inhibition of human glutamine synthetase by L-methionine-S,R-sulfoximine-relevance to the treatment of neurological diseases.

    PubMed

    Jeitner, Thomas M; Cooper, Arthur J L

    2014-12-01

    At high concentrations, the glutamine synthetase inhibitor L-methionine-S,R-sulfoximine (MSO) is a convulsant, especially in dogs. Nevertheless, sub-convulsive doses of MSO are neuroprotective in rodent models of hyperammonemia, acute liver disease, and amyotrophic lateral sclerosis and suggest MSO may be clinically useful. Previous work has also shown that much lower doses of MSO are required to produce convulsions in dogs than in primates. Evidence from the mid-20th century suggests that humans are also less sensitive. In the present work, the inhibition of recombinant human glutamine synthetase by MSO is shown to be biphasic-an initial reversible competitive inhibition (K i 1.19 mM) is followed by rapid irreversible inactivation. This K i value for the human enzyme accounts, in part, for relative insensitivity of primates to MSO and suggests that this inhibitor could be used to safely inhibit glutamine synthetase activity in humans.

  5. Neurological disorders and inflammatory bowel diseases

    PubMed Central

    Casella, Giovanni; Tontini, Gian Eugenio; Bassotti, Gabrio; Pastorelli, Luca; Villanacci, Vincenzo; Spina, Luisa; Baldini, Vittorio; Vecchi, Maurizio

    2014-01-01

    Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease (IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated with IBD are not frequent, being reported in 3% of patients, but they often represent an important cause of morbidity and a relevant diagnostic issue. In addition, the increasing use of immunosuppressant and biological therapies for IBD may also play a pivotal role in the development of neurological disorders of different type and pathogenesis. Hence, we provide a complete and profound review of the main features of neurological complications associated with IBD, with particular reference to those related to drugs and with a specific focus on their clinical presentation and possible pathophysiological mechanisms. PMID:25083051

  6. Toward precision medicine in neurological diseases.

    PubMed

    Tan, Lin; Jiang, Teng; Tan, Lan; Yu, Jin-Tai

    2016-03-01

    Technological development has paved the way for accelerated genomic discovery and is bringing precision medicine into view. The goal of precision medicine is to deliver optimally targeted and timed interventions tailored to an individual's molecular drivers of disease. Neurological diseases are promisingly suited models for precision medicine because of the rapidly expanding genetic knowledge base, phenotypic classification, the development of biomarkers and the potential modifying treatments. Moving forward, it is crucial that through these integrated research platforms to provide analysis both for accurate personal genome analysis and gene and drug discovery. Here we describe our vision of how precision medicine can bring greater clarity to the clinical and biological complexity of neurological diseases. PMID:27127757

  7. Epigenetic mechanisms in neurological and neurodegenerative diseases

    PubMed Central

    Landgrave-Gómez, Jorge; Mercado-Gómez, Octavio; Guevara-Guzmán, Rosalinda

    2015-01-01

    The role of epigenetic mechanisms in the function and homeostasis of the central nervous system (CNS) and its regulation in diseases is one of the most interesting processes of contemporary neuroscience. In the last decade, a growing body of literature suggests that long-term changes in gene transcription associated with CNS’s regulation and neurological disorders are mediated via modulation of chromatin structure. “Epigenetics”, introduced for the first time by Waddington in the early 1940s, has been traditionally referred to a variety of mechanisms that allow heritable changes in gene expression even in the absence of DNA mutation. However, new definitions acknowledge that many of these mechanisms used to perpetuate epigenetic traits in dividing cells are used by neurons to control a variety of functions dependent on gene expression. Indeed, in the recent years these mechanisms have shown their importance in the maintenance of a healthy CNS. Moreover, environmental inputs that have shown effects in CNS diseases, such as nutrition, that can modulate the concentration of a variety of metabolites such as acetyl-coenzyme A (acetyl-coA), nicotinamide adenine dinucleotide (NAD+) and beta hydroxybutyrate (β-HB), regulates some of these epigenetic modifications, linking in a precise way environment with gene expression. This manuscript will portray what is currently understood about the role of epigenetic mechanisms in the function and homeostasis of the CNS and their participation in a variety of neurological disorders. We will discuss how the machinery that controls these modifications plays an important role in processes involved in neurological disorders such as neurogenesis and cell growth. Moreover, we will discuss how environmental inputs modulate these modifications producing metabolic and physiological alterations that could exert beneficial effects on neurological diseases. Finally, we will highlight possible future directions in the field of epigenetics

  8. Wilson's disease and other neurological copper disorders.

    PubMed

    Bandmann, Oliver; Weiss, Karl Heinz; Kaler, Stephen G

    2015-01-01

    The copper metabolism disorder Wilson's disease was first defined in 1912. Wilson's disease can present with hepatic and neurological deficits, including dystonia and parkinsonism. Early-onset presentations in infancy and late-onset manifestations in adults older than 70 years of age are now well recognised. Direct genetic testing for ATP7B mutations are increasingly available to confirm the clinical diagnosis of Wilson's disease, and results from biochemical and genetic prevalence studies suggest that Wilson's disease might be much more common than previously estimated. Early diagnosis of Wilson's disease is crucial to ensure that patients can be started on adequate treatment, but uncertainty remains about the best possible choice of medication. Furthermore, Wilson's disease needs to be differentiated from other conditions that also present clinically with hepatolenticular degeneration or share biochemical abnormalities with Wilson's disease, such as reduced serum ceruloplasmin concentrations. Disordered copper metabolism is also associated with other neurological conditions, including a subtype of axonal neuropathy due to ATP7A mutations and the late-onset neurodegenerative disorders Alzheimer's disease and Parkinson's disease.

  9. Radiopharmaceutical stem cell tracking for neurological diseases.

    PubMed

    Rosado-de-Castro, Paulo Henrique; Pimentel-Coelho, Pedro Moreno; Gutfilen, Bianca; Lopes de Souza, Sergio Augusto; de Freitas, Gabriel Rodriguez; Mendez-Otero, Rosalia; Barbosa da Fonseca, Lea Mirian

    2014-01-01

    Although neurological ailments continue to be some of the main causes of disease burden in the world, current therapies such as pharmacological agents have limited potential in the restoration of neural functions. Cell therapies, firstly applied to treat different hematological diseases, are now being investigated in preclinical and clinical studies for neurological illnesses. However, the potential applications and mechanisms for such treatments are still poorly comprehended and are the focus of permanent research. In this setting, noninvasive in vivo imaging allows better understanding of several aspects of stem cell therapies. Amongst the various methods available, radioisotope cell labeling has become one of the most promising since it permits tracking of cells after injection by different routes to investigate their biodistribution. A significant increase in the number of studies utilizing this method has occurred in the last years. Here, we review the different radiopharmaceuticals, imaging techniques, and findings of the preclinical and clinical reports published up to now. Moreover, we discuss the limitations and future applications of radioisotope cell labeling in the field of cell transplantation for neurological diseases. PMID:24982880

  10. MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease.

    PubMed

    Yelamanchili, S V; Chaudhuri, A Datta; Chen, L-N; Xiong, Huangui; Fox, H S

    2010-01-01

    MicroRNAs (miRNAs) play important roles in regulating a plethora of physiological and pathophysiogical processes including neurodegeneration. In both HIV associated dementia in humans and its monkey model SIV encephalitis we find miR-21, a miRNA largely known for its link to oncogenesis, to be significantly upregulated in the brain. In situ hybridization of the diseased brain sections revealed induction of miR-21 in neurons. MiR-21 can be induced in neurons by prolonged N-methyl-D-aspartic acid receptor stimulation, an excitotoxic process active in HIV and other neurodegenerative diseases. Introduction of miR-21 into human neurons leads to pathological functional defects. Furthermore, we show that miR-21 specifically targets the mRNA of myocyte enhancer factor 2C (MEF2C), a transcription factor crucial for neuronal function, and reduces its expression. MEF2C is dramatically downregulated in neurons of HIV-associated dementia patients as well as monkeys with SIVE. Together, this study elucidates a novel role for miR-21 in the brain, not only as a potential signature of neurological disease but also as a crucial effector of HIV induced neuronal dysfunction and neurodegeneration.

  11. Progress in stem cell therapy for major human neurological disorders.

    PubMed

    Martínez-Morales, P L; Revilla, A; Ocaña, I; González, C; Sainz, P; McGuire, D; Liste, I

    2013-10-01

    Human neurological disorders such as Alzheimer's disease (AD), Parkinson's disease, stroke or spinal cord injury are caused by the loss of neurons and glial cells in the brain or spinal cord in the Central Nervous System (CNS). Stem cell technology has become an attractive option to investigate and treat these diseases. Several types of neurons and glial cells have successfully been generated from stem cells, which in some cases, have ameliorated some dysfunctions both in animal models of neurological disorders and in patients at clinical level. Stem cell-based therapies can be beneficial by acting through several mechanisms such as cell replacement, modulation of inflammation and trophic actions. Here we review recent and current remarkable clinical studies involving stem cell-based therapy for AD and stroke and provide an overview of the different types of stem cells available nowadays, their main properties and how they are developing as a possible therapy for neurological disorders.

  12. The role of RNA metabolism in neurological diseases

    PubMed Central

    Abou Al-Shaar, H; Shariff, RK; Albakr, A

    2015-01-01

    Abstract Neurodegenerative disorders are commonly encountered in medical practices. Such diseases can lead to major morbidity and mortality among the affected individuals. The molecular pathogenesis of these disorders is not yet clear. Recent literature has revealed that mutations in RNA-binding proteins are a key cause of several human neuronal-based diseases. This review discusses the role of RNA metabolism in neurological diseases with specific emphasis on roles of RNA translation and microRNAs in neurodegeneration, RNA-mediated toxicity, repeat expansion diseases and RNA metabolism, molecular pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia, and neurobiology of survival motor neuron (SMN) and spinal muscular atrophy. PMID:27785391

  13. A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease.

    PubMed

    Wolf, Heike; Damme, Markus; Stroobants, Stijn; D'Hooge, Rudi; Beck, Hans Christian; Hermans-Borgmeyer, Irm; Lüllmann-Rauch, Renate; Dierks, Thomas; Lübke, Torben

    2016-09-01

    Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here, we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fucosidase (Fuca1) was disrupted by gene targeting. Homozygous knockout mice completely lack α-L-fucosidase activity in all tested organs leading to highly elevated amounts of the core-fucosylated glycoasparagine Fuc(α1,6)-GlcNAc(β1-N)-Asn and, to a lesser extent, other fucosylated glycoasparagines, which all were also partially excreted in urine. Lysosomal storage pathology was observed in many visceral organs, such as in the liver, kidney, spleen and bladder, as well as in the central nervous system (CNS). On the cellular level, storage was characterized by membrane-limited cytoplasmic vacuoles primarily containing water-soluble storage material. In the CNS, cellular alterations included enlargement of the lysosomal compartment in various cell types, accumulation of secondary storage material and neuroinflammation, as well as a progressive loss of Purkinje cells combined with astrogliosis leading to psychomotor and memory deficits. Our results demonstrate that this new fucosidosis mouse model resembles the human disease and thus will help to unravel underlying pathological processes. Moreover, this model could be utilized to establish diagnostic and therapeutic strategies for fucosidosis.

  14. A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease

    PubMed Central

    Wolf, Heike; Stroobants, Stijn; D'Hooge, Rudi; Hermans-Borgmeyer, Irm; Lüllmann-Rauch, Renate; Dierks, Thomas; Lübke, Torben

    2016-01-01

    ABSTRACT Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here, we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fucosidase (Fuca1) was disrupted by gene targeting. Homozygous knockout mice completely lack α-L-fucosidase activity in all tested organs leading to highly elevated amounts of the core-fucosylated glycoasparagine Fuc(α1,6)-GlcNAc(β1-N)-Asn and, to a lesser extent, other fucosylated glycoasparagines, which all were also partially excreted in urine. Lysosomal storage pathology was observed in many visceral organs, such as in the liver, kidney, spleen and bladder, as well as in the central nervous system (CNS). On the cellular level, storage was characterized by membrane-limited cytoplasmic vacuoles primarily containing water-soluble storage material. In the CNS, cellular alterations included enlargement of the lysosomal compartment in various cell types, accumulation of secondary storage material and neuroinflammation, as well as a progressive loss of Purkinje cells combined with astrogliosis leading to psychomotor and memory deficits. Our results demonstrate that this new fucosidosis mouse model resembles the human disease and thus will help to unravel underlying pathological processes. Moreover, this model could be utilized to establish diagnostic and therapeutic strategies for fucosidosis. PMID:27491075

  15. Efficacy of Intravenous Immunoglobulin in Neurological Diseases.

    PubMed

    Lünemann, Jan D; Quast, Isaak; Dalakas, Marinos C

    2016-01-01

    Owing to its anti-inflammatory efficacy in various autoimmune disease conditions, intravenous immunoglobulin (IVIG)-pooled IgG obtained from the plasma of several thousands individuals-has been used for nearly three decades and is proving to be efficient in a growing number of neurological diseases. IVIG therapy has been firmly established for the treatment of Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy, either as first-line therapy or adjunctive treatment. IVIG is also recommended as rescue therapy in patients with worsening myasthenia gravis and is beneficial as a second-line therapy for dermatomyositis and stiff-person syndrome. Subcutaneous rather than intravenous administration of IgG is gaining momentum because of its effectiveness in patients with primary immunodeficiency and the ease with which it can be administered independently from hospital-based infusions. The demand for IVIG therapy is growing, resulting in rising costs and supply shortages. Strategies to replace IVIG with recombinant products have been developed based on proposed mechanisms that confer the anti-inflammatory activity of IVIG, but their efficacy has not been tested in clinical trials. This review covers new developments in the immunobiology and clinical applications of IVIG in neurological diseases.

  16. Lower numbers of circulating Natural Killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease.

    PubMed

    Ndhlovu, L C; Snyder-Cappione, J E; Carvalho, K I; Leal, F E; Loo, C P; Bruno, F R; Jha, A R; Devita, D; Hasenkrug, A M; Barbosa, H M R; Segurado, A C; Nixon, D F; Murphy, E L; Kallas, E G

    2009-12-01

    Human T lymphotropic virus type 1 (HTLV-1) infects 10-20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4(+) and fewer CD8(+) cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4(+) NK T subset are associated with HTLV-1 disease progression.

  17. Synaptic pathology: A shared mechanism in neurological disease.

    PubMed

    Henstridge, Christopher M; Pickett, Eleanor; Spires-Jones, Tara L

    2016-07-01

    Synaptic proteomes have evolved a rich and complex diversity to allow the exquisite control of neuronal communication and information transfer. It is therefore not surprising that many neurological disorders are associated with alterations in synaptic function. As technology has advanced, our ability to study the anatomical and physiological function of synapses in greater detail has revealed a critical role for both central and peripheral synapses in neurodegenerative disease. Synapse loss has a devastating effect on cellular communication, leading to wide ranging effects such as network disruption within central neural systems and muscle wastage in the periphery. These devastating effects link synaptic pathology to a diverse range of neurological disorders, spanning Alzheimer's disease to multiple sclerosis. This review will highlight some of the current literature on synaptic integrity in animal models of disease and human post-mortem studies. Synaptic changes in normal brain ageing will also be discussed and finally the current and prospective treatments for neurodegenerative disorders will be summarised. PMID:27108053

  18. Chelation treatment of neurological Wilson's disease.

    PubMed

    Walshe, J M; Yealland, M

    1993-03-01

    The results of chelation treatment of 137 patients presenting with neurological Wilson's disease are described, together with the more commonly observed toxic reactions to the various drugs employed. Fifty-seven patients made an excellent response to treatment and became symptom free. Thirty-six patients made a good recovery, but were left with some minor neurological deficit. Twenty-four patients had a poor response: although the disease process was arrested they were left more or less disabled. Twenty patients died: nine had little or no treatment, but 11 died despite apparently adequate chelation therapy. There was no obvious reason for this failure. The liver copper level was estimated in six of these patients: it was still significantly elevated in only one, but in all four in whom it was possible to make the determination, the concentration of copper in the basal ganglia was in excess of 45 micrograms/g wet weight. It was not apparent why adequate therapy failed to remove copper from the brains of these patients. There was no obvious clinical, histological or biochemical indicator of failure to respond to treatment. Initial deterioration before improvement was seen in 30 patients: the prognosis for a useful recovery was not necessarily worse than that in patients who did not show this phenomenon.

  19. Type I interferon dysregulation and neurological disease.

    PubMed

    McGlasson, Sarah; Jury, Alexa; Jackson, Andrew; Hunt, David

    2015-09-01

    Type I interferon is an essential component of the brain's innate immune defence, conferring protection against viral infection. Recently, dysregulation of the type I interferon pathway has been implicated in the pathogenesis of a spectrum of neuroinfectious and neuroinflammatory disorders. Underactivity of the type I interferon response is associated with a predisposition to herpes simplex encephalitis. Conversely, a group of 'interferonopathic' disorders, characterized by severe neuroinflammation and overactivity of type I interferon, has been described. Elucidation of the genetic basis of these Mendelian neuroinflammatory diseases has uncovered important links between nucleic acid sensors, innate immune activation and neuroinflammatory disease. These mechanisms have an important role in the pathogenesis of more common polygenic diseases that can affect the brain, such as lupus and cerebral small vessel disease. In this article, we review the spectrum of neurological disease associated with type I interferon dysregulation, as well as advances in our understanding of the molecular and cellular pathogenesis of these conditions. We highlight the potential utility of type I interferon as both a biomarker and a therapeutic target in neuroinflammatory disease. PMID:26303851

  20. Cyclodextrins, blood-brain barrier, and treatment of neurological diseases.

    PubMed

    Vecsernyés, Miklós; Fenyvesi, Ferenc; Bácskay, Ildikó; Deli, Mária A; Szente, Lajos; Fenyvesi, Éva

    2014-11-01

    Biological barriers are the main defense systems of the homeostasis of the organism and protected organs. The blood-brain barrier (BBB), formed by the endothelial cells of brain capillaries, not only provides nutrients and protection to the central nervous system but also restricts the entry of drugs, emphasizing its importance in the treatment of neurological diseases. Cyclodextrins are increasingly used in human pharmacotherapy. Due to their favorable profile to form hydrophilic inclusion complexes with poorly soluble active pharmaceutical ingredients, they are present as excipients in many marketed drugs. Application of cyclodextrins is widespread in formulations for oral, parenteral, nasal, pulmonary, and skin delivery of drugs. Experimental and clinical data suggest that cyclodextrins can be used not only as excipients for centrally acting marketed drugs like antiepileptics, but also as active pharmaceutical ingredients to treat neurological diseases. Hydroxypropyl-β-cyclodextrin received orphan drug designation for the treatment of Niemann-Pick type C disease. In addition to this rare lysosomal storage disease with neurological symptoms, experimental research revealed the potential therapeutic use of cyclodextrins and cyclodextrin nanoparticles in neurodegenerative diseases, stroke, neuroinfections and brain tumors. In this context, the biological effects of cyclodextrins, their interaction with plasma membranes and extraction of different lipids are highly relevant at the level of the BBB.

  1. Wilson's disease and other neurological copper disorders.

    PubMed Central

    Bandmann, Oliver; Weiss, Karl Heinz; Kaler, Stephen G.

    2015-01-01

    Summary The classic copper metabolism disorder, Wilson disease (WD), was first defined in 1912. Both early onset presentations in infancy and late onset manifestations in adults > 70 years are now well recognized. Modern biochemical and genetic prevalence studies suggest that WD may be considerably more common than previously appreciated. Early diagnosis of WD is crucial to ensure that patients can be started on adequate treatment but uncertainty remains about the best possible choice of medication. Direct genetic testing for ATP7B mutations is increasingly available to confirm the clinical diagnosis of WD. WD needs to be differentiated from other conditions that present clinically with hepatolenticular degeneration or share biochemical abnormalities with WD, such as reduced serum cerulo plasmin levels. Disordered copper metabolism is also implied in an increasing number of other neurological conditions, including a subtype of axonal neuropathy due to ATP7A mutations, and the common late-onset neurodegenerative disorders Alzheimer’s disease and Parkinson’s disease. PMID:25496901

  2. [Neurologic diseases associated with the HTLV-1 virus in Panama].

    PubMed

    Gracia, F; Castillo, L; de Lao, S L; Archibold, C A; Larreátegui, M; Reeves, W C; Levine, P

    1990-09-01

    Studies of the prevalence of the human T-cell lymphotropic virus (HTLV-1) in 1984 to 1986 in the Republic of Panama revealed a national seroprevalence of 1 to 2%. Since 1985 clinical epidemiological studies of neurological diseases associated to HTLV-1 are being done. Two hundred and fitly six clinical cases of thirty eight different neurological diseases of unknown etiology studied in the Neurology Services of the Santo Tomas Hospital and the Social Security Metropolitan Hospital Complex have been associated in some way to the HTLV-1. Twelve cases of progressive spastic paraparesis were identified and related to HLTV-1 as an etiologic agent. The ratio of men to women was maintained at 1:1 with the average age at onset at 44 years and without racial preference. There are important doubts about the association of this virus to multiple sclerosis. The seroprevalence of the HTLV-1 virus in Panama is found to be similar to that reported in neighboring countries and the association of tropical spastic paraparesis to THLV-1 infection is identified.

  3. Immune aging, dysmetabolism, and inflammation in neurological diseases

    PubMed Central

    Deleidi, Michela; Jäggle, Madeline; Rubino, Graziella

    2015-01-01

    As we age, the immune system undergoes a process of senescence accompanied by the increased production of proinflammatory cytokines, a chronic subclinical condition named as “inflammaging”. Emerging evidence from human and experimental models suggest that immune senescence also affects the central nervous system and promotes neuronal dysfunction, especially within susceptible neuronal populations. In this review we discuss the potential role of immune aging, inflammation and metabolic derangement in neurological diseases. The discovery of novel therapeutic strategies targeting age-linked inflammation may promote healthy brain aging and the treatment of neurodegenerative as well as neuropsychiatric disorders. PMID:26089771

  4. NEUROLOGICAL ASPECTS OF HUMAN GLYCOSYLATION DISORDERS

    PubMed Central

    Freeze, Hudson H.; Eklund, Erik A.; Ng, Bobby G.; Patterson, Marc C.

    2016-01-01

    This review will present principles of glycosylation, describe the relevant glycosylation pathways and their related disorders, and highlight some of the neurological aspects and issues that continue to challenge researchers. Over 100 rare human genetic disorders that result from deficiencies in the different glycosylation pathways are known today. Most of these disorders impact the central and/or peripheral nervous systems. Patients typically have developmental delay/intellectual disability, hypotonia, seizures, neuropathy, and metabolic abnormalities in multiple organ systems. Between these disorders there is great clinical diversity because all cell types differentially glycosylate proteins and lipids. The patients have hundreds of mis-glycosylated products afflicting a myriad of processes including cell signaling, cell-cell interaction and cell migration. This vast complexity in glycan composition and function, along with limited analytic tools has impeded the identification of key glycosylated molecules that cause pathologies, and to date few critical target proteins have been pinpointed. PMID:25840006

  5. [Traditional tattoos with neurological diseases in Togo].

    PubMed

    Balogou, A A; Dodzro, K C; Grunitzky, E K

    2000-01-01

    In Africa, there are two types of health systems: the modern system and the traditional one. Traditional medicine attracts more patients, because it is more financially accessible and corresponds to cultural representations of disease in society. Traditional therapeutic tattoos are not well known by the conventional health system in West Africa, although they are commonly used by traditional healers. We report here our experience of these tattoos. We examined the skin of 36,000 patients in the neurological department of the teaching hospital of Lome from 1985 to 1995. We found three types of tattoos amongst patients. The first are tribal or social tattoos: they are large, homogeneous, located on exposed parts of the body and can be seen easily by others (fig 1: g, h, i), whilst therapeutic tattoos are slight and hidden under clothes and can also be repeated (heterogeneous). The second type of tattoo is one that reveals the patient's pathological history. The third is linked to the motive of consultation. Seventy-five per cent (75%) of patients had traditional therapeutic tattoos. Epilepsy tattoos are slim, located on the forehead (fig 1a); peripheral facial paralysis tattoos are found on the facial nerve (fig 1 b). In cases of peripheral neuropathy, tattoos are symmetrically distributed on hands and legs (fig 1 f). As for medullar compression, the highest tattoos correspond to the level of compression. Studying the localisation, age, and aim of tattoos brings to light their diagnostic, prognostic, and epidemiological interests. Skin can thus reveal itself to medical staff as an open, though coded, medical file. They need only to learn how to read it. PMID:11775325

  6. Transgenic models for cytokine-induced neurological disease

    PubMed Central

    Campbell, Iain L.; Hofer, Markus J.; Pagenstecher, Axel

    2009-01-01

    Considerable evidence supports the idea that cytokines are important mediators of pathophysiologic processes within the central nervous system (CNS). Numerous studies have documented the increased production of various cytokines in the human CNS in a variety of neurological and neuropsychiatric disorders. Deciphering cytokine actions in the intact CNS has important implications for our understanding of the pathogenesis and treatment of these disorders. One approach to address this problem that has been used widely employs transgenic mice with CNS-targeted production of different cytokines. Transgenic production of cytokines in the CNS of mice allows not only for the investigation of complex cellular responses at a localized level in the intact brain, but also more closely recapitulates the expression of these mediators as found in disease states. As discussed in this review, the findings show that these transgenic animals exhibit wide-ranging structural and functional deficits that are linked to the development of distinct neuroinflammatory responses which are relatively specific for each cytokine. These cytokine-induced alterations often recapitulate those found in various human neurological disorders not only underscoring the relevance of these models but also reinforcing the clinicopathogenetic significance of cytokines in diseases of the CNS. PMID:19835956

  7. Astrocytes: The missing link in neurological disease?

    PubMed Central

    Lin, Chia-Ching John; Deneen, Benjamin

    2013-01-01

    The central nervous system (CNS) is comprised of numerous cell types that work in concert to facilitate proper function and homeostasis. Disruption of these carefully orchestrated networks results in neuronal dysfunction, manifesting itself in a variety of neurological disorders. While neuronal dysregulation is causative of symptoms manifest in the clinic, the etiology of these disorders is often more complex than simply a loss of neurons or intrinsic dysregulation of their function. In the adult brain, astrocytes comprise the most abundant cell type and play key roles in CNS physiology, therefore it stands to reason that dysregulation of normal astrocyte function contributes to the etiology and progression of varied neurological disorders. We review here some neurological disorders associated with an astrocyte factor and discuss how the related astrocyte dysfunction contributes to the etiology and/or progression of these disorders. PMID:24365571

  8. Remote Physical Activity Monitoring in Neurological Disease: A Systematic Review

    PubMed Central

    Block, Valerie A. J.; Pitsch, Erica; Tahir, Peggy; Cree, Bruce A. C.; Allen, Diane D.; Gelfand, Jeffrey M.

    2016-01-01

    Objective To perform a systematic review of studies using remote physical activity monitoring in neurological diseases, highlighting advances and determining gaps. Methods Studies were systematically identified in PubMed/MEDLINE, CINAHL and SCOPUS from January 2004 to December 2014 that monitored physical activity for ≥24 hours in adults with neurological diseases. Studies that measured only involuntary motor activity (tremor, seizures), energy expenditure or sleep were excluded. Feasibility, findings, and protocols were examined. Results 137 studies met inclusion criteria in multiple sclerosis (MS) (61 studies); stroke (41); Parkinson's Disease (PD) (20); dementia (11); traumatic brain injury (2) and ataxia (1). Physical activity levels measured by remote monitoring are consistently low in people with MS, stroke and dementia, and patterns of physical activity are altered in PD. In MS, decreased ambulatory activity assessed via remote monitoring is associated with greater disability and lower quality of life. In stroke, remote measures of upper limb function and ambulation are associated with functional recovery following rehabilitation and goal-directed interventions. In PD, remote monitoring may help to predict falls. In dementia, remote physical activity measures correlate with disease severity and can detect wandering. Conclusions These studies show that remote physical activity monitoring is feasible in neurological diseases, including in people with moderate to severe neurological disability. Remote monitoring can be a psychometrically sound and responsive way to assess physical activity in neurological disease. Further research is needed to ensure these tools provide meaningful information in the context of specific neurological disorders and patterns of neurological disability. PMID:27124611

  9. Subcutaneous IgG in neurologic diseases.

    PubMed

    Berger, Melvin

    2014-01-01

    Subcutaneous administration of IgG (SCIG) has become widely used in primary immune deficiency diseases but it has only recently been studied for maintenance therapy in autoimmune peripheral neuropathies, such as chronic idiopathic demyelinating polyneuropathy and multifocal motor neuropathy. Weekly self-administration of SCIG is safe and well-tolerated, and results in steady-state serum IgG levels, as contrasted with the peaks and troughs of monthly immune globulin (human) for intravenous use. Freedom from the need for venous access or medical personnel for infusions, flexibility in scheduling, convenience of home therapy, and improved clinical stability due to the steady-state IgG levels, lead many patients to prefer SCIG to immune globulin (human) for intravenous use. Long-term studies are needed to determine if the constant IgG levels and clinical stability translate into better long-term outcomes.

  10. Bovine diseases causing neurological signs and death in Mexican feedlots.

    PubMed

    Ramírez-Romero, Rafael; Ramírez-Hernández, Cecilia; García-Márquez, Luis Jorge; Macedo-Barragán, Rafael Julio; Martínez-Burnes, Julio; López-Mayagoitia, Alfonso

    2014-06-01

    The number of large feedlot operations, similar to that of USA and Canada, has notably increased in Mexico in the last three decades. Clinical and laboratory diagnoses of neurological diseases in feedlot cattle are crucial in Mexico and Central America because of the high incidence of bovine paralytic rabies (BPR). Because of its zoonotic potential, BPR must be promptly diagnosed and differentiated from other bovine neurological diseases such as thrombotic meningoencephalitis (TME), polioencephalomalacia (PEM) and botulism. More recently, BPR and botulism have been diagnosed with increasing frequency in Mexican feedlots. Neither BPR nor botulism has relevant gross lesions, thus post-mortem diagnosis without laboratory support is impossible. Herein, we describe five outbreaks of neurological diseases in Mexican feedlots in which BPR, botulism and PEM were diagnosed either independently or in combination. A diagram illustrating the most conspicuous pathologic findings and ancillary laboratory test required to confirm the diagnoses of these neurological diseases in feedlot cattle is proposed.

  11. Adverse neurological outcomes in Nigerian children with sickle cell disease.

    PubMed

    Lagunju, I A; Brown, B J

    2012-12-01

    Sickle cell disease (SCD) is reported to be the most common genetic disorder affecting Nigerians. Children with SCD are at a high risk of neurological morbidity. The main objective of this study was to determine the pattern of adverse neurological outcomes among a cohort of Nigerian children with SCD. All children with SCD seen in the Department of Paediatrics, University College Hospital, Ibadan, Nigeria, over a period of 2 years were carefully evaluated for symptoms and signs of neurological complications, defined as clinical outcomes referable to the central nervous system. Of the 214 children evaluated, 187 were diagnosed with Hb SS disease and 27 with Hb SC disease. Neurological complications were identified in 78 (36.4 %) of the cases. The most common complications were headache (17.8 %), seizure (9.3 %) and stroke (8.4 %). Other less frequent complications included bacterial meningitis (2.8 %), spontaneous visual loss (1.4 %), paraplegia (0.9 %) and transient ischaemic attacks (0.9 %). Neurological complications occurred more frequently in children with sickle cell anaemia than in those with Hb SC disease (P = 0.002, 95 % CI 1.450-82.870). Adverse neurological events are common in Nigerian children with SCD, with a significantly higher risk in Hb SS than Hb SC disease. Stroke represents a major underlying cause of symptomatic epilepsy in SCD. Institution of primary preventive measures for stroke in SCD will significantly reduce the burden of stroke and epilepsy associated with SCD in Nigeria.

  12. Adverse neurological outcomes in Nigerian children with sickle cell disease.

    PubMed

    Lagunju, I A; Brown, B J

    2012-12-01

    Sickle cell disease (SCD) is reported to be the most common genetic disorder affecting Nigerians. Children with SCD are at a high risk of neurological morbidity. The main objective of this study was to determine the pattern of adverse neurological outcomes among a cohort of Nigerian children with SCD. All children with SCD seen in the Department of Paediatrics, University College Hospital, Ibadan, Nigeria, over a period of 2 years were carefully evaluated for symptoms and signs of neurological complications, defined as clinical outcomes referable to the central nervous system. Of the 214 children evaluated, 187 were diagnosed with Hb SS disease and 27 with Hb SC disease. Neurological complications were identified in 78 (36.4 %) of the cases. The most common complications were headache (17.8 %), seizure (9.3 %) and stroke (8.4 %). Other less frequent complications included bacterial meningitis (2.8 %), spontaneous visual loss (1.4 %), paraplegia (0.9 %) and transient ischaemic attacks (0.9 %). Neurological complications occurred more frequently in children with sickle cell anaemia than in those with Hb SC disease (P = 0.002, 95 % CI 1.450-82.870). Adverse neurological events are common in Nigerian children with SCD, with a significantly higher risk in Hb SS than Hb SC disease. Stroke represents a major underlying cause of symptomatic epilepsy in SCD. Institution of primary preventive measures for stroke in SCD will significantly reduce the burden of stroke and epilepsy associated with SCD in Nigeria. PMID:23129067

  13. Non-coding RNAs in chromatin disease involving neurological defects.

    PubMed

    Della Ragione, Floriana; Gagliardi, Miriam; D'Esposito, Maurizio; Matarazzo, Maria R

    2014-01-01

    Novel classes of small and long non-coding RNAs (ncRNAs) are increasingly becoming apparent, being engaged in diverse structural, functional and regulatory activities. They take part in target gene silencing, play roles in transcriptional, post-transcriptional and epigenetic processes, such as chromatin remodeling, nuclear reorganization with the formation of silent compartments and fine-tuning of gene recruitment into them. Among their functions, non-coding RNAs are thought to act either as guide or scaffold for epigenetic modifiers that write, erase, and read the epigenetic signature over the genome. Studies on human disorders caused by defects in epigenetic modifiers and involving neurological phenotypes highlight the disruption of diverse classes of non-coding RNAs. Noteworthy, these molecules mediate a wide spectrum of neuronal functions, including brain development, and synaptic plasticity. These findings imply a significant contribution of ncRNAs in pathophysiology of the aforesaid diseases and provide new concepts for potential therapeutic applications. PMID:24616662

  14. Non-coding RNAs in chromatin disease involving neurological defects.

    PubMed

    Della Ragione, Floriana; Gagliardi, Miriam; D'Esposito, Maurizio; Matarazzo, Maria R

    2014-01-01

    Novel classes of small and long non-coding RNAs (ncRNAs) are increasingly becoming apparent, being engaged in diverse structural, functional and regulatory activities. They take part in target gene silencing, play roles in transcriptional, post-transcriptional and epigenetic processes, such as chromatin remodeling, nuclear reorganization with the formation of silent compartments and fine-tuning of gene recruitment into them. Among their functions, non-coding RNAs are thought to act either as guide or scaffold for epigenetic modifiers that write, erase, and read the epigenetic signature over the genome. Studies on human disorders caused by defects in epigenetic modifiers and involving neurological phenotypes highlight the disruption of diverse classes of non-coding RNAs. Noteworthy, these molecules mediate a wide spectrum of neuronal functions, including brain development, and synaptic plasticity. These findings imply a significant contribution of ncRNAs in pathophysiology of the aforesaid diseases and provide new concepts for potential therapeutic applications.

  15. Orthotropic liver transplantation for intractable neurological manifestations of Wilson's disease.

    PubMed

    Sutariya, Vaibhav K; Tank, Anad H; Modi, Pranjal R

    2015-01-01

    Wilson's disease (WD) is an inherited autosomal recessive disorder characterized by copper accumulation and toxicity, affecting mainly the liver and brain. Orthotopic liver transplantation (OLT) is the definitive therapy for patients with WD. Acute fulminant hepatic failure and decompensated cirrhosis are well-established indications for OLT. Patients with severe neurologic impairment can also be benefited by OLT. Here, we present a patient who underwent OLT for isolated neurological WD.

  16. Fertility treatment in spinal cord injury and other neurologic disease

    PubMed Central

    Trofimenko, Vera

    2016-01-01

    Infertility in individuals with neurologic disorders is complex in etiology and manifestation. Its management therefore often requires a multimodal approach. This review addresses the implications of spinal cord injury (SCI) and other neurologic disease on fertility, including the high prevalence of sexual dysfunction, ejaculation disorders and compromised semen parameters. Available treatment approaches discussed include assisted ejaculation techniques and assisted reproductive technology including surgical sperm retrieval and intracytoplasmic sperm injection (ICSI). PMID:26904416

  17. Fertility treatment in spinal cord injury and other neurologic disease.

    PubMed

    Trofimenko, Vera; Hotaling, James M

    2016-02-01

    Infertility in individuals with neurologic disorders is complex in etiology and manifestation. Its management therefore often requires a multimodal approach. This review addresses the implications of spinal cord injury (SCI) and other neurologic disease on fertility, including the high prevalence of sexual dysfunction, ejaculation disorders and compromised semen parameters. Available treatment approaches discussed include assisted ejaculation techniques and assisted reproductive technology including surgical sperm retrieval and intracytoplasmic sperm injection (ICSI). PMID:26904416

  18. Chagas disease in a Texan horse with neurologic deficits.

    PubMed

    Bryan, Laura K; Hamer, Sarah A; Shaw, Sarah; Curtis-Robles, Rachel; Auckland, Lisa D; Hodo, Carolyn L; Chaffin, Keith; Rech, Raquel R

    2016-01-30

    A 10-year-old Quarter Horse gelding presented to the Texas A&M University Veterinary Teaching Hospital with a six month-history of ataxia and lameness in the hind limbs. The horse was treated presumptively for equine protozoal myeloencephalitis (EPM) based on clinical signs but was ultimately euthanized after its condition worsened. Gross lesions were limited to a small area of reddening in the gray matter of the thoracic spinal cord. Histologically, trypanosome amastigotes morphologically similar to Trypanosoma cruzi, the agent of Chagas disease in humans and dogs, were sporadically detected within segments of the thoracic spinal cord surrounded by mild lymphoplasmacytic inflammation. Ancillary testing for Sarcocystis neurona, Neospora spp., Toxoplasma gondii and Leishmania spp. was negative. Conventional and real time polymerase chain reaction (PCR) of affected paraffin embedded spinal cord were positive for T. cruzi, and sequencing of the amplified T. cruzi satellite DNA PCR fragment from the horse was homologous with various clones of T. cruzi in GenBank. While canine Chagas disease cases have been widely reported in southern Texas, this is the first report of clinical T. cruzi infection in an equid with demonstrable amastigotes in the spinal cord. In contrast to previous instances of Chagas disease in the central nervous system (CNS) of dogs and humans, no inflammation or T. cruzi amastigotes were detected in the heart of the horse. Based on clinical signs, there is a potential for misdiagnosis of Chagas disease with other infectious diseases that affect the equine CNS. T. cruzi should be considered as a differential diagnosis in horses with neurologic clinical signs and histologic evidence of meningomyelitis that originate in areas where Chagas disease is present. The prevalence of T. cruzi in horses and the role of equids in the parasite life cycle require further study.

  19. Neurologic and Head and Neck Manifestations of Sickle Cell Disease.

    PubMed

    Steven, Andrew; Raghavan, Prashant; Rath, Tanya J; Gandhi, Dheeraj

    2016-08-01

    Sickle cell disease is a common, inherited disordered characterized by chronic hemolytic anemia with repetitive episodes of vasoocclusion resulting from deformed red blood cells. This article reviews the most significant neurologic and head and neck manifestations of this disease. PMID:27443997

  20. [Analysis of clinical pathway in changing and disabling neurological diseases].

    PubMed

    Cordesse, V; Jametal, T; Guy, C; Lefebvre, S; Roussel, M; Ruggeri, J; Schimmel, P; Holstein, J; Meininger, V

    2013-01-01

    Neurological diseases are characterized by the complexity of care and by a constant and changing disability. More and more frequently, their impact on the clinical pathway remains unknown. Seven postgraduate rehabilitation students (Master coordination du handicap, université Pierre-et-Marie-Curie, Paris) reconstructed the clinical pathway of 123 patients with various neurological diseases: multiple sclerosis, Alzheimer disease, amyotrophic lateral sclerosis, spinal trauma, Parkinson disease and brain tumors. There was a significant correlation between disease duration and the number of specialists involved in care, the number of prescribed drugs and the number of short-term hospitalizations; there was no correlation with age. This result suggests that with time an increasing number of complications related to the initial neurological disease developed. Hospitalization in rehabilitation units was highly correlated with the degree of disability and also with the help received by the patients during the course of their disease. This result suggests that these hospitalizations were a direct consequence of burn out among relatives. General practitioners (GP) were highly involved only during the initial part of the pathway, and their involvement rapidly declined thereafter, suggesting a probable relation with the specificities and the complexity of care for neurological diseases which induces a progressive transfer of responsibilities from the GP to the hospital. Social care was always incomplete and occurred too late during the course of the disease. The feeling by the patients that their care pathway was chaotic was highly correlated with the quality of the information given to the patient at the time of the announcement of their disease. This study confirms that cares for neurological diseases is highly specific and that expert centers and coordination networks are in a key position to ensure an efficient care pathway.

  1. Ketogenic diets, mitochondria, and neurological diseases

    PubMed Central

    Gano, Lindsey B.; Patel, Manisha; Rho, Jong M.

    2014-01-01

    The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate “classic KD”, as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad neuroprotective properties of such therapies may stem from improved cellular metabolism. Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle (i.e., anaplerosis), restoration of neurotransmitter and ion channel function, and enhanced mitochondrial respiration. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. These pathways, which include PPARs, AMP-activated kinase, mammalian target of rapamycin, and the sirtuins, have all been recently implicated in the neuroprotective effects of the KD. Further research in this area may lead to future therapeutic strategies aimed at mimicking the pleiotropic neuroprotective effects of the KD. PMID:24847102

  2. The role of cannabinoids and leptin in neurological diseases.

    PubMed

    Agar, E

    2015-12-01

    Cannabinoids exert a neuroprotective influence on some neurological diseases, including Alzheimer's, Parkinson's, Huntington's, multiple sclerosis and epilepsy. Synthetic cannabinoid receptor agonists/antagonists or compounds can provide symptom relief or control the progression of neurological diseases. However, the molecular mechanism and the effectiveness of these agents in controlling the progression of most of these diseases remain unclear. Cannabinoids may exert effects via a number of mechanisms and interactions with neurotransmitters, neurotropic factors and neuropeptides. Leptin is a peptide hormone involved in the regulation of food intake and energy balance via its actions on specific hypothalamic nuclei. Leptin receptors are widely expressed throughout the brain, especially in the hippocampus, basal ganglia, cortex and cerebellum. Leptin has also shown neuroprotective properties in a number of neurological disorders, such as Parkinson's and Alzheimer's. Therefore, cannabinoid and leptin hold therapeutic potential for neurological diseases. Further elucidation of the molecular mechanisms underlying the effects on these agents may lead to the development of new therapeutic strategies for the treatment of neurological disorders. PMID:25880465

  3. The role of cannabinoids and leptin in neurological diseases.

    PubMed

    Agar, E

    2015-12-01

    Cannabinoids exert a neuroprotective influence on some neurological diseases, including Alzheimer's, Parkinson's, Huntington's, multiple sclerosis and epilepsy. Synthetic cannabinoid receptor agonists/antagonists or compounds can provide symptom relief or control the progression of neurological diseases. However, the molecular mechanism and the effectiveness of these agents in controlling the progression of most of these diseases remain unclear. Cannabinoids may exert effects via a number of mechanisms and interactions with neurotransmitters, neurotropic factors and neuropeptides. Leptin is a peptide hormone involved in the regulation of food intake and energy balance via its actions on specific hypothalamic nuclei. Leptin receptors are widely expressed throughout the brain, especially in the hippocampus, basal ganglia, cortex and cerebellum. Leptin has also shown neuroprotective properties in a number of neurological disorders, such as Parkinson's and Alzheimer's. Therefore, cannabinoid and leptin hold therapeutic potential for neurological diseases. Further elucidation of the molecular mechanisms underlying the effects on these agents may lead to the development of new therapeutic strategies for the treatment of neurological disorders.

  4. Lyme disease: neurology, neurobiology, and behavior.

    PubMed

    Halperin, John J

    2014-05-01

    The Lyme disease controversy can be largely linked to the misconception that neurobehavioral effects of illness constitute evidence of nervous system infection. Appropriate differentiation between neuroborreliosis (nervous system Borrelia burgdorferi infection) and Lyme encephalopathy (altered nervous system function in individuals with systemic but not nervous system infection)-or encephalopathies of other etiologies-would lessen the controversy considerably, as the attribution of nonspecific symptoms to supposed ongoing central nervous system infection is a major factor perpetuating the debate. Epidemiologic considerations suggest that the entities referred to as "posttreatment Lyme disease" and "chronic Lyme disease" may not actually exist but rather reflect anchoring bias, linking common, nonspecific symptoms to an antecedent medical event. On the other hand, there are data suggesting possible mechanisms by which posttreatment Lyme disease could occur.

  5. Human neurologic function and the aging process.

    PubMed

    Potvin, A R; Syndulko, K; Tourtellotte, W W; Lemmon, J A; Potvin, J H

    1980-01-01

    Sixty-one normal men whose ages ranged from 20 to 80 years were evaluated on two occasions by means of a comprehensive series of 128 instrumented tests of neurologic function. The tests measured cognition, vision, strength, steadiness, reactions, speed, coordination, fatigue, gait, station, sensations, and tasks of daily living. The reliability of each test measured was determined, and any measure found unreliable (r less than or equal to 0.41) was not further analyzed. Significant age-related linear decreases were found for almost all neurologic functions. The declines over the age span varied from less than 10 percent to more than 90 percent for different functions. For the upper extremities, the largest declines (greater than 50 percent) were in hand-force steadiness, speed of hand-arm movements, and vibration sense; for the lower extremities, the largest declines were in one-legged balance with eyes closed and in vibration sense. For 13 of 14 tests in which significant dominant body-side effects were found, larger re-testing 7-10 days later, the subjects improved their scores by more than 5 percent on only 17 tests, 9 of which concerned the activities of daily living. No significant differential learning effects were found across age groups. The results point to the importance of developing a data bank on age-based neurologic function so that therapeutic effects can be evaluated in terms of age- and sex-matched normal functioning.

  6. Dynamic diseases in neurology and psychiatry

    NASA Astrophysics Data System (ADS)

    Milton, John; Black, Deborah

    1995-03-01

    Thirty-two (32) periodic diseases of the nervous system are identified in which symptoms and/or signs recur. In 10/32, the recurrence of a symptom complex is one of the defining features of the illness, whereas in 22/32 oscillatory signs occur in the setting of an ongoing nervous system disorder. We discuss the possibility that these disorders may be dynamic diseases.

  7. Bullous pemphigoid and neurological disease: statistics from a dermatology service*

    PubMed Central

    Tarazona, Monica Jidid Mateus; Mota, Amanda Nascimento Cavalleiro de Macedo; Gripp, Alexandre Carlos; Unterstell, Natasha; Bressan, Aline Lopes

    2015-01-01

    Bullous pemphigoid (BP) is an autoimmune, acquired, cutaneous disease caused by the production of autoantibodies against hemidesmosomes' components in the basement membrane. The estimated incidence in Europe ranges from 7 to 43 cases per million inhabitants per year. Several studies have reported an association between BP and neurological disorders (ND). Our cohort of Bullous pemphigoid and ND is the first in Brazil and showed a significantly high prevalence of neurological and/or psychiatric diseases, especially cerebrovascular accident (CVA) and dementia, in agreement with the prevalence reported in several studies published in the medical literature in recent years. PMID:25831008

  8. Epigenetics and Triplet-Repeat Neurological Diseases

    PubMed Central

    Nageshwaran, Sathiji; Festenstein, Richard

    2015-01-01

    The term “junk DNA” has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterochromatinized resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions frequently exist as dinucleotide, trinucleotide, and tetranucleotide repeats. The association between repetitive regions and disease was emphasized following the discovery of abnormal trinucleotide repeats underlying spinal and bulbar muscular atrophy (Kennedy’s disease) and fragile X syndrome of mental retardation (FRAXA) in 1991. In this review, we provide a brief overview of epigenetic mechanisms and then focus on several diseases caused by DNA triplet-repeat expansions, which exhibit diverse epigenetic effects. It is clear that the emerging field of epigenetics is already generating novel potential therapeutic avenues for this group of largely incurable diseases. PMID:26733936

  9. Epigenetics and Triplet-Repeat Neurological Diseases.

    PubMed

    Nageshwaran, Sathiji; Festenstein, Richard

    2015-01-01

    The term "junk DNA" has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterochromatinized resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions frequently exist as dinucleotide, trinucleotide, and tetranucleotide repeats. The association between repetitive regions and disease was emphasized following the discovery of abnormal trinucleotide repeats underlying spinal and bulbar muscular atrophy (Kennedy's disease) and fragile X syndrome of mental retardation (FRAXA) in 1991. In this review, we provide a brief overview of epigenetic mechanisms and then focus on several diseases caused by DNA triplet-repeat expansions, which exhibit diverse epigenetic effects. It is clear that the emerging field of epigenetics is already generating novel potential therapeutic avenues for this group of largely incurable diseases. PMID:26733936

  10. Cerebellar transcranial direct current stimulation in neurological disease.

    PubMed

    Ferrucci, Roberta; Bocci, Tommaso; Cortese, Francesca; Ruggiero, Fabiana; Priori, Alberto

    2016-01-01

    Several studies have highlighted the therapeutic potential of transcranial direct current stimulation (tDCS) in patients with neurological diseases, including dementia, epilepsy, post-stroke dysfunctions, movement disorders, and other pathological conditions. Because of this technique's ability to modify cerebellar excitability without significant side effects, cerebellar tDCS is a new, interesting, and powerful tool to induce plastic modifications in the cerebellum. In this report, we review a number of interesting studies on the application of cerebellar tDCS for various neurological conditions (ataxia, Parkinson's disease, dystonia, essential tremor) and the possible mechanism by which the stimulation acts on the cerebellum. Study findings indicate that cerebellar tDCS is a promising therapeutic tool in treating several neurological disorders; however, this method's efficacy appears to be limited, given the current data. PMID:27595007

  11. [Cortical spreading depolarization: a new pathophysiological mechanism in neurological diseases].

    PubMed

    Sánchez-Porras, Renán; Robles-Cabrera, Adriana; Santos, Edgar

    2014-05-20

    Cortical spreading depolarization is a wave of almost complete depolarization of the neuronal and glial cells that occurs in different neurological diseases such as migraine with aura, subarachnoid hemorrhage, intracerebral hemorrhage, head trauma and stroke. These depolarization waves are characterized by a change in the negative potential with an amplitude between -10 and -30mV, duration of ∼1min and changes in the ion homeostasis between the intra- and extracellular space. This results in neuronal edema and dendritic distortion. Under pathologic states of hypoperfusion, cortical spreading depolarization can produce oxidative stress, worsen hypoxia and induce neuronal death. This is due to intense arterial vasoconstriction produced by an inverse response called spreading ischemia. Only in the last years there has been an electrophysiological confirmation of cortical spreading depolarization in human brains. Occurrence of cortical spreading depolarization has been associated with worse outcome in patients. Currently, increased knowledge regarding the pathophysiologic mechanisms supports the hypothetical correlation of cortical spreading depolarization with brain damage in humans. There are diverse therapeutic alternatives that promise inhibition of cortical spreading depolarization and subsequent better outcomes.

  12. [Cortical spreading depolarization: a new pathophysiological mechanism in neurological diseases].

    PubMed

    Sánchez-Porras, Renán; Robles-Cabrera, Adriana; Santos, Edgar

    2014-05-20

    Cortical spreading depolarization is a wave of almost complete depolarization of the neuronal and glial cells that occurs in different neurological diseases such as migraine with aura, subarachnoid hemorrhage, intracerebral hemorrhage, head trauma and stroke. These depolarization waves are characterized by a change in the negative potential with an amplitude between -10 and -30mV, duration of ∼1min and changes in the ion homeostasis between the intra- and extracellular space. This results in neuronal edema and dendritic distortion. Under pathologic states of hypoperfusion, cortical spreading depolarization can produce oxidative stress, worsen hypoxia and induce neuronal death. This is due to intense arterial vasoconstriction produced by an inverse response called spreading ischemia. Only in the last years there has been an electrophysiological confirmation of cortical spreading depolarization in human brains. Occurrence of cortical spreading depolarization has been associated with worse outcome in patients. Currently, increased knowledge regarding the pathophysiologic mechanisms supports the hypothetical correlation of cortical spreading depolarization with brain damage in humans. There are diverse therapeutic alternatives that promise inhibition of cortical spreading depolarization and subsequent better outcomes. PMID:23928069

  13. [Symptoms of obsessive-compulsive disorder in neurological diseases].

    PubMed

    Kutlubaev, M A

    2016-01-01

    Obsessive-compulsive disorder (OCD) is a common form of neurosis. Symptoms of OCD could develop as a sign of focal brain lesion, particularly in multiple sclerosis, extrapyramidal disorders, epilepsy, less frequently - in other diseases. Timely diagnosis and treatment of the symptoms of OCD is an important aspect in the management of mentioned neurological disorders. PMID:27240053

  14. Olfaction in Neurologic and Neurodegenerative Diseases: A Literature Review

    PubMed Central

    Godoy, Maria Dantas Costa Lima; Voegels, Richard Louis; Pinna, Fábio de Rezende; Imamura, Rui; Farfel, José Marcelo

    2014-01-01

    Introduction Loss of smell is involved in various neurologic and neurodegenerative diseases, such as Parkinson disease and Alzheimer disease. However, the olfactory test is usually neglected by physicians at large. Objective The aim of this study was to review the current literature about the relationship between olfactory dysfunction and neurologic and neurodegenerative diseases. Data Synthesis Twenty-seven studies were selected for analysis, and the olfactory system, olfaction, and the association between the olfactory dysfunction and dementias were reviewed. Furthermore, is described an up to date in olfaction. Conclusion Otolaryngologist should remember the importance of olfaction evaluation in daily practice. Furthermore, neurologists and physicians in general should include olfactory tests in the screening of those at higher risk of dementia. PMID:25992176

  15. Cerebrospinal fluid biomarkers in neurological diseases in children.

    PubMed

    Shahim, Pashtun; Månsson, Jan-Eric; Darin, Niklas; Zetterberg, Henrik; Mattsson, Niklas

    2013-01-01

    Analysis of cerebrospinal fluid (CSF) biomarkers is an integral part of neurology. Basic CSF biomarkers, such as CSF/serum albumin ratio and CSF cell counts, have been used to diagnose inflammatory and infectious CNS disorders in adults and children for decades. During recent years, however, numerous biomarkers for neuronal and astroglial injury, as well as disease-specific protein inclusions, have been developed for neurodegenerative disorders in adults. The overall aim of this paper is to give an updated overview of some of these biomarkers with special focus on their possible relevance to neurological disorders in children and adolescents.

  16. The neurologic examination in patients with probable Alzheimer's disease.

    PubMed

    Huff, F J; Boller, F; Lucchelli, F; Querriera, R; Beyer, J; Belle, S

    1987-09-01

    Abnormal findings on a standardized neurologic examination were compared between patients with a clinical diagnosis of probable Alzheimer's disease (AD) and healthy control subjects. Aside from mental status findings, the most useful examination findings for differentiating AD from control subjects were the presence of release signs, olfactory deficit, impaired stereognosis or graphesthesia, gait disorder, tremor, and abnormalities on cerebellar testing. These abnormalities probably reflect the different areas of the central nervous system that are affected pathologically in AD. In the clinical diagnosis of AD, particular attention should be given to these aspects of the neurologic examination.

  17. Epigenetic mechanisms of gene expression regulation in neurological diseases.

    PubMed

    Gos, Monika

    2013-01-01

    Neurological diseases are a heterogenous group of disorders that are related to alterations in nervous system function. The genetic background of neurological diseases is heterogenous and may include chromosomal aberrations, specific gene mutations and epigenetic defects. This review is aimed at presenting of selected diseases that are associated with different epigenetic alterations. The imprinting defects on chromosome 15 are the cause of Prader-Willi and Angelman syndromes that both are characterized by intellectual disability, developmental delay and specific behavioral phenotype. Besides the imprinting defect, these diseases can also be caused by deletion of chromosome 15 or uniparental disomy. Aberrant epigenetic regulation is also specific for Fragile X syndrome that is caused by expansion of CGG repeats in the FMR1 gene that leads to global methylation of the promoter region and repression of FMR1 transcription. A number of neurological diseases, mainly associated with intellectual impairment, may be caused by mutations in genes encoding proteins involved in epigenetic regulation. The number of such diseases is rapidly growing thanks to the implementation of genomic sequencing for the identification of their molecular causes. One of the best known diseases linked to defects in epigenetic modifiers is Rett syndrome caused by a mutation in the MECP2 gene or its variant - Rett-like syndrome caused by a mutation in CDKL5 or FOXG1 genes. As the epigenetic signature is potentially reversible, much attention is focused on possible therapies with drugs that influence DNA or histone modifications. This is especially important in the case of neurological disorders in which epigenetic changes are observed as the effect of the disease.

  18. Stem cell transplantation in neurological diseases: improving effectiveness in animal models

    PubMed Central

    Adami, Raffaella; Scesa, Giuseppe; Bottai, Daniele

    2014-01-01

    Neurological diseases afflict a growing proportion of the human population. There are two reasons for this: first, the average age of the population (especially in the industrialized world) is increasing, and second, the diagnostic tools to detect these pathologies are now more sophisticated and can be used on a higher percentage of the population. In many cases, neurological disease has a pharmacological treatment which, as in the case of Alzheimer's disease, Parkinson's disease, Epilepsy, and Multiple Sclerosis can reduce the symptoms and slow down the course of the disease but cannot reverse its effects or heal the patient. In the last two decades the transplantation approach, by means of stem cells of different origin, has been suggested for the treatment of neurological diseases. The choice of slightly different animal models and the differences in methods of stem cell preparation make it difficult to compare the results of transplantation experiments. Moreover, the translation of these results into clinical trials with human subjects is difficult and has so far met with little success. This review seeks to discuss the reasons for these difficulties by considering the differences between human and animal cells (including isolation, handling and transplantation) and between the human disease model and the animal disease model. PMID:25364724

  19. Translational neurophysiology in sheep: measuring sleep and neurological dysfunction in CLN5 Batten disease affected sheep

    PubMed Central

    Perentos, Nicholas; Martins, Amadeu Q.; Watson, Thomas C.; Bartsch, Ullrich; Mitchell, Nadia L.; Palmer, David N.; Jones, Matthew W.

    2015-01-01

    Creating valid mouse models of slowly progressing human neurological diseases is challenging, not least because the short lifespan of rodents confounds realistic modelling of disease time course. With their large brains and long lives, sheep offer significant advantages for translational studies of human disease. Here we used normal and CLN5 Batten disease affected sheep to demonstrate the use of the species for studying neurological function in a model of human disease. We show that electroencephalography can be used in sheep, and that longitudinal recordings spanning many months are possible. This is the first time such an electroencephalography study has been performed in sheep. We characterized sleep in sheep, quantifying characteristic vigilance states and neurophysiological hallmarks such as sleep spindles. Mild sleep abnormalities and abnormal epileptiform waveforms were found in the electroencephalographies of Batten disease affected sheep. These abnormalities resemble the epileptiform activity seen in children with Batten disease and demonstrate the translational relevance of both the technique and the model. Given that both spontaneous and engineered sheep models of human neurodegenerative diseases already exist, sheep constitute a powerful species in which longitudinal in vivo studies can be conducted. This will advance our understanding of normal brain function and improve our capacity for translational research into neurological disorders. PMID:25724202

  20. Dysprosody nonassociated with neurological diseases--a case report.

    PubMed

    Pinto, José Antonio; Corso, Renato José; Guilherme, Ana Cláudia Rocha; Pinho, Sílvia Rebelo; Nóbrega, Monica de Oliveira

    2004-03-01

    Dysprosody also known as pseudo-foreign dialect, is the rarest neurological speech disorder. It is characterized by alterations in intensity, in the timing of utterance segments, and in rhythm, cadency, and intonation of words. The terms refers to changes as to duration, fundamental frequency, and intensity of tonic and atonic syllables of the sentences spoken, which deprive an individual's particular speech of its characteristics. The cause of this disease is usually associated with neurological pathologies such as brain vascular accidents, cranioencephalic traumatisms, and brain tumors. The authors report a case of dysprosody attended to at the Núcleo de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço de São Paulo (NOSP). It is about a female patient with bilateral III degree Reinke's edema and normal neurological examinations that started presenting characteristics of the German dialect following a larynx microsurgery.

  1. Liver transplantation for hepatic and neurological Wilson's disease.

    PubMed

    Geissler, I; Heinemann, K; Rohm, S; Hauss, J; Lamesch, P

    2003-06-01

    Wilson's disease (WD) is an autosomal-recessive inherited disorder of copper metabolism characterized by excessive deposition of copper throughout the body. If medical treatment fails in cases of fulminant hepatic failure and progressive hepatic dysfunction due to advanced cirrhosis, liver transplantation (OLTx) has been demonstrated to be a valuable treatment option. Between December 1993 and December 2002, 225 OLTxs in 198 patients were performed in our institution. In this consecutive series six patients (three females and three males) were liver grafted for WD. The follow-up ranged from 3 to 7 years. All patients are alive with well-functioning grafts at present. The ceruloplasmin levels increased after transplantation and remained normal. The Kayser-Fleischer ring disappeared in all patients, and urinary copper excretion normalized. The neurological manifestations in the two patients with severe neurological symptoms showed after 2 to 5 years a downward tendency; in one the ataxic movements disappeared completely. The psychiatric disorder in one patient disappeared as well the mild neurological symptoms in the patient with CHILD A cirrhosis. These two patients are fully recovered and returned to work. OLTx should be considered as a treatment option in patients with severe progressive neurological deficits even in cases with stable liver function since liver grafting definitely cures the underlying biochemical defect. In such cases an early decision for liver transplantation is justified because neurological deficits may become irreversible.

  2. Neurological control of human sexual behaviour: insights from lesion studies

    PubMed Central

    Baird, Amee D; Wilson, Sarah J; Bladin, Peter F; Saling, Michael M; Reutens, David C

    2007-01-01

    We review the human literature examining the effects of neurological insult on human sexual behaviour. We provide a synthesis of the findings to date, and identify key brain regions associated with specific aspects of human sexual behaviour. These include subcortical and cortical regions, with the mesial temporal lobe and the amygdala in particular being a crucial structure in the mediation of human sexual drive. PMID:17189299

  3. Approaching neurological diseases to reduce mobility limitations in older persons.

    PubMed

    Lauretani, Fulvio; Ceda, Gian Paolo; Pelliccioni, Pio; Ruffini, Livia; Nardelli, Anna; Cherubini, Antonio; Maggio, Marcello

    2014-01-01

    The rapidly increasing elderly population poses a major challenge for future health-care systems. Neurological diseases in older persons are particularly common and coexist with other clinical conditions. This is not surprising given that, for example, even patients with Alzheimer Disease (AD) could have relevant extrapyramidal signs at the moment of the diagnosis with motor signs having more negative prognostic value. Longitudinal studies conducted on Parkinson Disease (PD) showed that, after 20 years, dementia is not only present in almost all survivors but is also the main factor influencing nursing home admission. Recently, it has been reported the importance of Comprehensive Geriatric Assessment (CGA: comprehensive evaluation of cognition, depressive symptoms, mobility and functional assessment) as a tool reducing morbidity in frail older patients admitted to any acute hospital unit. The CGA should be considered as a technological device, for physicians who take care of older persons affected by overlapping neurological diseases. CGA is an extraordinary and cost effective instrument even in patients with advanced neurological diseases where allows to collect valuable information for an effective plan of management.

  4. Neurologic and Psychiatric Manifestations of Celiac Disease and Gluten Sensitivity

    PubMed Central

    Jackson, Jessica R.; Eaton, William W.; Cascella, Nicola G.; Fasano, Alessio

    2013-01-01

    Celiac Disease (CD) is an immune-mediated disease dependent on gluten (a protein present in wheat, rye or barley) that occurs in about 1% of the population and is generally characterized by gastrointestinal complaints. More recently the understanding and knowledge of gluten sensitivity (GS), has emerged as an illness distinct from celiac disease with an estimated prevalence 6 times that of CD. Gluten sensitive people do not have villous atrophy or antibodies that are present in celiac disease, but rather they can test positive for antibodies to gliadin. Both CD and GS may present with a variety of neurologic and psychiatric co-morbidities, however, extraintestinal symptoms may be the prime presentation in those with GS. However, gluten sensitivity remains undertreated and underrecognized as a contributing factor to psychiatric and neurologic manifestiations. This review focuses on neurologic and psychiatric manifestations implicated with gluten sensitivity, reviews the emergence of gluten sensitivity distinct from celiac disease, and summarizes the potential mechanisms related to this immune reaction. PMID:21877216

  5. Brain Molecular Aging, Promotion of Neurological Disease and Modulation by Sirtuin5 Longevity Gene Polymorphism

    PubMed Central

    Glorioso, Christin; Oh, Sunghee; Douillard, Gaelle Guilloux; Sibille, Etienne

    2010-01-01

    Mechanisms determining characteristic age of onset for neurological diseases are largely unknown. Normal brain aging associates with robust and progressive transcriptome changes (“molecular aging”), but the intersection with disease pathways is mostly uncharacterized. Here, using cross-cohort microarray analysis of four human brain areas, we show that neurological disease pathways largely overlap with molecular aging and that subjects carrying a newly-characterized low-expressing polymorphism in a putative longevity gene (Sirtuin5; SIRT5prom2) have older brain molecular ages. Specifically, molecular aging was remarkably conserved across cohorts and brain areas, and included numerous developmental and transcription-regulator genes. Neurological disease-associated genes were highly overrepresented within age-related genes and changed almost unanimously in pro-disease directions, together suggesting an underlying genetic “program” of aging that progressively promotes disease. To begin testing this putative pathway, we developed and used an age-biosignature to assess five candidate longevity gene polymorphisms association with molecular aging rates. Most robustly, aging was accelerated in cingulate, but not amygdala, of subjects carrying a SIRT5 promoter polymorphism (+9yrs, p=0.004), in concordance with cingulate-specific decreased SIRT5 expression. This effect was driven by a set of core transcripts (+24 yrs, p=0.0004), many of which were mitochondrial, including Parkinson’s disease genes, PINK1 and DJ1/PARK7, hence suggesting that SIRT5prom2 may represent a risk factor for mitochondrial dysfunction-related diseases, including Parkinson s, through accelerated molecular aging of disease-related genes. Based on these results we speculate that a “common mechanism” may underlie age of onset across several neurological diseases. Confirming this pathway and its regulation by common genetic variants would provide new strategies for predicting, delaying, and

  6. Rare neurological diseases: a practical approach to management.

    PubMed

    Dani, Krishna A; Murray, Lesley J; Razvi, Saif

    2013-08-01

    Although neurologists are frequently faced with the management of rare diseases, there is little generic guidance for the approach to management. There are complexities with respect to diagnosis, counselling, treatment and monitoring which are idiosyncratic to rare diseases. Here we use a case report as the basis for discussion of the management of rare neurological diseases. We discuss current issues, guidance from regulatory bodies, and offer practical tips for diagnosis, treatment and monitoring, including the use of decision tree analysis. We offer a generic algorithm to aid neurologists when facing rare conditions.

  7. K-Cl cotransporters, cell volume homeostasis, and neurological disease.

    PubMed

    Kahle, Kristopher T; Khanna, Arjun R; Alper, Seth L; Adragna, Norma C; Lauf, Peter K; Sun, Dandan; Delpire, Eric

    2015-08-01

    K(+)-Cl(-) cotransporters (KCCs) were originally characterized as regulators of red blood cell (RBC) volume. Since then, four distinct KCCs have been cloned, and their importance for volume regulation has been demonstrated in other cell types. Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1-related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have demonstrated the evolutionary necessity of these molecules for nervous system cell volume regulation, structure, and function, and their involvement in neurological disease. The recent characterization of a swelling-activated dephosphorylation mechanism that potently stimulates the KCCs has pinpointed a potentially druggable switch of KCC activity. An improved understanding of WNK/SPAK-mediated KCC cell volume regulation in the nervous system might reveal novel avenues for the treatment of multiple neurological diseases. PMID:26142773

  8. Divergent Astrovirus Associated with Neurologic Disease in Cattle

    PubMed Central

    Li, Linlin; Diab, Santiago; McGraw, Sabrina; Barr, Bradd; Traslavina, Ryan; Higgins, Robert; Talbot, Tom; Blanchard, Pat; Rimoldi, Guillermo; Fahsbender, Elizabeth; Page, Brady; Phan, Tung Gia; Wang, Chunlin; Deng, Xutao; Delwart, Eric

    2013-01-01

    Using viral metagenomics of brain tissue from a young adult crossbreed steer with acute onset of neurologic disease, we sequenced the complete genome of a novel astrovirus (BoAstV-NeuroS1) that was phylogenetically related to an ovine astrovirus. In a retrospective analysis of 32 cases of bovine encephalitides of unknown etiology, 3 other infected animals were detected by using PCR and in situ hybridization for viral RNA. Viral RNA was restricted to the nervous system and detected in the cytoplasm of affected neurons within the spinal cord, brainstem, and cerebellum. Microscopically, the lesions were of widespread neuronal necrosis, microgliosis, and perivascular cuffing preferentially distributed in gray matter and most severe in the cerebellum and brainstem, with increasing intensity caudally down the spinal cord. These results suggest that infection with BoAstV-NeuroS1 is a potential cause of neurologic disease in cattle. PMID:23965613

  9. Nutritional Alterations Associated with Neurological and Neurosurgical Diseases.

    PubMed

    Dionyssiotis, Yannis; Papachristos, Aris; Petropoulou, Konstantina; Papathanasiou, Jannis; Papagelopoulos, Panayiotis

    2016-01-01

    Neurological and neurosurgical diseases lead to complications producing malnutrition increasing pathology and mortality. In order to avoid complications because of malnutrition or overcome deficiencies in nutrients supplements are often used for these subjects. The physiopathological mechanisms of malnutrition, methods of nutritional assessment and the supplemental support are reviewed in this paper based on the assumption that patients need to receive adequate nutrition to promote optimal recovery, placing nutrition as a first line treatment and not an afterthought in the rehabilitation. PMID:27563361

  10. Nutritional Alterations Associated with Neurological and Neurosurgical Diseases

    PubMed Central

    Dionyssiotis, Yannis; Papachristos, Aris; Petropoulou, Konstantina; Papathanasiou, Jannis; Papagelopoulos, Panayiotis

    2016-01-01

    Neurological and neurosurgical diseases lead to complications producing malnutrition increasing pathology and mortality. In order to avoid complications because of malnutrition or overcome deficiencies in nutrients supplements are often used for these subjects. The physiopathological mechanisms of malnutrition, methods of nutritional assessment and the supplemental support are reviewed in this paper based on the assumption that patients need to receive adequate nutrition to promote optimal recovery, placing nutrition as a first line treatment and not an afterthought in the rehabilitation. PMID:27563361

  11. [Features of neurologic semiotics at chronic obstructive pulmonary disease].

    PubMed

    Litvinenko, I V; Baranov, V L; Kolcheva, Iu A

    2011-01-01

    Chronic obstructive pulmonary disease (COPD) is actual pathology, when it forms the mixed hypoxemia. In the conditions of a chronic hypoxemia structures of organism with high level of metabolic processes, namely brain tissues, suffer. Character of defeat of the central nervous system at that pathology is insufficiently studied. In this article we studied and analysed the presence of such changes as depression, anxiety, cognitive impairment and features of neurologic semiotics at COPD in 50 patients.

  12. Diametrical diseases reflect evolutionary-genetic tradeoffs: Evidence from psychiatry, neurology, rheumatology, oncology and immunology.

    PubMed

    Crespi, Bernard J; Go, Matthew C

    2015-01-01

    Tradeoffs centrally mediate the expression of human adaptations. We propose that tradeoffs also influence the prevalence and forms of human maladaptation manifest in disease. By this logic, increased risk for one set of diseases commonly engenders decreased risk for another, diametric, set of diseases. We describe evidence for such diametric sets of diseases from epidemiological, genetic and molecular studies in four clinical domains: (i) psychiatry (autism vs psychotic-affective conditions), (ii) rheumatology (osteoarthritis vs osteoporosis), (iii) oncology and neurology (cancer vs neurodegenerative disorders) and (iv) immunology (autoimmunity vs infectious disease). Diametric disorders are important to recognize because genotypes or environmental factors that increase risk for one set of disorders protect from opposite disorders, thereby providing novel and direct insights into disease causes, prevention and therapy. Ascertaining the mechanisms that underlie disease-related tradeoffs should also indicate means of circumventing or alleviating them, and thus reducing the incidence and impacts of human disease in a more general way. PMID:26354001

  13. Unintended Effects of Orphan Product Designation for Rare Neurological Diseases

    PubMed Central

    Murphy, Sinéad M; Puwanant, Araya; Griggs, Robert C.

    2012-01-01

    Since the introduction of the Orphan Drug Act in 1983, designed to promote development of treatments for rare diseases, at least 378 orphan drugs have been approved. Incentives include financial support, tax credits and, perhaps most importantly, extended market exclusivity. These incentives have encouraged industry interest and accelerated research on rare diseases, allowing patients with orphan diseases access to treatments. However, extended market exclusivity has been associated with unacceptably high drug costs; both for newly developed drugs and even for drugs which were previously widely available. We suggest that a paradoxical effect of orphan product exclusivity can be reduced patient access to existing drugs. In addition, the costs of each new drug are arguably unsustainable for patients and for the American health care system. Of all the specialties, neurology has the third highest number of orphan product designations, and neurological diseases account for at least one fifth of rare diseases. Citing the use of tetrabenazine for chorea in Huntington’s disease, adrenocorticotropic hormone for infantile spasms and enzyme replacement therapy with alglucosidase alpha for Pompe’s disease we highlight these paradoxical effects. PMID:23109143

  14. Unintended effects of orphan product designation for rare neurological diseases.

    PubMed

    Murphy, Sinéad M; Puwanant, Araya; Griggs, Robert C

    2012-10-01

    Since the introduction of the Orphan Drug Act in 1983, designed to promote development of treatments for rare diseases, at least 378 orphan drugs have been approved. Incentives include financial support, tax credits, and perhaps most importantly, extended market exclusivity. These incentives have encouraged industry interest and accelerated research on rare diseases, allowing patients with orphan diseases access to treatments. However, extended market exclusivity has been associated with unacceptably high drug costs, both for newly developed drugs and for drugs that were previously widely available. We suggest that a paradoxical effect of orphan product exclusivity can be reduced patient access to existing drugs. In addition, the costs of each new drug are arguably unsustainable for patients and for the American health care system. Of all the specialties, neurology has the third highest number of orphan product designations, and neurological diseases account for at least one-fifth of rare diseases. Citing the use of tetrabenazine for chorea in Huntington disease, adrenocorticotropic hormone for infantile spasms, and enzyme replacement therapy with alglucosidase alpha for Pompe disease, we highlight these paradoxical effects.

  15. Primary Epstein-Barr-virus infections in acute neurologic diseases.

    PubMed

    Grose, C; Henle, W; Henle, G; Feorino, P M

    1975-02-20

    Infectious mononucleosis has been associated with Guillain--Barré syndrome, Bell's palsy, meningoencephalitis and transverse myelitis. Since it is not known that many children with infectious mononucleosis do not develop heterophil antibodies, we looked for evidence of current or recent Epstein-Barr virus infection in young patients with these neurologic diseases by using serodiagnostic procedures for detection and titration of antibodies to various antigens related to Epstein-Barr virus. Seven of 24 cases with Guillain-Barre syndrome and three of 16 with facial palsy were definitely associated with primary infection with Epstein-Barr virus as were two cases each of the other two neurologic diseases. Only one of these patients had obvious clinical infectious mononucleosis, and only a few demonstrated heterophil agglutinins. It is evident that the virus must be considered in the diagnosis of various acute neurologic diseases affecting children and young adults, even in the absence of heterophil-antibody response or other signs of infectious mononucleosis.

  16. Understanding neurological disease mechanisms in the era of epigenetics.

    PubMed

    Qureshi, Irfan A; Mehler, Mark F

    2013-06-01

    The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type-specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues.

  17. Could a neurological disease be a part of Mozart's pathography?

    PubMed

    Ivkić, Goran; Erdeljić, Viktorija

    2011-01-01

    As expected, since we recently celebrated the 250th anniversary of birth of Wolfgang Amadeus Mozart, there has been again a renewal of interest in his short but intensive life, as well as in the true reason of his untimely dead. Mozart lived and died in time when the medical knowledge was based mostly on subjective observations, without the established basics of standardized medical terminology and methodology. This leaves a great space for hypothesizing about his health problems, as well as about the cause of his death. The medical academic community attributed to Mozart approximately 150 different medical diagnoses. There is much speculation on the possible causes of Mozart's death: uremia, infection, rheumatic fever, trichinellosis, etc. Recently some authors have raised the question about a possible concomitant neurological disease. According to available records, Mozart has shown some elements of cyclotimic disorder, epilepsy and Gilles de la Tourette syndrome. Furthermore, the finding of a temporal fracture on (allegedly) Mozart's skull, gives a way to speculations about the possibility of a chronic subdural hematoma and its compressive effect on the temporal lobe. Despite numerous theories on Mozart's pathography that also include a concomitant neurological disorder, the medical and history records about Mozart's health status indicate that he probably had suffered from an infective illness, followed most likely by the reactivation of rheumatic fever, which was followed by strong immunologic reaction in the last days of his life. Taking all the above into consideration, it is reasonably to conclude that Mozart's neurological disturbances were caused by the intensity of the infective disease, and not primarily by a neurological disease.

  18. An autoinflammatory neurological disease due to interleukin 6 hypersecretion

    PubMed Central

    2013-01-01

    Autoinflammatory diseases are rare illnesses characterized by apparently unprovoked inflammation without high-titer auto-antibodies or antigen-specific T cells. They may cause neurological manifestations, such as meningitis and hearing loss, but they are also characterized by non-neurological manifestations. In this work we studied a 30-year-old man who had a chronic disease characterized by meningitis, progressive hearing loss, persistently raised inflammatory markers and diffuse leukoencephalopathy on brain MRI. He also suffered from chronic recurrent osteomyelitis of the mandible. The hypothesis of an autoinflammatory disease prompted us to test for the presence of mutations in interleukin-1−pathway genes and to investigate the function of this pathway in the mononuclear cells obtained from the patient. Search for mutations in genes associated with interleukin-1−pathway demonstrated a novel NLRP3 (CIAS1) mutation (p.I288M) and a previously described MEFV mutation (p.R761H), but their combination was found to be non-pathogenic. On the other hand, we uncovered a selective interleukin-6 hypersecretion within the central nervous system as the likely pathogenic mechanism. This is also supported by the response to the anti-interleukin-6−receptor monoclonal antibody tocilizumab, but not to the recombinant interleukin-1−receptor antagonist anakinra. Exome sequencing failed to identify mutations in other genes known to be involved in autoinflammatory diseases. We propose that the disease described in this patient might be a prototype of a novel category of autoinflammatory diseases characterized by prominent neurological involvement. PMID:23432807

  19. Therapeutic Effects of Bee Venom on Immunological and Neurological Diseases

    PubMed Central

    Hwang, Deok-Sang; Kim, Sun Kwang; Bae, Hyunsu

    2015-01-01

    Bee Venom (BV) has long been used in Korea to relieve pain symptoms and to treat inflammatory diseases, such as rheumatoid arthritis. The underlying mechanisms of the anti-inflammatory and analgesic actions of BV have been proved to some extent. Additionally, recent clinical and experimental studies have demonstrated that BV and BV-derived active components are applicable to a wide range of immunological and neurodegenerative diseases, including autoimmune diseases and Parkinson’s disease. These effects of BV are known to be mediated by modulating immune cells in the periphery, and glial cells and neurons in the central nervous system. This review will introduce the scientific evidence of the therapeutic effects of BV and its components on several immunological and neurological diseases, and describe their detailed mechanisms involved in regulating various immune responses and pathological changes in glia and neurons. PMID:26131770

  20. An overview of neurological and neuromuscular signs in mitochondrial diseases.

    PubMed

    Chaussenot, A; Paquis-Flucklinger, V

    2014-05-01

    Mitochondrial disorders have a broad clinical spectrum and are genetically heterogeneous, involving two genomes. These disorders may be develop at any age, with isolated or multiple system involvement, and any pattern of inheritance. Neurological involvement is the most frequent, and concerns muscular, peripheral and central nervous system. Among these diverse signs, some are suggestive of mitochondrial disease, such as progressive external ophthalmoplegia, exercise intolerance, psychomotor regression, stroke-like episodes, refractory epilepsy and Epilepsia Partialis Continua. Others are less specific and mitochondrial hypothesis may be evocated because of either association of different neuromuscular signs or a multisystemic involvement. This review describes the wealth of this neurological and neuromuscular symptomatology through different syndromes reported in the literature, according to preponderant signs and to modes of inheritance, as key elements to guide genetics testing.

  1. Texas Occurrence of Lyme Disease and Its Neurological Manifestations

    PubMed Central

    Dandashi, Jad A; Nizamutdinov, Damir; Dayawansa, Samantha; Fonkem, Ekokobe; Huang, Jason H

    2016-01-01

    Today, Lyme disease is the most commonly reported tick-borne disease in the United States and Europe. The culprits behind Lyme disease are the Borrelia species of bacteria. In the USA, Borrelia burgdorferi causes the majority of cases, while in Europe and Asia Borrelia afzelii and Borrelia garinii carry the greatest burden of disease. The clinical manifestations of Lyme disease have been identified as early localized, early disseminated, and late chronic. The neurological effects of Lyme disease include both peripheral and central nervous systems involvement, including focal nerve abnormalities, cranial neuropathies, painful radiculoneuritis, meningitis, and/or toxic metabolic encephalopathy, known as Lyme encephalopathy. Given the geographic predominance of Lyme disease in the Northeast and Midwest of the USA, no major studies have been conducted regarding Southern states. Between 2005 and 2014, the Center for Disease Control has reported 582 confirmed cases of Lyme disease in Texas. Because of the potential for increased incidence and prevalence in Texas, it has become essential for research and clinical efforts to be diverted to the region. The Texas A&M College of Veterinary Medicine and Biomedical Sciences Lyme Lab has been investigating the ecology of Lyme disease in Texas and developing a pan-specific serological test for Lyme diagnosis. This report aimed to exposure materials and raise awareness of Lyme disease to healthcare providers. PMID:27478852

  2. Progress and prospects: stem cells and neurological diseases.

    PubMed

    Gögel, S; Gubernator, M; Minger, S L

    2011-01-01

    The central nervous system has limited capacity of regenerating lost tissue in slowly progressive, degenerative neurological conditions such as Parkinson's disease (PD), Alzheimer's disease or Huntington's disease (HD), or in acute injuries resulting in rapid cell loss for example, in cerebrovascular damage (for example, stroke) or spinal cord injury. Although the adult brain contains small numbers of stem cells in restricted areas, they do not contribute significantly to functional recovery. Transplantation of stem cells or stem cell-derived progenitors has long been seen as a therapeutic solution to repair the damaged brain. With the advent of the induced pluripotent stem cells technique a new and potentially better source for transplantable cells may be available in future. This review aims to highlight current strategies to replace lost cellular populations in neurodegenerative diseases with the focus on HD and PD and traumatic brain injuries such as stroke, discussing many of the technical and biological issues associated with central nervous system cell transplantation. PMID:20882052

  3. Neurological findings in Alzheimer's disease and normal aging.

    PubMed

    Galasko, D; Kwo-on-Yuen, P F; Klauber, M R; Thal, L J

    1990-06-01

    To determine the potential value of abnormal neurological findings as markers of Alzheimer's disease (AD) and their relationship to the stage of AD, we compared standardized neurological examinations in 135 community-dwelling patients with AD and 91 nondemented elderly individuals. After correcting for differences in age and education between the two groups, we found that rigidity, stooped posture, graphesthesia, neglect of simultaneous tactile stimuli (face-hand test), and snout, grasp, and glabella reflexes were present significantly more often in patients with AD than in control subjects. These findings increased in prevalence in patients with AD according to the severity of dementia. However, in a multivariate logistic regression model only the grasp reflex, graphesthesia, and the face-hand test were statistically significantly associated with the degree of cognitive impairment. Although abnormal neurological findings occur regularly in AD, they are too infrequent early in the course of AD to serve as diagnostic markers. Prospective studies are needed to determine whether patients with the early onset of extrapyramidal or other findings form a distinct subgroup of AD.

  4. Genomic Discoveries and Personalized Medicine in Neurological Diseases

    PubMed Central

    Zhang, Li; Hong, Huixiao

    2015-01-01

    In the past decades, we have witnessed dramatic changes in clinical diagnoses and treatments due to the revolutions of genomics and personalized medicine. Undoubtedly we also met many challenges when we use those advanced technologies in drug discovery and development. In this review, we describe when genomic information is applied in personal healthcare in general. We illustrate some case examples of genomic discoveries and promising personalized medicine applications in the area of neurological disease particular. Available data suggest that individual genomics can be applied to better treat patients in the near future. PMID:26690205

  5. Imaging Microglial Activation with TSPO PET: Lighting Up Neurologic Diseases?

    PubMed

    Vivash, Lucy; O'Brien, Terence J

    2016-02-01

    Neuroinflammation is implicated in the pathogenesis of a wide range of neurologic and neuropsychiatric diseases. For over 20 years, (11)C-PK11195 PET, which aims to image expression of the translocator protein (TSPO) on activated microglia in the brain, has been used in preclinical and clinical research to investigate neuroinflammation in vivo in patients with brain diseases. However, (11)C-PK11195 suffers from two major limitations: its low brain permeability and high nonspecific and plasma binding results in a low signal-to-noise ratio, and the use of (11)C restricts its use to PET research centers and hospitals with an on-site cyclotron. In recent years, there has been a great deal of work into the development of new TSPO-specific PET radiotracers. This work has focused on fluorinated radiotracers, which would enable wider use and improved signal-to-noise ratios. These radiotracers have been utilized in preclinical and clinical studies of several neurologic diseases with varying degrees of success. Unfortunately, the application of these second-generation TSPO radiotracers has revealed additional problems, including a polymorphism that affects TSPO binding. In this review, the developments in TSPO imaging are discussed, and current limitations and suggestions for future directions are explored.

  6. Molecular genetics, recombinant DNA techniques, and genetic neurological disease.

    PubMed

    Rosenberg, R N

    1984-06-01

    The molecular defects responsible for Huntington's disease, the spinocerebellar degenerations, myotonic muscular dystrophy, neurofibromatosis, and tuberous sclerosis, among other major dominant inherited diseases of the nervous system, will be identified using the new techniques of molecular genetics. With synthesized nucleic acid segments complementary to portions of the patient's DNA, known as complementary DNA probes, it will be possible to identify and isolate the mutant gene responsible for a particular disease. These events are referred to as gene cloning. In addition, complex genetic regulatory mechanisms involved in cell differentiation during neuroembryogenesis will be elucidated with the application of these strategies. It is important for the clinician to become familiar with the precision and potential of these new methodologies, because they will soon influence significantly the practice of neurology.

  7. Frontiers in therapeutic development of allopregnanolone for Alzheimer’s disease and other neurological disorders

    PubMed Central

    Irwin, Ronald W.; Solinsky, Christine M.; Brinton, Roberta Diaz

    2014-01-01

    Allopregnanolone (Allo), a neurosteroid, has emerged as a promising promoter of endogenous regeneration in brain. In a mouse model of Alzheimer’s disease, Allo induced neurogenesis, oligodendrogenesis, white matter generation and cholesterol homeostasis while simultaneously reducing β-amyloid and neuroinflammatory burden. Allo activates signaling pathways and gene expression required for regeneration of neural stem cells and their differentiation into neurons. In parallel, Allo activates systems to sustain cholesterol homeostasis and reduce β-amyloid generation. To advance Allo into studies for chronic human neurological conditions, we examined translational and clinical parameters: dose, regimen, route, formulation, outcome measures, and safety regulations. A treatment regimen of once per week at sub-sedative doses of Allo was optimal for regeneration and reduction in Alzheimer’s pathology. This regimen had a high safety profile following chronic exposure in aged normal and Alzheimer’s mice. Formulation of Allo for multiple routes of administration has been developed for both preclinical and clinical testing. Preclinical evidence for therapeutic efficacy of Allo spans multiple neurological diseases including Alzheimer’s, Parkinson’s, multiple sclerosis, Niemann-Pick, diabetic neuropathy, status epilepticus, and traumatic brain injury. To successfully translate Allo as a therapeutic for multiple neurological disorders, it will be necessary to tailor dose and regimen to the targeted therapeutic mechanisms and disease etiology. Treatment paradigms conducted in accelerated disease models in young animals have a low probability of successful translation to chronic diseases in adult and aged humans. Gender, genetic risks, stage and burden of disease are critical determinants of efficacy. This review focuses on recent advances in development of Allo for Alzheimer’s disease (AD) that have the potential to accelerate therapeutic translation for multiple unmet

  8. Stem and Progenitor Cell-Derived Astroglia Therapies for Neurological Diseases.

    PubMed

    Chen, Chen; Chan, Albert; Wen, Han; Chung, Seung-Hyuk; Deng, Wenbin; Jiang, Peng

    2015-11-01

    Astroglia are a major cellular constituent of the central nervous system (CNS) and play crucial roles in brain development, function, and integrity. Increasing evidence demonstrates that astroglia dysfunction occurs in a variety of neurological disorders ranging from CNS injuries to genetic diseases and chronic degenerative conditions. These new insights herald the concept that transplantation of astroglia could be of therapeutic value in treating the injured or diseased CNS. Recent technological advances in the generation of human astroglia from stem and progenitor cells have been prominent. We propose that a better understanding of the suitability of astroglial cells in transplantation as well as of their therapeutic effects in animal models may lead to the establishment of astroglia-based therapies to treat neurological diseases. PMID:26443123

  9. Neurologic Complications of HIV Disease and Their Treatment

    PubMed Central

    Letendre, Scott L.; Ellis, Ronald J.; Everall, Ivan; Ances, Beau; Bharti, Ajay; McCutchan, J. Allen

    2011-01-01

    Substantial work on the peripheral and central nervous system complications of HIV was presented at the 16th Conference on Retroviruses and Opportunistic Infections. Six studies of more than 4500 volunteers identified that distal sensory polyneuropathy remains common, ranging from 19% to 66%, with variation based on disease stage, type of antiretroviral therapy, age, and height. Eight studies of more than 2500 volunteers identified that neurocognitive disorders are also common, ranging from 25% to 69%, with variation based on stage of disease, antiretroviral use, diabetes mellitus, and coinfection with hepatitis viruses. Therapy-focused studies identified that resistance testing of cerebrospinal fluid (CSF)-derived HIV may improve management of people with HIV-associated neurologic complications, that poorly penetrating antiretroviral therapy is associated with persistent low-level HIV RNA in CSF, and that efavirenz concentrations in CSF are low but in the therapeutic range in most individuals. Neuroimaging reports identified that people living with HIV had abnormal findings on magnetic resonance imaging (gray matter atrophy, abnormal white matter), magnetic resonance spectroscopy (lower neuronal metabolites), and blood-oxygen-level dependent functional magnetic resonance imaging (lower cerebral blood flow). Other important findings on the basic neuroscience of HIV and diagnosis and management of neurologic opportunistic infections are discussed. PMID:19401607

  10. [Neurological and psychiatric aspects of some gastrointestinal diseases].

    PubMed

    Aszalós, Zsuzsa

    2008-11-01

    The gastrointestinal tract is controlled by the independent enteric nervous system. It is also closely connected to the central nervous system, and bi-directional communication exists between them. The communication involves neural pathways as well as immune and endocrine mechanisms. The brain-gut axis plays a prominent role in the modulation of gut functions. Signals from different sources (e.g. sound, sight, smell, somatic and visceral sensations, pain) reach the brain. These inputs are modified by memory, cognition and affective mechanisms and integrated within the neural circuits of the central nervous system, spinal cord, autonomic and enteral nervous systems. These inputs can have physiologic effects, such as changes in motility, secretion, immune function, and blood flow to the gastrointestinal tract. One of the most important neurotransmitters is serotonin that plays a key role in the pathogenesis of the most common chronic functional gastrointestinal disorder: the irritable bowel syndrome. It is a biopsychosocial disease, resulting from the dysregulation of the brain-gut axis. Endogenous pain facilitation rather than inhibition, pathologic gradation of visceral perception and reduced threshold for pain are all evident in these patients. Abuse history is common in their anamnesis. Exaggerated conscientiousness, perfectionism, oversensitivity, feeling of deficiency in effectiveness, and higher demand for social parity, neuroticism and alexithymia have been detected among their constant personality features. Females are also characterized by gender role conflict and low assertiveness. Antidepressants and psychotherapy have important roles in their treatment. Also patients with inflammatory bowel disease are characterized by neuroticism and alexithymia and altered mother-child attachment is often described in their anamnesis. Autonomic neuropathy is a frequent and early neurological complication. Reflux disease and obstructive sleep apnea mutually generate

  11. PPAR agonists as therapeutics for CNS trauma and neurological diseases

    PubMed Central

    Mandrekar-Colucci, Shweta; Sauerbeck, Andrew; Popovich, Phillip G.; McTigue, Dana M.

    2013-01-01

    Traumatic injury or disease of the spinal cord and brain elicits multiple cellular and biochemical reactions that together cause or are associated with neuropathology. Specifically, injury or disease elicits acute infiltration and activation of immune cells, death of neurons and glia, mitochondrial dysfunction, and the secretion of substrates that inhibit axon regeneration. In some diseases, inflammation is chronic or non-resolving. Ligands that target PPARs (peroxisome proliferator-activated receptors), a group of ligand-activated transcription factors, are promising therapeutics for neurologic disease and CNS injury because their activation affects many, if not all, of these interrelated pathologic mechanisms. PPAR activation can simultaneously weaken or reprogram the immune response, stimulate metabolic and mitochondrial function, promote axon growth and induce progenitor cells to differentiate into myelinating oligodendrocytes. PPAR activation has beneficial effects in many pre-clinical models of neurodegenerative diseases and CNS injury; however, the mechanisms through which PPARs exert these effects have yet to be fully elucidated. In this review we discuss current literature supporting the role of PPAR activation as a therapeutic target for treating traumatic injury and degenerative diseases of the CNS. PMID:24215544

  12. Therapeutic targets in prostaglandin E2 signaling for neurologic disease

    PubMed Central

    Cimino, P.J.; Keene, C. Dirk; Breyer, Richard M.; Montine, Kathleen S.; Montine, Thomas J.

    2009-01-01

    Prostaglandins (PGs) are potent autocrine and paracrine oxygenated lipid molecules that contribute appreciably to physiologic and pathophysiologic responses in almost all organs, including brain. Emerging data indicate that the PGs, and more specifically PGE2, play a central role in brain diseases including ischemic injury and several neurodegenerative diseases. Given concerns over the potential toxicity from protracted use of cyclooxygenase inhibitors in the elderly, attention is now focused on blocking PGE2 signaling that is mediated by interactions with four distinct G protein-coupled receptors, EP1-4, which are differentially expressed on neuronal and glial cells throughout the central nervous system. EP1 activation has been shown to mediate Ca2+-dependent neurotoxicity in ischemic injury. EP2 activation has been shown to mediate microglial-induced paracrine neurotoxicity as well as suppress microglia internalization of aggregated neurotoxic peptides. Animal models support the potential efficacy of targeting specific EP receptor subtypes in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and ischemic stroke. However promising these preclinical studies are, they have yet to be followed by clinical trials targeting any EP receptor in neurologic diseases. PMID:18691044

  13. Shiga Toxin Mediated Neurologic Changes in Murine Model of Disease

    PubMed Central

    Pradhan, Suman; Pellino, Christine; MacMaster, Kayleigh; Coyle, Dennis; Weiss, Alison A.

    2016-01-01

    Seizures and neurologic involvement have been reported in patients infected with Shiga toxin (Stx) producing E. coli, and hemolytic uremic syndrome (HUS) with neurologic involvement is associated with more severe outcome. We investigated the extent of renal and neurologic damage in mice following injection of the highly potent form of Stx, Stx2a, and less potent Stx1. As observed in previous studies, Stx2a brought about moderate to acute tubular necrosis of proximal and distal tubules in the kidneys. Brain sections stained with hematoxylin and eosin (H&E) appeared normal, although some red blood cell congestion was observed. Microglial cell responses to neural injury include up-regulation of surface-marker expression (e.g., Iba1) and stereotypical morphological changes. Mice injected with Stx2a showed increased Iba1 staining, mild morphological changes associated with microglial activation (thickening of processes), and increased microglial staining per unit area. Microglial changes were observed in the cortex, hippocampus, and amygdala regions, but not the nucleus. Magnetic resonance imaging (MRI) of Stx2a-treated mice revealed no hyper-intensities in the brain, although magnetic resonance spectroscopy (MRS) revealed significantly decreased levels of phosphocreatine in the thalamus. Less dramatic changes were observed following Stx1 challenge. Neither immortalized microvascular endothelial cells from the cerebral cortex of mice (bEnd.3) nor primary human brain microvascular endothelial cells were found to be susceptible to Stx1 or Stx2a. The lack of susceptibility to Stx for both cell types correlated with an absence of receptor expression. These studies indicate Stx causes subtle, but identifiable changes in the mouse brain. PMID:27747196

  14. Systems Biology as a Comparative Approach to Understand Complex Gene Expression in Neurological Diseases

    PubMed Central

    Diaz-Beltran, Leticia; Cano, Carlos; Wall, Dennis P.; Esteban, Francisco J.

    2013-01-01

    Systems biology interdisciplinary approaches have become an essential analytical tool that may yield novel and powerful insights about the nature of human health and disease. Complex disorders are known to be caused by the combination of genetic, environmental, immunological or neurological factors. Thus, to understand such disorders, it becomes necessary to address the study of this complexity from a novel perspective. Here, we present a review of integrative approaches that help to understand the underlying biological processes involved in the etiopathogenesis of neurological diseases, for example, those related to autism and autism spectrum disorders (ASD) endophenotypes. Furthermore, we highlight the role of systems biology in the discovery of new biomarkers or therapeutic targets in complex disorders, a key step in the development of personalized medicine, and we demonstrate the role of systems approaches in the design of classifiers that can shorten the time for behavioral diagnosis of autism. PMID:25379238

  15. Neurological Disease Produced by Varicella Zoster Virus Reactivation Without Rash

    PubMed Central

    Gilden, Don; Cohrs, Randall J.; Mahalingam, Ravi; Nagel, Maria A.

    2010-01-01

    Reactivation of varicella zoster virus (VZV) from latently infected human ganglia usually produces herpes zoster (shingles), characterized by dermatomal distribution pain and rash. Zoster is often followed by chronic pain (postherpetic neuralgia or PHN) as well as meningitis or meningoencephalitis, cerebellitts, isolated cranial nerve palsies that produce ophthalmoplegia or the Ramsay Hunt syndrome, multiple cranial nerve palsies (polyneuritis cranialis), vasculopathy. myelopathy, and various inflammatory disorders of the eye. Importantly, VZV reactivation can produce chronic radicular pain without rash (zoster sine herpete), as well as all the neurological disorders listed above without rash. The protean neurological and ocular disorders produced by VZV in the absence of rash are a challenge to the practicing clinician. The presentation of these conditions vanes from acute to subacute to chronic. Virological confirmation requires the demonstration of amplifiable VZV DNA in cerebrospinal fluid (CSF) or in blood mononuclear cells, or the presence of anti-VZV IgG antibody in CSF or of anti-VZV IgM antibody in CSF or serum. PMID:20186614

  16. [Neurological diseases after lightning strike : Lightning strikes twice].

    PubMed

    Gruhn, K M; Knossalla, Frauke; Schwenkreis, Peter; Hamsen, Uwe; Schildhauer, Thomas A; Tegenthoff, Martin; Sczesny-Kaiser, Matthias

    2016-06-01

    Lightning strikes rarely occur but 85 % of patients have lightning-related neurological complications. This report provides an overview about different modes of energy transfer and neurological conditions related to lightning strikes. Moreover, two case reports demonstrate the importance of interdisciplinary treatment and the spectrum of neurological complications after lightning strikes. PMID:26873252

  17. [Neurological diseases after lightning strike : Lightning strikes twice].

    PubMed

    Gruhn, K M; Knossalla, Frauke; Schwenkreis, Peter; Hamsen, Uwe; Schildhauer, Thomas A; Tegenthoff, Martin; Sczesny-Kaiser, Matthias

    2016-06-01

    Lightning strikes rarely occur but 85 % of patients have lightning-related neurological complications. This report provides an overview about different modes of energy transfer and neurological conditions related to lightning strikes. Moreover, two case reports demonstrate the importance of interdisciplinary treatment and the spectrum of neurological complications after lightning strikes.

  18. Samuel Alexander Kinnier Wilson. Wilson's disease, Queen Square and neurology.

    PubMed

    Broussolle, E; Trocello, J-M; Woimant, F; Lachaux, A; Quinn, N

    2013-12-01

    This historical article describes the life and work of the British physician Samuel Alexander Kinnier Wilson (1878-1937), who was one of the world's greatest neurologists of the first half of the 20th century. Early in his career, Wilson spent one year in Paris in 1903 where he learned from Pierre-Marie at Bicêtre Hospital. He subsequently retained uninterrupted links with French neurology. He also visited in Leipzig the German anatomist Paul Flechsig. In 1904, Wilson returned to London, where he worked for the rest of his life at the National Hospital for the Paralysed and Epileptic (later the National Hospital for Nervous Diseases, and today the National Hospital for Neurology and Neurosurgery) in Queen Square, and also at Kings' College Hospital. He wrote on 'the old motor system and the new', on disorders of motility and muscle tone, on the epilepsies, on aphasia, apraxia, tics, and pathologic laughing and crying, and most importantly on Wilson's disease. The other objective of our paper is to commemorate the centenary of Wilson's most important work published in 1912 in Brain, and also in Revue Neurologique, on an illness newly recognized and characterized by him entitled "Progressive lenticular degeneration, a familial nervous disease associated with liver cirrhosis". He analyzed 12 clinical cases, four of whom he followed himself, but also four cases previously published by others and a further two that he considered in retrospect had the same disease as he was describing. The pathological profile combined necrotic damage in the lenticular nuclei of the brain and hepatic cirrhosis. This major original work is summarized and discussed in the present paper. Wilson not only delineated what was later called hepato-lenticular degeneration and Wilson's disease, but also introduced for the first time the terms extrapyramidal syndrome and extrapyramidal system, stressing the role of the basal ganglia in motility. The present historical work emphasizes the special

  19. Major neurological disease and occupational exposure to organic solvents.

    PubMed

    Seaton, A; Jellinek, E H; Kennedy, P

    1992-09-01

    Five patients are described who presented with major organic brain disease affecting one or more of pyramidal and extrapyramidal tracts, cerebellum, and higher cortical functions. All had a history of 10 years or more of regular occupational exposure to solvents in confined spaces, three in painting inside ships and the others in weapons maintenance and printing. All had been regularly exposed to high air vapour peaks as well as to skin contamination. Four showed some evidence of improvement after the exposure ceased. None was initially suspected of having a toxic encephalopathy by the consultant to whom he was referred. The spectrum of neurological disease presented by these men mirrors closely that described in solvent abusers. All were forced by illness to retire from their work, a circumstance which might have in the past have led to such conditions being missed in cross-sectional studies, which in general have not shown evidence of major disease. We suggest that when such disease occurs nowadays, its cause is usually not suspected. Further epidemiological study of the problem is necessary.

  20. Psychiatric manifestations of neurologic disease: where are we headed?

    PubMed Central

    Lyketsos, Constantin G.; Kozauer, Nicholas; Rabins, Peter V.

    2007-01-01

    Neuropsychiatry represents a field of medicine situated at the crossroads of neurology and psychiatry, and deals with the interface of behavioral phenomena driven by brain dysfunction. Psychiatric symptoms are highly prevalent in these conditions, are a major source of disability and diminished quality of life, and potentially represent the target of treatment interventions that stand to significantly decrease the suffering they generate. In this article, the disease paradigm is explained, with particular attention to its role as an organizing principle for the field. Specific diseases including traumatic brain injury, stroke, Parkinson's disease, Alzheimer's disease, multiple sclerosis, and epilepsy are explored in relation to the presentation of multiple psychiatric phenotypes in each, associations with underlying brain pathology, and existing treatment approaches. Finally, the afticle explores the inherent complexities in this area of research and proposes a framework for future work based on the understanding of phenomenology and associated risk factors, the involvement of the rapidly advancing field of neuroscience, and targeted treatment development to serve as a road map for advancement in the field. PMID:17726911

  1. [Palliative Care for Neurological Intractable Diseases and Home Medical Support].

    PubMed

    Yokoyama, Kazumasa; Ogino, Mieko; Ishigaki, Yasunori; Hattori, Nobutaka

    2015-08-01

    Many medical doctors regard the end stage and palliative care of neurological intractable diseases as the point at which aggressive treatment should be interrupted and death is imminent. However, the definition of health by the World Health Organization as the physical, psychological, and social goal to achieve a fully favorable health condition should be revisited. In the real clinical setting, the health condition, as the ability to adapt and self-manage in the face of social, physical, and emotional challenges with the aim to overcome stress (resilience), is dynamic and involves a healthy condition and satisfaction with one's own living. The most important step in palliative therapy that is shared by neurologists is the maintenance of the health status with the help of multi-disciplinary team with the view to improving the quality of life. PMID:26241362

  2. [Prevention of virus-related neurological diseases by vaccines].

    PubMed

    Takahashi, M

    1997-04-01

    Prevention of virus-related neurological diseases are surveyed. Patients of poliomyelitis has recently been drastically reduced by world-wide administrating live vaccines. In view of rare incidence of paralysis after giving live vaccine, adoption of inactivated vaccine has recently been reconsidered. A live varicella vaccine was developed and has been world-wide used for normal and high-risk children. Incidence of zoster in vaccinated acute leukemic children is several times higher in those who with rash after vaccination as compared with those without rash, and as no or few rash appears after vaccination of normal children, it is expected that vaccination of normal children would lead to reduction of zoster after their aging. Measles encephalitis has rapidly been reduced by world-wide use of live vaccines. Mouse-brain derived vaccine against Japanese encephalitis(JE) has been used in Asian countries. Development of tissue-culture derived JE vaccine is under way. PMID:9103901

  3. Neurological Complications Following Endoluminal Repair of Thoracic Aortic Disease

    SciTech Connect

    Morales, J. P.; Taylor, P. R.; Bell, R. E.; Chan, Y. C.; Sabharwal, T.; Carrell, T. W. G.; Reidy, J. F.

    2007-09-15

    Open surgery for thoracic aortic disease is associated with significant morbidity and the reported rates for paraplegia and stroke are 3%-19% and 6%-11%, respectively. Spinal cord ischemia and stroke have also been reported following endoluminal repair. This study reviews the incidence of paraplegia and stroke in a series of 186 patients treated with thoracic stent grafts. From July 1997 to September 2006, 186 patients (125 men) underwent endoluminal repair of thoracic aortic pathology. Mean age was 71 years (range, 17-90 years). One hundred twenty-eight patients were treated electively and 58 patients had urgent procedures. Anesthesia was epidural in 131, general in 50, and local in 5 patients. Seven patients developed paraplegia (3.8%; two urgent and five elective). All occurred in-hospital apart from one associated with severe hypotension after a myocardial infarction at 3 weeks. Four of these recovered with cerebrospinal fluid (CSF) drainage. One patient with paraplegia died and two had permanent neurological deficit. The rate of permanent paraplegia and death was 1.6%. There were seven strokes (3.8%; four urgent and three elective). Three patients made a complete recovery, one had permanent expressive dysphasia, and three died. The rate of permanent stroke and death was 2.1%. Endoluminal treatment of thoracic aortic disease is an attractive alternative to open surgery; however, there is still a risk of paraplegia and stroke. Permanent neurological deficits and death occurred in 3.7% of the patients in this series. We conclude that prompt recognition of paraplegia and immediate insertion of a CSF drain can be an effective way of recovering spinal cord function and improving the prognosis.

  4. Association of Pesticide Exposure with Neurologic Dysfunction and Disease

    PubMed Central

    Kamel, Freya; Hoppin, Jane A.

    2004-01-01

    Poisoning by acute high-level exposure to certain pesticides has well-known neurotoxic effects, but whether chronic exposure to moderate levels of pesticides is also neurotoxic is more controversial. Most studies of moderate pesticide exposure have found increased prevalence of neurologic symptoms and changes in neurobehavioral performance, reflecting cognitive and psychomotor dysfunction. There is less evidence that moderate exposure is related to deficits in sensory or motor function or peripheral nerve conduction, but fewer studies have considered these outcomes. It is possible that the most sensitive manifestation of pesticide neurotoxicity is a general malaise lacking in specificity and related to mild cognitive dysfunction, similar to that described for Gulf War syndrome. Most studies have focused on organophosphate insecticides, but some found neuro-toxic effects from other pesticides, including fungicides, fumigants, and organochlorine and carbamate insecticides. Pesticide exposure may also be associated with increased risk of Parkinson disease; several classes of pesticides, including insecticides, herbicides, and fungicides, have been implicated. Studies of other neurodegenerative diseases are limited and inconclusive. Future studies will need to improve assessment of pesticide exposure in individuals and consider the role of genetic susceptibility. More studies of pesticides other than organophosphates are needed. Major unresolved issues include the relative importance of acute and chronic exposure, the effect of moderate exposure in the absence of poisoning, and the relationship of pesticide-related neurotoxicity to neurodegenerative disease. PMID:15198914

  5. Exposure to lipophilic chemicals as a cause of neurological impairments, neurodevelopmental disorders and neurodegenerative diseases

    PubMed Central

    2013-01-01

    Many studies have associated environmental exposure to chemicals with neurological impairments (NIs) including neuropathies, cognitive, motor and sensory impairments; neurodevelopmental disorders (NDDs) including autism and attention deficit hyperactivity disorder (ADHD); neurodegenerative diseases (NDGs) including Alzheimer′s disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS). The environmental chemicals shown to induce all these diseases include persistent organic pollutants (POPs), the plastic exudates bisphenol A and phthalates, low molecular weight hydrocarbons (LMWHCs) and polynuclear aromatic hydrocarbons (PAHs). It is reported here that though these chemicals differ widely in their chemical properties, reactivities and known points of attack in humans, a common link does exist between them. All are lipophilic species found in serum and they promote the sequential absorption of otherwise non-absorbed toxic hydrophilic species causing these diseases. PMID:24678247

  6. Exposure to lipophilic chemicals as a cause of neurological impairments, neurodevelopmental disorders and neurodegenerative diseases.

    PubMed

    Zeliger, Harold I

    2013-09-01

    Many studies have associated environmental exposure to chemicals with neurological impairments (NIs) including neuropathies, cognitive, motor and sensory impairments; neurodevelopmental disorders (NDDs) including autism and attention deficit hyperactivity disorder (ADHD); neurodegenerative diseases (NDGs) including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS). The environmental chemicals shown to induce all these diseases include persistent organic pollutants (POPs), the plastic exudates bisphenol A and phthalates, low molecular weight hydrocarbons (LMWHCs) and polynuclear aromatic hydrocarbons (PAHs). It is reported here that though these chemicals differ widely in their chemical properties, reactivities and known points of attack in humans, a common link does exist between them. All are lipophilic species found in serum and they promote the sequential absorption of otherwise non-absorbed toxic hydrophilic species causing these diseases.

  7. Therapeutic plasma exchange in patients with neurological diseases: multicenter retrospective analysis.

    PubMed

    Kaya, Emin; Keklik, Muzaffer; Sencan, Mehmet; Yilmaz, Mehmet; Keskin, Ali; Kiki, Ilhami; Erkurt, Mehmet Ali; Sivgin, Serdar; Korkmaz, Serdal; Okan, Vahap; Doğu, Mehmet Hilmi; Unal, Ali; Cetin, Mustafa; Altuntaş, Fevzi; Ilhan, Osman

    2013-06-01

    Therapeutic plasma exchange (TPE), is a procedure, changing pathologic substances in the plasma of patients with replacement fluid. TPE has an increasing list of indications in recent years such as neurological, connective tissue, hematological, nephrological, endocrinological and metabolic disorders. We report our multicenter data about therapeutic plasma exchange in patients with neurological diseases. Six University Hospitals' aphaeresis units medical records about neurologic diseases were reviewed retrospectively. Hundred and fifteen patients and 771 TPE sessions from six aphaeresis units' were included to this study. Of the 115 patients, 53 (46%) were men and 62 (54%) were women. The median age was 50 (range: 5-85) years. Of these patients 58.3% were Guillain-Barre syndrome (GBS), 17.4% were acute disseminated encephalomyelitis (ADEM), 10.4% were chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), 7% were multiple sclerosis, 6.1% were myasthenia gravis (MG) and 0.9% were Wilson disease (WD). The median number of TPE sessions per patient was 5 (range 1-72). Human albumin was used as a replacement fluid in 66% and fresh frozen plasma was used in 34% of cases. TPE was done through central venous catheters in 66%, and peripheral venous access in 34% of patients. Some complications were seen in patients (18.3%) during TPE sessions. These complications were, complications related to catheter placement procedure (8.7%), hypotension (3.5%), hypocalcaemia (3.5%) and allergic reactions (1.7%). The complication ratios were 2.7% in total 771 TPE procedures. TPE procedure was terminated in 6% of sessions depending on these complications. Overall responses to TPE were noted in 89.5% of patients. In conclusion; Therapeutic plasma exchange is an effective treatment option in several neurologic diseases.

  8. [Neurologic characteristics of diseases caused by Inkoo and Tahyna viruses].

    PubMed

    Demikhov, V G; Chaĭtsev, V G

    1995-01-01

    Two principal forms of diseases caused by Inkoo and Tahyna viruses were observed, fever (25 pts, 61%) and neuroinfection (13 pts, 31.7%). In 3 (7.3%) subjects the infection was inapparent. Ten patients presented with mixed forms of infection (virus-virus or virus-bacterial). Clinical manifestations were characterized by marked polymorphism and low specificity. The onset was acute with expressed symptoms of infection and weak catarrhal manifestations. Of the patients with the neuroinfectious form of the disease 3 presented with aseptic meningitis, 2 with meningoencephalitis, and 5 with encephalitis. Aseptic meningitis was characterized by a combination of general infectious and moderately expressed meningeal syndromes with weak inflammatory changes in the spinal fluid. Encephalitides were associated with numerous neurological symptoms which manifested on days 3-7 of the illness. These symptoms were asymmetry of nasolabial folds, hemiparesis, dysarthria, dysphagia, generalized tremor, tongue deviation. No significant differences in the clinical manifestations of Inkoo and Tahyna infections were observed. PMID:7740783

  9. Iron as a risk factor in neurological diseases

    NASA Astrophysics Data System (ADS)

    Galazka-Friedman, Jolanta

    2008-02-01

    In this review the properties of iron in various human brain structures (e.g. Substantia nigra, globus pallidus, hippocampus) were analyzed to assess the possibility of initiation of oxidative stress leading to such diseases as Parkinson’s and Alzheimer’s disease, and progressive supranuclear palsy. Our own studies with the use of Mössbauer spectroscopy, electron microscopy and enzyme-linked immuno-absorbent assay (ELISA) were confronted with other methods used in other laboratories. Our results suggest that hippocampus is the most fragile for oxidative stress structure in human brain (the death of nervous cells in hippocampus leads to Alzheimer’s disease). Changes in iron metabolism were also found in substantia nigra (the death of nervous cells of this structure produces Parkinson’s disease) and in globus pallidus (neurodegeneration of this structure causes progressive supranuclear palsy).

  10. Sindbis and Middelburg Old World Alphaviruses Associated with Neurologic Disease in Horses, South Africa

    PubMed Central

    van Niekerk, Stephanie; Human, Stacey; Williams, June; van Wilpe, Erna; Pretorius, Marthi; Swanepoel, Robert

    2015-01-01

    Old World alphaviruses were identified in 52 of 623 horses with febrile or neurologic disease in South Africa. Five of 8 Sindbis virus infections were mild; 2 of 3 fatal cases involved co-infections. Of 44 Middelburg virus infections, 28 caused neurologic disease; 12 were fatal. Middelburg virus likely has zoonotic potential. PMID:26583836

  11. Neurologic presentations of AIDS.

    PubMed

    Singer, Elyse J; Valdes-Sueiras, Miguel; Commins, Deborah; Levine, Andrew

    2010-02-01

    The human immunodeficiency virus (HIV), the cause of AIDS, has infected an estimated 33 million individuals worldwide. HIV is associated with immunodeficiency, neoplasia, and neurologic disease. The continuing evolution of the HIV epidemic has spurred an intense interest in a hitherto neglected area of medicine, neuroinfectious diseases and their consequences. This work has broad applications for the study of central nervous system (CNS) tumors, dementias, neuropathies, and CNS disease in other immunosuppressed individuals. HIV is neuroinvasive (can enter the CNS), neurotrophic (can live in neural tissues), and neurovirulent (causes disease of the nervous system). This article reviews the HIV-associated neurologic syndromes, which can be classified as primary HIV neurologic disease (in which HIV is both necessary and sufficient to cause the illness), secondary or opportunistic neurologic disease (in which HIV interacts with other pathogens, resulting in opportunistic infections and tumors), and treatment-related neurologic disease (such as immune reconstitution inflammatory syndrome). PMID:19932385

  12. Neurological channelopathies

    PubMed Central

    Graves, T; Hanna, M

    2005-01-01

    Ion channels are membrane-bound proteins that perform key functions in virtually all human cells. Such channels are critically important for the normal function of the excitable tissues of the nervous system, such as muscle and brain. Until relatively recently it was considered that dysfunction of ion channels in the nervous system would be incompatible with life. However, an increasing number of human diseases associated with dysfunctional ion channels are now recognised. Such neurological channelopathies are frequently genetically determined but may also arise through autoimmune mechanisms. In this article clinical, genetic, immunological, and electrophysiological aspects of this expanding group of neurological disorders are reviewed. Clinical situations in which a neurological channelopathy should enter into the differential diagnosis are highlighted. Some practical guidance on how to investigate and treat this complex group of disorders is also included. PMID:15640425

  13. Functional Neurons Generated from T Cell-Derived Induced Pluripotent Stem Cells for Neurological Disease Modeling

    PubMed Central

    Matsumoto, Takuya; Fujimori, Koki; Andoh-Noda, Tomoko; Ando, Takayuki; Kuzumaki, Naoko; Toyoshima, Manabu; Tada, Hirobumi; Imaizumi, Kent; Ishikawa, Mitsuru; Yamaguchi, Ryo; Isoda, Miho; Zhou, Zhi; Sato, Shigeto; Kobayashi, Tetsuro; Ohtaka, Manami; Nishimura, Ken; Kurosawa, Hiroshi; Yoshikawa, Takeo; Takahashi, Takuya; Nakanishi, Mahito; Ohyama, Manabu; Hattori, Nobutaka; Akamatsu, Wado; Okano, Hideyuki

    2016-01-01

    Summary Modeling of neurological diseases using induced pluripotent stem cells (iPSCs) derived from the somatic cells of patients has provided a means of elucidating pathogenic mechanisms and performing drug screening. T cells are an ideal source of patient-specific iPSCs because they can be easily obtained from samples. Recent studies indicated that iPSCs retain an epigenetic memory relating to their cell of origin that restricts their differentiation potential. The classical method of differentiation via embryoid body formation was not suitable for T cell-derived iPSCs (TiPSCs). We developed a neurosphere-based robust differentiation protocol, which enabled TiPSCs to differentiate into functional neurons, despite differences in global gene expression between TiPSCs and adult human dermal fibroblast-derived iPSCs. Furthermore, neurons derived from TiPSCs generated from a juvenile patient with Parkinson's disease exhibited several Parkinson's disease phenotypes. Therefore, we conclude that TiPSCs are a useful tool for modeling neurological diseases. PMID:26905201

  14. Autoimmunity due to molecular mimicry as a cause of neurological disease

    PubMed Central

    Levin, Michael C.; Lee, Sang Min; Kalume, Franck; Morcos, Yvette; Dohan, F. Curtis; Hasty, Karen A.; Callaway, Joseph C.; Zunt, Joseph; Desiderio, Dominic M.; Stuart, John M.

    2009-01-01

    One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease1,2. This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS)1–4. There is limited direct evidence linking causative agents with pathogenic immune reactions in these diseases. Our study establishes a clear link between viral infection, autoimmunity and neurological disease in humans. As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5–7). HAM/TSP patients develop antibodies to neurons8. We hypothesized these antibodies would identify a central nervous system (CNS) autoantigen. Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1 cross-reacted with HTLV-1-tax, the immune response to which is associated with HAM/TSP (refs. 5,9). Immunoglobulin G specifically stained human Betz cells, whose axons are preferentially damaged7. Infusion of autoantibodies in brain sections inhibited neuronal firing, indicative of their pathogenic nature. These data demonstrate the importance of molecular mimicry between an infecting agent and hnRNP-A1 in autoimmune disease of the CNS. PMID:11984596

  15. [Cannabinoid drugs for neurological diseases: what is behind?].

    PubMed

    Fernández-Ruiz, Javier

    2012-05-16

    In recent years progress has been made in the development of pharmaceuticals based on the plant Cannabis sativa or on synthetic molecules with a similar action. Some of these pharmaceuticals, such as the mouth spray Sativex, have recently been approved for the treatment of spasticity in multiple sclerosis, but they are not the first and others, such as Marinol or Cesamet for the treatment of vomiting and nausea, and anorexia-cachexia syndrome, had already been approved. This incipient clinical use of cannabinoid drugs confirms something that was already known from fairly ancient times up to practically the last century, which is the potential use of this plant for medicinal applications - something which was brought to a standstill by the abusive use of preparations of the plant for recreational purposes. In any case, this incipient clinical use of cannabinoid drugs is not backed just by the anecdote of the medicinal use of cannabis since ancient times, but instead the boost it has been given by scientific research, which has made it possible to identify the target molecules that are activated or inhibited by these substances. These targets are part of a new system of intercellular communication that is especially active in the central nervous system, which is called the 'endogenous cannabinoid system' and, like many other systems, can be manipulated pharmacologically. The aim of this review is to probe further into the scientific knowledge about this system generated in the last few years, as a necessary step to justify the development of pharmaceuticals based on its activation or inhibition and which can be useful in different neurological diseases. PMID:22573509

  16. Use of "omics" technologies to dissect neurologic disease.

    PubMed

    Tosto, G; Reitz, C

    2016-01-01

    Over the past 5 years, the advent of massively parallel technologies for understanding disease at the molecular level accompanied by simultaneous rapid development of the computational tools needed to analyze and filter such data has revolutionized medical science. These "next-generation" "omics" technologies include next-generation sequencing technology for detection of disease-associated DNA sequence variants, RNA sequencing for transcriptome and noncoding RNA analysis, quantitative detection of epigenomic dynamics, and chromatin immunoprecipitation sequencing analysis for DNA-protein interactions, interactome analysis for networks formed by protein-protein interactions, and metabolome analysis for metabolic systems. The analysis and integration of data derived from massively parallel technologies will significantly deepen our understanding of human disease, will inform functional studies, in vitro and in vivo model generation, and will advance the development of improved, personalized diagnostic tools and more effective therapeutic targets. In this chapter we review the classic genomic approaches for identifying mechanisms underlying human disease, and summarize the emerging "omics" technologies allowing massively parallel interrogation of biologic systems. PMID:27637954

  17. Immigration and neurological diseases: a longitudinal study in an acute neurological care.

    PubMed

    Rinaldi, Fabrizio; Liberini, Paolo; Rao, Renata; Venturelli, Elisabetta; Gipponi, Stefano; Pari, Elisa; Sapia, Eluisa; Padovani, Alessandro

    2012-10-01

    Very few data exist on causes and outcomes of hospitalization of immigrants in Italy. Even though immigration is a real challenge for the western countries, we are still unaware of how it reflects on the costs and the management of an acute care department. This study was aimed to compare the patterns of hospital use by immigrants incoming to the Acute Care Department of Neurology in Brescia, Italy, with those of the resident Italian people. The study was based on the hospital discharge data. Discharges of immigrants were compared to those of a random selection of Italian patients matched by age and sex. The length of the study period was of 2.5 years. A similar pattern of hospital use by age was observed between foreigners and Italian patients; however, average length of hospitalization was significantly longer in immigrant population.

  18. [Wilson's disease with severe neurological manifestations: response to trientine plus zinc therapy].

    PubMed

    Serra, B; Primo, J; García, M; Amorós, I; Aragó, M; Merino, C

    2004-05-01

    In patients with Wilson's disease and neurological manifestations, treatment with D-penicillamine can cause worsening of neurological symptoms, usually in the first few weeks of treatment. Because the neurological damage can be severe and irreversible, the use of D-penicillamine is controversial, and several authors believe that it should be avoided. Studies of the use of ammonium tetrathiomolybdate as an alternative chelating agent for the initial treatment of neurologic Wilson's disease are still in the experimental phase. Published experience on the simultaneous use of trientine, another chelating agent, and zinc, which blocks intestinal absorption of copper, is promising but limited. We present the case of a 17 year-old boy with severe neurologic Wilson's disease that had first presented six years previously. The patient showed a complete recovery after six months of treatment with a combination of trientine and zinc acetate.

  19. Structural basis for early-onset neurological disorders caused by mutations in human selenocysteine synthase

    PubMed Central

    Puppala, Anupama K.; French, Rachel L.; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Simonović, Miljan

    2016-01-01

    Selenocysteine synthase (SepSecS) catalyzes the terminal reaction of selenocysteine, and is vital for human selenoproteome integrity. Autosomal recessive inheritance of mutations in SepSecS–Ala239Thr, Thr325Ser, Tyr334Cys and Tyr429*–induced severe, early-onset, neurological disorders in distinct human populations. Although harboring different mutant alleles, patients presented remarkably similar phenotypes typified by cerebellar and cerebral atrophy, seizures, irritability, ataxia, and extreme spasticity. However, it has remained unclear how these genetic alterations affected the structure of SepSecS and subsequently elicited the development of a neurological pathology. Herein, our biophysical and structural characterization demonstrates that, with the exception of Tyr429*, pathogenic mutations decrease protein stability and trigger protein misfolding. We propose that the reduced stability and increased propensity towards misfolding are the main causes for the loss of SepSecS activity in afflicted patients, and that these factors contribute to disease progression. We also suggest that misfolding of enzymes regulating protein synthesis should be considered in the diagnosis and study of childhood neurological disorders. PMID:27576344

  20. Structural basis for early-onset neurological disorders caused by mutations in human selenocysteine synthase.

    PubMed

    Puppala, Anupama K; French, Rachel L; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Simonović, Miljan

    2016-01-01

    Selenocysteine synthase (SepSecS) catalyzes the terminal reaction of selenocysteine, and is vital for human selenoproteome integrity. Autosomal recessive inheritance of mutations in SepSecS-Ala239Thr, Thr325Ser, Tyr334Cys and Tyr429*-induced severe, early-onset, neurological disorders in distinct human populations. Although harboring different mutant alleles, patients presented remarkably similar phenotypes typified by cerebellar and cerebral atrophy, seizures, irritability, ataxia, and extreme spasticity. However, it has remained unclear how these genetic alterations affected the structure of SepSecS and subsequently elicited the development of a neurological pathology. Herein, our biophysical and structural characterization demonstrates that, with the exception of Tyr429*, pathogenic mutations decrease protein stability and trigger protein misfolding. We propose that the reduced stability and increased propensity towards misfolding are the main causes for the loss of SepSecS activity in afflicted patients, and that these factors contribute to disease progression. We also suggest that misfolding of enzymes regulating protein synthesis should be considered in the diagnosis and study of childhood neurological disorders. PMID:27576344

  1. Trientine-induced neurological deterioration in a patient with Wilson's disease.

    PubMed

    Kim, Bomi; Chung, Sun Ju; Shin, Hae-Won

    2013-04-01

    Trientine (triethylenetetramine dihydrochloride) is a copper-chelating agent used to treat patients with Wilson's disease (WD). It has been considered safe, rarely causing neurological deterioration during initial treatment. We describe a patient diagnosed with WD who became neurologically disabled after treatment with trientine. On a fluid attenuated inversion recovery sequence, brain MRI showed increased areas of high signal intensity compared with initial brain MRI. The patient's neurological signs partially resolved after cessation of trientine treatment. Our findings suggest that treatment with trientine is associated with a risk of neurological deterioration in patients with WD.

  2. Association of sickle cell disease, priapism, exchange transfusion and neurological events: ASPEN syndrome.

    PubMed

    Siegel, J F; Rich, M A; Brock, W A

    1993-11-01

    Priapism and acute neurological events are believed to be unrelated complications of sickle cell hemoglobinopathy. We describe a syndrome based on our experience and a review of the literature of significant neurological events after partial exchange transfusion to treat priapism in sicklemic patients. Severe headache is often the initiating symptom of this complex. The ensuing neurological events range from seizure activity to obtundation requiring ventilatory support. The proposed pathophysiology of these neurological events is related to cerebral ischemia after an acute increase in per cent total hemoglobin, concomitant decrease in per cent hemoglobin S and subsequent release of vasoactive substances during penile detumescence. We have termed this constellation of events the ASPEN syndrome, an eponym for association of sickle cell disease, priapism, exchange transfusion and neurological events. Early recognition and aggressive medical management resulted in complete reversal of neurological sequela. PMID:8411432

  3. Noise-Induced Sensitization of Human Brain: Toward the Neurological Application of Stochastic Resonance

    NASA Astrophysics Data System (ADS)

    Yamamoto, Yoshiharu; Soma, Rika; Hidaka, Ichiro; Nozaki, Daichi; Iso-o, Noriko; Kwak, Shin

    2003-05-01

    In the past decade, it has been recognized that noise can enhance the response of nonlinear systems to weak signals, via a mechanism known as stochastic resonance (SR). Particularly, the concept of SR has generated considerable interest in sensory biology, because it has been shown in several experimental studies that noise can assist neural systems in detecting weak signals which could not be detected in its absence. Recently, we have shown a similar type of noise-induced sensitization of human brain; externally added noise to the brain stem baroreflex centers sensitized their responses in maintaining adequate blood perfusion to the brain itself. Furthermore, the addition of noise has also shown to be useful in compensating for dysfunctions of the baroreflex centers in certain neurological diseases. It is concluded that the statistical physics concept of SR could be useful in sensitizing human brain in health and disease.

  4. Therapeutic potential of human adipose-derived stem cells in neurological disorders.

    PubMed

    Chang, Keun-A; Lee, Jun-Ho; Suh, Yoo-Hun

    2014-01-01

    Stem cell therapy has been noted as a novel strategy to various diseases including neurological disorders such as Alzheimer's disease, Parkinson's disease, stroke, amyotrophic lateral sclerosis, and Huntington's disease that have no effective treatment available to date. The adipose-derived stem cells (ASCs), mesenchymal stem cells (MSCs) isolated from adipose tissue, are well known for their pluripotency with the ability to differentiate into various types of cells and immuno-modulatory property. These biological features make ASCs a promising source for regenerative cell therapy in neurological disorders. Here we discuss the recent progress of regenerative therapies in various neurological disorders utilizing ASCs.

  5. Intravenous immunoglobulin in neurological disease: a specialist review

    PubMed Central

    Wiles, C; Brown, P; Chapel, H; Guerrini, R; Hughes, R; Martin, T; McCrone, P; Newsom-Davis, J; Palace, J; Rees, J; Rose, M; Scolding, N; Webster, A

    2002-01-01

    Treatment of neurological disorders with intravenous immunoglobulin (IVIg) is an increasing feature of our practice for an expanding range of indications. For some there is evidence of benefit from randomised controlled trials, whereas for others evidence is anecdotal. The relative rarity of some of the disorders means that good randomised control trials will be difficult to deliver. Meanwhile, the treatment is costly and pressure to "do something" in often distressing disorders considerable. This review follows a 1 day meeting of the authors in November 2000 and examines current evidence for the use of IVIg in neurological conditions and comments on mechanisms of action, delivery, safety and tolerability, and health economic issues. Evidence of efficacy has been classified into levels for healthcare interventions (tables 1 and 2). PMID:11909900

  6. Biomedical and clinical promises of human pluripotent stem cells for neurological disorders.

    PubMed

    Jongkamonwiwat, Nopporn; Noisa, Parinya

    2013-01-01

    Neurological disorders are characterized by the chronic and progressive loss of neuronal structures and functions. There is a variability of the onsets and causes of clinical manifestations. Cell therapy has brought a new concept to overcome brain diseases, but the advancement of this therapy is limited by the demands of specialized neurons. Human pluripotent stem cells (hPSCs) have been promised as a renewable resource for generating human neurons for both laboratory and clinical purposes. By the modulations of appropriate signalling pathways, desired neuron subtypes can be obtained, and induced pluripotent stem cells (iPSCs) provide genetically matched neurons for treating patients. These hPSC-derived neurons can also be used for disease modeling and drug screening. Since the most urgent problem today in transplantation is the lack of suitable donor organs and tissues, the derivation of neural progenitor cells from hPSCs has opened a new avenue for regenerative medicine. In this review, we summarize the recent reports that show how to generate neural derivatives from hPSCs, and discuss the current evidence of using these cells in animal studies. We also highlight the possibilities and concerns of translating these hPSC-derived neurons for biomedical and clinical uses in order to fight against neurological disorders.

  7. Physiological Transgene Regulation and Functional Complementation of a Neurological Disease Gene Deficiency in Neurons

    PubMed Central

    Peruzzi, Pier Paolo; Lawler, Sean E; Senior, Steve L; Dmitrieva, Nina; Edser, Pauline AH; Gianni, Davide; Chiocca, E Antonio; Wade-Martins, Richard

    2009-01-01

    The microtubule-associated protein tau (MAPT) and α-synuclein (SNCA) genes play central roles in neurodegenerative disorders. Mutations in each gene cause familial disease, whereas common genetic variation at both loci contributes to susceptibility to sporadic neurodegenerative disease. Here, we demonstrate exquisite gene regulation of the human MAPT and SNCA transgene loci and functional complementation in neuronal cell cultures and organotypic brain slices using the herpes simplex virus type 1 (HSV-1) amplicon-based infectious bacterial artificial chromosome (iBAC) vector to express complete loci >100 kb. Cell cultures transduced by iBAC vectors carrying a 143 kb MAPT or 135 kb SNCA locus expressed the human loci similar to the endogenous gene. We focused on analysis of the iBAC-MAPT vector carrying the complete MAPT locus. On transduction into neuronal cultures, multiple MAPT transcripts were expressed from iBAC-MAPT under strict developmental and cell type–specific control. In primary neurons from Mapt−/− mice, the iBAC-MAPT vector expressed the human tau protein, as detected by enzyme-linked immunosorbent assay and immunocytochemistry, and restored sensitivity of Mapt−/− neurons to Aβ peptide treatment in dissociated neuronal cultures and in organotypic slice cultures. The faithful retention of gene expression and phenotype complementation by the system provides a novel method to analyze neurological disease genes. PMID:19352323

  8. Liver cirrhosis in patients newly diagnosed with neurological phenotype of Wilson's disease.

    PubMed

    Przybyłkowski, Adam; Gromadzka, Grażyna; Chabik, Grzegorz; Wierzchowska, Agata; Litwin, Tomasz; Członkowska, Anna

    2014-01-01

    Wilson's disease (WD) can manifest itself in different clinical forms, the neurological and hepatic ones being the most common. It is suggested that neurological signs and psychiatric symptoms develop secondary to liver involvement. The aim of this study was to characterize the liver disease in patients newly diagnosed with the neurological form of WD. Treatment-naive patients diagnosed with WD were classified into three phenotypic groups: hepatic, neurological and pre-symptomatic. Liver involvement was ascertained through surrogate markers: abdominal ultrasound and laboratory parameters. In addition, study participants were screened for esophageal varices. Of 53 consecutively diagnosed WD patients, 23 individuals (43.4%) had a predominantly neurological presentation. In this group, cirrhosis was diagnosed in 11 (47.8%) subjects. Esophageal varices were present in all of them. In every patient with neurological WD, there was at least one sign of hepatic disease on ultrasound examination, indicating universal presence of liver involvement. The prevalence of surrogate signs of cirrhosis was similar in patients with the neurological and in those with the hepatic phenotype.

  9. Aptamer-targeted oligonucleotide theranostics: a smarter approach for brain delivery and the treatment of neurological diseases.

    PubMed

    Sriramoju, Bhasker; Kanwar, Rupinder; Veedu, Rakesh N; Kanwar, Jagat R

    2015-01-01

    Aptamers represent the novel class of oligonucleotides holding multiple applications in the area of biomedicine. The advancements introduced with the Systematic Evolution of Ligands by EXponential enrichment (SELEX) approach further eased the scope of producing modified aptamers within a short span yet retaining the properties of stability and applicability. In the recent times, aptamers were identified to have the potential for penetrating into the deep human crevices and thus can be utilized in addressing the issues of complex neurological disorders. Considering the specificity and stability enhancement by chemical modifications, aptamer-based nanotechnologies may have great potential for future therapeutics and diagnostics (theranostics). The research community has already witnessed success with the approval of macugen (an anti-vascular endothelial growth factor aptamer) for treating degenerating eye disease, and hopefully those that are in the clinical trials will soon be translated for human application. Herein, we have summarized the aptamer chemistry, aptamer-nanoconjugates and their applications against neurological diseases.

  10. The early molecular processes underlying the neurological manifestations of an animal model of Wilson's disease.

    PubMed

    Lee, Beom Hee; Kim, Joo Hyun; Kim, Jae-Min; Heo, Sun Hee; Kang, Minji; Kim, Gu-Hwan; Choi, Jin-Ho; Yoo, Han-Wook

    2013-05-01

    The Long-Evans Cinnamon (LEC) rat shows age-dependent hepatic manifestations that are similar to those of Wilson's disease (WD). The pathogenic process in the brain has, however, not been evaluated in detail due to the rarity of the neurological symptoms. However, copper accumulation is noted in LEC rat brain tissue from 24 weeks of age, which results in oxidative injuries. The current study investigated the gene expression profiles of LEC rat brains at 24 weeks of age in order to identify the important early molecular changes that underlie the development of neurological symptoms in WD. Biological ontology-based analysis revealed diverse altered expressions of the genes related to copper accumulation. Of particular interest, we found altered expression of genes connected to mitochondrial respiration (Sdhaf2 and Ndufb7), calcineurin-mediated cellular processes (Ppp3ca, Ppp3cb, and Camk2a), amyloid precursor protein (Anks1b and A2m) and alpha-synuclein (Snca). In addition to copper-related changes, compensatory upregulations of Cp and Hamp reflect iron-mediated neurotoxicity. Of note, reciprocal expression of Asmt and Bhmt is an important clue that altered S-adenosylhomocysteine metabolism underlies brain injury in WD, which is directly correlated to the decreased expression of S-adenosylhomocysteine hydrolase in hepatic tissue in LEC rats. In conclusion, our study indicates that diverse molecular changes, both variable and complex, underlie the development of neurological manifestations in WD. Copper-related injuries were found to be the principal pathogenic process, but Fe- or adenosylhomocysteine-related injuries were also implicated. Investigations using other animal models or accessible human samples will be required to confirm our observations.

  11. Adaptive preconditioning in neurological diseases – therapeutic insights from proteostatic perturbations

    PubMed Central

    Mollereau, B.; Rzechorzek, N.M.; Roussel, B.D.; Sedru, M.; Van den Brink, D.M.; Bailly-Maitre, B.; Palladino, F.; Medinas, D.B.; Domingos, P.M.; Hunot, S.; Chandran, S.; Birman, S.; Baron, T.; Vivien, D.; Duarte, C.B.; Ryoo, H.D.; Steller, H.; Urano, F.; Chevet, E.; Kroemer, G.; Ciechanover, A.; Calabrese, E.J.; Kaufman, R.J.; Hetz, C.

    2016-01-01

    In neurological disorders, both acute and chronic neural stress can disrupt cellular proteostasis, resulting in the generation of pathological protein. However in most cases, neurons adapt to these proteostatic perturbations by activating a range of cellular protective and repair responses, thus maintaining cell function. These interconnected adaptive mechanisms comprise a ‘proteostasis network’ and include the unfolded protein response, the ubiquitin proteasome system and autophagy. Interestingly, several recent studies have shown that these adaptive responses can be stimulated by preconditioning treatments, which confer resistance to a subsequent toxic challenge – the phenomenon known as hormesis. In this review we discuss the impact of adaptive stress responses stimulated in diverse human neuropathologies including Parkinson’s disease, Wolfram syndrome, brain ischemia, and brain cancer. Further, we examine how these responses and the molecular pathways they recruit might be exploited for therapeutic gain. PMID:26923166

  12. Histone turnover and chromatin accessibility: Critical mediators of neurological development, plasticity, and disease

    PubMed Central

    Wenderski, Wendy; Maze, Ian

    2016-01-01

    In postmitotic neurons, nucleosomal turnover was long considered to be a static process that is inconsequential to transcription. However, our recent studies in human and rodent brain indicate that replication-independent (RI) nucleosomal turnover, which requires the histone variant H3.3, is dynamic throughout life and is necessary for activity-dependent gene expression, synaptic connectivity, and cognition. H3.3 turnover also facilitates cellular lineage specification and plays a role in suppressing the expression of heterochromatic repetitive elements, including mutagenic transposable sequences, in mouse embryonic stem cells. In this essay, we review mechanisms and functions for RI nucleosomal turnover in brain and present the hypothesis that defects in histone dynamics may represent a common mechanism underlying neurological aging and disease. PMID:26990528

  13. Dysregulation of gene expression as a cause of Cockayne syndrome neurological disease.

    PubMed

    Wang, Yuming; Chakravarty, Probir; Ranes, Michael; Kelly, Gavin; Brooks, Philip J; Neilan, Edward; Stewart, Aengus; Schiavo, Giampietro; Svejstrup, Jesper Q

    2014-10-01

    Cockayne syndrome (CS) is a multisystem disorder with severe neurological symptoms. The majority of CS patients carry mutations in Cockayne syndrome group B (CSB), best known for its role in transcription-coupled nucleotide excision repair. Indeed, because various repair pathways are compromised in patient cells, CS is widely considered a genome instability syndrome. Here, we investigate the connection between the neuropathology of CS and dysregulation of gene expression. Transcriptome analysis of human fibroblasts revealed that even in the absence of DNA damage, CSB affects the expression of thousands of genes, many of which are neuronal genes. CSB is present in a significant subset of these genes, suggesting that regulation is direct, at the level of transcription. Importantly, reprogramming of CS fibroblasts to neuron-like cells is defective unless an exogenous CSB gene is introduced. Moreover, neuroblastoma cells from which CSB is depleted show defects in gene expression programs required for neuronal differentiation, and fail to differentiate and extend neurites. Likewise, neuron-like cells cannot be maintained without CSB. Finally, a number of disease symptoms may be explained by marked gene expression changes in the brain of patients with CS. Together, these data point to dysregulation of gene regulatory networks as a cause of the neurological symptoms in CS. PMID:25249633

  14. Reaction time of patients with Parkinson's disease, with reference to asymmetry of neurological signs.

    PubMed Central

    Yokochi, F; Nakamura, R; Narabayashi, H

    1985-01-01

    Electromyographic reaction times of the left and the right finger extensor muscles in extension movement of the wrist were examined in 42 patients with Parkinson's disease, and 20 normal subjects. Compared to the normal subjects and the patients with neurological signs confined to the right side, the patients with neurological signs on the left side or on both sides showed slowing of reaction times regardless of the side of responding hand. The patients with asymmetry of bilateral neurological signs showed slower RTs on the more affected side. PMID:4031916

  15. Astrocyte Differentiation of Human Pluripotent Stem Cells: New Tools for Neurological Disorder Research

    PubMed Central

    Chandrasekaran, Abinaya; Avci, Hasan X.; Leist, Marcel; Kobolák, Julianna; Dinnyés, Andras

    2016-01-01

    Astrocytes have a central role in brain development and function, and so have gained increasing attention over the past two decades. Consequently, our knowledge about their origin, differentiation and function has increased significantly, with new research showing that astrocytes cultured alone or co-cultured with neurons have the potential to improve our understanding of various central nervous system diseases, such as amyotrophic lateral sclerosis, Alzheimer’s disease, or Alexander disease. The generation of astrocytes derived from pluripotent stem cells (PSCs) opens up a new area for studying neurologic diseases in vitro; these models could be exploited to identify and validate potential drugs by detecting adverse effects in the early stages of drug development. However, as it is now known that a range of astrocyte populations exist in the brain, it will be important in vitro to develop standardized protocols for the in vitro generation of astrocyte subsets with defined maturity status and phenotypic properties. This will then open new possibilities for co-cultures with neurons and the generation of neural organoids for research purposes. The aim of this review article is to compare and summarize the currently available protocols and their strategies to generate human astrocytes from PSCs. Furthermore, we discuss the potential role of human-induced PSCs derived astrocytes in disease modeling. PMID:27725795

  16. Current neurology

    SciTech Connect

    Appel, S.H. )

    1988-01-01

    The topics covered in this book include: Duchenne muscular dystrophy: DNA diagnosis in practice; Central nervous system magnetic resonance imaging; and Magnetic resonance spectroscopy of neurologic diseases.

  17. New techniques for positron emission tomography in the study of human neurological disorders

    SciTech Connect

    Kuhl, D.E.

    1989-11-01

    This progress report represents a summary of our performance during the two year period following initial start-up of these research activities at Michigan. Productivity has been excellent; already over 47 papers and abstracts have been published or accepted for publication from this still young program. They represent significant contributions to extending the technology of positron emission tomography in the study of human neurological disorders. Our focus is to develop more cost effective and efficient means for producing new functionally specific tracers and simpler, less expensive, means for acquiring and interpreting quantitative data. These improved processes are required for the future growth of PET as a sophisticated research tool and for the transfer of this technology to clinical use. Our approach concentrates on two separate yet related areas, radiosynthesis and data analysis. In subproject 1, Drs. Jewett and Mulholland have introduced innovative methods for improving 11C and 18F synthetic processes. In Subproject 2, Dr. Hutchins has laid the foundations for an objective analysis of the limitations and opportunities for quantifying regional PET data. In Subproject 3, Dr. Koeppe has extended rapid techniques for parameter estimation in kinetic modeling of new ligands. Finally, in Subproject 4, Dr. Frey has applied kinetic analysis to ligand tracing of the cholinergic neurotransmitter system in animal and human brain. These DOE supported studies have direct impact on clinical research here and elsewhere which is expected to improve diagnosis and treatment of degenerative neurological diseases, mental illness and brain tumors. 47 refs., 7 figs., 4 tabs.

  18. Recent achievements in restorative neurology: Progressive neuromuscular diseases

    SciTech Connect

    Dimitrijevic, M.R.; Kakulas, B.A.; Vrbova, G.

    1986-01-01

    This book contains 27 chapters. Some of the chapter titles are: Computed Tomography of Muscles in Neuromuscular Disease; Mapping the Genes for Muscular Dystrophy; Trophic Factors and Motor Neuron Development; Size of Motor Units and Firing Rate in Muscular Dystrophy; Restorative Possibilities in Relation to the Pathology of Progressive Neuromuscular Disease; and An Approach to the Pathogenesis of some Congenital Myopathies.

  19. WW domain-containing oxidoreductase in neuronal injury and neurological diseases.

    PubMed

    Chang, Hsin-Tzu; Liu, Chan-Chuan; Chen, Shur-Tzu; Yap, Ye Vone; Chang, Nan-Shang; Sze, Chun-I

    2014-12-15

    The human and mouse WWOX/Wwox gene encodes a candidate tumor suppressor WW domain-containing oxidoreductase protein. This gene is located on a common fragile site FRA16D. WWOX participates in a variety of cellular events and acts as a transducer in the many signal pathways, including TNF, chemotherapeutic drugs, UV irradiation, Wnt, TGF-β, C1q, Hyal-2, sex steroid hormones, and others. While transiently overexpressed WWOX restricts relocation of transcription factors to the nucleus for suppressing cancer survival, physiological relevance of this regard in vivo has not been confirmed. Unlike many tumor suppressor genes, mutation of WWOX is rare, raising a question whether WWOX is a driver for cancer initiation. WWOX/Wwox was initially shown to play a crucial role in neural development and in the pathogenesis of Alzheimer's disease and neuronal injury. Later on, WWOX/Wwox was shown to participate in the development of epilepsy, mental retardation, and brain developmental defects in mice, rats and humans. Up to date, most of the research and review articles have focused on the involvement of WWOX in cancer. Here, we review the role of WWOX in neural injury and neurological diseases, and provide perspectives for the WWOX-regulated neurodegeneration. PMID:25537520

  20. Genetics of complex neurological disease: Challenges and opportunities for modeling epilepsy in mice and rats

    PubMed Central

    Frankel, Wayne N.

    2009-01-01

    Epilepsy is a complex neurological disease. Currently ~20 genetic variants are known to cause Mendelian forms of human epilepsy, leaving a vast heritability undefined with future hopes resting on candidate gene resequencing and/or large scale genome-wide association studies. Rodent models for genetically complex epilepsy have been studied for many years, but only recently have strong candidate genes emerged, including Cacna1g in the GAERS rat model of absence epilepsy and Kcnj10 in the low seizure threshold of DBA/2 mice. In parallel, a growing number of mouse mutations studied on multiple strain backgrounds reveal how genetic modifiers have an enormous impact on seizure severity, incidence or form - perhaps mimicking the complexity seen in humans. The field of experimental genetics in rodents is now poised to study discrete epilepsy mutations on a diverse choice of strain backgrounds to develop better models and identify modifiers. But it must find the right balance between embracing the strain diversity available, with the ability to detect and characterize genetic effects. In practice, the use of alternate strain backgrounds when studying epilepsy mutations will enhance the modeling of epilepsy as a complex genetic disease. PMID:19665252

  1. Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies

    PubMed Central

    Samsel, Anthony; Seneff, Stephanie

    2015-01-01

    Manganese (Mn) is an often overlooked but important nutrient, required in small amounts for multiple essential functions in the body. A recent study on cows fed genetically modified Roundup®-Ready feed revealed a severe depletion of serum Mn. Glyphosate, the active ingredient in Roundup®, has also been shown to severely deplete Mn levels in plants. Here, we investigate the impact of Mn on physiology, and its association with gut dysbiosis as well as neuropathologies such as autism, Alzheimer's disease (AD), depression, anxiety syndrome, Parkinson's disease (PD), and prion diseases. Glutamate overexpression in the brain in association with autism, AD, and other neurological diseases can be explained by Mn deficiency. Mn superoxide dismutase protects mitochondria from oxidative damage, and mitochondrial dysfunction is a key feature of autism and Alzheimer’s. Chondroitin sulfate synthesis depends on Mn, and its deficiency leads to osteoporosis and osteomalacia. Lactobacillus, depleted in autism, depend critically on Mn for antioxidant protection. Lactobacillus probiotics can treat anxiety, which is a comorbidity of autism and chronic fatigue syndrome. Reduced gut Lactobacillus leads to overgrowth of the pathogen, Salmonella, which is resistant to glyphosate toxicity, and Mn plays a role here as well. Sperm motility depends on Mn, and this may partially explain increased rates of infertility and birth defects. We further reason that, under conditions of adequate Mn in the diet, glyphosate, through its disruption of bile acid homeostasis, ironically promotes toxic accumulation of Mn in the brainstem, leading to conditions such as PD and prion diseases. PMID:25883837

  2. Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies.

    PubMed

    Samsel, Anthony; Seneff, Stephanie

    2015-01-01

    Manganese (Mn) is an often overlooked but important nutrient, required in small amounts for multiple essential functions in the body. A recent study on cows fed genetically modified Roundup(®)-Ready feed revealed a severe depletion of serum Mn. Glyphosate, the active ingredient in Roundup(®), has also been shown to severely deplete Mn levels in plants. Here, we investigate the impact of Mn on physiology, and its association with gut dysbiosis as well as neuropathologies such as autism, Alzheimer's disease (AD), depression, anxiety syndrome, Parkinson's disease (PD), and prion diseases. Glutamate overexpression in the brain in association with autism, AD, and other neurological diseases can be explained by Mn deficiency. Mn superoxide dismutase protects mitochondria from oxidative damage, and mitochondrial dysfunction is a key feature of autism and Alzheimer's. Chondroitin sulfate synthesis depends on Mn, and its deficiency leads to osteoporosis and osteomalacia. Lactobacillus, depleted in autism, depend critically on Mn for antioxidant protection. Lactobacillus probiotics can treat anxiety, which is a comorbidity of autism and chronic fatigue syndrome. Reduced gut Lactobacillus leads to overgrowth of the pathogen, Salmonella, which is resistant to glyphosate toxicity, and Mn plays a role here as well. Sperm motility depends on Mn, and this may partially explain increased rates of infertility and birth defects. We further reason that, under conditions of adequate Mn in the diet, glyphosate, through its disruption of bile acid homeostasis, ironically promotes toxic accumulation of Mn in the brainstem, leading to conditions such as PD and prion diseases. PMID:25883837

  3. Translational research on cognitive and behavioural disorders in neurological and psychiatric diseases.

    PubMed

    Corvol, Jean-Christophe; Goni, Sylvia; Bordet, Régis

    2016-02-01

    The important medical and social burden of nervous system diseases contrasts with the currently limited therapeutic armamentarium and with the difficulty encountered in developing new therapeutic options. These failures can be explained by the conjunction of various phenomena related to the limitations of animal models, the narrow focus of research on precise pathophysiological mechanisms, and methodological issues in clinical trials. It is perhaps the paradigm itself of the way research is conducted that may be the real reason for our incapacity to find effective strategies. The purpose of this workshop was to define overall lines of research that could lead to the development of effective novel therapeutic solutions. Research has long focused on diseases per se rather than on cognitive and behavioural dimensions common to several diseases. Their expression is often partial and variable, but can today be well-characterised using neurophysiological or imaging methods. This dimensional or syndromic vision should enable a new insight to the question, taking a transnosographic approach to re-position research and to propose: translational models exploring the same functions in animal models and in humans; identification of homogeneous groups of patients defined according to the clinical, anatomico-functional and molecular characteristics; and preclinical and clinical developments enriched by the use of cognitive-behavioural, biological neurological, and imaging biomarkers. For this mutation to be successful, it must be accompanied by synchronised action from the public authorities and by ad hoc measures from the regulatory agencies. PMID:27080626

  4. Translational research on cognitive and behavioural disorders in neurological and psychiatric diseases.

    PubMed

    Corvol, Jean-Christophe; Goni, Sylvia; Bordet, Régis

    2016-02-01

    The important medical and social burden of nervous system diseases contrasts with the currently limited therapeutic armamentarium and with the difficulty encountered in developing new therapeutic options. These failures can be explained by the conjunction of various phenomena related to the limitations of animal models, the narrow focus of research on precise pathophysiological mechanisms, and methodological issues in clinical trials. It is perhaps the paradigm itself of the way research is conducted that may be the real reason for our incapacity to find effective strategies. The purpose of this workshop was to define overall lines of research that could lead to the development of effective novel therapeutic solutions. Research has long focused on diseases per se rather than on cognitive and behavioural dimensions common to several diseases. Their expression is often partial and variable, but can today be well-characterised using neurophysiological or imaging methods. This dimensional or syndromic vision should enable a new insight to the question, taking a transnosographic approach to re-position research and to propose: translational models exploring the same functions in animal models and in humans; identification of homogeneous groups of patients defined according to the clinical, anatomico-functional and molecular characteristics; and preclinical and clinical developments enriched by the use of cognitive-behavioural, biological neurological, and imaging biomarkers. For this mutation to be successful, it must be accompanied by synchronised action from the public authorities and by ad hoc measures from the regulatory agencies.

  5. Neurological Management of Von Hippel-Lindau Disease.

    PubMed

    Hodgson, Trent S; Nielsen, Sarah M; Lesniak, Maciej S; Lukas, Rimas V

    2016-09-01

    Von Hippel-Lindau disease is a genetic condition due to mutation of the Von Hippel-Lindau gene, which leads to an increased risk in the development of hemangioblastomas of the brain and spinal cord. The pathophysiology of disease and its clinical manifestations, as they pertain to the general neurologist, are discussed. Therapeutic management of central nervous system hemangioblastomas ranging from neurosurgical resection, radiation therapy, and systemic therapies is reviewed. PMID:27564075

  6. Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders.

    PubMed

    Barral, Serena; Kurian, Manju A

    2016-01-01

    The study of neurological disorders often presents with significant challenges due to the inaccessibility of human neuronal cells for further investigation. Advances in cellular reprogramming techniques, have however provided a new source of human cells for laboratory-based research. Patient-derived induced pluripotent stem cells (iPSCs) can now be robustly differentiated into specific neural subtypes, including dopaminergic, inhibitory GABAergic, motorneurons and cortical neurons. These neurons can then be utilized for in vitro studies to elucidate molecular causes underpinning neurological disease. Although human iPSC-derived neuronal models are increasingly regarded as a useful tool in cell biology, there are a number of limitations, including the relatively early, fetal stage of differentiated cells and the mainly two dimensional, simple nature of the in vitro system. Furthermore, clonal variation is a well-described phenomenon in iPSC lines. In order to account for this, robust baseline data from multiple control lines is necessary to determine whether a particular gene defect leads to a specific cellular phenotype. Over the last few years patient-derived neural cells have proven very useful in addressing several mechanistic questions related to central nervous system diseases, including early-onset neurological disorders of childhood. Many studies report the clinical utility of human-derived neural cells for testing known drugs with repurposing potential, novel compounds and gene therapies, which then can be translated to clinical reality. iPSCs derived neural cells, therefore provide great promise and potential to gain insight into, and treat early-onset neurological disorders. PMID:27656126

  7. Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders

    PubMed Central

    Barral, Serena; Kurian, Manju A.

    2016-01-01

    The study of neurological disorders often presents with significant challenges due to the inaccessibility of human neuronal cells for further investigation. Advances in cellular reprogramming techniques, have however provided a new source of human cells for laboratory-based research. Patient-derived induced pluripotent stem cells (iPSCs) can now be robustly differentiated into specific neural subtypes, including dopaminergic, inhibitory GABAergic, motorneurons and cortical neurons. These neurons can then be utilized for in vitro studies to elucidate molecular causes underpinning neurological disease. Although human iPSC-derived neuronal models are increasingly regarded as a useful tool in cell biology, there are a number of limitations, including the relatively early, fetal stage of differentiated cells and the mainly two dimensional, simple nature of the in vitro system. Furthermore, clonal variation is a well-described phenomenon in iPSC lines. In order to account for this, robust baseline data from multiple control lines is necessary to determine whether a particular gene defect leads to a specific cellular phenotype. Over the last few years patient-derived neural cells have proven very useful in addressing several mechanistic questions related to central nervous system diseases, including early-onset neurological disorders of childhood. Many studies report the clinical utility of human-derived neural cells for testing known drugs with repurposing potential, novel compounds and gene therapies, which then can be translated to clinical reality. iPSCs derived neural cells, therefore provide great promise and potential to gain insight into, and treat early-onset neurological disorders. PMID:27656126

  8. Meningeal worm-induced neurologic disease in black-tailed deer.

    PubMed

    Nettles, V F; Prestwood, A K; Nichols, R G; Whitehead, C J

    1977-04-01

    Neurologic disease attributable to Parelaphostrongylus tenuis was diagnosed in five black-tailed deer (Odocoileus hemionus columbianus) relocated from Oregon to Tennessee. Mortality occurred in the pre-release enclosure and in the release area. Infection with P. tenuis was considered the cause of an unsuccessful stocking attempt. In addition, neurologic disease was produced by experimental infection of a black-tailed x white-tailed deer hybrid. Clinical and pathologic findings were described for black-tailed and hybrid deer, and epizootiologic aspects of P. tenuis infections were discussed.

  9. Antibodies to neuronal targets in neurological and psychiatric diseases.

    PubMed

    Vincent, Angela; Dalton, Paola; Clover, Linda; Palace, Jackie; Lang, Bethan

    2003-05-01

    The role of antibodies to specific neuronal and muscle ion channels in the etiology of neuromuscular transmission disorders is now well accepted. In addition, maternal antibodies can cross the placenta and cause neonatal disease or even alter the development of the infant, raising the possibility that some neurodevelopmental conditions could be caused by maternal antibodies. Voltage-gated ion channels are expressed in the brain as well as at the neuromuscular junction, and in recent years it has become clear that antibodies to some central nervous system (CNS) channels can be associated with CNS disease. This review highlights features of these conditions, preliminary investigations into neurodevelopmental disorders, and areas for further study.

  10. 76 FR 36993 - Medical Devices; Neurological Devices; Clarification of Classification for Human Dura Mater...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... classification for human dura mater. This action is being taken to improve the accuracy of the regulations. DATES... HUMAN SERVICES Food and Drug Administration 21 CFR Part 882 (formerly Docket No. 1997N-0484P) Medical Devices; Neurological Devices; Clarification of Classification for Human Dura Mater; Technical...

  11. Looks can be deceiving: three cases of neurological diseases mimicking Guillain-Barrè syndrome.

    PubMed

    Sciacca, G; Nicoletti, A; Fermo, S Lo; Mostile, G; Giliberto, C; Zappia, Mario

    2016-04-01

    Guillain-Barrè syndrome (GBS) is an acute, paralyzing, inflammatory peripheral nerve disease, featured by monophasic disease course, symmetrical limb weakness and areflexia. Several pathologies can mimic the clinical presentation of GBS, making hard the differential diagnosis for patients complaining of acute flaccid paralysis. In this paper we describe three cases of different neurological diseases presenting with acute motor symptoms mimicking GBS, reviewing the relevant literature on misdiagnosis of GBS.

  12. Fahr's disease: a rare neurological presentation in a tropical setting

    PubMed Central

    Otu, Akaninyene Asuquo; Anikwe, Jude Chinedu; Cocker, Derek

    2015-01-01

    Key Clinical Message While rare, Fahr's disease should be considered as a differential diagnosis for seizures, movement disorders, or cognitive impairment in tropical settings. Classically, bilateral calcification of the basal ganglia is seen on CT. Endemic infections, metabolic, and toxic causes should be excluded. Treatment using Levodopa is often beneficial. PMID:26509011

  13. Lymphatics in Neurological Disorders: A Neuro-Lympho-Vascular Component of Multiple Sclerosis and Alzheimer's Disease?

    PubMed

    Louveau, Antoine; Da Mesquita, Sandro; Kipnis, Jonathan

    2016-09-01

    Lymphatic vasculature drains interstitial fluids, which contain the tissue's waste products, and ensures immune surveillance of the tissues, allowing immune cell recirculation. Until recently, the CNS was considered to be devoid of a conventional lymphatic vasculature. The recent discovery in the meninges of a lymphatic network that drains the CNS calls into question classic models for the drainage of macromolecules and immune cells from the CNS. In the context of neurological disorders, the presence of a lymphatic system draining the CNS potentially offers a new player and a new avenue for therapy. In this review, we will attempt to integrate the known primary functions of the tissue lymphatic vasculature that exists in peripheral organs with the proposed function of meningeal lymphatic vessels in neurological disorders, specifically multiple sclerosis and Alzheimer's disease. We propose that these (and potentially other) neurological afflictions can be viewed as diseases with a neuro-lympho-vascular component and should be therapeutically targeted as such. PMID:27608759

  14. EXAMINER executive function battery and neurologic morbidity in pediatric sickle cell disease.

    PubMed

    Schatz, Jeffrey; Stancil, Melita; Katz, Tal; Sanchez, Carmen E

    2014-01-01

    Sickle cell disease (SCD) is blood disorder with a high risk for cerebral vascular morbidities that impact neurocognitive functioning. Specific cognitive abilities are known to be more sensitive to neurologic effects of SCD than IQ scores, yet there is little consensus about which measures to use to assess neurocognitive functioning. We evaluated the ability of the Executive Abilities: Methods and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) Battery to detect neurologic effects in SCD. Thirty-two youth with SCD and sixty demographically-matched comparison youth completed the EXAMINER Battery and selected tests from the Woodcock-Johnson Tests of Cognitive Ability, 3rd edition (WJ-III). Neurologic severity was examined via clinical history for morbidities and midsagittal corpus callosum (CC) area. Results indicated cognitive performance decreased with increasing neurologic morbidity across all cognitive measures; two of four EXAMINER factors were related to CC area. The association with clinical history and midsagittal CC area appeared at least as large for the Examiner Battery scores as for the WJ-III measures. The Examiner Battery showed sensitivity to neurologic history and white matter effects in SCD; this new measure compares favorably to established measures of disease-related neurocognitive effects, but would benefit from further development. PMID:24280593

  15. Simultaneous expression of Borrelia OspA and OspC and IgM response in cerebrospinal fluid in early neurologic Lyme disease.

    PubMed Central

    Schutzer, S E; Coyle, P K; Krupp, L B; Deng, Z; Belman, A L; Dattwyler, R; Luft, B J

    1997-01-01

    Lyme disease is the major tick-borne disease, caused by Borrelia burgdorferi (Bb). Neurological involvement is common in all stages. In vivo expression of Bb antigens (Ags) and the immune response to them has not been well investigated in the cerebrospinal fluid (CSF). Upregulation of outer surface protein (Osp) C and concomitant downregulation of OspA before tick inoculation of the spirochete has been reported in skin and blood in animals. CSF OspA Ag in early disease suggests otherwise in CSF. Early Ag expression and IgM response in human CSF was investigated here. Paired CSF and serum was collected from 16 early, predominantly erythema migrans Lyme disease patients with neurologic problems, 13 late Lyme disease patients, and 19 other neurologic disease (OND) controls. Samples were examined for IgM reactivity to recombinant Bb-specific Osps using ELISA and immunoblot. Of 12 early Lyme disease patients with neurologic involvement with both CSF and serum IgM against OspC, 7 (58%) had IgM to OspA (n = 5) or OspB (n = 2) that was restricted to the CSF, not serum. Overall, 12 of 16 (75%) of these early Lyme disease patients with neurologic involvement had CSF and serum IgM against OspC. Only 3 of 13 (23%) late Lyme disease patients and none of 19 OND controls had CSF IgM directed against OspC. In conclusion, in CSF, OspC and OspA can be coexpressed, and IgM response to them occurs in early Lyme disease patients with neurologic involvement. This biologic finding may also provide a discriminating marker for CNS infection in Lyme disease. PMID:9259573

  16. Human disease genes.

    PubMed

    Jimenez-Sanchez, G; Childs, B; Valle, D

    2001-02-15

    The complete human genome sequence will facilitate the identification of all genes that contribute to disease. We propose that the functional classification of disease genes and their products will reveal general principles of human disease. We have determined functional categories for nearly 1,000 documented disease genes, and found striking correlations between the function of the gene product and features of disease, such as age of onset and mode of inheritance. As knowledge of disease genes grows, including those contributing to complex traits, more sophisticated analyses will be possible; their results will yield a deeper understanding of disease and an enhanced integration of medicine with biology.

  17. Human neuro-specimen banking 1961-1992. The National Neurological Research Specimen Bank (a donor program of pre- and post-mortem tissues and cerebrospinal fluid/blood; and a collection of cryopreserved human neurological specimens for neuroscientists).

    PubMed

    Tourtellotte, W W; Rosario, I P; Conrad, A; Syndulko, K

    1993-01-01

    The National Neurological Research Specimen Bank (The Bank) was established in 1961 to provide a vital service to neuroscientists. Our purpose is to support medical research which seeks the etiopathogenesis for devastating neurological disorders with no known cause, treatment or precise animal model. It serves as a bridge between the neurology clinician who diagnoses and cares for patients with incurable disease and the basic scientist who has need for specimens to find their etiopathogenesis. In the long run this service should advance neurologic diagnoses and serve as the basis for designing treatment. The Bank has grown to be the largest, most diverse neurological specimen bank of its kind in the world. It is a type of "tissue bank" where donor members "will" their central nervous system tissues to science. Then we collect, photograph, seal in air tight bags, quick freeze, cryogenically store and distribute on request the donated tissue to research scientists around the world. All tissue diagnoses are confirmed by clinical records and neuropathologic examination; further histology is conducted on request. In addition to brain and spinal cord tissues, the Bank has samples of other tissues. There are also samples of pre- and post-mortem CSF and sera from normal individuals and patients with various neurological disorders, especially serial specimens on multiple sclerosis patients and HIV-1 seropositive and at risk individuals. This paper outlines the global operations of our human brain bank, based on protocols developed and used by the authors. These operations include donor solicitation, tissue acquisition and documentation, tissue processing and storage, specimen dissemination to users, outcome assessment of banking, quality control, cost of our operation, table of organization and the future. PMID:8360665

  18. Dolphins, dogs, and robot seals for the treatment of neurological disease.

    PubMed

    Burton, Adrian

    2013-09-01

    A growing body of evidence suggests that animal-assisted therapies and activities involving all kinds of real and even robotic animals can have beneficial eff ects in people with neurological disease or mental illness. But what is the quality of that evidence and do these interventions really provide any health benefits? Adrian Burton investigates.

  19. The use of complementary and alternative medicine in children with common neurologic diseases

    PubMed Central

    Yeon, Gyu-Min

    2016-01-01

    Complementary and alternative medicine (CAM) is a phrase used to describe additional health care methods such as mind/body practices and natural products not regarded as treatments by conventional medicine. The use of CAM in children with common neurologic diseases is more frequent than its use in healthy children (24%–78% vs. 12%). However, less than half of patients report such use to their physicians. The preferred modalities of CAM vary in different countries due to their different cultures and traditions. The most common factor significantly associated with the use of CAM is parental CAM use in most studies. The frequency of the use of CAM in children and adults with neurologic diseases is similar, and both rates are higher than the rates in those without these conditions. The preferred modalities of CAM in adults are diverse, and megavitamins and mind/body therapy (prayer and chiropractic care) are included. The most common factor significantly associated with the use of CAM in adults with neurologic diseases is high educational level. Physicians need to be concerned with patients' use of CAM and provide correct information about CAM so that patients may make the right decisions. Further study is needed to determine the evidence-based efficacy of CAM use in children with common neurologic diseases.

  20. Dolphins, dogs, and robot seals for the treatment of neurological disease.

    PubMed

    Burton, Adrian

    2013-09-01

    A growing body of evidence suggests that animal-assisted therapies and activities involving all kinds of real and even robotic animals can have beneficial eff ects in people with neurological disease or mental illness. But what is the quality of that evidence and do these interventions really provide any health benefits? Adrian Burton investigates. PMID:23948175

  1. The use of complementary and alternative medicine in children with common neurologic diseases.

    PubMed

    Yeon, Gyu-Min; Nam, Sang Ook

    2016-08-01

    Complementary and alternative medicine (CAM) is a phrase used to describe additional health care methods such as mind/body practices and natural products not regarded as treatments by conventional medicine. The use of CAM in children with common neurologic diseases is more frequent than its use in healthy children (24%-78% vs. 12%). However, less than half of patients report such use to their physicians. The preferred modalities of CAM vary in different countries due to their different cultures and traditions. The most common factor significantly associated with the use of CAM is parental CAM use in most studies. The frequency of the use of CAM in children and adults with neurologic diseases is similar, and both rates are higher than the rates in those without these conditions. The preferred modalities of CAM in adults are diverse, and megavitamins and mind/body therapy (prayer and chiropractic care) are included. The most common factor significantly associated with the use of CAM in adults with neurologic diseases is high educational level. Physicians need to be concerned with patients' use of CAM and provide correct information about CAM so that patients may make the right decisions. Further study is needed to determine the evidence-based efficacy of CAM use in children with common neurologic diseases. PMID:27610179

  2. The use of complementary and alternative medicine in children with common neurologic diseases

    PubMed Central

    Yeon, Gyu-Min

    2016-01-01

    Complementary and alternative medicine (CAM) is a phrase used to describe additional health care methods such as mind/body practices and natural products not regarded as treatments by conventional medicine. The use of CAM in children with common neurologic diseases is more frequent than its use in healthy children (24%–78% vs. 12%). However, less than half of patients report such use to their physicians. The preferred modalities of CAM vary in different countries due to their different cultures and traditions. The most common factor significantly associated with the use of CAM is parental CAM use in most studies. The frequency of the use of CAM in children and adults with neurologic diseases is similar, and both rates are higher than the rates in those without these conditions. The preferred modalities of CAM in adults are diverse, and megavitamins and mind/body therapy (prayer and chiropractic care) are included. The most common factor significantly associated with the use of CAM in adults with neurologic diseases is high educational level. Physicians need to be concerned with patients' use of CAM and provide correct information about CAM so that patients may make the right decisions. Further study is needed to determine the evidence-based efficacy of CAM use in children with common neurologic diseases. PMID:27610179

  3. [A spectrum of neurological diseases with anti-VGKC antibody].

    PubMed

    Arimura, Kimiyoshi; Watanabe, Osamu; Nagado, Tatsui

    2007-11-01

    Anti-VGKC antibody causing peripheral nerve hyperexcitability is already an established clinical entity. Recently, many patients with non-herpetic limbic encephalitis (NHLE) with anti-VGKC antibody have been reported. The characteristic clinical features are low serum Na+ concentration and good response to immunotherapy. Anti-VGK antibody positive NHLE is relatively frequent among immune-mediated NHLE. It is important to know that this disease is responsive to immunotherapy. Furthermore, anti-VGKC antibody is also positive in some intractable epilepsies. These findings suggest that anti-VGKC is correlated with hyperexcitability in both the peripheral and central nervous system and that the spectrum of anti-VGKC antibody syndrome is now expanding.

  4. Neurologic Complications of HIV Disease and Their Treatment

    PubMed Central

    Letendre, Scott L.; Ellis, Ronald J.; Ances, Beau M.; McCutchan, J. Allen

    2015-01-01

    Findings on the nervous system complications of HIV disease and their impact on people living with HIV continue to accumulate. New reports at the 17th Conference on Retroviruses and Opportunistic Infections this year confirmed that HIV-associated neurocognitive disorders (HAND) are common, even among effectively treated individuals. Risk of HAND correlated with nadir CD4+ cell counts and with cerebrospinal fluid (CSF) viral loads that were at least as high as plasma viral loads. Other new data regarding risk factors for HAND implicated vascular disease, apolipoprotein E and mannose binding lectin genotypes, reduced resting cerebral blood flow, and HIV mutants that cause macrophages to shed the HIV gp120 protein. Two analyses linked worse neurocognitive performance to use of efavirenz, raising concerns about neurotoxicity. Analyses comparing differences in estimated distribution of antiretroviral drugs into the central nervous system (CNS) to neurocognitive outcomes using the 2008 version of the CNS penetration-effectiveness (CPE) ranking system did not support a hypothesis of neurotoxicity but did have mixed results, some supporting a benefit and some supporting no effect. Of note, a revised version of the CPE ranking system was presented that was more strongly associated with CSF viral loads than the 2008 version. Reports also estimated that primary CSF virologic failure occurs in 3% to 10% of treated individuals, although the clinical consequences of this remain uncertain. New data on common coinfections in people with HIV identified that a specific strain of Treponema pallidum may be more neurovirulent than other strains, that hepatitis C virus Core protein may be neurotoxic, and that hepatitis B virus may replicate in the nervous system. The extensive data presented will inform new research and clinical decisions in the coming year. PMID:20516524

  5. Predicting targets of compounds against neurological diseases using cheminformatic methodology.

    PubMed

    Nikolic, Katarina; Mavridis, Lazaros; Bautista-Aguilera, Oscar M; Marco-Contelles, José; Stark, Holger; do Carmo Carreiras, Maria; Rossi, Ilaria; Massarelli, Paola; Agbaba, Danica; Ramsay, Rona R; Mitchell, John B O

    2015-02-01

    Recently developed multi-targeted ligands are novel drug candidates able to interact with monoamine oxidase A and B; acetylcholinesterase and butyrylcholinesterase; or with histamine N-methyltransferase and histamine H3-receptor (H3R). These proteins are drug targets in the treatment of depression, Alzheimer's disease, obsessive disorders, and Parkinson's disease. A probabilistic method, the Parzen-Rosenblatt window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Molecular structures were represented based on the circular fingerprint methodology. The same approach was used to build a "predictor" model from the DrugBank dataset to determine the main pharmacological groups of the compound. The study of off-target interactions is now recognised as crucial to the understanding of both drug action and toxicology. Primary pharmaceutical targets and off-targets for the novel multi-target ligands were examined by use of the developed cheminformatic method. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. The cheminformatic targets identifications were in agreement with four 3D-QSAR (H3R/D1R/D2R/5-HT2aR) models and by in vitro assays for serotonin 5-HT1a and 5-HT2a receptor binding of the most promising ligand (71/MBA-VEG8).

  6. Variance of gene expression identifies altered network constraints in neurological disease.

    PubMed

    Mar, Jessica C; Matigian, Nicholas A; Mackay-Sim, Alan; Mellick, George D; Sue, Carolyn M; Silburn, Peter A; McGrath, John J; Quackenbush, John; Wells, Christine A

    2011-08-01

    Gene expression analysis has become a ubiquitous tool for studying a wide range of human diseases. In a typical analysis we compare distinct phenotypic groups and attempt to identify genes that are, on average, significantly different between them. Here we describe an innovative approach to the analysis of gene expression data, one that identifies differences in expression variance between groups as an informative metric of the group phenotype. We find that genes with different expression variance profiles are not randomly distributed across cell signaling networks. Genes with low-expression variance, or higher constraint, are significantly more connected to other network members and tend to function as core members of signal transduction pathways. Genes with higher expression variance have fewer network connections and also tend to sit on the periphery of the cell. Using neural stem cells derived from patients suffering from Schizophrenia (SZ), Parkinson's disease (PD), and a healthy control group, we find marked differences in expression variance in cell signaling pathways that shed new light on potential mechanisms associated with these diverse neurological disorders. In particular, we find that expression variance of core networks in the SZ patient group was considerably constrained, while in contrast the PD patient group demonstrated much greater variance than expected. One hypothesis is that diminished variance in SZ patients corresponds to an increased degree of constraint in these pathways and a corresponding reduction in robustness of the stem cell networks. These results underscore the role that variation plays in biological systems and suggest that analysis of expression variance is far more important in disease than previously recognized. Furthermore, modeling patterns of variability in gene expression could fundamentally alter the way in which we think about how cellular networks are affected by disease processes.

  7. Liver transplantation in neurological Wilson's Disease: is there indication? A case report.

    PubMed

    Mocchegiani, F; Gemini, S; Vincenzi, P; Montalti, R; Vecchi, A; Nicolini, D; Federici, A; Coletta, M; Pansini, M; Lanari, J; Svegliati Baroni, G; Risaliti, A; Vivarelli, M

    2014-09-01

    Wilson's disease (WD) is an autosomal recessive disorder characterized by copper overload. In this disease, inadequate hepatic excretion leads to copper accumulation in the liver, brain, kidney, and cornea. Severe neurological symptoms can develop in patients with WD, often in the absence of relevant liver damage: it is unclear whether liver transplantation (LT) could reverse neurological symptoms, and at present LT is not recommended in this setting. We report a case of regression of neurological symptoms in a patient affected by WD with prevalent neurological involvement. A 19-year-old man with disabling neuropsychiatric symptoms from WD that included frontal ataxia, akinesia, dystonia, tremors, and behavioral disorders in the presence of preserved liver function (Model for End-Stage Liver Disease score=7; Child-Turcotte-Pugh score=A5) underwent LT in November 2009. At the time of LT, encephalic magnetic resonance imaging (MRI) indicated diffuse neurodegenerative alterations involving subtentorial and supratentorial structures; bilateral Kayser-Fleischer ring was present. Four years after LT, laboratory tests show normalized copper metabolism and excellent liver function test results. Encephalic MRI shows a substantial improvement of already-known signal alterations at nuclei thalamus and putamen, mesencephalon, and pons. Kayser-Fleischer ring disappeared from the right eye, but a little remnant is still visible in the left eye. At neurological examination, all of the previous symptoms and signs are no longer present and behavioral disorders are no longer present; psychosocial functions are completely restored. The present case provides some evidence that LT may be a valid therapeutic option for WD patients with marked neurological impairment, particularly in those no longer responsive to chelation therapy.

  8. 123I-Meta-iodobenzylguanidine Sympathetic Imaging: Standardization and Application to Neurological Diseases

    PubMed Central

    Yamada, Masahito

    2016-01-01

    123I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of 123I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of 123I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity. Since H/M ratios significantly vary according to acquisition and processing conditions, quality control should be appropriate, and quantitation should be standardized. The threshold H/M ratio for differentiating Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to comparable values of medium-energy collimators. Parkinson's disease can be separated from various types of parkinsonian syndromes using cardiac 123I-MIBG, whereas activity is decreased on images of Lewy-body diseases using both 123I-ioflupane for the striatum and 123I-MIBG. Despite being a simple index, the H/M ratio of 123I-MIBG uptake is reproducible and can serve as an effective tool to support a diagnosis of Lewy-body diseases in neurological practice. PMID:27689024

  9. 123I-Meta-iodobenzylguanidine Sympathetic Imaging: Standardization and Application to Neurological Diseases

    PubMed Central

    Yamada, Masahito

    2016-01-01

    123I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of 123I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of 123I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity. Since H/M ratios significantly vary according to acquisition and processing conditions, quality control should be appropriate, and quantitation should be standardized. The threshold H/M ratio for differentiating Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to comparable values of medium-energy collimators. Parkinson's disease can be separated from various types of parkinsonian syndromes using cardiac 123I-MIBG, whereas activity is decreased on images of Lewy-body diseases using both 123I-ioflupane for the striatum and 123I-MIBG. Despite being a simple index, the H/M ratio of 123I-MIBG uptake is reproducible and can serve as an effective tool to support a diagnosis of Lewy-body diseases in neurological practice.

  10. (123)I-Meta-iodobenzylguanidine Sympathetic Imaging: Standardization and Application to Neurological Diseases.

    PubMed

    Nakajima, Kenichi; Yamada, Masahito

    2016-09-01

    (123)I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of (123)I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of (123)I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity. Since H/M ratios significantly vary according to acquisition and processing conditions, quality control should be appropriate, and quantitation should be standardized. The threshold H/M ratio for differentiating Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to comparable values of medium-energy collimators. Parkinson's disease can be separated from various types of parkinsonian syndromes using cardiac (123)I-MIBG, whereas activity is decreased on images of Lewy-body diseases using both (123)I-ioflupane for the striatum and (123)I-MIBG. Despite being a simple index, the H/M ratio of (123)I-MIBG uptake is reproducible and can serve as an effective tool to support a diagnosis of Lewy-body diseases in neurological practice. PMID:27689024

  11. Thymosin β4 as a restorative/regenerative therapy for neurological injury and neurodegenerative diseases.

    PubMed

    Chopp, Michael; Zhang, Zheng Gang

    2015-01-01

    Thymosin β4 (Tβ4) promotes CNS and peripheral nervous system (PNS) plasticity and neurovascular remodeling leading to neurological recovery in a range of neurological diseases. Treatment of neural injury and neurodegenerative disease 24 h or more post-injury and disease onset with Tβ4 enhances angiogenesis, neurogenesis, neurite and axonal outgrowth, and oligodendrogenesis, and thereby, significantly improves functional and behavioral outcomes. We propose that oligodendrogenesis is a common link by which Tβ4 promotes recovery after neural injury and neurodegenerative disease. The ability to target many diverse restorative processes via multiple molecular pathways that drive oligodendrogenesis and neurovascular remodeling may be mediated by the ability of Tβ4 to alter cellular expression of microRNAs (miRNAs). However, further investigations on the essential role of miRNAs in regulating protein expression and the remarkable exosomal intercellular communication network via exosomes will likely provide insight into mechanisms of action and means to amplify the therapeutic effects of Tβ4.

  12. How embodied is action language? Neurological evidence from motor diseases.

    PubMed

    Cardona, Juan F; Kargieman, Lucila; Sinay, Vladimiro; Gershanik, Oscar; Gelormini, Carlos; Amoruso, Lucia; Roca, María; Pineda, David; Trujillo, Natalia; Michon, Maëva; García, Adolfo M; Szenkman, Daniela; Bekinschtein, Tristán; Manes, Facundo; Ibáñez, Agustín

    2014-05-01

    Although motor-language coupling is now being extensively studied, its underlying mechanisms are not fully understood. In this sense, a crucial opposition has emerged between the non-representational and the representational views of embodiment. The former posits that action language is grounded on the non-brain motor system directly engaged by musculoskeletal activity - i.e., peripheral involvement of ongoing actions. Conversely, the latter proposes that such grounding is afforded by the brain's motor system - i.e., activation of neural areas representing motor action. We addressed this controversy through the action-sentence compatibility effect (ACE) paradigm, which induces a contextual coupling of motor actions and verbal processing. ACEs were measured in three patient groups - early Parkinson's disease (EPD), neuromyelitis optica (NMO), and acute transverse myelitis (ATM) patients - as well as their respective healthy controls. NMO and ATM constitute models of injury to non-brain motor areas and the peripheral motor system, whereas EPD provides a model of brain motor system impairment. In our study, EPD patients exhibited impaired ACE and verbal processing relative to healthy participants, NMO, and ATM patients. These results indicate that the processing of action-related words is mainly subserved by a cortico-subcortical motor network system, thus supporting a brain-based embodied view on action language. More generally, our findings are consistent with contemporary perspectives for which action/verb processing depends on distributed brain networks supporting context-sensitive motor-language coupling. PMID:24594627

  13. Mast cell activation disease: An underappreciated cause of neurologic and psychiatric symptoms and diseases.

    PubMed

    Afrin, Lawrence B; Pöhlau, Dieter; Raithel, Martin; Haenisch, Britta; Dumoulin, Franz L; Homann, Juergen; Mauer, Uwe M; Harzer, Sabrina; Molderings, Gerhard J

    2015-11-01

    Neurologists and psychiatrists frequently encounter patients whose central and/or peripheral neurologic and/or psychiatric symptoms (NPS) are accompanied by other symptoms for which investigation finds no unifying cause and for which empiric therapy often provides little to no benefit. Systemic mast cell activation disease (MCAD) has rarely been considered in the differential diagnosis in such situations. Traditionally, MCAD has been considered as just one rare (neoplastic) disease, mastocytosis, generally focusing on the mast cell (MC) mediators tryptase and histamine and the suggestive, blatant symptoms of flushing and anaphylaxis. Recently another form of MCAD, MC activation syndrome (MC), has been recognized, featuring inappropriate MC activation with little to no neoplasia and likely much more heterogeneously clonal and far more prevalent than mastocytosis. There also has developed greater appreciation for the truly very large menagerie of MC mediators and their complex patterns of release, engendering complex, nebulous presentations of chronic and acute illness best characterized as multisystem polymorbidity of generally inflammatory ± allergic themes--including very wide arrays of central and peripheral NPS. Significantly helpful treatment--including for neuropsychiatric issues--usually can be identified once MCAD is accurately diagnosed. We describe MCAD's pathogenesis, presentation (focusing on NPS), and therapy, especially vis-à-vis neuropsychotropes. Since MCAD patients often present NPS, neurologists and psychiatrists have the opportunity, in recognizing the diagnostic possibility of MCAD, to short-circuit the often decades-long delay in establishing the correct diagnosis required to identify optimal therapy.

  14. MicroRNAs: Key Regulators in the Central Nervous System and Their Implication in Neurological Diseases

    PubMed Central

    Cao, Dan-Dan; Li, Lu; Chan, Wai-Yee

    2016-01-01

    MicroRNAs (miRNAs) are a class of small, well-conserved noncoding RNAs that regulate gene expression post-transcriptionally. They have been demonstrated to regulate a lot of biological pathways and cellular functions. Many miRNAs are dynamically regulated during central nervous system (CNS) development and are spatially expressed in adult brain indicating their essential roles in neural development and function. In addition, accumulating evidence strongly suggests that dysfunction of miRNAs contributes to neurological diseases. These observations, together with their gene regulation property, implicated miRNAs to be the key regulators in the complex genetic network of the CNS. In this review, we first focus on the ways through which miRNAs exert the regulatory function and how miRNAs are regulated in the CNS. We then summarize recent findings that highlight the versatile roles of miRNAs in normal CNS physiology and their association with several types of neurological diseases. Subsequently we discuss the limitations of miRNAs research based on current studies as well as the potential therapeutic applications and challenges of miRNAs in neurological disorders. We endeavor to provide an updated description of the regulatory roles of miRNAs in normal CNS functions and pathogenesis of neurological diseases. PMID:27240359

  15. Clinical and immunological relevance of anti-neuronal antibodies in celiac disease with neurological manifestations

    PubMed Central

    Caio, Giacomo; Giorgio, Roberto De; Venturi, Alessandro; Giancola, Fiorella; Latorre, Rocco; Boschetti, Elisa; Serra, Mauro; Ruggeri, Eugenio; Volta, Umberto

    2015-01-01

    Aim: To assess anti-neuronal antibodies (NA) prevalence and their correlation with neurological disorders and bowel habits in celiac disease (CD) patients. Background: Neurological manifestations are estimated to occur in about 10% of celiac disease patients and NA to central nervous system (CNS) and enteric nervous system (ENS) are found in a significant proportion of them. Little is known about the clinical and immunological features in CD patients with neurological manifestations. Patients and methods: NA to CNS and ENS were investigated in 106 CD patients and in 60 controls with autoimmune disorders by indirect immunofluorescence on rat / primate cerebellar cortex and intestinal (small and large bowel) sections. Results: IgG NA to CNS (titer 1:50 - 1:400) were positive in 23 celiacs (21%), being more frequently detected in those with neurological disorders that in those without neurological dysfunction (49% vs. 8%, P< 0.0001). Of the 26 celiacs (24%) with IgG NA to ENS, 11 out of 12 with an antibody titer > 1:200 had severe constipation. Only one patient with cerebellar ataxia and intestinal sub-occlusion was positive for NA to CNS and ENS. NA to CNS and ENS were found in 7% and 5% of controls, respectively. Conclusion: In CD the positivity of NA to CNS can be regarded as a marker of neurological manifestations. High titer NA to ENS are associated with severe constipation. The demonstration of NA to CNS and ENS suggests an immune-mediated pathogenesis leading to central neural impairment as well as gut dysfunction (hence constipation), respectively. PMID:25926940

  16. Minds on replay: musical hallucinations and their relationship to neurological disease.

    PubMed

    Golden, Erin C; Josephs, Keith A

    2015-12-01

    The phenomenon of musical hallucinations, in which individuals perceive music in the absence of an external auditory stimulus, has been described sparingly in the literature through small case reports and series. Musical hallucinations have been linked to multiple associated conditions, including psychiatric and neurologic disease, brain lesions, drug effect, and hearing impairment. This study aimed to review the demographics of subjects with musical hallucinations and to determine the prevalence of neurological disorders, particularly neurodegenerative disease. Through the Mayo medical record, 393 subjects with musical hallucinations were identified and divided into five categories based on comorbid conditions that have been associated with musical hallucinations: neurological, psychiatric, structural, drug effect and not otherwise classifiable. Variables, including hearing impairment and the presence of visual and other auditory hallucinations, were evaluated independently in all five groups. The mean age at onset of the hallucinations was 56 years, ranging from 18 to 98 years, and 65.4% of the subjects were female. Neurological disease and focal brain lesions were found in 25% and 9% of the total subjects, respectively. Sixty-five subjects were identified with a neurodegenerative disorder, with the Lewy body disorders being the most common. Visual hallucinations were more common in the group with neurological disease compared to the psychiatric, structural, and not otherwise classifiable groups (P < 0.001), whereas auditory hallucinations were more common in the psychiatric group compared to all other groups (P < 0.001). Structural lesions associated with musical hallucinations involved both hemispheres with a preference towards the left, and all but two included the temporal lobe. Hearing impairment was common, particularly in the not otherwise classifiable category where 67.2% had documented hearing impairment, more than in any other group (P < 0.001). Those

  17. An update of neurological manifestations of vasculitides and connective tissue diseases: a literature review.

    PubMed

    Bougea, Anastasia; Anagnostou, Evangelos; Spandideas, Nikolaos; Triantafyllou, Nikolaos; Kararizou, Evangelia

    2015-01-01

    Vasculitides comprise a heterogeneous group of autoimmune disorders, occurring as primary or secondary to a broad variety of systemic infectious, malignant or connective tissue diseases. The latter occur more often but their pathogenic mechanisms have not been fully established. Frequent and varied central and peripheral nervous system complications occur in vasculitides and connective tissue diseases. In many cases, the neurological disorders have an atypical clinical course or even an early onset, and the healthcare professionals should be aware of them. The purpose of this brief review was to give an update of the main neurological disorders of common vasculitis and connective tissue diseases, aiming at accurate diagnosis and management, with an emphasis on pathophysiologic mechanisms.

  18. Radiolabeled neurogenesis marker imaging: a revolution in the neurological diseases management?

    PubMed

    Nemati, Reza; Mehdizadeh, Somayeh; Nabipour, Iraj; Salimipour, Hooman; Iranpour, Darioush; Assadi, Majid

    2014-02-01

    A reduced rate of neurogenesis occurs in the adult brain of patients with neurological diseases, with the rate of new neuron proliferation not sufficient to replace neuron loss. Neurogenesis can be induced by several factors, including basic fibroblast growth factor, epidermal growth factor, and brain-derived neurotrophic factor. Neurogenesis determination is a valuable parameter for determining disease progression and monitoring various treatments. Currently, neurogenesis detection is possible by invasive methods, such as bromodeoxyuridine (BrdU) cell labeling and immunohistological analysis of immature neuron markers. However, these are not compatible with alive model examination. Neurogenesis detection by noninvasive methods, such as radiolabeling of specific antibodies and scintigraphy imaging, could shed light on immature neuronal markers. We propose that brain scintigraphy after radiolabeling of a specific antibody of an immature neuronal marker is a useful new modality for neurogenesis detection and that it would aid the management of neurological diseases. PMID:24365279

  19. RNA structures as mediators of neurological diseases and as drug targets

    PubMed Central

    Bernat, Viachaslau; Disney, Matthew D.

    2015-01-01

    RNAs adopt diverse folded structures that are essential for function and thus play critical roles in cellular biology. A striking example of this is the ribosome, a complex, three-dimensionally folded macromolecular machine that orchestrates protein synthesis. Advances in RNA biochemistry, structural and molecular biology, and bioinformatics have revealed other non-coding RNAs whose functions are dictated by their structure. It is not surprising that aberrantly folded RNA structures contribute to disease. In this review, we provide a brief introduction into RNA structural biology and then describe how RNA structures function in cells and cause or contribute to neurological disease. Finally, we highlight successful applications of rational design principles to provide chemical probes and lead compounds targeting structured RNAs. Based on several examples of well-characterized RNA-driven neurological disorders, we demonstrate how designed small molecules can facilitate study of RNA dysfunction, elucidating previously unknown roles for RNA in disease, and provide lead therapeutics. PMID:26139368

  20. An update of neurological manifestations of vasculitides and connective tissue diseases: a literature review

    PubMed Central

    Bougea, Anastasia; Anagnostou, Evangelos; Spandideas, Nikolaos; Triantafyllou, Nikolaos; Kararizou, Evangelia

    2015-01-01

    Vasculitides comprise a heterogeneous group of autoimmune disorders, occurring as primary or secondary to a broad variety of systemic infectious, malignant or connective tissue diseases. The latter occur more often but their pathogenic mechanisms have not been fully established. Frequent and varied central and peripheral nervous system complications occur in vasculitides and connective tissue diseases. In many cases, the neurological disorders have an atypical clinical course or even an early onset, and the healthcare professionals should be aware of them. The purpose of this brief review was to give an update of the main neurological disorders of common vasculitis and connective tissue diseases, aiming at accurate diagnosis and management, with an emphasis on pathophysiologic mechanisms. PMID:26313435

  1. Neuropsychological assessment of driving safety risk in older adults with and without neurologic disease.

    PubMed

    Anderson, Steven W; Aksan, Nazan; Dawson, Jeffrey D; Uc, Ergun Y; Johnson, Amy M; Rizzo, Matthew

    2012-01-01

    Decline in cognitive abilities can be an important contributor to the driving problems encountered by older adults, and neuropsychological assessment may provide a practical approach to evaluating this aspect of driving safety risk. The purpose of the present study was to evaluate several commonly used neuropsychological tests in the assessment of driving safety risk in older adults with and without neurological disease. A further goal of this study was to identify brief combinations of neuropsychological tests that sample performances in key functional domains and thus could be used to efficiently assess driving safety risk. A total of 345 legally licensed and active drivers over the age of 50, with no neurologic disease (N = 185), probable Alzheimer's disease (N = 40), Parkinson's disease (N = 91), or stroke (N = 29), completed vision testing, a battery of 10 neuropsychological tests, and an 18-mile drive on urban and rural roads in an instrumented vehicle. Performances on all neuropsychological tests were significantly correlated with driving safety errors. Confirmatory factor analysis was used to identify 3 key cognitive domains assessed by the tests (speed of processing, visuospatial abilities, and memory), and several brief batteries consisting of one test from each domain showed moderate corrected correlations with driving performance. These findings are consistent with the notion that driving places demands on multiple cognitive abilities that can be affected by aging and age-related neurological disease, and that neuropsychological assessment may provide a practical off-road window into the functional status of these cognitive systems.

  2. Neuropsychological Assessment of Driving Safety Risk in Older Adults With and Without Neurologic Disease

    PubMed Central

    Anderson, Steven W.; Aksan, Nazan; Dawson, Jeffrey D.; Uc, Ergun Y.; Johnson, Amy M.; Rizzo, Matthew

    2013-01-01

    Decline in cognitive abilities can be an important contributor to the driving problems encountered by older adults, and neuropsychological assessment may provide a practical approach to evaluating this aspect of driving safety risk. The purpose of the present study was to evaluate several commonly used neuropsychological tests in the assessment of driving safety risk in older adults with and without neurological disease. A further goal of this study was to identify brief combinations of neuropsychological tests that sample performances in key functional domains and thus could be used to efficiently assess driving safety risk. 345 legally licensed and active drivers over the age of 50, with either no neurologic disease (N=185), probable Alzheimer's disease (N=40), Parkinson's disease (N=91), or stroke (N=29), completed vision testing, a battery of 10 neuropsychological tests, and an 18 mile drive on urban and rural roads in an instrumented vehicle. Performances on all neuropsychological tests were significantly correlated with driving safety errors. Confirmatory factor analysis was used to identify 3 key cognitive domains assessed by the tests (speed of processing, visuospatial abilities, and memory), and several brief batteries consisting of one test from each domain showed moderate corrected correlations with driving performance. These findings are consistent with the notion that driving places demands on multiple cognitive abilities that can be affected by aging and age-related neurological disease, and that neuropsychological assessment may provide a practical off-road window into the functional status of these cognitive systems. PMID:22943767

  3. The crystal structure of human GlnRS provides basis for the development of neurological disorders

    PubMed Central

    Ognjenović, Jana; Wu, Jiang; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Ling, Jiqiang; Simonović, Miljan

    2016-01-01

    Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggest that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. This report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. PMID:26869582

  4. The crystal structure of human GlnRS provides basis for the development of neurological disorders

    DOE PAGES

    Ognjenovic, Jana; Wu, Jiang; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Ling, Jiqiang; Simonovic, Miljan

    2016-02-10

    Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggestmore » that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. As a result, this report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. Keywords« less

  5. A hypothetical neurological association between dehumanization and human rights abuses

    PubMed Central

    Murrow, Gail B.; Murrow, Richard

    2015-01-01

    Dehumanization is anecdotally and historically associated with reduced empathy for the pain of dehumanized individuals and groups and with psychological and legal denial of their human rights and extreme violence against them. We hypothesize that ‘empathy’ for the pain and suffering of dehumanized social groups is automatically reduced because, as the research we review suggests, an individual's neural mechanisms of pain empathy best respond to (or produce empathy for) the pain of people whom the individual automatically or implicitly associates with her or his own species. This theory has implications for the philosophical conception of ‘human’ and of ‘legal personhood’ in human rights jurisprudence. It further has implications for First Amendment free speech jurisprudence, including the doctrine of ‘corporate personhood’ and consideration of the potential harm caused by dehumanizing hate speech. We suggest that the new, social neuroscience of empathy provides evidence that both the vagaries of the legal definition or legal fiction of ‘personhood’ and hate speech that explicitly and implicitly dehumanizes may (in their respective capacities to artificially humanize or dehumanize) manipulate the neural mechanisms of pain empathy in ways that could pose more of a true threat to human rights and rights-based democracy than previously appreciated. PMID:27774198

  6. Barriers to care for patients with neurologic disease in rural Zambia.

    PubMed

    Birbeck, G L

    2000-03-01

    The awesome burden of treatable yet untreated neurologic disease in the developing world presents a humanitarian crisis to those of us with neurologic expertise from more privileged situations. Although increased economic resources are critically needed, a shortage of personnel to care for these patients is as great a problem. It is neither feasible nor desirable to propose training neurologists to work in these regions. However, COs could be selected to receive additional training and return to their home regions to serve as resources for referrals and as community educators. Such a training program would not require massive financial commitments. A handful of dedicated neurologists could conceivably accomplish this in 6- to 8-week training sessions. Ideally, educational materials, such as posters and pamphlets in both English and the native language of the various regions, would be provided at no cost. Existing textbooks in neurology are written for physicians and often focus on diagnostic evaluations and therapies far beyond the services available in developing countries. A text for practical use by COs and community health workers that discusses the application of available medicines and therapies for common neurologic problems would be invaluable. Similar books exist that address general medical and obstetrical problems (for example, Where There Is No Doctor: A Village Health Care Handbook). Where There Is No Neurologist could be developed as a primary teaching tool and a valuable reference for COs with neurologic expertise. Neuroscience researchers, clinical neurologists, and neurology residents from industrialized countries have much to offer and to gain by working in the Third World. Research to monitor the incidence and resource utilization of emerging problems such as stroke is needed to influence public policy. The economic burden and lost productivity caused by neurologic disease in this part of the world has not been appreciated or explored. Disease

  7. Inhibitory system overstimulation plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis

    PubMed Central

    Tuk, Bert

    2016-01-01

    Based upon a thorough review of published clinical observations regarding the inhibitory system, I hypothesize that this system may play a key role in the pathogenesis of a variety of neuromuscular and neurological diseases. Specifically, excitatory overstimulation, which is commonly reported in neuromuscular and neurological diseases, may be a homeostatic response to inhibitory overstimulation. Involvement of the inhibitory system in disease pathogenesis is highly relevant, given that most approaches currently being developed for treating neuromuscular and neurological diseases focus on reducing excitatory activity rather than reducing inhibitory activity. PMID:27547379

  8. Overstimulation of the inhibitory nervous system plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis

    PubMed Central

    Tuk, Bert

    2016-01-01

    Based upon a thorough review of published clinical observations regarding the inhibitory system, I hypothesize that this system may play a key role in the pathogenesis of a variety of neuromuscular and neurological diseases. Specifically, excitatory overstimulation, which is commonly reported in neuromuscular and neurological diseases, may be a homeostatic response to inhibitory overstimulation. Involvement of the inhibitory system in disease pathogenesis is highly relevant, given that most approaches currently being developed for treating neuromuscular and neurological diseases focus on reducing excitatory activity rather than reducing inhibitory activity. PMID:27547379

  9. An unusual neurological disorder of copper metabolism clinically resembling Wilson's disease but biochemically a distinct entity.

    PubMed

    Godwin-Austen, R B; Robinson, A; Evans, K; Lascelles, P T

    1978-11-01

    A patient with progressive neurological disease resembling Wilson's disease but in whom Kayser-Fleischer rings were absent, was given 67Cu and 64Cu, orally and intravenously, to measure the rate of absorption of copper using a convolution integral. The data show an abnormal distribution of body copper resulting in low copper concentrations in plasma, urine and liver but with an accumulation in the lower bowel probably due to a defect in mucosal transport. The importance of differentiating this condition from Wilson's disease is stressed.

  10. Newer insights to the neurological diseases among biblical characters of old testament.

    PubMed

    Mathew, Stephen K; Pandian, Jeyaraj D

    2010-07-01

    Many people over the years have studied the Bible from a medical point of view offering diagnoses for the symptoms and signs that appear to have afflicted numerous individuals in the Bible. We review the biblical characters in the Old Testament and offer newer insights to their neurological diseases. We first look at the battle between Goliath and David. Interestingly, Goliath probably suffered from acromegaly. We propose autism as a diagnosis for Samson which would precede the first known case of autism by centuries. Isaac was a diabetic, and he probably had autonomic neuropathy. Few verses from the books of I Samuel, Psalms, and Ezekiel reveal symptoms suggestive of stroke. Jacob suffered from sciatica, and the child of the Shunnamite woman in II Kings had a subarachnoid hemorrhage. These instances among others found in the Old Testament of the Bible offer newer insights on the history of current neurological diseases.

  11. THE PSYCHIATRIC ASPECTS OF WILSON'S DISEASE-A STUDY FROM A NEUROLOGY UNIT

    PubMed Central

    Kumar, Rajeev; Datta, Sunil; Jayaseelan, L.; Gnanmuthu, Chandran; Kuruvilla, K.

    1996-01-01

    A series of 31 cases of Wilson's disease (WD) were assessed retrospectively on a range of variables including psychiatric, neurologic and biochemical data recorded at index admission over a period of 7 years. 18 patients (58%) showed psychopathological features. 5 patients (16.1%) were reported to have poor scholastic performance at the onset of illness and 1 patient (3.2%) had abnormal behaviour (mania like) many years prior to the appearance of neurological symptoms. The most common psychiatric features were cognitive impairment (45.2%), affective symptomatology (41.9%) and behavioural abnormalities (29%). Only one patient had a schizophrenia like psychosis. The psychiatric manifestation of Wilson′s disease as they present in our setting and their clinical relevance are discussed. PMID:21584132

  12. Newer insights to the neurological diseases among biblical characters of old testament

    PubMed Central

    Mathew, Stephen K.; Pandian, Jeyaraj D.

    2010-01-01

    Many people over the years have studied the Bible from a medical point of view offering diagnoses for the symptoms and signs that appear to have afflicted numerous individuals in the Bible. We review the biblical characters in the Old Testament and offer newer insights to their neurological diseases. We first look at the battle between Goliath and David. Interestingly, Goliath probably suffered from acromegaly. We propose autism as a diagnosis for Samson which would precede the first known case of autism by centuries. Isaac was a diabetic, and he probably had autonomic neuropathy. Few verses from the books of I Samuel, Psalms, and Ezekiel reveal symptoms suggestive of stroke. Jacob suffered from sciatica, and the child of the Shunnamite woman in II Kings had a subarachnoid hemorrhage. These instances among others found in the Old Testament of the Bible offer newer insights on the history of current neurological diseases. PMID:21085524

  13. Neurological disease in man following administration of suckling mouse brain antirabies vaccine*

    PubMed Central

    Held, J. R.; Adaros, H. Lopez

    1972-01-01

    In Latin America, suckling mouse brain (SMB) vaccine has become the most commonly used vaccine for immunization of both man and animals against rabies. This vaccine is highly immunogenic, is relatively economical and easy to produce, and is believed to be free of the immunoencephalitogenic factor. From 1964 to the end of 1969, there were 40 reported cases of neurological disease following administration of SMB vaccine, 32 of which met the criteria for inclusion in this report. These 32 cases occurred in 8 different countries. In contrast to neurological disease following the administration of other types of nervous tissue vaccine, the majority of the cases following vaccination with SMB vaccine had a Guillain—Barré-type syndrome with peripheral nervous system involvement and a higher case—fatality rate. The causative agent has not been demonstrated. Modifications in the production and handling of the vaccine may be producing changes that are responsible. PMID:4339746

  14. Physiochemical basis of human degenerative disease

    PubMed Central

    Lipinski, Boguslaw

    2015-01-01

    The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers. PMID:27486355

  15. Approach to Neurometabolic Diseases from a Pediatric Neurological Point of View

    PubMed Central

    KARIMZADEH, Parvaneh

    2015-01-01

    Objective Neurometabolic disorders are an important group of diseases that mostly are presented in newborns and infants. Neurological manifestations are the prominent signs and symptoms in this group of diseases. Seizures are a common sign and are often refractory to antiepileptic drugs in untreated neurometabolic patients. The onset of symptoms for neurometabolic disorders appears after an interval of normal or near normal growth and development.Additionally, affected children may fare well until a catabolic crisis occurs. Patients with neurometabolic disorders during metabolic decompensation have severe clinical presentation, which include poor feeding, vomiting, lethargy, seizures, and loss of consciousness. This symptom is often fatal but severe neurological insult and regression in neurodevelopmental milestones can result as a prominent sign in patients who survived. Acute symptoms should be immediately treated regardless of the cause. A number of patients with neurometabolic disorders respond favorably and, in some instances, dramatically respond to treatment. Early detection and early intervention is invaluable in some patients to prevent catabolism and normal or near normal neurodevelopmental milestones. This paper discusses neurometabolic disorders, approaches to this group of diseases (from the view of a pediatric neurologist), clinical and neurological manifestations, neuroimaging and electroencephalography findings, early detection, and early treatment. PMID:25767534

  16. Error awareness and the insula: links to neurological and psychiatric diseases

    PubMed Central

    Klein, Tilmann A.; Ullsperger, Markus; Danielmeier, Claudia

    2013-01-01

    Becoming aware of errors that one has committed might be crucial for strategic behavioral and neuronal adjustments to avoid similar errors in the future. This review addresses conscious error perception (“error awareness”) in healthy subjects as well as the relationship between error awareness and neurological and psychiatric diseases. We first discuss the main findings on error awareness in healthy subjects. A brain region, that appears consistently involved in error awareness processes, is the insula, which also provides a link to the clinical conditions reviewed here. Then we focus on a neurological condition whose core element is an impaired awareness for neurological consequences of a disease: anosognosia for hemiplegia (AHP). The insular cortex has been implicated in both error awareness and AHP, with anterior insular regions being involved in conscious error processing and more posterior areas being related to AHP. In addition to cytoarchitectonic and connectivity data, this reflects a functional and structural gradient within the insula from anterior to posterior. Furthermore, studies dealing with error awareness and lack of insight in a number of psychiatric diseases are reported. Especially in schizophrenia, attention-deficit hyperactivity disorder, (ADHD) and autism spectrum disorders (ASD) the performance monitoring system seems impaired, thus conscious error perception might be altered. PMID:23382714

  17. Clinical studies on rising and re-rising neurological diseases in Japan – A personal contribution –

    PubMed Central

    Igata, Akihiro

    2010-01-01

    Throughout my research life, I experienced to discover the causes of some neurological diseases in Japan. SMON (subacute myelo-optico-neuropathy). Since the early 1960s, a peculiar neurological disease became prevalent throughout Japan. Through the chemical analysis of the green urine, characteristic of this disease, it was found that this disease was caused by intoxication of the administered clioquinol, an anti-diarrheal drug. This discovery is a big topic in the history of Japanese medicine.In early 1970s, I experienced many young patients with oedema and polyneuropathy in Kagoshima. Finally it was found that the disease was the long-forgotten beriberi, which had disappeared several decades ago. We must always be aware of beriberi even now, as far as we eat well-polished rice.In 1972, we noticed a group of sporadic paraparesis in Kagoshima, which was 20 years later confirmed to be induced by human T lymphotropic virus type-I (HTLV-I). We named this disease as “HTLV-I associated myelopathy” (HAM). It gave a strong impact that the causative virus of adult T cell leukemia (ATL) can induce entirely different diseases, in terms of both the clinical course and the pathological features. It was also proven that HAM was identical with tropical spastic paraparesis, (TSP), which had been prevalent in many areas of tropical zones. These experiences are good examples of our slogan “to keep in mind to send message of scientific progress from the local area to the international stage”. PMID:20431261

  18. An overview on the correlation of neurological disorders with cardiovascular disease

    PubMed Central

    Firoz, C.K.; Jabir, Nasimudeen R.; Khan, Mohd Shahnawaz; Mahmoud, Maged; Shakil, Shazi; Damanhouri, Ghazi A.; Zaidi, Syed Kashif; Tabrez, Shams; Kamal, Mohammad A.

    2014-01-01

    Neurological disorders (NDs) are one of the leading causes of death especially in the developed countries. Among those NDs, Alzheimer’s disease (AD) and Parkinson disease (PD) are heading the table. There have been several reports in the scientific literatures which suggest the linkage between cardiovascular disorders (CVDs) and NDs. In the present communication, we have tried to compile NDs (AD and PD) association with CVDs reported in the literature. Based on the available scientific literature, we believe that further comprehensive study needs to be done to elucidate the molecular linking points associated with the above mentioned disorders. PMID:25561878

  19. Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease

    PubMed Central

    Scoles, Drew; Higgins, Brian P.; Cooper, Robert F.; Dubis, Adam M.; Summerfelt, Phyllis; Weinberg, David V.; Kim, Judy E.; Stepien, Kimberly E.; Carroll, Joseph; Dubra, Alfredo

    2014-01-01

    Purpose. We surveyed inner retinal microscopic features in retinal and neurologic disease using a reflectance confocal adaptive optics scanning light ophthalmoscope (AOSLO). Methods. Inner retinal images from 101 subjects affected by one of 38 retinal or neurologic conditions and 11 subjects with no known eye disease were examined for the presence of hyper-reflective features other than vasculature, retinal nerve fiber layer, and foveal pit reflex. The hyper-reflective features in the AOSLO images were grouped based on size, location, and subjective texture. Clinical imaging, including optical coherence tomography (OCT), scanning laser ophthalmoscopy, and fundus photography was analyzed for comparison. Results. Seven categories of hyper-reflective inner retinal structures were identified, namely punctate reflectivity, nummular (disc-shaped) reflectivity, granular membrane, waxy membrane, vessel-associated membrane, microcysts, and striate reflectivity. Punctate and nummular reflectivity also was found commonly in normal volunteers, but the features in the remaining five categories were found only in subjects with retinal or neurologic disease. Some of the features were found to change substantially between follow up imaging months apart. Conclusions. Confocal reflectance AOSLO imaging revealed a diverse spectrum of normal and pathologic hyper-reflective inner and epiretinal features, some of which were previously unreported. Notably, these features were not disease-specific, suggesting that they might correspond to common mechanisms of degeneration or repair in pathologic states. Although prospective studies with larger and better characterized populations, along with imaging of more extensive retinal areas are needed, the hyper-reflective structures reported here could be used as disease biomarkers, provided their specificity is studied further. PMID:24894394

  20. Neurologic Disease in Captive Lions (Panthera leo) with Low-Titer Lion Lentivirus Infection▿

    PubMed Central

    Brennan, Greg; Podell, Michael D.; Wack, Raymund; Kraft, Susan; Troyer, Jennifer L.; Bielefeldt-Ohmann, Helle; VandeWoude, Sue

    2006-01-01

    Lion lentivirus (LLV; also known as feline immunodeficiency virus of lion, Panthera leo [FIVPle]) is present in free-ranging and captive lion populations at a seroprevalence of up to 100%; however, clinical signs are rarely reported. LLV displays up to 25% interclade sequence diversity, suggesting that it has been in the lion population for some time and may be significantly host adapted. Three captive lions diagnosed with LLV infection displayed lymphocyte subset alterations and progressive behavioral, locomotor, and neuroanatomic abnormalities. No evidence of infection with other potential neuropathogens was found. Antemortem electrodiagnostics and radiologic imaging indicated a diagnosis consistent with lentiviral neuropathy. PCR was used to determine a partial lentiviral genomic sequence and to quantify the proviral burden in eight postmortem tissue specimens. Phylogenetic analysis demonstrated that the virus was consistent with the LLV detected in other captive and free-ranging lions. Despite progressive neurologic signs, the proviral load in tissues, including several regions of the brain, was low; furthermore, gross and histopathologic changes in the brain were minimal. These findings suggest that the symptoms in these animals resulted from nonspecific encephalopathy, similar to human immunodeficiency virus, FIV, and simian immunodeficiency virus (SIV) neuropathies, rather than a direct effect of active viral replication. The association of neuropathy and lymphocyte subset alterations with chronic LLV infection suggests that long-term LLV infection can have detrimental effects for the host, including death. This is similar to reports of aged sootey mangabeys dying from diseases typically associated with end-stage SIV infection and indicates areas for further research of lentiviral infections of seemingly adapted natural hosts, including mechanisms of host control and viral adaptation. PMID:17005739

  1. Therapeutic targeting of complement to modify disease course and improve outcomes in neurological conditions.

    PubMed

    Brennan, Faith H; Lee, John D; Ruitenberg, Marc J; Woodruff, Trent M

    2016-06-01

    The recognition that complement proteins are abundantly present and can have pathological roles in neurological conditions offers broad scope for therapeutic intervention. Accordingly, an increasing number of experimental investigations have explored the potential of harnessing the unique activation pathways, proteases, receptors, complexes, and natural inhibitors of complement, to mitigate pathology in acute neurotrauma and chronic neurodegenerative diseases. Here, we review mechanisms of complement activation in the central nervous system (CNS), and explore the effects of complement inhibition in cerebral ischemic-reperfusion injury, traumatic brain injury, spinal cord injury, Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease and Huntington's disease. We consider the challenges and opportunities arising from these studies. As complement therapies approach clinical translation, we provide perspectives on how promising complement-targeted therapeutics could become part of novel and effective future treatment options to improve outcomes in the initiation and progression stages of these debilitating CNS disorders. PMID:27049459

  2. Focused ultrasound as a non-invasive intervention for neurological disease: a review.

    PubMed

    Piper, Rory J; Hughes, Mark A; Moran, Carmel M; Kandasamy, Jothy

    2016-06-01

    Focused ultrasound (FUS) is an incision-less intervention that is a Food and Drug Association (FDA) approved surgical treatment for various pathologies including uterine fibroids and bone metastases. Recent advances in magnetic resonance imaging thermometry and ability to use FUS across the intact calvarium have re-opened interest in the use of FUS in the treatment of neurological diseases. FUS currently has a European CE mark for use in movement disorders. However, it shows potential in the treatment of other neuropathologies including tumours and as a lesional tool in epilepsy. FUS may exert its therapeutic effect through thermal or mechanical fragmentation of intracranial lesions, or by enhancing delivery of pharmaceutical agents across the blood-brain barrier. In this review, we summarise the mechanisms, clinical applications and potential future of FUS for the treatment of neurological disease. We have searched for and described the recently completed and on-going clinical trials investigating FUS for the treatment of neurological disorders. We identified phase one trials investigating utility of FUS in: movement disorders (including essential tremor and Parkinson's disease), chronic pain, obsessive-compulsive disorder and cerebral tumours. Current literature also reports pre-clinical work exploring utility in epilepsy, neurodegenerative conditions (such as Alzheimer's disease) and thrombolysis. Safety and early efficacy data are now emerging, suggesting that transcalvarial FUS is a feasible and safe intervention. Further evidence is required to determine whether FUS is an effective alternative in comparison to current neurosurgical interventions. The cost of requisite hardware is currently a barrier to widespread uptake in UK neurosurgical centres. PMID:27101792

  3. Focused ultrasound as a non-invasive intervention for neurological disease: a review.

    PubMed

    Piper, Rory J; Hughes, Mark A; Moran, Carmel M; Kandasamy, Jothy

    2016-06-01

    Focused ultrasound (FUS) is an incision-less intervention that is a Food and Drug Association (FDA) approved surgical treatment for various pathologies including uterine fibroids and bone metastases. Recent advances in magnetic resonance imaging thermometry and ability to use FUS across the intact calvarium have re-opened interest in the use of FUS in the treatment of neurological diseases. FUS currently has a European CE mark for use in movement disorders. However, it shows potential in the treatment of other neuropathologies including tumours and as a lesional tool in epilepsy. FUS may exert its therapeutic effect through thermal or mechanical fragmentation of intracranial lesions, or by enhancing delivery of pharmaceutical agents across the blood-brain barrier. In this review, we summarise the mechanisms, clinical applications and potential future of FUS for the treatment of neurological disease. We have searched for and described the recently completed and on-going clinical trials investigating FUS for the treatment of neurological disorders. We identified phase one trials investigating utility of FUS in: movement disorders (including essential tremor and Parkinson's disease), chronic pain, obsessive-compulsive disorder and cerebral tumours. Current literature also reports pre-clinical work exploring utility in epilepsy, neurodegenerative conditions (such as Alzheimer's disease) and thrombolysis. Safety and early efficacy data are now emerging, suggesting that transcalvarial FUS is a feasible and safe intervention. Further evidence is required to determine whether FUS is an effective alternative in comparison to current neurosurgical interventions. The cost of requisite hardware is currently a barrier to widespread uptake in UK neurosurgical centres.

  4. Zygomycetes in Human Disease

    PubMed Central

    Ribes, Julie A.; Vanover-Sams, Carolyn L.; Baker, Doris J.

    2000-01-01

    The Zygomycetes represent relatively uncommon isolates in the clinical laboratory, reflecting either environmental contaminants or, less commonly, a clinical disease called zygomycosis. There are two orders of Zygomycetes containing organisms that cause human disease, the Mucorales and the Entomophthorales. The majority of human illness is caused by the Mucorales. While disease is most commonly linked to Rhizopus spp., other organisms are also associated with human infection, including Mucor, Rhizomucor, Absidia, Apophysomyces, Saksenaea, Cunninghamella, Cokeromyces, and Syncephalastrum spp. Although Mortierella spp. do cause disease in animals, there is no longer sufficient evidence to suggest that they are true human pathogens. The spores from these molds are transmitted by inhalation, via a variety of percutaneous routes, or by ingestion of spores. Human zygomycosis caused by the Mucorales generally occurs in immunocompromised hosts as opportunistic infections. Host risk factors include diabetes mellitus, neutropenia, sustained immunosuppressive therapy, chronic prednisone use, iron chelation therapy, broad-spectrum antibiotic use, severe malnutrition, and primary breakdown in the integrity of the cutaneous barrier such as trauma, surgical wounds, needle sticks, or burns. Zygomycosis occurs only rarely in immunocompetent hosts. The disease manifestations reflect the mode of transmission, with rhinocerebral and pulmonary diseases being the most common manifestations. Cutaneous, gastrointestinal, and allergic diseases are also seen. The Mucorales are associated with angioinvasive disease, often leading to thrombosis, infarction of involved tissues, and tissue destruction mediated by a number of fungal proteases, lipases, and mycotoxins. If the diagnosis is not made early, dissemination often occurs. Therapy, if it is to be effective, must be started early and requires combinations of antifungal drugs, surgical intervention, and reversal of the underlying risk

  5. Retrospective study of the clinical effects of acupuncture on cervical neurological diseases in dogs.

    PubMed

    Liu, Ching Ming; Chang, Fang Chia; Lin, Chung Tien

    2016-09-30

    This study was conducted to evaluate new acupuncture protocols for the clinical treatment of cervical spinal cord diseases in 19 dogs. Three treatment options containing Jing-jiaji (cervical jiaji) were developed to treat neck pain, hemiparesis, and tetraparesis depending on the severity. The interval between the neurological disease onset and treatment (duration of signs), time to improvement after treatment, and recovery time were compared in dogs by body weight, age, and dry needle acupuncture (AP) with or without electro-AP (EAP). The duration of signs was longer in dogs weighing greater than 10 kg than in those weighing less than 10 kg (p< 0.05). Improvement and recovery times did not vary by body weight. Additionally, improvement and recovery times did not vary by age. The improvement and recovery times were longer in the AP+EAP group than the AP group (p< 0.05). Acupuncture with Jing-jiaji was effective in cervical spinal cord diseases in different sized dogs and in middle-aged and senior dogs. This report standardized AP treatment containing Jing-jiaji for canine cervical problems and evaluated its effects. The newly standardized AP methodology offers clinical practitioners an effective way to improve the outcomes of cervical neurological diseases in dogs.

  6. Retrospective study of the clinical effects of acupuncture on cervical neurological diseases in dogs

    PubMed Central

    Liu, Ching Ming; Chang, Fang Chia

    2016-01-01

    This study was conducted to evaluate new acupuncture protocols for the clinical treatment of cervical spinal cord diseases in 19 dogs. Three treatment options containing Jing-jiaji (cervical jiaji) were developed to treat neck pain, hemiparesis, and tetraparesis depending on the severity. The interval between the neurological disease onset and treatment (duration of signs), time to improvement after treatment, and recovery time were compared in dogs by body weight, age, and dry needle acupuncture (AP) with or without electro-AP (EAP). The duration of signs was longer in dogs weighing greater than 10 kg than in those weighing less than 10 kg (p < 0.05). Improvement and recovery times did not vary by body weight. Additionally, improvement and recovery times did not vary by age. The improvement and recovery times were longer in the AP+EAP group than the AP group (p < 0.05). Acupuncture with Jing-jiaji was effective in cervical spinal cord diseases in different sized dogs and in middle-aged and senior dogs. This report standardized AP treatment containing Jing-jiaji for canine cervical problems and evaluated its effects. The newly standardized AP methodology offers clinical practitioners an effective way to improve the outcomes of cervical neurological diseases in dogs. PMID:26645331

  7. HCN channels in behavior and neurological disease: too hyper, or not active enough?

    PubMed Central

    Lewis, Alan S.; Chetkovich, Dane M.

    2010-01-01

    The roles of cells within the nervous system are based on their properties of excitability, which are in part governed by voltage-gated ion channels. HCN channels underlie the hyperpolarization-activated current, Ih, an important regulator of excitability and rhythmicity through control of basic membrane properties. Ih is present in multiple neuronal types and regions of the central nervous system, and changes in Ih alter cellular input-output properties and neuronal circuitry important for behavior such as learning and memory. Furthermore, the pathophysiology of neurological diseases of both the central and peripheral nervous system involves defects in excitability, rhythmicity, and signaling, and animal models of many of these disorders have implicated changes in HCN channels and Ih as critical for pathogenesis. In this review, we focus on recent research elucidating the role of HCN channels and Ih in behavior and disease. These studies have utilized knockout mice as well as animal models of disease to examine how Ih may be important in regulating learning and memory, sleep, and consciousness, as well as how misregulation of Ih may contribute to epilepsy, chronic pain, and other neurological disorders. This review will help guide future studies aimed at further understanding the function of this unique conductance in both health and disease of the mammalian brain. PMID:21130878

  8. Bullous pemphigoid in a leg affected with hemiparesia: a possible relation of neurological diseases with bullous pemphigoid?

    PubMed

    Foureur, N; Descamps, V; Lebrun-Vignes, B; Picard-Dahan, C; Grossin, M; Belaich, S; Crickx, B

    2001-01-01

    We report a typical case of bullous pemphigoid (BP) associated with a neurological disorder and study a possible link between neurological disorders and BP. An 84-year-old hemiplegic woman presented with unilateral BP on the hemiparetic side. BP was confirmed by histological and immunofluorescence data. The medical records of the previous 46 consecutive patients with BP were retrospectively analyzed (average age: 79; median age: 85). Thirty of the 46 patients with BP had neurological disorders. These disorders included dementia, epilepsy, multiple sclerosis, cerebral stroke, Parkinson's disease, gonadotropic adenoma, trembling, dyskinesia, lumbar spinal stenosis. In a control group of the 46 consecutive oldest patients (older than 71; average age: 82,5; median age: 80) with another skin disease referred during the previous two-year-period to our one-day-unit only, 13 patients had a neurological disorder. This study demonstrates that there is a high prevalence of neurological disorders in patients with BP (p = 0.0004). A prospective case control study with neurological examination and psychometrical evaluation is warranted to confirm these data. We speculate that neuroautoimmunity associated with the aging process or neurological disorders may be involved in pemphigoid development via an autoimmune response against dystonin which shares homology with bullous pemphigoid antigen 1. Bullous pemphigoid could be considered to be a marker of neurological disorder. PMID:11358730

  9. [A study of trientine therapy in Wilson's disease with neurological symptoms].

    PubMed

    Suda, M; Kubota, J; Yamaguchi, Y; Fujioka, Y; Saito, Y; Aoki, T

    1993-09-01

    D-penicillamine, an orally-administered chelating agent, is effective for Wilson's disease (WD). However 25% of WD patients showed serious adverse reactions to D-penicillamine cause this drug to be discontinued after months or years of treatment. For these cases, trientine-2HCl and trientine-4HCl, less toxic agents, are investigated. Three patients with WD, associated with neurological symptoms, were given either trientine-2HCl or trientine-4HCl. These patients had been on therapy with D-penicillamine. Severe adverse reactions had developed during the course of therapy, and D-penicillamine was discontinued, pancytopenia in case 1, nephrotic syndrome in case 2, and myasthenia gravis in case 3. Trientine-2HCl for case 1, and trientine-4HCl for cases 2 and 3 were instituted and continued. The neurological findings in all patients were extremely improved without side effects by trientine therapy. Though the chelating action on copper is weaker than that of D-penicillamine, it is efficient in improvement of the clinical neurological symptoms.

  10. The mTOR signalling cascade: paving new roads to cure neurological disease.

    PubMed

    Crino, Peter B

    2016-07-01

    Defining the multiple roles of the mechanistic (formerly 'mammalian') target of rapamycin (mTOR) signalling pathway in neurological diseases has been an exciting and rapidly evolving story of bench-to-bedside translational research that has spanned gene mutation discovery, functional experimental validation of mutations, pharmacological pathway manipulation, and clinical trials. Alterations in the dual contributions of mTOR - regulation of cell growth and proliferation, as well as autophagy and cell death - have been found in developmental brain malformations, epilepsy, autism and intellectual disability, hypoxic-ischaemic and traumatic brain injuries, brain tumours, and neurodegenerative disorders. mTOR integrates a variety of cues, such as growth factor levels, oxygen levels, and nutrient and energy availability, to regulate protein synthesis and cell growth. In line with the positioning of mTOR as a pivotal cell signalling node, altered mTOR activation has been associated with a group of phenotypically diverse neurological disorders. To understand how altered mTOR signalling leads to such divergent phenotypes, we need insight into the differential effects of enhanced or diminished mTOR activation, the developmental context of these changes, and the cell type affected by altered signalling. A particularly exciting feature of the tale of mTOR discovery is that pharmacological mTOR inhibitors have shown clinical benefits in some neurological disorders, such as tuberous sclerosis complex, and are being considered for clinical trials in epilepsy, autism, dementia, traumatic brain injury, and stroke. PMID:27340022

  11. The human disease network.

    PubMed

    Goh, Kwang-Il; Cusick, Michael E; Valle, David; Childs, Barton; Vidal, Marc; Barabási, Albert-László

    2007-05-22

    A network of disorders and disease genes linked by known disorder-gene associations offers a platform to explore in a single graph-theoretic framework all known phenotype and disease gene associations, indicating the common genetic origin of many diseases. Genes associated with similar disorders show both higher likelihood of physical interactions between their products and higher expression profiling similarity for their transcripts, supporting the existence of distinct disease-specific functional modules. We find that essential human genes are likely to encode hub proteins and are expressed widely in most tissues. This suggests that disease genes also would play a central role in the human interactome. In contrast, we find that the vast majority of disease genes are nonessential and show no tendency to encode hub proteins, and their expression pattern indicates that they are localized in the functional periphery of the network. A selection-based model explains the observed difference between essential and disease genes and also suggests that diseases caused by somatic mutations should not be peripheral, a prediction we confirm for cancer genes. PMID:17502601

  12. Epigenetic Modifications in Neurological Diseases: Natural Products as Epigenetic Modulators a Treatment Strategy.

    PubMed

    Gangisetty, Omkaram; Murugan, Sengottuvelan

    2016-01-01

    Epigenetic modifications, including DNA methylation, covalent histone modifications, and small noncoding RNAs, play a key role in regulating the gene expression. This regulatory mechanism is important in cellular differentiation and development. Recent advances in the field of epigenetics extended the role of epigenetic mechanisms in controlling key biological processes such as genome imprinting and X-chromosome inactivation. Aberrant epigenetic modifications are associated with the development of many diseases. The role of epigenetic modifications in various neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington disease, epilepsy, and multiple sclerosis is rapidly emerging. The use of epigenetic modifying drugs to treat these diseases has been the interest in recent years. A number of natural products having diverse mechanism of action are used for drug discovery. For many years, natural compounds have been used to treat various neurodegenerative diseases, but the use of such compounds as epigenetic modulators to reverse or treat neurological diseases are not well studied. In this chapter, we mainly focus on how various epigenetic modifications play a key role in neurodegenerative diseases, their mechanism of action, and how it acts as a potential therapeutic target for epigenetic drugs to treat these diseases will be discussed.

  13. Epigenetic Modifications in Neurological Diseases: Natural Products as Epigenetic Modulators a Treatment Strategy.

    PubMed

    Gangisetty, Omkaram; Murugan, Sengottuvelan

    2016-01-01

    Epigenetic modifications, including DNA methylation, covalent histone modifications, and small noncoding RNAs, play a key role in regulating the gene expression. This regulatory mechanism is important in cellular differentiation and development. Recent advances in the field of epigenetics extended the role of epigenetic mechanisms in controlling key biological processes such as genome imprinting and X-chromosome inactivation. Aberrant epigenetic modifications are associated with the development of many diseases. The role of epigenetic modifications in various neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington disease, epilepsy, and multiple sclerosis is rapidly emerging. The use of epigenetic modifying drugs to treat these diseases has been the interest in recent years. A number of natural products having diverse mechanism of action are used for drug discovery. For many years, natural compounds have been used to treat various neurodegenerative diseases, but the use of such compounds as epigenetic modulators to reverse or treat neurological diseases are not well studied. In this chapter, we mainly focus on how various epigenetic modifications play a key role in neurodegenerative diseases, their mechanism of action, and how it acts as a potential therapeutic target for epigenetic drugs to treat these diseases will be discussed. PMID:27651245

  14. Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases

    PubMed Central

    Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

    2016-01-01

    Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability

  15. Respiratory and neurological disease in rabbits experimentally infected with equid herpesvirus 1.

    PubMed

    Kanitz, Fábio A; Cargnelutti, Juliana F; Anziliero, Deniz; Gonçalves, Kelley V; Masuda, Eduardo K; Weiblen, Rudi; Flores, Eduardo F

    2015-10-01

    Equid herpesvirus type 1 (EHV-1) is an important pathogen of horses worldwide, associated with respiratory, reproductive and/or neurological disease. A mouse model for EHV-1 infection has been established but fails to reproduce some important aspects of the viral pathogenesis. Then, we investigated the susceptibility of rabbits to EHV-1 aiming at proposing this species as an alternative model for EHV-1 infection. Weanling rabbits inoculated intranasal with EHV-1 Kentucky D (10(7) TCID50/animal) shed virus in nasal secretions up to day 8-10 post-inoculation (pi), presented viremia up to day 14 pi and seroconverted to EHV-1 (virus neutralizing titers 4 to 64). Most rabbits (75%) developed respiratory disease, characterized by serous to hemorrhagic nasal discharge and mild to severe dyspnea. Some animals (20%) presented neurological signs as circling, bruxism and opisthotonus. Six animals died during acute disease (days 3-6); infectious virus and/or viral DNA were detected in the lungs, trigeminal ganglia (TG), olfactory bulbs (OBs) and cerebral cortex/brain (CC). Histological examination showed necrohemorrhagic, multifocal to coalescent bronchointerstitial pneumonia and diffuse alveolar edema. In two rabbits euthanized at day 50 pi, latent EHV-1 DNA was detected in the OBs. Dexamethasone administration at day 50 pi resulted in virus reactivation, demonstrated by virus shedding, viremia, clinical signs, and increase in VN titers and/or by detection of virus DNA in lungs, OBs, TGs and/or CC. These results demonstrate that rabbits are susceptible to EHV-1 infection and develop respiratory and neurological signs upon experimental inoculation. Thus, rabbits may be used to study selected aspects of EHV-1 biology and pathogenesis, extending and complementing the mouse model. PMID:26187161

  16. Respiratory and neurological disease in rabbits experimentally infected with equid herpesvirus 1.

    PubMed

    Kanitz, Fábio A; Cargnelutti, Juliana F; Anziliero, Deniz; Gonçalves, Kelley V; Masuda, Eduardo K; Weiblen, Rudi; Flores, Eduardo F

    2015-10-01

    Equid herpesvirus type 1 (EHV-1) is an important pathogen of horses worldwide, associated with respiratory, reproductive and/or neurological disease. A mouse model for EHV-1 infection has been established but fails to reproduce some important aspects of the viral pathogenesis. Then, we investigated the susceptibility of rabbits to EHV-1 aiming at proposing this species as an alternative model for EHV-1 infection. Weanling rabbits inoculated intranasal with EHV-1 Kentucky D (10(7) TCID50/animal) shed virus in nasal secretions up to day 8-10 post-inoculation (pi), presented viremia up to day 14 pi and seroconverted to EHV-1 (virus neutralizing titers 4 to 64). Most rabbits (75%) developed respiratory disease, characterized by serous to hemorrhagic nasal discharge and mild to severe dyspnea. Some animals (20%) presented neurological signs as circling, bruxism and opisthotonus. Six animals died during acute disease (days 3-6); infectious virus and/or viral DNA were detected in the lungs, trigeminal ganglia (TG), olfactory bulbs (OBs) and cerebral cortex/brain (CC). Histological examination showed necrohemorrhagic, multifocal to coalescent bronchointerstitial pneumonia and diffuse alveolar edema. In two rabbits euthanized at day 50 pi, latent EHV-1 DNA was detected in the OBs. Dexamethasone administration at day 50 pi resulted in virus reactivation, demonstrated by virus shedding, viremia, clinical signs, and increase in VN titers and/or by detection of virus DNA in lungs, OBs, TGs and/or CC. These results demonstrate that rabbits are susceptible to EHV-1 infection and develop respiratory and neurological signs upon experimental inoculation. Thus, rabbits may be used to study selected aspects of EHV-1 biology and pathogenesis, extending and complementing the mouse model.

  17. Selenium in the Therapy of Neurological Diseases. Where is it Going?

    PubMed Central

    Dominiak, Agnieszka; Wilkaniec, Anna; Wroczyńsk, Piotr; Adamczyk, Agata

    2016-01-01

    Selenium (34Se), an antioxidant trace element, is an important regulator of brain function. These beneficial properties that Se possesses are attributed to its ability to be incorporated into selenoproteins as an amino acid. Several selenoproteins are expressed in the brain, in which some of them, e.g. glutathione peroxidases (GPxs), thioredoxin reductases (TrxRs) or selenoprotein P (SelP), are strongly involved in antioxidant defence and in maintaining intercellular reducing conditions. Since increased oxidative stress has been implicated in neurological disorders, including Parkinson’s disease, Alzheimer’s disease, stroke, epilepsy and others, a growing body of evidence suggests that Se depletion followed by decreased activity of Se-dependent enzymes may be important factors connected with those pathologies. Undoubtedly, the remarkable progress that has been made in understanding the biological function of Se in the brain has opened up new potential possibilities for the treatment of neurological diseases by using Se as a potential drug. However, further research in the search for optimal Se donors is necessary in order to achieve an effective and safe therapeutic income. PMID:26549649

  18. Demyelinizing Neurological Disease after Treatment with Tumor Necrosis Factor-α Antagonists

    PubMed Central

    Bruè, Claudia; Mariotti, Cesare; Rossiello, Ilaria; Saitta, Andrea; Giovannini, Alfonso

    2016-01-01

    Purpose Demyelinizing neurological disease is a rare complication after treatment with tumor necrosis factor (TNF)α antagonists. We report on a case of multiple sclerosis after TNFα antagonist treatment and discuss its differential diagnosis. Methods This is an observational case study. Results A 48-year-old male was referred to Ophthalmology in January 2015 for an absolute scotoma in the superior quadrant of the visual field in his right eye. Visual acuity was 20/50 in the right eye and 20/20 in the left. Fundus examination was unremarkable bilaterally. Spectral domain optical coherence tomography revealed a normal macular retina structure. Visual field examination revealed a superior hemianopsia in the right eye. Head magnetic resonance imaging showed findings compatible with optic neuritis. The visual evoked potentials confirmed the presence of optic neuritis. The patient had been under therapy with adalimumab since January 2014, for Crohn's disease. Suspension of adalimumab was recommended, and it was substituted with tapered deltacortene, from 1 mg/kg/day. After 1 month, the scotoma was resolved completely. Conclusions TNFα antagonists can provide benefit to patients with inflammatory autoimmune diseases. However, they can also be associated with severe adverse effects. Therefore, adequate attention should be paid to neurological abnormalities in patients treated with TNFα antagonists. PMID:27504093

  19. Neurological approaches for investigating West Nile virus disease and its treatment in rodents.

    PubMed

    Morrey, John D; Siddharthan, Venkatraman; Wang, Hong

    2013-11-01

    West Nile virus (WNV) has had a major public health impact since its emergence in the Western Hemisphere; in 2012, nearly 3000 cases of WN neuroinvasive disease were identified in the United States. The underlying mechanisms of WN neurologic disease can only be studied to a limited extent in patients, but can be investigated in much greater detail in animal models. In this paper, we describe how we and others have employed a variety of electrophysiological and neurological techniques to study experimental WNV infections in hamsters and mice. The methods have included electrophysiological motor unit number estimation; optogenetic photoactivation of the spinal cord and electromyography; plethysmography; measurement of heart rate variability as an indication of autonomic nervous system dysfunction; and an assessment of spatial memory loss using the Morris water maze. These techniques provide a more refined assessment of disease manifestations in rodents than traditional measurements of weight loss and mortality, and should make it possible to identify targets for therapeutic intervention and to directly assess the effects of novel treatments. PMID:24055448

  20. Selenium in the Therapy of Neurological Diseases. Where is it Going?

    PubMed

    Dominiak, Agnieszka; Wilkaniec, Anna; Wroczyński, Piotr; Adamczyk, Agata

    2016-01-01

    Selenium (34Se), an antioxidant trace element, is an important regulator of brain function. These beneficial properties that Se possesses are attributed to its ability to be incorporated into selenoproteins as an amino acid. Several selenoproteins are expressed in the brain, in which some of them, e.g. glutathione peroxidases (GPxs), thioredoxin reductases (TrxRs) or selenoprotein P (SelP), are strongly involved in antioxidant defence and in maintaining intercellular reducing conditions. Since increased oxidative stress has been implicated in neurological disorders, including Parkinson's disease, Alzheimer's disease, stroke, epilepsy and others, a growing body of evidence suggests that Se depletion followed by decreased activity of Se-dependent enzymes may be important factors connected with those pathologies. Undoubtedly, the remarkable progress that has been made in understanding the biological function of Se in the brain has opened up new potential possibilities for the treatment of neurological diseases by using Se as a potential drug. However, further research in the search for optimal Se donors is necessary in order to achieve an effective and safe therapeutic income.

  1. Introduction to Focus Issue: Rhythms and Dynamic Transitions in Neurological Disease: Modeling, Computation, and Experiment

    SciTech Connect

    Kaper, Tasso J. Kramer, Mark A.; Rotstein, Horacio G.

    2013-12-15

    Rhythmic neuronal oscillations across a broad range of frequencies, as well as spatiotemporal phenomena, such as waves and bumps, have been observed in various areas of the brain and proposed as critical to brain function. While there is a long and distinguished history of studying rhythms in nerve cells and neuronal networks in healthy organisms, the association and analysis of rhythms to diseases are more recent developments. Indeed, it is now thought that certain aspects of diseases of the nervous system, such as epilepsy, schizophrenia, Parkinson's, and sleep disorders, are associated with transitions or disruptions of neurological rhythms. This focus issue brings together articles presenting modeling, computational, analytical, and experimental perspectives about rhythms and dynamic transitions between them that are associated to various diseases.

  2. Introduction to Focus Issue: Rhythms and Dynamic Transitions in Neurological Disease: Modeling, Computation, and Experiment

    NASA Astrophysics Data System (ADS)

    Kaper, Tasso J.; Kramer, Mark A.; Rotstein, Horacio G.

    2013-12-01

    Rhythmic neuronal oscillations across a broad range of frequencies, as well as spatiotemporal phenomena, such as waves and bumps, have been observed in various areas of the brain and proposed as critical to brain function. While there is a long and distinguished history of studying rhythms in nerve cells and neuronal networks in healthy organisms, the association and analysis of rhythms to diseases are more recent developments. Indeed, it is now thought that certain aspects of diseases of the nervous system, such as epilepsy, schizophrenia, Parkinson's, and sleep disorders, are associated with transitions or disruptions of neurological rhythms. This focus issue brings together articles presenting modeling, computational, analytical, and experimental perspectives about rhythms and dynamic transitions between them that are associated to various diseases.

  3. Introduction to Focus Issue: Rhythms and Dynamic Transitions in Neurological Disease: Modeling, Computation, and Experiment

    PubMed Central

    Kaper, Tasso J.; Kramer, Mark A.; Rotstein, Horacio G.

    2013-01-01

    Rhythmic neuronal oscillations across a broad range of frequencies, as well as spatiotemporal phenomena, such as waves and bumps, have been observed in various areas of the brain and proposed as critical to brain function. While there is a long and distinguished history of studying rhythms in nerve cells and neuronal networks in healthy organisms, the association and analysis of rhythms to diseases are more recent developments. Indeed, it is now thought that certain aspects of diseases of the nervous system, such as epilepsy, schizophrenia, Parkinson's, and sleep disorders, are associated with transitions or disruptions of neurological rhythms. This focus issue brings together articles presenting modeling, computational, analytical, and experimental perspectives about rhythms and dynamic transitions between them that are associated to various diseases. PMID:24387579

  4. Infliximab is a plausible alternative for neurologic complications of Behçet disease

    PubMed Central

    Zeydan, Burcu; Uygunoglu, Ugur; Saip, Sabahattin; Demirci, Onat N.; Seyahi, Emire; Ugurlu, Serdal; Hamuryudan, Vedat; Siva, Aksel

    2016-01-01

    Objective: We evaluated the effectiveness of infliximab in patients with neuro-Behçet syndrome for whom other immunosuppressive medications had failed. Methods: Patients whose common immunosuppressive medications fail in recurrent neuro-Behçet syndrome need an alternative. We report our experience with the tumor necrosis factor α blocker infliximab for long-term treatment of neuro-Behçet syndrome. We recruited patients within a multidisciplinary referral practice of Behçet disease and prospectively followed everyone with a neurologic symptom(s). Patients (n = 16) with ≥2 neurologic bouts (excluding purely progressive disease) while on another immunosuppressive treatment were switched to and successfully sustained on infliximab (5 mg/kg in weeks 0, 2, and 6, then once every 8 weeks; minimum follow-up duration ≥12 months). Infliximab was stopped within 2 months after initiation in one patient because of pulmonary and CNS tuberculosis. Results: Patients had stepwise worsening due to relapses in the Expanded Disability Status Scale modified for neuro-Behçet syndrome before switching to infliximab (median score of 5.0, range 2.0–7.0; median neuro-Behçet syndrome duration 29.1 months, range 5.0–180.7). Median duration of preinfliximab immunosuppressive medication use was 20.0 months (range 3.0–180.7). In all 15 patients, during infliximab treatment (median score 4.0, range 2.0–7.0; median duration 39.0 months, range 16.0–104.9 months), neurologic relapses were completely aborted and there was no further disability accumulation. Conclusion: We observed a significant beneficial effect of infliximab in neuro-Behçet syndrome. Classification of evidence: This study provides Class IV evidence that for patients with neuro-Behçet syndrome whose other immunosuppressive medications failed, infliximab prevents further relapses and stabilizes disability. PMID:27458602

  5. [Change in number of residents who plan to specialize in cerebrovascular disease and neurointervention in the Department of Neurology of Kyushu University Hospital].

    PubMed

    Matsumoto, Shoji

    2014-01-01

    As an example of the Neurology Department of the University, I will report on the human resources education and changes in the number of young neurologists who want to specialize in cerebrovascular disease and neurointervention therapy in the Department of Neurology of Kyushu University. In our department, 12% (14/116) of residents planned to specialize in cerebrovascular diseases and 9% (11/116) of residents wanted to learn neurointerventional therapy. These rates are not high. However, in the past year, four out of seven residents want to specialize in cerebrovascular diseases and all want to learn neurointerventional therapy. It is possible that advances in neurointerventional therapy have influenced young neurologists. It is necessary to develop a system that encourages young neurologists to undertake these specializations in universities all over Japan. PMID:25672746

  6. Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases

    PubMed Central

    Fox, Michael D.; Buckner, Randy L.; Liu, Hesheng; Chakravarty, M. Mallar; Lozano, Andres M.; Pascual-Leone, Alvaro

    2014-01-01

    Brain stimulation, a therapy increasingly used for neurological and psychiatric disease, traditionally is divided into invasive approaches, such as deep brain stimulation (DBS), and noninvasive approaches, such as transcranial magnetic stimulation. The relationship between these approaches is unknown, therapeutic mechanisms remain unclear, and the ideal stimulation site for a given technique is often ambiguous, limiting optimization of the stimulation and its application in further disorders. In this article, we identify diseases treated with both types of stimulation, list the stimulation sites thought to be most effective in each disease, and test the hypothesis that these sites are different nodes within the same brain network as defined by resting-state functional-connectivity MRI. Sites where DBS was effective were functionally connected to sites where noninvasive brain stimulation was effective across diseases including depression, Parkinson's disease, obsessive-compulsive disorder, essential tremor, addiction, pain, minimally conscious states, and Alzheimer’s disease. A lack of functional connectivity identified sites where stimulation was ineffective, and the sign of the correlation related to whether excitatory or inhibitory noninvasive stimulation was found clinically effective. These results suggest that resting-state functional connectivity may be useful for translating therapy between stimulation modalities, optimizing treatment, and identifying new stimulation targets. More broadly, this work supports a network perspective toward understanding and treating neuropsychiatric disease, highlighting the therapeutic potential of targeted brain network modulation. PMID:25267639

  7. Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A.

    PubMed

    Krajewski, K M; Lewis, R A; Fuerst, D R; Turansky, C; Hinderer, S R; Garbern, J; Kamholz, J; Shy, M E

    2000-07-01

    Charcot-Marie-Tooth disease type 1A (CMT1A), the most frequent form of CMT, is caused by a 1.5 Mb duplication on the short arm of chromosome 17. Patients with CMT1A typically have slowed nerve conduction velocities (NCVs), reduced compound motor and sensory nerve action potentials (CMAPs and SNAPs), distal weakness, sensory loss and decreased reflexes. In order to understand further the molecular pathogenesis of CMT1A, as well as to determine which features correlate with neurological dysfunction and might thus be amenable to treatment, we evaluated the clinical and electrophysiological phenotype in 42 patients with CMT1A. In these patients, muscle weakness, CMAP amplitudes and motor unit number estimates correlated with clinical disability, while motor NCV did not. In addition, loss of joint position sense and reduction in SNAP amplitudes also correlated with clinical disability, while sensory NCV did not. Taken together, these data strongly support the hypothesis that neurological dysfunction and clinical disability in CMT1A are caused by loss or damage to large calibre motor and sensory axons. Therapeutic approaches to ameliorate disability in CMT1A, as in amyotrophic lateral sclerosis and other neurodegenerative diseases, should thus be directed towards preventing axonal degeneration and/or promoting axonal regeneration. PMID:10869062

  8. Neurologic disease in range goats associated with Oxytropis sericea (Locoweed) poisoning and water deprivation.

    PubMed

    Stegelmeier, B L; James, L F; Hall, J O; Mattix, M T

    2001-10-01

    About 200/2500 Spanish goats foraging on mountain rangelands of western Montana developed neurologic disease with severe rear limb weakness, knuckling of the rear fetlocks, and a hopping gait. Sick goats were of all ages and in good flesh, though they often had dull, shaggy coats. Some mildly affected animals recovered after being moved to feed lots, but others progressed to recumbency, seizures and death. At necropsy both moribund and clinically affected animals had few gross lesions; 1 animal had contusions and puncture wounds on rear legs and perineum, suggestive of predator bites. Histologic lesions included mild vacuolation of neurons and visceral epithelial cells, mild diffuse cerebral edema with minimal neuronal pyknosis, and random, multifocal Wallarian degeneration of spinal cord axons. Affected animals had elevated serum sodium, potassium and chloride levels; other mineral analyses and serum biochemistries were within normal limits. Locoweed-induced depression and inhibition of neuromuscular function coupled with water deprivation due to predation pressure allowed development of neurologic disease and hypernatremia. PMID:11577940

  9. [The present issues to advocate rights of patients with neurological diseases in Japan].

    PubMed

    Narita, Yugo

    2007-11-01

    To advocate patient's right is an inevitable assignment of all neurologists who have clinical activities for patients with neurological diseases, though the assignment has very broad fields and is impossible to perform by one. The author summarized present issues of guardianship, the program to protect the social welfare rights in communities, and advance directives for patients with neurological diseases. The new guardianship for adults in Japan started in 2000 and has been increasingly used mainly for the demented. Proxy decision making for a medical care by the guardian is still unsettled. The author raised a possible question on identification of the person who wants medical certification for guardianship and his her intention to obtain such a document, in order to avoid unexpected troubles in the family or involved parties. Replies about the identification from an inspector at a family court, lawyers, judicial scriveners, social workers and Japan National Council of Social Welfare were shown on the table. In May 2007, the Ministry of Health. Labour and Welfare presented the guideline of process to decide the end-of-life-care. But advance directives for medical cares are still controversial in Japan. Multidisciplinary team to advocate patients' rights was stressed in this presentation.

  10. Neurologic disease in range goats associated with Oxytropis sericea (Locoweed) poisoning and water deprivation.

    PubMed

    Stegelmeier, B L; James, L F; Hall, J O; Mattix, M T

    2001-10-01

    About 200/2500 Spanish goats foraging on mountain rangelands of western Montana developed neurologic disease with severe rear limb weakness, knuckling of the rear fetlocks, and a hopping gait. Sick goats were of all ages and in good flesh, though they often had dull, shaggy coats. Some mildly affected animals recovered after being moved to feed lots, but others progressed to recumbency, seizures and death. At necropsy both moribund and clinically affected animals had few gross lesions; 1 animal had contusions and puncture wounds on rear legs and perineum, suggestive of predator bites. Histologic lesions included mild vacuolation of neurons and visceral epithelial cells, mild diffuse cerebral edema with minimal neuronal pyknosis, and random, multifocal Wallarian degeneration of spinal cord axons. Affected animals had elevated serum sodium, potassium and chloride levels; other mineral analyses and serum biochemistries were within normal limits. Locoweed-induced depression and inhibition of neuromuscular function coupled with water deprivation due to predation pressure allowed development of neurologic disease and hypernatremia.

  11. Botulinum toxin use in neuro-rehabilitation to treat obstetrical plexus palsy and sialorrhea following neurological diseases: a review.

    PubMed

    Intiso, Domenico; Basciani, M

    2012-01-01

    In neuro-rehabilitation, botulinum toxin (BTX) as adjunct to other interventions can result in a useful therapeutic tool treating disabled people. Other than spasticity, numerous motor and non motor disorders can complicate clinical course and hamper rehabilitative process of neurological impaired patients. A review of BTX use in treating muscular imbalance of children with obstetrical brachial plexus palsy and in reducing sialorrhea following neurological diseases including amyotrophic lateral sclerosis (ASL), Parkinson disease and cerebral palsy (CP) is provided. Clinicians have to face unique and difficult to treat clinical conditions such as ulcers, sores and abnormal posture and movement disorders due to neurological affections. BTX effectiveness in treating some of these conditions is also provided. Since, neurologically disabled subjects can show complex dysfunction, prior to initiating BTX therapy, specific functional limitations, goals and expected outcomes of treatment should be evaluated and discussed with family and caregivers.

  12. Brain protein preservation largely depends on the postmortem storage temperature: implications for study of proteins in human neurologic diseases and management of brain banks: a BrainNet Europe Study.

    PubMed

    Ferrer, Isidre; Santpere, Gabriel; Arzberger, Thomas; Bell, Jeanne; Blanco, Rosa; Boluda, Susana; Budka, Herbert; Carmona, Margarita; Giaccone, Giorgio; Krebs, Bjarne; Limido, Lucia; Parchi, Piero; Puig, Berta; Strammiello, Rosaria; Ströbel, Thomas; Kretzschmar, Hans

    2007-01-01

    The present study was designed to reveal protein modifications in control cases related with postmortem delay and temperature of storage in 3 paradigms in which the same postmortem tissue sample (frontal cortex) was frozen a short time after death or stored at 1 degrees C, 4 degrees C, or room temperature and then frozen at -80 degrees C at different intervals. No evidence of protein degradation as revealed with monodimensional gel electrophoresis and Western blotting was observed in samples artificially stored at 1 degrees C and then frozen at different intervals up to 50 hours after death. However, the levels of several proteins were modified in samples stored at 4 degrees C and this effect was more marked in samples stored at room temperature. Two-dimensional gel electrophoresis and mass spectrometry further corroborated these observations and permitted the identification of other proteins vulnerable or resistant to postmortem delay. Finally, gel electrophoresis and Western blotting of sarkosyl-insoluble fractions in Alzheimer disease showed reduced intensity of phospho-tau-specific bands with postmortem delay with the effects being more dramatic when the brain samples were stored at room temperature for long periods. These results emphasize the necessity of reducing the body temperature after death to minimize protein degradation.

  13. Copper mediated neurological disorder: visions into amyotrophic lateral sclerosis, Alzheimer and Menkes disease.

    PubMed

    Ahuja, Anami; Dev, Kapil; Tanwar, Ranjeet S; Selwal, Krishan K; Tyagi, Pankaj K

    2015-01-01

    Copper (Cu) is a vital redox dynamic metal that is possibly poisonous in superfluous. Metals can traditionally or intricately cause propagation in reactive oxygen species (ROS) accretion in cells and this may effect in programmed cell death. Accumulation of Cu causes necrosis that looks to be facilitated by DNA damage, followed by activation of P53. Cu dyshomeostasis has also been concerned in neurodegenerative disorders such as Alzheimer, Amyotrophic lateral sclerosis (ALS) or Menkes disease and is directly related to neurodegenerative syndrome that usually produces senile dementia. These mortal syndromes are closely related with an immense damage of neurons and synaptic failure in the brain. This review focuses on copper mediated neurological disorders with insights into amyotrophic lateral sclerosis, Alzheimer and Menkes disease.

  14. Konzo: From Poverty, Cassava, and Cyanogen Intake to Toxico-Nutritional Neurological Disease

    PubMed Central

    Nzwalo, Hipólito; Cliff, Julie

    2011-01-01

    Konzo is a distinct neurological entity with selective upper motor neuron damage, characterized by an abrupt onset of an irreversible, non-progressive, and symmetrical spastic para/tetraparesis. Despite its severity, konzo remains a neglected disease. The disease is associated with high dietary cyanogen consumption from insufficiently processed roots of bitter cassava combined with a protein-deficient diet. Epidemics occur when these conditions coincide at times of severe food shortage. Up to 1993, outbreaks in poor rural areas in Africa contributed to more than 3,700 cases of konzo. The number of affected people is underestimated. From unofficial reports, the number of cases was estimated to be at least 100,000 in 2000, in contrast to the 6,788 cases reported up to 2009 from published papers. PMID:21738800

  15. Clinical NMR imaging of the brain in children: normal and neurologic disease

    SciTech Connect

    Johnson, M.A,; Pennock, J.M.; Bydder, G.M.; Steiner, R.E.; Thomas, D.J.; Hayward, R.; Bryant, D.R.T.; Payne, J.A.; Levene, M.I.; Whitelaw, A.; Dubowitz, L.M.S.; Dubowitz, V.

    1983-11-01

    The results of initial clinical nuclear magnetic resonance imaging of the brain in eight normal and 52 children with a wide variety of neurologic diseases were reviewed. The high level of gray-white matter contrast available with inversion-recovery sequences provided a basis for visualizing normal myelination as well as delays or deficits in this process. The appearances seen in cases of parenchymal hemorrhage, cerebral infarction, and proencephalic cysts are described. Ventricular enlargement was readily identified and marginal edema was demonstrated with spin-echo sequences. Abnormalities were seen in cerebral palsy, congenital malformations, Hallervorden-Spatz disease, aminoaciduria, and meningitis. Space-occupying lesions were identified by virtue of their increased relaxation times and mass effects. Nuclear magnetic resonance imaging has considerable potential in pediatric neuroradiologic practice, in some conditions supplying information not available by computed tomography or sonography.

  16. Copper mediated neurological disorder: visions into amyotrophic lateral sclerosis, Alzheimer and Menkes disease.

    PubMed

    Ahuja, Anami; Dev, Kapil; Tanwar, Ranjeet S; Selwal, Krishan K; Tyagi, Pankaj K

    2015-01-01

    Copper (Cu) is a vital redox dynamic metal that is possibly poisonous in superfluous. Metals can traditionally or intricately cause propagation in reactive oxygen species (ROS) accretion in cells and this may effect in programmed cell death. Accumulation of Cu causes necrosis that looks to be facilitated by DNA damage, followed by activation of P53. Cu dyshomeostasis has also been concerned in neurodegenerative disorders such as Alzheimer, Amyotrophic lateral sclerosis (ALS) or Menkes disease and is directly related to neurodegenerative syndrome that usually produces senile dementia. These mortal syndromes are closely related with an immense damage of neurons and synaptic failure in the brain. This review focuses on copper mediated neurological disorders with insights into amyotrophic lateral sclerosis, Alzheimer and Menkes disease. PMID:24975171

  17. In vivo Expression of Inducible Nitric Oxide Synthase in Experimentally Induced Neurologic Diseases

    NASA Astrophysics Data System (ADS)

    Koprowski, Hilary; Zheng, Yong Mu; Heber-Katz, Ellen; Fraser, Nigel; Rorke, Lucy; Fu, Zhen Fang; Hanlon, Cathleen; Dietzschold, Bernhard

    1993-04-01

    The purpose of this study was to investigate the induction of inducible nitric oxide synthase (iNOS) mRNA in the brain tissue of rats and mice under the following experimental conditions: in rats infected with borna disease virus and rabies virus, in mice infected with herpes simplex virus, and in rats after the induction of experimental allergic encephalitis. The results showed that iNOS mRNA, normally nondetectable in the brain, was present in animals after viral infection or after induction of experimental allergic encephalitis. The induction of iNOS mRNA coincided with the severity of clinical signs and in some cases with the presence of inflammatory cells in the brain. The results indicate that nitric oxide produced by cells induced by iNOS may be the toxic factor accounting for cell damage and this may open the door to approaches to the study of the pathogenesis of neurological diseases.

  18. Studies of generalized elemental imbalances in neurological disease patients using INAA (instrumental neutron activation analysis)

    SciTech Connect

    Ehmann, W.D.; Vance, D.E.; Khare, S.S.; Kasarskis, E.J.; Markesbery, W.R.

    1988-01-01

    Evidence has been presented in the literature to implicate trace elements in the etiology of several age-related neurological diseases. Most of these studies are based on brain analyses. Using instrumental neutron activation analysis (INAA), we have observed trace element imbalances in brains of patients with Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Picks's disease. The most prevalent elemental imbalances found in the brain were for bromine, mercury, and the alkali metals. In this study the authors report INAA studies of trace elements in nonneural tissues from Alzheimer's disease and ALS patients. Samples from household relatives were collected for use as controls wherever possible. Hair samples were washed according to the International Atomic Energy Agency recommended procedure. Fingernail samples were scraped with a quartz knife prior to washing by the same procedure. For ALS patients, blood samples were also collected. These data indicate that elemental imbalances in Alzheimer's disease and ALS are not restricted to the brain. Many elements perturbed in the brain are also altered in the several nonneural tissues examined to date. The imbalances in different tissues, however, are not always in the same direction. The changes observed may represent causes, effects, or simply epiphenomena. Longitudinal studies of nonneural tissues and blood, as well as tissue microprobe analyses at the cellular and subcellular level, will be required in order to better assess the role of trace elements in the etiology of these diseases.

  19. The role of hyperhomocysteinemia in neurological features associated with coeliac disease.

    PubMed

    Ferretti, Alessandro; Parisi, Pasquale; Villa, Maria Pia

    2013-10-01

    Although a range of neurological and psychiatric disorders are widely reported to be associated with coeliac patients, their pathogenesis remains unclear. Some such disorders are believed to be secondary to vitamin deficiency due to malabsorption, others to immune mechanisms. We hypothesise that hyperhomocysteinemia might, by damaging the blood-brain barrier, expose neuronal tissue to all neuro-irritative metabolites, such as homocysteine itself, a neurotoxic excitatory and proconvulsant amino acid. Neurons respond to these stimuli through hyperexcitability, thereby predisposing subjects to neurological disorders such as epilepsy and headache. Furthermore, persisting endothelial damage may cause blood extravasation and subsequent deposition of calcium salts. We suggest that this might be the pathogenesis of the CEC syndrome, which is characterized by the association of coeliac disease, epilepsy and cerebral calcifications. Indeed, homocysteine plays a well-known role in cardiovascular endothelial dysfunction, with high serum and cerebrospinal fluid levels often being reported in coeliac patients. Moreover, data in the literature show a strong, growing association of homocysteine with epilepsy and migraine in non-coeliac subjects. Despite these findings, homocysteine has never been held directly responsible for neuronal functional features (neuronal hyperexcitability underlying epilepsy and migraine) and structural brain damage (expressed as cerebral calcification) in coeliac patients. Damage to the blood-brain barrier might also facilitate immune reactions against neuronal tissue to a considerable extent. This hypothesis combines the two afore-mentioned theories (vitamin deficiency due to malabsorption and immune mechanisms). We also wish to point out that no studies have yet investigated the prevalence of neuronal hyperexcitability and subclinical electroencephalic abnormalities in children and adults with newly-diagnosed coeliac disease before the introduction of

  20. Nongenital human papillomavirus disease.

    PubMed

    Mayeaux, E J; Khan, Michelle J

    2013-06-01

    Human papillomavirus (HPV) is the most common viral cause of cancer, and is responsible for 5% of cancers worldwide. Following demonstration of the causative link between HPV and cervical cancer, HPV has been shown to be associated with several anogenital malignancies and with oral pharyngeal cancers. HPV-related anal and oral pharyngeal disease is rising in incidence and includes anal warts and neoplasia, recurrent respiratory papillomatosis, and oral pharyngeal neoplasia. This article presents an overview of the epidemiology, clinical manifestations, diagnosis, and treatment of nongenital HPV-related disease.

  1. Impact of maternal diet on human milk composition and neurological development of infants.

    PubMed

    Innis, Sheila M

    2014-03-01

    Maternal nutrition has little or no effect on many nutrients in human milk; for others, human milk may not be designed as a primary nutritional source for the infant; and for a few, maternal nutrition can lead to substantial variations in human milk quality. Human milk fatty acids are among the nutrients that show extreme sensitivity to maternal nutrition and are implicated in neurological development. Extensive development occurs in the infant brain, with growth from ∼ 350 g at birth to 925 g at 1 y, with this growth including extensive dendritic and axonal arborization. Transfer of n-6 (omega-6) and n-3 (omega-3) fatty acids from the maternal diet into human milk occurs with little interconversion of 18:2n-6 to 20:4n-6 or 18:3n-3 to docosahexaenoic acid (DHA) and little evidence of mammary gland regulation to maintain individual fatty acids constant with varying maternal fatty acid nutrition. DHA has gained attention because of its high concentrations and roles in the brain and retina. Studies addressing DHA intakes by lactating women or human milk amounts of DHA at levels above those typical in the United States and Canada on infant outcomes are inconsistent. However, separating effects of the fatty acid supply in gestation or in the weaning diet from effects on neurodevelopment solely due to human milk fatty acids is complex, particularly when neurodevelopment is assessed after the period of exclusive human milk feeding. Information on infant fatty acid intakes, including milk volume consumed and energy density, will aid in understanding of the human milk fatty acids that best support neurological development.

  2. The role of nanotechnology and nano and micro-electronics in monitoring and control of cardiovascular diseases and neurological disorders

    NASA Astrophysics Data System (ADS)

    Varadan, Vijay K.

    2007-04-01

    controlled manipulation of individual molecules and atoms that can interact with the human body at sub-cellular level. The recent progress in microelectronics and nanosensors crates very powerful tools for the early detection and diagnosis. The nanowire integrated potassium and dopamine sensors are ideal for the monitoring and control of many cardiovascular diseases and neurological disorders. Selected movies illustrating the applications of nanodevices to patients will be shown at the talk.

  3. Deep Vein Thrombosis in the Lower Extremities in Comatose Elderly Patients with Acute Neurological Diseases

    PubMed Central

    Tomita, Yusuke; Murakami, Hideki; Nakane, Makoto

    2016-01-01

    Purpose Comatose elderly patients with acute neurological illness have a great risk of deep vein thrombosis (DVT). In this study, the incidence of DVT and the effectiveness of early initiation of treatment were evaluated in those patients. Materials and Methods Total 323 patients were admitted to our ward due to neurological diseases in one year, and 43 patients, whose Glasgow Coma Scale was ≤11 and who was older than ≥60 years, were included in this study. D-dimer was measured on admission and day 7, and lower-extremity ultrasonography was performed on day 7. When DVT was positive, heparin treatment was initiated, and further evaluation of pulmonary embolism (PE) was conducted. Vena cava filter protection was inserted in PE-positive patients. Incidence of DVT and PE, alteration of D-dimer value, and effect of heparin treatment were analyzed. Results DVT was positive in 19 (44.2%) patients, and PE was in 4 (9.3%). D-dimer was significantly higher in DVT-positive group on day 7 (p<0.01). No DVT were identified in patients with ischemic disease, while 66.7% of intracerebral hemorrhage and 53.3% of brain contusion patients were DVT positive. Surgery was a definite risk factor for DVT, with an odds ratio of 5.25. DVT and PE disappeared by treatment in all cases, and no patients were succumbed to the thrombosis. Conclusion Patients with hemorrhagic diseases or who undergo operation possess high risk of DVT, and initiation of heparin treatment in 7 days after admission is an effective prophylaxis for DVT in comatose elderly patients without causing bleeding. PMID:26847291

  4. Neurological involvement in North Italian patients with Behçet disease.

    PubMed

    Lo Monaco, Andrea; La Corte, Renato; Caniatti, Luisa; Borrelli, Massimo; Trotta, Francesco

    2006-10-01

    The aim of this study was to evaluate neurological involvement in a series of 110 North Italian patients with Behçet disease (BD), a multisystemic vasculitis of unknown origin, followed up for a period of 5 years. During this time, 27 (24.5%) patients with neuro-BD were identified. Twenty out of 27 showed at least one acute attack in their clinical course. In 14 of them, a neurological evaluation was carried out during the attack. The other 13 patients were evaluated during a remission phase. The onset of neuro-BD was usually characterized by an acute attack with motor symptoms (66.6%) and behavioural/cognitive changes (47.6%), while headache was more frequent in the remission phase (76.9%). On magnetic resonance imaging, large brain-stem/diencephalon lesions were usually seen during the attack. In the remission phase, they were often located in the white-matter. Aspecific cerebrospinal fluid abnormalities were usually seen during the attacks. Cerebrospinal fluid analysis together with radiological and clinical features seems to be useful for the differential diagnosis in these patients. PMID:16794844

  5. Neurologic Complications Associated with Sjögren's Disease: Case Reports and Modern Pathogenic Dilemma

    PubMed Central

    Colaci, Michele; Cassone, Giulia; Manfredi, Andreina; Sebastiani, Marco; Giuggioli, Dilia; Ferri, Clodoveo

    2014-01-01

    Objectives. Sjögren's syndrome (SS) may be complicated by some neurological manifestations, generally sensory polyneuropathy. Furthermore, involvement of cranial nerves was described as rare complications of SS. Methods. We reported 2 cases: the first one was a 40-year-old woman who developed neuritis of the left optic nerve as presenting symptom few years before the diagnosis of SS; the second was a 54-year-old woman who presented a paralysis of the right phrenic nerve 7 years after the SS onset. An exhaustive review of the literature on patients with cranial or phrenic nerve involvements was also carried out. Results. To the best of our knowledge, our second case represents the first observation of SS-associated phrenic nerve mononeuritis, while optic neuritis represents the most frequent cranial nerve involvement detectable in this connective tissue disease. Trigeminal neuropathy is also frequently reported, whereas neuritis involving the other cranial nerves is quite rare. Conclusions. Cranial nerve injury is a harmful complication of SS, even if less commonly recorded compared to peripheral neuropathy. Neurological manifestations may precede the clinical onset of SS; therefore, in patients with apparently isolated cranial nerve involvement, a correct diagnosis of the underlying SS is often delayed or overlooked entirely; in these instances, standard clinicoserological assessment is recommendable. PMID:25161786

  6. A neuropsychological comparison of siblings with neurological versus hepatic symptoms of Wilson's Disease.

    PubMed

    Arguedas, Deborah; Stewart, Jeanette; Hodgkinson, Suzanne; Batchelor, Jennifer

    2015-01-01

    Wilson's Disease (WD) (also known as hepatolenticular degeneration) is a rare inherited autosomal recessive disorder of abnormal copper metabolism, with an estimated prevalence of approximately 1 in 30,000. The clinical features associated with WD are highly varied. However, subtypes generally reflect neurological, hepatic, and psychiatric symptoms. The present case study reports two brothers with a recent diagnosis of WD. Neurological symptoms and cognitive deficits were exhibited in one brother (BL) in the form of extrapyramidal features, while the other brother (AL) only exhibited hepatic symptoms. Extensive neuropsychological testing was conducted on both siblings to compare cognitive profiles. Results for BL indicated significantly impaired motor functioning and information processing speed, which impacted him significantly at school. Aspects of executive dysfunction were also apparent in addition to reduced visual and verbal memory, working memory, and attention. Results for AL revealed evidence of verbal memory difficulties and aspects of executive dysfunction. Comparison is made of the distinct and common cognitive characteristics of the cases presented in terms of implications for early intervention and management of cognitive difficulties.

  7. The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases.

    PubMed

    Obeid, Rima; McCaddon, Andrew; Herrmann, Wolfgang

    2007-01-01

    Hyperhomocysteinemia (HHcy) is related to central nervous system diseases. Epidemiological studies show a positive, dose-dependent relationship between plasma total homocysteine (tHcy) concentration and neurodegenerative disease risk. tHcy is a marker of B-vitamin (folate, B(12), B(6)) status. Hypomethylation, caused by low B-vitamin status and HHcy, is linked to key pathomechanisms of dementia; B-vitamin supplementation could potentially reduce neurological damage. In retrospective studies, the association between tHcy and cognition is impressive; there is also evidence that tHcy-lowering treatment could be effective in primary and secondary stroke prevention. Increased tHcy and low serum folate occur in patients with Parkinson's disease, especially those receiving L-dopa. There is also an association between HHcy and multiple sclerosis, and between B-vitamin status and depression. Studies also confirm a causal role for tHcy in epilepsy, and certain anti-epileptics enhance HHcy. B-vitamin status should be optimized by ensuring sufficient intake in patients with neuropsychiatric diseases. HHcy occurs commonly in the elderly and can contribute to age-related neurodegeneration. Treatment with folic acid, B(12) and B(6) lowers tHcy. For secondary and primary prevention from several neuropsychiatric disorders, it seems prudent to actively identify deficient subjects and ensure sufficient vitamin intake.

  8. [My way to "Keep Pioneering": integrated neuroscience and immunology research produces a paradigm shift for intractable neurological disease].

    PubMed

    Kira, Jun-ichi

    2014-01-01

    The motto of Prof. Yoshigoro Kuroiwa, who established the first independent neurology department in Japan at Kyushu University, is "Keep Pioneering". His students have followed this motto in all fields. I hereby present my efforts to keep pioneering in the following fields: (1) multiple sclerosis (MS); (2) central nervous system (CNS) involvement associated with peripheral atopic inflammation; and (3) care network for patients with intractable neurological disease. In MS, I propose that Th1/Th17 cell-mediated connexin astrocytopathy may play a critical role in producing huge demyelinating lesions in MS, neuromyelitis optica (NMO), and Baló's concentric sclerosis. I discovered a peculiar myelitis that occurred in patients with atopic disorders, and designated it atopic myelitis. In this condition, allodynia and neuropathic pain are cardinal features, regardless of the presence or absence of spinal cord MRI lesions. We found that peripheral atopic inflammation in mice produces allodynia as well as activation of microglia and astroglia in the spinal cord. It is important to involve a variety of medical specialists and care coordinators for collaborative work on medical and social care issues for people with intractable disease. The motto of "Keep Pioneering" in neurology covers not only advanced research for the creation of new therapies for intractable neurological disease, but also caring for actual people with intractable disease, which I believe is the corporate social responsibility of our neurological society. I think that "Keep Pioneering" is a challenging process that never ends throughout one's life. PMID:25672676

  9. Opinion: neural stem cell therapy for neurological diseases: dreams and reality.

    PubMed

    Rossi, Ferdinando; Cattaneo, Elena

    2002-05-01

    There is a pressing need for treatments for neurodegenerative diseases. Hopes have been raised by the prospect of neural stem cell therapy; however, despite intense research activities and media attention, stem cell therapy for neurological disorders is still a distant goal. Effective strategies must be developed to isolate, enrich and propagate homogeneous populations of neural stem cells, and to identify the molecules and mechanisms that are required for their proper integration into the injured brain. This article examines these requirements, discusses the results obtained so far, and considers the steps that need to be taken to provide instruction to donor cells and to elucidate the neurogenic potential of the adult central nervous system environment.

  10. Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders

    PubMed Central

    Barral, Serena; Kurian, Manju A.

    2016-01-01

    The study of neurological disorders often presents with significant challenges due to the inaccessibility of human neuronal cells for further investigation. Advances in cellular reprogramming techniques, have however provided a new source of human cells for laboratory-based research. Patient-derived induced pluripotent stem cells (iPSCs) can now be robustly differentiated into specific neural subtypes, including dopaminergic, inhibitory GABAergic, motorneurons and cortical neurons. These neurons can then be utilized for in vitro studies to elucidate molecular causes underpinning neurological disease. Although human iPSC-derived neuronal models are increasingly regarded as a useful tool in cell biology, there are a number of limitations, including the relatively early, fetal stage of differentiated cells and the mainly two dimensional, simple nature of the in vitro system. Furthermore, clonal variation is a well-described phenomenon in iPSC lines. In order to account for this, robust baseline data from multiple control lines is necessary to determine whether a particular gene defect leads to a specific cellular phenotype. Over the last few years patient-derived neural cells have proven very useful in addressing several mechanistic questions related to central nervous system diseases, including early-onset neurological disorders of childhood. Many studies report the clinical utility of human-derived neural cells for testing known drugs with repurposing potential, novel compounds and gene therapies, which then can be translated to clinical reality. iPSCs derived neural cells, therefore provide great promise and potential to gain insight into, and treat early-onset neurological disorders. PMID:27656126

  11. Intracerebroventricular gene therapy that delays neurological disease progression is associated with selective preservation of retinal ganglion cells in a canine model of CLN2 disease.

    PubMed

    Whiting, Rebecca E H; Jensen, Cheryl A; Pearce, Jacqueline W; Gillespie, Lauren E; Bristow, Daniel E; Katz, Martin L

    2016-05-01

    CLN2 disease is one of a group of lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs). The disease results from mutations in the TPP1 gene that cause an insufficiency or complete lack of the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). TPP1 is involved in lysosomal protein degradation, and lack of this enzyme results in the accumulation of protein-rich autofluorescent lysosomal storage bodies in numerous cell types including neurons throughout the central nervous system and the retina. CLN2 disease is characterized primarily by progressive loss of neurological functions and vision as well as generalized neurodegeneration and retinal degeneration. In children the progressive loss of neurological functions typically results in death by the early teenage years. A Dachshund model of CLN2 disease with a null mutation in TPP1 closely recapitulates the human disorder with a progression from disease onset at approximately 4 months of age to end-stage at 10-11 months. Delivery of functional TPP1 to the cerebrospinal fluid (CSF), either by periodic infusion of the recombinant protein or by a single administration of a TPP1 gene therapy vector to the CSF, significantly delays the onset and progression of neurological signs and prolongs life span but does not prevent the loss of vision or modest retinal degeneration that occurs by 11 months of age. In this study we found that in dogs that received the CSF gene therapy treatment, the degeneration of the retina and loss of retinal function continued to progress during the prolonged life spans of the treated dogs. Eventually the normal cell layers of the retina almost completely disappeared. An exception was the ganglion cell layer. In affected dogs that received TPP1 gene therapy to the CSF and survived an average of 80 weeks, ganglion cell axons were present in numbers comparable to those of normal Dachshunds of similar age. The selective preservation of the retinal ganglion cells suggests

  12. The History of Parkinson's Disease: Early Clinical Descriptions and Neurological Therapies

    PubMed Central

    Goetz, Christopher G.

    2011-01-01

    Although components of possible Parkinson's disease can be found in very early documents, the first clear medical description was written in 1817 by James Parkinson. In the mid-1800s, Jean-Martin Charcot was particularly influential in refining and expanding this early description and in disseminating information internationally about Parkinson's disease. He separated Parkinson's disease from multiple sclerosis and other disorders characterized by tremor, and he recognized cases that later would likely be classified among the Parkinsonism-plus syndromes. Early treatments of Parkinson's disease were based on empirical observation, and anticholinergic drugs were used as early as the nineteenth century. The discovery of dopaminergic deficits in Parkinson's disease and the synthetic pathway of dopamine led to the first human trials of levodopa. Further historically important anatomical, biochemical, and physiological studies identified additional pharmacological and neurosurgical targets for Parkinson's disease and allow modern clinicians to offer an array of therapies aimed at improving function in this still incurable disease. PMID:22229124

  13. [Peroxisomal neurologic diseases and Refsum disease: very long chain fatty acids and phytanic acid as diagnostic markers].

    PubMed

    Molzer, B; Stöckler, S; Bernheimer, H

    1992-01-01

    Peroxisomal disorders are genetic metabolic diseases with generalized, multiple, or single functional disturbances of the peroxisome. According to the extent of the functional disturbances 3 groups of diseases can be differentiated: disorders with generalized loss of peroxisomal functions (Zellweger syndrome, ZS; neonatal adrenoleukodystrophy, NALD; infantile Refsum's disease), disorders with multiple enzymatic defects (e.g. rhizomelic chondrodysplasia punctata), and disorders with a single enzymatic defect in the peroxisome, the most important being adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN). Adult Refsum's disease, a genetic neurological disorder with phytanic acid accumulation, is due to a mitochondrial enzyme deficiency, but is often considered together with peroxisomal diseases because of phytanic acid (PHYT) accumulation in most peroxisomal diseases. The main clinical and pathological criteria of the major disorders and the biochemical parameters of their differentiation are presented. Elevated levels of very long chain fatty acids (VLCFA) and/or PHYT are the primary diagnostic markers for all peroxisomal disorders and adult Refsum's disease, respectively. Our investigations disclosed 30 ALD/AMN hemizygotes, 16 ALD/AMN heterozygotes, 8 cases of ZS/NALD and 7 patients with adult Refsum's disease. In addition, 15 cases of peroxisomal disorders were confirmed by biochemical investigations in autopsy material. With regard to peroxisomal disorders, therapeutic concepts exist only for ALD/AMN: corticosteroid substitution for adrenal insufficiency, dietary treatment, and bone marrow transplantation (BMT). Adult Refsum's disease can be treated successfully by dietary therapy. In case of dietary treatment and BMT, assay of VLCFA and/or PHYT is important for the biochemical evaluation of these therapies.

  14. Recurrent headaches: a case of neurological Behçet's disease.

    PubMed

    Ismail, Alaa M; Dubrey, Simon W; Patel, Maneesh C

    2013-10-01

    A 48-year-old black male, of Nigerian heritage, presented with a 24-hour history of frontal headache of gradual onset. The headache characteristic was migranous, being described as throbbing in nature and located to the right frontal area with associated blurring of vision. Although similar to prior frequent headaches, there was now increasing unsteadiness on walking. Diagnosed 10 years earlier with Behçet's disease, the initial presentation was with oral and genital ulceration. Recurrent episodes of headache caused by neurological flare-ups resulted in a stroke at the age of 46 years. This previous stroke was ischaemic in character with involvement of the brainstem, pons, midbrain and right cerebral peduncle with extension into the right internal capsule. Surveillance brain imaging (computed tomographic and magnetic resonance imaging with venography) 10 months earlier showed brainstem disease activity (Figure 1a) with disease quiescence a month later (Figure 1b) following an escalation of immunosuppressant therapy. Regular medications comprised prednisolone 10 mg (however, regular recurrences had resulted in him taking doses of between 20 and 30 mg/day of prednisolone for most of the past 24 months) and azathioprine 150 mg daily, aspirin 75 mg daily, one adcal D3 twice daily with weekly alendronic acid, and omeprazole 20 mg daily. For headache he took topiramate 25 mg daily and for depression mirtazepine 15 mg daily. The patient was also addicted to a high level of cannabis use which he was reluctant to stop as he felt it helped his symptoms. On examination he was apyrexial and cardiovascularly stable. Neurological examination revealed a residual horizontal nystagmus to the right on lateral gaze, mild left hemiparesis with moderate spasticity, in addition to dysarthria and dysphonia from his prior stroke. A new feature was an exacerbation of gait unsteadiness. Blood tests were unremarkable and specifically the erythrocyte sedimentation rate was normal at 2 mm

  15. [Evaluation of repetitive transcranial magnetic stimulation effectiveness in treatment of psychiatric and neurologic diseases].

    PubMed

    Pastuszak, Żanna; Stępień, Anna; Piusińska-Macoch, Renata; Brodacki, Bogdan; Tomczykiewicz, Kazimierz

    2016-06-01

    Repetitive transcranial magnetic stimulation (rTMS) is a treatment option with proved effectiveness especially in drug resist depression. It is used in functional brain mapping before neurosurgery operations and diagnostic of corticospinal tract transmission. Many studies are performed to evaluate rTMS using in treatment of obsessive - compulsive disorder, schizophrenia, autism, strokes, tinnitus, Alzheimer and Parkinson diseases, cranial traumas. Moreover rTMS was used in treatment of multiple sclerosis, migraine, dystonia. Electromagnetical field generated by rTMS penetrate skin of the scalp and infiltrate brain tissues to a depth of 2 cm, cause neurons depolarization and generating motor, cognitive and affective effects. Depending on the stimulation frequency rTMS can stimuli or inhibit brain cortex. rTMS mechanism of action remains elusive. Probably it is connected with enhancement of neurotransmitters, modulation of signals transductions pathways in Central Nervous System, gene transcription and release of neuroprotective substances. Studies with use of animals revealed that rTMS stimulation can generate brain changes similar to those seen after electric shock therapy without provoking seizures. The aim of presenting study was to analyze actual researches evaluating rTMS use in treatment of psychiatric and neurological diseases. PMID:27403908

  16. Serum brain-derived neurotrophic factor levels in different neurological diseases.

    PubMed

    Ventriglia, Mariacarla; Zanardini, Roberta; Bonomini, Cristina; Zanetti, Orazio; Volpe, Daniele; Pasqualetti, Patrizio; Gennarelli, Massimo; Bocchio-Chiavetto, Luisella

    2013-01-01

    Consistent evidence indicates the involvement of the brain-derived neurotrophic factor (BDNF) in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). In the present study, we compared serum BDNF in 624 subjects: 266 patients affected by AD, 28 by frontotemporal dementia (FTD), 40 by Lewy body dementia (LBD), 91 by vascular dementia (VAD), 30 by PD, and 169 controls. Our results evidenced lower BDNF serum levels in AD, FTD, LBD, and VAD patients (P < 0.001) and a higher BDNF concentration in patients affected by PD (P = 0.045). Analyses of effects of pharmacological treatments suggested significantly higher BDNF serum levels in patients taking mood stabilizers/antiepileptics (P = 0.009) and L-DOPA (P < 0.001) and significant reductions in patients taking benzodiazepines (P = 0.020). In conclusion, our results support the role of BDNF alterations in neurodegenerative mechanisms common to different forms of neurological disorders and underline the importance of including drug treatment in the analyses to avoid confounding effects. PMID:24024214

  17. Role of Nicotinic and Muscarinic Receptors on Synaptic Plasticity and Neurological Diseases.

    PubMed

    Fuenzalida, Marco; Pérez, Miguel Ángel; Arias, Hugo R

    2016-01-01

    The cholinergic activity in the brain is fundamental for cognitive functions. The modulatory activity of the neurotransmitter acetylcholine (ACh) is mediated by activating a variety of nicotinic acetylcholine receptors (nAChR) and muscarinic acetylcholine receptors (mAChR). Accumulating evidence indicates that both nAChR and mAChRs can modulate the release of several other neurotransmitters, modify the threshold of long-term plasticity, finally improving learning and memory processes. Importantly, the expression, distribution, and/or function of these systems are altered in several neurological diseases. The aim of this review is to discuss our current knowledge on cholinergic receptors and their regulating synaptic functions and neuronal network activities as well as their use as targets for the development of new and clinically useful cholinergic ligands. These new therapies involve the development of novel and more selective cholinergic agonists and allosteric modulators as well as selective cholinesterase inhibitors, which may improve cognitive and behavioral symptoms, and also provide neuroprotection in several brain diseases. The review will focus on two nAChR receptor subtypes found in the mammalian brain and the most commonly targeted in drug discovery programs for neuropsychiatric disorder, the ligands of α4β2 nAChR and α7 nAChRs. PMID:26818867

  18. IgG-index predicts neurological morbidity in patients with infectious central nervous system diseases

    PubMed Central

    2010-01-01

    Background Prognosis assessment of patients with infectious and neoplastic disorders of the central nervous system (CNS) may still pose a challenge. In this retrospective cross-sectional study the prognostic value of basic cerebrospinal fluid (CSF) parameters in patients with bacterial meningitis, viral meningoencephalitis and leptomeningeal metastases were evaluated. Methods White blood cell count, CSF/serum glucose ratio, protein, CSF/serum albumin quotient and Immunoglobulin indices for IgG, IgA and IgM were analyzed in 90 patients with bacterial meningitis, 117 patients with viral meningoencephalitis and 36 patients with leptomeningeal metastases in a total of 480 CSF samples. Results In the initial spinal tap, the IgG-index was the only independent predictor for unfavorable outcome (GOS < 5) in patients with infectious CNS diseases but not in patients with leptomeningeal metastases. The sensitivity and specificity of an IgG-index of 0.75 and higher for predicting unfavorable outcome was 40.9% and 80.8% in bacterial meningitis and 40% and 94.8% in viral meningoencephalitis, respectively. No significant associations between CSF parameters and outcome could be observed in follow-up CSF samples. Conclusion The present study suggests that in infectious CNS diseases an elevated IgG-Index might be an additional marker for the early identification of patients at risk for neurological morbidity. PMID:20618966

  19. Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features

    PubMed Central

    Ouyang, Qing; Nakayama, Tojo; Baytas, Ozan; Davidson, Shawn M.; Yang, Chendong; Schmidt, Michael; Lizarraga, Sofia B.; Mishra, Sasmita; EI-Quessny, Malak; Niaz, Saima; Gul Butt, Mirrat; Imran Murtaza, Syed; Javed, Afzal; Chaudhry, Haroon Rashid; Vaughan, Dylan J.; Hill, R. Sean; Partlow, Jennifer N.; Yoo, Seung-Yun; Lam, Anh-Thu N.; Nasir, Ramzi; Al-Saffar, Muna; Barkovich, A. James; Schwede, Matthew; Nagpal, Shailender; Rajab, Anna; DeBerardinis, Ralph J.; Housman, David E.; Mochida, Ganeshwaran H.; Morrow, Eric M.

    2016-01-01

    Mutations that cause neurological phenotypes are highly informative with regard to mechanisms governing human brain function and disease. We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in large kindreds initially ascertained for intellectual and developmental disability (IDD). GPT2 [also known as alanine transaminase 2 (ALT2)] is one of two related transaminases that catalyze the reversible addition of an amino group from glutamate to pyruvate, yielding alanine and α-ketoglutarate. In addition to IDD, all affected individuals show postnatal microcephaly and ∼80% of those followed over time show progressive motor symptoms, a spastic paraplegia. Homozygous nonsense p.Arg404* and missense p.Pro272Leu mutations are shown biochemically to be loss of function. The GPT2 gene demonstrates increasing expression in brain in the early postnatal period, and GPT2 protein localizes to mitochondria. Akin to the human phenotype, Gpt2-null mice exhibit reduced brain growth. Through metabolomics and direct isotope tracing experiments, we find a number of metabolic abnormalities associated with loss of Gpt2. These include defects in amino acid metabolism such as low alanine levels and elevated essential amino acids. Also, we find defects in anaplerosis, the metabolic process involved in replenishing TCA cycle intermediates. Finally, mutant brains demonstrate misregulated metabolites in pathways implicated in neuroprotective mechanisms previously associated with neurodegenerative disorders. Overall, our data reveal an important role for the GPT2 enzyme in mitochondrial metabolism with relevance to developmental as well as potentially to neurodegenerative mechanisms. PMID:27601654

  20. Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features.

    PubMed

    Ouyang, Qing; Nakayama, Tojo; Baytas, Ozan; Davidson, Shawn M; Yang, Chendong; Schmidt, Michael; Lizarraga, Sofia B; Mishra, Sasmita; Ei-Quessny, Malak; Niaz, Saima; Gul Butt, Mirrat; Imran Murtaza, Syed; Javed, Afzal; Chaudhry, Haroon Rashid; Vaughan, Dylan J; Hill, R Sean; Partlow, Jennifer N; Yoo, Seung-Yun; Lam, Anh-Thu N; Nasir, Ramzi; Al-Saffar, Muna; Barkovich, A James; Schwede, Matthew; Nagpal, Shailender; Rajab, Anna; DeBerardinis, Ralph J; Housman, David E; Mochida, Ganeshwaran H; Morrow, Eric M

    2016-09-20

    Mutations that cause neurological phenotypes are highly informative with regard to mechanisms governing human brain function and disease. We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in large kindreds initially ascertained for intellectual and developmental disability (IDD). GPT2 [also known as alanine transaminase 2 (ALT2)] is one of two related transaminases that catalyze the reversible addition of an amino group from glutamate to pyruvate, yielding alanine and α-ketoglutarate. In addition to IDD, all affected individuals show postnatal microcephaly and ∼80% of those followed over time show progressive motor symptoms, a spastic paraplegia. Homozygous nonsense p.Arg404* and missense p.Pro272Leu mutations are shown biochemically to be loss of function. The GPT2 gene demonstrates increasing expression in brain in the early postnatal period, and GPT2 protein localizes to mitochondria. Akin to the human phenotype, Gpt2-null mice exhibit reduced brain growth. Through metabolomics and direct isotope tracing experiments, we find a number of metabolic abnormalities associated with loss of Gpt2. These include defects in amino acid metabolism such as low alanine levels and elevated essential amino acids. Also, we find defects in anaplerosis, the metabolic process involved in replenishing TCA cycle intermediates. Finally, mutant brains demonstrate misregulated metabolites in pathways implicated in neuroprotective mechanisms previously associated with neurodegenerative disorders. Overall, our data reveal an important role for the GPT2 enzyme in mitochondrial metabolism with relevance to developmental as well as potentially to neurodegenerative mechanisms. PMID:27601654

  1. Consensus Statement on medication use in multiple sclerosis by the Spanish Society of Neurology's study group for demyelinating diseases.

    PubMed

    García-Merino, A; Fernández, O; Montalbán, X; de Andrés, C; Oreja-Guevara, C; Rodríguez-Antigüedad, A; Arbizu, T

    2013-01-01

    Treatments for multiple sclerosis therapy are rapidly evolving. It is believed that new drugs will be approved in the near future, thereby changing current indications for treatment. In this context, the Spanish Society of Neurology's study group on demyelinating diseases, which evaluates medication use in MS, has decided to draw up a consensus statement on the current indications and guidelines for multiple sclerosis treatment.

  2. Epilepsy and Other Neurological Diseases in the Parents of Children with Infantile Autism. A Case Control Study

    ERIC Educational Resources Information Center

    Mouridsen, Svend Erik; Rich, Bente; Isager, Torben

    2008-01-01

    In order to study the broader phenotype of infantile autism (IA) we compared the rates and types of epilepsy and other neurological diseases in the parents of 111 consecutively admitted patients with IA with a matched control group of parents of 330 children from the general population. All participants were screened through the nationwide Danish…

  3. Perspectives on cognitive domains, H3 receptor ligands and neurological disease.

    PubMed

    Hancock, Arthur A; Fox, Gerard B

    2004-10-01

    Histamine H(3) receptor agonists and antagonists have been evaluated in numerous in vitro and in vivo animal models to better understand how H(3) receptors modulate neurotransmitter function in the central nervous system. Likewise, behavioural models have explored the hypothesis that changes in neurotransmitter release could enhance cognitive function in human diseases. This review examines the reported effects of H(3) receptor ligands and how they influence cognitive behaviour. These data are interpreted on the basis of different cognitive domains that are relevant to neuropsychiatric diseases. Because of the diversity of H(3) receptors, their function and their influence on neurotransmitter systems, considerable promise exists for H(3) ligands to treat diseases in which aspects of learning and memory are impaired. However, because of the complexities of the histaminergic system and H(3) receptors and the lack of clinical data so far, proof of principle for use in human disease remains to be established.

  4. Neurology in the developing world.

    PubMed

    Singhal, B S; Khadilkar, Satish V

    2014-01-01

    The social and economic impact of neurologic disorders is being increasingly recognized in the developing world. Demographic transition, especially in large Asian populations, has resulted in a significant increase in the elderly population, bringing to the fore neurologic illnesses such as strokes, Alzheimer's disease, and Parkinson's disease. CNS infections such as retroviral diseases, tuberculosis, and malaria still account for high mortality and morbidity. Traumatic brain injury due to traffic accidents takes a high toll of life. Epilepsy continues to be a major health concern with large segments of the developing world's population receiving no treatment. A significant mismatch between the provision of specialized neurologic services and the requirement for them exists, especially in rural areas. Also, health insurance is not available for the majority, with patients having bear the costs themselves, thus limiting the procurement of available healthcare facilities. Neurologic training centers are few and the availability of laboratory facilities and equipment is largely limited to the metropolitan areas. Cultural practices, superstitious beliefs, ignorance, and social stigma may also impede the delivery of neurologic care. Optimizing available human resources, integrating primary, secondary, and tertiary healthcare tiers and making medical treatment more affordable will improve the neurologic care in the developing world.

  5. [Current status of the predictive genetic testing for hereditary neurological diseases in Shinshu University Hospital].

    PubMed

    Tanaka, Keiko; Sekijima, Yoshiki; Yoshida, Kunihiro; Mizuuchi, Asako; Yamashita, Hiromi; Tamai, Mariko; Ikeda, Shu-ichi; Fukushima, Yoshimitsu

    2013-01-01

    The current status of predictive genetic testing for late-onset hereditary neurological diseases in Japan is largely unknown. In this study, we analyzed data from 73 clients who visited the Division of Clinical and Molecular Genetics, Shinshu University Hospital, for the purpose of predictive genetic testing. The clients consisted of individuals with family histories of familial amyloid polyneuropathy (FAP; n=30), Huntington's disease (HD; n=16), spinocerebellar degeneration (SCD; n=14), myotonic dystrophy type 1 (DM1; n=9), familial amyotrophic lateral sclerosis type 1 (ALS1; n=3), and Alzheimer's disease (AD; n=1). Forty-nine of the 73 (67.1%) clients were in their twenties or thirties. Twenty-seven of the 73 (37.0%) clients visited a medical institution within 3 months after becoming aware of predictive genetic testing. The most common reason for requesting predictive genetic testing was a need for certainty or to reduce uncertainty and anxiety. The decision-making about marriage and having a child was also a main reason in clients in the twenties and thirties. The numbers of clients who actually underwent predictive genetic testing was 22 of 30 (73.3%) in FAP, 3 of 16 (18.8%) in HD, 6 of 10 (60.0%) in SCD, 7 of 9 (77.8%) in DM1, and 0 of 3 (0%) in ALS1 (responsible gene of the disease was unknown in 4 SCD patients and an AD patient). The percentage of test usage was lower in untreatable diseases such as HD and SCD than that in FAP, suggesting that many clients changed their way of thinking on the significance of testing through multiple genetic counseling sessions. In addition, it was obvious that existence of disease-modifying therapy promoted usage of predictive genetic testing in FAP. Improvement of genetic counseling system to manage predictive genetic testing is necessary, as consultation concerning predictive genetic testing is the main motivation to visit genetic counseling clinic in many at-risk clients.

  6. International Classification of Diseases (ICD-11) and neurologic disorders: the future.

    PubMed

    Shakir, Raad; Bergen, Donna

    2013-07-01

    When the WHO's Topic Advisory Group for Neurology (TAG) started work on revision of the ICD-10 diagnostic codes in June 2009, the issues were daunting. The existing classification was produced a generation ago and the need to move to the digital age was becoming imperative. Appreciating modern advances in genetics and immunology, and the consequent changes in understanding of the pathophysiology of disorders of the nervous system, WHO's charge to the TAG was to produce a comprehensive, up-to-date disease classification, while providing published or consensus evidence for each coding change. In addition, the task would be to focus on ways to reduce the treatment gap while considering the utility of ICD-11 when used in primary care and nonspecialist settings. The project mushroomed over the 3 years since our first meeting and continues to do so. The work was made even more difficult as the group needed to add "content models" for the major codes for the first time (i.e., providing a definition for each disorder, along with appropriate diagnostic tests and outcome). The ICD-11 is meant to be updated as new knowledge develops, rather than waiting some years for another whole-scale revision, but this process has yet to be defined.

  7. Antiglycosphingolipid immune responses in neurology. The Vienna experience with isotypes, subclasses, and disease.

    PubMed

    Gatterbauer, B; Neisser, A; Bernheimer, H; Schwerer, B

    1998-06-19

    IgM, IgG, IgA, and IgG subclass anti-GM1, anti-GQ1b, and anti-asialo-GM1 (anti-GA1) antibodies, respectively, were investigated by ELISA in serum from neurological and other patients. Increased anti-GM1 occurred mostly in approximately 15-35% of the cases without statistical differences; high percentages were found in Guillain-Barré syndrome (GBS) preceded by gastrointestinal infection and multifocal motor neuropathy. Roughly, IgM anti-GM1 was most frequent; however, distinct IgG and IgA reactions were found i.a. in GBS. A particular IgM anti-mono- and disialoganglioside pattern occurred in a patient with sensorimotor neuropathy and paraproteinemia. Anti-GQ1b was elevated in all Miller-Fisher patients, with some prevalence of IgG2 among IgG subclasses. Cross-reactivity of anti-GQ1b was demonstrated with Campylobacter jejuni lipopolysaccharides. Increased anti-GM1 and/or anti-GA1 was more frequent in systemic lupus erythematosus with central nervous system involvement than without. Incidence of anti-GM1 and anti-GA1 in X-adrenoleukodystrophy was relatively high. Although anti-GSL antibodies seem to have limited diagnostic value, studies of isotypes, subclass patterns, and cross-reactivities may lead to further insight into the origin of (auto) immune responses and their immunepathogenetic role in disease. PMID:9668368

  8. Role of Oxidative Stress in the Worsening of Neurologic Wilson Disease Following Chelating Therapy.

    PubMed

    Kalita, Jayantee; Kumar, Vijay; Ranjan, Abhay; Misra, Usha K

    2015-12-01

    Patients with neurologic Wilson disease (NWD) may worsen on treatment, but there is no study evaluating the role of oxidative stress. We report the role of plasma glutathione (GSH), total antioxidant capacity (TAC) and malondialdehyde (MDA) in the worsening of NWD following treatment. Fifty-one treatment-naïve NWD patients were subjected to detailed clinical evaluation. The severity of NWD was noted, and dystonia was measured by Burke-Fahn-Marsden (BFM) score. Their hematological, serum chemistry, ultrasound abdomen and cranial MRI changes were noted. Plasma GSH, TAC and MDA, serum free copper (Cu) and 24-h urinary Cu were measured at admission and at 3 and 6 months after treatment. The patients were considered worsened if there was one or more grade deterioration in severity scale, >10 % deterioration in BFM score or appearance of new neurologic signs. The median age of the patients was 11 (5-37) years, and 12 were females. Following treatment, 25 patients improved, 12 worsened, and 14 had stationary course. The worsened group at 3 months had lower GSH (1.99 ± 0.17 vs. 2.30 ± 0.30 mg/dl; P = 0.004) and TAC (1.59 ± 0.12 vs. 1.82 ± 0.17 mmol Trolox equivalent/L; P = 0.001) and higher MDA (5.24 ± 0.22 vs. 4.34 ± 0.46 nmol/ml; P < 0.001) levels compared to the improved group. These changes were associated with increased serum free Cu (41.81 ± 3.31 vs. 35.62 ± 6.40 µg/dl; P = 0.02) and 24-h urinary Cu (206.42 ± 41.61 vs. 121.99 ± 23.72 µg/24 h; P < 0.001) in the worsened compared to the improved group. All the patients having worsening were on penicillamine. Worsening following chelating treatment in NWD may be due to oxidative stress which is induced by increased serum free Cu. These results may have future therapeutic implication and needs further study.

  9. Age-Dependent Myeloid Dendritic Cell Responses Mediate Resistance to La Crosse Virus-Induced Neurological Disease

    PubMed Central

    Taylor, Katherine G.; Woods, Tyson A.; Winkler, Clayton W.; Carmody, Aaron B.

    2014-01-01

    ABSTRACT La Crosse virus (LACV) is the major cause of pediatric viral encephalitis in the United States; however, the mechanisms responsible for age-related susceptibility in the pediatric population are not well understood. Our current studies in a mouse model of LACV infection indicated that differences in myeloid dendritic cell (mDC) responses between weanling and adult mice accounted for susceptibility to LACV-induced neurological disease. We found that type I interferon (IFN) responses were significantly stronger in adult than in weanling mice. Production of these IFNs required both endosomal Toll-like receptors (TLRs) and cytoplasmic RIG-I-like receptors (RLRs). Surprisingly, IFN expression was not dependent on plasmacytoid DCs (pDCs) but rather was dependent on mDCs, which were found in greater number and induced stronger IFN responses in adults than in weanlings. Inhibition of these IFN responses in adults resulted in susceptibility to LACV-induced neurological disease, whereas postinfection treatment with type I IFN provided protection in young mice. These studies provide a definitive mechanism for age-related susceptibility to LACV encephalitis, where mDCs in young mice are insufficiently activated to control peripheral virus replication, thereby allowing virus to persist and eventually cause central nervous system (CNS) disease. IMPORTANCE La Crosse virus (LACV) is the primary cause of pediatric viral encephalitis in the United States. Although the virus infects both adults and children, over 80% of the reported neurological disease cases are in children. To understand why LACV causes neurological disease primarily in young animals, we used a mouse model where weanling mice, but not adult mice, develop neurological disease following virus infection. We found that an early immune response cell type, myeloid dendritic cells, was critical for protection in adult animals and that these cells were reduced in young animals. Activation of these cells during

  10. Generation of the Human Biped Stance by a Neural Controller Able to Compensate Neurological Time Delay

    PubMed Central

    Jiang, Ping; Chiba, Ryosuke; Takakusaki, Kaoru; Ota, Jun

    2016-01-01

    The development of a physiologically plausible computational model of a neural controller that can realize a human-like biped stance is important for a large number of potential applications, such as assisting device development and designing robotic control systems. In this paper, we develop a computational model of a neural controller that can maintain a musculoskeletal model in a standing position, while incorporating a 120-ms neurological time delay. Unlike previous studies that have used an inverted pendulum model, a musculoskeletal model with seven joints and 70 muscular-tendon actuators is adopted to represent the human anatomy. Our proposed neural controller is composed of both feed-forward and feedback controls. The feed-forward control corresponds to the constant activation input necessary for the musculoskeletal model to maintain a standing posture. This compensates for gravity and regulates stiffness. The developed neural controller model can replicate two salient features of the human biped stance: (1) physiologically plausible muscle activations for quiet standing; and (2) selection of a low active stiffness for low energy consumption. PMID:27655271

  11. Hippocrates: the forefather of neurology.

    PubMed

    Breitenfeld, T; Jurasic, M J; Breitenfeld, D

    2014-09-01

    Hippocrates is one of the most influential medical doctors of all times. He started observing and experimenting in times of mysticism and magic. He carried a holistic and humanitarian approach to the patient with examination as the principal approach-inspection, palpation and auscultation are still the most important tools in diagnosing algorithms of today. He had immense experience with the human body most likely due to numerous wound treatments he had performed; some even believe he performed autopsies despite the negative trend at the time. Hippocrates identified the brain as the analyst of the outside world, the interpreter of consciousness and the center of intelligence and willpower. Interestingly, Hippocrates was aware of many valid concepts in neurology; his treatise On the Sacred Disease was the most important for understanding neurology and epilepsy. His other ideas pioneered modern day neurology mentioning neurological diseases like apoplexy, spondylitis, hemiplegia, and paraplegia. Today, 10 % of neurological Pubmed and 7 % of neuroscience Scopus reviews mention Corpus Hippocraticum as one of the sources. Therefore, Hippocrates may be considered as the forefather of neurology. PMID:25027011

  12. Application of Tauroursodeoxycholic Acid for Treatment of Neurological and Non-neurological Diseases: Is There a Potential for Treating Traumatic Brain Injury?

    PubMed

    Gronbeck, Kyle R; Rodrigues, Cecilia M P; Mahmoudi, Javad; Bershad, Eric M; Ling, Geoffrey; Bachour, Salam P; Divani, Afshin A

    2016-08-01

    The objective of this review was to evaluate the potential of tauroursodeoxycholic acid (TUDCA) for neuroprotection in traumatic brain injury (TBI) patients in the neurocritical care setting. Specifically, we surveyed preclinical studies describing the neuroprotective and systemic effects of TUDCA, and the potential therapeutic application of TUDCA. Preclinical studies have provided promising data supporting its use in neurological disease characterized by apoptosis-induced neuronal loss. TUDCA inhibits multiple proteins involved in apoptosis and upregulates cell survival pathways. In addition, TUDCA exhibits anti-inflammatory effects in models of neuroinflammation and attenuates neuronal loss in chronic neurodegenerative diseases. This may be applicable to TBI, which also triggers inflammatory and apoptotic processes. Additionally, preliminary data support the use of pharmacological therapies that reduce apoptosis and inflammation associated with TBI. The anti-apoptotic and anti-inflammatory mechanisms of TUDCA could prove promising in the treatment of TBI. Currently, there are no published data supporting improvement in clinical outcomes of TBI by treatment with TUDCA, but future studies should be considered. PMID:26759227

  13. Anti-B-Cell Therapies in Autoimmune Neurological Diseases: Rationale and Efficacy Trials.

    PubMed

    Alexopoulos, Harry; Biba, Angie; Dalakas, Marinos C

    2016-01-01

    B cells have an ever-increasing role in the etiopathology of a number of autoimmune neurological disorders, acting as antibody-producing cells and, most importantly, as sensors, coordinators, and regulators of the immune response. B cells, among other functions, regulate the T-cell activation process through their participation in antigen presentation and production of cytokines. The availability of monoclonal antibodies or fusion proteins against B-cell surface molecules or B-cell trophic factors bestows a rational approach for treating autoimmune neurological disorders, even when T cells are the main effector cells. This review summarizes basic aspects of B-cell biology, discusses the role(s) of B cells in neurological autoimmunity, and presents anti-B-cell drugs that are either currently on the market or are expected to be available in the near future for treating neurological autoimmune disorders.

  14. Congenital and inherited neurologic diseases in dogs and cats: Legislation and its effect on purchase in Italy.

    PubMed

    Passantino, Annamaria; Masucci, Marisa

    2016-05-01

    Many of the congenital neurologic diseases can result in incapacity or death of the animal. Some of them, such as idiopathic epilepsy and hydrocephalus, exhibit breed or familial predisposition and a genetic basis was proved or suggested. Some diseases can be presumptively diagnosed after a detailed signalment (breed predisposition), history (e.g. family history because many of these defects have familial tendencies), and through physical exam; other diagnostic methods (radiography, computed tomography, magnetic resonance, electrophysiologic tests, etc.) can provide supportive evidence for the congenital defect and help to confirm the diagnosis. Some cases can lead to civil law-suits when the lesions are congenital, but not easily recognizable, or when the lesions are hereditary but tend to became manifest only after some time (more than 12 months after the date of purchase, e.g., after the vice-free guarantee period has expired). Moreover, quite frequently an early diagnosis is not made because there are delays in consulting the veterinarian or the general practitioner veterinarian does not perceive subtle signs. This study was designed to focus on the medico-legal aspects concerning the buying and selling in Italy of dogs and cats affected by congenital and hereditary neurologic diseases that could constitute vice in these animals. While adequate provisions to regulate in detail the various aspects of pet sale have still to be drawn up by legislators, it may be helpful to involve breeders, by obliging them by contract to extend guarantees in the case of hereditary lesions, including neurologic diseases.

  15. Understanding complex transcriptome dynamics in schizophrenia and other neurological diseases using RNA sequencing.

    PubMed

    Wang, Xi; Cairns, Murray J

    2014-01-01

    How the human brain develops and adapts with its trillions of functionally integrated synapses remains one of the greatest mysteries of life. With tremendous advances in neuroscience, genetics, and molecular biology, we are beginning to appreciate the scope of this complexity and define some of the parameters of the systems that make it possible. These same tools are also leading to advances in our understanding of the pathophysiology of neurocognitive and neuropsychiatric disorders. Like the substrate for these problems, the etiology is usually complex-involving an array of genetic and environmental influences. To resolve these influences and derive better interventions, we need to reveal every aspect of this complexity and model their interactions and define the systems and their regulatory structure. This is particularly important at the tissue-specific molecular interface between the underlying genetic and environmental influence defined by the transcriptome. Recent advances in transcriptome analysis facilitated by RNA sequencing (RNA-Seq) can provide unprecedented insight into the functional genomics of neurological disorders. In this review, we outline the advantages of this approach and highlight some early application of this technology in the investigation of the neuropathology of schizophrenia. Recent progress of RNA-Seq studies in schizophrenia has shown that there is extraordinary transcriptome dynamics with significant levels of alternative splicing. These studies only scratch the surface of this complexity and therefore future studies with greater depth and samples size will be vital to fully explore transcriptional diversity and its underlying influences in schizophrenia and provide the basis for new biomarkers and improved treatments.

  16. Neurologic Music Therapy Training for Mobility and Stability Rehabilitation with Parkinson's Disease - A Pilot Study.

    PubMed

    Bukowska, Anna A; Krężałek, Piotr; Mirek, Elżbieta; Bujas, Przemysław; Marchewka, Anna

    2015-01-01

    Idiopathic Parkinson's Disease (PD) is a progressive condition with gait disturbance and balance disorder as the main symptoms. Previous research studies focused on the application of Rhythmic Auditory Stimulation (RAS) in PD gait rehabilitation. The key hypothesis of this pilot study, however, assumes the major role of the combination of all three Neurologic Music Therapy (NMT) sensorimotor techniques in improving spatio-temporal gait parameters, and postural stability in the course of PD. The 55 PD-diagnosed subjects invited to the study were divided into two groups: 30 in the experimental and 25 in the control group. Inclusion criteria included Hoehn and Yahr stages 2 or 3, the ability to walk independently without any aid and stable pharmacological treatment for the duration of the experiment. In order to evaluate the efficacy of the chosen therapy procedure the following measures were applied: Optoelectrical 3D Movement Analysis, System BTS Smart for gait, and Computerized Dynamic Posturography CQ Stab for stability and balance. All measures were conducted both before and after the therapy cycle. The subjects from the experimental group attended music therapy sessions four times a week for 4 weeks. Therapeutic Instrumental Music Performance (TIMP), Pattern Sensory Enhancement (PSE) and RAS were used in every 45-min session for practicing daily life activities, balance, pre-gait, and gait pattern. Percussion instruments, the metronome and rhythmic music were the basis for each session. The subjects from the control group were asked to stay active and perform daily life activities between the measures. The research showed that the combination of the three NMT sensorimotor techniques can be used to improve gait and other rhythmical activities in PD rehabilitation. The results demonstrated significant improvement in the majority of the spatiotemporal gait parameters in the experimental group in comparison to the control group. In the stability tests with eyes

  17. Neurologic Music Therapy Training for Mobility and Stability Rehabilitation with Parkinson's Disease - A Pilot Study.

    PubMed

    Bukowska, Anna A; Krężałek, Piotr; Mirek, Elżbieta; Bujas, Przemysław; Marchewka, Anna

    2015-01-01

    Idiopathic Parkinson's Disease (PD) is a progressive condition with gait disturbance and balance disorder as the main symptoms. Previous research studies focused on the application of Rhythmic Auditory Stimulation (RAS) in PD gait rehabilitation. The key hypothesis of this pilot study, however, assumes the major role of the combination of all three Neurologic Music Therapy (NMT) sensorimotor techniques in improving spatio-temporal gait parameters, and postural stability in the course of PD. The 55 PD-diagnosed subjects invited to the study were divided into two groups: 30 in the experimental and 25 in the control group. Inclusion criteria included Hoehn and Yahr stages 2 or 3, the ability to walk independently without any aid and stable pharmacological treatment for the duration of the experiment. In order to evaluate the efficacy of the chosen therapy procedure the following measures were applied: Optoelectrical 3D Movement Analysis, System BTS Smart for gait, and Computerized Dynamic Posturography CQ Stab for stability and balance. All measures were conducted both before and after the therapy cycle. The subjects from the experimental group attended music therapy sessions four times a week for 4 weeks. Therapeutic Instrumental Music Performance (TIMP), Pattern Sensory Enhancement (PSE) and RAS were used in every 45-min session for practicing daily life activities, balance, pre-gait, and gait pattern. Percussion instruments, the metronome and rhythmic music were the basis for each session. The subjects from the control group were asked to stay active and perform daily life activities between the measures. The research showed that the combination of the three NMT sensorimotor techniques can be used to improve gait and other rhythmical activities in PD rehabilitation. The results demonstrated significant improvement in the majority of the spatiotemporal gait parameters in the experimental group in comparison to the control group. In the stability tests with eyes

  18. Early Diagnosis of Cerebral X-linked Adrenoleukodystrophy in Boys with Addison’s Disease Improves Survival and Neurological Outcomes

    PubMed Central

    Polgreen, LE; Chahla, S; Miller, W; Rothman, S.; Tolar, J; Kivisto, T; Nascene, D.; Orchard, PJ; Petryk, A

    2011-01-01

    Approximately one-third of boys with X-linked adrenoleukodystophy (X-ALD) develop an acute, progressive inflammatory process of the central nervous system, resulting in rapid neurologic deterioration and death. Hematopoietic cell transplantation (HCT) can halt the progression of neurologic disease if performed early in the course of the cerebral form of X-ALD. We describe a retrospective cohort study of 90 boys with X-ALD evaluated at our institution between 2000 and 2009, to determine if early diagnosis of X-ALD following the diagnosis of unexplained adrenal insufficiency (AI) improves outcomes. We describe 7 cases with a delay in the diagnosis of X-ALD, and compare their outcomes to 10 controls with the diagnosis of ALD made within 12 months following diagnosis of AI. At the time of evaluation for HCT, boys with a delay in the diagnosis of X-ALD had more extensive cerebral involvement and more limited functioning. These boys also were 3.9 times more likely to die, and had significant advancement of cerebral disease after HCT, compared to boys with a timely diagnosis of X-ALD. Conclusion Early diagnosis of cerebral X-ALD following the diagnosis of unexplained AI, and subsequent treatment with HCT, improves both neurological outcomes and survival in boys with cerebral X-ALD. PMID:21279382

  19. Risk of psychiatric and neurological diseases in patients with workplace mobbing experience in Germany: a retrospective database analysis

    PubMed Central

    Kostev, Karel; Rex, Juliana; Waehlert, Lilia; Hog, Daniela; Heilmaier, Christina

    2014-01-01

    Introduction: The number of mobbing experiences recorded has increased during recent years and it has now been established as global phenomenon among the working population. The goal of our study was to analyze the incidence of certain neurologic and psychiatric diseases as a consequence of mobbing as compared with a control group and to examine the possible influence of previous diseases that occurred within one year before the first mobbing documentation on the incidence of mobbing. Material & methods: We used a large database (IMS® Disease Analyzer, Germany) to collect data from general practitioners in Germany from 01/2003 until 12/2012. Based on age, gender, and health insurance, patients with experience of mobbing were matched with a control group of patients who had not reported workplace mobbing and who were being treated by the same physicians. At first, diseases that occurred within one year before the bullying experience took place (“index date”) were noted and compared to a control group of similar composition in terms of gender, age, and health insurance. Subsequently, the prevalence of depression, anxiety, somatoform disorders, and sleep disorders following experiences of mobbing were determined. After adjustment to take into account the odds of bullying, the ratios of these diseases were assessed using a logistic regression model. Results: The study population consisted of n=2,625 patients and n=2,625 controls, of which 33% were men. The number of cases of bullying documented rose continuously from 2003 to 2011 and remained high in 2012. Those who would later become victims of mobbing demonstrated a considerably higher prevalence of diseases in general – these diseases were not confined to the neurologic-psychiatric spectrum. Following experiences of bullying, depression, anxiety, somatoform disorders, and sleep disorders were significantly more prevalent than in the control group (for all, p<0.05). Similarly, odds ratios (OR) representing the

  20. Congenital and inherited neurologic diseases in dogs and cats: Legislation and its effect on purchase in Italy.

    PubMed

    Passantino, Annamaria; Masucci, Marisa

    2016-05-01

    Many of the congenital neurologic diseases can result in incapacity or death of the animal. Some of them, such as idiopathic epilepsy and hydrocephalus, exhibit breed or familial predisposition and a genetic basis was proved or suggested. Some diseases can be presumptively diagnosed after a detailed signalment (breed predisposition), history (e.g. family history because many of these defects have familial tendencies), and through physical exam; other diagnostic methods (radiography, computed tomography, magnetic resonance, electrophysiologic tests, etc.) can provide supportive evidence for the congenital defect and help to confirm the diagnosis. Some cases can lead to civil law-suits when the lesions are congenital, but not easily recognizable, or when the lesions are hereditary but tend to became manifest only after some time (more than 12 months after the date of purchase, e.g., after the vice-free guarantee period has expired). Moreover, quite frequently an early diagnosis is not made because there are delays in consulting the veterinarian or the general practitioner veterinarian does not perceive subtle signs. This study was designed to focus on the medico-legal aspects concerning the buying and selling in Italy of dogs and cats affected by congenital and hereditary neurologic diseases that could constitute vice in these animals. While adequate provisions to regulate in detail the various aspects of pet sale have still to be drawn up by legislators, it may be helpful to involve breeders, by obliging them by contract to extend guarantees in the case of hereditary lesions, including neurologic diseases. PMID:27284217

  1. Congenital and inherited neurologic diseases in dogs and cats: Legislation and its effect on purchase in Italy

    PubMed Central

    Passantino, Annamaria; Masucci, Marisa

    2016-01-01

    Many of the congenital neurologic diseases can result in incapacity or death of the animal. Some of them, such as idiopathic epilepsy and hydrocephalus, exhibit breed or familial predisposition and a genetic basis was proved or suggested. Some diseases can be presumptively diagnosed after a detailed signalment (breed predisposition), history (e.g. family history because many of these defects have familial tendencies), and through physical exam; other diagnostic methods (radiography, computed tomography, magnetic resonance, electrophysiologic tests, etc.) can provide supportive evidence for the congenital defect and help to confirm the diagnosis. Some cases can lead to civil law-suits when the lesions are congenital, but not easily recognizable, or when the lesions are hereditary but tend to became manifest only after some time (more than 12 months after the date of purchase, e.g., after the vice-free guarantee period has expired). Moreover, quite frequently an early diagnosis is not made because there are delays in consulting the veterinarian or the general practitioner veterinarian does not perceive subtle signs. This study was designed to focus on the medico-legal aspects concerning the buying and selling in Italy of dogs and cats affected by congenital and hereditary neurologic diseases that could constitute vice in these animals. While adequate provisions to regulate in detail the various aspects of pet sale have still to be drawn up by legislators, it may be helpful to involve breeders, by obliging them by contract to extend guarantees in the case of hereditary lesions, including neurologic diseases. PMID:27284217

  2. Chapter 38: American neurology.

    PubMed

    Freemon, Frank R

    2010-01-01

    The great formative event in the history of North America, the Civil War of 1861 to 1865, was the stimulus for the development of clinical neurology and the neurosciences. The first neurological research center on the continent was the US Army hospital at Turner's Lane, Philadelphia, PA. Silas Weir Mitchell and his colleagues described causalgia (reflex sympathetic dystrophy), phantom limb sensation, and Horner's syndrome (before Horner). The medical leader of the Northern army was William Hammond. After the conclusion of hostilities, he began a huge clinical practice in New York City. In the United States, clinical neurology began in private practice, unlike Europe, where neurology began in institutions. Hammond's textbook, which first used the term athetosis, was used by a generation of physicians who encountered patients with neurological signs and symptoms. Early in the 20th century, neurological institutions were formed around universities; probably the most famous was the Montreal Neurological Institute founded by Wilder Penfield. The US federal government sponsored extensive research into the function and dysfunction of the nervous system through the Neurological Institute of Neurological Diseases and Blindness, later called the National Institute of Neurological Diseases and Stroke. The government officially classified the final 10 years of the 20th century as the Decade of the Brain and provided an even greater level of research funding. PMID:19892141

  3. Modeling oscillatory dynamics in brain microcircuits as a way to help uncover neurological disease mechanisms: A proposal

    SciTech Connect

    Skinner, F. K.; Ferguson, K. A.

    2013-12-15

    There is an undisputed need and requirement for theoretical and computational studies in Neuroscience today. Furthermore, it is clear that oscillatory dynamical output from brain networks is representative of various behavioural states, and it is becoming clear that one could consider these outputs as measures of normal and pathological brain states. Although mathematical modeling of oscillatory dynamics in the context of neurological disease exists, it is a highly challenging endeavour because of the many levels of organization in the nervous system. This challenge is coupled with the increasing knowledge of cellular specificity and network dysfunction that is associated with disease. Recently, whole hippocampus in vitro preparations from control animals have been shown to spontaneously express oscillatory activities. In addition, when using preparations derived from animal models of disease, these activities show particular alterations. These preparations present an opportunity to address challenges involved with using models to gain insight because of easier access to simultaneous cellular and network measurements, and pharmacological modulations. We propose that by developing and using models with direct links to experiment at multiple levels, which at least include cellular and microcircuit, a cycling can be set up and used to help us determine critical mechanisms underlying neurological disease. We illustrate our proposal using our previously developed inhibitory network models in the context of these whole hippocampus preparations and show the importance of having direct links at multiple levels.

  4. Modeling oscillatory dynamics in brain microcircuits as a way to help uncover neurological disease mechanisms: A proposal

    NASA Astrophysics Data System (ADS)

    Skinner, F. K.; Ferguson, K. A.

    2013-12-01

    There is an undisputed need and requirement for theoretical and computational studies in Neuroscience today. Furthermore, it is clear that oscillatory dynamical output from brain networks is representative of various behavioural states, and it is becoming clear that one could consider these outputs as measures of normal and pathological brain states. Although mathematical modeling of oscillatory dynamics in the context of neurological disease exists, it is a highly challenging endeavour because of the many levels of organization in the nervous system. This challenge is coupled with the increasing knowledge of cellular specificity and network dysfunction that is associated with disease. Recently, whole hippocampus in vitro preparations from control animals have been shown to spontaneously express oscillatory activities. In addition, when using preparations derived from animal models of disease, these activities show particular alterations. These preparations present an opportunity to address challenges involved with using models to gain insight because of easier access to simultaneous cellular and network measurements, and pharmacological modulations. We propose that by developing and using models with direct links to experiment at multiple levels, which at least include cellular and microcircuit, a cycling can be set up and used to help us determine critical mechanisms underlying neurological disease. We illustrate our proposal using our previously developed inhibitory network models in the context of these whole hippocampus preparations and show the importance of having direct links at multiple levels.

  5. Genome-wide association studies in neurology

    PubMed Central

    Tan, Meng-Shan; Jiang, Teng

    2014-01-01

    Genome-wide association studies (GWAS) are a powerful tool for understanding the genetic underpinnings of human disease. In this article, we briefly review the role and findings of GWAS in common neurological diseases, including Stroke, Alzheimer’s disease, Parkinson’s disease, epilepsy, multiple sclerosis, migraine, amyotrophic lateral sclerosis, frontotemporal lobar degeneration, restless legs syndrome, intracranial aneurysm, human prion diseases and moyamoya disease. We then discuss the present and future implications of these findings with regards to disease prediction, uncovering basic biology, and the development of potential therapeutic agents. PMID:25568877

  6. The neurological basis of occupation.

    PubMed

    Gutman, Sharon A; Schindler, Victoria P

    2007-01-01

    The purpose of the present paper was to survey the literature about the neurological basis of human activity and its relationship to occupation and health. Activities related to neurological function were organized into three categories: those that activate the brain's reward system; those that promote the relaxation response; and those that preserve cognitive function into old age. The results from the literature review correlating neurological evidence and activities showed that purposeful and meaningful activities could counter the effects of stress-related diseases and reduce the risk for dementia. Specifically, it was found that music, drawing, meditation, reading, arts and crafts, and home repairs, for example, can stimulate the neurogical system and enhance health and well-being, Prospective research studies are needed to examine the effects of purposeful activities on reducing stress and slowing the rate of cognitive decline.

  7. The neurological basis of occupation.

    PubMed

    Gutman, Sharon A; Schindler, Victoria P

    2007-01-01

    The purpose of the present paper was to survey the literature about the neurological basis of human activity and its relationship to occupation and health. Activities related to neurological function were organized into three categories: those that activate the brain's reward system; those that promote the relaxation response; and those that preserve cognitive function into old age. The results from the literature review correlating neurological evidence and activities showed that purposeful and meaningful activities could counter the effects of stress-related diseases and reduce the risk for dementia. Specifically, it was found that music, drawing, meditation, reading, arts and crafts, and home repairs, for example, can stimulate the neurogical system and enhance health and well-being, Prospective research studies are needed to examine the effects of purposeful activities on reducing stress and slowing the rate of cognitive decline. PMID:17623380

  8. MicroRNAs in Human Diseases: From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases.

    PubMed

    Ha, Tai-You

    2011-10-01

    MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their target messenger RNAs (mRNAs). Recent studies have clearly demonstrated that miRNAs play critical roles in several biologic processes, including cell cycle, differentiation, cell development, cell growth, and apoptosis and that miRNAs are highly expressed in regulatory T (Treg) cells and a wide range of miRNAs are involved in the regulation of immunity and in the prevention of autoimmunity. It has been increasingly reported that miRNAs are associated with various human diseases like autoimmune disease, skin disease, neurological disease and psychiatric disease. Recently, the identification of mi- RNAs in skin has added a new dimension in the regulatory network and attracted significant interest in this novel layer of gene regulation. Although miRNA research in the field of dermatology is still relatively new, miRNAs have been the subject of much dermatological interest in skin morphogenesis and in regulating angiogenesis. In addition, miRNAs are moving rapidly onto center stage as key regulators of neuronal development and function in addition to important contributions to neurodegenerative disorder. Moreover, there is now compelling evidence that dysregulation of miRNA networks is implicated in the development and onset of human neruodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, Down syndrome, depression and schizophrenia. In this review, I briefly summarize the current studies about the roles of miRNAs in various autoimmune diseases, skin diseases, psychoneurological disorders and mental stress.

  9. Neurology and neurologic practice in China.

    PubMed

    Shi, Fu-Dong; Jia, Jian-Ping

    2011-11-29

    In the wake of dramatic economic success during the past 2 decades, the specialized field of neurology has undergone a significant transformation in China. With an increase in life expectancy, the problems of aging and cognition have grown. Lifestyle alterations have been associated with an epidemiologic transition both in the incidence and etiology of stroke. These changes, together with an array of social issues and institution of health care reform, are creating challenges for practicing neurologists throughout China. Notable problems include overcrowded, decrepit facilities, overloaded physician schedules, deteriorating physician-patient relationships, and an insufficient infrastructure to accommodate patients who need specialized neurologic care. Conversely, with the creation of large and sophisticated neurology centers in many cities across the country, tremendous opportunities exist. Developments in neurologic subspecialties enable delivery of high-quality care. Clinical and translational research based on large patient populations as well as highly sophisticated technologies are emerging in many neurologic centers and pharmaceutical companies. Child neurology and neurorehabilitation will be fast-developing subdisciplines. Given China's extensive population, the growth and progress of its neurology complex, and its ever-improving quality control, it is reasonable to anticipate that Chinese neurologists will contribute notably to unraveling the pathogenic factors causing neurologic diseases and to providing new therapeutic solutions. PMID:22123780

  10. Neurology and neurologic practice in China.

    PubMed

    Shi, Fu-Dong; Jia, Jian-Ping

    2011-11-29

    In the wake of dramatic economic success during the past 2 decades, the specialized field of neurology has undergone a significant transformation in China. With an increase in life expectancy, the problems of aging and cognition have grown. Lifestyle alterations have been associated with an epidemiologic transition both in the incidence and etiology of stroke. These changes, together with an array of social issues and institution of health care reform, are creating challenges for practicing neurologists throughout China. Notable problems include overcrowded, decrepit facilities, overloaded physician schedules, deteriorating physician-patient relationships, and an insufficient infrastructure to accommodate patients who need specialized neurologic care. Conversely, with the creation of large and sophisticated neurology centers in many cities across the country, tremendous opportunities exist. Developments in neurologic subspecialties enable delivery of high-quality care. Clinical and translational research based on large patient populations as well as highly sophisticated technologies are emerging in many neurologic centers and pharmaceutical companies. Child neurology and neurorehabilitation will be fast-developing subdisciplines. Given China's extensive population, the growth and progress of its neurology complex, and its ever-improving quality control, it is reasonable to anticipate that Chinese neurologists will contribute notably to unraveling the pathogenic factors causing neurologic diseases and to providing new therapeutic solutions.

  11. Neurological complications and risk factors of cardiopulmonary failure of EV-A71-related hand, foot and mouth disease.

    PubMed

    Long, Lili; Xu, Lin; Xiao, Zhenghui; Hu, Shixiong; Luo, Ruping; Wang, Hua; Lu, Xiulan; Xu, Zhiyue; Yao, Xu; Zhou, Luo; Long, Hongyu; Gong, Jiaoe; Song, Yanmin; Zhao, Li; Luo, Kaiwei; Zhang, Mengqi; Feng, Li; Yang, Liming; Sheng, Xiaoqi; Fan, Xuegong; Xiao, Bo

    2016-01-01

    From 2010 to 2012, large outbreaks of EV-A71-related- hand foot and mouth disease (HFMD) occurred annually in China. Some cases had neurological complications and were closely associated with fatal cardiopulmonary collapse, but not all children with central nervous system (CNS) involvement demonstrated a poor prognosis. To identify which patients and which neurological complications are more likely to progress to cardiopulmonary failure, we retrospectively studied 1,125 paediatric inpatients diagnosed with EV-A71-related HFMD in Hunan province, including 1,017 cases with CNS involvement. These patients were divided into cardiopulmonary failure (976 people) group and group without cardiopulmonary failure (149 people). A logistic regression analysis was used to compare the clinical symptoms, laboratory test results, and neurological complications between these two groups. The most significant risk factors included young age, fever duration ≥3 days, coma, limb weakness, drowsiness and ANS involvement. Patients with brainstem encephalitis and more CNS-involved regions were more likely to progress to cardiopulmonary failure. These findings can help front-line clinicians rapidly and accurately determine patient prognosis, thus rationally distributing the limited medical resources and implementing interventions as early as possible. PMID:27001010

  12. Neurological complications and risk factors of cardiopulmonary failure of EV-A71-related hand, foot and mouth disease

    PubMed Central

    Long, Lili; Xu, Lin; Xiao, Zhenghui; Hu, Shixiong; Luo, Ruping; Wang, Hua; Lu, Xiulan; Xu, Zhiyue; Yao, Xu; Zhou, Luo; Long, Hongyu; Gong, Jiaoe; Song, Yanmin; Zhao, Li; Luo, Kaiwei; Zhang, Mengqi; Feng, Li; Yang, Liming; Sheng, Xiaoqi; Fan, Xuegong; Xiao, Bo

    2016-01-01

    From 2010 to 2012, large outbreaks of EV-A71-related- hand foot and mouth disease (HFMD) occurred annually in China. Some cases had neurological complications and were closely associated with fatal cardiopulmonary collapse, but not all children with central nervous system (CNS) involvement demonstrated a poor prognosis. To identify which patients and which neurological complications are more likely to progress to cardiopulmonary failure, we retrospectively studied 1,125 paediatric inpatients diagnosed with EV-A71-related HFMD in Hunan province, including 1,017 cases with CNS involvement. These patients were divided into cardiopulmonary failure (976 people) group and group without cardiopulmonary failure (149 people). A logistic regression analysis was used to compare the clinical symptoms, laboratory test results, and neurological complications between these two groups. The most significant risk factors included young age, fever duration ≥3 days, coma, limb weakness, drowsiness and ANS involvement. Patients with brainstem encephalitis and more CNS-involved regions were more likely to progress to cardiopulmonary failure. These findings can help front-line clinicians rapidly and accurately determine patient prognosis, thus rationally distributing the limited medical resources and implementing interventions as early as possible. PMID:27001010

  13. Mouse models of human disease

    PubMed Central

    Perlman, Robert L.

    2016-01-01

    The use of mice as model organisms to study human biology is predicated on the genetic and physiological similarities between the species. Nonetheless, mice and humans have evolved in and become adapted to different environments and so, despite their phylogenetic relatedness, they have become very different organisms. Mice often respond to experimental interventions in ways that differ strikingly from humans. Mice are invaluable for studying biological processes that have been conserved during the evolution of the rodent and primate lineages and for investigating the developmental mechanisms by which the conserved mammalian genome gives rise to a variety of different species. Mice are less reliable as models of human disease, however, because the networks linking genes to disease are likely to differ between the two species. The use of mice in biomedical research needs to take account of the evolved differences as well as the similarities between mice and humans. PMID:27121451

  14. Chapter 50: history of tropical neurology.

    PubMed

    Ogunniyi, Adesola

    2010-01-01

    Tropical neurology began less than two centuries ago. Consumption of dietary toxins predominated at the beginning and gave birth to the geographic entity. The story moved from lathyrism through Jamaican neuropathy to cassava-induced epidemic neuropathy, which was contrasted with Konzo, also associated with cassava. Other tropical diseases enumerated with chronological details include: Chaga's diseases, kwashiorkor, Madras type of motor neuron disease, atlanto-axial dislocation, Burkitt's lymphoma and Kuru, associated with cannibalism among the Fore linguistic group in New Guinea. More recent documentation includes the Cuban neuropathy in 1991 with an epidemic of visual loss and neuropathy, Anaphe venata entomophagy in Nigeria presenting as seasonal ataxia, and neurological aspects of the human immunodeficiency virus infection complete the picture. With time, professional associations were formed and the pioneers were given prominence. The World Federation of Neurology featured Geographic Neurology as a theme in 1977 and Tropical Neurology was given prominence at its 1989 meeting in New Delhi, India. The situation remains unchanged with regards to rare diseases like Meniere's, multiple sclerosis, hereditary disorders. However, with westernization and continued urbanization, changing disease patterns are being observed and tropical neurology may depart from dietary toxins to more western world-type disorders. PMID:19892153

  15. Biochemical and toxicological evidence of neurological effects of pesticides: the example of Parkinson's disease.

    PubMed

    Moretto, A; Colosio, C

    2011-08-01

    Parkinson's disease (PD) is frequently reported to be associated with pesticide exposure but the issue has not yet been solved because the data are inconsistent and the studies suffer from several biases and limitations. The aim of this article is to summarise available biochemical and toxicological data on some pesticides, particularly on paraquat, that might help in the evaluation of epidemiological data. The nigrostriatal system appears to be particularly sensitive to oxidative damage caused by different mechanisms and agents, thus supporting the epidemiological evidence that Parkinson's disease is in fact an environmental disease. In available experimental studies, animals have been treated with a high single or a few doses of pesticide, and have been followed up for a few days or weeks after treatment. Moreover, experimental data indicate additive/synergistic effects of different pesticides that act on different targets within the dopaminergic system. In these conditions and to a different extent, pesticides such as paraquat, maneb and other dithiocarbamates, pyrethroids, rotenone, and dieldrin cause neurotoxic effects that may suggest a possible role in the development of a PD-like syndrome in animals. Although, all the characteristics of PD cannot be reproduced by any single chemical, these data can be of help for understanding the role of pesticide exposure in human PD development. On the other hand farmers are exposed for days or weeks during several years to much lower doses than those used in experimental studies. Therefore, a firm conclusion on the role of pesticide exposure on the increased risk of developing PD cannot be drawn. However, it is suggested that close follow up of survivors of acute poisonings by these pesticides, or identification in epidemiological studies of such subjects or of those reporting episodes of accidentally high exposure will certainly provide information useful for the understanding of the relevance of actual human exposure

  16. Reflections: Neurology and The Humanities. The case of the locked house. The finished mystery.

    PubMed

    Joynt, Robert J; Kempster, Peter A; Lee, Andrew J

    2014-08-12

    After the death in 2012 of Dr. Robert Joynt, who served Neurology® as CPC Section Editor, an unfinished manuscript was found on his computer. It would have been his sixth Sherlock Holmes pastiche. Intrigued by the story but deflated at the lack of an ending, the editors published the case in the September 10, 2013, issue of Neurology and requested that readers finish it. A panel of editors reviewed over 30 submissions and the top 4 were posted online and on the iPad. Readers voted online, on the iPad, and during the 2014 American Academy of Neurology Annual Meeting in Philadelphia. The winning coauthors are Peter A. Kempster, from Melbourne, and Andrew J. Lees, from London. The runners-up are Anonymous (ending 1), Gerald Honch (ending 2), and Clifton Gooch (ending 4). The editors thank all participants and voters. The rule on page 662 indicates where the winning ending begins.

  17. Neurology and international organizations.

    PubMed

    Mateen, Farrah J

    2013-07-23

    A growing number of international stakeholders are engaged with neurologic diseases. This article provides a brief overview of important international stakeholders in the practice of neurology, including global disease-specific programs, United Nations agencies, governmental agencies with international influence, nongovernmental organizations, international professional organizations, large private donors, private-public partnerships, commercial interests, armed forces, and universities and colleges. The continued engagement of neurologists is essential for the growing number of international organizations that can and should incorporate neurologic disease into their global agendas.

  18. Barefoot Plantar Pressure Indicates Progressive Neurological Damage in Patients with Human T-Cell Lymphotropic Virus Type 1 Infection

    PubMed Central

    Vasconcelos, Beatriz Helena B.; Souza, Givago S.; Barroso, Tatiana G. C. P.; Silveira, Luiz Carlos L.; Sousa, Rita Catarina M.; Callegari, Bianca; Xavier, Marília B.

    2016-01-01

    Background The human T-Cell Lymphotropic Virus Type 1 (HTLV-1) is a retrovirus associated with neurological alterations; individuals with HTLV-1 infection may develop HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP). Frequent neurological complaints include foot numbness and leg weakness. In this study, we compared the distribution of the body weight on different areas of the foot in HTLV-1 patients with HAM/TSP, asymptomatic HTLV-1 patients, and healthy individuals. Methodology We studied 36 HTLV-1 infected patients, who were divided in two groups of 18 patients each based on whether or not they had been diagnosed with HAM/TSP, and 17 control subjects. The evaluation included an interview on the patient’s clinical history and examinations of the patient’s reflexes, foot skin tactile sensitivity, and risk of falling. The pressure distribution on different areas of the foot was measured with baropodometry, using a pressure platform, while the patients had their eyes open or closed. Main Findings The prevalence of neurological disturbances—altered reflexes and skin tactile sensitivity and increased risk of falling—was higher in HTLV-1 HAM/TSP patients than in HTLV-1 asymptomatic patients. The medium and maximum pressure values were higher in the forefoot than in the midfoot and hindfoot in both HTLV-1 groups. In addition, the pressure on the hindfoot was lower in HAM/TSP patients compared to control subjects. Conclusions The neurological disturbances associated with HTLV-1 infection gradually worsened from HTLV-1 asymptomatic patients to HAM/TSP patients. Baropodometry is a valuable tool to establish the extent of neurological damage in patients suffering from HTLV-1 infection. PMID:26998608

  19. Improved neurological outcome in children with chronic renal disease from infancy.

    PubMed

    Elzouki, A; Carroll, J; Butinar, D; Moosa, A

    1994-04-01

    Progressive encephalopathy, developmental delay, microcephaly, electroencephalogram (EEG) and computed tomographic (CT) scan abnormalities have been reported in 80% of children with chronic renal failure (CRF) in infancy. Malnutrition, aluminium intoxication and psychosocial deprivation are proposed as causes. In 15 children with CRF from infancy we evaluated the effect of no aluminium salts and early vigorous nutritional and psychosocial support, in addition to the standard therapy, on neurological development. Six patients underwent dialysis (2 at birth) and 3 received transplants. None of our patients were given aluminium therapy. The nutritional status of the patients in the first 2 years of life was assessed with the waterlow classification. At the end of the follow-up period (mean 50 months range 14-148 months), patients underwent neurodevelopmental assessment, head CT scan, EEG, nerve conduction velocity (NCV) and auditory brain stem evoked response (ABER). None of our patients developed progressive encephalopathy or recurrent seizures. All have a normal neurological examination apart from hypotonia. Microcephaly was present in 5 patients. There was a good correlation between malnutrition in the first 2 years of life and microcephaly. Developmental delay was present in 3 patients; all 3 were microcephalic. There was evidence of brain atrophy on CT scan in only 3 patients. EEG was abnormal in 6 patients, but only severe in 1 patient. Only 1 patient had diminished NCV; all patients had a normal ABER. We conclude that a policy of no oral aluminium therapy and early nutritional support leads to better neurological outcome in children with CRF from infancy. PMID:8018500

  20. The discovery of human auditory-motor entrainment and its role in the development of neurologic music therapy.

    PubMed

    Thaut, Michael H

    2015-01-01

    The discovery of rhythmic auditory-motor entrainment in clinical populations was a historical breakthrough in demonstrating for the first time a neurological mechanism linking music to retraining brain and behavioral functions. Early pilot studies from this research center were followed up by a systematic line of research studying rhythmic auditory stimulation on motor therapies for stroke, Parkinson's disease, traumatic brain injury, cerebral palsy, and other movement disorders. The comprehensive effects on improving multiple aspects of motor control established the first neuroscience-based clinical method in music, which became the bedrock for the later development of neurologic music therapy. The discovery of entrainment fundamentally shifted and extended the view of the therapeutic properties of music from a psychosocially dominated view to a view using the structural elements of music to retrain motor control, speech and language function, and cognitive functions such as attention and memory.

  1. The discovery of human auditory-motor entrainment and its role in the development of neurologic music therapy.

    PubMed

    Thaut, Michael H

    2015-01-01

    The discovery of rhythmic auditory-motor entrainment in clinical populations was a historical breakthrough in demonstrating for the first time a neurological mechanism linking music to retraining brain and behavioral functions. Early pilot studies from this research center were followed up by a systematic line of research studying rhythmic auditory stimulation on motor therapies for stroke, Parkinson's disease, traumatic brain injury, cerebral palsy, and other movement disorders. The comprehensive effects on improving multiple aspects of motor control established the first neuroscience-based clinical method in music, which became the bedrock for the later development of neurologic music therapy. The discovery of entrainment fundamentally shifted and extended the view of the therapeutic properties of music from a psychosocially dominated view to a view using the structural elements of music to retrain motor control, speech and language function, and cognitive functions such as attention and memory. PMID:25725919

  2. A novel unbiased proteomic approach to detect the reactivity of cerebrospinal fluid in neurological diseases.

    PubMed

    Menon, Krishnakumar N; Steer, David L; Short, Martin; Petratos, Steven; Smith, Ian; Bernard, Claude C A

    2011-06-01

    Neurodegenerative diseases, such as multiple sclerosis represent global health issues. Accordingly, there is an urgent need to understand the pathogenesis of this and other central nervous system disorders, so that more effective therapeutics can be developed. Cerebrospinal fluid is a potential source of important reporter molecules released from various cell types as a result of central nervous system pathology. Here, we report the development of an unbiased approach for the detection of reactive cerebrospinal fluid molecules and target brain proteins from patients with multiple sclerosis. To help identify molecules that may serve as clinical biomarkers for multiple sclerosis, we have biotinylated proteins present in the cerebrospinal fluid and tested their reactivity against brain homogenate as well as myelin and myelin-axolemmal complexes. Proteins were separated by two-dimensional gel electrophoresis, blotted onto membranes and probed separately with biotinylated unprocessed cerebrospinal fluid samples. Protein spots that reacted to two or more multiple sclerosis-cerebrospinal fluids were further analyzed by matrix assisted laser desorption ionization-time-of-flight time-of-flight mass spectrometry. In addition to previously reported proteins found in multiple sclerosis cerebrospinal fluid, such as αβ crystallin, enolase, and 14-3-3-protein, we have identified several additional molecules involved in mitochondrial and energy metabolism, myelin gene expression and/or cytoskeletal organization. These include aspartate aminotransferase, cyclophilin-A, quaking protein, collapsin response mediator protein-2, ubiquitin carboxy-terminal hydrolase L1, and cofilin. To further validate these findings, the cellular expression pattern of collapsin response mediator protein-2 and ubiquitin carboxy-terminal hydrolase L1 were investigated in human chronic-active MS lesions by immunohistochemistry. The observation that in multiple sclerosis lesions phosphorylated collapsin

  3. Clinical efficacy of combined sodium dimercaptopropanesulfonate and zinc treatment in neurological Wilson’s disease with D-penicillamine treatment failure

    PubMed Central

    Chen, Dingbang; Zhou, Xiangxue; Hou, Haiman; Feng, Li; Liu, JunXiu; Liang, Yinyin; Lin, Xiaopu; Zhang, Jiwei; Wu, Chao; Liang, Xiuling; Pei, Zhong; Li, Xunhua

    2016-01-01

    Objectives: There are limited pharmacological treatments for patients with neurological Wilson’s disease (WD) and a history of copper-chelating treatment failure. Methods: We retrospectively evaluated the clinical records of 38 patients with WD who were treated with sodium dimercaptopropanesulfonate (DMPS) and zinc (group 1) or zinc alone (group 2). All patients had a history of neurological deterioration during their previous treatment with D-penicillamine (DPA). Results: Twenty-one patients were treated with intravenous DMPS for 4 weeks, followed by zinc gluconate for 6 months, and the treatment protocol was repeated twice. Relative to the baseline, repeated DMPS therapy and zinc maintenance therapy decreased neurological scores continuously (p < 0.01). Sixteen patients (76.2%) demonstrated neurological improvements after 1 year of therapy and four patients (19.0%) exhibited neurological deterioration at the follow-up session. In addition, 17 patients were treated with zinc monotherapy for 12 months. Two patients (11.8%) demonstrated neurological improvements and five patients (29.4%) exhibited neurological deterioration. Compared with the patients in group 2, a greater improvement ratio (p < 0.01) and lower deterioration ratio (p < 0.01) were observed in the patients in group 1 after 1 year of therapy. Conclusions: Our findings indicate that the safety and efficacy of combined treatment of DMPS and zinc is superior to those of zinc monotherapy in patients with neurological WD with a history of DPA treatment failure. PMID:27366238

  4. A new clinical tool for assessing numerical abilities in neurological diseases: numerical activities of daily living.

    PubMed

    Semenza, Carlo; Meneghello, Francesca; Arcara, Giorgio; Burgio, Francesca; Gnoato, Francesca; Facchini, Silvia; Benavides-Varela, Silvia; Clementi, Maurizio; Butterworth, Brian

    2014-01-01

    The aim of this study was to build an instrument, the numerical activities of daily living (NADL), designed to identify the specific impairments in numerical functions that may cause problems in everyday life. These impairments go beyond what can be inferred from the available scales evaluating activities of daily living in general, and are not adequately captured by measures of the general deterioration of cognitive functions as assessed by standard clinical instruments like the MMSE and MoCA. We assessed a control group (n = 148) and a patient group affected by a wide variety of neurological conditions (n = 175), with NADL along with IADL, MMSE, and MoCA. The NADL battery was found to have satisfactory construct validity and reliability, across a wide age range. This enabled us to calculate appropriate criteria for impairment that took into account age and education. It was found that neurological patients tended to overestimate their abilities as compared to the judgment made by their caregivers, assessed with objective tests of numerical abilities. PMID:25126077

  5. Neurological disease associated with Mycoplasma pneumoniae infection. PCR evidence against a direct invasive mechanism

    PubMed Central

    Fink, C G; Sillis, M; Read, S J; Butler, L; Pike, M

    1995-01-01

    Aims—To investigate the pathology in patients presenting with sudden onset neurological illnesses associated with Mycoplasma pneumoniae infection. Methods—M pneumoniae infection was diagnosed by a highly rigorous interpretation of serological markers initially using complement fixation, agglutination and IgM antibodies. Confirmation of the serological diagnosis was achieved using indirect immunofluorescence for IgM, IgA, and IgG. Serum and cerebrospinal fluid (CSF) samples from these patients were examined using the polymerase chain reaction to look for evidence of M pneumoniae DNA. Results—No M pneumoniae DNA was found in any serum or CSF samples. Diagnosis of M pneumoniae infection by agglutination and complement fixation antibodies was not always confirmed by indirect immunofluorescence. Conclusion—The neurological lesions in these patients do not appear to be caused by the direct invasion of M pneumoniae into the nervous system. The lesions may be an immune response to infection. Serological diagnosis of M pneumoniae continues to be a laboratory problem. PMID:16695976

  6. A new clinical tool for assessing numerical abilities in neurological diseases: numerical activities of daily living

    PubMed Central

    Semenza, Carlo; Meneghello, Francesca; Arcara, Giorgio; Burgio, Francesca; Gnoato, Francesca; Facchini, Silvia; Benavides-Varela, Silvia; Clementi, Maurizio; Butterworth, Brian

    2014-01-01

    The aim of this study was to build an instrument, the numerical activities of daily living (NADL), designed to identify the specific impairments in numerical functions that may cause problems in everyday life. These impairments go beyond what can be inferred from the available scales evaluating activities of daily living in general, and are not adequately captured by measures of the general deterioration of cognitive functions as assessed by standard clinical instruments like the MMSE and MoCA. We assessed a control group (n = 148) and a patient group affected by a wide variety of neurological conditions (n = 175), with NADL along with IADL, MMSE, and MoCA. The NADL battery was found to have satisfactory construct validity and reliability, across a wide age range. This enabled us to calculate appropriate criteria for impairment that took into account age and education. It was found that neurological patients tended to overestimate their abilities as compared to the judgment made by their caregivers, assessed with objective tests of numerical abilities. PMID:25126077

  7. A new clinical tool for assessing numerical abilities in neurological diseases: numerical activities of daily living.

    PubMed

    Semenza, Carlo; Meneghello, Francesca; Arcara, Giorgio; Burgio, Francesca; Gnoato, Francesca; Facchini, Silvia; Benavides-Varela, Silvia; Clementi, Maurizio; Butterworth, Brian

    2014-01-01

    The aim of this study was to build an instrument, the numerical activities of daily living (NADL), designed to identify the specific impairments in numerical functions that may cause problems in everyday life. These impairments go beyond what can be inferred from the available scales evaluating activities of daily living in general, and are not adequately captured by measures of the general deterioration of cognitive functions as assessed by standard clinical instruments like the MMSE and MoCA. We assessed a control group (n = 148) and a patient group affected by a wide variety of neurological conditions (n = 175), with NADL along with IADL, MMSE, and MoCA. The NADL battery was found to have satisfactory construct validity and reliability, across a wide age range. This enabled us to calculate appropriate criteria for impairment that took into account age and education. It was found that neurological patients tended to overestimate their abilities as compared to the judgment made by their caregivers, assessed with objective tests of numerical abilities.

  8. An inside job: how endosomal Na+/H+ exchangers link to autism and neurological disease

    PubMed Central

    Kondapalli, Kalyan C.; Prasad, Hari; Rao, Rajini

    2014-01-01

    Autism imposes a major impediment to childhood development and a huge emotional and financial burden on society. In recent years, there has been rapidly accumulating genetic evidence that links the eNHE, a subset of Na+/H+ exchangers that localize to intracellular vesicles, to a variety of neurological conditions including autism, attention deficit hyperactivity disorder (ADHD), intellectual disability, and epilepsy. By providing a leak pathway for protons pumped by the V-ATPase, eNHE determine luminal pH and regulate cation (Na+, K+) content in early and recycling endosomal compartments. Loss-of-function mutations in eNHE cause hyperacidification of endosomal lumen, as a result of imbalance in pump and leak pathways. Two isoforms, NHE6 and NHE9 are highly expressed in brain, including hippocampus and cortex. Here, we summarize evidence for the importance of luminal cation content and pH on processing, delivery and fate of cargo. Drawing upon insights from model organisms and mammalian cells we show how eNHE affect surface expression and function of membrane receptors and neurotransmitter transporters. These studies lead to cellular models of eNHE activity in pre- and post-synaptic neurons and astrocytes, where they could impact synapse development and plasticity. The study of eNHE has provided new insight on the mechanism of autism and other debilitating neurological disorders and opened up new possibilities for therapeutic intervention. PMID:25002837

  9. A High-Performance Multiplex Immunoassay for Serodiagnosis of Flavivirus-Associated Neurological Diseases in Horses

    PubMed Central

    Beck, Cécile; Desprès, Philippe; Paulous, Sylvie; Vanhomwegen, Jessica; Lowenski, Steeve; Nowotny, Norbert; Durand, Benoit; Garnier, Annabelle; Blaise-Boisseau, Sandra; Guitton, Edouard; Yamanaka, Takashi; Zientara, Stéphan; Lecollinet, Sylvie

    2015-01-01

    West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV) are flaviviruses responsible for severe neuroinvasive infections in humans and horses. The confirmation of flavivirus infections is mostly based on rapid serological tests such as enzyme-linked immunosorbent assays (ELISAs). These tests suffer from poor specificity, mainly due to antigenic cross-reactivity among flavivirus members. Robust diagnosis therefore needs to be validated through virus neutralisation tests (VNTs) which are time-consuming and require BSL3 facilities. The flavivirus envelope (E) glycoprotein ectodomain is composed of three domains (D) named DI, DII, and DIII, with EDIII containing virus-specific epitopes. In order to improve the serological differentiation of flavivirus infections, the recombinant soluble ectodomain of WNV E (WNV.sE) and EDIIIs (rEDIIIs) of WNV, JEV, and TBEV were synthesised using the Drosophila S2 expression system. Purified antigens were covalently bonded to fluorescent beads. The microspheres coupled to WNV.sE or rEDIIIs were assayed with about 300 equine immune sera from natural and experimental flavivirus infections and 172 nonimmune equine sera as negative controls. rEDIII-coupled microspheres captured specific antibodies against WNV, TBEV, or JEV in positive horse sera. This innovative multiplex immunoassay is a powerful alternative to ELISAs and VNTs for veterinary diagnosis of flavivirus-related diseases. PMID:26457301

  10. Neurologic complications of vaccinations.

    PubMed

    Miravalle, Augusto A; Schreiner, Teri

    2014-01-01

    This chapter reviews the most common neurologic disorders associated with common vaccines, evaluates the data linking the disorder with the vaccine, and discusses the potential mechanism of disease. A literature search was conducted in PubMed using a combination of the following terms: vaccines, vaccination, immunization, and neurologic complications. Data were also gathered from publications of the American Academy of Pediatrics Committee on Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the Vaccine Adverse Event Reporting System. Neurologic complications of vaccination are rare. Many associations have been asserted without objective data to support a causal relationship. Rarely, patients with a neurologic complication will have a poor outcome. However, most patients recover fully from the neurologic complication. Vaccinations have altered the landscape of infectious disease. However, perception of risk associated with vaccinations has limited the success of disease eradication measures. Neurologic complications can be severe, and can provoke fear in potential vaccines. Evaluating whether there is causal link between neurologic disorders and vaccinations, not just temporal association, is critical to addressing public misperception of risk of vaccination. Among the vaccines available today, the cost-benefit analysis of vaccinations and complications strongly argues in favor of vaccination.

  11. DNA analysis in human disease.

    PubMed Central

    Wright, A F

    1986-01-01

    The analysis of human DNA using recombinant DNA technology is fast becoming an integral part of the diagnosis, assessment, and prevention of inherited and somatic genetic disease. The rationale underlying these methods of analysis is discussed, and the nature and extent of mutational change in heritable disorders and neoplastic development is outlined. PMID:3543064

  12. Animal models for human diseases.

    PubMed

    Rust, J H

    1982-01-01

    The use of animal models for the study of human disease is, for the most part, a recent development. This discussion of the use of animal models for human diseases directs attention to the sterile period, early advances, some personal experiences, the human as the model, biological oddities among common laboratory animals, malignancies in laboratory animals, problems created by federal regulations, cancer tests with animals, and what the future holds in terms of the use of animal models as an aid to understanding human disease. In terms of early use of animal models, there was a school of rabbis, some of whom were also physicians, in Babylon who studied and wrote extensively on ritual slaughter and the suitability of birds and beasts for food. Considerable detailed information on animal pathology, physiology, anatomy, and medicine in general can be found in the Soncino Babylonian Talmudic Translations. The 1906 edition of the "Jewish Encyclopedia," has been a rich resource. Although it has not been possible to establish what diseases of animals were studied and their relationship to the diseases of humans, there are fascinating clues to pursue, despite the fact that these were sterile years for research in medicine. The quotation from the Talmud is of interest: "The medical knowledge of the Talmudist was based upon tradition, the dissection of human bodies, observation of disease and experiments upon animals." A bright light in the lackluster years of medical research was provided by Galen, considered the originator of research in physiology and anatomy. His dissection of animals and work on apes and other lower animals were models for human anatomy and physiology and the bases for many treatises. Yet, Galen never seemed to suggest that animals could serve as models for human diseases. Most early physicians who can be considered to have been students of disease developed their medical knowledge by observing the sick under their care. 1 early medical investigator

  13. Dihydropteridine reductase deficiency associated with severe neurologic disease and mild hyperphenylalaninemia.

    PubMed

    Brewster, T G; Moskowitz, M A; Kaufman, S; Breslow, J L; Milstien, S; Abroms, I F

    1979-01-01

    A deficiency of hepatic dihydropteridine reductase (DHPR) activity was found in a neurologically impaired infant with mild hyperphenylalaninemia and normal levels of hepatic phenylalanine hydroxylase. DHPR is required for the regeneration of tetrahydrobiopterin, an essential cofactor in aromatic amino acid hydroxylation, a necessary step in the biosynthesis of the neurotransmitters, dopamine and serotonin. Evidence for decreased synthesis of these transmitters in this patient was provided by the finding of reduced levels of homovanillic acid and 5-hydroxyindole acetic acid, metabolites of dopamine and serotonin, respectively, in the cerebrospinal fluid and urine. Treatment with dopamine and serotonin precursors, L-3,4 dihydroxyphenylalanine and 5-hydroxytryptophan, respectively, was associated with improvement in temperament and motor tone and less frequent seizures. However, there was no improvement in gross motor function or language development.

  14. Marcel Proust's diseases and doctors: the neurological story of a life.

    PubMed

    Bogousslavsky, Julien

    2007-01-01

    Marcel Proust (1871-1922), one of the greatest writers of all times, suffered from asthma beginning at age 9, in an era when the illness was considered a 'nervous' disorder belonging to what Beard, in 1870, called 'neurasthenia'. Proust's father, Adrien, was himself a professor of medicine (hygiene) who had met Charcot, and who contributed to neurology with studies on aphasia, stroke, hysteria, and neurasthenia - a condition about which he, along with Gilbert Ballet, published a book in 1897. Through his father, Proust met Edouard Brissaud, the co-founder of the Revue Neurologique in 1893, and, in 1896, the author of The Hygiene of the Asthmatics, with a foreword by Adrien Proust. Shortly after his mother's death in 1905, Proust contemplated admitting himself to a private hospital to reset his irregular sleep patterns and to improve his asthma. He hesitated in his choice of care between Jules Dejerine in Paris, Henry-Auguste Widmer at Valmont, and Paul Dubois in Bern. Finally, he decided to enter Paul Sollier's clinic, in Boulogne-sur-Seine, on the advice of Brissaud, and stayed there for 6 weeks in semi-isolation. Together with Babinski, Sollier was, at that time, considered the most gifted follower of Charcot. He was a forerunner of studies on emotional memory, which strongly influenced Proust. In Proust's opus magnum work In Search of Lost Time, 'involuntary memory' indeed forms the core mechanism of the entire novel, counterbalancing the decaying effects of time. A few years before his death from complicated bronchopneumonia at age 52, Proust became terrified of developing a stroke, like his mother and father, and he consulted with Joseph Babinski, who tried to reassure him. Proust's life followed an unusual neurological itinerary, which has been largely overlooked, but which is in fact critical for an understanding of his literary work.

  15. Avian vacuolar myelinopathy: a newly recognized fatal neurologic disease of eagles, waterfowl, and other birds

    USGS Publications Warehouse

    Fischer, John R.; Lewis, L.A.; Augspurger, T.; Rocke, T.E.

    2002-01-01

    Wildlife biologists and health specialists have been frustrated by a long list of negative findings in their AVM investigations, however studies continue to provide pieces of information to aid the determination of the cause and its source. Available data indicated that AVM may have been present since at least 1990, occurs in at least five states, has been documented during October through April at sites of wintering populations of birds where the exposure apparently occurs, and has killed at least 90 bald eagles. Birds with AVM have difficulty or inability to fly, swim, walk, or perch, but there has been resolution of clinical signs in some affected coots. The list of affected species continues to grow, but remains confined to wild avians, including bald eagle, American coot, great horned owl, killdeer, Canada goose, mallard, ring-necked duck and bufflehead. The effects of the AVM agent on mammals, including human beings, are unknown. A neurotoxicant of manmade or natural origin is the suspected cause of AVM because no infectious disease agents, such as viruses, bacteria, parasites and prions, have been found, and the lesion and epizootiology of AVM resemble those of toxicoses. Additionally it is documented, experimentally, that exposure to raptors can occur through ingestion of infected coots. Collaborative studies will continue in the effort to identify the cause of AVM, its geographic distribution, and the range of species susceptibility. Hopefully, this information can be used to identify measures that might be taken to reduce the impact of AVM on the wildlife resource. Multiple agencies, institutions, and individuals must rely on each other's expertise in the multidisciplinary approach to this problem, persevere in their efforts and take advantage of serendipity that presents itself during investigations of this newly recognized cause of wild bird mortality.

  16. Neurological Outcomes after Human Umbilical Cord Patch for In Utero Spina Bifida Repair in a Sheep Model

    PubMed Central

    Papanna, Ramesha; Mann, Lovepreet K.; Snowise, Saul; Morales, Yisel; Prabhu, Sanjay P.; Tseng, Scheffer C. G.; Grill, Raymond; Fletcher, Stephen; Moise, Kenneth J.

    2016-01-01

    Objectives  The objective of our study was to test the hypothesis that in utero repair of surgically created spina bifida in a sheep model using cryopreserved human umbilical cord (HUC) patch improves neurological outcome. Methods  Spina bifida with myelotomy was surgically created in timed pregnant ewes at gestational day (GD) 75. The fetuses were randomly assigned to unrepaired versus HUC and treated at GD 95 and then delivered at GD 140. Neurological evaluation was performed using the Texas Spinal Cord Injury Scale (TSCIS), bladder control using ultrasound, and the hindbrain herniation. Results  Three lambs without the spina bifida creation served as controls. There were four lambs with spina bifida: two were unrepaired and two underwent HUC repair. The control lambs had normal function. Both unrepaired lambs had nonhealed skin lesions with leakage of cerebrospinal fluid, a 0/20 TSCIS score, no bladder control, and the hindbrain herniation. In contrast, both HUC lambs had a completely healed skin defect and survived to day 2 of life, a 3/20 and 4/20 TSCIS score (nociception), partial bladder control, and normal hindbrain anatomy. Conclusions  Cryopreserved HUC patch appears to improve survival and neurological outcome in this severe form of the ovine model of spina bifida. PMID:27621952

  17. Neurological Outcomes after Human Umbilical Cord Patch for In Utero Spina Bifida Repair in a Sheep Model

    PubMed Central

    Papanna, Ramesha; Mann, Lovepreet K.; Snowise, Saul; Morales, Yisel; Prabhu, Sanjay P.; Tseng, Scheffer C. G.; Grill, Raymond; Fletcher, Stephen; Moise, Kenneth J.

    2016-01-01

    Objectives The objective of our study was to test the hypothesis that in utero repair of surgically created spina bifida in a sheep model using cryopreserved human umbilical cord (HUC) patch improves neurological outcome. Methods Spina bifida with myelotomy was surgically created in timed pregnant ewes at gestational day (GD) 75. The fetuses were randomly assigned to unrepaired versus HUC and treated at GD 95 and then delivered at GD 140. Neurological evaluation was performed using the Texas Spinal Cord Injury Scale (TSCIS), bladder control using ultrasound, and the hindbrain herniation. Results Three lambs without the spina bifida creation served as controls. There were four lambs with spina bifida: two were unrepaired and two underwent HUC repair. The control lambs had normal function. Both unrepaired lambs had nonhealed skin lesions with leakage of cerebrospinal fluid, a 0/20 TSCIS score, no bladder control, and the hindbrain herniation. In contrast, both HUC lambs had a completely healed skin defect and survived to day 2 of life, a 3/20 and 4/20 TSCIS score (nociception), partial bladder control, and normal hindbrain anatomy. Conclusions Cryopreserved HUC patch appears to improve survival and neurological outcome in this severe form of the ovine model of spina bifida. PMID:27621952

  18. Proteins aggregation and human diseases

    NASA Astrophysics Data System (ADS)

    Hu, Chin-Kun

    2015-04-01

    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease.

  19. Virtual reality interface devices in the reorganization of neural networks in the brain of patients with neurological diseases.

    PubMed

    Gatica-Rojas, Valeska; Méndez-Rebolledo, Guillermo

    2014-04-15

    Two key characteristics of all virtual reality applications are interaction and immersion. Systemic interaction is achieved through a variety of multisensory channels (hearing, sight, touch, and smell), permitting the user to interact with the virtual world in real time. Immersion is the degree to which a person can feel wrapped in the virtual world through a defined interface. Virtual reality interface devices such as the Nintendo® Wii and its peripheral nunchuks-balance board, head mounted displays and joystick allow interaction and immersion in unreal environments created from computer software. Virtual environments are highly interactive, generating great activation of visual, vestibular and proprioceptive systems during the execution of a video game. In addition, they are entertaining and safe for the user. Recently, incorporating therapeutic purposes in virtual reality interface devices has allowed them to be used for the rehabilitation of neurological patients, e.g., balance training in older adults and dynamic stability in healthy participants. The improvements observed in neurological diseases (chronic stroke and cerebral palsy) have been shown by changes in the reorganization of neural networks in patients' brain, along with better hand function and other skills, contributing to their quality of life. The data generated by such studies could substantially contribute to physical rehabilitation strategies.

  20. Virtual reality interface devices in the reorganization of neural networks in the brain of patients with neurological diseases

    PubMed Central

    Gatica-Rojas, Valeska; Méndez-Rebolledo, Guillermo

    2014-01-01

    Two key characteristics of all virtual reality applications are interaction and immersion. Systemic interaction is achieved through a variety of multisensory channels (hearing, sight, touch, and smell), permitting the user to interact with the virtual world in real time. Immersion is the degree to which a person can feel wrapped in the virtual world through a defined interface. Virtual reality interface devices such as the Nintendo® Wii and its peripheral nunchuks-balance board, head mounted displays and joystick allow interaction and immersion in unreal environments created from computer software. Virtual environments are highly interactive, generating great activation of visual, vestibular and proprioceptive systems during the execution of a video game. In addition, they are entertaining and safe for the user. Recently, incorporating therapeutic purposes in virtual reality interface devices has allowed them to be used for the rehabilitation of neurological patients, e.g., balance training in older adults and dynamic stability in healthy participants. The improvements observed in neurological diseases (chronic stroke and cerebral palsy) have been shown by changes in the reorganization of neural networks in patients’ brain, along with better hand function and other skills, contributing to their quality of life. The data generated by such studies could substantially contribute to physical rehabilitation strategies. PMID:25206907

  1. Esophagogastric disconnection following failed fundoplication for the treatment of gastroesophageal reflux disease (GERD) in children with severe neurological impairment.

    PubMed

    Buratti, Silvia; Kamenwa, Rose; Dohil, Ranjan; Collins, David; Lavine, Joel E

    2004-10-01

    This report describes our experience with esophagogastric disconnection and Roux-en-Y esophagojejunostomy for the treatment of gastroesophageal reflux disease (GERD) in seven neurologically impaired children as a second antireflux operation following failed Nissen fundoplication. After a mean follow-up of 3 years, three children (43%) were completely or almost completely symptom-free and had improved nutritional status. Early complications occurred in three patients (43%): small bowel obstruction, wound infection, and necrosis of the Roux-en-Y loop. Three patients (43%) presented long-term complications: jejunoesophageal bile reflux and bile reflux with gastric irritation. Two patients required reoperation (28%), and two deaths occurred in the postoperative period (28%). In three previous reports in the surgical literature, severe postoperative complications occurred in 0-44%, requiring reoperation in 0-22% of the patients, and the mortality rate was 0-11%. Esophagogastric disconnection for the treatment of GERD in neurologically impaired children is associated with major complications and should be considered after more conservative procedures fail.

  2. REM Sleep Behavior Disorder and REM Sleep Without Atonia as an Early Manifestation of Degenerative Neurological Disease

    PubMed Central

    McCarter, Stuart J.; St Louis, Erik K.

    2013-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by repeated episodes of dream enactment behavior and REM sleep without atonia (RSWA) during polysomnography recording. RSWA is characterized by increased phasic or tonic muscle activity seen on polysomnographic electromyogram channels. RSWA is a requisite diagnostic feature of RBD, but may also be seen in patients without clinical symptoms or signs of dream enactment as an incidental finding in neurologically normal individuals, especially in patients receiving antidepressant therapy. RBD may be idiopathic or symptomatic. Patients with idiopathic RBD often later develop other neurological features including parkinsonism, orthostatic hypotension, anosmia, or cognitive impairment. RSWA without clinical symptoms as well as clinically overt RBD also often occurs concomitantly with the α-synucleinopathy family of neurodegenerative disorders, which includes idiopathic Parkinson disease, Lewy body dementia, and multiple system atrophy. This review article considers the epidemiology of RBD, clinical and polysomnographic diagnostic standards for both RBD and RSWA, previously reported associations of RSWA and RBD with neurodegenerative disorders and other potential causes, the pathophysiology of which brain structures and networks mediate dysregulation of REM sleep muscle atonia, and considerations for the effective and safe management of RBD. PMID:22328094

  3. Arsenic: toxicity, oxidative stress and human disease.

    PubMed

    Jomova, K; Jenisova, Z; Feszterova, M; Baros, S; Liska, J; Hudecova, D; Rhodes, C J; Valko, M

    2011-03-01

    Arsenic (As) is a toxic metalloid element that is present in air, water and soil. Inorganic arsenic tends to be more toxic than organic arsenic. Examples of methylated organic arsenicals include monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)]. Reactive oxygen species (ROS)-mediated oxidative damage is a common denominator in arsenic pathogenesis. In addition, arsenic induces morphological changes in the integrity of mitochondria. Cascade mechanisms of free radical formation derived from the superoxide radical, combined with glutathione-depleting agents, increase the sensitivity of cells to arsenic toxicity. When both humans and animals are exposed to arsenic, they experience an increased formation of ROS/RNS, including peroxyl radicals (ROO•), the superoxide radical, singlet oxygen, hydroxyl radical (OH•) via the Fenton reaction, hydrogen peroxide, the dimethylarsenic radical, the dimethylarsenic peroxyl radical and/or oxidant-induced DNA damage. Arsenic induces the formation of oxidized lipids which in turn generate several bioactive molecules (ROS, peroxides and isoprostanes), of which aldehydes [malondialdehyde (MDA) and 4-hydroxy-nonenal (HNE)] are the major end products. This review discusses aspects of chronic and acute exposures of arsenic in the etiology of cancer, cardiovascular disease (hypertension and atherosclerosis), neurological disorders, gastrointestinal disturbances, liver disease and renal disease, reproductive health effects, dermal changes and other health disorders. The role of antioxidant defence systems against arsenic toxicity is also discussed. Consideration is given to the role of vitamin C (ascorbic acid), vitamin E (α-tocopherol), curcumin, glutathione and antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase in their protective roles against arsenic-induced oxidative stress.

  4. [Certification for specialists on neurology by Japanese Society of Neurology].

    PubMed

    Suzuki, Norihiro

    2009-11-01

    In accordance with recent ever increasing numbers in elder population in Japan, number of patients of age-related neurological diseases such as stroke, dementia and neurodegenerative diseases, etc., also remarkably increasing. Naturally, social needs for medical intervention in neurological fields inevitably become indispensable. The role of the neurologists, especially specialists of neurology, must be substantially important in the near future. The Japanese Society of Neurology has already launched the system for quality-certified specialists for neurology in 1970's. The aim of the system to educate and certify specialists for neurology has been announced as follows; the specialist of neurology must widely experienced and practiced in clinical fields, and must properly diagnose and judge the neurological illness even they are so complicate and difficult to manage (Rinsho Shinkeigaku (Clinical Neurology) 38 (6): 593-619, 1998). However, in future, the specialists for neurology must cultivate and keep the minds of "Professionalism" of physicians as well as their skills for clinical neurology. The Professionalism consists of altruism, accountability, excellence, duty, honor and integrity, respect and a personal commitment to life-long learning (ABIM: American Board of Internal Medicine, Project Professionalism, 1990-). The specialists of neurology with recent privilege in clinical insurance system for their special ability and techniques for neurological examination, should not only share their clinical specialty but also provide their opinion based upon Professionalism to all over the world. PMID:20030199

  5. The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis.

    PubMed

    Minagar, Alireza; Shapshak, Paul; Fujimura, Robert; Ownby, Ray; Heyes, Melvin; Eisdorfer, Carl

    2002-10-15

    Macrophage/microglia (M phi) are the principal immune cells in the central nervous system (CNS) concomitant with inflammatory brain disease and play a significant role in the host defense against invading microorganisms. Astrocytes, as a significant component of the blood-brain barrier, behave as one of the immune effector cells in the CNS as well. However, both cell types may play a dual role, amplifying the effects of inflammation and mediating cellular damage as well as protecting the CNS. Interactions of the immune system, M phi, and astrocytes result in altered production of neurotoxins and neurotrophins by these cells. These effects alter the neuronal structure and function during pathogenesis of HIV-1-associated dementia (HAD), Alzheimer disease (AD), and multiple sclerosis (MS). HAD primarily involves subcortical gray matter, and both HAD and MS affect sub-cortical white matter. AD is a cortical disease. The process of M phi and astrocytes activation leading to neurotoxicity share similarities among the three diseases. Human Immunodeficiency Virus (HIV)-1-infected M phi are involved in the pathogenesis of HAD and produce toxic molecules including cytokines, chemokines, and nitric oxide (NO). In AD, M phis produce these molecules and are activated by beta-amyloid proteins and related oligopeptides. Demyelination in MS involves M phi that become lipid laden, spurred by several possible antigens. In these three diseases, cytokine/chemokine communications between M phi and astrocytes occur and are involved in the balance of protective and destructive actions by these cells. This review describes the role of M phi and astrocytes in the pathogenesis of these three progressive neurological diseases, examining both beneficent and deleterious effects in each disease.

  6. Infectious Diseases as Causes of Mental Retardation and Other Concomitant Neurological Sequelae.

    ERIC Educational Resources Information Center

    Iivanainen, Matti; Lahdevirta, Juhani

    1988-01-01

    Examination of 1,000 Finnish patients with mental retardation indicated that infectious diseases were the only cause of mental retardation in 11.1 percent and a contributory cause in a further 1.5 percent. Among the former group of 111 patients, the causative infectious disease operated prenatally in 18 percent and perinatally/postnatally in 82…

  7. An Acoustic Study of the Relationships among Neurologic Disease, Dysarthria Type, and Severity of Dysarthria

    ERIC Educational Resources Information Center

    Kim, Yunjung; Kent, Raymond D.; Weismer, Gary

    2011-01-01

    Purpose: This study examined acoustic predictors of speech intelligibility in speakers with several types of dysarthria secondary to different diseases and conducted classification analysis solely by acoustic measures according to 3 variables (disease, speech severity, and dysarthria type). Method: Speech recordings from 107 speakers with…

  8. Favipiravir (T-705) protects against peracute Rift Valley fever virus infection and reduces delayed-onset neurologic disease observed with ribavirin treatment.

    PubMed

    Scharton, Dionna; Bailey, Kevin W; Vest, Zachary; Westover, Jonna B; Kumaki, Yohichi; Van Wettere, Arnaud; Furuta, Yousuke; Gowen, Brian B

    2014-04-01

    Rift Valley fever is a zoonotic, arthropod-borne disease that affects livestock and humans. The etiologic agent, Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) is primarily transmitted through mosquito bites, but can also be transmitted by exposure to infectious aerosols. There are presently no licensed vaccines or therapeutics to prevent or treat severe RVFV infection in humans. We have previously reported on the activity of favipiravir (T-705) against the MP-12 vaccine strain of RVFV and other bunyaviruses in cell culture. In addition, efficacy has also been documented in mouse and hamster models of infection with the related Punta Toro virus. Here, hamsters challenged with the highly pathogenic ZH501 strain of RVFV were used to evaluate the activity of favipiravir against lethal infection. Subcutaneous RVFV challenge resulted in substantial serum and tissue viral loads and caused severe disease and mortality within 2-3 days of infection. Oral favipiravir (200 mg/kg/day) prevented mortality in 60% or greater of hamsters challenged with RVFV when administered within 1 or 6h post-exposure and reduced RVFV titers in serum and tissues relative to the time of treatment initiation. In contrast, although ribavirin (75 mg/kg/day) was effective at protecting animals from the peracute RVFV disease, most ultimately succumbed from a delayed-onset neurologic disease associated with high RVFV burden observed in the brain in moribund animals. When combined, T-705 and ribavirin treatment started 24 h post-infection significantly improved survival outcome and reduced serum and tissue virus titers compared to monotherapy. Our findings demonstrate significant post-RVFV exposure efficacy with favipiravir against both peracute disease and delayed-onset neuroinvasion, and suggest added benefit when combined with ribavirin.

  9. Favipiravir (T-705) protects against peracute Rift Valley fever virus infection and reduces delayed-onset neurologic disease observed with ribavirin treatment

    PubMed Central

    Scharton, Dionna; Bailey, Kevin W.; Vest, Zachary; Westover, Jonna B.; Kumaki, Yohichi; Van Wettere, Arnaud; Furuta, Yousuke; Gowen, Brian B.

    2014-01-01

    Rift Valley Fever is a zoonotic, arthropod-borne disease that affects livestock and humans. The etiologic agent, Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) is primarily transmitted through mosquito bites, but can also be transmitted by exposure to infectious aerosols. There are presently no licensed vaccines or therapeutics to prevent or treat severe RVFV infection in humans. We have previously reported on the activity of favipiravir (T-705) against the MP-12 vaccine strain of RVFV and other bunyaviruses in cell culture. In addition, efficacy has also been documented in mouse and hamster models of infection with the related Punta Toro virus. Here, we challenged hamsters with the highly pathogenic ZH501 strain of RVFV to evaluate the activity of favipiravir against lethal infection. Subcutaneous RVFV challenge resulted in substantial serum and tissue viral loads and caused severe disease and mortality within 2–3 days after infection. Oral favipiravir (200 mg/kg/day) prevented mortality in 60% or greater in hamsters challenged with RVFV when administered within 1 or 6 h post-exposure and reduced RVFV titers in serum and tissues relative to the time of treatment initiation. In contrast, although ribavirin (75 mg/kg/day) was effective at protecting animals from the peracute RVFV disease, most ultimately succumbed from a delayed-onset neurologic disease associated with high RVFV burden in the brain observed in moribund animals. When combined, T-705 and ribavirin treatment started 24 h post-infection significantly improved survival outcome and reduced serum and tissue virus titers compared to monotherapy. Our findings demonstrate significant post-RVFV exposure efficacy with favipiravir against both peracute disease and delayed-onset neuroinvasion, and suggest added benefit when combined with ribavirin. PMID:24486952

  10. Rac GTPases in Human Diseases

    PubMed Central

    Pai, Sung-Yun; Kim, Chaekyun; Williams, David A.

    2010-01-01

    Rho GTPases are members of the Ras superfamily of GTPases that regulate a wide variety of cellular functions. While Rho GTPase pathways have been implicated in various pathological conditions in humans, to date coding mutations in only the hematopoietic specific GTPase, RAC2, have been found to cause a human disease, a severe phagocytic immunodeficiency characterized by life-threatening infections in infancy. Interestingly, the phenotype was predicted by a mouse knock-out of RAC2 and resembles leukocyte adhesion deficiency (LAD). Here we review Rho GTPases with a specific focus on Rac GTPases. In particular, we discuss a new understanding of the unique and overlapping roles of Rac2 in blood cells that has developed since the generation of mice deficient in Rac1, Rac2 and Rac3 proteins. We propose that Rac2 mutations leading to disease be termed LAD type IV. PMID:21178276

  11. Nicotinamide Phosphoribosyltransferase in Human Diseases

    PubMed Central

    Zhang, Li Qin; Heruth, Daniel P.; Ye, Shui Qing

    2011-01-01

    Nicotinamide phosphoribosyltransferase (NAMPT) was first reported as a pre-B-cell colony enhancing factor in 1994 with little notice, but it has received increasing attention in recent years due to accumulating evidence indicating that NAMPT is a pleiotropic protein such as a growth factor, a cytokine, an enzyme and a visfatin. Now, NAMPT has been accepted as an official name of this protein. Because of NAMPT’s multiple functions in a variety of physiological processes, their dysregulations have been implicated in the pathogenesis of a number of human diseases or conditions such as acute lung injury, aging, atherosclerosis, cancer, diabetes, rheumatoid arthritis and sepsis. This review will cover the current understanding of NAMPT’s structure and functions with an emphasis on recent progress of nicotinamide phosphoribosyltransferase’s pathological roles in various human diseases and conditions. Future directions on exploring its Terra incognita will be offered in the end. PMID:22140607

  12. [Neurologic aspects of clinical manifestations, pathophysiology and therapy of reflex sympathetic dystrophy (causalgia, Sudeck's disease)].

    PubMed

    Blumberg, H; Griesser, H J; Hornyak, M

    1991-04-01

    The symptomatology of reflex sympathetic dystrophy (RSD), a diagnostic term which today includes causalgia and M. Sudeck, is characterized clinically by a triad of autonomic (sympathetic), motor and sensory disturbances. They develop following a noxious event--though independent of its nature and location--in a generalized distribution pattern at the distal site of the affected extremity. Pathophysiologically, a complex disturbance of the sympathetic vasoconstrictor system is involved, which mediates the dominant symptoms of RSD, namely the spontaneous pain and the swelling. This disturbance is thought to be initiated by nociceptive impulses, occurring in conjunction with the preceding noxious event, and to be maintained reflexly, in a form of a vicious circle, by means of the typical pain sensation accompanying the RSD-syndrome. From these ideas, an important part of the RSD therapy is deduced; i.e. the early interruption of the neuronal sympathetic activity by means of a sympathetic blockade. Such a blockade can interrupt the pain and at the same time also the vicious circle of RSD. Altogether, for the RSD syndrome there are relevant neurological aspects with respect to its clinical symptomatology, its pathophysiology and its therapy. PMID:1713305

  13. Clinical neurologic indices of toxicity in animals.

    PubMed Central

    O'Donoghue, J L

    1996-01-01

    The fundamental structures and functions of the nervous systems of animals and humans are conserved in many ways across species. These similarities provide a basis for developing common neurologic examinations for a number of species of animals and also provide a basis for developing risk assessments across species for neurologic end points. The neurologic examination requires no expensive equipment and can be conducted in the field or wherever impaired animals are identified. The proper conduct of neurologic examinations in animals assumes that the examiner has a fundamental understanding of the normal structure and function of the nervous system as well as knowledge about the spontaneous disease background of the species being studied. PMID:9182039

  14. New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases

    PubMed Central

    Mitra, Joy; Guerrero, Erika N.; Hegde, Pavana M.; Wang, Haibo; Boldogh, Istvan; Rao, Kosagi Sharaf; Mitra, Sankar; Hegde, Muralidhar L.

    2014-01-01

    The primary cause(s) of neuronal death in most cases of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are still unknown. However, the association of certain etiological factors, e.g., oxidative stress, protein misfolding/aggregation, redox metal accumulation and various types of damage to the genome, to pathological changes in the affected brain region(s) have been consistently observed. While redox metal toxicity received major attention in the last decade, its potential as a therapeutic target is still at a cross-roads, mostly because of the lack of mechanistic understanding of metal dyshomeostasis in affected neurons. Furthermore, previous studies have established the role of metals in causing genome damage, both directly and via the generation of reactive oxygen species (ROS), but little was known about their impact on genome repair. Our recent studies demonstrated that excess levels of iron and copper observed in neurodegenerative disease-affected brain neurons could not only induce genome damage in neurons, but also affect their repair by oxidatively inhibiting NEIL DNA glycosylases, which initiate the repair of oxidized DNA bases. The inhibitory effect was reversed by a combination of metal chelators and reducing agents, which underscore the need for elucidating the molecular basis for the neuronal toxicity of metals in order to develop effective therapeutic approaches. In this review, we have focused on the oxidative genome damage repair pathway as a potential target for reducing pro-oxidant metal toxicity in neurological diseases. PMID:25036887

  15. Progress in pediatrics in 2013: choices in allergology, endocrinology, gastroenterology, hypertension, infectious diseases, neonatology, neurology, nutrition and respiratory tract illnesses.

    PubMed

    Caffarelli, Carlo; Santamaria, Francesca; Vottero, Alessandra; Dascola, Carlotta Povesi; Mirra, Virginia; Sperli, Francesco; Bernasconi, Sergio

    2014-07-12

    This review will provide new information related to pathophysiology and management of specific diseases that have been addressed by selected articles published in the Italian Journal of Pediatrics in 2013, focusing on allergology, endocrinology, gastroenterology, hypertension, infectious diseases, neonatology, neurology, nutrition and respiratory tract illnesses in children. Recommendations for interpretation of skin prick test to foods in atopic eczema, management of allergic conjunctivitis, hypertension and breastfeeding in women treated with antiepileptic drugs and healthy breakfast have been reported. Epidemiological studies have given emphasis to high incidence of autoimmune disorders in patients with Turner syndrome, increasing prevalence of celiac disease, frequency of hypertension in adolescents, incidence and risk factor for retinopathy of prematurity. Advances in prevention include elucidation of the role of probiotics in reducing occurrence of allergies and feeding intolerance, and events of foetal life that influence later onset of diseases. Mechanistic studies suggested a role for vitamin D deficiency in asthma and type 1 diabetes and for reactivation of Varicella-Zoster virus in aseptic meningitis. Regarding diagnosis, a new mean for the diagnosis of hyperbilirubinaemia in newborns, a score for recognition of impaired nutritional status and growth and criteria for early Dyke-Davidoff-Masson Syndrome have been suggested. New therapeutic approaches consist of use of etanercept for reducing insulin dose in type 1 diabetes, probiotics in atopic eczema, and melatonin in viral infections.

  16. Neurology issues in schizophrenia.

    PubMed

    Hüfner, Katharina; Frajo-Apor, Beatrice; Hofer, Alex

    2015-05-01

    Schizophrenia ranks among the leading causes of disability worldwide. The presence of neurological signs co-occurring with the psychiatric symptoms is indicative of an organic brain pathology. In the present article, we review the current literature on neurology issues in schizophrenia. Firstly, common neurological signs found in patients with schizophrenia (neurological soft signs and smell abnormalities) and their association with imaging findings are reviewed. Secondly, the significant association of schizophrenia with epilepsy and stroke is described as well as the absent association with other organic brain diseases such as multiple sclerosis. Thirdly, we discuss the potential role of NMDA receptor antibodies in schizophrenia. Fourthly, neurological side effects of antipsychotic drugs and their treatment are reviewed; and lastly, we discuss neurocognitive deficits in patients with schizophrenia and their treatment. The focus of the review remains on articles with relevance to the clinician. PMID:25773225

  17. Neurological lesions in chickens experimentally infected with virulent Newcastle disease virus isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neuropil reaction was evaluated in chickens inoculated with four different Newcastle disease virus (NDV) isolates, including Texas GB, Turkey North Dakota, Nevada Cormorant (velogenic neurotropic) and Anhinga (mesogenic). Tissues for this study included archived formalin-fixed, paraffin embedded br...

  18. Multi-resolution entropy analysis of gait symmetry in neurological degenerative diseases and amyotrophic lateral sclerosis.

    PubMed

    Liao, Fuyuan; Wang, Jue; He, Ping

    2008-04-01

    Gait rhythm of patients with Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS) has been studied focusing on the fractal and correlation properties of stride time fluctuations. In this study, we investigated gait asymmetry in these diseases using the multi-resolution entropy analysis of stance time fluctuations. Since stance time is likely to exhibit fluctuations across multiple spatial and temporal scales, the data series were decomposed into appropriate levels by applying stationary wavelet transform. The similarity between two corresponding wavelet coefficient series in terms of their regularities at each level was quantified based on a modified sample entropy method and a weighted sum was then used as gait symmetry index. We found that gait symmetry in subjects with PD and HD, especially with ALS is significantly disturbed. This method may be useful in characterizing certain pathologies of motor control and, possibly, in monitoring disease progression and evaluating the effect of an individual treatment.

  19. Multi-resolution entropy analysis of gait symmetry in neurological degenerative diseases and amyotrophic lateral sclerosis.

    PubMed

    Liao, Fuyuan; Wang, Jue; He, Ping

    2008-04-01

    Gait rhythm of patients with Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS) has been studied focusing on the fractal and correlation properties of stride time fluctuations. In this study, we investigated gait asymmetry in these diseases using the multi-resolution entropy analysis of stance time fluctuations. Since stance time is likely to exhibit fluctuations across multiple spatial and temporal scales, the data series were decomposed into appropriate levels by applying stationary wavelet transform. The similarity between two corresponding wavelet coefficient series in terms of their regularities at each level was quantified based on a modified sample entropy method and a weighted sum was then used as gait symmetry index. We found that gait symmetry in subjects with PD and HD, especially with ALS is significantly disturbed. This method may be useful in characterizing certain pathologies of motor control and, possibly, in monitoring disease progression and evaluating the effect of an individual treatment. PMID:17569571

  20. Behcet's Disease

    MedlinePlus

    ... neurological disorders such as Behcet's disease. The National Human Genome Research Institute, another Institute of the National Institutes of Health, conducts research into the genomic basis of Behcet's disease. This research is aimed ...

  1. Neurologic effects of exogenous saccharides: A review of controlled human, animal, and in vitro studies

    PubMed Central

    Nelson, Erika D.; Ramberg, Jane E.; Best, Talitha; Sinnott, Robert A.

    2012-01-01

    Objectives Current research efforts are centered on delineating the novel health benefits of naturally derived saccharides, including growing interest in their abilities to influence neurologic health. We performed a comprehensive review of the literature to consolidate all controlled studies assessing various roles of exogenous saccharide compounds and polysaccharide-rich extracts from plants, fungi, and other natural sources on brain function, with a significant focus on benefits derived from oral intake. Methods Studies were identified by conducting electronic searches on PubMed and Google Scholar. Reference lists of articles were also reviewed for additional relevant studies. Only articles published in English were included in this review. Results Six randomized, double-blind, placebo-controlled clinical studies were identified in which consumption of a blend of plant-derived polysaccharides showed positive effects on cognitive function and mood in healthy adults. A separate controlled clinical study observed improvements in well-being with ingestion of a yeast beta-glucan. Numerous animal and in vitro studies have demonstrated the ability of individual saccharide compounds and polysaccharide-rich extracts to modify behavior, enhance synaptic plasticity, and provide neuroprotective effects. Discussion Although the mechanisms by which exogenous saccharides can influence brain function are not well understood at this time, the literature suggests that certain naturally occurring compounds and polysaccharide-rich extracts show promise, when taken orally, in supporting neurologic health and function. Additional well-controlled clinical studies on larger populations are necessary, however, before specific recommendations can be made. PMID:22417773

  2. Blinded by the UV light: How the focus on transcription-coupled NER has distracted from understanding the mechanisms of Cockayne syndrome neurologic disease

    PubMed Central

    Brooks, P.J.

    2014-01-01

    Cockayne syndrome (CS) is a devastating neurodevelopmental disorder, with growth abnormalities, progeriod features, and sun sensitivity. CS is typically considered to be a DNA repair disorder, since cells from CS patients have a defect in transcription-coupled nucleotide excision repair (TC-NER). However, cells from UV-sensitive syndrome patients also lack TC-NER, but these patients do not suffer from the neurologic and other abnormalities that CS patients do. Also, the neurologic abnormalities that affect CS patients (CS neurologic disease) are qualitatively different from those seen in NER-deficient XP patients. Therefore, the TC-NER defect explains the sun sensitive phenotype common to both CS and UVsS, but cannot explain CS neurologic disease. However, as CS neurologic disease is of much greater clinical significance than the sun sensitivity, there is a pressing need to understand its molecular basis. While there is evidence for defective repair of oxidative DNA damage and mitochondrial abnormalities in CS cells, here I propose that the defects in transcription by both RNA polymerases I and II that have been documented in CS cells provide a better explanation for many of the severe growth and neurodevelopmental defects in CS patients than defective DNA repair. The implications of these ideas for interpreting results from mouse models of CS, and for the development of treatments and therapies for CS patients are discussed. PMID:23683874

  3. Oxidative stress and autophagy in cardiac disease, neurological disorders, aging and cancer

    PubMed Central

    Essick, Eric E

    2010-01-01

    Autophagy is a catalytic process of the bulk degradation of long-lived cellular components, ultimately resulting in lysosomal digestion within mature cytoplasmic compartments known as autophagolysosomes. Autophagy serves many functions in the cell, including maintaining cellular homeostasis, a means of cell survival during stress (e.g., nutrient deprivation or starvation) or conversely as a mechanism for cell death. Increased reactive oxygen species (ROS) production and the resulting oxidative cell stress that occurs in many disease states has been shown to induce autophagy. The following review focuses on the roles that autophagy plays in response to the ROS generated in several diseases. PMID:20716941

  4. William Shakespeare's neurology.

    PubMed

    Paciaroni, Maurizio; Bogousslavsky, Julien

    2013-01-01

    Many of Shakespeare's plays contain characters who appear to be afflicted by neurological or psychiatric disorders. Shakespeare, in his descriptive analysis of his protagonists, was contributing to the understanding of these disorders. In fact, Charcot frequently used Shakespearean references in his neurological teaching sessions, stressing how acute objective insight is essential to achieving expert clinical diagnosis. Charcot found in Shakespeare the same rigorous observational techniques for which he himself became famous. This chapter describes many of Shakespearean characters suffering from varied neurological disorders, including Parkinsonism, epilepsy, sleeping disturbances, dementia, headache, prion disease, and paralyses. PMID:24290473

  5. A Darwinian approach to Huntington's disease: subtle health benefits of a neurological disorder.

    PubMed

    Eskenazi, Benjamin R; Wilson-Rich, Noah S; Starks, Philip T

    2007-01-01

    Huntington's disease (HD) is a neurodegenerative disorder that, unlike most autosomal dominant disorders, is not being selected against. One explanation for the maintenance of the mutant HD allele is that it is transparent to natural selection because disease symptoms typically occur subsequent to an individual's peak reproductive years. While true, this observation does not explain the population-level increase in HD. The increase in HD is at least partly the result of enhanced fitness: HD+ individuals have more offspring than unaffected relatives. This phenomenon has previously been explained as the result of elevated promiscuity of HD+ individuals. For this to be true, disease symptoms must be expressed during the otherwise asymptomatic peak reproductive years and promiscuity must increase offspring production; however, neither prediction is supported by data. Instead, new data suggest that the mutant HD allele bestows health benefits on its carriers. HD+ individuals show elevated levels of the tumor suppressor protein p53 and experience significantly less cancer than unaffected siblings. We hypothesize that the mutant HD allele elevates carriers' immune activity and thus HD+ individuals are, on average, healthier than HD- individuals during reproductive years. As health and reproductive output are positively related, data suggest a counterintuitive relationship: health benefits may lead to an increased prevalence of Huntington's disease.

  6. Models of neurological disease (substance abuse): self-administration in monkeys.

    PubMed

    Platt, Donna M; Carey, Galen; Spealman, Roger D

    2011-12-01

    Drug self-administration is a procedure in which a subject performs a specified response that results in the delivery of a drug injection. This procedure is viewed as a relevant model for the study of human drug-taking behavior. Drug self-administration in primates has several characteristics that resemble drug-taking behavior in humans, and agents commonly abused by humans also generally maintain self-administration behavior in monkeys. Self-administration procedures allow for the study of a variety of drug properties. For instance, they can be used to investigate the abuse potential of new compounds and to study the effects of candidate medications for the treatment of drug addiction. These procedures can also be employed for examining drug reinforcement mechanisms. Described in this unit are procedures for studying intravenous drug self-administration in large primates, such as rhesus macaques, and smaller primates, such as squirrel monkeys.

  7. Models of Neurological Disease (Substance Abuse): Self-Administration in Monkeys

    PubMed Central

    Platt, Donna M.; Carey, Galen; Spealman, Roger D.

    2012-01-01

    Drug self-administration is a procedure in which a subject performs a specified response that results in the delivery of a drug injection. This procedure is viewed as a relevant model for the study of human drug-taking behavior. Drug self-administration in primates has several characteristics that resemble drug-taking behavior in humans, and agents commonly abused by humans also generally maintain self-administration behavior in monkeys. Self-administration procedures allow for the study of a variety of drug properties. For instance, they can be used to investigate the abuse potential of new compounds and to study the effects of candidate medications for the treatment of drug addiction. These procedures also can be employed for examining drug reinforcement mechanisms. Described in this unit are procedures for studying intravenous drug self-administration in large primates, such as rhesus macaques, and smaller primates, such as squirrel monkeys. PMID:22382996

  8. Beyond membrane channelopathies: alternative mechanisms underlying complex human disease

    PubMed Central

    Boudoulas, Konstantinos Dean; Mohler, Peter J

    2011-01-01

    Over the past fifteen years, our understanding of the molecular mechanisms underlying human disease has flourished in large part due to the discovery of gene mutations linked with membrane ion channels and transporters. In fact, ion channel defects (“channelopathies” — the focus of this review series) have been associated with a spectrum of serious human disease phenotypes including cystic fibrosis, cardiac arrhythmia, diabetes, skeletal muscle defects, and neurological disorders. However, we now know that human disease, particularly excitable cell disease, may be caused by defects in non-ion channel polypeptides including in cellular components residing well beneath the plasma membrane. For example, over the past few years, a new class of potentially fatal cardiac arrhythmias has been linked with cytoplasmic proteins that include sub-membrane adapters such as ankyrin-B (ANK2), ankyrin-G (ANK3), and alpha-1 syntrophin, membrane coat proteins including caveolin-3 (CAV3), signaling platforms including yotiao (AKAP9), and cardiac enzymes (GPD1L). The focus of this review is to detail the exciting role of lamins, yet another class of gene products that have provided elegant new insight into human disease. PMID:21642948

  9. Aleutian Mink Disease Virus and Humans

    PubMed Central

    d’Amore, Francesco; Baandrup, Ulrik; Clausen, Michael Roost; Gottschalck, Elisabeth; Aasted, Bent

    2009-01-01

    Reports of a possible relationship between Aleutian mink disease parvovirus (AMDV) and human infection are rare. However, 2 mink farmers with vascular disease and microangiopathy similar to that in mink with Aleutian disease were found to have AMDV-specific antibodies and AMDV DNA. These findings raise the suspicion that AMDV may play a role in human disease. PMID:19961696

  10. Aleutian mink disease virus and humans.

    PubMed

    Jepsen, Jørgen R; d'Amore, Francesco; Baandrup, Ulrik; Clausen, Michael Roost; Gottschalck, Elisabeth; Aasted, Bent

    2009-12-01

    Reports of a possible relationship between Aleutian mink disease parvovirus (AMDV) and human infection are rare. However, 2 mink farmers with vascular disease and microangiopathy similar to that in mink with Aleutian disease were found to have AMDV-specific antibodies and AMDV DNA. These findings raise the suspicion that AMDV may play a role in human disease. PMID:19961696

  11. [The Biological Function of SHP2 in Human Disease].

    PubMed

    Li, S M

    2016-01-01

    Tyrosyl phosphorylation participates in various pathological and physiological processes, which are regulated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). The Src homology-2 domain containing phosphatase SHP2 (encoded by PTPN11) is an important phosphatase, which was found to be implicated in the regulation of genetic disease, development, metabolic, neurological, muscle, skeletal disease and cancer. Germline mutations in PTPN11 cause the Noonan Syndrome, LEOPARD syndrome and metachondromatosis. Somatic PTPN11 mutations occur in hematologic malignancies and in solid tumors. SHP2 is also an important component in oncogenic signaling pathways. It may play different roles in different stages and positions of human cancers. Whether SHP2 is an oncogene or cancer suppressor gene remains to be elucidated. Elucidation of the regulatory mechanisms of SHP2 in human disease will provide new insights into disease and new targets for therapy. Here, we summarized the structural basis and recent research progression on SHP2 in various human disease, including genetic and cancer diseases. PMID:27028808

  12. Human Microbiota and Ophthalmic Disease

    PubMed Central

    Lu, Louise J.; Liu, Ji

    2016-01-01

    The human ocular surface, consisting of the cornea and conjunctiva, is colonized by an expansive, diverse microbial community. Molecular-based methods, such as 16S rRNA sequencing, has allowed for more comprehensive and precise identification of the species composition of the ocular surface microbiota compared to traditional culture-based methods. Evidence suggests that the normal microbiota plays a protective immunological role in preventing the proliferation of pathogenic species and thus, alterations in the homeostatic microbiome may be linked to ophthalmic pathologies. Further investigation of the ocular surface microbiome, as well as the microbiome of other areas of the body such as the oral mucosa and gut, and their role in the pathophysiology of diseases is a significant, emerging field of research, and may someday enable the development of novel probiotic approaches for the treatment and prevention of ophthalmic diseases. PMID:27698616

  13. Human Microbiota and Ophthalmic Disease

    PubMed Central

    Lu, Louise J.; Liu, Ji

    2016-01-01

    The human ocular surface, consisting of the cornea and conjunctiva, is colonized by an expansive, diverse microbial community. Molecular-based methods, such as 16S rRNA sequencing, has allowed for more comprehensive and precise identification of the species composition of the ocular surface microbiota compared to traditional culture-based methods. Evidence suggests that the normal microbiota plays a protective immunological role in preventing the proliferation of pathogenic species and thus, alterations in the homeostatic microbiome may be linked to ophthalmic pathologies. Further investigation of the ocular surface microbiome, as well as the microbiome of other areas of the body such as the oral mucosa and gut, and their role in the pathophysiology of diseases is a significant, emerging field of research, and may someday enable the development of novel probiotic approaches for the treatment and prevention of ophthalmic diseases.

  14. A Parent's Journey: Incorporating Principles of Palliative Care into Practice for Children with Chronic Neurologic Diseases.

    PubMed

    Brown, Allyson; Clark, Jonna D

    2015-09-01

    Rather than in conflict or in competition with the curative model of care, pediatric palliative care is a complementary and transdisciplinary approach used to optimize medical care for children with complex medical conditions. It provides care to the whole child, including physical, mental, and spiritual dimensions, in addition to support for the family. Through the voice of a parent, the following case-based discussion demonstrates how the fundamentals of palliative care medicine, when instituted early in the course of disease, can assist parents and families with shared medical decision making, ultimately improving the quality of life for children with life-limiting illnesses. Pediatric neurologists, as subspecialists who provide medical care for children with chronic and complex conditions, should consider invoking the principles of palliative care early in the course of a disease process, either through applying general facets or, if available, through consultation with a specialty palliative care service. PMID:26358425

  15. DNA Secondary Structure at Chromosomal Fragile Sites in Human Disease

    PubMed Central

    Thys, Ryan G; Lehman, Christine E; Pierce, Levi C. T; Wang, Yuh-Hwa

    2015-01-01

    DNA has the ability to form a variety of secondary structures that can interfere with normal cellular processes, and many of these structures have been associated with neurological diseases and cancer. Secondary structure-forming sequences are often found at chromosomal fragile sites, which are hotspots for sister chromatid exchange, chromosomal translocations, and deletions. Structures formed at fragile sites can lead to instability by disrupting normal cellular processes such as DNA replication and transcription. The instability caused by disruption of replication and transcription can lead to DNA breakage, resulting in gene rearrangements and deletions that cause disease. In this review, we discuss the role of DNA secondary structure at fragile sites in human disease. PMID:25937814

  16. CNVs, Aneuploidies and Human Disease

    PubMed Central

    Martin, Christa L.; Kirkpatrick, Brianne E.; Ledbetter, David H.

    2015-01-01

    In the perinatal setting, chromosome imbalances cause a wide range of clinically significant disorders and increase risk for other particular phenotypes. As technologies have improved to detect increasingly smaller deletions and duplications, collectively referred to as copy number variants (CNVs), we are learning the significant role that these types of genomic variants play in human disease and their relatively high frequency in ~1% of all pregnancies. In this overview, we will highlight key aspects of CNV detection and interpretation used during the course of clinical care in the prenatal and neonatal periods. Since CNVs are one of the most frequent causes of a broad spectrum of human disorders, early diagnosis and accurate interpretation is important to implement timely interventions and targeted clinical management. PMID:26042902

  17. Altered manifestations of skin disease at sites affected by neurological deficit

    PubMed Central

    Azimi, E.; Lerner, E.A.; Elmariah, S.B.

    2014-01-01

    The contribution of the nervous system to inflammation in general and inflammatory skin disease in particular has been underappreciated. It is now apparent that the conventional clinical manifestations of many inflammatory skin diseases require an intact neural component. We reviewed the literature and identified 23 cases of alterations in the appearance or distribution of skin disorders in patients with acquired central or peripheral neural damage or dysfunction. In 19 cases, near or complete resolution of pre-existing skin lesions occurred in areas directly or indirectly supplied by a subsequently injured nervous system. Exacerbation or new onset of skin lesions occurred in only 4 cases. The neural deficits described included damage within the peripheral or central nervous system resulting in pure sensory, pure motor, or combined sensory and motor deficits. These cases highlight the importance of neural innervation and neurogenic inflammation in the development of inflammatory skin disease and prompt further examination of the use of neural blockade as an adjunctive therapy in the treatment of inflammatory dermatoses. PMID:25132518

  18. Wikipedia and neurological disorders.

    PubMed

    Brigo, Francesco; Igwe, Stanley C; Nardone, Raffaele; Lochner, Piergiorgio; Tezzon, Frediano; Otte, Willem M

    2015-07-01

    Our aim was to evaluate Wikipedia page visits in relation to the most common neurological disorders by determining which factors are related to peaks in Wikipedia searches for these conditions. Millions of people worldwide use the internet daily as a source of health information. Wikipedia is a popular free online encyclopedia used by patients and physicians to search for health-related information. The following Wikipedia articles were considered: Alzheimer's disease; Amyotrophic lateral sclerosis; Dementia; Epilepsy; Epileptic seizure; Migraine; Multiple sclerosis; Parkinson's disease; Stroke; Traumatic brain injury. We analyzed information regarding the total article views for 90 days and the rank of these articles among all those available in Wikipedia. We determined the highest search volume peaks to identify possible relation with online news headlines. No relation between incidence or prevalence of neurological disorders and the search volume for the related articles was found. Seven out of 10 neurological conditions showed relations in search volume peaks and news headlines. Six out of these seven peaks were related to news about famous people suffering from neurological disorders, especially those from showbusiness. Identification of discrepancies between disease burden and health seeking behavior on Wikipedia is useful in the planning of public health campaigns. Celebrities who publicly announce their neurological diagnosis might effectively promote awareness programs, increase public knowledge and reduce stigma related to diagnoses of neurological disorders.

  19. Aluminium and human breast diseases.

    PubMed

    Darbre, P D; Pugazhendhi, D; Mannello, F

    2011-11-01

    The human breast is exposed to aluminium from many sources including diet and personal care products, but dermal application of aluminium-based antiperspirant salts provides a local long-term source of exposure. Recent measurements have shown that aluminium is present in both tissue and fat of the human breast but at levels which vary both between breasts and between tissue samples from the same breast. We have recently found increased levels of aluminium in noninvasively collected nipple aspirate fluids taken from breast cancer patients (mean 268 ± 28 μg/l) compared with control healthy subjects (mean 131 ± 10 μg/l) providing evidence of raised aluminium levels in the breast microenvironment when cancer is present. The measurement of higher levels of aluminium in type I human breast cyst fluids (median 150 μg/l) compared with human serum (median 6 μg/l) or human milk (median 25 μg/l) warrants further investigation into any possible role of aluminium in development of this benign breast disease. Emerging evidence for aluminium in several breast structures now requires biomarkers of aluminium action in order to ascertain whether the presence of aluminium has any biological impact. To this end, we report raised levels of proteins that modulate iron homeostasis (ferritin, transferrin) in parallel with raised aluminium in nipple aspirate fluids in vivo, and we report overexpression of mRNA for several S100 calcium binding proteins following long-term exposure of MCF-7 human breast cancer cells in vitro to aluminium chlorhydrate.

  20. Aluminium and human breast diseases.

    PubMed

    Darbre, P D; Pugazhendhi, D; Mannello, F

    2011-11-01

    The human breast is exposed to aluminium from many sources including diet and personal care products, but dermal application of aluminium-based antiperspirant salts provides a local long-term source of exposure. Recent measurements have shown that aluminium is present in both tissue and fat of the human breast but at levels which vary both between breasts and between tissue samples from the same breast. We have recently found increased levels of aluminium in noninvasively collected nipple aspirate fluids taken from breast cancer patients (mean 268 ± 28 μg/l) compared with control healthy subjects (mean 131 ± 10 μg/l) providing evidence of raised aluminium levels in the breast microenvironment when cancer is present. The measurement of higher levels of aluminium in type I human breast cyst fluids (median 150 μg/l) compared with human serum (median 6 μg/l) or human milk (median 25 μg/l) warrants further investigation into any possible role of aluminium in development of this benign breast disease. Emerging evidence for aluminium in several breast structures now requires biomarkers of aluminium action in order to ascertain whether the presence of aluminium has any biological impact. To this end, we report raised levels of proteins that modulate iron homeostasis (ferritin, transferrin) in parallel with raised aluminium in nipple aspirate fluids in vivo, and we report overexpression of mRNA for several S100 calcium binding proteins following long-term exposure of MCF-7 human breast cancer cells in vitro to aluminium chlorhydrate. PMID:22099158

  1. Genomics in Neurological Disorders

    PubMed Central

    Han, Guangchun; Sun, Jiya; Wang, Jiajia; Bai, Zhouxian; Song, Fuhai; Lei, Hongxing

    2014-01-01

    Neurological disorders comprise a variety of complex diseases in the central nervous system, which can be roughly classified as neurodegenerative diseases and psychiatric disorders. The basic and translational research of neurological disorders has been hindered by the difficulty in accessing the pathological center (i.e., the brain) in live patients. The rapid advancement of sequencing and array technologies has made it possible to investigate the disease mechanism and biomarkers from a systems perspective. In this review, recent progresses in the discovery of novel risk genes, treatment targets and peripheral biomarkers employing genomic technologies will be discussed. Our major focus will be on two of the most heavily investigated neurological disorders, namely Alzheimer’s disease and autism spectrum disorder. PMID:25108264

  2. Genetic Analysis in Neurology

    PubMed Central

    Pittman, Alan; Hardy, John

    2014-01-01

    In recent years, neurogenetics research had made some remarkable advances owing to the advent of genotyping arrays and next-generation sequencing. These improvements to the technology have allowed us to determine the whole-genome structure and its variation and to examine its effect on phenotype in an unprecedented manner. The identification of rare disease-causing mutations has led to the identification of new biochemical pathways and has facilitated a greater understanding of the etiology of many neurological diseases. Furthermore, genome-wide association studies have provided information on how common genetic variability impacts on the risk for the development of various complex neurological diseases. Herein, we review how these technological advances have changed the approaches being used to study the genetic basis of neurological disease and how the research findings will be translated into clinical utility. PMID:23571731

  3. Aluminum-Induced Entropy in Biological Systems: Implications for Neurological Disease

    PubMed Central

    Shaw, Christopher A.; Seneff, Stephanie; Kette, Stephen D.; Tomljenovic, Lucija; Oller, John W.; Davidson, Robert M.

    2014-01-01

    Over the last 200 years, mining, smelting, and refining of aluminum (Al) in various forms have increasingly exposed living species to this naturally abundant metal. Because of its prevalence in the earth's crust, prior to its recent uses it was regarded as inert and therefore harmless. However, Al is invariably toxic to living systems and has no known beneficial role in any biological systems. Humans are increasingly exposed to Al from food, water, medicinals, vaccines, and cosmetics, as well as from industrial occupational exposure. Al disrupts biological self-ordering, energy transduction, and signaling systems, thus increasing biosemiotic entropy. Beginning with the biophysics of water, disruption progresses through the macromolecules that are crucial to living processes (DNAs, RNAs, proteoglycans, and proteins). It injures cells, circuits, and subsystems and can cause catastrophic failures ending in death. Al forms toxic complexes with other elements, such as fluorine, and interacts negatively with mercury, lead, and glyphosate. Al negatively impacts the central nervous system in all species that have been studied, including humans. Because of the global impacts of Al on water dynamics and biosemiotic systems, CNS disorders in humans are sensitive indicators of the Al toxicants to which we are being exposed. PMID:25349607

  4. The Complexity Signature: Developing a Tool to Communicate Biopsychosocial Severity of Disease for Children with Chronic Neurological Complexity.

    PubMed

    Krieg, Sandro M; Sonanini, Sebastian; Sollmann, Nico; Focke, Axel; Gerstl, Lucia; Heinen, Florian

    2016-08-01

    Aim For children with medical complexity, interdisciplinary treatment approaches are required to address the various aspects defined within the biopsychosocial model. Methods The present study identifies dimensions of the biopsychosocial model to generate a standardized visualized severity score for chronic neurological diseases in children. We demonstrate the score's applicability and usefulness in clinical practice among clinicians with and without pediatric board certification with the aid of illustrative patient cases. The results are compared by Spearman correlation coefficient. Results Nine dimensions were identified as the basis for the development of the score, which consists of five grades of severity for each of the selected neuropediatric subsections. All board-certified pediatricians would recommend the application of the severity score in clinical routine. Furthermore, a good correlation was revealed between direct and indirect (severity score) assessment. Interpretation The severity score developed in this study takes into account biopsychosocial aspects of chronic diseases while being comprehensible and easily applicable in clinical routine-a biopsychosocial signature serving as an excellent, striking communication basis within the interdisciplinary team. However, upcoming studies including more patient cases are needed for further refinement. PMID:27228000

  5. Pathophysiology of Parkinson's disease: from clinical neurology to basic neuroscience and back.

    PubMed

    Bergman, Hagai; Deuschl, Günther

    2002-01-01

    Parkinson's disease (PD) is characterized by motor and nonmotor (cognitive and limbic) deficits. The motor signs of PD include hypokinetic signs such as akinesia/bradykinesia, rigidity and loss of normal postural reflexes, and hyperkinetic signs such as tremor. Dopamine depletion in the striatum is the hallmark of PD and of its animal models, still the pathophysiology of the parkinsonian symptoms and especially of parkinsonian tremor are under debate. The most extreme hypotheses argue about peripheral versus central nervous system origin, intrinsic cellular oscillator versus network oscillators, and basal ganglia-based pathophysiology versus cerebellar-thalamic based pathophysiology. Recent studies support the view that parkinsonian symptoms are most likely due to abnormal synchronous oscillating neuronal activity within the basal ganglia. Peripheral factors do only play a minor role for the generation, maintenance, and modulation of PD tremor and other signs. The most likely candidates producing these neuronal oscillations are the weakly coupled neural networks of the basal ganglia-thalamo-cortical loops. However, the present evidence supports the view that the basal ganglia loops are influenced by other neuronal structures and systems and that the tuning of these loops by cerebello-thalamic mechanisms and by other modulator neurotransmitter systems entrain the abnormal synchronized oscillations. Neurosurgical procedures, such as lesions or high-frequency stimulation of different parts of the loop, might resume the normal unsynchronized activity of the basal ganglia circuitry, and, therefore, ameliorate the clinical symptoms of Parkinson's disease. PMID:11948753

  6. A neurological perspective on the enhancement debate: Lessons learned from Parkinson's disease.

    PubMed

    Kehagia, Angie A

    2016-10-01

    Cognitive enhancement is signified by adaptive behavioural change following an intervention that targets the brain. Although much of the discussion and research into cognitive enhancement focuses on the effects of neural interventions in healthy individuals, it is useful to consider evidence from clinical populations. Diseases of the central nervous system represent the primary and richest source of evidence on the effects of brain manipulations, which are in the first instance therapeutic. Parkinson's disease (PD) is used as a model for understanding the effects of pharmacological agents that target systems with a central role in cognition. The mixed outcomes of deep brain stimulation on cognition will also be discussed. By illustrating the psychopharmacological principle of diverse and malleable neurochemical optima for different cognitive functions, and the role of individual differences, it will be argued that the entire spectrum of cognitive effects in any one individual following any given manipulation, such as the administration of a drug, often includes enhancement as well as impairment. Predicting these effects represents a complex multivariate problem, and the accuracy of this predictive effort, as well as the harm prevention it connotes, is determined by our evolving understanding of the brain and cognition. A manipulation can be said to confer cognitive enhancement; however, it is argued that using the global term cognitive enhancer to refer to such a manipulation without qualification is of limited utility. PMID:27604630

  7. Neurology in Asia.

    PubMed

    Tan, Chong-Tin

    2015-02-10

    Asia is important as it accounts for more than half of the world population. The majority of Asian countries fall into the middle income category. As for cultural traditions, Asia is highly varied, with many languages spoken. The pattern of neurologic diseases in Asia is largely similar to the West, with some disease features being specific to Asia. Whereas Asia constitutes 60% of the world's population, it contains only 20% of the world's neurologists. This disparity is particularly evident in South and South East Asia. As for neurologic care, it is highly variable depending on whether it is an urban or rural setting, the level of economic development, and the system of health care financing. To help remedy the shortage of neurologists, most counties with larger populations have established training programs in neurology. These programs are diverse, with many areas of concern. There are regional organizations serving as a vehicle for networking in neurology and various subspecialties, as well as an official journal (Neurology Asia). The Asian Epilepsy Academy, with its emphasis on workshops in various locations, EEG certification examination, and fellowships, may provide a template of effective regional networking for improving neurology care in the region.

  8. Modeling cognition and disease using human glial chimeric mice.

    PubMed

    Goldman, Steven A; Nedergaard, Maiken; Windrem, Martha S

    2015-08-01

    As new methods for producing and isolating human glial progenitor cells (hGPCs) have been developed, the disorders of myelin have become especially compelling targets for cell-based therapy. Yet as animal modeling of glial progenitor cell-based therapies has progressed, it has become clear that transplanted hGPCs not only engraft and expand within murine hosts, but dynamically outcompete the resident progenitors so as to ultimately dominate the host brain. The engrafted human progenitor cells proceed to generate parenchymal astrocytes, and when faced with a hypomyelinated environment, oligodendrocytes as well. As a result, the recipient brains may become inexorably humanized with regards to their resident glial populations, yielding human glial chimeric mouse brains. These brains provide us a fundamentally new tool by which to assess the species-specific attributes of glia in modulating human cognition and information processing. In addition, the cellular humanization of these brains permits their use in studying glial infectious and inflammatory disorders unique to humans, and the effects of those disorders on the glial contributions to cognition. Perhaps most intriguingly, by pairing our ability to construct human glial chimeras with the production of patient-specific hGPCs derived from pluripotential stem cells, we may now establish mice in which a substantial proportion of resident glia are both human and disease-derived. These mice in particular may provide us new opportunities for studying the human-specific contributions of glia to psychopathology, as well as to higher cognition. As such, the assessment of human glial chimeric mice may provide us new insight into the species-specific contributions of glia to human cognitive evolution, as well as to the pathogenesis of human neurological and neuropsychiatric disease.

  9. [Child neurology and rehabilitation].

    PubMed

    Kumagai, K

    2000-05-01

    The history of child neurology and the changing pattern of research methods in this field are reviewed with special reference to holoprosencephaly and recent technical advances in sleep research. This is followed by a discussion on the relationship between child neurology and rehabilitation. The majority of child neurologic disorders are developmental disabilities, but acquired child neurological diseases also show chronic progressive course in many cases. Therefore, child neurologist should understand the basis of rehabilitation approach and appreciate the three classes of disabilities; subsequently, a plan needs to be incorporating medical treatment and a program of rehabilitation for the disabled children. It is important that the role of the various rehabilitation specialists (rehabilitation doctor, physiotherapist, occupational therapist, and others) are understood in relation to the work of pediatric neurologist. Finally, a brief discussion is presented on the rehabilitation approach of patients with hypoxic encephalopathy and the information of welfare equipment.

  10. Neurologic complications of cardiac tumors.

    PubMed

    Roeltgen, David; Kidwell, Chelsea S

    2014-01-01

    Cardiac tumors are an uncommon cause for neurologic disease, but if undiagnosed can be associated with devastating neurologic consequences. Primary cardiac tumors, both benign and neoplastic, and metastatic tumors occur. Primary cardiac tumors are more likely to be associated with neurologic embolic complications. Metastatic cardiac tumors are more likely to be associated with valvular distraction, arrhythmia, diminished cardiac output and indirect neurological dysfunction. Primary and metastatic cardiac tumors may result in cerebral metastatic disease. Atrial myxoma, a benign primary cardiac tumor, is the most common cardiac tumor associated with neurologic disease, and most commonly causes cerebral embolization and stroke. The use of thrombolytic therapy for these strokes is controversial. Additionally, delayed manifestations, including aneurysm formation and intracranial hemorrhage, are possible. Aneurysm formation has been described as occurring after removal of the primary tumor. The availability of noninvasive cardiac imaging has significantly helped decrease the neurologic morbidity of cardiac tumors and has led to frequent successful intervention. PMID:24365298

  11. Myiasis as a risk factor for prion diseases in humans.

    PubMed

    Lupi, O

    2006-10-01

    Prion diseases are transmissible spongiform encephalopathies of humans and animals. The oral route is clearly associated with some prion diseases, according to the dissemination of bovine spongiform encephalopathy (BSE or mad cow disease) in cattle and kuru in humans. However, other prion diseases such as scrapie (in sheep) and chronic wasting disease (CWD) (in cervids) cannot be explained in this way and are probably more associated with a pattern of horizontal transmission in both domestic and wild animals. The skin and mucous membranes are a potential target for prion infections because keratinocytes and lymphocytes are susceptible to the abnormal infective isoform of the prion protein. Iatrogenic transmission of Creutzfeldt-Jakob disease (CJD) was also recognized after corneal transplants in humans and scrapie was successfully transmitted to mice after ocular instillation of infected brain tissue, confirming that these new routes could also be important in prion infections. Some ectoparasites have been proven to harbour prion rods in laboratory experiments. Prion rods were identified in both fly larvae and pupae; adult flies are also able to express prion proteins. The most common causes of myiasis in cattle and sheep, closely related animals with previous prion infections, are Hypoderma bovis and Oestrus ovis, respectively. Both species of flies present a life cycle very different from human myiasis, as they have a long contact with neurological structures, such as spinal canal and epidural fat, which are potentially rich in prion rods. Ophthalmomyiases in humans is commonly caused by both species of fly larvae worldwide, providing almost direct contact with the central nervous system (CNS). The high expression of the prion protein on the skin and mucosa and the severity of the inflammatory response to the larvae could readily increase the efficiency of transmission of prions in both animals and humans. PMID:16987255

  12. Effects of copper metabolism on neurological functions in Wistar and Wilson's disease model rats.

    PubMed

    Fujiwara, Noriko; Iso, Hiroyuki; Kitanaka, Nobue; Kitanaka, Junichi; Eguchi, Hironobu; Ookawara, Tomomi; Ozawa, Keiichiro; Shimoda, Shigero; Yoshihara, Daisaku; Takemura, Motohiko; Suzuki, Keiichiro

    2006-10-27

    Behavioral functions of Wistar and Long-Evans Cinnamon (LEC) rats, Wilson's disease animal model, were compared by measuring the open-field, acoustic startle reflex and prepulse inhibition (PPI), and shuttle-box avoidance learning tests with or without oral supplementation with copper or D-penicillamine, copper chelator. All of the LEC rats, irrespective of the treatment, exhibited higher locomotor activity, a decreased habituation to startle response or a lower PPI, compared with Wistar rats. The copper content of all brain regions examined, except for the medulla oblongata of LEC rats, was significantly lower than those in Wistar rats. Besides, in the region of the striatum and the nucleus accumbens of the LEC rats, lower content of norepinephrine, and higher content of dopamine and serotonin were observed compared with Wistar rats. Although copper supplementation did not affect the brain copper content, it reduced the PPI in both Wistar and LEC rats. In contrast, D-penicillamine supplementation decreased both the brain copper content and locomotor activity, and enhanced the startle amplitude only in Wistar rats. These findings suggest that an imbalance in copper homeostasis affects monoamine metabolism and behavioral functions.

  13. Impaired functional default mode network in patients with mild neurological Wilson's disease.

    PubMed

    Han, Yongsheng; Cheng, Hewei; Toledo, Jon B; Wang, Xun; Li, Bo; Han, Yongzhu; Wang, Kai; Fan, Yong

    2016-09-01

    Wilson's disease (WD) is an autosomal recessive metabolic disorder characterized by cognitive, psychiatric and motor signs and symptoms that are associated with structural and pathological brain abnormalities, in addition to liver changes. However, functional brain connectivity pattern of WD patients remains largely unknown. In the present study, we investigated functional brain connectivity pattern of WD patients using resting state functional magnetic resonance imaging. Particularly, we studied default mode network (DMN) using posterior cingulate cortex (PCC) based seed functional connectivity analysis and graph theoretic functional brain network analysis tools, and investigated the relationship between the DMN's functional connectivity pattern of WD patients and their attention functions examined using the attention network test (ANT). Our results demonstrated that WD patients had altered DMN's functional connectivity and lower local and global network efficiency compared with normal controls (NCs). In addition, the functional connectivity between left inferior temporal cortex and right lateral parietal cortex was correlated with altering function, one of the attention functions, across WD and NC subjects. These findings indicated that the DMN's functional connectivity was altered in WD patients, which might be correlated with their attention dysfunction.

  14. Neurological lesions in chickens experimentally infected with virulent Newcastle disease virus isolates.

    PubMed

    Ecco, Roselene; Susta, Leonardo; Afonso, Claudio L; Miller, Patti J; Brown, Corrie

    2011-04-01

    Distribution, character, and severity of lesions were evaluated in tissues from the central nervous system of chickens inoculated with 10 different Newcastle disease virus (NDV) isolates: CA 1083, Korea 97-147, Australia (all velogenic viscerotropic), Texas GB and Turkey North Dakota (both velogenic neurotropic), Nevada cormorant, Anhinga and Roakin (all mesogenic), and B1 and QV4 (lentogenic). Tissues for the present study included archived formalin-fixed, paraffin-embedded brain (all strains) plus spinal cord (two strains). Encephalitis was observed in all velogenic viscerotropic and velogenic neurotropic strains, and in some mesogenic strains. In general, the encephalitic lesions began at 5 days post infection, with more severe lesions occurring around 10 days post infection. At this time point, especially in the grey matter of the brain, cerebellum and spinal cord, there were neuronal necrosis, neuronal phagocytosis, and clusters of cells with microglial morphology. Axonal degeneration and demyelination was also observed. Immunohistochemistry (IHC) for viral nucleoprotein confirmed the presence of virus. In the areas of encephalomyelitis, IHC for CD3 revealed that many of the inflammatory cells were T lymphocytes. IHC using an antibody for glial fibrillar acid protein showed reactive astrogliosis, which was most pronounced at the later time points. PMID:21500034

  15. Impaired functional default mode network in patients with mild neurological Wilson's disease.

    PubMed

    Han, Yongsheng; Cheng, Hewei; Toledo, Jon B; Wang, Xun; Li, Bo; Han, Yongzhu; Wang, Kai; Fan, Yong

    2016-09-01

    Wilson's disease (WD) is an autosomal recessive metabolic disorder characterized by cognitive, psychiatric and motor signs and symptoms that are associated with structural and pathological brain abnormalities, in addition to liver changes. However, functional brain connectivity pattern of WD patients remains largely unknown. In the present study, we investigated functional brain connectivity pattern of WD patients using resting state functional magnetic resonance imaging. Particularly, we studied default mode network (DMN) using posterior cingulate cortex (PCC) based seed functional connectivity analysis and graph theoretic functional brain network analysis tools, and investigated the relationship between the DMN's functional connectivity pattern of WD patients and their attention functions examined using the attention network test (ANT). Our results demonstrated that WD patients had altered DMN's functional connectivity and lower local and global network efficiency compared with normal controls (NCs). In addition, the functional connectivity between left inferior temporal cortex and right lateral parietal cortex was correlated with altering function, one of the attention functions, across WD and NC subjects. These findings indicated that the DMN's functional connectivity was altered in WD patients, which might be correlated with their attention dysfunction. PMID:27372239

  16. The human RBPome: from genes and proteins to human disease.

    PubMed

    Neelamraju, Yaseswini; Hashemikhabir, Seyedsasan; Janga, Sarath Chandra

    2015-09-01

    RNA binding proteins (RBPs) play a central role in mediating post transcriptional regulation of genes. However less is understood about them and their regulatory mechanisms. In this study, we construct a catalogue of 1344 experimentally confirmed RBPs. The domain architecture of RBPs enabled us to classify them into three groups - Classical (29%), Non-classical (19%) and unclassified (52%). A higher percentage of proteins with unclassified domains reveals the presence of various uncharacterised motifs that can potentially bind RNA. RBPs were found to be highly disordered compared to Non-RBPs (p<2.2e-16, Fisher's exact test), suggestive of a dynamic regulatory role of RBPs in cellular signalling and homeostasis. Evolutionary analysis in 62 different species showed that RBPs are highly conserved compared to Non-RBPs (p<2.2e-16, Wilcox-test), reflecting the conservation of various biological processes like mRNA splicing and ribosome biogenesis. The expression patterns of RBPs from human proteome map revealed that ~40% of them are ubiquitously expressed and ~60% are tissue-specific. RBPs were also seen to be highly associated with several neurological disorders, cancer and inflammatory diseases. Anatomical contexts like B cells, T-cells, foetal liver and foetal brain were found to be strongly enriched for RBPs, implying a prominent role of RBPs in immune responses and different developmental stages. The catalogue and meta-analysis presented here should form a foundation for furthering our understanding of RBPs and the cellular networks they control, in years to come. This article is part of a Special Issue entitled: Proteomics in India. PMID:25982388

  17. A Stochastic Multiscale Model That Explains the Segregation of Axonal Microtubules and Neurofilaments in Neurological Diseases

    PubMed Central

    Xue, Chuan; Shtylla, Blerta; Brown, Anthony

    2015-01-01

    The organization of the axonal cytoskeleton is a key determinant of the normal function of an axon, which is a long thin projection of a neuron. Under normal conditions two axonal cytoskeletal polymers, microtubules and neurofilaments, align longitudinally in axons and are interspersed in axonal cross-sections. However, in many neurotoxic and neurodegenerative disorders, microtubules and neurofilaments segregate apart from each other, with microtubules and membranous organelles clustered centrally and neurofilaments displaced to the periphery. This striking segregation precedes the abnormal and excessive neurofilament accumulation in these diseases, which in turn leads to focal axonal swellings. While neurofilament accumulation suggests an impairment of neurofilament transport along axons, the underlying mechanism of their segregation from microtubules remains poorly understood for over 30 years. To address this question, we developed a stochastic multiscale model for the cross-sectional distribution of microtubules and neurofilaments in axons. The model describes microtubules, neurofilaments and organelles as interacting particles in a 2D cross-section, and is built upon molecular processes that occur on a time scale of seconds or shorter. It incorporates the longitudinal transport of neurofilaments and organelles through this domain by allowing stochastic arrival and departure of these cargoes, and integrates the dynamic interactions of these cargoes with microtubules mediated by molecular motors. Simulations of the model demonstrate that organelles can pull nearby microtubules together, and in the absence of neurofilament transport, this mechanism gradually segregates microtubules from neurofilaments on a time scale of hours, similar to that observed in toxic neuropathies. This suggests that the microtubule-neurofilament segregation can be a consequence of the selective impairment of neurofilament transport. The model generates the experimentally testable

  18. A Stochastic Multiscale Model That Explains the Segregation of Axonal Microtubules and Neurofilaments in Neurological Diseases.

    PubMed

    Xue, Chuan; Shtylla, Blerta; Brown, Anthony

    2015-08-01

    The organization of the axonal cytoskeleton is a key determinant of the normal function of an axon, which is a long thin projection of a neuron. Under normal conditions two axonal cytoskeletal polymers, microtubules and neurofilaments, align longitudinally in axons and are interspersed in axonal cross-sections. However, in many neurotoxic and neurodegenerative disorders, microtubules and neurofilaments segregate apart from each other, with microtubules and membranous organelles clustered centrally and neurofilaments displaced to the periphery. This striking segregation precedes the abnormal and excessive neurofilament accumulation in these diseases, which in turn leads to focal axonal swellings. While neurofilament accumulation suggests an impairment of neurofilament transport along axons, the underlying mechanism of their segregation from microtubules remains poorly understood for over 30 years. To address this question, we developed a stochastic multiscale model for the cross-sectional distribution of microtubules and neurofilaments in axons. The model describes microtubules, neurofilaments and organelles as interacting particles in a 2D cross-section, and is built upon molecular processes that occur on a time scale of seconds or shorter. It incorporates the longitudinal transport of neurofilaments and organelles through this domain by allowing stochastic arrival and departure of these cargoes, and integrates the dynamic interactions of these cargoes with microtubules mediated by molecular motors. Simulations of the model demonstrate that organelles can pull nearby microtubules together, and in the absence of neurofilament transport, this mechanism gradually segregates microtubules from neurofilaments on a time scale of hours, similar to that observed in toxic neuropathies. This suggests that the microtubule-neurofilament segregation can be a consequence of the selective impairment of neurofilament transport. The model generates the experimentally testable

  19. The molecular basis of memantine action in Alzheimer's disease and other neurologic disorders: low-affinity, uncompetitive antagonism.

    PubMed

    Lipton, Stuart A

    2005-04-01

    In western countries, Alzheimer's disease (AD) is the most common form of dementia. In fact, if left uncurbed, the economic cost of caring for AD patients could consume the entire gross national product of the USA by the middle of this century. Until recently, the only available drugs for this condition were cholinergic treatments, which symptomatically enhance cognitive state to some degree, but they were not neuroprotective. In fact, many potential neuroprotective drugs tested in clinical trials failed because they were poorly tolerated. However, after our discovery of its clinically-tolerated mechanism of action, one neuroprotective drug, memantine, was recently approved by the European Union and the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer's disease. Recent phase 3 clinical trials have shown that memantine is effective in the treatment of both mild and moderate-to-severe Alzheimer's disease and possibly vascular dementia (multi-infarct dementia). Here we review the molecular mechanism of memantine's action and also the basis for the drug's use in these neurological diseases, which are mediated at least in part by excitotoxicity. Excitotoxicity is defined as excessive exposure to the neurotransmitter glutamate or overstimulation of its membrane receptors, leading to neuronal injury or death. Excitotoxic neuronal cell death is mediated in part by overactivation of N-methyl-d-aspartate (NMDA)-type glutamate receptors, which results in excessive Ca2+ influx through the receptor's associated ion channel. Physiological NMDA receptor activity, however, is also essential for normal neuronal function. This means that potential neuroprotective agents that block virtually all NMDA receptor activity will very likely have unacceptable clinical side effects. For this reason many previous NMDA receptor antagonists have disappointingly failed advanced clinical trials for a number of neurodegenerative disorders. In contrast, studies in our

  20. Human prion diseases: surgical lessons learned from iatrogenic prion transmission.

    PubMed

    Bonda, David J; Manjila, Sunil; Mehndiratta, Prachi; Khan, Fahd; Miller, Benjamin R; Onwuzulike, Kaine; Puoti, Gianfranco; Cohen, Mark L; Schonberger, Lawrence B; Cali, Ignazio

    2016-07-01

    The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood "infectious protein" has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial transmission

  1. [Neurological diseases and SPECT--analysis using easy Z-score imaging system (eZIS)].

    PubMed

    Matsuda, Hiroshi

    2007-05-01

    We developed a method for automated diagnosis of brain perfusion SPECT and designated this method as an easy Z-score imaging system (eZIS). In this software program, voxel-by-voxel Z-score analysis after voxel normalization to global mean or cerebellar values; Z-score = ( [control mean] - [individual value] )/ (control SD) is performed. These Z-score maps are displayed by overlay on tomographic sections and by projection with averaged Z-score of 14mm thickness to surface rendering of the anatomically standardized MRI template. Anatomical standardization of SPECT images into a stereotactic space is performed using statistical parametric mapping (SPM) 2. This program has an advantage of capability of incorporation of SPM results into automated analysis of Z-score values as a volume of interest (VOI). A specific VOI can be determined by group comparison of SPECT images for patients with a neuropsychiatric disease with those for healthy volunteers using SPM. Even if a center can construct a normal database with good quality comprising a large number of healthy volunteers, other centers have not been able to use this normal database because of differences between the used gamma cameras, collimators and physical correction algorithms. Since SPECT exhibits greater variations in image quality among different centers than PET, conversion of SPECT images may be necessary for sharing a normal database. In this eZIS software, we incorporated a newly developed program for making it possible to share a normal database in SPECT studies. A Hoffman 3-dimensional brain phantom experiment was conducted to determine systematic differences between SPECT scanners. SPECT images for the brain phantom were obtained using two different scanners. Dividing these two phantom images after anatomical standardization by SPM created a 3-dimensional conversion map. The use of a conversion map obtained from SPECT images of the same phantom provided very similar SPECT data despite extreme differences

  2. Endosomal phosphoinositides and human diseases.

    PubMed

    Nicot, Anne-Sophie; Laporte, Jocelyn

    2008-08-01

    Phosphoinositides (PIs) are lipid second messengers implicated in signal transduction and membrane trafficking. Seven distinct PIs can be synthesized by phosphorylation of the inositol ring of phosphatidylinositol (PtdIns), and their metabolism is accurately regulated by PI kinases and phosphatases. Two of the PIs, PtdIns3P and PtdIns(3,5)P(2), are present on intracellular endosomal compartments, and several studies suggest that they have a role in membrane remodeling and trafficking. We refer to them as 'endosomal PIs'. An increasing number of human genetic diseases including myopathy and neuropathies are associated to mutations in enzymes regulating the turnover of these endosomal PIs. The PtdIns3P and PtdIns(3,5)P(2) 3-phosphatase myotubularin gene is mutated in X-linked centronuclear myopathy, whereas its homologs MTMR2 and MTMR13 and the PtdIns(3,5)P(2) 5-phosphatase SAC3/FIG4 are implicated in Charcot-Marie-Tooth peripheral neuropathies. Mutations in the gene encoding the PtdIns3P 5-kinase PIP5K3/PIKfyve have been found in patients affected with François-Neetens fleck corneal dystrophy. This review presents the roles of the endosomal PIs and their regulators and proposes defects of membrane remodeling as a common pathological mechanism for the corresponding diseases.

  3. Tight junctions and human diseases.

    PubMed

    Sawada, Norimasa; Murata, Masaki; Kikuchi, Keisuke; Osanai, Makoto; Tobioka, Hirotoshi; Kojima, Takashi; Chiba, Hideki

    2003-09-01

    Tight junctions are intercellular junctions adjacent to the apical end of the lateral membrane surface. They have two functions, the barrier (or gate) function and the fence function. The barrier function of tight junctions regulates the passage of ions, water, and various macromolecules, even of cancer cells, through paracellular spaces. The barrier function is thus relevant to edema, jaundice, diarrhea, and blood-borne metastasis. On the other hand, the fence function maintains cell polarity. In other words, tight junctions work as a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membrane. This function is deeply involved in cancer cell biology, in terms of loss of cell polarity. Of the proteins comprising tight junctions, integral membrane proteins occludin, claudins, and JAMs have been recently discovered. Of these molecules, claudins are exclusively responsible for the formation of tight-junction strands and are connected with the actin cytoskeleton mediated by ZO-1. Thus, both functions of tight junctions are dependent on the integrity of the actin cytoskeleton as well as ATP. Mutations in the claudin14 and the claudin16 genes result in hereditary deafness and hereditary hypomagnesemia, respectively. Some pathogenic bacteria and viruses target and affect the tight-junction function, leading to diseases. In this review, the relationship between tight junctions and human diseases is summarized.

  4. The Effect of tDCS on Cognition and Neurologic Recovery of Rats with Alzheimer’s Disease

    PubMed Central

    Yu, Seong Hun; Park, Seong Doo; Sim, Ki Chel

    2014-01-01

    [Purpose] This study examined the effect of the application of transcranial direct current stimulation (tDCS) on neurologic recovery and cognitive function of rats with Alzheimer-like dementia induced by scopolamine injections. [Subjects] To create a cognition dysfunction model, intraperitoneal injection of scopolamine was given to Sprague-Dawley rats that subsequently received tDCS for 4 weeks. [Methods] Changes in motor behavior were evaluated by conducting an open field test. Acetylcholine content in the cerebral cortex and hippocampus was examined for a biochemical assessment. [Results] With respect to changes in motor behavior, group II showed the most meaningful difference after scopolamine injection, followed by group III. In the biochemical assessment, the results of the examination of acetylcholine content in the tissue of the cerebral cortex and the hippocampus on the 14th and 28th days, respectively, showed the most significant increase in group II, followed by group III. [Conclusion] The above findings confirm that tDCS application after the onset of cognitive dysfunction caused by Alzheimer’s disease leads to a positive effect on motor behavior and biochemical changes, and this effect is maintained over a specific period of time. PMID:24648641

  5. Demyelinizing neurological disease after treatment with tumor necrosis factor alpha-inhibiting agents in a rheumatological outpatient clinic: description of six cases.

    PubMed

    Theibich, Ali; Dreyer, Lene; Magyari, Melinda; Locht, Henning

    2014-05-01

    Biological treatment with inhibitors of the pro-inflammatory cytokine TNF-alpha has dramatically improved the disease course of several chronic rheumatologic conditions. Adverse events (AEs) are primarily infections and hypersensitivity reactions. Demyelinizing neurological symptoms resembling multiple sclerosis (MS) have been described as a rare AE. During about 10-year use of anti TNF-alpha, the Danish Medicines Agency has recorded eight cases of MS like AEs. The objective of this study was to estimate the incidence of demyelinizing AEs both in the central and peripheral nervous system after treatment with anti TNF-alpha in a cohort of patients from a large rheumatologic outpatient clinic in Copenhagen. In a 4-year period from January 2008 to December 2011, approximately 550 patients annually were undergoing treatment with anti TNF-alpha inhibitors in our department. We collected data on all patients who developed neurological symptoms during this time period. We found six patients with signs of demyelinizing neurological disorders: four resembling MS, one MS-like condition, and one multifocal motor neuropathy. During a relatively short time period, we found a remarkably high number of neurological demyelinizing AEs probably linked to anti TNF-alpha treatment. The AEs were not associated with a single anti TNF-alpha agent and were thus presumably a class effect. The data presented suggest that neurological AEs may be underreported. We advocate that physicians handling patients during treatment with TNF inhibitors are aware of this potentially serious AE and report these events to the proper medical authorities.

  6. Adult neurology training during child neurology residency.

    PubMed

    Schor, Nina F

    2012-08-21

    As it is currently configured, completion of child neurology residency requires performance of 12 months of training in adult neurology. Exploration of whether or not this duration of training in adult neurology is appropriate for what child neurology is today must take into account the initial reasons for this requirement and the goals of adult neurology training during child neurology residency.

  7. Progress in Pediatrics in 2012: choices in allergy, endocrinology, gastroenterology, hematology, infectious diseases, neurology, nutrition and respiratory tract illnesses.

    PubMed

    Caffarelli, Carlo; Santamaria, Francesca; Vottero, Alessandra; Bernasconi, Sergio

    2013-01-01

    In this review, we summarize the progresses in allergy, endocrinology, gastroenterology, hematology, infectious diseases, neurology, nutrition and respiratory tract illnesses that have been published in The Italian Journal of Pediatrics in 2012. The induction of Treg activity by probiotics might be effective for promoting tolerance towards food allergens. Nasal cytology is useful in patients with rhinitis for diagnosing chronic non-allergic non-infectious diseases. Atopic eczema is associated both with an aberrant skin matrix and impaired systemic immune response. Therefore, isolated topical treatment may have suboptimal effect. Diagnostic work-up of exercise-induced anaphylaxis, including exercise challenge test, is necessary to reach a diagnosis. Studies may support a role for nutrition on prevention of asthma and cardiovascular diseases. Clinicians need to early identify adolescent menstrual abnormalities to minimize sequelae, and to promote health information. In Multiple Endocrine Neoplasia type 2B investigations include acetylcholinesterase study of rectal mucosa followed by the molecular analysis of RET mutation. Low adherence to gluten-free diet and osteopenia are common problems in children with diabetes mellitus type 1 and celiac disease. In infantile colic, laboratory tests are usually unnecessary and the treatment is based on reassurance. Prevalence of obesity and stunting is elucidated by several studies. Evidences are growing that dietetic measures are needed to prevent obesity in children with acute leukemia. Treatment studies for infectious diseases show promise for probiotics along with standard triple therapy in children with Helicobacter pilori infection, while zinc has no effect on pneumonia. Educational programs about the proper management of the febrile child are warranted. A new hour-specific total serum bilirubin nomogram has been shown to be able to predict newborns without hyperbilirubinemia after 48 to 72 hours of life. Newborns with

  8. Progress in Pediatrics in 2012: choices in allergy, endocrinology, gastroenterology, hematology, infectious diseases, neurology, nutrition and respiratory tract illnesses.

    PubMed

    Caffarelli, Carlo; Santamaria, Francesca; Vottero, Alessandra; Bernasconi, Sergio

    2013-05-08

    In this review, we summarize the progresses in allergy, endocrinology, gastroenterology, hematology, infectious diseases, neurology, nutrition and respiratory tract illnesses that have been published in The Italian Journal of Pediatrics in 2012. The induction of Treg activity by probiotics might be effective for promoting tolerance towards food allergens. Nasal cytology is useful in patients with rhinitis for diagnosing chronic non-allergic non-infectious diseases. Atopic eczema is associated both with an aberrant skin matrix and impaired systemic immune response. Therefore, isolated topical treatment may have suboptimal effect. Diagnostic work-up of exercise-induced anaphylaxis, including exercise challenge test, is necessary to reach a diagnosis. Studies may support a role for nutrition on prevention of asthma and cardiovascular diseases. Clinicians need to early identify adolescent menstrual abnormalities to minimize sequelae, and to promote health information. In Multiple Endocrine Neoplasia type 2B investigations include acetylcholinesterase study of rectal mucosa followed by the molecular analysis of RET mutation. Low adherence to gluten-free diet and osteopenia are common problems in children with diabetes mellitus type 1 and celiac disease. In infantile colic, laboratory tests are usually unnecessary and the treatment is based on reassurance. Prevalence of obesity and stunting is elucidated by several studies. Evidences are growing that dietetic measures are needed to prevent obesity in children with acute leukemia. Treatment studies for infectious diseases show promise for probiotics along with standard triple therapy in children with Helicobacter pilori infection, while zinc has no effect on pneumonia. Educational programs about the proper management of the febrile child are warranted. A new hour-specific total serum bilirubin nomogram has been shown to be able to predict newborns without hyperbilirubinemia after 48 to 72 hours of life. Newborns with

  9. Leading the way: finding genes for neurologic disease in dogs using genome-wide mRNA sequencing.

    PubMed

    Ostrander, Elaine A; Beale, Holly C

    2012-07-10

    Because of dogs' unique population structure, human-like disease biology, and advantageous genomic features, the canine system has risen dramatically in popularity as a tool for discovering disease alleles that have been difficult to find by studying human families or populations. To date, disease studies in dogs have primarily employed either linkage analysis, leveraging the typically large family size, or genome-wide association, which requires only modest-sized case and control groups in dogs. Both have been successful but, like most techniques, each requires a specific combination of time and money, and there are inherent problems associated with each. Here we review the first report of mRNA-Seq in the dog, a study that provides insights into the potential value of applying high-throughput sequencing to the study of genetic diseases in dogs. Forman and colleagues apply high-throughput sequencing to a single case of canine neonatal cerebellar cortical degeneration. This implementation of whole genome mRNA sequencing, the first reported in dog, is additionally unusual due to the analysis: the data was used not to examine transcript levels or annotate genes, but as a form of target capture that revealed the sequence of transcripts of genes associated with ataxia in humans. This approach entails risks. It would fail if, for example, the relevant transcripts were not sufficiently expressed for genotyping or were not associated with ataxia in humans. But here it pays off handsomely, identifying a single frameshift mutation that segregates with the disease. This work sets the stage for similar studies that take advantage of recent advances in genomics while exploiting the historical background of dog breeds to identify disease-causing mutations.

  10. Mapping Gene Associations in Human Mitochondria using Clinical Disease Phenotypes

    PubMed Central

    Scharfe, Curt; Lu, Henry Horng-Shing; Neuenburg, Jutta K.; Allen, Edward A.; Li, Guan-Cheng; Klopstock, Thomas; Cowan, Tina M.; Enns, Gregory M.; Davis, Ronald W.

    2009-01-01

    Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects within the

  11. Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress

    PubMed Central

    ZHANG, Xiao-Liang; PANG, Wei; HU, Xin-Tian; LI, Jia-Li; YAO, Yong-Gang; ZHENG, Yong-Tang

    2014-01-01

    Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China’s growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China’s life sciences and pharmaceutical industry, and enhance China’s position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China. PMID:25465081

  12. [Epigenome: what we learned from Rett syndrome, a neurological disease caused by mutation of a methyl-CpG binding protein].

    PubMed

    Kubota, Takeo

    2013-01-01

    Epigenome is defined as DNA and histone modification-dependent gene regulation system. Abnormalities in this system are known to cause various neuro-developmental diseases. We recently reported that neurological symptoms of Rett syndrome, which is an autistic disorder caused by mutations in methyl-CpG binding protein 2 (MeCP2), was associated with failure of epigenomic gene regulation in neuronal cells, and that clinical differences in the identical twins with Rett syndrome in the differences in DNA methylation in neuronal genes, but not caused by DNA sequence differences. Since central nervus system requires precise gene regulation, neurological diseases including Alzheimer and Parkinson diseases may be caused by acquired DNA modification (epigenomic) changes that results in aberrant gene regulation as well as DNA sequence changes congenitally occurred (mutation). PMID:24291980

  13. Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders

    PubMed Central

    Carter, C. J.

    2013-01-01

    Toxoplasma gondii is not only implicated in schizophrenia and related disorders, but also in Alzheimer's or Parkinson's disease, cancer, cardiac myopathies, and autoimmune disorders. During its life cycle, the pathogen interacts with ~3000 host genes or proteins. Susceptibility genes for multiple sclerosis, Alzheimer's disease, schizophrenia, bipolar disorder, depression, childhood obesity, Parkinson's disease, attention deficit hyperactivity disorder (P  from  8.01E − 05  (ADHD)  to  1.22E − 71) (multiple sclerosis), and autism (P = 0.013), but not anorexia or chronic fatigue are highly enriched in the human arm of this interactome and 18 (ADHD) to 33% (MS) of the susceptibility genes relate to it. The signalling pathways involved in the susceptibility gene/interactome overlaps are relatively specific and relevant to each disease suggesting a means whereby susceptibility genes could orient the attentions of a single pathogen towards disruption of the specific pathways that together contribute (positively or negatively) to the endophenotypes of different diseases. Conditional protein knockdown, orchestrated by T. gondii proteins or antibodies binding to those of the host (pathogen derived autoimmunity) and metabolite exchange, may contribute to this disruption. Susceptibility genes may thus be related to the causes and influencers of disease, rather than (and as well as) to the disease itself. PMID:23533776

  14. Improved Neurological Outcome by Intramuscular Injection of Human Amniotic Fluid Derived Stem Cells in a Muscle Denervation Model

    PubMed Central

    Su, Hong-Lin; Sheu, Meei-Ling; Lu, Zong-Han; Chiang, Chien-Yi; Yang, Dar-Yu; Sheehan, Jason; Pan, Hung-Chuan

    2015-01-01

    Purpose The skeletal muscle develops various degrees of atrophy and metabolic dysfunction following nerve injury. Neurotrophic factors are essential for muscle regeneration. Human amniotic fluid derived stem cells (AFS) have the potential to secrete various neurotrophic factors necessary for nerve regeneration. In the present study, we assess the outcome of neurological function by intramuscular injection of AFS in a muscle denervation and nerve anastomosis model. Materials and Methods Seventy two Sprague-Dawley rats weighing 200–250 gm were enrolled in this study. Muscle denervation model was conducted by transverse resection of a sciatic nerve with the proximal end sutured into the gluteal muscle. The nerve anastomosis model was performed by transverse resection of the sciatic nerve followed by four stitches reconnection. These animals were allocated to three groups: control, electrical muscle stimulation, and AFS groups. Results NT-3 (Neurotrophin 3), BDNF (Brain derived neurotrophic factor), CNTF (Ciliary neurotrophic factor), and GDNF (Glia cell line derived neurotrophic factor) were highly expressed in AFS cells and supernatant of culture medium. Intra-muscular injection of AFS exerted significant expression of several neurotrophic factors over the distal end of nerve and denervated muscle. AFS caused high expression of Bcl-2 in denervated muscle with a reciprocal decrease of Bad and Bax. AFS preserved the muscle morphology with high expression of desmin and acetylcholine receptors. Up to two months, AFS produced significant improvement in electrophysiological study and neurological functions such as SFI (sciatic nerve function index) and Catwalk gait analysis. There was also significant preservation of the number of anterior horn cells and increased nerve myelination as well as muscle morphology. Conclusion Intramuscular injection of AFS can protect muscle apoptosis and likely does so through the secretion of various neurotrophic factors. This protection

  15. [The deterministic concept of human diseases].

    PubMed

    Petlenko, V P; Strukov, A I; Khmel'nitskiĭ, O K

    1984-01-01

    Human disease is a complex systemic event, the theoretical analysis of which requires application of the methodological appratus of investigation. As such, the authors used the concept of Marxist-Leninist determinism. The latter is a system of universal interconnections and causative dependence of natural events, society, and human diseases in particular. Analysis of human diseases from the position of the Marxist-Leninist theory of determinism is one of the basic problems of the theory of pathology. A logical analysis of evolutionary, systemic, morphological and causative determinism is given which characterizes on the whole human diseases. PMID:6391430

  16. Neurological complications of transplantation.

    PubMed

    Pustavoitau, Aliaksei; Bhardwaj, Anish; Stevens, Robert

    2011-01-01

    Recipients of solid organ or hematopoietic cell transplants are at risk of life-threatening neurological disorders including encephalopathy, seizures, infections and tumors of the central nervous system, stroke, central pontine myelinolysis, and neuromuscular disorders-often requiring admission to, or occurring in, the intensive care unit (ICU). Many of these complications are linked directly or indirectly to immunosuppressive therapy. However, neurological disorders may also result from graft versus host disease, or be an expression of the underlying disease which prompted transplantation, as well as injury induced during radiation, chemotherapy, surgery, and ICU stay. In rare cases, neuroinfectious pathogens may be transmitted with the transplanted tissue or organ. Diagnosis may be a challenge because clinical symptoms and findings on neuroimaging lack specificity, and a biological specimen or tissue diagnosis is often needed for definitive diagnosis. Management is centered on preventing further neurological injury, etiology-targeted therapy, and balancing the benefits and toxicities of specific immunosuppressive agents. PMID:21764765

  17. N-methyl-D-aspartate receptor antibody-mediated neurological disease: results of a UK-based surveillance study in children

    PubMed Central

    Wright, Sukhvir; Hacohen, Yael; Jacobson, Leslie; Agrawal, Shakti; Gupta, Rajat; Philip, Sunny; Smith, Martin; Lim, Ming; Wassmer, Evangeline; Vincent, Angela

    2015-01-01

    Objective N-methyl-D-aspartate receptor antibody (NMDAR-Ab) encephalitis is a well-recognised clinico-immunological syndrome that presents with neuropsychiatric symptoms cognitive decline, movement disorder and seizures. This study reports the clinical features, management and neurological outcomes of paediatric NMDAR-Ab-mediated neurological disease in the UK. Design A prospective surveillance study. Children with NMDAR-Ab-mediated neurological diseases were voluntarily reported to the British Neurological Surveillance Unit (BPNSU) from November 2010 to December 2011. Initial and follow-up questionnaires were sent out to physicians. Results Thirty-one children fulfilled the criteria for the study. Eight presented during the study period giving an incidence of 0.85 per million children per year (95% CI 0.64 to 1.06); 23 cases were historical. Behavioural change and neuropsychiatric features were present in 90% of patients, and seizures and movement disorders both in 67%. Typical NMDAR-Ab encephalitis was reported in 24 children and partial phenotype without encephalopathy in seven, including predominantly psychiatric (four) and movement disorder (three). All patients received steroids, 22 (71%) received intravenous immunoglobulin, 9 (29%) received plasma exchange,and 10 (32%) received second-line immunotherapy. Of the 23 patients who were diagnosed early, 18 (78%) made a full recovery compared with only 1 of 8 (13%) of the late diagnosed patients (p=0.002, Fisher's exact test). Seven patients relapsed, with four needing additional second-line immunotherapy. Conclusions Paediatric NMDAR-Ab-mediated neurological disease appears to be similar to adult NMDAR-Ab encephalitis, but some presented with a partial phenotype. Early treatment was associated with a quick and often full recovery. PMID:25637141

  18. Therapeutic strategy of erythropoietin in neurological disorders.

    PubMed

    Liu, Xiang-Bao; Wang, Jiang-An; Yu, Shan Ping; Keogh, Christine L; Wei, Ling

    2008-06-01

    Erythropoietin (EPO) was first identified as a hematopoietic cytokine that stimulates proliferation and differentiation of erythroid progenitor cells and was approved by the Food and Drug Administration as a treatment for chronic renal disease patients with anemia. In neural tissues, EPO is working via EPO receptors and induces non-hematopoietic effects. Recent studies have demonstrated that EPO exerts therapeutic potentials on neurological disorders such as ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury, and Parkinson's disease. EPO treatment has been shown to reduce the ischemic infarct and hemorrhage volume, decrease neuronal death including apoptosis, and improve survival rates in animal models. The mechanism of EPO action in neurological disorders involves neuroprotection and promotion of neurogenesis and angiogenesis. Clinical trials of EPO treatments in neurological diseases have accumulated positive results. In stroke patients, EPO treatment may reduce infarct volume and improve functional outcomes. EPO administration has proven safe in animal studies and adult human patients, although safety and efficacy data in neonates and infants are incomplete and long-term multi-center patient evaluations are necessary. Available information suggests that EPO is a promising therapeutic drug for the treatment of neurological diseases.

  19. Occupational neurology.

    PubMed

    Feldman, R G

    1987-01-01

    The nervous system is vulnerable to the effects of certain chemicals and physical conditions found in the work environment. The activities of an occupational neurologist focus on the evaluation of patients with neurological disorders caused by occupational or environmental conditions. When one is making a differential diagnosis in patients with neurological disorders, the possibility of toxic exposure or encounters with physical factors in the workplace must not be overlooked. Central to an accurate clinical diagnosis is the patient's history. A diagnosis of an occupational or environmental neurological problem requires a careful assessment of the clinical abnormalities and confirmation of these disabilities by objective tests such as nerve conduction velocity, evoked potentials, electroencephalogram, neuropsychological batteries, or nerve biopsy. On the basis of information about hazards in the workplace, safety standards and environmental and biological monitoring can be implemented in the workplace to reduce the risks of undue injury. Clinical manifestations of headache, memory disturbance, and peripheral neuropathy are commonly encountered presentations of the effects of occupational hazards. Physicians in everyday clinical practice must be aware of the signs and symptoms associated with exposure to possible neurotoxins and work methods. Occupational and environmental circumstances must be explored when evaluating patients with neurologic disorders.

  20. A Neurological Enigma: The Inborn Numerical Competence of Humans and Animals

    NASA Astrophysics Data System (ADS)

    Gross, Hans J.

    2012-03-01

    "Subitizing" means our ability to recognize and memorize object numbers precisely under conditions where counting is impossible. This is an inborn archaic process which was named after the Latin "subito" = suddenly, immediately, indicating that the objects in question are presented to test persons only for the fraction of a second in order to prevent counting. Sequential counting, however, is an outstanding cultural achievement of mankind and means to count "1, 2, 3, 4, 5, 6, 7, 8 ..." without a limit. In contrast to inborn "subitizing", counting has to be trained, beginning in our early childhood with the help of our fingers. For humans we know since 140 years that we can "subitize" only up to 4 objects correctly and that mistakes occur from 5 objects on. Similar results have been obtained for a number of non-human vertebrates from salamanders to pigeons and dolphins. To our surprise, we have detected this inborn numerical competence for the first time in case of an invertebrate, the honeybee which recognizes and memorizes 3 to 4 objects under rigorous test conditions. This common ability of humans and honeybees to "subitize" up to 4 objects correctly and the miraculous but rare ability of persons with Savant syndrome to "subitize" more than hundred objects precisely raises a number of intriguing questions concerning the evolution and the significance of this biological enigma.

  1. Rabbit Models for Studying Human Infectious Diseases

    PubMed Central

    Peng, Xuwen; Knouse, John A; Hernon, Krista M

    2015-01-01

    Using an appropriate animal model is crucial for mimicking human disease conditions, and various facets including genetics, anatomy, and pathophysiology should be considered before selecting a model. Rabbits (Oryctolagus cuniculus) are well known for their wide use in production of antibodies, eye research, atherosclerosis and other cardiovascular diseases. However, a systematic description of the rabbit as primary experimental models for the study of various human infectious diseases is unavailable. This review focuses on the human infectious diseases for which rabbits are considered a classic or highly appropriate model, including AIDS (caused by HIV1), adult T-cell leukemia–lymphoma (human T-lymphotropic virus type 1), papilloma or carcinoma (human papillomavirus) , herpetic stromal keratitis (herpes simplex virus type 1), tuberculosis (Mycobacterium tuberculosis), and syphilis (Treponema pallidum). In addition, particular aspects of the husbandry and care of rabbits used in studies of human infectious diseases are described. PMID:26678367

  2. Rabbit Models for Studying Human Infectious Diseases.

    PubMed

    Peng, Xuwen; Knouse, John A; Hernon, Krista M

    2015-12-01

    Using an appropriate animal model is crucial for mimicking human disease conditions, and various facets including genetics, anatomy, and pathophysiology should be considered before selecting a model. Rabbits (Oryctolagus cuniculus) are well known for their wide use in production of antibodies, eye research, atherosclerosis and other cardiovascular diseases. However, a systematic description of the rabbit as primary experimental models for the study of various human infectious diseases is unavailable. This review focuses on the human infectious diseases for which rabbits are considered a classic or highly appropriate model, including AIDS (caused by HIV1), adult T-cell leukemia-lymphoma (human T-lymphotropic virus type 1), papilloma or carcinoma (human papillomavirus) , herpetic stromal keratitis (herpes simplex virus type 1), tuberculosis (Mycobacterium tuberculosis), and syphilis (Treponema pallidum). In addition, particular aspects of the husbandry and care of rabbits used in studies of human infectious diseases are described. PMID:26678367

  3. Neurological manifestations of filarial infections.

    PubMed

    Bhalla, Devender; Dumas, Michel; Preux, Pierre-Marie

    2013-01-01

    Filarial infections cause a huge public health burden wherever they are endemic. These filaria may locate anywhere in the human body. Their manifestations and pathogenic mechanisms, except the most common ones, are rarely investigated systematically. Their neurological manifestations, however, are being increasingly recognized particularly with onchocerciasis or Loa loa infections, Wuchereria bancrofti, or Mansonella perstans. The risk of developing these manifestations may also increase in cases that harbor multiple filariasis or coinfections, for instance as with Plasmodium. The microfilaria of Onchocerca and Loa loa are seen in cerebrospinal fluid. The pathogenesis of neurological manifestations of these infections is complex; however, pathogenic reactions may be caused by mechanical disruption, e.g., degeneration often followed by granulomas, causing fibrosis or mass effects on other tissues, vascular lesions, e.g., vascular block of cerebral vessels, or disordered inflammatory responses resulting in meningitis, encephalitis or localized inflammatory responses. The chances of having neurological manifestations may also depend upon the frequency and"heaviness"of infection over a lifetime. Hence, this type of infection should no longer be considered a disease of the commonly affected areas but one that may produce systemic effects or other manifestations, and these should be considered in populations where they are endemic. PMID:23829914

  4. [Diagnosis of Alzheimer's disease in Brazil: cognitive and functional evaluation. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology].

    PubMed

    Nitrini, Ricardo; Caramelli, Paulo; Bottino, Cássio Machado de Campos; Damasceno, Benito Pereira; Brucki, Sonia Maria Dozzi; Anghinah, Renato

    2005-09-01

    The educational and cultural heterogeneity of the Brazilian population leads to peculiar characteristics regarding the diagnosis of Alzheimer's disease (AD). This consensus had the objective of recommending evidence-based guidelines for the clinical diagnosis of AD in Brazil. Studies on the diagnosis of AD published in Brazil were systematically evaluated in a thorough research of PUBMED and LILACS databases. For global cognitive evaluation, the Mini-Mental State Examination was recommended; for memory evaluation: delayed recall subtest of CERAD or of objects presented as drawings; attention: trail-making or digit-span; language: Boston naming, naming test from ADAS-Cog or NEUROPSI; executive functions: verbal fluency or clock-drawing; conceptualization and abstraction: similarities from CAMDEX or NEUROPSI; construction: drawings from CERAD. For functional evaluation, IQCODE, or Pfeffer Questionnaire or Bayer Scale for Activities of Daily Living was recommended. The panel concluded that the combined use of cognitive and functional evaluation based on interview with informant is recommended. PMID:16172733

  5. [Diagnosis of Alzheimer's disease in Brazil: cognitive and functional evaluation. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology].

    PubMed

    Nitrini, Ricardo; Caramelli, Paulo; Bottino, Cássio Machado de Campos; Damasceno, Benito Pereira; Brucki, Sonia Maria Dozzi; Anghinah, Renato

    2005-09-01

    The educational and cultural heterogeneity of the Brazilian population leads to peculiar characteristics regarding the diagnosis of Alzheimer's disease (AD). This consensus had the objective of recommending evidence-based guidelines for the clinical diagnosis of AD in Brazil. Studies on the diagnosis of AD published in Brazil were systematically evaluated in a thorough research of PUBMED and LILACS databases. For global cognitive evaluation, the Mini-Mental State Examination was recommended; for memory evaluation: delayed recall subtest of CERAD or of objects presented as drawings; attention: trail-making or digit-span; language: Boston naming, naming test from ADAS-Cog or NEUROPSI; executive functions: verbal fluency or clock-drawing; conceptualization and abstraction: similarities from CAMDEX or NEUROPSI; construction: drawings from CERAD. For functional evaluation, IQCODE, or Pfeffer Questionnaire or Bayer Scale for Activities of Daily Living was recommended. The panel concluded that the combined use of cognitive and functional evaluation based on interview with informant is recommended.

  6. Fasciculations in human hereditary disease.

    PubMed

    Finsterer, Josef; Aliyev, Rahim

    2015-06-01

    Fasciculations are a manifestation of peripheral nerve hyperexcitability in addition to myokymia, neuromyotonia, cramps, or tetany. Fasciculations occur in hereditary and non-hereditary diseases. Among the hereditary diseases, fasciculations are most frequently reported in familial amyotrophic lateral sclerosis (FALS), and spinal muscular atrophy (SMA). Among the non-hereditary diseases, fasciculations occur most frequently in peripheral nerve hyperexcitability syndromes (Isaac's syndrome, voltage-gated potassium channelopathy, cramp fasciculation syndrome, Morvan syndrome). If the cause of fasciculations remains unknown, they are called benign. Systematically reviewing the literature about fasciculations in hereditary disease shows that fasciculations can be a phenotypic feature in bulbospinal muscular atrophy (BSMA), GM2-gangliosidosis, triple-A syndrome, or hereditary neuropathy. Additionally, fasciculations have been reported in familial amyloidosis, spinocerebellar ataxias, Huntington's disease, Rett syndrome, central nervous system disease due to L1-cell adhesion molecule (L1CAM) mutations, Fabry's disease, or Gerstmann-Sträussler disease. Rarely, fasciculations may be a phenotypic feature in patients with mitochondrial disorders or other myopathies. Fasciculations are part of the phenotype in much more genetic disorders than commonly assumed. Fasciculations not only occur in motor neuron disease, but also in hereditary neuropathy, spinocerebellar ataxia, GM2-gangliosidosis, Huntington's disease, Rett syndrome, Fabry's disease, Gerstmann-Sträussler disease, mitochondrial disorders, or muscular dystrophies. PMID:25073774

  7. [Neurological rehabilitation].

    PubMed

    Hömberg, V

    2010-10-01

    This article describes state of the art concepts of neurological rehabilitation in Germany. In parallel to enormous growth of knowledge in the neurosciences also neurological rehabilitation has made significant progress. The increasing use of concepts of evidence based medicine and an early translation of knowledge from the neurosciences into clinical rehabilitation practice contribute to therapeutic advances. It is now widely accepted, that rehabilitation should start early and should be organized in a multidisciplinary professional team. Therapeutic procedures selected should be evidence based and have to be modified to find custom tailored solutions for individual patients. General rules derived from neuroscientific knowledge have been shown to be useful to design new therapeutic techniques. Neuromodulatory stimulation and special pharmacological treatments provide further options for enhancing results of rehabilitation.

  8. [Vitamin D and neurology].

    PubMed

    Thouvenot, Éric; Camu, William

    2013-10-01

    Vitamin D deficiency is associated with a higher risk of multiple sclerosis and also with a higher relapse rate as well as a higher number of MRI lesions. Elders with vitamin D deficiency have worse cognitive performance. Vitamin D deficiency is a risk factor for developing Alzheimer's disease. Ischemic stroke are more frequent and more severe in patients with low vitamin D levels. Carotid atherosclerosis is more frequent and more severe in patients with vitamin D deficiency. Vitamin D deficiency is associated with a higher risk and worse prognosis of Parkinson's disease. In the different neurological disorders discussed herein, gene polymorphisms that could alter vitamin D metabolism are also associated with a higher incidence or a worse disease prognosis. Despite the links between vitamin D deficiency and the risks of developing neurological disorders, there is, to date, no proof that supplementation could alter the course of these diseases.

  9. Structural Variation of Alu Element and Human Disease

    PubMed Central

    Kim, Songmi; Cho, Chun-Sung; Han, Kyudong

    2016-01-01

    Transposable elements are one of major sources to cause genomic instability through various mechanisms including de novo insertion, insertion-mediated genomic deletion, and recombination-associated genomic deletion. Among them is Alu element which is the most abundant element, composing ~10% of the human genome. The element emerged in the primate genome 65 million years ago and has since propagated successfully in the human and non-human primate genomes. Alu element is a non-autonomous retrotransposon and therefore retrotransposed using L1-enzyme machinery. The 'master gene' model has been generally accepted to explain Alu element amplification in primate genomes. According to the model, different subfamilies of Alu elements are created by mutations on the master gene and most Alu elements are amplified from the hyperactive master genes. Alu element is frequently involved in genomic rearrangements in the human genome due to its abundance and sequence identity between them. The genomic rearrangements caused by Alu elements could lead to genetic disorders such as hereditary disease, blood disorder, and neurological disorder. In fact, Alu elements are associated with approximately 0.1% of human genetic disorders. The first part of this review discusses mechanisms of Alu amplification and diversity among different Alu subfamilies. The second part discusses the particular role of Alu elements in generating genomic rearrangements as well as human genetic disorders. PMID:27729835

  10. Does biodiversity protect humans against infectious disease?

    PubMed

    Wood, Chelsea L; Lafferty, Kevin D; DeLeo, Giulio; Young, Hillary S; Hudson, Peter J; Kuris, Armand M

    2014-04-01

    Control of human infectious disease has been promoted as a valuable ecosystem service arising from the conservation of biodiversity. There are two commonly discussed mechanisms by which biodiversity loss could increase rates of infectious disease in a landscape. First, loss of competitors or predators could facilitate an increase in the abundance of competent reservoir hosts. Second, biodiversity loss could disproportionately affect non-competent, or less competent reservoir hosts, which would otherwise interfere with pathogen transmission to human populations by, for example, wasting the bites of infected vectors. A negative association between biodiversity and disease risk, sometimes called the "dilution effect hypothesis," has been supported for a few disease agents, suggests an exciting win-win outcome for the environment and society, and has become a pervasive topic in the disease ecology literature. Case studies have been assembled to argue that the dilution effect is general across disease agents. Less touted are examples in which elevated biodiversity does not affect or increases infectious disease risk for pathogens of public health concern. In order to assess the likely generality of the dilution effect, we review the association between biodiversity and public health across a broad variety of human disease agents. Overall, we hypothesize that conditions for the dilution effect are unlikely to be met for most important diseases of humans. Biodiversity probably has little net effect on most human infectious diseases but, when it does have an effect, observation and basic logic suggest that biodiversity will be more likely to increase than to decrease infectious disease risk.

  11. The Human Phenotypic Disease Network

    NASA Astrophysics Data System (ADS)

    Hidalgo, Cesar; Blumm, Nicholas; Barabasi, Albert-Laszlo; Christakis, Nicholas

    2008-03-01

    We study the evolution of patient illness using a network summarizing the disease associations extracted from 32 million Medicare claims recorded from 13 million elders using the ICD9-CM format. We find that the evolution of patients' illness is accurately described by a process in which once a patient develops a particular disease, subsequent disease are seen to occur among diseases lying close by in the network. In addition, we find that patients affected with diseases with high network connectivity are more likely to die during a follow-up period of eight years.

  12. New techniques for positron emission tomography in the study of human neurological disorders

    SciTech Connect

    Kuhl, D.E.

    1992-07-01

    The general goals of the physics and kinetic modeling projects are to: (1) improve the quantitative information extractable from PET images, and (2) develop, implement and optimize tracer kinetic models for new PET neurotransmitter/receptor ligands aided by computer simulations. Work towards improving PET quantification has included projects evaluating: (1) iterative reconstruction algorithms using supplemental boundary information, (2) automated registration of dynamic PET emission and transmission data using sinogram edge detection, and (3) automated registration of multiple subjects to a common coordinate system, including the use of non-linear warping methods. Simulation routines have been developed providing more accurate representation of data generated from neurotransmitter/receptor studies. Routines consider data generated from complex compartmental models, high or low specific activity administrations, non-specific binding, pre- or post-injection of cold or competing ligands, temporal resolution of the data, and radiolabeled metabolites. Computer simulations and human PET studies have been performed to optimize kinetic models for four new neurotransmitter/receptor ligands, [{sup 11}C]TRB (muscarinic), [{sup 11}C]flumazenil (benzodiazepine), [{sup 18}F]GBR12909, (dopamine), and [{sup 11}C]NMPB (muscarinic).

  13. New techniques for positron emission tomography in the study of human neurological disorders

    SciTech Connect

    Kuhl, D.E.

    1992-01-01

    The general goals of the physics and kinetic modeling projects are to: (1) improve the quantitative information extractable from PET images, and (2) develop, implement and optimize tracer kinetic models for new PET neurotransmitter/receptor ligands aided by computer simulations. Work towards improving PET quantification has included projects evaluating: (1) iterative reconstruction algorithms using supplemental boundary information, (2) automated registration of dynamic PET emission and transmission data using sinogram edge detection, and (3) automated registration of multiple subjects to a common coordinate system, including the use of non-linear warping methods. Simulation routines have been developed providing more accurate representation of data generated from neurotransmitter/receptor studies. Routines consider data generated from complex compartmental models, high or low specific activity administrations, non-specific binding, pre- or post-injection of cold or competing ligands, temporal resolution of the data, and radiolabeled metabolites. Computer simulations and human PET studies have been performed to optimize kinetic models for four new neurotransmitter/receptor ligands, ({sup 11}C)TRB (muscarinic), ({sup 11}C)flumazenil (benzodiazepine), ({sup 18}F)GBR12909, (dopamine), and ({sup 11}C)NMPB (muscarinic).

  14. Parasitic diseases in humans transmitted by vectors.

    PubMed

    Cholewiński, Marcin; Derda, Monika; Hadaś, Edward

    2015-01-01

    Despite the considerable progress of medicine, parasitic diseases still pose a great threat to human health and life. Among parasitic diseases, those transmitted by vectors, mainly arthropods, play a particular role. These diseases occur most frequently in the poorest countries and affect a vast part of the human population. They include malaria, babesiosis, trypanosomiasis, leishmaniasis and filariasis. This study presents those vector-transmitted diseases that are responsible for the greatest incidence and mortality of people on a global scale. Attention is focused primarily on diseases transmitted by mosquitoes, flies, Hemiptera and ticks.

  15. Hooked! Modeling human disease in zebrafish.

    PubMed

    Santoriello, Cristina; Zon, Leonard I

    2012-07-01

    Zebrafish have been widely used as a model system for studying developmental processes, but in the last decade, they have also emerged as a valuable system for modeling human disease. The development and function of zebrafish organs are strikingly similar to those of humans, and the ease of creating mutant or transgenic fish has facilitated the generation of disease models. Here, we highlight the use of zebrafish for defining disease pathways and for discovering new therapies. PMID:22751109

  16. History of neurologic examination books.

    PubMed

    Boes, Christopher J

    2015-04-01

    The objective of this study was to create an annotated list of textbooks dedicated to teaching the neurologic examination. Monographs focused primarily on the complete neurologic examination published prior to 1960 were reviewed. This analysis was limited to books with the word "examination" in the title, with exceptions for the texts of Robert Wartenberg and Gordon Holmes. Ten manuals met the criteria. Works dedicated primarily to the neurologic examination without a major emphasis on disease description or treatment first appeared in the early 1900s. Georg Monrad-Krohn's "Blue Book of Neurology" ("Blue Bible") was the earliest success. These treatises served the important purpose of educating trainees on proper neurologic examination technique. They could make a reputation and be profitable for the author (Monrad-Krohn), highlight how neurology was practiced at individual institutions (McKendree, Denny-Brown, Holmes, DeJong, Mayo Clinic authors), and honor retiring mentors (Mayo Clinic authors).

  17. History of neurologic examination books.

    PubMed

    Boes, Christopher J

    2015-04-01

    The objective of this study was to create an annotated list of textbooks dedicated to teaching the neurologic examination. Monographs focused primarily on the complete neurologic examination published prior to 1960 were reviewed. This analysis was limited to books with the word "examination" in the title, with exceptions for the texts of Robert Wartenberg and Gordon Holmes. Ten manuals met the criteria. Works dedicated primarily to the neurologic examination without a major emphasis on disease description or treatment first appeared in the early 1900s. Georg Monrad-Krohn's "Blue Book of Neurology" ("Blue Bible") was the earliest success. These treatises served the important purpose of educating trainees on proper neurologic examination technique. They could make a reputation and be profitable for the author (Monrad-Krohn), highlight how neurology was practiced at individual institutions (McKendree, Denny-Brown, Holmes, DeJong, Mayo Clinic authors), and honor retiring mentors (Mayo Clinic authors). PMID:25829645

  18. [Neurological sleep disorders].

    PubMed

    Khatami, Ramin

    2014-11-01

    Neurological sleep disorders are common in the general population and may have a strong impact on quality of life. General practitioners play a key role in recognizing and managing sleep disorders in the general population. They should therefore be familiar with the most important neurological sleep disorders. This review provides a comprehensive overview of the most prevalent and important neurological sleep disorders, including Restless legs syndrome (with and without periodic limb movements in sleep), narcolepsy, NREM- and REM-sleep parasomnias and the complex relationship between sleep and epilepsies. Although narcolepsy is considered as a rare disease, recent discoveries in narcolepsy research provided insight in the function of brain circuitries involved in sleep wake regulation. REM sleep behavioral parasomnia (RBD) is increasingly recognized to represent an early manifestation of neurodegenerative disorders, in particular evolving synucleinopathies. Early diagnosis may thus open new perspectives for developing novel treatment options by targeting neuroprotective substances.

  19. OrthoDisease: a database of human disease orthologs.

    PubMed

    O'Brien, Kevin P; Westerlund, Isabelle; Sonnhammer, Erik L L

    2004-08-01

    One of the greatest promises of genome sequencing projects is to further the understanding of human diseases and to develop new therapies. Model organism genomes have been sequenced in parallel to human genomes to provide effective tools for the investigation of human gene function. Many of their genes share a common ancestry and function with human genes, and this is particularly true for orthologous genes. Here we present OrthoDisease, a comprehensive database of model organism genes that are orthologous to human disease genes. OrthoDisease was constructed by applying the Inparanoid ortholog detection algorithm to disease genes derived from the Online Mendelian Inheritance in Man database (OMIM). Pairwise whole genome/proteome comparisons between Homo sapiens and six other organisms were performed to identify ortholog clusters. OMIM numbers were extracted from the OMIM Morbid Map and were converted to gene sequences using the Locuslink mim2loc and loc2acc tables. These were mapped to Inparanoid ortholog clusters using Blast. The number of ortholog clusters in OrthoDisease with each respective species is currently: M. musculus, 1,354; D. melanogaster, 724; C. elegans, 533; A. thaliana, 398; S. cerevisiae, 290; and E. coli, 153. The database is accessible online at http://orthodisease.cgb.ki.se, and can be searched with disease or protein names. The web interface presents all ortholog clusters that include a selected disease gene. A capability to download the entire dataset is also provided.

  20. Neurological Complications of Transplantation

    PubMed Central

    Pruitt, Amy A.; Graus, Francesc; Rosenfeld, Myrna R.

    2013-01-01

    Hematopoietic cell transplantation (HCT) is the preferred treatment for an expanding range of neoplastic and nonmalignant conditions. Increasing numbers of solid organ transplantations (SOTs) add an additional population of immunosuppressed patients with multiple potential neurological problems. While the spectrum of neurological complications varies with conditioning procedure and hematopoietic cell or solid organ source, major neurological complications occur with all transplantation procedures. This 2 part review emphasizes a practical consultative approach to central and peripheral nervous system problems related to HCT or SOT with clinical and neuroimaging examples from the authors’ institutional experience with the following conditions: the diversity of manifestations of common infections such as varicella zoster virus, Aspergillus, and progressive multifocal leukoencephalopathy (PML), drug therapy-related complications, stroke mechanisms, the spectrum of graft versus host disease (GVHD), and neurologically important syndromes of immune reconstitution inflammatory syndrome (IRIS), posterior reversible encephalopathy syndrome (PRES), and posttransplantation lymphoproliferative disorder (PTLD). These complications preferentially occur at specific intervals after HCT and SOT, and neurological consultants must recognize an extensive spectrum of syndromes in order to effect timely diagnosis and expedite appropriate treatment. PMID:23983885

  1. Demyelinizing neurological disease after treatment with tumor necrosis factor alpha-inhibiting agents in a rheumatological outpatient clinic: description of six cases.

    PubMed

    Theibich, Ali; Dreyer, Lene; Magyari, Melinda; Locht, Henning

    2014-05-01

    Biological treatment with inhibitors of the pro-inflammatory cytokine TNF-alpha has dramatically improved the disease course of several chronic rheumatologic conditions. Adverse events (AEs) are primarily infections and hypersensitivity reactions. Demyelinizing neurological symptoms resembling multiple sclerosis (MS) have been described as a rare AE. During about 10-year use of anti TNF-alpha, the Danish Medicines Agency has recorded eight cases of MS like AEs. The objective of this study was to estimate the incidence of demyelinizing AEs both in the central and peripheral nervous system after treatment with anti TNF-alpha in a cohort of patients from a large rheumatologic outpatient clinic in Copenhagen. In a 4-year period from January 2008 to December 2011, approximately 550 patients annually were undergoing treatment with anti TNF-alpha inhibitors in our department. We collected data on all patients who developed neurological symptoms during this time period. We found six patients with signs of demyelinizing neurological disorders: four resembling MS, one MS-like condition, and one multifocal motor neuropathy. During a relatively short time period, we found a remarkably high number of neurological demyelinizing AEs probably linked to anti TNF-alpha treatment. The AEs were not associated with a single anti TNF-alpha agent and were thus presumably a class effect. The data presented suggest that neurological AEs may be underreported. We advocate that physicians handling patients during treatment with TNF inhibitors are aware of this potentially serious AE and report these events to the proper medical authorities. PMID:24202614

  2. Tissue Specificity of Human Disease Module

    PubMed Central

    Kitsak, Maksim; Sharma, Amitabh; Menche, Jörg; Guney, Emre; Ghiassian, Susan Dina; Loscalzo, Joseph; Barabási, Albert-László

    2016-01-01

    Genes carrying mutations associated with genetic diseases are present in all human cells; yet, clinical manifestations of genetic diseases are usually highly tissue-specific. Although some disease genes are expressed only in selected tissues, the expression patterns of disease genes alone cannot explain the observed tissue specificity of human diseases. Here we hypothesize that for a disease to manifest itself in a particular tissue, a whole functional subnetwork of genes (disease module) needs to be expressed in that tissue. Driven by this hypothesis, we conducted a systematic study of the expression patterns of disease genes within the human interactome. We find that genes expressed in a specific tissue tend to be localized in the same neighborhood of the interactome. By contrast, genes expressed in different tissues are segregated in distinct network neighborhoods. Most important, we show that it is the integrity and the completeness of the expression of the disease module that determines disease manifestation in selected tissues. This approach allows us to construct a disease-tissue network that confirms known and predicts unexpected disease-tissue associations. PMID:27748412

  3. Genetically Engineered Pig Models for Human Diseases

    PubMed Central

    Prather, Randall S.; Lorson, Monique; Ross, Jason W.; Whyte, Jeffrey J.; Walters, Eric

    2015-01-01

    Although pigs are used widely as models of human disease, their utility as models has been enhanced by genetic engineering. Initially, transgenes were added randomly to the genome, but with the application of homologous recombination, zinc finger nucleases, and transcription activator-like effector nuclease (TALEN) technologies, now most any genetic change that can be envisioned can be completed. To date these genetic modifications have resulted in animals that have the potential to provide new insights into human diseases for which a good animal model did not exist previously. These new animal models should provide the preclinical data for treatments that are developed for diseases such as Alzheimer's disease, cystic fibrosis, retinitis pigmentosa, spinal muscular atrophy, diabetes, and organ failure. These new models will help to uncover aspects and treatments of these diseases that were otherwise unattainable. The focus of this review is to describe genetically engineered pigs that have resulted in models of human diseases. PMID:25387017

  4. Neurologic Music Therapy Training for Mobility and Stability Rehabilitation with Parkinson’s Disease – A Pilot Study

    PubMed Central

    Bukowska, Anna A.; Krężałek, Piotr; Mirek, Elżbieta; Bujas, Przemysław; Marchewka, Anna

    2016-01-01

    Idiopathic Parkinson’s Disease (PD) is a progressive condition with gait disturbance and balance disorder as the main symptoms. Previous research studies focused on the application of Rhythmic Auditory Stimulation (RAS) in PD gait rehabilitation. The key hypothesis of this pilot study, however, assumes the major role of the combination of all three Neurologic Music Therapy (NMT) sensorimotor techniques in improving spatio-temporal gait parameters, and postural stability in the course of PD. The 55 PD-diagnosed subjects invited to the study were divided into two groups: 30 in the experimental and 25 in the control group. Inclusion criteria included Hoehn and Yahr stages 2 or 3, the ability to walk independently without any aid and stable pharmacological treatment for the duration of the experiment. In order to evaluate the efficacy of the chosen therapy procedure the following measures were applied: Optoelectrical 3D Movement Analysis, System BTS Smart for gait, and Computerized Dynamic Posturography CQ Stab for stability and balance. All measures were conducted both before and after the therapy cycle. The subjects from the experimental group attended music therapy sessions four times a week for 4 weeks. Therapeutic Instrumental Music Performance (TIMP), Pattern Sensory Enhancement (PSE) and RAS were used in every 45-min session for practicing daily life activities, balance, pre-gait, and gait pattern. Percussion instruments, the metronome and rhythmic music were the basis for each session. The subjects from the control group were asked to stay active and perform daily life activities between the measures. The research showed that the combination of the three NMT sensorimotor techniques can be used to improve gait and other rhythmical activities in PD rehabilitation. The results demonstrated significant improvement in the majority of the spatiotemporal gait parameters in the experimental group in comparison to the control group. In the stability tests with eyes

  5. Chemopreventative effects of tetrahydrocurcumin on human diseases.

    PubMed

    Wu, Jia-Ching; Tsai, Mei-Ling; Lai, Ching-Shu; Wang, Ying-Jan; Ho, Chi-Tang; Pan, Min-Hsiung

    2014-01-01

    Chemoprevention is a relatively new and promising strategy to prevent human degenerative diseases, including cancer, and is defined as the use of natural dietary compounds and/or synthetic substances to block, inhibit, reverse, or retard the progress of human diseases. Tetrahydrocurcumin (THC) is a major metabolite of curcumin (extracted from the roots of the Curcuma longa Linn). THC has been demonstrated to prevent oxidative stress and inflammation, to act against neurodegeneration, and to possess anti-cancer activity. In this review, we summarize the current knowledge and underlying molecular mechanisms of the chemopreventative activities of THC and its potential effects on the development of various human diseases. PMID:24220621

  6. Chemopreventative effects of tetrahydrocurcumin on human diseases.

    PubMed

    Wu, Jia-Ching; Tsai, Mei-Ling; Lai, Ching-Shu; Wang, Ying-Jan; Ho, Chi-Tang; Pan, Min-Hsiung

    2014-01-01

    Chemoprevention is a relatively new and promising strategy to prevent human degenerative diseases, including cancer, and is defined as the use of natural dietary compounds and/or synthetic substances to block, inhibit, reverse, or retard the progress of human diseases. Tetrahydrocurcumin (THC) is a major metabolite of curcumin (extracted from the roots of the Curcuma longa Linn). THC has been demonstrated to prevent oxidative stress and inflammation, to act against neurodegeneration, and to possess anti-cancer activity. In this review, we summarize the current knowledge and underlying molecular mechanisms of the chemopreventative activities of THC and its potential effects on the development of various human diseases.

  7. Tyrosine Kinase Inhibitors as a New Therapy for Ischemic Stroke and other Neurologic Diseases: Is there any Hope for a Better Outcome?

    PubMed Central

    Gągało, Iwona; Rusiecka, Izabela; Kocić, Ivan

    2015-01-01

    The relevance of tyrosine kinase inhibitors (TKIs) in the treatment of malignancies has been already defined. Aberrant activation of tyrosine kinase signaling pathways has been causally linked not only to cancers but also to other non-oncological diseases. This review concentrates on the novel plausible usage of this group of drugs in neurological disorders, such as ischemic brain stroke, subarachnoid hemorrhage, Alzheimer’s disease, multiple sclerosis. The drugs considered here are representatives of both receptor and non-receptor TKIs. Among them imatinib and masitinib have the broadest spectrum of therapeutic usage. Both drugs are effective in ischemic brain stroke and multiple sclerosis, but only imatinib produces a therapeutic effect in subarachnoid hemorrhage. Masitinib and dasatinib reduce the symptoms of Alzheimer’s disease. In the case of multiple sclerosis several TKIs are useful, including apart from imatinib and masitinib, also sunitinib, sorafenib, lestaurtinib. Furthermore, the possible molecular targets for the drugs are described in connection with the underlying pathophysiological mechanisms in the diseases in question. The most frequent target for the TKIs is PDGFR which plays a pivotal role particularly in ischemic brain stroke and subarachnoid hemorrhage. The collected data indicates that TKIs are very promising candidates for new therapeutic interventions in neurological diseases. PMID:26630962

  8. Human migration and infectious diseases.

    PubMed

    Soto, S M

    2009-01-01

    Emerging infectious diseases (EID) are defined as diseases that have appeared recently or that have recently increased in their frequency, geographical distribution or both. Commercial globalisation, population movements and environmental changes are the main factors favouring the international spread of microorganisms. Transport and communication development constitutes also a remarkable factor in the worldwide dispersion of microorganisms. The mass movement of large numbers of people creates new opportunities for the spread and establishment of common or novel infectious diseases. A surveillance system to detect emergent and re-emergent infections, a rapid responsiveness of healthcare systems and laboratories, vector control, and the provision of healthcare education programmes to inform the population of how to avoid infections are needed in order to stop the spread of infectious diseases. PMID:19220349

  9. Human migration and infectious diseases.

    PubMed

    Soto, S M

    2009-01-01

    Emerging infectious diseases (EID) are defined as diseases that have appeared recently or that have recently increased in their frequency, geographical distribution or both. Commercial globalisation, population movements and environmental changes are the main factors favouring the international spread of microorganisms. Transport and communication development constitutes also a remarkable factor in the worldwide dispersion of microorganisms. The mass movement of large numbers of people creates new opportunities for the spread and establishment of common or novel infectious diseases. A surveillance system to detect emergent and re-emergent infections, a rapid responsiveness of healthcare systems and laboratories, vector control, and the provision of healthcare education programmes to inform the population of how to avoid infections are needed in order to stop the spread of infectious diseases.

  10. Pentraxin-3 is upregulated in the central nervous system during MS and EAE, but does not modulate experimental neurological disease.

    PubMed

    Ummenthum, Kimberley; Peferoen, Laura A N; Finardi, Annamaria; Baker, David; Pryce, Gareth; Mantovani, Alberto; Bsibsi, Malika; Bottazzi, Barbara; Peferoen-Baert, Regina; van der Valk, Paul; Garlanda, Cecilia; Kipp, Markus; Furlan, Roberto; van Noort, Johannes M; Amor, Sandra

    2016-03-01

    Pentraxin-3 (PTX3), an acute-phase protein released during inflammation, aids phagocytic clearance of pathogens and apoptotic cells, and plays diverse immunoregulatory roles in tissue injury. In neuroinflammatory diseases, like MS, resident microglia could become activated by endogenous agonists for Toll like receptors (TLRs). Previously we showed a strong TLR2-mediated induction of PTX3 in cultured human microglia and macrophages by HspB5, which accumulates in glia during MS. Given the anti-inflammatory effects of HspB5, we examined the contribution of PTX3 to these effects in MS and its animal model EAE. Our data indicate that TLR engagement effectively induces PTX3 expression in human microglia, and that such expression is readily detectable in MS lesions. Enhanced PTX3 expression is prominently expressed in microglia in preactive MS lesions, and in microglia/macrophages engaged in myelin phagocytosis in actively demyelinating lesions. Yet, we did not detect PTX3 in cerebrospinal fluid of MS patients. PTX3 expression is also elevated in spinal cords during chronic relapsing EAE in Biozzi ABH mice, but the EAE severity and time course in PTX3-deficient mice did not differ from WT mice. Moreover, systemic PTX3 administration did not alter the disease onset or severity. Our findings reveal local functions of PTX3 during neuroinflammation in facilitating myelin phagocytosis, but do not point to a role for PTX3 in controlling the development of autoimmune neuroinflammation.

  11. Large Animal Models of Neurological Disorders for Gene Therapy

    PubMed Central

    Gagliardi, Christine; Bunnell, Bruce A.

    2009-01-01

    The development of therapeutic interventions for genetic disorders and diseases that affect the central nervous system (CNS) has proven challenging. There has been significant progress in the development of gene therapy strategies in murine models of human disease, but gene therapy outcomes in these models do not always translate to the human setting. Therefore, large animal models are crucial to the development of diagnostics, treatments, and eventual cures for debilitating neurological disorders. This review focuses on the description of large animal models of neurological diseases such as lysosomal storage diseases, Parkinson’s disease, Huntington’s disease, and neuroAIDS. The review also describes the contributions of these models to progress in gene therapy research. PMID:19293458

  12. Glial biomarkers in human central nervous system disease.

    PubMed

    Garden, Gwenn A; Campbell, Brian M

    2016-10-01

    There is a growing understanding that aberrant GLIA function is an underlying factor in psychiatric and neurological disorders. As drug discovery efforts begin to focus on glia-related targets, a key gap in knowledge includes the availability of validated biomarkers to help determine which patients suffer from dysfunction of glial cells or who may best respond by targeting glia-related drug mechanisms. Biomarkers are biological variables with a significant relationship to parameters of disease states and can be used as surrogate markers of disease pathology, progression, and/or responses to drug treatment. For example, imaging studies of the CNS enable localization and characterization of anatomical lesions without the need to isolate tissue for biopsy. Many biomarkers of disease pathology in the CNS involve assays of glial cell function and/or response to injury. Each major glia subtype (oligodendroglia, astroglia and microglia) are connected to a number of important and useful biomarkers. Here, we describe current and emerging glial based biomarker approaches for acute CNS injury and the major categories of chronic nervous system dysfunction including neurodegenerative, neuropsychiatric, neoplastic, and autoimmune disorders of the CNS. These descriptions are highlighted in the context of how biomarkers are employed to better understand the role of glia in human CNS disease and in the development of novel therapeutic treatments. GLIA 2016;64:1755-1771.

  13. Glial biomarkers in human central nervous system disease.

    PubMed

    Garden, Gwenn A; Campbell, Brian M

    2016-10-01

    There is a growing understanding that aberrant GLIA function is an underlying factor in psychiatric and neurological disorders. As drug discovery efforts begin to focus on glia-related targets, a key gap in knowledge includes the availability of validated biomarkers to help determine which patients suffer from dysfunction of glial cells or who may best respond by targeting glia-related drug mechanisms. Biomarkers are biological variables with a significant relationship to parameters of disease states and can be used as surrogate markers of disease pathology, progression, and/or responses to drug treatment. For example, imaging studies of the CNS enable localization and characterization of anatomical lesions without the need to isolate tissue for biopsy. Many biomarkers of disease pathology in the CNS involve assays of glial cell function and/or response to injury. Each major glia subtype (oligodendroglia, astroglia and microglia) are connected to a number of important and useful biomarkers. Here, we describe current and emerging glial based biomarker approaches for acute CNS injury and the major categories of chronic nervous system dysfunction including neurodegenerative, neuropsychiatric, neoplastic, and autoimmune disorders of the CNS. These descriptions are highlighted in the context of how biomarkers are employed to better understand the role of glia in human CNS disease and in the development of novel therapeutic treatments. GLIA 2016;64:1755-1771. PMID:27228454

  14. Evolutionary Conservation and Expression of Human RNA-Binding Proteins and Their Role in Human Genetic Disease

    PubMed Central

    Gerstberger, Stefanie; Hafner, Markus; Ascano, Manuel

    2014-01-01

    RNA-binding proteins (RBPs) are effectors and regulators of posttranscriptional gene regulation (PTGR). RBPs regulate stability, maturation, and turnover of all RNAs, often binding thousands of targets at many sites. The importance of RBPs is underscored by their dysregulation or mutations causing a variety of developmental and neurological diseases. This chapter globally discusses human RBPs and provides a brief introduction to their identification and RNA targets. We review RBPs based on common structural RNA-binding domains, study their evolutionary conservation and expression, and summarize disease associations of different RBP classes. PMID:25201102

  15. Evolutionary conservation and expression of human RNA-binding proteins and their role in human genetic disease.

    PubMed

    Gerstberger, Stefanie; Hafner, Markus; Ascano, Manuel; Tuschl, Thomas

    2014-01-01

    RNA-binding proteins (RBPs) are effectors and regulators of posttranscriptional gene regulation (PTGR). RBPs regulate stability, maturation, and turnover of all RNAs, often binding thousands of targets at many sites. The importance of RBPs is underscored by their dysregulation or mutations causing a variety of developmental and neurological diseases. This chapter globally discusses human RBPs and provides a brief introduction to their identification and RNA targets. We review RBPs based on common structural RNA-binding domains, study their evolutionary conservation and expression, and summarize disease associations of different RBP classes.

  16. Stem cell differentiation and human liver disease

    PubMed Central

    Zhou, Wen-Li; Medine, Claire N; Zhu, Liang; Hay, David C

    2012-01-01

    Human stem cells are scalable cell populations capable of cellular differentiation. This makes them a very attractive in vitro cellular resource and in theory provides unlimited amounts of primary cells. Such an approach has the potential to improve our understanding of human biology and treating disease. In the future it may be possible to deploy novel stem cell-based approaches to treat human liver diseases. In recent years, efficient hepatic differentiation from human stem cells has been achieved by several research groups including our own. In this review we provide an overview of the field and discuss the future potential and limitations of stem cell technology. PMID:22563188

  17. Human genome project and sickle cell disease.

    PubMed

    Norman, Brenda J; Miller, Sheila D

    2011-01-01

    Sickle cell disease is one of the most common genetic blood disorders in the United States that affects 1 in every 375 African Americans. Sickle cell disease is an inherited condition caused by abnormal hemoglobin in the red blood cells. The Human Genome Project has provided valuable insight and extensive research advances in the understanding of the human genome and sickle cell disease. Significant progress in genetic knowledge has led to an increase in the ability for researchers to map and sequence genes for diagnosis, treatment, and prevention of sickle cell disease and other chronic illnesses. This article explores some of the recent knowledge and advances about sickle cell disease and the Human Genome Project.

  18. Global change and human susceptibility to disease

    SciTech Connect

    Daily, G.C.; Ehrlich, P.R.

    1996-12-31

    Although the loss of good health is inherently unpredictable, human behavior at the individual and societal levels profoundly influences the incidence and evolution of disease. In this review, the authors define the human epidemiological environment and describe key biophysical, economic, sociocultural, and political factors that shape it. The potential impact upon the epidemiological environment of biophysical aspects of global change--changes in the size; mobility, and geographic distribution of the human population; land conversion; agricultural intensification; and climate change--is then examined. Human vulnerability to disease is strongly and deleteriously influenced by many of these ongoing, intensifying alterations. The authors then examine threats to human defenses against disease, including immune suppression, loss of biodiversity and indigenous knowledge, and the evolution of antibiotic resistance. Effective responses will require greatly enhanced attention by and collaboration among experts in diverse academic disciplines, in the private sector, and in government worldwide. 157 refs.

  19. Atypical prion diseases in humans and animals.

    PubMed

    Tranulis, Michael A; Benestad, Sylvie L; Baron, Thierry; Kretzschmar, Hans

    2011-01-01

    Although prion diseases, such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protease-resistant conformers of the prion protein (PrP), known as the "scrapie form" (PrP(Sc)), are used as disease markers, and for taxonomic purposes, in correlation with clinical, pathological, and genetic data. In humans, prion diseases can arise sporadically (sCJD) or genetically (gCJD and others), caused by mutations in the PrP-gene (PRNP), or as a foodborne infection, with the agent of bovine spongiform encephalopathy (BSE) causing variant CJD (vCJD). Person-to-person spread of human prion disease has only been known to occur following cannibalism (kuru disease in Papua New Guinea) or through medical or surgical treatment (iatrogenic CJD, iCJD). In contrast, scrapie in small ruminants and chronic wasting disease (CWD) in cervids behave as infectious diseases within these species. Recently, however, so-called atypical forms of prion diseases have been discovered in sheep (atypical/Nor98 scrapie) and in cattle, BSE-H and BSE-L. These maladies resemble sporadic or genetic human prion diseases and might be their animal equivalents. This hypothesis also raises the significant public health question of possible epidemiological links between these diseases and their counterparts in humans. PMID:21598097

  20. Epidemiological characteristics of human prion diseases.

    PubMed

    Chen, Cao; Dong, Xiao-Ping

    2016-01-01

    Human prion diseases are a group of transmissible, progressive, and invariably fatal neurodegenerative disorders, which include Kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. Human prion diseases affect approximately 1-2 persons per million worldwide annually, occurring in sporadic, inherited, and acquired forms. These diseases have attracted both scientific and public attention not only because of their mysterious pathogen, but also due to their considerable threat to public health since the emergence of the variant CJD.There are still no specific therapeutic and prophylactic interventions available for prion diseases, thus active surveillance of human prion diseases is critical for disease control and prevention. Since 1993, CJD surveillance systems have been established in many countries and regions, and several long-term multinational cooperative projects have been conducted.In this paper, the epidemiological characteristics of various human prion diseases and the active surveillance systems pertaining to them in different countries and regions are summarized and reviewed. PMID:27251305

  1. Evolutionary Response to Human Infectious Diseases

    ERIC Educational Resources Information Center

    Armelagos, George J.; Dewey, John R.

    1970-01-01

    Gives an overview of human history, relating cultural changes with resulting changes in population density and in ecological balance to patterns of infectious diseases in man. Discusses mechanisms of evolution of resistance. Suggests that in populations where infectious diseases can be controlled, attention should shift to degenerative diseases…

  2. A cellular star atlas: using astrocytes from human pluripotent stem cells for disease studies

    PubMed Central

    Krencik, Robert; Ullian, Erik M.

    2013-01-01

    What roles do astrocytes play in human disease?This question remains unanswered for nearly every human neurological disorder. Yet, because of their abundance and complexity astrocytes can impact neurological function in many ways. The differentiation of human pluripotent stem cells (hPSCs) into neuronal and glial subtypes, including astrocytes, is becoming routine, thus their use as tools for modeling neurodevelopment and disease will provide one important approach to answer this question. When designing experiments, careful consideration must be given to choosing paradigms for differentiation, maturation, and functional analysis of these temporally asynchronous cellular populations in culture. In the case of astrocytes, they display heterogeneous characteristics depending upon species of origin, brain region, developmental stage, environmental factors, and disease states, all of which may render experimental results highly variable. In this review, challenges and future directions are discussed for using hPSC-derived astroglial progenitors and mature astrocytes for neurodevelopmental studies with a focus on exploring human astrocyte effects upon neuronal function. As new technologies emerge to measure the functions of astrocytes in vitro and in vivo, there is also a need for a standardized source of human astrocytes that are most relevant to the diseases of interest. PMID:23503583

  3. Human Echinococcosis: A Neglected Disease

    PubMed Central

    da Silva, António Menezes

    2010-01-01

    Echinococcosis is among the most neglected parasitic diseases. Development of new drugs and other treatment modalities receives very little attention, if any. In most developed countries, Cystic Echinococcosis (CE) is an imported disease of very low incidence and prevalence and is found almost exclusively in migrants from endemic regions. In endemic regions, predominantly settings with limited resources, patient numbers are high. Whole communities do not have access to appropriate treatment. The choice of treatment modalities is limited because of poor infrastructure and shortage of equipment and drugs. In this context, CE meets the criteria for a neglected disease. Furthermore, the terminology related to the designations around the parasite, its evolution and some therapeutic procedures is not uniform and sometimes inappropriate terms and wrong designations are used based on incorrect concepts. Although all of us know the different aspects of the disease it is pertinent to remember some important points and, above all, to clarify some aspects concerning the hydatid cyst's nomenclature in order to understand better the therapeutic options in the liver locations, particularly the different surgical approaches. PMID:20862339

  4. Melanized Fungi in Human Disease

    PubMed Central

    Revankar, Sanjay G.; Sutton, Deanna A.

    2010-01-01

    Summary: Melanized or dematiaceous fungi are associated with a wide variety of infectious syndromes. Many are soil organisms and are generally distributed worldwide, though certain species appear to have restricted geographic ranges. Though they are uncommon causes of disease, melanized fungi have been increasingly recognized as important pathogens, with most reports occurring in the past 20 years. The spectrum of diseases with which they are associated has also broadened and includes allergic disease, superficial and deep local infections, pneumonia, brain abscess, and disseminated infection. For some infections in immunocompetent individuals, such as allergic fungal sinusitis and brain abscess, they are among the most common etiologic fungi. Melanin is a likely virulence factor for these fungi. Diagnosis relies on careful microscopic and pathological examination, as well as clinical assessment of the patient, as these fungi are often considered contaminants. Therapy varies depending upon the clinical syndrome. Local infection may be cured with excision alone, while systemic disease is often refractory to therapy. Triazoles such as voriconazole, posaconazole, and itraconazole have the most consistent in vitro activity. Further studies are needed to better understand the pathogenesis and optimal treatment of these uncommon infections. PMID:20930077

  5. Global biogeography of human infectious diseases.

    PubMed

    Murray, Kris A; Preston, Nicholas; Allen, Toph; Zambrana-Torrelio, Carlos; Hosseini, Parviez R; Daszak, Peter

    2015-10-13

    The distributions of most infectious agents causing disease in humans are poorly resolved or unknown. However, poorly known and unknown agents contribute to the global burden of disease and will underlie many future disease risks. Existing patterns of infectious disease co-occurrence could thus play a critical role in resolving or anticipating current and future disease threats. We analyzed the global occurrence patterns of 187 human infectious diseases across 225 countries and seven epidemiological classes (human-specific, zoonotic, vector-borne, non-vector-borne, bacterial, viral, and parasitic) to show that human infectious diseases exhibit distinct spatial grouping patterns at a global scale. We demonstrate, using outbreaks of Ebola virus as a test case, that this spatial structuring provides an untapped source of prior information that could be used to tighten the focus of a range of health-related research and management activities at early stages or in data-poor settings, including disease surveillance, outbreak responses, or optimizing pathogen discovery. In examining the correlates of these spatial patterns, among a range of geographic, epidemiological, environmental, and social factors, mammalian biodiversity was the strongest predictor of infectious disease co-occurrence overall and for six of the seven disease classes examined, giving rise to a striking congruence between global pathogeographic and "Wallacean" zoogeographic patterns. This clear biogeographic signal suggests that infectious disease assemblages remain fundamentally constrained in their distributions by ecological barriers to dispersal or establishment, despite the homogenizing forces of globalization. Pathogeography thus provides an overarching context in which other factors promoting infectious disease emergence and spread are set.

  6. TOXICOGENOMICS AND HUMAN DISEASE RISK ASSESSMENT

    EPA Science Inventory


    Toxicogenomics and Human Disease Risk Assessment.

    Complete sequencing of human and other genomes, availability of large-scale gene
    expression arrays with ever-increasing numbers of genes displayed, and steady
    improvements in protein expression technology can hav...

  7. Glycoprotein G of herpes simplex virus 2 as a novel vaccine antigen for immunity to genital and neurological disease.

    PubMed

    Görander, Staffan; Harandi, Ali M; Lindqvist, Madelene; Bergström, Tomas; Liljeqvist, Jan-Åke

    2012-07-01

    The envelope glycoproteins of herpes simplex virus 1 (HSV-1) and HSV-2, with the exception of glycoprotein G, elicit cross-reactive B- and T-cell responses. Human vaccine trials, using the cross-reactive glycoproteins B and D, have shown no protection against genital HSV-2 infection or disease. In this study, the mature form of glycoprotein G (mgG-2) of HSV-2 was used for immunization of mice, either alone or in combination with adjuvant CpG, followed by an intravaginal challenge with a lethal dose of a fully virulent HSV-2 strain. Mice immunized with mgG-2 plus CpG showed low disease scores and a significantly higher survival rate (73%) than mice immunized with mgG-2 alone (20%) or controls (0%). Accordingly, limited numbers of infectious HSV-2 particles were detected in the spinal cord of mice immunized with mgG-2 plus CpG. The observed protection was associated with a gamma interferon (IFN-γ) response by splenic CD4(+) T cells upon antigen restimulation in vitro and in vaginal washes 1 day postinfection. The majority of sera collected from mice immunized with mgG-2 plus CpG showed macrophage-mediated antibody-dependent cellular cytotoxicity and antibody-dependent complement-mediated cytolysis, while no neutralization activity was observed. In conclusion, we have shown that immunization with the type-specific mgG-2 protein in combination with CpG could elicit protective immunity against an otherwise lethal vaginal HSV-2 challenge. The mgG-2 protein may therefore constitute a promising HSV-2 vaccine antigen to be considered for future human trials. PMID:22553328

  8. Glycoprotein G of Herpes Simplex Virus 2 as a Novel Vaccine Antigen for Immunity to Genital and Neurological Disease

    PubMed Central

    Görander, Staffan; Harandi, Ali M.; Lindqvist, Madelene; Bergström, Tomas

    2012-01-01

    The envelope glycoproteins of herpes simplex virus 1 (HSV-1) and HSV-2, with the exception of glycoprotein G, elicit cross-reactive B- and T-cell responses. Human vaccine trials, using the cross-reactive glycoproteins B and D, have shown no protection against genital HSV-2 infection or disease. In this study, the mature form of glycoprotein G (mgG-2) of HSV-2 was used for immunization of mice, either alone or in combination with adjuvant CpG, followed by an intravaginal challenge with a lethal dose of a fully virulent HSV-2 strain. Mice immunized with mgG-2 plus CpG showed low disease scores and a significantly higher survival rate (73%) than mice immunized with mgG-2 alone (20%) or controls (0%). Accordingly, limited numbers of infectious HSV-2 particles were detected in the spinal cord of mice immunized with mgG-2 plus CpG. The observed protection was associated with a gamma interferon (IFN-γ) response by splenic CD4+ T cells upon antigen restimulation in vitro and in vaginal washes 1 day postinfection. The majority of sera collected from mice immunized with mgG-2 plus CpG showed macrophage-mediated antibody-dependent cellular cytotoxicity and antibody-dependent complement-mediated cytolysis, while no neutralization activity was observed. In conclusion, we have shown that immunization with the type-specific mgG-2 protein in combination with CpG could elicit protective immunity against an otherwise lethal vaginal HSV-2 challenge. The mgG-2 protein may therefore constitute a promising HSV-2 vaccine antigen to be considered for future human trials. PMID:22553328

  9. [Primary human demodicosis. A disease sui generis].

    PubMed

    Hsu, C-K; Zink, A; Wei, K-J; Dzika, E; Plewig, G; Chen, W

    2015-03-01

    Human Demodex mites (Demodex folliculorum and Demodex brevis) are unique in that they are an obligate human ectoparasite that can inhabit the pilosebaceous unit lifelong without causing obvious host immune response in most cases. The mode of symbiosis between humans and human Demodex mites is unclear, while the pathogenicity of human Demodex mites in many inflammatory skin diseases is now better understood. Primary human demodicosis is a skin disease sui generis not associated with local or systemic immunosuppression. Diagnosis is often underestimated and differentiation from folliculitis, papulopustular rosacea and perioral dermatitis is not always straightforward. Dependent on the morphology and degree of inflammation, the clinical manifestations can be classified into spinulate, papulopustular, nodulocystic, crustic and fulminant demodicosis. Therapy success can be achieved only with acaricides/arachidicides. The effective doses, optimal regimen and antimicrobial resistance remain to be determined. PMID:25744530

  10. Comparative Genomic and Phylogenetic Analysis of the First Usutu Virus Isolate from a Human Patient Presenting with Neurological Symptoms

    PubMed Central

    Gaibani, Paolo; Cavrini, Francesca; Gould, Ernest A.; Rossini, Giada; Pierro, Anna; Landini, Maria Paola; Sambri, Vittorio

    2013-01-01

    Usutu virus (USUV) is a mosquito-borne flavivirus, belonging to the Japanese encephalitis antigenic complex, that circulates among mosquitoes and birds. We describe and analyze the complete genome sequence of the first USUV strain isolated from an immunocompromised patient with neuroinvasive disease. This USUV isolate showed an overall nucleotide identity of 99% and 96%, respectively, with the genomes of isolates from Europe and Africa. Comparison of the human USUV complete polyprotein sequence with bird-derived strains, showed two unique amino acid substitutions. In particular, one substitution (S595G) was situated in the DIII domain of the viral Envelope protein that is recognized by flavivirus neutralizing antibodies. An additional amino acid substitution (D3425E) was identified in the RNA-dependent RNA polymerase (RdRp) domain of the NS5 protein. This substitution is remarkable since E3425 is highly conserved among the other USUV isolates that were not associated with human infection. However, a similar substitution was observed in Japanese encephalitis and in West Nile viruses isolated from humans. Phylogenetic analysis of the human USUV strain revealed a close relationship with an Italian strain isolated in 2009. Analysis of synonymous nucleotide substitutions (SNSs) among the different USUV genomes showed a specific evolutionary divergence among different countries. In addition, 15 SNSs were identified as unique in the human isolate. We also identified four specific nucleotide substitutions in the 5′ and 3′ untranslated regions (UTRs) in the human isolate that were not present in the other USUV sequences. Our analyses provide the basis for further experimental studies aimed at defining the effective role of these mutations in the USUV genome, their potential role in the development of viral variants pathogenic for humans and their evolution and dispersal out of Africa. PMID:23741387

  11. Addressing the burden of mental, neurological, and substance use disorders: key messages from Disease Control Priorities, 3rd edition.

    PubMed

    Patel, Vikram; Chisholm, Dan; Parikh, Rachana; Charlson, Fiona J; Degenhardt, Louisa; Dua, Tarun; Ferrari, Alize J; Hyman, Steve; Laxminarayan, Ramanan; Levin, Carol; Lund, Crick; Medina Mora, María Elena; Petersen, Inge; Scott, James; Shidhaye, Rahul; Vijayakumar, Lakshmi; Thornicroft, Graham; Whiteford, Harvey

    2016-04-16

    The burden of mental, neurological, and substance use (MNS) disorders increased by 41% between 1990 and 2010 and now accounts for one in every 10 lost years of health globally. This sobering statistic does not take into account the substantial excess mortality associated with these disorders or the social and economic consequences of MNS disorders on affected persons, their caregivers, and society. A wide variety of effective interventions, including drugs, psychological treatments, and social interventions, can prevent and treat MNS disorders. At the population-level platform of service delivery, best practices include legislative measures to restrict access to means of self-harm or suicide and to reduce the availability of and demand for alcohol. At the community-level platform, best practices include life-skills training in schools to build social and emotional competencies. At the health-care-level platform, we identify three delivery channels. Two of these delivery channels are especially relevant from a public health perspective: self-management (eg, web-based psychological therapy for depression and anxiety disorders) and primary care and community outreach (eg, non-specialist health worker delivering psychological and pharmacological management of selected disorders). The third delivery channel, hospital care, which includes specialist services for MNS disorders and first-level hospitals providing other types of services (such as general medicine, HIV, or paediatric care), play an important part for a smaller proportion of cases with severe, refractory, or emergency presentations and for the integration of mental health care in other health-care channels, respectively. The costs of providing a significantly scaled up package of specified cost-effective interventions for prioritised MNS disorders in low-income and lower-middle-income countries is estimated at US$3-4 per head of population per year. Since a substantial proportion of MNS disorders run a

  12. Addressing the burden of mental, neurological, and substance use disorders: key messages from Disease Control Priorities, 3rd edition.

    PubMed

    Patel, Vikram; Chisholm, Dan; Parikh, Rachana; Charlson, Fiona J; Degenhardt, Louisa; Dua, Tarun; Ferrari, Alize J; Hyman, Steve; Laxminarayan, Ramanan; Levin, Carol; Lund, Crick; Medina Mora, María Elena; Petersen, Inge; Scott, James; Shidhaye, Rahul; Vijayakumar, Lakshmi; Thornicroft, Graham; Whiteford, Harvey

    2016-04-16

    The burden of mental, neurological, and substance use (MNS) disorders increased by 41% between 1990 and 2010 and now accounts for one in every 10 lost years of health globally. This sobering statistic does not take into account the substantial excess mortality associated with these disorders or the social and economic consequences of MNS disorders on affected persons, their caregivers, and society. A wide variety of effective interventions, including drugs, psychological treatments, and social interventions, can prevent and treat MNS disorders. At the population-level platform of service delivery, best practices include legislative measures to restrict access to means of self-harm or suicide and to reduce the availability of and demand for alcohol. At the community-level platform, best practices include life-skills training in schools to build social and emotional competencies. At the health-care-level platform, we identify three delivery channels. Two of these delivery channels are especially relevant from a public health perspective: self-management (eg, web-based psychological therapy for depression and anxiety disorders) and primary care and community outreach (eg, non-specialist health worker delivering psychological and pharmacological management of selected disorders). The third delivery channel, hospital care, which includes specialist services for MNS disorders and first-level hospitals providing other types of services (such as general medicine, HIV, or paediatric care), play an important part for a smaller proportion of cases with severe, refractory, or emergency presentations and for the integration of mental health care in other health-care channels, respectively. The costs of providing a significantly scaled up package of specified cost-effective interventions for prioritised MNS disorders in low-income and lower-middle-income countries is estimated at US$3-4 per head of population per year. Since a substantial proportion of MNS disorders run a

  13. Cis-regulatory mutations in human disease

    PubMed Central

    2009-01-01

    Cis-acting regulatory sequences are required for the proper temporal and spatial control of gene expression. Variation in gene expression is highly