Science.gov

Sample records for acute neurological disease

  1. 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.

  2. 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.

  3. 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 ...

  4. 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

  5. [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

  6. Neurological emergencies: acute stroke

    PubMed Central

    Davenport, R.; Dennis, M.

    2000-01-01

    Stroke causes a vast amount of death and disability throughout the world, yet for many healthcare professionals it remains an area of therapeutic nihilism, and thus uninteresting. This negative perception is shared by the general public, who often have a poor understanding of the early symptoms and significance of a stroke. Yet within the past few years there have been many important developments in the approach to caring for stroke patients, for both the acute management and secondary prevention. After the completion of numerous clinical trials, there is now robust evidence to either support or discredit various interventions. Even more exciting is the prospect of yet more data becoming available in the near future, testing a whole array of treatments, as clinical interest in stroke expands exponentially. In this review an evidence based approach to the management of acute stroke within the first few days is presented, including ischaemic and haemorrhagic events, but not subarachnoid haemorrhage. It is explained why stroke is regarded as a medical emergency, and the importance of a rational, methodic approach to the initial assessment, which is the key to accurate diagnosis and subsequent management, is emphasised. The potential early problems associated with stroke are identified and specific interventions for different stroke types are discussed. The review ends with a brief discussion of the implications that the evolving treatments have for the organisation of modern stroke services.

 PMID:10675208

  7. 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

  8. The neurologic manifestations of the acute porphyrias.

    PubMed

    Simon, Neil G; Herkes, Geoffrey K

    2011-09-01

    The porphyrias are diseases characterised by accumulation of porphyrins and porphyrin precursors owing to enzymatic deficiencies of the haem synthetic pathway. In the acute hepatic porphyrias accumulation of porphyrin precursors, in particular delta-aminolaevulinic acid (ALA), cause dysfunction of the central, peripheral and autonomic nervous systems. This leads to the characteristic clinical findings of abdominal pain, neuropsychiatric symptoms and neuropathy. The exact pathogenic mechanism is not clear but evidence to date suggests both direct toxic effects of ALA and intracellular metabolic derangement contribute to the neurologic disorders. This review explores the mechanisms of neural dysfunction in the acute porphyrias and the resultant clinical features of an acute attack.

  9. 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.

  10. 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

  11. 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

  12. Pregnancy-induced acute neurologic emergencies and neurologic conditions encountered in pregnancy.

    PubMed

    Alvis, Jeffrey S; Hicks, Richard J

    2012-02-01

    Neurologic complications and conditions associated with pregnancy are rare. Frequently, presenting symptoms of neurologic conditions are nonspecific and can overlap with normal symptoms of pregnancy. As a result, clinical assessment can be insufficient to differentiate symptoms of a normal pregnancy from a neurologic disorder. It is imperative that the radiologist have a basic familiarity with the most common neurologic conditions encountered in pregnancy. The most commonly imaged acute and nonemergent disorders will be described, including eclampsia, cerebrovascular disease including cerebral venous thrombosis, postpartum cerebral angiopathy, multiple sclerosis, tumors, Bell palsy, Guillain-Barré syndrome, and pituitary disorders. PMID:22264902

  13. 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

  14. Neurological crisis mimicking acute pancreatitis in tyrosinemia type I.

    PubMed

    Kalkanoğlu, H S; Coşkun, T

    1999-01-01

    Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. Neurological manifestations have been reported in nearly half of patients during illness to have characteristics of altered consciousness, weakness, anorexia, vomiting, and pain in the extremities and abdomen. His physical findings and laboratory results pointed out acute pancreatitis. There have been some reports of acute and chronic pancreatitis in patients with metabolic diseases; however, this is the first case with tyrosinemia type I who exhibited clinical and biochemical findings of acute pancreatitis during neurological crisis. The presented case suggests the possibility that the pancreas is affected in neurological crisis. The determination of amylase concentration both in serum and urine samples of further cases will clarity the association between pancreatitis and neurological crisis. PMID:10770119

  15. 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

  16. 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

  17. Neurological Manifestations of Acute Posterior Multifocal Placoid Pigment Epitheliopathy

    PubMed Central

    Alkhotani, Ashjan; Shirah, Bader

    2016-01-01

    Background and Purpose Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an immune-mediated chorioretinal disease that causes acute visual symptoms with characteristic ophthalmoscopic findings. Neurological complications are rarely reported in the literature. Here we report two new cases of APMPPE that presented with neurological manifestations, one of which was associated with peripheral neuropathy, which has not been described before. Methods A retrospective database review of all patients with a diagnosis of APMPPE was performed. Clinical, ophthalmological, and neurological data were analyzed, and only cases of APMPPE with neurological complications were included. A literature review of several databases was also performed, and previous case reports were reviewed and analyzed in detail. Results In total, 56 cases of APMPPE-associated neurological complications were included in the analyses: 54 from the literature and 2 from our own practice. The most common complication was cerebral vasculitis, which affected 28 patients (50%), followed by headaches in 15 patients (26.8%). The other complications include sixth-cranial-nerve palsy, transient hearing loss, meningoencephalitis, cavernous sinus thrombosis, and viral meningitis. Conclusions This report adds to the literature of a novel association of APMPPE with peripheral neuropathy, and comprehensively reviews the neurological manifestations of this disease. A high level of suspicion should be applied when dealing with a case of APMPPE. We recommend applying detailed clinical neurological examinations and magnetic resonance imaging to APMPPE patients, and then early steroid treatment if the examination is positive or even suspicious. Early treatment with steroids and long-term treatment with immunosuppressive azathioprine with interval neurological evaluations will contribute positively to the outcomes and avoid fatal complications, namely strokes.

  18. 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.

  19. Acute Neurological Involvement in Diarrhea-Associated Hemolytic Uremic Syndrome

    PubMed Central

    Kwon, Thérésa; Elmaleh, Monique; Charbit, Marina; Launay, Emma Allain; Harambat, Jérôme; Brun, Muriel; Ranchin, Bruno; Bandin, Flavio; Cloarec, Sylvie; Bourdat-Michel, Guylhene; Piètrement, Christine; Champion, Gérard; Ulinski, Tim; Deschênes, Georges

    2010-01-01

    Background and objectives: Neurologic involvement is the most threatening complication of diarrhea-associated hemolytic uremic syndrome (D+HUS). Design, setting, participants, & measurements: We report a retrospective multicenter series of 52 patients with severe initial neurologic involvement that occurred in the course of D+HUS. Results: Verotoxigenic Escherichia coli infection was documented in 24. All except two patients had acute renal failure that required peritoneal dialysis, hemodialysis, or both techniques. A first group of eight patients remained with normal consciousness; five of them had protracted seizures. A second group of 23 patients had stuporous coma; five of these had protracted severe seizures, and 18 had a neurologic defect including pyramidal syndrome, hemiplegia or hemiparesia, and extrapyramidal syndrome. A third group of 21 patients had severe coma. Plasma exchanges were undertaken in 25 patients, 11 of whom were treated within 24 hours after the first neurologic sign; four died, two survived with severe sequelae, and five were alive without neurologic defect. Magnetic resonance imaging (MRI) for 29 patients showed that (1) every structure of the central nervous system was susceptible to involvement; (2) no correlation seemed to exist between special profile of localization on early MRI and the final prognosis; and (3) MRI did not exhibit any focal lesions in three patients. The overall prognosis of the series was marked by the death of nine patients and severe sequelae in 13. Conclusions: Neurologic involvement is associated with a severe renal disease but does not lead systematically to death or severe disability. PMID:20498239

  20. Endovascular treatment for acute pulmonary embolism in neurological patient.

    PubMed

    Paul, Gunchan; Paul, Birinder S; Gautam, Parshotam L; Mohan, Bishav; Sharma, Shruti

    2015-07-01

    Among the spectrum of venous thrombo-embolic disease, acute pulmonary embolism accounts for the most life threatening manifestations with mortality exceeding 50%. It can affect many patient populations across various disciplines, hence immediate attention and aggressive treatment is crucial. With the advancement of technologies, various catheter-based devices are available to treat massive or submassive PE. In this paper we report two patients of acute pulmonary embolism with neurological issues where the life threatening emergency was successfully managed by utilizing endovascular directed thrombolytic reperfusion therapy. PMID:26609298

  1. [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.

  2. 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.

  3. Neurologic Disorders in Immunocompetent Patients with Autochthonous Acute Hepatitis E

    PubMed Central

    Perrin, H. Blasco; Cintas, P.; Abravanel, F.; Gérolami, R.; d'Alteroche, L.; Raynal, J.-N.; Alric, L.; Dupuis, E.; Prudhomme, L.; Vaucher, E.; Couzigou, P.; Liversain, J.-M.; Bureau, C.; Vinel, J.-P.; Kamar, N.; Izopet, J.

    2015-01-01

    Neurologic disorders, mainly Guillain-Barré syndrome and Parsonage–Turner syndrome (PTS), have been described in patients with hepatitis E virus (HEV) infection in industrialized and developing countries. We report a wider range of neurologic disorders in nonimmunocompromised patients with acute HEV infection. Data from 15 French immunocompetent patients with acute HEV infection and neurologic disorders were retrospectively recorded from January 2006 through June 2013. The disorders could be divided into 4 main entities: mononeuritis multiplex, PTS, meningoradiculitis, and acute demyelinating neuropathy. HEV infection was treated with ribavirin in 3 patients (for PTS or mononeuritis multiplex). One patient was treated with corticosteroids (for mononeuropathy multiplex), and 5 others received intravenous immunoglobulin (for PTS, meningoradiculitis, Guillain-Barré syndrome, or Miller Fisher syndrome). We conclude that pleiotropic neurologic disorders are seen in HEV-infected immunocompetent patients. Patients with acute neurologic manifestations and aminotransferase abnormalities should be screened for HEV infection. PMID:26490255

  4. 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 ...

  5. 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

  6. Predation as a cause of neurologic signs and acute mortality in a pheasant flock.

    PubMed

    Martin, M P; Anderson, C M; Johnson, B; Wakenell, P S

    2006-09-01

    A flock of approximately 15,000 ring-necked pheasants (Phasianus colchicus) was evaluated for a sudden increase in mortality and acute neurological signs after having been previously diagnosed 3 wk earlier with a chronic respiratory disease of undetermined etiology. Approximately 25 live birds were displaying neurological signs including circling, ataxia, and obtunded behavior and 50 birds were dead. Three birds with neurological signs were submitted for evaluation. Extensive subcutaneous hemorrhage over the head and penetrating puncture wounds through the skull and into the brain were found. Trauma from a wild predatory mammal, most likely the long-tailed weasel (Mustela frenata) that had invaded the pheasant house and expressed surplus killing behavior was determined to be the cause of the acute neurological signs and mortality. The relationship of the chronic respiratory disease to the predation episode was not determined but it is possible that pheasants with severe respiratory disease may have had increased susceptibility to predation.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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…

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. Pertussis immunisation and serious acute neurological illnesses in children.

    PubMed Central

    Miller, D; Madge, N; Diamond, J; Wadsworth, J; Ross, E

    1993-01-01

    OBJECTIVE--To determine long term outcome in children who had a severe acute neurological illness in early childhood associated with pertussis immunisation. DESIGN--Follow up study of cases and matched controls. SETTING--Assessment of children at home and at school throughout Britain. SUBJECTS--Children recruited into the national childhood encephalopathy study in 1976-9 were followed up, with one of their two original matched controls, in 1986-9. MAIN OUTCOME MEASURES--Performance in educational attainment tests; behaviour problems reported by teachers and parents; continuing convulsions; evidence of other neurological or physical dysfunction. RESULTS--Over 80% of cases and controls were traced. Case children were significantly more likely than controls to have died or to have some form of educational, behavioural, neurological, or physical dysfunction a decade after their illness. The prevalence of one or more of these adverse outcomes in case children who had been immunised with diphtheria, tetanus, and pertussis vaccine within seven days before onset of their original illness was similar to that in case children who had not been immunised recently. The relative risk for recent diphtheria, tetanus, and pertussis immunisation in children who had died or had any dysfunction in comparison with controls was 5.5 (95% confidence interval 1.6 to 23.7). However, the number of cases associated with vaccine (12) was extremely small and statistically vulnerable, and other possible agents or predisposing factors could not be excluded. CONCLUSIONS--Diphtheria, tetanus, and pertussis vaccine may on rare occasions be associated with the development of severe acute neurological illnesses that can have serious sequelae. Some cases may occur by chance or have other causes. The role of pertussis vaccine as a prime or concomitant factor in the aetiology of these illnesses cannot be determined in any individual case. The balance of possible risk against known benefits from pertussis

  13. 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

  14. [Neurological and psychiatric disorders following acute arsine poisoning (author's transl)].

    PubMed

    Frank, G

    1976-07-15

    Follow-up study of 6 workers, who after survival of an acute arsine poisoning, developed psychopathologic and neurologic abnormalities. The symptoms appeared after a latency of 1 to 6 months indicating a toxic polyneuropathy and a mild psycho-organic syndrome. The severity of these reversible manifestations was directly related to the period of time of exposure to arsine. The clinical picture of arsine polyneuropathy was similar to that observed in arsenic poisoning, suggesting that arsine polyneuropathy is due to the action of arsenic. The psychopathologic syndrome corresponds to the so-called "Vergiftungsspätfolgesyndrom" and therefore does not appear to be a specific sequel of arsine poisoning.

  15. 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

  16. 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

  17. [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

  18. [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

  19. Neurological complications of acute and persistent Epstein-Barr virus infection in paediatric patients.

    PubMed

    Häusler, Martin; Ramaekers, Vincent Thomas; Doenges, Martin; Schweizer, Klaus; Ritter, Klaus; Schaade, Lars

    2002-10-01

    Neurological complications of Epstein-Barr virus (EBV) have been reported almost exclusively in the course of acute primary infections. The role of EBV in paediatric neurological disease was investigated prospectively over a 2-year period, searching for acute primary, chronic, and reactivated EBV infections. Active EBV infections were diagnosed in 10/48 patients, including two with acute primary EBV infections (cranial neuritis and cerebellitis), one with chronic active infection (T/NK cell lymphoma with cranial neuritis), and seven with reactivated infections. Among these seven patients, three showed "Alice in Wonderland" syndrome, one facial nerve palsy, one progressive macrocephaly, and two prolonged encephalitic illness. The prognosis was good except for the patient with lethal T/NK cell lymphoma and the two girls with encephalitic illness. Despite steroid treatment, these girls suffered prolonged cognitive impairment and epileptic seizures. Both developed left-sided hippocampal atrophy, and one of them hippocampal sclerosis. Like primary infections, reactivated EBV infections cause neurological complications in a considerable number of paediatric patients, lead to serious long-term complications, and may contribute to the pathogenesis of hippocampal lesions. PMID:12210416

  20. 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

  1. 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

  2. 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

  3. 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.

  4. [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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. [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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Severe neurologic manifestations in acute intermittent porphyria developed after spine surgery under general anesthesia: a case report

    PubMed Central

    Park, Eun Young; Kim, Yi Seul; Lim, Kyung-Jee; Lee, Hye Kyoung; Lee, Soo Kyung; Choi, Hyun

    2014-01-01

    Porphyrias are inherited metabolic disorders resulting from a specific enzyme defect in the heme biosynthetic pathway. Porphyrias are induced by various precipitants. Clinical features include abdominal pain, neurologic manifestations, autonomic neuropathy, and mental disturbance. Diagnosis may be delayed because of variable symptoms that mimic other diseases and because of the rarity of of porphyrias. Although most patients with known porphyria can complete anesthesia and surgery safely, undiagnosed porphyric patients are in danger of porphyric crisis due to inadvertent exposure to precipitating drugs and environment. We report a case of a patient who experienced delayed emergence with neurological disturbance after general anesthesia, ultimately diagnosed as acute intermittent porphyria. PMID:25302100

  19. Nonmydriatic retinal photography in the evaluation of acute neurologic conditions

    PubMed Central

    Bidot, Samuel; Bruce, Beau B.; Newman, Nancy J.; Biousse, Valérie

    2013-01-01

    Summary Ocular fundus examination is a fundamental component of the neurologic examination. Finding papilledema in headache patients or retinal arterial emboli in stroke patients can be extremely useful. Although examination of the ocular fundus with a direct ophthalmoscope is an important skill for all neurologists, it is rarely and unreliably performed. Nonmydriatic ocular fundus photography, which allows direct visualization of high-quality photographs of the ocular fundus, has been recently proposed for screening neurologic patients in urgent care settings such as emergency departments. This new technology has many potential applications in neurology, including e-transmission of images for remote interpretation. PMID:24353924

  20. 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

  1. 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

  2. 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

  3. [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

  4. 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.

  5. 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

  6. Shunt malfunction causing acute neurological deterioration in 2 patients with previously asymptomatic Chiari malformation Type I. Report of two cases.

    PubMed

    Elliott, Robert; Kalhorn, Stephen; Pacione, Donato; Weiner, Howard; Wisoff, Jeffrey; Harter, David

    2009-08-01

    Patients with symptomatic Chiari malformation Type I (CM-I) typically exhibit a chronic, slowly progressive disease course with evolution of symptoms. However, some authors have reported acute neurological deterioration in the setting of CM-I and acquired Chiari malformations. Although brainstem dysfunction has been documented in patients with CM-II and hydrocephalus or shunt malfunction, to the authors' knowledge only 1 report describing ventriculoperitoneal (VP) shunt malfunction causing neurological deterioration in a patient with CM-I exists. The authors report on their experience with the treatment of previously asymptomatic CM-I in 2 children who experienced quite different manifestations of acute neurological deterioration secondary to VP shunt malfunction. Presumably, VP shunt malfunction created a positive rostral pressure gradient across a stenotic foramen magnum, resulting in tetraparesis from foramen magnum syndrome in 1 patient and acute ataxia and cranial nerve deficits from syringobulbia in the other. Although urgent shunt revisions yielded partial recovery of neurological function in both patients, marked improvement occurred only after posterior fossa decompression.

  7. 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.

  8. 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.

  9. 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.

  10. [Neurology].

    PubMed

    Sokolov, Arseny A; Rossetti, Andrea O; Michel, Patrik; Benninger, David; Nater, Bernard; Wider, Christian; Hirt, Lorenz; Kuntzer, Thierry; Démonet, Jean-François; Du Pasquier, Renaud A; Vingerhoets, François

    2016-01-13

    In 2015, cerebral stimulation becomes increasingly established in the treatment of pharmacoresistant epilepsy. Efficacy of endovascular treatment has been demonstrated for acute ischemic stroke. Deep brain stimulation at low frequency improves dysphagia and freezing of gait in Parkinson patients. Bimagrumab seems to increase muscular volume and force in patients with inclusion body myositis. In cluster-type headache, a transcutaneous vagal nerve stimulator is efficient in stopping acute attacks and also reducing their frequency. Initial steps have been undertaken towards modulating memory by stimulation of the proximal fornix. Teriflunomide is the first oral immunomodulatory drug for which efficacy has been shown in preventing conversion from clinical isolated syndrome to multiple sclerosis. PMID:26946707

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. [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.

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. [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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. Acute Neurological Illness in a Kidney Transplant Recipient Following Infection With Enterovirus-D68: An Emerging Infection?

    PubMed

    Wali, R K; Lee, A H; Kam, J C; Jonsson, J; Thatcher, A; Poretz, D; Ambardar, S; Piper, J; Lynch, C; Kulkarni, S; Cochran, J; Djurkovic, S

    2015-12-01

    We report the first case of enterovirus-D68 infection in an adult living-donor kidney transplant recipient who developed rapidly progressive bulbar weakness and acute flaccid limb paralysis following an upper respiratory infection. We present a 45-year-old gentleman who underwent pre-emptive living-donor kidney transplantation for IgA nephropathy. Eight weeks following transplantation, he developed an acute respiratory illness from enterovirus/rhinovirus that was detectable in nasopharyngeal (NP) swabs. Within 24 h of onset of respiratory symptoms, the patient developed binocular diplopia which rapidly progressed to multiple cranial nerve dysfunctions (acute bulbar syndrome) over the next 24 h. Within the next 48 h, asymmetric flaccid paralysis of the left arm and urinary retention developed. While his neurological symptoms were evolving, the Centers for Disease Control reported that the enterovirus strain from the NP swabs was, in fact, Enterovirus-D68 (EV-D68). Magnetic resonance imaging of the brain demonstrated unique gray matter and anterior horn cell changes in the midbrain and spinal cord, respectively. Constellation of these neurological symptoms and signs was suggestive for postinfectious encephalomyelitis (acute disseminated encephalomyelitis [ADEM]) from EV-D68. Treatment based on the principles of ADEM included intensive physical therapy and other supportive measures, which resulted in a steady albeit slow improvement in his left arm and bulbar weakness, while maintaining stable allograft function. PMID:26228743

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. Enterovirus 71 infection-associated acute flaccid paralysis: a case series of long-term neurologic follow-up.

    PubMed

    Lee, Hsiu-Fen; Chi, Ching-Shiang

    2014-10-01

    The authors undertook long-term neurologic outcomes of 27 patients aged 0 to 15 years with enterovirus 71-related acute flaccid paralysis from June 1998 to July 2012. Motor function outcome was graded from class I (complete recovery) to class V (permanent paralytic limbs). Twelve of 20 patients (60%) who received intravenous immunoglobulin for treatment of acute flaccid paralysis had motor function outcomes in classes III to V. The median duration of follow-up was 6 months, during which time 7 of 13 patients (54%) with central nervous system infection, 3 of 6 patients (50%) with autonomic nervous system dysregulation, and 3 of 8 patients (37%) with heart failure showed motor function outcomes in classes III to V. These findings suggested that the usage of intravenous immunoglobulin and the severity of disease staging at disease onset might not be able to predict long-term motor function outcomes.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. [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

  10. 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

  11. 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

  12. [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

  13. [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.

  14. 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

  15. 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.

  16. 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

  17. Open biopsy in patients with acute progressive neurologic decline and absence of mass lesion(Podcast)(CME)

    PubMed Central

    Schuette, Albert J.; Taub, Jason S.; Hadjipanayis, Costas G.; Olson, Jeffrey J.

    2010-01-01

    Objective: Patients with acute to subacute neurologic decline undergo a battery of imaging and laboratory tests to determine a diagnosis and treatment plan. Often, after an extensive evaluation, a brain biopsy is recommended as yet another tool to assist in determining the diagnosis. The goal of this retrospective cohort analysis is to measure the sensitivity of open brain biopsy in this patient population, compare these results with the preoperative presumed diagnosis, and evaluate if the biopsy result significantly alters treatment. Methods: The authors reviewed the medical records of 135 consecutive patients who underwent open brain biopsies for acute to subacute progressive neurologic decline between January 1999 and September 2008 at a single institution. All patients with mass lesions, with HIV/AIDS, and who were younger than 20 years of age were excluded from the study. Fifty-one patients met these criteria and all preoperative tests, imaging, and treatment plans were examined and compared with postbiopsy interventions to determine the impact of the biopsy on patient outcome. Results: The sensitivity of open brain biopsy at our institution was 35%. The most common preoperative presumed diagnosis was vasculitis and the most common postoperative finding was Creutzfeldt-Jakob disease, followed by amyloid angiopathy. Postbiopsy hemorrhage was a complication in 4% of patients. Treatment plans changed as a direct result of the biopsy in 8% of patients, and in only 4% did the biopsy findings make a difference in disease course. Conclusion: In patients with progressive neurologic decline without a radiographic mass lesion or immunodeficiency, open brain biopsy often fails to provide a diagnosis and even more rarely does it significantly alter treatment. GLOSSARY CJD = Creutzfeldt-Jakob disease; PCNSL = primary CNS lymphoma. PMID:20679635

  18. 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

  19. 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.

  20. [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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. [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.

  8. [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

  9. 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

  10. Transverse Myelitis in Acute Hepatitis A Infection: The Rare Co-Occurrence of Hepatology and Neurology

    PubMed Central

    Chonmaitree, Piyanant; Methawasin, Kulthida

    2016-01-01

    Transverse myelitis refers to the inflammatory process involving the spinal cord. Clinical features can be either acute or subacute onset that results in neurological deficits such as weakness and/or numbness of extremities as well as autonomic dysfunctions. While there are some etiologies related, a viral infection is common. However, the hepatitis A virus rarely causes myelitis. This report provides details of a hepatitis A infectious patient who developed myelitis as comorbidity. Although, the disability was initially severe, the patient successfully recovered with corticosteroid treatment. PMID:27403101

  11. Transverse Myelitis in Acute Hepatitis A Infection: The Rare Co-Occurrence of Hepatology and Neurology.

    PubMed

    Chonmaitree, Piyanant; Methawasin, Kulthida

    2016-01-01

    Transverse myelitis refers to the inflammatory process involving the spinal cord. Clinical features can be either acute or subacute onset that results in neurological deficits such as weakness and/or numbness of extremities as well as autonomic dysfunctions. While there are some etiologies related, a viral infection is common. However, the hepatitis A virus rarely causes myelitis. This report provides details of a hepatitis A infectious patient who developed myelitis as comorbidity. Although, the disability was initially severe, the patient successfully recovered with corticosteroid treatment. PMID:27403101

  12. [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

  13. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    SciTech Connect

    Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil K.; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.

    2012-10-05

    Acute Lyme disease results from transmission of and infection by the bacterium Borrelia burgdorferi following a tick bite. During acute infection, bacteria can disseminate to the central nervous system (CNS) leading to the development of Lyme meningitis. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing for a deep view into the proteome for a cohort of patients with early-disseminated Lyme disease and CSF inflammation leading to the identification of proteins that reflect host responses, which are distinct for subjects with acute Lyme disease. Additionally, we analyzed individual patient samples and quantified changes in protein abundance employing label-free quantitative mass spectrometry based methods. The measured changes in protein abundances reflect the impact of acute Lyme disease on the CNS as presented in CSF. We have identified 89 proteins that differ significantly in abundance in patients with acute Lyme disease. A number of the differentially abundant proteins have been found to be localized to brain synapse and thus constitute important leads for better understanding of the neurological consequence of disseminated Lyme disease.

  14. (-)-Epigallocatechin-3-gallate (EGCG) modulates neurological function when intravenously infused in acute and, chronically injured spinal cord of adult rats.

    PubMed

    Renno, Waleed M; Al-Khaledi, Ghanim; Mousa, Alyaa; Karam, Shaima M; Abul, Habib; Asfar, Sami

    2014-02-01

    Spinal cord injury (SCI) causes severe and long lasting motor and sensory deficits, chronic pain, and autonomic dysreflexia. (-)-epigallocatechin-3-gallate (EGCG) has shown to produce neuroprotective effect in a broad range of neurodegenerative disease animal models. This study designed to test the efficacy of intravenous infusion of EGCG for 36 h, in acutely injured rats' spinal cord: within first 4 h post-injury and, in chronically SC injured rats: after one year of injury. Functional outcomes measured using standard BBB scale, The Louisville Swim Scale (LSS) and, pain behavior assessment tests. 72 Female adult rats subjected to moderate thoracic SCI using MASCIS Impactor, blindly randomized as the following: (I) Acute SCI + EGCG (II) Acute SCI + saline. (III) Chronic SCI + EGCG. (IV) Chronic SCI + saline and, sham SCI animals. EGCG i.v. treatment of acute and, chronic SCI animals resulted in significantly better recovery of motor and sensory functions, BBB and LSS (P < 0.005) and (P < 0.05) respectively. Tactile allodynia, mechanical nociception (P < 0.05) significantly improved. Paw withdrawal and, tail flick latencies increase significantly (P < 0.05). Moreover, in the EGCG treated acute SCI animals the percentage of lesion size area significantly reduced (P < 0.0001) and, the number of neurons in the spinal cord increased (P < 0.001). Percent areas of GAP-43 and GFAP immunohistochemistry showed significant (P < 0.05) increase. We conclude that the therapeutic window of opportunity for EGCG to depict neurological recovery in SCI animals, is viable up to one year post SCI when intravenously infused for 36 h. PMID:24071567

  15. (-)-Epigallocatechin-3-gallate (EGCG) modulates neurological function when intravenously infused in acute and, chronically injured spinal cord of adult rats.

    PubMed

    Renno, Waleed M; Al-Khaledi, Ghanim; Mousa, Alyaa; Karam, Shaima M; Abul, Habib; Asfar, Sami

    2014-02-01

    Spinal cord injury (SCI) causes severe and long lasting motor and sensory deficits, chronic pain, and autonomic dysreflexia. (-)-epigallocatechin-3-gallate (EGCG) has shown to produce neuroprotective effect in a broad range of neurodegenerative disease animal models. This study designed to test the efficacy of intravenous infusion of EGCG for 36 h, in acutely injured rats' spinal cord: within first 4 h post-injury and, in chronically SC injured rats: after one year of injury. Functional outcomes measured using standard BBB scale, The Louisville Swim Scale (LSS) and, pain behavior assessment tests. 72 Female adult rats subjected to moderate thoracic SCI using MASCIS Impactor, blindly randomized as the following: (I) Acute SCI + EGCG (II) Acute SCI + saline. (III) Chronic SCI + EGCG. (IV) Chronic SCI + saline and, sham SCI animals. EGCG i.v. treatment of acute and, chronic SCI animals resulted in significantly better recovery of motor and sensory functions, BBB and LSS (P < 0.005) and (P < 0.05) respectively. Tactile allodynia, mechanical nociception (P < 0.05) significantly improved. Paw withdrawal and, tail flick latencies increase significantly (P < 0.05). Moreover, in the EGCG treated acute SCI animals the percentage of lesion size area significantly reduced (P < 0.0001) and, the number of neurons in the spinal cord increased (P < 0.001). Percent areas of GAP-43 and GFAP immunohistochemistry showed significant (P < 0.05) increase. We conclude that the therapeutic window of opportunity for EGCG to depict neurological recovery in SCI animals, is viable up to one year post SCI when intravenously infused for 36 h.

  16. Cerebrolysin effects on neurological outcomes and cerebral blood flow in acute ischemic stroke

    PubMed Central

    Amiri-Nikpour, Mohammad Reza; Nazarbaghi, Surena; Ahmadi-Salmasi, Babak; Mokari, Tayebeh; Tahamtan, Urya; Rezaei, Yousef

    2014-01-01

    Background Cerebrolysin, a brain-derived neuropeptide, has been shown to improve the neurological outcomes of stroke, but no study has demonstrated its effect on cerebral blood flow. This study aimed to determine the cerebrolysin impact on the neurological outcomes and cerebral blood flow. Methods In a randomized, double-blinded, placebo-controlled trial, 46 patients who had acute focal ischemic stroke were randomly assigned into two groups to receive intravenously either 30 mL of cerebrolysin diluted in normal saline daily for 10 days (n=23) or normal saline alone (n=23) adjunct to 100 mg of aspirin daily. All patients were examined using the National Institutes of Health Stroke Scale and transcranial Doppler to measure the mean flow velocity and pulsatility index (PI) of their cerebral arteries at baseline as well as on days 30, 60, and 90. Results The patients’ mean age was 60±9.7 years, and 51.2% of patients were male. The National Institutes of Health Stroke Scale was significantly lower in the cerebrolysin group compared with the placebo group on day 60 (median 10, interquartile range 9–11, P=0.008) and day 90 (median 11, interquartile range 10–13.5, P=0.001). The median of PI in the right middle cerebral artery was significantly lower in the cerebrolysin group compared with the placebo group on days 30, 60, and 90 (P<0.05). One patient in the cerebrolysin group and two patients in the placebo group died before day 30 (4.3% versus 8.7%). Conclusion Cerebrolysin can be useful to improve the neurological outcomes and the PI of middle cerebral artery in patients with acute focal ischemic stroke. PMID:25516711

  17. [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.

  18. 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.

  19. Aggressive and acute periodontal diseases.

    PubMed

    Albandar, Jasim M

    2014-06-01

    Inflammatory periodontal diseases are highly prevalent, although most of these diseases develop and progress slowly, often unnoticed by the affected individual. However, a subgroup of these diseases include aggressive and acute forms that have a relatively low prevalence but show a rapid-course, high rate of progression leading to severe destruction of the periodontal tissues, or cause systemic symptoms that often require urgent attention from healthcare providers. Aggressive periodontitis is an early-onset, destructive disease that shows a high rate of periodontal progression and distinctive clinical features. A contemporary case definition of this disease is presented. Population studies show that the disease is more prevalent in certain geographic regions and ethnic groups. Aggressive periodontitis is an infectious disease, and recent data show that in affected subjects the subgingival microbiota is composed of a mixed microbial infection, with a wide heterogeneity in the types and proportions of microorganisms recovered. Furthermore, there are significant differences in the microbiota of the disease among different geographic regions and ethnicities. There is also evidence that the Aggregatibacter actinomycetemycomitans-JP2 clone may play an important role in the development of the disease in certain populations. The host response plays an important role in the susceptibility to aggressive periodontitis, where the immune response may be complex and involve multiple mechanisms. Also, genetic factors seem to play an important role in the pathogenesis of this disease, but the mechanisms of increased susceptibility are complex and not yet fully understood. The available data suggest that aggressive periodontitis is caused by mutations either in a few major genes or in multiple small-effect genes, and there is also evidence of gene-gene and gene-environment interaction effects. Diagnostic methods for this disease, based on a specific microbiologic, immunologic or

  20. 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

  1. Urine specific gravity as a predictor of early neurological deterioration in acute ischemic stroke.

    PubMed

    Lin, L C; Fann, W C; Chou, M H; Chen, H W; Su, Y C; Chen, J C

    2011-07-01

    We previously found that a blood urea nitrogen/creatinine (BUN/Cr) ratio>15 is an independent predictor of early neurological deterioration after acute ischemic stroke, which suggests that dehydration may be a cause of early deterioration. The aim of this study was to determine whether urine specific gravity, which is another indicator of hydration status and one that is more easily obtained, is also an independent predictor of early deterioration or stroke-in-evolution (SIE). Demographic and clinical data were recorded at admission from patients with acute ischemic stroke who were prospectively enrolled from October 2007 to June 2010. We compared patients with and without stroke-in-evolution (based on an increase of 3 points or more points on the National Institutes of Health Stroke Scale within 3 days). Univariate and multivariate statistical analyses were carried out. A total of 317 patients (43 SIE and 274 non-SIE) were enrolled; the first 196 patients comprised the cohort of our previous study. The only two independent predictors of early deterioration or SIE were BUN/Cr>15 and urine specific gravity>1.010. After adjusting for age and gender, patients with a urine specific gravity>1.010 were 2.78 times more likely to develop SIE (95% CI=1.11-6.96; P=0.030). Urine specific gravity may be useful as an early predictor of early deterioration in patients with acute ischemic stroke. Patients with urine specific gravity ≤ 1.010 therefore may have a reduced likelihood of early neurological deterioration.

  2. 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

  3. Acute encephalomyelitis complicated with severe neurological sequelae after intrathecal administration of methotrexate in a patient with acute lymphoblastic leukemia.

    PubMed

    Nishikawa, Takuro; Okamoto, Yasuhiro; Maruyama, Shinsuke; Tanabe, Takayuki; Kurauchi, Koichiro; Kodama, Yuichi; Nakagawa, Shunsuke; Shinkoda, Yuichi; Kawano, Yoshifumi

    2014-11-01

    A four-year-old girl on maintenance therapy for acute lymphoblastic leukemia (ALL) complained of a headache and low back pain on the day she received her 21st intrathecal methotrexate (it-MTX) administration, and the next day experienced numbness and pain in her foot. This numbness gradually spread to her hand. She thereafter developed a fever and was hospitalized on day 8. After antibiotic therapy, the fever disappeared. However, her lower limbs became paralyzed, and she also developed urinary retention. On day 12, her paralysis progressed upwards, and she also developed paralysis of the upper limbs. Finally, she experienced convulsions with an impairment of consciousness. A magnetic resonance imaging study of the brain and spinal cord showed abnormal signals in the brain cortex and anterior horn. Accordingly, we diagnosed acute encephalomyelitis associated with it-MTX. High-dose intravenous immunoglobulin, steroid pulse therapy, plasma exchange, and dextromethorphan administration were initiated, while she received mechanical ventilation. Despite this intensive treatment, she suffered severe neurological damage and had to be maintained on mechanical ventilation due to persistent flaccid quadriplegia one year after the onset. When patients have symptoms of ascending paralysis during it-MTX treatment, clinicians should carefully consider the possibility of acute encephalomyelitis due to it-MTX. PMID:25501412

  4. Acute Chagas Disease in a Returning Traveler

    PubMed Central

    Carter, Yvonne L.; Juliano, Jonathan J.; Montgomery, Susan P.; Qvarnstrom, Yvonne

    2012-01-01

    Acute Chagas disease is rarely recognized, and the risk for acquiring the disease is undefined in travelers to Central America. We describe a case of acute Chagas disease in a traveler to Costa Rica and highlight the need for increased awareness of this infection in travelers to Chagas-endemic areas. PMID:23091192

  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. Acute Neurologic Disorder from an Inhibitor of Fatty Acid Amide Hydrolase.

    PubMed

    Kerbrat, Anne; Ferré, Jean-Christophe; Fillatre, Pierre; Ronzière, Thomas; Vannier, Stéphane; Carsin-Nicol, Béatrice; Lavoué, Sylvain; Vérin, Marc; Gauvrit, Jean-Yves; Le Tulzo, Yves; Edan, Gilles

    2016-11-01

    Background A decrease in fatty acid amide hydrolase (FAAH) activity increases the levels of endogenous analogues of cannabinoids, or endocannabinoids. FAAH inhibitors have shown analgesic and antiinflammatory activity in animal models, and some have been tested in phase 1 and 2 studies. In a phase 1 study, BIA 10-2474, an orally administered reversible FAAH inhibitor, was given to healthy volunteers to assess safety. Methods Single doses (0.25 to 100 mg) and repeated oral doses (2.5 to 20 mg for 10 days) of BIA 10-2474 had been administered to 84 healthy volunteers in sequential cohorts; no severe adverse events had been reported. Another cohort of participants was then assigned to placebo (2 participants) or 50 mg of BIA 10-2474 per day (6 participants). This report focuses on neurologic adverse events in participants in this final cohort. A total of 4 of the 6 participants who received active treatment consented to have their clinical and radiologic data included in this report. Results An acute and rapidly progressive neurologic syndrome developed in three of the four participants starting on the fifth day of drug administration. The main clinical features were headache, a cerebellar syndrome, memory impairment, and altered consciousness. Magnetic resonance imaging showed bilateral and symmetric cerebral lesions, including microhemorrhages and hyperintensities on fluid-attenuated inversion recovery and diffusion-weighted imaging sequences predominantly involving the pons and hippocampi. One patient became brain dead; the condition of two patients subsequently improved, but one patient had residual memory impairment, and the other patient had a residual cerebellar syndrome. One patient remained asymptomatic. Conclusions An unanticipated severe neurologic disorder occurred after ingestion of BIA 10-2474 at the highest dose level used in a phase 1 trial. The underlying mechanism of this toxic cerebral syndrome remains unknown.

  7. Hippotherapy acute impact on heart rate variability non-linear dynamics in neurological disorders.

    PubMed

    Cabiddu, Ramona; Borghi-Silva, Audrey; Trimer, Renata; Trimer, Vitor; Ricci, Paula Angélica; Italiano Monteiro, Clara; Camargo Magalhães Maniglia, Marcela; Silva Pereira, Ana Maria; Rodrigues das Chagas, Gustavo; Carvalho, Eliane Maria

    2016-05-15

    Neurological disorders are associated with autonomic dysfunction. Hippotherapy (HT) is a therapy treatment strategy that utilizes a horse in an interdisciplinary approach for the physical and mental rehabilitation of people with physical, mental and/or psychological disabilities. However, no studies have been carried out which evaluated the effects of HT on the autonomic control in these patients. Therefore, the objective of the present study was to investigate the effects of a single HT session on cardiovascular autonomic control by time domain and non-linear analysis of heart rate variability (HRV). The HRV signal was recorded continuously in twelve children affected by neurological disorders during a HT session, consisting in a 10-minute sitting position rest (P1), a 15-minute preparatory phase sitting on the horse (P2), a 15-minute HT session (P3) and a final 10-minute sitting position recovery (P4). Time domain and non-linear HRV indices, including Sample Entropy (SampEn), Lempel-Ziv Complexity (LZC) and Detrended Fluctuation Analysis (DFA), were calculated for each treatment phase. We observed that SampEn increased during P3 (SampEn=0.56±0.10) with respect to P1 (SampEn=0.40±0.14, p<0.05), while DFA decreased during P3 (DFA=1.10±0.10) with respect to P1 (DFA=1.26±0.14, p<0.05). A significant SDRR increase (p<0.05) was observed during the recovery period P4 (SDRR=50±30ms) with respect to the HT session period P3 (SDRR=30±10ms). Our results suggest that HT might benefit children with disabilities attributable to neurological disorders by eliciting an acute autonomic response during the therapy and during the recovery period.

  8. Hippotherapy acute impact on heart rate variability non-linear dynamics in neurological disorders.

    PubMed

    Cabiddu, Ramona; Borghi-Silva, Audrey; Trimer, Renata; Trimer, Vitor; Ricci, Paula Angélica; Italiano Monteiro, Clara; Camargo Magalhães Maniglia, Marcela; Silva Pereira, Ana Maria; Rodrigues das Chagas, Gustavo; Carvalho, Eliane Maria

    2016-05-15

    Neurological disorders are associated with autonomic dysfunction. Hippotherapy (HT) is a therapy treatment strategy that utilizes a horse in an interdisciplinary approach for the physical and mental rehabilitation of people with physical, mental and/or psychological disabilities. However, no studies have been carried out which evaluated the effects of HT on the autonomic control in these patients. Therefore, the objective of the present study was to investigate the effects of a single HT session on cardiovascular autonomic control by time domain and non-linear analysis of heart rate variability (HRV). The HRV signal was recorded continuously in twelve children affected by neurological disorders during a HT session, consisting in a 10-minute sitting position rest (P1), a 15-minute preparatory phase sitting on the horse (P2), a 15-minute HT session (P3) and a final 10-minute sitting position recovery (P4). Time domain and non-linear HRV indices, including Sample Entropy (SampEn), Lempel-Ziv Complexity (LZC) and Detrended Fluctuation Analysis (DFA), were calculated for each treatment phase. We observed that SampEn increased during P3 (SampEn=0.56±0.10) with respect to P1 (SampEn=0.40±0.14, p<0.05), while DFA decreased during P3 (DFA=1.10±0.10) with respect to P1 (DFA=1.26±0.14, p<0.05). A significant SDRR increase (p<0.05) was observed during the recovery period P4 (SDRR=50±30ms) with respect to the HT session period P3 (SDRR=30±10ms). Our results suggest that HT might benefit children with disabilities attributable to neurological disorders by eliciting an acute autonomic response during the therapy and during the recovery period. PMID:26988283

  9. Urgent carotid endarterectomy in patients with acute neurological ischemic events within six hours after symptoms onset.

    PubMed

    Gajin, P; Radak, Dj; Tanaskovic, S; Babic, S; Nenezic, D

    2014-06-01

    To analyze the outcome of urgent carotid endarterectomy (CEA) performed within less than six hours in patients with crescendo transient ischemic attack (TIA) and stroke in progression. From January 1998 to December 2008, 58 urgent CEAs were done for acute neurological ischemic events--46 patients with crescendo TIA and 12 patients with stroke in progression. Brain computed tomography (CT) was done prior and after the surgery. Disability level was assessed prior to and after urgent CEA using modified Rankin scale. Median follow-up was 42.1 ± 16.6 months. In the early postoperative period stroke rate was 0% for the patients in crescendo TIA group while in patients with stroke in progression group 3 patients (25%) had positive postoperative brain CT, yet neurological status significantly improved. Mid-term stroke rate was 2.2% in crescendo TIA group and 8.3% in stroke in progression group. In the early postoperative period there were no lethal outcomes, mid-term mortality was 8.3% in stroke in progression while in crescendo TIA group lethal outcomes were not observed. In conclusion, based on our results urgent CEA is a safe and effective treatment option for patients with crescendo TIA and stroke in progression with acceptable rate of postoperative complications.

  10. Neurologic Melioidosis: Case Report of a Rare Cause of Acute Flaccid Paralysis.

    PubMed

    Andersen, Erik W; Mackay, Mark T; Ryan, Monique M

    2016-03-01

    Acute flaccid paralysis is associated with inflammation, infection, or tumors in the spinal cord or peripheral nerves. Melioidosis (Burkholderia pseudomallei infection) can rarely cause this presentation. We describe a case of spinal melioidosis in a 4-year-old boy presenting with flaccid paralysis, and review the literature on this rare disease. PMID:26778096

  11. 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.

  12. Acute cerebrovascular disease in women.

    PubMed

    Arboix, A; Oliveres, M; García-Eroles, L; Maragall, C; Massons, J; Targa, C

    2001-01-01

    In 2,000 consecutive stroke patients collected in a prospective hospital-based stroke registry over a 10-year period, we assessed whether stroke in men and women was different in respect to vascular risk factors, clinical features and natural history. The frequency of the different variable in men and women was analyzed by means of univariate analysis and logistic regression models. Women accounted for 48% of the study population (n = 967) and were older than men (mean age 75 vs. 69 years, p < 0.001). In the age group of 85 years or older, stroke was more frequent in women than in men (69.8 vs. 30.2%, p < 0.001). Women showed a higher frequency of cardioembolic infarction and a lower occurrence of lacunar infarction and stroke of undetermined cause than men. In-hospital mortality (17.4 vs. 13.3%) and length of hospital stay (19.6 vs. 16.7 days) was significantly higher (p < 0.001) in women than in men. In the model based on demographic variables and cardiovascular risk factors, obesity, heart failure, atrial fibrillation and age were significant predictors of stroke in women, while intermittent claudication, ischemic heart disease, chronic obstructive pulmonary disease, cigarette smoking and alcohol abuse were predictors in male sex. Hypertension and limb weakness were predictors for stroke in women, and absence of neurological deficit at hospital discharge, lacunar syndrome and ataxia were predictors in men in the models based on all variables. Women differ from men in the distribution of risk factors and stroke subtype, stroke severity and outcome. Differences in stroke pathology and/or differences in functional anatomy or plasticity of the brain between sexes may account for these findings.

  13. 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

  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. 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.

  16. 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

  17. The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders.

    PubMed

    Masliah, E; Díez-Tejedor, E

    2012-04-01

    Neurotrophic factors are considered as part of the therapeutic strategy for neurological disorders like dementia, stroke and traumatic brain injury. Cerebrolysin is a neuropeptide preparation which mimics the action of endogenous neurotrophic factors on brain protection and repair. In dementia models, Cerebrolysin decreases β-amyloid deposition and microtubule-associated protein tau phosphorylation by regulating glycogen synthase kinase-3β and cyclin-dependent kinase 5 activity, increases synaptic density and restores neuronal cytoarchitecture. These effects protect integrity of the neuronal circuits and thus result in improved cognitive and behavioral performance. Furthermore, Cerebrolysin enhances neurogenesis in the dentate gyrus, the basis for neuronal replacement therapy in neurodegenerative diseases. Experimental studies in stroke animal models have shown that Cerebrolysin stabilizes the structural integrity of cells by inhibition of calpain and reduces the number of apoptotic cells after ischemic lesion. Cerebrolysin induces restorative processes, decreases infarct volume and edema formation and promotes functional recovery. Stroke-induced neurogenesis in the subventricular zone was also promoted by Cerebrolysin, thus supporting the brain's self-repair after stroke. Both, traumatic brain and spinal cord injury conditions stimulate the expression of natural neurotrophic factors to promote repair and regeneration processes -axonal regeneration, neuronal plasticity and neurogenesis- that is considered to be crucial for the future recovery. Neuroprotective effects of Cerebrolysin on experimentally induced traumatic spinal cord injury have shown that Cerebrolysin prevents apoptosis of lesioned motoneurons and promotes functional recovery. This section summarizes the most relevant data on the pharmacology of Cerebrolysin obtained from in vitro assays (biochemical and cell cultures) and in vivo animal models of acute and chronic neurological disorders.

  18. 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

  19. Acute exacerbations of fibrotic interstitial lung disease.

    PubMed

    Churg, Andrew; Wright, Joanne L; Tazelaar, Henry D

    2011-03-01

    An acute exacerbation is the development of acute lung injury, usually resulting in acute respiratory distress syndrome, in a patient with a pre-existing fibrosing interstitial pneumonia. By definition, acute exacerbations are not caused by infection, heart failure, aspiration or drug reaction. Most patients with acute exacerbations have underlying usual interstitial pneumonia, either idiopathic or in association with a connective tissue disease, but the same process has been reported in patients with fibrotic non-specific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, desquamative interstitial pneumonia and asbestosis. Occasionally an acute exacerbation is the initial manifestation of underlying interstitial lung disease. On biopsy, acute exacerbations appear as diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (BOOP) superimposed upon the fibrosing interstitial pneumonia. Biopsies may be extremely confusing, because the acute injury pattern can completely obscure the underlying disease; a useful clue is that diffuse alveolar damage and organizing pneumonia should not be associated with old dense fibrosis and peripheral honeycomb change. Consultation with radiology can also be extremely helpful, because the fibrosing disease may be evident on old or concurrent computed tomography scans. The aetiology of acute exacerbations is unknown, and the prognosis is poor; however, some patients survive with high-dose steroid therapy.

  20. 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.

  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. 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).

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. Four-Stage Audit Demonstrating Increased Uptake of HIV Testing in Acute Neurology Admissions Using Staged Practical Interventions

    PubMed Central

    Sokhi, Dilraj Singh; Oxenham, Chantal; Coates, Rebecca; Forbes, Mhairi; Gupta, Nadi K.; Blackburn, Daniel J.

    2015-01-01

    Background UK National Guidelines (UKNG) advise HIV testing in clinically indicated neurological presentations. We audited the impact of our practical strategies to increase uptake of HIV testing at a regional acute neurology admissions unit. Methods We audited HIV testing in 4 periods over 2 years: before we designed a UKNG-based “HIV testing in Neurology” protocol (“pre-protocol”); after dissemination of the protocol alone (“post-protocol”); post-protocol dissemination combined with both a tailored departmental admissions clerking proforma to prompt for HIV testing & consenting, and regular focussed tutorials to doctors on HIV testing in neurological patients (“post-proforma”); and finally one year after the post-proforma period (“+1 year”). We also looked at the total number of HIV tests sent from the unit during the two-year period. We assessed significance using Fisher’s exact test. Results 47.8% of all acute neurology non-stroke admissions were eligible for HIV testing during all the audit periods. Testing rates were as follows: pre-protocol 21.9%; post-protocol 36.6%; post-proforma 83.3%; and at +1 year 65.4% (p<0.05 for both post-protocol and +1 year when compared to pre-protocol). Documentation of consent for HIV testing improved from 25% to 67.6% with the HIV-tailored clerking proforma. The total number of HIV tests requested from the unit doubled in the post-proforma period compared to pre-protocol (p<0.05). Conclusion In conclusion: the combination of an HIV testing protocol, a tailored departmental clerking proforma and regular focussed teaching to doctors on indications for HIV testing led to a sustained increase in HIV testing uptake in our regional acute neurology admissions unit. PMID:26335351

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. [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.

  20. Leukocytosis in Patients with Neurologic Deterioration after Acute Ischemic Stroke is Associated with Poor Outcomes

    PubMed Central

    Kumar, Andre D.; Boehme, Amelia K.; Siegler, James E.; Gillette, Michael; Albright, Karen C.; Martin-Schild, Sheryl

    2016-01-01

    Background Neurologic deterioration (ND) after acute ischemic stroke (AIS) has been shown to result in poor outcomes. ND is thought to arise from penumbral excitotoxic cell death caused in part by leukocytic infiltration. Elevated admission peripheral leukocyte levels are associated with poor outcomes in stroke patients who suffer ND, but little is known about the dynamic changes that occur in leukocyte counts around the time of ND. We sought to determine if peripheral leukocyte levels in the days surrounding ND are correlated with poor outcomes. Methods Patients with AIS who presented to our center within 48 hours of symptom onset between July 2008 and June 2010 were retrospectively identified by chart review and screened for ND (defined as an increase in National Institutes of Health Stroke Scale score ≥2 within a 24-hour period). Patients were excluded for steroid use during hospitalization or in the month before admission and infection within the 48 hours before or after ND. Demographics, daily leukocyte counts, and poor functional outcome (modified Rankin Scale score 3–6) were investigated. Results Ninety-six of the 292 (33%) patients screened had ND. The mean age was 69.5 years; 62.5% were male and 65.6% were black. Patients with a poor functional outcome had significantly higher leukocyte and neutrophil levels 1 day before ND (P =.048 and P =.026, respectively), and on the day of ND (P =.013 and P =.007, respectively), compared to patients with good functional outcome. Conclusions Leukocytosis at the time of ND correlates with poor functional outcomes and may represent a marker of greater cerebral damage through increased parenchymal inflammation. PMID:23031742

  1. 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

  2. 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).

  3. 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.

  4. 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

  5. 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.

  6. (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

  7. 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.

  8. 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.

  9. 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

  10. [Peripheral artery disease and acute coronary syndrome].

    PubMed

    Martínez-Quintana, Efrén; Rodríguez-González, Fayna

    2015-01-01

    Peripheral arterial disease is a common manifestation of systemic atherosclerosis that is associated with increased cardiovascular risk. When presented in the context of an acute coronary syndrome a differential diagnosis with aorta dissection should be made, because peripheral arterial disease may be asymptomatic despite the absence or asymmetry of femoral pulses.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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

  2. Small Cell Lung Cancer Patient with Profound Hyponatremia and Acute Neurological Symptoms: An Effective Treatment with Fludrocortisone

    PubMed Central

    Jaal, Jana; Jõgi, Tõnu; Altraja, Alan

    2015-01-01

    Hyponatremia is a frequent electrolyte abnormality in patients with small cell lung cancer (SCLC). Being usually asymptomatic, hyponatremia may cause symptoms like nausea, fatigue, disorientation, headache, muscle cramps, or even seizures, particularly if severe and rapid decrease of serum sodium levels occurs. Here we report a case of SCLC patient with severe hyponatremia and acute neurological symptoms that developed 2 days after the first course of second-line chemotherapy, most probably due to the release of antidiuretic hormone (ADH, also known as arginine vasopressin) during lysis of the tumour cells. Initial treatment consisted of continuous administration of hypertonic saline that resulted in improvement of patient's neurological status. However, to obtain a persistent increase in serum sodium level, pharmacological intervention with oral fludrocortisone 0.1 mg twice daily was needed. We can therefore conclude that mineralocorticoids may be used to correct hyponatremia in SCLC patients when appropriate. PMID:26240768

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. Hyponatremia in acute brain disease: the cerebral salt wasting syndrome.

    PubMed

    Betjes, Michiel G.H.

    2002-02-01

    Hyponatremia in acute brain disease is a common occurrence, especially after an aneurysmal subarachnoid hemorrhage. Originally, excessive natriuresis, called cerebral salt wasting, and later the syndrome of inappropriate antidiuretic hormone secretion (SIADH), were considered to be the causes of hyponatremia. In recent years, it has become clear that most of these patients are volume-depleted and have a negative sodium balance, consistent with the original description of cerebral salt wasting. Elevated plasma concentrations of atrial or brain natriuretic peptide have been identified as the putative natriuretic factor. Hyponatremia and volume depletion may aggravate neurological symptoms, and timely treatment with adequate replacement of water and NaCl is essential. The use of fludrocortisone to increase sodium reabsorption by the renal tubules may be an alternative approach.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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

  19. Neurologic Emergencies in the Elderly.

    PubMed

    Nentwich, Lauren M; Grimmnitz, Benjamin

    2016-08-01

    Neurologic diseases are a major cause of death and disability in elderly patients. Due to the physiologic changes and increased comorbidities that occur as people age, neurologic diseases are more common in geriatric patients and a major cause of death and disability in this population. This article discusses the elderly patient presenting to the emergency department with acute ischemic stroke, transient ischemic attack, intracerebral hemorrhage, subarachnoid hemorrhage, chronic subdural hematoma, traumatic brain injury, seizures, and central nervous system infections. This article reviews the subtle presentations, difficult workups, and complicated treatment decisions as they pertain to our older patients." PMID:27475016

  20. Neurologic morbidity and quality of life in survivors of childhood acute lymphoblastic leukemia: a prospective cross-sectional study

    PubMed Central

    Khan, Raja B.; Hudson, Melissa M.; Ledet, Davonna S.; Morris, E. Brannon; Pui, Ching-Hon; Howard, Scott C.; Krull, Kevin R.; Hinds, Pamela S.; Crom, Debbie; Browne, Emily; Zhu, Liang; Rai, Shesh; Srivastava, Deokumar; Ness, Kirsten K.

    2014-01-01

    Purpose Childhood acute lymphoblastic leukemia (ALL) is treated with potentially neurotoxic drugs and neurologic complications in long-term survivors are inadequately studied. This study investigated neurologic morbidity and its effect on quality of life in long-term survivors of childhood ALL. Methods Prospective, single institution, cross-sectional, institutional review board-approved study of long-term ALL survivors. Participants were recruited from institutional clinics. Participants answered an investigator-administered questionnaire followed by evaluation by a neurologist. Quality of life (QOL) was also assessed. Results Of the 162 participants recruited over a 3-year period, 83.3 % reported at least one neurologic symptom of interest, 16.7 % had single symptom, 11.1 % had two symptoms, and 55.6 % had three or more symptoms. Symptoms were mild and disability was low in the majority of participants with neurologic symptoms. Median age at ALL diagnosis was 3.9 years (0.4–18.6), median age at study enrollment was 15.7 years (6.9–28.9), and median time from completion of ALL therapy was 7.4 years (1.9–20.3). On multivariable analyses, female sex correlated with presence of dizziness, urinary incontinence, constipation, and neuropathy; use of≥10 doses of triple intrathecal chemotherapy correlated with uri-nary incontinence, back pain, and neuropathy; cranial radiation with ataxia; history of ALL relapse with fatigue; and CNS leukemia at diagnosis with seizures. Decline in mental QOL was associated with migraine and tension type headaches, while physical QOL was impaired by presence of dizziness and falls. Overall, good QOL and physical function was maintained by a majority of participants. Conclusions Neurologic symptoms were present in 83 % long-term ALL survivors. Symptoms related morbidity and QOL impairment is low in majority of survivors. Female sex, ≥10 doses of intrathecal chemotherapy, and history of ALL relapse predispose to impaired QOL

  1. 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

  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.

  3. 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

  4. 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.

  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. 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

  9. 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

  10. [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.

  11. 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

  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. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. [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.

  7. 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.

  8. Anorexia during acute and chronic disease.

    PubMed

    Plata-Salamán, C R

    1996-02-01

    Anorexia is associated with disorders of all systems. Anorexia represents a consistent clinical manifestation during acute and chronic pathophysiological processes (infection, inflammation, injury, toxins, immunological reactions, malignancy and necrosis). Anorexia during disease can be beneficial or deleterious depending on the timing and duration. Temporary anorexia during acute disease may be beneficial to an organism since a restriction in the intake of micro- and macro-nutrients will inhibit bacterial growth. Long-term anorexia during chronic disease, however, is deleterious to an organism and may be associated with cachexia, which can ultimately result in death. Various mechanisms participate in the anorexia observed during disease, including cytokine action. Anorexia induced by cytokines is proposed to involve modulation of hypothalamic-feeding associated sites, prostaglandin-dependent mechanisms, modifications of neurotransmitter systems, gastrointestinal, metabolic, and endocrine factors. In addition, the anorexia-cachexia syndrome is multifactorial and may involve chronic pain, depression or anxiety, hypogeusia and hyposmia, chronic nausea, early satiety, malfunction of the gastrointestinal system, metabolic alterations, cytokine action, production of other anorexigenic substances and/or iatrogenic causes (chemotherapy, radiotherapy). Cachexia may result not only from anorexia and a decreased caloric intake, but also from malabsorption and losses from the body (ulcers, hemorrhage, effusions), or a change in body metabolism. Research has focused on potential interventions to modify anorexia during disease and the anorexia-cachexia syndrome. Nutritional modifications and the use of specific steroids (such as megestrol acetate) are being tested in the clinical setting. Understanding the specific mechanisms responsible for anorexia during disease as well as their interactions is essential to develop interventions for the control of anorexia (during a critical

  9. 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.

  10. 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.

  11. 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

  12. 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.

  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. PMID:24975171

  14. 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.

  15. 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

  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. 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.

  18. 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

  19. Crohn's disease and acute pancreatitis. A review of literature.

    PubMed

    Jasdanwala, Sarfaraz; Babyatsky, Mark

    2015-03-01

    Crohn's disease, a transmural inflammatory bowel disease, has many well-known extra-intestinal manifestations and complications. Although acute pancreatitis has a higher incidence in patients with Crohn's disease as compared to the general population, acute pancreatitis is still relatively uncommon in patients with Crohn's disease. Patients with Crohn's disease are at an approximately fourfold higher risk than the general population to develop acute pancreatitis. The risk of developing acute pancreatitis is higher in females as compared to males. Acute pancreatitis can occur at any age with higher incidence reported in patients in their 20s and between 40-50 years of age. The severity and prognosis of acute pancreatitis in patients with Crohn's disease is the same as in general population. Acute pancreatitis can occur before onset of intestinal Crohn's disease, this presentation being more common in children than adults. It can also occur as the presenting symptom. However, most commonly it occurs after intestinal symptoms have manifest with a mean time interval between the initial presentation and development of acute pancreatitis being 2 years. There are several etiological factors contributing to acute pancreatitis in patients with Crohn's disease. It is not clear whether acute pancreatitis is a direct extra-intestinal manifestation of Crohn's disease; however, majority of the cases of acute pancreatitis in patients with Crohn's disease are due to GS and medications. Drugs used for the treatment of Crohn's disease that have been reported to cause acute pancreatitis include 5-ASA agents, azathioprine and 6 mercaptopurine, metornidazole and corticosteroids. Recent evidence has emerged correlating both type 1 and 2 autoimmune pancreatitis with Crohn's disease. Understanding the association between the two disease entities is key to effectively manage patients with Crohn's disease and acute pancreatitis.

  20. The radical scavenger edaravone improves neurologic function and perihematomal glucose metabolism after acute intracerebral hemorrhage.

    PubMed

    Shang, Hanbing; Cui, Derong; Yang, Dehua; Liang, Sheng; Zhang, Weifeng; Zhao, Weiguo

    2015-01-01

    Oxidative injury caused by reactive oxygen species plays an important role in the progression of intracerebral hemorrhage (ICH)-induced secondary brain injury. Previous studies have demonstrated that the free radical scavenger edaravone may prevent neuronal injury and brain edema after ICH. However, the influence of edaravone on cerebral metabolism in the early stages after ICH and the underlying mechanism have not been fully investigated. In the present study, we investigated the effect of edaravone on perihematomal glucose metabolism using (18)F-fluorordeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Additionally, the neurologic deficits, brain edemas, and cell death that followed ICH were quantitatively analyzed. After blood infusion, the rats treated with edaravone showed significant improvement in both forelimb placing and corner turn tests compared with those treated with vehicle. Moreover, the brain water content of the edaravone-treated group was significantly decreased compared with that of the vehicle group on day 3 after ICH. PET/CT images of ICH rats exhibited obvious decreases in FDG standardized uptake values in perihematomal region on day 3, and the lesion-to-normal ratio of the edaravone-treated ICH rats was significantly increased compared with that of the control rats. Calculation of the brain injury volumes from the PET/CT images revealed that the volumes of the blood-induced injuries were significantly smaller in the edaravone group compared with the vehicle group. Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling assays performed 3 days after ICH revealed that the numbers of apoptotic cells in perihematomal region of edaravone-treated ICH rats were decreased relative to the vehicle group. Thus, the present study demonstrates that edaravone has scavenging properties that attenuate neurologic behavioral deficits and brain edema in the early period of ICH. Additionally, edaravone may improve

  1. Correlation between ADAMTS13 activity and neurological impairment in acute thrombotic microangiopathy patients.

    PubMed

    Berti de Marinis, Giulia; Novello, Stefano; Ferrari, Silvia; Barzon, Isabella; Cortella, Irene; Businaro, Maria Antonietta; Fabris, Fabrizio; Lombardi, Anna Maria

    2016-11-01

    Differential diagnosis between thrombotic thrombocytopenic purpura (TTP) and other thrombotic microangiopathies (TMA) is usually difficult because of frequently overlapping clinical presentations. Severely depressed ADAMTS13 activity (<10 %) seems distinctive for TTP because of its pathogenetic role. However a long debate exists in the literature about its sensibility and specificity. Our aim was to search for clinical differences between TMA patients referred to our laboratory, comparing them for protease activity <10 versus ≥10 %. ADAMTS13 activity ≥10 % patients (n = 73) showed a higher prevalence of drug- (p = 0.005) and cancer-associated (p < 0.001) TMA. Mean platelet count and renal dysfunction prevalence was lower (p < 0.001), while neurological impairment was more frequent (p = 0.001) in the <10 % ADAMTS13 activity group (n = 109), confirming previous literature findings. When taken neurological manifestations singularly, epilepsy (p = 0.04), focal motor deficit (p < 0.001) and cranial nerve palsy (p = 0.007) were more frequent in the <10 % activity group. In our case series, a <10 % ADAMTS13 activity depicts a group of patients with clinical features similar to TTP patients. Focal motor impairment or epileptic manifestations could further address toward a TTP diagnosis. Studies about treatment efficacy and follow-up are advised to determine whether laboratory findings can guide therapeutic decisions.

  2. 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.

  3. [Acute encephalic manifestations in Senegalese children with sickle cell disease].

    PubMed

    Diagne, I; Diagne-Guèye, N R; Fall, L; Ndiaye, O; Camara, B; Diouf, S; Signate-Sy, H; Kuakuvi, N

    2001-01-01

    The course of sickle cell disease (SCD) may be complicated by neurologic events, mainly bactérial meningitidis and stroke. We retrospectively studied all cases with acute encephalic manifestations (AEM) in a cohort of 461 children and adolescents with SCD followed at Albert Royer Children Hospital of Dakar (Senegal) from january 1991 to december 2000 (ten years). Among them 438 had sickle cell anemia (SCA), 19 SC disease and 4 S-beta thalassemia (3 S-beta+, 1 S-beta0). Seven patients, all with SCA, presented antecedents of AEM revealed by flacid and proportionnal hemiplegia evoking stroke. Prevalence of these AEM was 1.5 per cent among patients with SCD and 1.6 per cent among those with SCA. They were 4 girls and 3 boys (sex ratio = 0.75) aged 4 to 8.5 years when occurred the first accident. We observed no clinical or biological distinctive characteristic of SCA in these patients compared to those without crebrovascular accident. Recurrence was observed once in a boy after a 12 months interval and twice in a girl after 20 and 60 months intervals successively. No transfusionnal program was applied to prevent recurrent stroke because of insufficient conditions for long-term transfusion. Stroke appears to be rare in senegalese children with SCD. However it poses in our context the major problem of applicability of transfusionnal program which constitute the only therapy universally recognised to be effective to prevent recurrence. Nevertheless hydroxyurea could be a satisfactory alternative.

  4. Recommendations for Haemodynamic and Neurological Monitoring in Repair of Acute Type A Aortic Dissection

    PubMed Central

    Harrington, Deborah K.; Ranasinghe, Aaron M.; Shah, Anwar; Oelofse, Tessa; Bonser, Robert S.

    2011-01-01

    During treatment of acute type A aortic dissection there is potential for both pre- and intra-operative malperfusion. There are a number of monitoring strategies that may allow for earlier detection of potentially catastrophic malperfusion (particularly cerebral malperfusion) phenomena available for the anaesthetist and surgeon. This review article sets out to discuss the benefits of the current standard monitoring techniques available as well as desirable/experimental techniques which may serve as adjuncts in the monitoring of these complex patients. PMID:21776255

  5. 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

  6. 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

  7. 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.

  8. Blood pressure control in acute cerebrovascular disease.

    PubMed

    Owens, William B

    2011-03-01

    Acute cerebrovascular diseases (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) affect 780,000 Americans each year. Physicians who care for patients with these conditions must be able to recognize when acute hypertension requires treatment and should understand the principles of cerebral autoregulation and perfusion. Physicians should also be familiar with the various pharmacologic agents used in the treatment of cerebrovascular emergencies. Acute ischemic stroke frequently presents with hypertension, but the systemic blood pressure should not be treated unless the systolic pressure exceeds 220 mm Hg or the diastolic pressure exceeds 120 mm Hg. Overly aggressive treatment of hypertension can compromise collateral perfusion of the ischemic penumbra. Hypertension associated with intracerebral hemorrhage can be treated more aggressively to minimize hematoma expansion during the first 3 to 6 hours of illness. Subarachnoid hemorrhage is usually due to aneurysmal rupture; systolic blood pressure should be kept <150 mm Hg to prevent re-rupture of the aneurysm. Nicardipine and labetalol are recommended for rapidly treating hypertension during cerebrovascular emergencies. Sodium nitroprusside is not recommended due to its adverse effects on cerebral autoregulation and intracranial pressure. Hypoperfusion of the injured brain should be avoided at all costs.

  9. Linking the Activity Measure for Post-acute Care and the Quality of Life Outcomes in Neurological Disorders

    PubMed Central

    Ni, Pengsheng; Lai, Jin-shei; Tian, Feng; Coster, Wendy J.; Jette, Alan M.; Straub, Donald; Cella, David

    2012-01-01

    Objective To use item response theory (IRT) methods to link physical functioning items in the Activity Measure for Post-acute Care (AM-PAC) and the Quality of Life Outcomes in Neurological Disorders (Neuro-QOL) Design Secondary data analysis of the physical functioning items of AM-PAC and Neuro-QOL. We used a non-equivalent group design with 36 core items common to both instruments. We used a test characteristic curve transformation method to for linking AM-PAC and Neuro-QOL scores. Linking was conducted so that both raw scores and scaled AM-PAC and Neuro-QOL scores (converted-logit scores with mean = 50 and SD = 10) could be compared. Setting AM-PAC items were administered to rehabilitation patients in post-acute care settings. Neuro-QOL items were administered to a community sample of adults via the Internet. Participants The AM-PAC sample consisted of 1,041 post acute care patients; the Neuro-QOL sample was 549 community-dwelling adults. Interventions Not applicable. Main Outcome Measures 25 Mobility items and 11 ADL items common to both instruments were included in the analysis. Results Neuro-QOL items were linked to the AM-PAC scale using the Generalized Partial Credit Model. Mobility and ADL subscale scores from the two instruments were calibrated to the AM-PAC metric. Conclusions An IRT-based linking method placed AM-PAC and NeuroQOL Mobility and ADL scores on a common metric. This linking allowed estimation of AM-PAC Mobility and ADL subscale scores based on Neuro-QOL Mobility and ADL subscale scores, and vice versa. The accuracy of these results should be validated in a future sample in which participants respond to both instruments. PMID:21958921

  10. PATHOLOGICAL FRACTURE OF LUMBAR VERTEBRA IN CHILDREN WITH ACUTE NEUROLOGICAL DEFICIT: CASE REPORT

    PubMed Central

    Bortoletto, Adalberto; Rodrigues, Luiz Cláudio Lacerda; Matsumoto, Marcelo Hide

    2015-01-01

    This study reports on a case of lymphoma in a 13-year-old patient who came to a consultation with lumbar pain. The patient had suffered low-intensity trauma in the lumbar region that resulted in persistent pain of progressive nature. In an emergency evaluation, radiographic examination showed a spinal fracture. The patient was then sent to the specialist outpatient clinic of the same hospital. The initial examinations confirmed the diagnosis of a pathological fracture surrounded by a tissue mass, thus indicating the presence of a tumor. Subsequently, the patient evolved with lower-limb paresthesia and urine retention, without any pathological diagnosis for the lesion. The patient then underwent emergency surgery to achieve stabilization and neurological decompression, and material from the lesion was sent for anatomopathological examination. The result from the anatomopathological examination suggested that the lesion was a small-cell tumor, although leaving some doubt. Immunohistochemistry defined the diagnosis of lymphoma. The patient was then sent for oncological treatment. The aim of this study was to report on a rare case of lymphoma in a child with an initial diagnosis of a pathological fracture in the lumbar spine. It is important to investigate fractures associated with mild trauma in children. Precise diagnosis results in effective attendance with better results for these patients. This patient underwent chemotherapy and achieved a good response, with positive repercussions for his prognosis. PMID:27047825

  11. Minimal residual disease in acute promyelocytic leukemia.

    PubMed

    Weil, S C

    2000-03-01

    In the last decade our understanding of acute promyelocytic leukemia (APL) has advanced tremendously. The recognition of all-trans retinoic acid (ATRA) as a powerful therapeutic agent paralleled the cloning of the t(15;17) breakpoint. RtPCR for the PML-RARA hybrid mRNA has become the hallmark of molecular diagnosis and molecular monitoring in APL. Current techniques are useful in predicting complete remission and a possible cure in many patients who repeatedly test negative by PCR. Standardizing techniques and improving the sensitivity of the assay are important. Doing this in a way so that clinically relevant minimal residual disease can be distinguished from "indolent disease" remains among the future challenges in APL. PMID:10702899

  12. 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.

  13. [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

  14. 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.

  15. 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

  16. Plasma copeptin as a predictor of intoxication severity and delayed neurological sequelae in acute carbon monoxide poisoning.

    PubMed

    Pang, Li; Wang, He-Lei; Wang, Zhi-Hao; Wu, Yang; Dong, Ning; Xu, Da-Hai; Wang, Da-Wei; Xu, Hong; Zhang, Nan

    2014-09-01

    The present study was designed to assess the usefulness of measuring plasma levels of copeptin (a peptide co-released with the hypothalamic stress hormone vasopressin) as a biomarker for the severity of carbon monoxide (CO) poisoning and for predicting delayed neurological sequelae (DNS). Seventy-two patients with CO poisoning and 72 sex and age matched healthy individuals were recruited. Plasma copeptin levels were measured on admission from CO poisoning patients and for healthy individuals at study entry by using a sandwich immunoassay. The CO poisoning patients were divided into two groups according to severity (unconscious and conscious) and occurrence of DNS. The mean plasma copeptin levels (52.5±18.5 pmol/L) in the unconscious group were significantly higher than in the conscious group (26.3±12.7 pmol/L) (P<0.001). Plasma copeptin levels of more than 39.0 pmol/L detected CO poisoning with severe neurological symptoms e.g. unconsciousness (sensitivity 84.6% and specificity 81.4%). The plasma copeptin levels were higher in patients with DNS compared to patients without DNS (52.2±20.6 pmol/L vs. 27.9±14.8 pmol/L, P<0.001). Plasma copeptin levels higher than 40.5 pmol/L predicted the development of DNS (sensitivity 77.8%, specificity 82.1%). Plasma copeptin levels were identified as an independent predictor for intoxication severity [odds ratio (OR) 1.261, 95% confidence interval (CI) 1.112-1.638, P=0.002] and DNS (OR 1.313, 95% CI 1.106-1.859, P=0.001). Thus, plasma copeptin levels independently related to intoxication severity and were identified as a novel biomarker for predicting DNS after acute CO poisoning.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. [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.

  2. 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

  3. 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

  4. Acute rheumatic fever and rheumatic heart disease.

    PubMed

    Carapetis, Jonathan R; Beaton, Andrea; Cunningham, Madeleine W; Guilherme, Luiza; Karthikeyan, Ganesan; Mayosi, Bongani M; Sable, Craig; Steer, Andrew; Wilson, Nigel; Wyber, Rosemary; Zühlke, Liesl

    2016-01-01

    Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus. The long-term damage to cardiac valves caused by ARF, which can result from a single severe episode or from multiple recurrent episodes of the illness, is known as rheumatic heart disease (RHD) and is a notable cause of morbidity and mortality in resource-poor settings around the world. Although our understanding of disease pathogenesis has advanced in recent years, this has not led to dramatic improvements in diagnostic approaches, which are still reliant on clinical features using the Jones Criteria, or treatment practices. Indeed, penicillin has been the mainstay of treatment for decades and there is no other treatment that has been proven to alter the likelihood or the severity of RHD after an episode of ARF. Recent advances - including the use of echocardiographic diagnosis in those with ARF and in screening for early detection of RHD, progress in developing group A streptococcal vaccines and an increased focus on the lived experience of those with RHD and the need to improve quality of life - give cause for optimism that progress will be made in coming years against this neglected disease that affects populations around the world, but is a particular issue for those living in poverty. PMID:27188830

  5. Acute Respiratory Distress: from syndrome to disease.

    PubMed

    Cardinal-Fernández, P; Correger, E; Villanueva, J; Rios, F

    2016-04-01

    The acute respiratory distress syndrome (ARDS) is currently one of the most important critical entities given its high incidence, rate of mortality, long-term sequelae and non-specific pharmacological treatment. The histological hallmark of ARDS is diffuse alveolar damage (DAD). Approximately 50% of ARDS patients present DAD, the rest is made up of a heterogeneous group of histological patterns, many of which correspond to a well-recognized disease. For that reason, if these patterns could be diagnosed, patients could benefit from a treatment. Recently, the effect of DAD in clinical and analytical evolution of ARDS has been demonstrated, so the classical approach to ARDS as an entity defined solely by clinical, radiological and gasometrical variables should be reconsidered. This narrative review aims to examine the need to evolve from the concept of ARDS as a syndrome to ARDS as a specific disease. So we have raised 4 critical questions: a) What is a disease?; b) what is DAD?; c) how is DAD considered according to ARDS definition?, and d) what is the relationship between ARDS and DAD?

  6. Acute rheumatic fever and rheumatic heart disease.

    PubMed

    Carapetis, Jonathan R; Beaton, Andrea; Cunningham, Madeleine W; Guilherme, Luiza; Karthikeyan, Ganesan; Mayosi, Bongani M; Sable, Craig; Steer, Andrew; Wilson, Nigel; Wyber, Rosemary; Zühlke, Liesl

    2016-01-14

    Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus. The long-term damage to cardiac valves caused by ARF, which can result from a single severe episode or from multiple recurrent episodes of the illness, is known as rheumatic heart disease (RHD) and is a notable cause of morbidity and mortality in resource-poor settings around the world. Although our understanding of disease pathogenesis has advanced in recent years, this has not led to dramatic improvements in diagnostic approaches, which are still reliant on clinical features using the Jones Criteria, or treatment practices. Indeed, penicillin has been the mainstay of treatment for decades and there is no other treatment that has been proven to alter the likelihood or the severity of RHD after an episode of ARF. Recent advances - including the use of echocardiographic diagnosis in those with ARF and in screening for early detection of RHD, progress in developing group A streptococcal vaccines and an increased focus on the lived experience of those with RHD and the need to improve quality of life - give cause for optimism that progress will be made in coming years against this neglected disease that affects populations around the world, but is a particular issue for those living in poverty.

  7. [Acute bacterial meningitis as an occupational disease].

    PubMed

    Seixas, Diana; Lebre, Ana; Crespo, Pedro; Ferreira, Eugénia; Serra, José Eduardo; Saraiva da Cunha, José Gabriel

    2014-01-01

    Streptococcus suis is a zoonotic pathogen with worldwide distribution, responsible for more than 700 human cases globally reported. This infection affects mostly men, exposed to pig or pork, which leads to its usual classification as an occupational disease. We report a case of acute bacterial meningitis in a 44 years old male. According to his past medical history, the patient had chronic alcoholism and worked in a restaurant as a piglet roaster. Microbiological examination of blood and CSF revealed S. suis. After 14 days of ceftriaxone the patient fully recovered. The authors review the clinical reports previously described in Portugal. In all of them was possible to identify risk exposition to pork. We alert to this microorganism's importance in Portugal where it is probably underdiagnosed.

  8. 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

  9. [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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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…

  19. Acute neurological visual loss in young adults: causes, diagnosis and management.

    PubMed

    Sawaya, R; El Ayoubi, N; Hamam, R

    2015-12-01

    Visual loss in the young adult can be caused by demyelinating diseases, inflammatory and autoimmune processes, infections, ischaemic events, and compressive lesions of the optic nerve. Diagnosis of the aetiologies of visual loss is reached by combining data from radiological studies, electrophysiological tests, and blood and cerebrospinal fluid analysis. Treatment is primarily aimed at decreasing the insult on the optic nerve and eventually controlling the primary disorder. The literature discusses separately the different aetiologies of visual loss. We present a review of the clinical characteristics of visual loss in the young adult, the different diagnostic measures, and the latest therapeutic strategies. The aim of this work is to summarise this entity in a practical way to guide clinicians in the diagnosis and management of this disorder. PMID:26504248

  20. [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.

  1. 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.

  2. 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

  3. 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.

  4. Association of Blood Lead Level with Neurological Features in 972 Children Affected by an Acute Severe Lead Poisoning Outbreak in Zamfara State, Northern Nigeria

    PubMed Central

    Greig, Jane; Thurtle, Natalie; Cooney, Lauren; Ariti, Cono; Ahmed, Abdulkadir Ola; Ashagre, Teshome; Ayela, Anthony; Chukwumalu, Kingsley; Criado-Perez, Alison; Gómez-Restrepo, Camilo; Meredith, Caitlin; Neri, Antonio; Stellmach, Darryl; Sani-Gwarzo, Nasir; Nasidi, Abdulsalami; Shanks, Leslie; Dargan, Paul I.

    2014-01-01

    Background In 2010, Médecins Sans Frontières (MSF) investigated reports of high mortality in young children in Zamfara State, Nigeria, leading to confirmation of villages with widespread acute severe lead poisoning. In a retrospective analysis, we aimed to determine venous blood lead level (VBLL) thresholds and risk factors for encephalopathy using MSF programmatic data from the first year of the outbreak response. Methods and Findings We included children aged ≤5 years with VBLL ≥45 µg/dL before any chelation and recorded neurological status. Odds ratios (OR) for neurological features were estimated; the final model was adjusted for age and baseline VBLL, using random effects for village of residence. 972 children met inclusion criteria: 885 (91%) had no neurological features; 34 (4%) had severe features; 47 (5%) had reported recent seizures; and six (1%) had other neurological abnormalities. The geometric mean VBLLs for all groups with neurological features were >100 µg/dL vs 65.9 µg/dL for those without neurological features. The adjusted OR for neurological features increased with increasing VBLL: from 2.75, 95%CI 1.27–5.98 (80–99.9 µg/dL) to 22.95, 95%CI 10.54–49.96 (≥120 µg/dL). Neurological features were associated with younger age (OR 4.77 [95% CI 2.50–9.11] for 1–<2 years and 2.69 [95%CI 1.15–6.26] for 2–<3 years, both vs 3–5 years). Severe neurological features were seen at VBLL <105 µg/dL only in those with malaria. Interpretation Increasing VBLL (from ≥80 µg/dL) and age 1–<3 years were strongly associated with neurological features; in those tested for malaria, a positive test was also strongly associated. These factors will help clinicians managing children with lead poisoning in prioritising therapy and developing chelation protocols. PMID:24740291

  5. 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

  6. MINIMAL RESIDUAL DISEASE IN ACUTE LYMPHOBLASTIC LEUKEMIA

    PubMed Central

    Campana, Dario

    2009-01-01

    In patients with acute lymphoblastic leukemia (ALL), monitoring of minimal residual disease (MRD) offers a way to precisely assess early treatment response and detect relapse. Established methods to study MRD are flow cytometric detection of abnormal immunophenotypes, polymerase chain reaction (PCR) amplification of antigen-receptor genes, and PCR amplification of fusion transcripts. The strong correlation between MRD levels and risk of relapse in childhood ALL is well established; studies in adult patients also support its prognostic value. Hence, results of MRD studies can be used to select treatment intensity and duration, and estimate the optimal timing for hematopoietic stem cell transplantation. Practical issues in the implementation of MRD assays in clinical studies include determining the most informative time point to study MRD, the levels of MRD that will trigger changes in treatment intensity, as well as the relative cost and informative power of different methodologies. The identification of new markers of leukemia and the use of increasingly refined assays should further facilitate routine monitoring of MRD and help clarifying the cellular and biologic features of leukemic cells that resist chemotherapy in vivo. PMID:19100372

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. Diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch is associated with better neurologic response to intravenous thrombolytic therapy in acute ischemic stroke patients

    PubMed Central

    Jeong, Jong Yeong; Han, Sang Kuk; Shin, Dong Hyuk; Na, Ji Ung; Lee, Hyun Jung; Choi, Pil Cho; Lee, Jeong Hun

    2015-01-01

    Objective To investigate differences in the effect of intravenous (IV) thrombolysis regarding the mismatch of diffusion-weighted imaging–fluid-attenuated inversion recovery (DWI-FLAIR) among acute ischemic stroke patients who visited the emergency department (ED) within 3 hours from the onset of symptoms. Methods Among ED patients presenting with an acute ischemic stroke between January 2011 and May 2013 at a tertiary hospital, those who underwent magnetic resonance imaging before IV thrombolytic therapy were included in this retrospective study. Patients were divided into DWI-FLAIR mismatch and match groups. National Institutes of Health Stroke Scale (NIHSS) scores obtained initially, 24 hours after thrombolytic therapy, and on discharge, and early neurologic improvement (ENI) and major neurologic improvement (MNI) were compared. Results During the study period, 50 of the 213 acute ischemic stroke patients who presented to the ED were included. The DWI-FLAIR mismatch group showed a statistically significantly greater reduction in NIHSS both at 24 hours after thrombolytic therapy and upon discharge than did the match group (5.5 vs. 1.2, P<0.001; 6.0 vs. 2.3, P<0.01, respectively). Moreover, ENI and MNI were significantly greater for the DWI-FLAIR mismatch group than for the match group (27/36 vs. 2/14, P<0.001; 12/36 vs. 0/14, P=0.012, respectively). Conclusion Among acute ischemic stroke patients who visited the ED within 3 hours from the onset of symptoms, patients who showed DWI-FLAIR mismatch showed a significantly better response to IV thrombolytic therapy than did the DWI-FLAIR match group in terms of neurologic outcome.

  14. Acute promyelocytic leukemia: a curable disease.

    PubMed

    Lo Coco, F; Nervi, C; Avvisati, G; Mandelli, F

    1998-12-01

    The Second International Symposium on Acute Promyelocytic Leukemia (APL) was held in Rome in 12-14 November 1997. Clinical and basic investigators had the opportunity to discuss in this meeting the important advances in the biology and treatment of this disease achieved in the last 4 years, since the First Roman Symposium was held in 1993. The first part of the meeting was dedicated to relevant aspects of laboratory research, and included the following topics: molecular mechanisms of leukemogenesis and of response/resistance to retinoids, biologic and therapeutic effects of new agents such as arsenicals and novel synthetic retinoids; characterization of APL heterogeneity at the morphological, cytogenetic and immunophenotypic level. The updated results of large cooperative clinical trials using variable combinations of all-trans retinoic acid (ATRA) and chemotherapy were presented by the respective group chairmen, and formed the 'core' part of the meeting. These studies, which in most cases integrated the molecular assessment of response to treatment, provided a stimulating framework for an intense debate on the most appropriate frontline treatment options to be adopted in the future. The last day was dedicated to special entities such as APL in the elderly and in the child, as well as the role of bone marrow transplantation. The prognostic value of molecular monitoring studies was also discussed in the final session of the meeting. In this article, we review the major advances and controversial issues in APL biology and treatment discussed in this symposium and emerging from very recent publications. We would like to credit the successful outcome of this meeting to the active and generous input of all invited speakers and to participants from all over the world who provided constructive and fruitful discussions.

  15. Acquired Cell-Mediated Immunodepression in Acute Chagas' Disease

    PubMed Central

    Teixeira, Antonio R. L.; Teixeira, Glória; Macêdo, Vanize; Prata, Aluizio

    1978-01-01

    In this study two groups of patients with acute Chagas' disease were identified. Group one consisted of five patients with apparent acute Chagas' disease. These patients showed symptoms and signals of an acute illness, such as high fever and enlarged spleen. One of these patients developed severe myocarditis and heart failure. Group two consisted of seven patients with inapparent acute Chagas' disease. This was a nonclinical entity, not perceived by the patient who did not seek medical care. The diagnosis was made by the shift of a serologic test which indicates the presence of immunoglobulin M antibodies to Trypanosoma cruzi. The patients with apparent acute Chagas' disease showed positive delayed-type skin response to T. cruzi antigen. Also, their leukocytes showed significant inhibition of migration in the presence of this antigen. By contrast, the patients with the inapparent acute Chagas' disease did not show positive delayed-type skin response to T. cruzi antigen and no significant inhibition was observed when their cells migrated in the presence of this antigen. Of interest, none of these patients was capable of developing contact sensitivity to 2,4-dinitrochlorobenzene. However, three out of five patients with the apparent acute disease and all the normal control subjects showed positive contact reaction after sensitization to this drug. The results of these experiments would suggest that the thymus-derived (T)-lymphocyte function is depressed in patients with the clinically inapparent acute Chagas' disease. This immunodepression seems to be acquired in the course of the T. cruzi infection because all patients showed positive delayed-type skin response to at least one ubiquitous microbial extract, thus indicating previously normal T-cell function. We hypothesize that T. cruzi antigens may directly stimulate T cells with the concomitant release of factors that might become supressive for T-cell responses. Furthermore, the suppressive effect might interfere

  16. Does surgical treatment within 4 hours after trauma have an influence on neurological remission in patients with acute spinal cord injury?

    PubMed Central

    Biglari, Bahram; Child, Christopher; Yildirim, Timur Mert; Swing, Tyler; Reitzel, Tim; Moghaddam, Arash

    2016-01-01

    Background The proper timing for surgery in patients with acute spinal cord injury is controversial. This study was conducted to detect if there is an advantage in early (within the first 4 hours after trauma) compared to late (between 4 and 24 hours after trauma) surgery on neurological outcome. Methods In this single institution prospective cohort study, data were analyzed from 51 spinal cord injured patients with an average age of 43.4 (±19.2) years. The influence of early (29 patients within the first 4 hours) as opposed to late (22 patients between 4 and 24 hours) decompression was evaluated by comparing data for neurological outcome. Patients of the study collectively suffered acute spinal fractures from C2 to L3 (cervical 39.2%, thoracic 29.4%, and lumbal 21.6%) or nonosseous lesions (9.8%). American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades were assessed at time of admission and 6 months after trauma or longer depending on the time of release. Surgical treatment included early stabilization and decompression within 24 hours. Results No significant difference between improved neurological function, measured with the AIS, and an early or late surgery time can be seen (P=0.402). Furthermore, binary logistic regression shows no significant difference between sex or age, and AIS improvement as possible confounders. Conclusion In our study, all patients with spinal cord injury were treated with spine stabilization and decompression within the first 24 hours after trauma. Surgical decompression within the first 4 hours after trauma was not associated with improved neurological outcome compared to treatment between 4 and 24 hours. In a clinical context, this indicates that there is a time frame of at least 1 day in which optimal care is possible. PMID:27621643

  17. Acute Kidney Disease After Liver and Heart Transplantation.

    PubMed

    Rossi, Ana P; Vella, John P

    2016-03-01

    After transplantation of nonrenal solid organs, an acute decline in kidney function develops in the majority of patients. In addition, a significant number of nonrenal solid organ transplant recipients develop chronic kidney disease, and some develop end-stage renal disease, requiring renal replacement therapy. The incidence varies depending on the transplanted organ. Acute kidney injury after nonrenal solid organ transplantation is associated with prolonged length of stay, cost, increased risk of death, de novo chronic kidney disease, and end-stage renal disease. This overview focuses on the risk factors for posttransplant acute kidney injury after liver and heart transplantation, integrating discussion of proteinuria and chronic kidney disease with emphasis on pathogenesis, histopathology, and management including the use of mechanistic target of rapamycin inhibition and costimulatory blockade.

  18. 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

  19. 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

  20. 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

  1. Porphyria and its neurologic manifestations.

    PubMed

    Tracy, Jennifer A; Dyck, P James B

    2014-01-01

    Porphyrias are rare disorders resulting from a defect in the heme biosynthetic pathway. They can produce significant disease of both the peripheral and central nervous systems, in addition to other organ systems, with acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria as the subtypes associated with neurologic manifestations. The presence of a motor-predominant peripheral neuropathy (axonal predominant), accompanied by gastrointestinal distress and neuropsychiatric manifestations, should be a strong clue to the diagnosis of porphyria. Clinical confirmation can be made through evaluation of urine porphyrins during an exacerbation of disease. While hematin is helpful for acute treatment, long-term effective management requires avoidance of overstimulation of the cytochrome P450 pathway, as well as other risk factor control.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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.

  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. PMID:22123780

  11. 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.

  12. 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

  13. 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

  14. 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

  15. Family history of autoimmune thyroid disease and childhood acute leukemia.

    PubMed

    Perillat-Menegaux, Florence; Clavel, Jacqueline; Auclerc, Marie-Françoise; Baruchel, André; Leverger, Guy; Nelken, Brigitte; Philippe, Noël; Sommelet, Danièle; Vilmer, Etienne; Hémon, Denis

    2003-01-01

    The association between a familial history of autoimmune disease and childhood acute leukemia was investigated in a French case-control study that, overall, was designed to assess the role of perinatal, infectious, environmental, and genetic factors in the etiology of childhood acute leukemia. Familial histories of autoimmune disease in first- and second-degree relatives were compared in 279 incident cases, 240 cases of acute lymphocytic leukemia (ALL) and 39 cases of acute non-lymphoblastic leukemia (ANLL), and 285 controls. Recruitment was frequency matched by age, gender, hospital, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. A statistically significant association between a history of autoimmune disease in first- or second-degree relatives and ALL (OR, 1.7; 95% confidence interval (CI), 1.0-2.8) was found. A relationship between thyroid diseases overall and ALL (OR, 2.0; 95% CI, 1.0-3.9) was observed. This association was more pronounced for potentially autoimmune thyroid diseases (Grave's disease and/or hyperthyroidism and Hashimoto's disease and/or hypothyroidism) (OR, 3.5; 95% CI, 1.1-10.7 and OR, 5.6; 95% CI, 1.0-31.1, respectively for ALL and ANLL), whereas it was not statistically significant for the other thyroid diseases (thyroid goiter, thyroid nodule, and unspecified thyroid disorders) (OR, 1.6; 95% CI, 0.7-3.5 and OR, 1.3; 95% CI, 0.2-7.0, respectively, for ALL and ANLL). The results suggest that a familial history of autoimmune thyroid disease may be associated with childhood acute leukemia.

  16. The acute haemolytic syndrome in Wilson's disease--a review of 22 patients.

    PubMed

    Walshe, J M

    2013-11-01

    An analysis of 321 case notes of patients with Wilson's disease seen between 1955 and 2000 and one case seen in 1949 has revealed that 22 patients presented with a haemolytic crisis. This study was not a specific research project but a retrospective analysis of 321 patients with Wilson's disease seen between 1949 and 2000. All investigations were carried out in the best interests of diagnosis and management of patients referred to my clinic. The delay in diagnosis in 18 cases resulted in progression to severe hepatic disease in 14 cases and to neurological disease in 4 cases. One patient had no symptoms at the time her sister's illness was diagnosed as Wilson's disease. In a second patient, with liver disease, the diagnosis was also made when a sister was found to have Wilson's disease. There was a female to male ratio of 15:7. The average age of onset was 12.6 years and the incidence 6.9%. Delay in diagnosis resulted in nine deaths. Three patients, late in the series, were admitted in the acute phase, two female and one male; of these two responded to chelation therapy, the third required liver transplantation. Haemolysis appeared to be extravascular, and possible mechanisms of the haemolysis are discussed.

  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. 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

  19. 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

  20. 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

  1. Neurological complication of dengue infection.

    PubMed

    Murthy, J M K

    2010-01-01

    Dengue infection is endemic in more than 100 countries, mostly in the developing world. Recent observations indicate that the clinical profile of dengue is changing, and that neurological manifestations are being reported more frequently. The exact incidence of various neurological complications is uncertain. The pathogenesis of neurological manifestations is multiple and includes: neurotrophic effect of the dengue virus, related to the systemic effects of dengue infection, and immune mediated. In countries endemic to dengue, it will be prudent to investigate for dengue infection in patients with fever and acute neurological manifestations. There is need for understanding of the pathogenesis of various neurological manifestations.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. Acute diarrhoeal disease in less developed countries

    PubMed Central

    Gordon, John E.; Guzmán, Miguel A.; Ascoli, Werner; Scrimshaw, Nevin S.

    1964-01-01

    A number of primary epidemiological characteristics are recognized as common to members of a syndrome designated “acute undifferentiated diarrhoeal disease”. This syndrome includes both specific and non-specific diarrhoeal disorders. Within the existing knowledge and with the facilities available in less developed countries, an epidemiological basis for control, directed against the syndrome as a whole, is presented as the practical approach to community management. Clinical and microbiological distinctions do not extend to the main bulk of the problem. Individual epidemiological patterns exist according to age and varying social and ecological conditions. Field study by periodic home visits over four years has defined these patterns in highland rural villages in Guatemala. The chief problem was weanling diarrhoea. PMID:14230899

  9. Acute Chagas Disease: New Global Challenges for an Old Neglected Disease

    PubMed Central

    Andrade, Daniela V.; Gollob, Kenneth J.; Dutra, Walderez O.

    2014-01-01

    Chagas disease is caused by infection with the protozoan Trypanosoma cruzi, and although over 100 years have passed since the discovery of Chagas disease, it still presents an increasing problem for global public health. A plethora of information concerning the chronic phase of human Chagas disease, particularly the severe cardiac form, is available in the literature. However, information concerning events during the acute phase of the disease is scarce. In this review, we will discuss (1) the current status of acute Chagas disease cases globally, (2) the immunological findings related to the acute phase and their possible influence in disease outcome, and (3) reactivation of Chagas disease in immunocompromised individuals, a key point for transplantation and HIV infection management. PMID:25077613

  10. Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

    PubMed

    Cowgill, Larry D; Polzin, David J; Elliott, Jonathan; Nabity, Mary B; Segev, Gilad; Grauer, Gregory F; Brown, Scott; Langston, Cathy; van Dongen, Astrid M

    2016-11-01

    International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats.

  11. Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

    PubMed

    Cowgill, Larry D; Polzin, David J; Elliott, Jonathan; Nabity, Mary B; Segev, Gilad; Grauer, Gregory F; Brown, Scott; Langston, Cathy; van Dongen, Astrid M

    2016-11-01

    International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats. PMID:27593574

  12. 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.

  13. 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.

  14. [Acute atrioventricular block in chronic Lyme disease].

    PubMed

    Wagner, Vince; Zima, Endre; Gellér, László; Merkely, Béla

    2010-09-26

    The tick bite transmitted Lyme disease is one of the most common antropozoonosis, about 10 000 new infections are reported in Hungary each year. The progress and clinical presentation can vary, and carditis can occur in later stages. A serologically verified Lyme disease caused third degree atrioventricular block in young male presenting with presyncope. Based on the tick-bites mentioned a few weeks prior to hospital admission, Lyme carditis was considered with the administration of antibiotics and monitor observation. Typical skin lesions were not recognized and laboratory findings showed no pathology. An electrophysiological study recorded a predominant supra-His atrioventricular block. Total regression of conduction could be detected later and the serological tests established an underlying Lyme disease. Currently no definite treatment recommendation is available for the potentially reversible Lyme carditis. The tick bite seemed to be the key on our way to diagnosis; however, serological tests proved the disease to be older than one year. A detailed medical history and serological tests are essential in identifying the cause and pacemaker implantation can be avoided.

  15. 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

  16. Neurological Complications of Ebola Virus Infection.

    PubMed

    Billioux, Bridgette Jeanne; Smith, Bryan; Nath, Avindra

    2016-07-01

    Ebola virus disease is one of the deadliest pathogens known to man, with a mortality rate between 25-90% depending on the species and outbreak of Ebola. Typically, it presents with fever, headache, voluminous vomiting and diarrhea, and can progress to a hemorrhagic illness; neurologic symptoms, including meningoencephalitis, seizures, and coma, can also occur. Recently, an outbreak occurred in West Africa, affecting > 28,000 people, and killing > 11,000. Owing to the magnitude of this outbreak, and the large number (>17,000) of Ebola survivors, the medical and scientific communities are learning much more about the acute manifestations and sequelae of Ebola. A number of neurologic complications can occur after Ebola, such as seizures, memory loss, headaches, cranial nerve abnormalities, and tremor. Ebola may also persist in some immunologically privileged sites, including the central nervous system, and can rarely lead to relapse in disease. Owing to these findings, it is important that survivors are evaluated and monitored for neurologic symptoms. Much is unknown about this disease, and treatment remains largely supportive; however, with ongoing clinical and basic science, the mechanisms of how Ebola affects the central nervous system and how it persists after acute disease will hopefully become more clear, and better treatments and clinical practices for Ebola patients will be developed. PMID:27412684

  17. Acute graft-vs-host disease: pathobiology and management.

    PubMed

    Goker, H; Haznedaroglu, I C; Chao, N J

    2001-03-01

    Acute graft-vs-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem cell transplantation (HSCT), leading to a significant morbidity and mortality. GVHD occurs when transplanted donor T lymphocytes react to foreign host cells. It causes a wide variety of host tissue injuries. This review focuses on the pathobiological basis, clinical aspects, and current management strategies of acute GVHD. Afferent phase of acute GVHD starts with myeloablative conditioning, i.e., before the infusion of the graft. Total-body irradiation (TBI) or high-dose chemotherapy regimens cause extensive damage and activation in host tissues, which release inflammatory cytokines and enhance recipient major histocompatibility complex (MHC) antigens. Recognition of the foreign host antigens by donor T cells and activation, stimulation, and proliferation of T cells is crucial in the afferent phase. Effector phase of acute GVHD results in direct and indirect damage to host cells. The skin, gastrointestinal tract, and liver are major target organs of acute GVHD. Combination drug prophylaxis in GVHD is essential in all patients undergoing allogeneic HSCT. Steroids have remained the standard for the treatment of acute GVHD. Several clinical trials have evaluated monoclonal antibodies or receptor antagonist therapy for steroid-resistant acute GVHD, with different successes in a variety of settings. There are some newer promising agents like mycophenolate mofetil, glutamic acid-lysine-alanine-tyrosine (GLAT), rapamycin, and trimetrexate currently entering in the clinical studies, and other agents are in development. Future experimental and clinical studies on GVHD will shed further light on the better understanding of the disease pathobiology and generate the tools to treat malignant disorders with allogeneic HSCT with specific graft-vs-tumor effects devoid of GVHD. PMID:11274753

  18. [Acute epidural hematoma of the posterior fossa in a case of von Willebrand's disease].

    PubMed

    Takenaka, N; Mine, T; Ikeda, E; Iwai, H; Kusano, S

    1988-01-01

    A rare case of acute epidural hematoma of the posterior fossa associated with von Willebrand's disease is reported. A 9-year-old boy fell down and hit his occipital region against a floor. Soon after he came home and slept, but three hours later he began to vomit and became drowsiness. He visited our hospital and his Glasgow Coma Scale showed 13 points. CT scan on admission showed acute epidural hematoma of left posterior fossa and contusional hematoma in the right temporal lobe. The bleeding time was over 18 minutes. He had been suspected to be suffering from von Willebrand's disease two years ago. Then fresh blood, fresh frozen plasma and anti-hemophilic globulin were prepared. Ten hours after injury, the operation was begun. Fresh epidural hematoma existed as a clot beyond transverse sinus. During the procedure of dural tenting suture, diffuse bleeding from bone, muscle, subcutaneous tissue and dura occurred and it was difficult to stop the bleeding. By using fresh blood and anti-hemophilic globulin, the bleeding was controlled, and then the operation was achieved. In the postoperative course a new epidural hematoma was found in the left temporal region and a new but asymptomatic retinal hemorrhage was found in his right eye. He was discharged without any neurological deficits 25 days after operation.

  19. 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

    Nanotechnology has been broadly defined as the one for not only the creation of functional materials and devices as well as systems through control of matter at the scale of 1-100 nm, but also the exploitation of novel properties and phenomena at the same scale. Growing needs in the point-of-care (POC) that is an increasing market for improving patient's quality of life, are driving the development of nanotechnologies for diagnosis and treatment of various life threatening diseases. This paper addresses the recent development of nanodiagnostic sensors and nanotherapeutic devices with functionalized carbon nanotube and/or nanowire on a flexible organic thin film electronics to monitor and control of the three leading diseases namely 1) neurodegenerative diseases, 2) cardiovascular diseases, and 3) diabetes and metabolic diseases. The sensors developed include implantable and biocompatible devices, light weight wearable devices in wrist-watches, hats, shoes and clothes. The nanotherapeutics devices include nanobased drug delivery system. Many of these sensors are integrated with the wireless systems for the remote physiological monitoring. The author's research team has also developed a wireless neural probe using nanowires and nanotubes for monitoring and control of Parkinson's disease. Light weight and compact EEG, EOG and EMG monitoring system in a hat developed is capable of monitoring real time epileptic patients and patients with neurological and movement disorders using the Internet and cellular network. Physicians could be able to monitor these signals in realtime using portable computers or cell phones and will give early warning signal if these signals cross a pre-determined threshold level. In addition the potential impact of nanotechnology for applications in medicine is that, the devices can be designed to interact with cells and tissues at the molecular level, which allows high degree of functionality. Devices engineered at nanometer scale imply a

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. Brain MRI Findings in Neurological Complications of Cancer Treatment.

    PubMed

    Cabaj, Astra; Bekiesińska-Figatowska, Monika; Duczkowska, Agnieszka; Duczkowski, Marek

    2016-01-01

    The amount of people living with cancer is increasing; they live longer and have thus a higher risk of developing neurological complications. Magnetic resonance as a diagnostic procedure of choice in detecting the reasons of neurological/psychiatric symptoms in oncological patients is nowadays relatively easily accessible. Early diagnosis established by radiologists familiar with neurological entities that may follow cancer treatment allow clinicians to provide proper treatment, even if the diagnosis seems unbelievable. The review of MR images of acute and chronic neurological complications of cancer treatment from the authors' own archive is the focus of this report. Neurological complications of cancer can be metastatic and non-metastatic; the first cannot be considered as a treatment complication, the latter can be chemoor radiotherapy-induced, acute, chronic and delayed. In our material we dealt with complications with dramatic course (stroke, PRES, acute leukoencephalopathy, Wernicke's encephalopathy) and with cases with milder and/or longer course (neuro-infections, chronic leukoencephalopathy, telangiectasias and/or cavernous hemangiomas, second tumors: glioma and meningioma after irradiation). The central nervous system is very susceptible to complications of systemic cancer and its treatment. Even though the first thought of clinicians and radiologists after a patient's first neurological/psychiatric symptoms appears concerns the metastatic spread of the disease, they need to have an understanding that there are a number of other causes of such symptoms. The knowledge of entities which can be expected and diagnostic experience prevent clinicians from making wrong diagnosis. PMID:27629856

  5. [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

  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. On the Pathogenesis of Acute Exacerbations of Mucoobstructive Lung Diseases.

    PubMed

    Boucher, Richard C

    2015-11-01

    Mucoobstructive lung diseases have highlighted the importance of a proper description of the normal mucus clearance system. A useful description of the normal mucus clearance apparatus requires the presence of two gels on the airway surface (i.e., a mucus layer gel and a periciliary gel). Importantly, most mucoobstructive lung diseases are distributed heterogeneously in the lung, and exacerbations may reflect spread of the disease to previously normal areas. The spread may reflect disturbances in the balance of water between the two gel layers, producing heterogeneous mucus adhesion and infection within the lung. Ultimately, spread can produce losses of lung function that may be associated with acute exacerbation frequency.

  9. On the Pathogenesis of Acute Exacerbations of Mucoobstructive Lung Diseases

    PubMed Central

    2015-01-01

    Mucoobstructive lung diseases have highlighted the importance of a proper description of the normal mucus clearance system. A useful description of the normal mucus clearance apparatus requires the presence of two gels on the airway surface (i.e., a mucus layer gel and a periciliary gel). Importantly, most mucoobstructive lung diseases are distributed heterogeneously in the lung, and exacerbations may reflect spread of the disease to previously normal areas. The spread may reflect disturbances in the balance of water between the two gel layers, producing heterogeneous mucus adhesion and infection within the lung. Ultimately, spread can produce losses of lung function that may be associated with acute exacerbation frequency. PMID:26595733

  10. [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

  11. 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

  12. 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.

  13. 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

  14. 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...

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. Acute combined pressure and temperature exposures on a shallow-water crustacean: novel insights into the stress response and high pressure neurological syndrome.

    PubMed

    Morris, J P; Thatje, S; Ravaux, J; Shillito, B; Fernando, D; Hauton, C

    2015-03-01

    Little is known about the ecological and physiological processes governing depth distribution limits in species. Temperature and hydrostatic pressure are considered to be two dominant factors. Research has shown that some marine ectotherms are shifting their bathymetric distributions in response to rapid anthropogenic ocean surface warming. Shallow-water species unable to undergo latitudinal range shifts may depend on bathymetric range shifts to seek refuge from warming surface waters. As a first step in constraining the molecular basis of pressure tolerance in shallow water crustaceans, we examined differential gene expression in response to acute pressure and temperature exposures in juveniles of the shallow-water shrimp Palaemonetes varians. Significant increases in the transcription of genes coding for an NMDA receptor-regulated protein, an ADP ribosylation factor, β-actin, two heat shock protein 70 kDa isoforms (HSP70), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were found in response to elevated pressure. NMDA receptors have been implicated in pathways of excitotoxic damage to neurons and the onset of high pressure neurological syndrome (HPNS) in mammals. These data indicate that the sub-lethal effects of acute barotrauma are associated with transcriptional disturbances within the nervous tissue of crustaceans, and cellular macromolecular damage. Such transcriptional changes lead to the onset of symptoms similar to that described as HPNS in mammals, and may act as a limit to shallow water organisms' prolonged survival at depth.

  20. Managing acute and chronic renal stone disease.

    PubMed

    Moran, Conor P; Courtney, Aisling E

    2016-02-01

    Nephrolithiasis, or renal stone disease, is common and the incidence is increasing globally. In the UK the lifetime risk is estimated to be 8-10%. On a population level, the increase in stone incidence, erosion of gender disparity, and younger age of onset is likely to reflect increasing prevalence of obesity and a Western diet with a high intake of animal protein and salt. Stones can be detected by a variety of imaging techniques. The gold standard is a non-contrast CT of kidneys, ureters and bladder (CT KUB) which can identify > 99% of stones. CT KUB should be the primary mode of imaging for all patients with colic unless contraindicated. In such instances, or if a CT KUB is not available, an ultrasound KUB is an alternative. This has advantages in terms of radiation exposure and cost, but is limited in sensitivity, particularly for ureteric stones. Once diagnosed, a plain film KUB can be used for follow-up of radiopaque stones. For most patients diclofenac is a reasonable first choice of analgesia, e.g. 50-100 mg rectally, or 75 mg IM. Opioid medication can worsen nausea and be less effective, but should be used if there is a contraindication to NSAIDs. A combination of diclofenac, paracetamol, and/or codeine regularly can provide adequate pain control in many cases. Failure of this analgesic combination should prompt consideration of secondary care support. If a ureteric stone < 5 mm in diameter is identified, the expectation is that this will pass without intervention. Initially medical management is still useful for stones between 5 and 10mm in diameter, but urology input is more likely to be necessary as up to 50% of these may require intervention. Stones that are >10 mm in diameter should be discussed with the urology service as they are unlikely to pass spontaneously.

  1. 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

  2. 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

  3. Acute viral E hepatitis with chronic liver disease (autoimmune hepatitis).

    PubMed

    Desai, H G; Naik, A S

    2005-03-01

    A 36 years old male presented with anorexia, jaundice and ascites. He was suffering from acute viral E hepatitis. In view of ascites, he was investigated for associated asymptomatic chronic liver disease (CLD). The CLD was diagnosed as cirrhosis with autoimmune hepatitis and was treated with steroid with good response. He is maintaining good health with low dose steroid, on follow up for 1 year.

  4. 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.

  5. Metabolomics and Its Application to Acute Lung Diseases

    PubMed Central

    Stringer, Kathleen A.; McKay, Ryan T.; Karnovsky, Alla; Quémerais, Bernadette; Lacy, Paige

    2016-01-01

    Metabolomics is a rapidly expanding field of systems biology that is gaining significant attention in many areas of biomedical research. Also known as metabonomics, it comprises the analysis of all small molecules or metabolites that are present within an organism or a specific compartment of the body. Metabolite detection and quantification provide a valuable addition to genomics and proteomics and give unique insights into metabolic changes that occur in tangent to alterations in gene and protein activity that are associated with disease. As a novel approach to understanding disease, metabolomics provides a “snapshot” in time of all metabolites present in a biological sample such as whole blood, plasma, serum, urine, and many other specimens that may be obtained from either patients or experimental models. In this article, we review the burgeoning field of metabolomics in its application to acute lung diseases, specifically pneumonia and acute respiratory disease syndrome (ARDS). We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized environmental toxins. Recent reports have suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe disease, such as sepsis, which kills many patients each year. In addition, metabolomics may provide more detailed phenotyping of patient heterogeneity, which is needed to achieve the goal of precision medicine. However, although several experimental and clinical metabolomics studies have been conducted assessing the application of the science to acute lung diseases, only incremental progress has been made. Specifically, little is known about the metabolic phenotypes of these illnesses. These data are needed to substantiate metabolomics biomarker credentials so that clinicians can employ them for clinical decision

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  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 origins of cachexia in acute and chronic inflammatory diseases.

    PubMed

    Delano, Matthew J; Moldawer, Lyle L

    2006-02-01

    The term cachexia originates from the Greek root kakos hexis, which translates into "bad condition," recognized for centuries as a progressive deterioration of body habitus. Cachexia is commonly associated with a number of disease states, including acute inflammatory processes associated with critical illness and chronic inflammatory diseases, such as cancer, congestive heart failure, chronic obstructive pulmonary disease, and human immunodeficiency virus infection. Cachexia is responsible for the deaths of 10%-22% of all patients with cancer and approximately 15% of the trauma deaths that occur from sepsis-induced organ dysfunction and malnutrition days to weeks after the initial traumatic event. The abnormalities associated with cachexia include anorexia, weight loss, a preferential loss of somatic muscle and fat mass, altered hepatic glucose and lipid metabolism, and anemia. Anorexia alone cannot fully explain the development of cachexia; metabolic alterations in carbohydrate, lipid, and protein metabolism contribute to the severe tissue losses. Despite significant advances in our understanding of specific disease processes, the mechanisms leading to cachexia remain unclear and multifactorial. Although complex, increasing evidence from both animal models and clinical studies suggests that an inflammatory response, mediated in part by a dysregulated production of proinflammatory cytokines, plays a role in the genesis of cachexia, associated with both critical illness and chronic inflammatory diseases. These cytokines are further thought to induce an acute phase protein response (APR) and produce the alterations in lipid and carbohydrate metabolism identified as crucial markers of acute inflammation in states of malignancy and critical illness. Although much is still unknown about the etiology of cachexia, there is growing appreciation that cachexia represents the endproduct of an inappropriate interplay between multiple cytokines, neuropeptides, classic stress

  13. Ischemia-modified albumin levels in the prediction of acute critical neurological findings in carbon monoxide poisoning.

    PubMed

    Daş, Murat; Çevik, Yunsur; Erel, Özcan; Çorbacioğlu, Şeref Kerem

    2016-04-01

    The aim of the study was to determine whether serum ischemia-modified albumin (IMA) levels in patients with carbon monoxide (CO) poisoning were higher compared with a control group of healthy volunteers. In addition, the study sought to determine if there was a correlation between serum IMA levels and carboxyhemoglobin (COHB) levels and other critical neurological findings (CNFs). In this prospective study, the IMA levels of 100 patients with CO poisoning and 50 control individuals were compared. In addition, the IMA and COHB levels were analyzed according to absence or presence CNFs in patients with CO poisoning. The levels of IMA (mg/dL) on admittance, and during the 1(st) hour and 3(rd) hour, in patients with CO poisoning (49.90 ± 35.43, 30.21 ± 14.81, and 21.87 ± 6.03) were significantly higher, compared with the control individuals (17.30 ± 2.88). The levels of IMA in the 6(th) hour were not higher compared with control individuals. The levels of IMA on admittance, and during the 1(st) hour, 3(rd) hour, and 6(th) hour, and COHB (%) levels in patients who had CNFs were higher compared with IMA levels and COHB levels in patients who had no CNFs (p < 0.001). However, when the multivariate model was created, it was observed that IMA level on admittance was a poor indicator for prediction of CNFs (odds ratio = 1.05; 95% confidence interval, 1.01-1.08). We therefore concluded that serum IMA levels could be helpful in the diagnosis of CO poisoning. However, we believe that IMA levels cannot be used to predict which patients will develop CNFs due to CO poisoning.

  14. Elevation of Serum Acid Sphingomyelinase Activity in Acute Kawasaki Disease.

    PubMed

    Konno, Yuuki; Takahashi, Ikuko; Narita, Ayuko; Takeda, Osamu; Koizumi, Hiromi; Tamura, Masamichi; Kikuchi, Wataru; Komatsu, Akira; Tamura, Hiroaki; Tsuchida, Satoko; Noguchi, Atsuko; Takahashi, Tsutomu

    2015-01-01

    Kawasaki disease (KD) is an acute systemic vasculitis that affects both small and medium-sized vessels including the coronary arteries in infants and children. Acid sphingomyelinase (ASM) is a lysosomal glycoprotein that hydrolyzes sphingomyelin to ceramide, a lipid, that functions as a second messenger in the regulation of cell functions. ASM activation has been implicated in numerous cellular stress responses and is associated with cellular ASM secretion, either through alternative trafficking of the ASM precursor protein or by means of an unidentified mechanism. Elevation of serum ASM activity has been described in several human diseases, suggesting that patients with diseases involving vascular endothelial cells may exhibit a preferential elevation of serum ASM activity. As acute KD is characterized by systemic vasculitis that could affect vascular endothelial cells, the elevation of serum ASM activity should be considered in these patients. In the present study, serum ASM activity in the sera of 15 patients with acute KD was determined both before and after treatment with infusion of high-dose intravenous immunoglobulin (IVIG), a first-line treatment for acute KD. Serum ASM activity before IVIG was significantly elevated in KD patients when compared to the control group (3.85 ± 1.46 nmol/0.1 ml/6 h vs. 1.15 ± 0.10 nmol/0.1 ml/6 h, p < 0.001), suggesting that ASM activation may be involved in the pathophysiology of this condition. Serum ASM activity before IVIG was significantly correlated with levels of C-reactive protein (p < 0.05). These results suggest the involvement of sphingolipid metabolism in the pathophysiology of KD. PMID:26447086

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. The SOS Pilot Study: A RCT of Routine Oxygen Supplementation Early after Acute Stroke—Effect on Recovery of Neurological Function at One Week

    PubMed Central

    Roffe, Christine; Ali, Khalid; Warusevitane, Anushka; Sills, Sheila; Pountain, Sarah; Allen, Martin; Hodsoll, John; Lally, Frank; Jones, Peter; Crome, Peter

    2011-01-01

    Mild hypoxia is common after stroke and associated with poor long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no significant benefit at 7 and 12 months. This pilot study reports the effects of routine oxygen supplementation for 72 hours on oxygen saturation and neurological outcomes at 1 week after a stroke. Methods Patients with a clinical diagnosis of acute stroke were recruited within 24 h of hospital admission between October 2004 and April 2008. Participants were randomized to oxygen via nasal cannulae (72 h) or control (room air, oxygen given only if clinically indicated). Clinical outcomes were assessed by research team members at 1 week. Baseline data for oxygen (n = 148) and control (n = 141) did not differ between groups. Results The median (interquartile range) National Institutes of Health Stroke Scale (NIHSS) score for the groups at baseline was 6 (7) and 5 (7) respectively. The median Nocturnal Oxygen Saturation during treatment was 1.4% (0.3) higher in the oxygen than in the control group (p<0.001) during the intervention. At 1 week, the median NIHSS score had reduced by 2 (3) in the oxygen and by 1 (2) in the control group. 31% of participants in the oxygen group and 14% in the control group had an improvement of ≥4 NIHSS points at 1 week doubling the odds of improvement in the oxygen group (OR: 2.9). Conclusion Our data show that routine oxygen supplementation started within 24 hours of hospital admission with acute stroke led to a small, but statistically significant, improvement in neurological recovery at 1 week. However, the difference in NIHSS improvement may be due to baseline imbalance in stroke severity between the two groups and needs to be confirmed in a larger study and linked to longer-term clinical outcome. Trial Registration Controlled-Trials.com ISRCTN12362720; European Clinical Trials Database 2004-001866-41 PMID:21625533

  2. Acute arthropathy in patients with rash diseases: a comparative study.

    PubMed

    de Oliveira, Solange Artimos; Bastos Camacho, Luiz Antonio; Fernandes Bruno, Letícia; de Gusmão, Rodrigo Coimbra; de Medeiros Pereira, Antonio Carlos; Coca Velarde, Luis Guillermo; Mendonça Siqueira, Marilda

    2009-09-01

    The aim of this study was to assess the association of acute arthropathy and selected clinical features in patients with acute rash diseases. Serum samples from 1,554 patients were tested for anti-measles, dengue, human parvovirus B19, and rubella virus IgM using enzyme immunoassay. Sera from children, in whom these infections were excluded, were studied for anti-human herpesvirus type 6 IgG antibodies using an indirect immunofluorescence test. Joint complaints occurred in 31.2% of the 862 patients with an etiologic diagnosis and were more frequently seen in adults than in children (OR 8.5). Among the adults, arthropathy prevailed in women compared to men (OR 1.8). Arthropathy was most frequently reported in rubella (41.2%) and in dengue fever cases (41.1%) than in the other rash diseases studied (p < 0.0001). Joint complaints were more frequently seen in patients with fever (OR 1.6) and with five or more days of onset of the disease (OR 1.6), regardless of serological diagnosis. Arthropathy appeared as a frequent condition in rash diseases, typically with low severity and no specific pattern of joint involvement.

  3. 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.

  4. [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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. Noninvasive imaging in acute coronary disease. A clinical perspective

    SciTech Connect

    Gersh, B.J. )

    1991-09-01

    Numerous highly complex and sensitive noninvasive imaging techniques have enhanced the care of patients with acute myocardial infarction. Optimum use requires specific objectives to be defined in advance, including a review of the potential impact of the test on subsequent decisions. An additional issue that is subject to scrutiny in the current climate of cost containment relates to the incremental value of a specific examination. The imaging modality to be used will partially depend on other issues, including accessibility, cost, and interindividual or institutional expertise with a particular technique. Major applications in noninvasive imaging in the acute coronary syndromes include the following: (1) diagnosis, including identification of associated diseases and contraindications for acute reperfusion; (2) evaluation and management of complications ; (3) determination of prognosis (both early and late); (4) estimation of myocardial viability; (5) assessment of therapeutic efficacy; (6) investigational approaches, including 99mTc-sestamibi tomographic imaging, ultrafast cine computed tomographic scanning, and nuclear magnetic resonance imaging. Previous studies in the prethrombolytic era have documented the powerful impact of radionuclide stress testing on prognosis, but this needs to be reevaluated in the light of the changing current population undergoing stress testing. Preliminary data imply that the prognostic accuracy of stress testing after thrombolytic therapy is diminished. Moreover, the role of the open infarct-related artery in traditional estimates of prognosis requires further study. Noninvasive imaging has multiple applications in the diagnosis and management of patients with acute coronary disease, but the decision to use a specific technology in a particular circumstance mandates good clinical judgment and selectivity. 82 references.

  12. Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV

    PubMed Central

    Valcour, Victor G.; Spudich, Serena S.; Sailasuta, Napapon; Phanuphak, Nittaya; Lerdlum, Sukalaya; Fletcher, James L. K.; Kroon, Eugene D. M. B.; Jagodzinski, Linda L.; Allen, Isabel E.; Adams, Collin L.; Prueksakaew, Peeriya; Slike, Bonnie M.; Hellmuth, Joanna M.; Kim, Jerome H.; Ananworanich, Jintanat

    2015-01-01

    Objective To compare central nervous system (CNS) outcomes in participants treated during acute HIV infection with standard combination antiretroviral therapy (cART) vs. cART plus integrase inhibitor and CCR5 antagonist (cART+). Design 24-week randomized open-label prospective evaluation. Method Participants were evaluated then randomized to initiate cART (efavirenz, tenofovir, and either emtricitabine or lamivudine) vs. cART+ (cART plus raltegravir and maraviroc) during acute HIV and re-evaluated at 4, 12 and 24 weeks. We examined plasma and CSF cytokines, HIV RNA levels, neurological and neuropsychological findings, and brain MRS across groups and compared to healthy controls. Results At baseline, 62 participants were in Fiebig stages I-V. Randomized groups were similar for mean age (27 vs. 25, p = 0.137), gender (each 94% male), plasma log10 HIV RNA (5.4 vs. 5.6, p = 0.382), CSF log10 HIV RNA (2.35 vs. 3.31, p = 0.561), and estimated duration of HIV (18 vs. 17 days, p = 0.546). Randomized arms did not differ at 24 weeks by any CNS outcome. Combining arms, all measures concurrent with antiretroviral treatment improved, for example, neuropsychological testing (mean NPZ-4 of -0.408 vs. 0.245, p<0.001) and inflammatory markers by MRS (e.g. mean frontal white matter (FWM) choline of 2.92 vs. 2.84, p = 0.045) at baseline and week 24, respectively. Plasma neopterin (p<0.001) and interferon gamma-induced protein 10 (IP-10) (p = 0.007) remained elevated in participants compared to controls but no statistically significant differences were seen in CSF cytokines compared to controls, despite individual variability among the HIV-infected group. Conclusions A 24-week course of cART+ improved CNS related outcomes, but was not associated with measurable differences compared to standard cART. PMID:26555069

  13. 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.

  14. 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

  15. 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

  16. 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

  17. [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

  18. Acute acalculous cholecystitis and cardiovascular disease: a land of confusion.

    PubMed

    Tana, Marco; Tana, Claudio; Cocco, Giulio; Iannetti, Giovanni; Romano, Marcello; Schiavone, Cosima

    2015-12-01

    Acute acalculous cholecystitis (AAC) can be defined as acute inflammatory disease of the gallbladder without evidence of gallstones. The first case was reported in 1844 by Duncan et al.; however, some cases may have been missed previously in view of the complexity of the diagnosis. Several risk factors have been identified, and cardiovascular disease (CVD), in view of its multiple mechanisms of action, seems to play a key role. Atypical clinical onset, paucity of symptoms, overlap with comorbidities, and lack of robust, controlled trials result often in under or misdiagnosed cases. Moreover, laboratory results may be negative or not specific in the late stage of the disease, when a surgical treatment cannot be longer helpful if complications arise. A rapid diagnosis is therefore essential to achieve a prompt treatment and to avoid further clinical deterioration. In this short review, we would present the current evidence regarding epidemiology, pathophysiology, and clinical presentation of the complex relation between AAC and CVD. Then, we fully emphasize the role of ultrasound to achieve an early diagnosis and an appropriate treatment in suspected cases, reducing mortality and complications rates.

  19. Lithium-Induced Minimal Change Disease and Acute Kidney Injury

    PubMed Central

    Tandon, Parul; Wong, Natalie; Zaltzman, Jeffrey S

    2015-01-01

    Context: Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD) and acute kidney injury (AKI). Case Report: A 32-year-old female with a medical history of bipolar disorder treated with chronic lithium therapy presented with anasarca, fatigue, and tremors. Work-up revealed supra-therapeutic lithium levels, hypoalbuminemia, and significant proteinuria. The patient was treated conservatively with fluids and discontinuation of lithium therapy. Subsequently, she developed significant AKI and persistent proteinuria. She underwent a renal biopsy that demonstrated effacement of podocyte foot processes consistent with lithium-induced MCD. This was treated with corticosteroids, which decreased the proteinuria and resolved all the patient's symptoms. Conclusion: Lithium-induced MCD is a rare disease that affects patients of all ages. It is often associated with therapeutic lithium and is typically resolved with discontinuation of lithium. In some cases, concurrent AKI may result due to vascular obstruction from hyperalbuminuria and associated renal interstitial edema. Corticosteroids may be needed to reduce the proteinuria and prevent progression to chronic kidney disease. As such, patients on lithium therapy may benefit from monitoring of glomerular function via urinalysis to prevent the onset of nephrotic syndrome. PMID:26258081

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. Epidemiology of coronary heart disease and acute coronary syndrome

    PubMed Central

    Perez-Quilis, Carme; Leischik, Roman; Lucia, Alejandro

    2016-01-01

    The aim of this review is to summarize the incidence, prevalence, trend in mortality, and general prognosis of coronary heart disease (CHD) and a related condition, acute coronary syndrome (ACS). Although CHD mortality has gradually declined over the last decades in western countries, this condition still causes about one-third of all deaths in people older than 35 years. This evidence, along with the fact that mortality from CHD is expected to continue increasing in developing countries, illustrates the need for implementing effective primary prevention approaches worldwide and identifying risk groups and areas for possible improvement. PMID:27500157

  6. Epidemiology of coronary heart disease and acute coronary syndrome.

    PubMed

    Sanchis-Gomar, Fabian; Perez-Quilis, Carme; Leischik, Roman; Lucia, Alejandro

    2016-07-01

    The aim of this review is to summarize the incidence, prevalence, trend in mortality, and general prognosis of coronary heart disease (CHD) and a related condition, acute coronary syndrome (ACS). Although CHD mortality has gradually declined over the last decades in western countries, this condition still causes about one-third of all deaths in people older than 35 years. This evidence, along with the fact that mortality from CHD is expected to continue increasing in developing countries, illustrates the need for implementing effective primary prevention approaches worldwide and identifying risk groups and areas for possible improvement. PMID:27500157

  7. [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

  8. [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

  9. 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.

  10. 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

  11. 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

  12. Acute Chagas disease in El Salvador 2000-2012 - Need for surveillance and control

    PubMed Central

    Sasagawa, Emi; de Aguilar, Ana Vilma Guevara; de Ramírez, Marta Alicia Hernández; Chévez, José Eduardo Romero; Nakagawa, Jun; Cedillos, Rafael Antonio; Kita, Kiyoshi

    2014-01-01

    Several parasitological studies carried out in El Salvador between 2000-2012 showed a higher frequency of acute cases of Chagas disease than that in other Central American countries. There is an urgent need for improved Chagas disease surveillance and vector control programs in the provinces where acute Chagas disease occurs and throughout El Salvador as a whole. PMID:24676660

  13. 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.

  14. Advancing the Minimal Residual Disease Concept in Acute Myeloid Leukemia.

    PubMed

    Hokland, Peter; Ommen, Hans B; Mulé, Matthew P; Hourigan, Christopher S

    2015-07-01

    The criteria to evaluate response to treatment in acute myeloid leukemia (AML) have changed little in the past 60 years. It is now possible to use higher sensitivity tools to measure residual disease burden in AML. Such minimal or measurable residual disease (MRD) measurements provide a deeper understanding of current patient status and allow stratification for risk of subsequent clinical relapse. Despite these obvious advantages, and after over a decade of laboratory investigation and preclinical validation, MRD measurements are not currently routinely used for clinical decision-making or drug development in non-acute promyelocytic leukemia (non-APL) AML. We review here some potential constraints that may have delayed adoption, including a natural hesitancy of end users, economic impact concerns, misperceptions regarding the meaning of and need for assay sensitivity, the lack of one single MRD solution for all AML patients, and finally the need to involve patients in decision-making based on such correlates. It is our opinion that none of these issues represent insurmountable barriers and our hope is that by providing potential solutions we can help map a path forward to a future where our patients will be offered personalized treatment plans based on the amount of AML they have left remaining to treat. PMID:26111465

  15. Neurovascular changes in acute, sub-acute and chronic mouse models of Parkinson's disease.

    PubMed

    Sarkar, Sumit; Raymick, James; Mann, Dushyant; Bowyer, John F; Hanig, Joseph P; Schmued, Larry C; Paule, Merle G; Chigurupati, Srinivasulu

    2014-02-01

    Although selective neurodegeneration of nigro-striatal dopaminergic neurons is widely accepted as a cause of Parkinson's disease (PD), the role of vascular components in the brain in PD pathology is not well understood. However, the neurodegeneration seen in PD is known to be associated with neuroinflammatory-like changes that can affect or be associated with brain vascular function. Thus, dysfunction of the capillary endothelial cell component of neurovascular units present in the brain may contribute to the damage to dopaminergic neurons that occurs in PD. An animal model of PD employing acute, sub-acute and chronic exposures of mice to methyl-phenyl-tetrahydropyridine (MPTP) was used to determine the extent to which brain vasculature may be damaged in PD. Fluoro-Turquoise gelatin labeling of microvessels and endothelial cells was used to determine the extent of vascular damage produced by MPTP. In addition, tyrosine hydroxylase (TH) and NeuN were employed to detect and quantify dopaminergic neuron damage in the striatum (CPu) and substantia nigra (SNc). Gliosis was evaluated through GFAP immunohistochemistry. MPTP treatment drastically reduced TH immunoreactive neurons in the SNc (20.68 ± 2.83 in acute; 22.98 ± 2.14 in sub-acute; 10.20 ± 2.24 in chronic vs 34.88 ± 2.91 in controls; p<0.001). Similarly, TH immunoreactive terminals were dramatically reduced in the CPu of MPTP treated mice. Additionally, all three MPTP exposures resulted in a decrease in the intensity, length, and number of vessels in both CPu and SNc. Degenerative vascular changes such as endothelial cell 'clusters' were also observed after MPTP suggesting that vasculature damage may be modifying the availability of nutrients and exposing blood cells and/or toxic substances to neurons and glia. In summary, vascular damage and degeneration could be an additional exacerbating factor in the progression of PD, and therapeutics that protect and insure vascular integrity may be novel treatments for

  16. Crohnic Kidney Disease: Recurrent Acute Kidney Failure in a Patient With Crohn's Disease

    PubMed Central

    Demir, Mehmet Emin; Ercan, Zafer; Karakas, Emel Yigit; Ulas, Turgay; Buyukhatipoglu, Hakan

    2014-01-01

    Context: Short bowel syndrome is a rare and devastating complication in chronic inflammatory bowel disease following functional or anatomic loss of extensive segments of the intestine. Case Report: A 60-year-old male patient with Crohn's disease had undergone multiple resections of the intestine and developed short bowel syndrome. Despite up to 4-5 liters of orally fluid, sufficient calcium and magnesium intake, he suffered from recurrent acute kidney injury due to profound volume depletion and those electrolyte deficiencies. Administration of intravenous fluid and electrolyte repleacement treatment at regular intervals prevented further kidney injuries. Conclusion: We present a case of recurrent acute kidney failure in a patient with Crohn's disease, and aimed to remark importance of receiving sufficient parenteral fluid and electrolyte support in those with short bowel syndrome. PMID:25599054

  17. [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

  18. [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.

  19. MRI of diffuse liver disease: characteristics of acute and chronic diseases.

    PubMed

    Chundru, Surya; Kalb, Bobby; Arif-Tiwari, Hina; Sharma, Puneet; Costello, James; Martin, Diego R

    2014-01-01

    Diffuse liver disease, including chronic liver disease, affects tens of millions of people worldwide, and there is a growing need for diagnostic evaluation as treatments become more readily available, particularly for viral liver diseases. Magnetic resonance imaging (MRI) provides unique capabilities for noninvasive characterization of the liver tissue that rival or surpass the diagnostic utility of liver biopsies. There has been incremental improvement in the use of standardized MRI sequences, acquired before and after administration of a contrast agent, for the evaluation of diffuse liver disease and the study of the liver parenchyma and blood supply. More recent developments have led to methods for quantifying important liver metabolites, including lipids and iron, and liver fibrosis, the hallmark of chronic liver disease. Here, we review the MRI techniques and diagnostic features associated with acute and chronic liver disease. PMID:24808418

  20. 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.

  1. Detection of acute hepatopancreatic necrosis disease (AHPND) in Mexico.

    PubMed

    Nunan, Linda; Lightner, Donald; Pantoja, Carlos; Gomez-Jimenez, Silvia

    2014-08-21

    Acute hepatopancreatic necrosis disease (AHPND), which has also been referred to as early mortality syndrome (EMS), initially emerged as a destructive disease of cultured shrimp species in Asia in 2009. The pathogen associated with the disease, Vibrio parahaemolyticus, subsequently spread to the Western Hemisphere and emerged in Mexico in early 2013. The spread to the Western Hemisphere is a major concern to shrimp producers in the region. To date, the only peer-reviewed published method for determining whether mortalities are due to AHPND is through histological examination. A novel PCR detection method was employed to assess samples from Mexico in order to confirm the presence of the pathogen in this country. This manuscript details the detection methods used to confirm the presence of AHPND in Mexico. Both immersion and per os challenge studies were used to expose the Penaeus vannamei to the bacteria in order to induce the disease. Histological analysis confirmed AHPND status following the challenge studies. Also provided are the details of the molecular test by PCR that was used for screening candidate V. parahaemolyticus isolates. A rapid PCR assay for detection of AHPND may help with early detection and help prevent the spread of AHPND to other countries.

  2. Efficacy and safety comparison of DL-3-n-butylphthalide and Cerebrolysin: Effects on neurological and behavioral outcomes in acute ischemic stroke

    PubMed Central

    XUE, LI-XIA; ZHANG, TING; ZHAO, YU-WU; GENG, ZHI; CHEN, JING-JIONG; CHEN, HAO

    2016-01-01

    Cerebrolysin and DL-3-n-butylphthalide (NBP) have each shown neuroprotective efficacy in preclinical models of acute ischemic stroke (AIS) and passed clinical trials as therapeutic drugs for AIS. The present study was a clinical trial to assess and compare the efficacy and safety of NBP and Cerebrolysin in the reduction of neurological and behavioral disability following AIS. A randomized, double-blind trial was conducted with enrolment of 60 patients within 12 h of AIS. In addition to routine treatment, patients were randomly assigned to receive a 10-day intravenous administration of NBP, Cerebrolysin or placebo. National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) scores were used to evaluate the efficacy of the treatment in the patients with AIS at 11 and 21 days after the initiation of therapy. Adverse events were also analyzed among the three groups. After 10 days of treatment with NBP or Cerebrolysin, the NIHSS and BI scores at day 21 showed statistical differences compared with those in the placebo group (P<0.05). The improvements of NIHSS and BI scores in the NBP and Cerebrolysin groups were higher than those in the placebo group at days 11 and 21 (P<0.05). A statistically significant difference in the improvement of 21-day NIHSS scores was observed between the two treatment groups (P<0.05). No significant difference was found among the three groups with regard to the rate of adverse events. Favorable outcomes and good safety were observed in the patients with moderate AIS treated with NBP or Cerebrolysin. The results indicate that NBP may be more effective than Cerebrolysin in improving short-term outcomes following AIS. This trial is registered at ClinicalTrials.gov with clinical trial identifier number NCT02149875. PMID:27168844

  3. [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.

  4. [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.

  5. 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).

  6. 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

  7. [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.

  8. Acute Psychosis as Major Clinical Presentation of Legionnaires' Disease

    PubMed Central

    Silva-dos-Santos, Amílcar; Talina, Miguel Cotrim

    2016-01-01

    We report a case of a 61-year-old woman who presented with acute psychosis as a major manifestation of Legionnaires' disease in the absence of other neuropsychiatric symptoms. Clinical history revealed dry cough and nausea. Observation showed fever and auscultation crackles in the lower lobe of the right lung. Laboratory testing demonstrated elevated C-reactive protein and lung chest radiograph showed patchy peribronchial and right lower lobe consolidation. Soon after admission, she started producing purulent sputum. Epidemiological data suggested Legionella pneumophila as possible cause of the clinical picture that was confirmed by urinary antigen detection and polymerase chain reaction of the sputum. She was treated with levofloxacin 750 mg/day for 10 days with complete remission of pulmonary and psychiatric symptoms. She has not had further psychotic symptoms. PMID:27547478

  9. CT appearance of acute inflammatory disease of the renal interstitium

    SciTech Connect

    Gold, R.P.; McClennan, B.L.; Rottenberg, R.R.

    1983-08-01

    Today, infection remains the most common disease of the urinary tract and constitutes almost 75% of patient problems requiring urologic evaluation. There have been several major factors responsible for our better understanding of the nature and pathophysiology of urinary tract infection. One has been quantitated urine bacteriology and another, the discovery that a significant part of the apparently healthy adult female population has asymptomatic bacteriuria. Abnormal conditions such as neurogenic bladder, bladder malignancy, prolonged catheter drainage and reflux, altered host resistance, diabetes mellitus, and urinary tract obstruction, as well as pregnancy, may either predispose to or be implicated in the pathogenesis of urinary tract infection. There is a wide range of conditions that result in acute renal inflammation and those under discussion affect primarily the interstitium. This term refers to the connective tissue elements separating the tubules in the cortex and medulla. Hence, the interstitial nephritides are to be distinguished from the glomerulonephritides and fall into two general etiologic categories: infectious and noninfectious.

  10. Acute Psychosis as Major Clinical Presentation of Legionnaires' Disease.

    PubMed

    Coentre, Ricardo; Silva-Dos-Santos, Amílcar; Talina, Miguel Cotrim

    2016-01-01

    We report a case of a 61-year-old woman who presented with acute psychosis as a major manifestation of Legionnaires' disease in the absence of other neuropsychiatric symptoms. Clinical history revealed dry cough and nausea. Observation showed fever and auscultation crackles in the lower lobe of the right lung. Laboratory testing demonstrated elevated C-reactive protein and lung chest radiograph showed patchy peribronchial and right lower lobe consolidation. Soon after admission, she started producing purulent sputum. Epidemiological data suggested Legionella pneumophila as possible cause of the clinical picture that was confirmed by urinary antigen detection and polymerase chain reaction of the sputum. She was treated with levofloxacin 750 mg/day for 10 days with complete remission of pulmonary and psychiatric symptoms. She has not had further psychotic symptoms. PMID:27547478

  11. Invasive fungal diseases in patients with acute lymphoid leukemia.

    PubMed

    Nicolato, Andrea; Nouér, Simone A; Garnica, Marcia; Portugal, Rodrigo; Maiolino, Angelo; Nucci, Marcio

    2016-09-01

    Invasive fungal disease (IFD) represents an important complication in patients with acute lymphoid leukemia (ALL). The objectives of this study were to determine the prevalence of IFD in ALL patients with neutropenia, identify factors associated with IFD, and estimate the impact of IFD on the outcome. All patients with ALL who developed febrile neutropenia from 1987 to 2013 were evaluated. Cases of IFD were classified as proven or probable. Factors associated with IFD were evaluated by comparing episodes with and without a diagnosis of IFD. Among 350 episodes of febrile neutropenia, 31 IFDs were diagnosed (8.8%). Prolonged neutropenia was the only factor associated with IFD caused by yeasts. Factors associated with IFD caused by molds by multivariate analysis were the period after 2008, receipt of allogeneic transplant, relapsed ALL and prolonged neutropenia. Patients in relapse should receive induction chemotherapy in rooms with HEPA filter and receive antifungal prophylaxis. PMID:26949001

  12. Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

    PubMed

    Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

    2015-10-01

    Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome.

  13. 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

  14. Neurovascular changes in acute, sub-acute and chronic mouse models of Parkinson's disease.

    PubMed

    Sarkar, Sumit; Raymick, James; Mann, Dushyant; Bowyer, John F; Hanig, Joseph P; Schmued, Larry C; Paule, Merle G; Chigurupati, Srinivasulu

    2014-02-01

    Although selective neurodegeneration of nigro-striatal dopaminergic neurons is widely accepted as a cause of Parkinson's disease (PD), the role of vascular components in the brain in PD pathology is not well understood. However, the neurodegeneration seen in PD is known to be associated with neuroinflammatory-like changes that can affect or be associated with brain vascular function. Thus, dysfunction of the capillary endothelial cell component of neurovascular units present in the brain may contribute to the damage to dopaminergic neurons that occurs in PD. An animal model of PD employing acute, sub-acute and chronic exposures of mice to methyl-phenyl-tetrahydropyridine (MPTP) was used to determine the extent to which brain vasculature may be damaged in PD. Fluoro-Turquoise gelatin labeling of microvessels and endothelial cells was used to determine the extent of vascular damage produced by MPTP. In addition, tyrosine hydroxylase (TH) and NeuN were employed to detect and quantify dopaminergic neuron damage in the striatum (CPu) and substantia nigra (SNc). Gliosis was evaluated through GFAP immunohistochemistry. MPTP treatment drastically reduced TH immunoreactive neurons in the SNc (20.68 ± 2.83 in acute; 22.98 ± 2.14 in sub-acute; 10.20 ± 2.24 in chronic vs 34.88 ± 2.91 in controls; p<0.001). Similarly, TH immunoreactive terminals were dramatically reduced in the CPu of MPTP treated mice. Additionally, all three MPTP exposures resulted in a decrease in the intensity, length, and number of vessels in both CPu and SNc. Degenerative vascular changes such as endothelial cell 'clusters' were also observed after MPTP suggesting that vasculature damage may be modifying the availability of nutrients and exposing blood cells and/or toxic substances to neurons and glia. In summary, vascular damage and degeneration could be an additional exacerbating factor in the progression of PD, and therapeutics that protect and insure vascular integrity may be novel treatments for

  15. 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

  16. 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

  17. POEMS syndrome with Guillan-Barre syndrome-like acute onset: a case report and review of neurological progression in 30 cases.

    PubMed

    Isose, S; Misawa, S; Kanai, K; Shibuya, K; Sekiguchi, Y; Nasu, S; Fujimaki, Y; Noto, Y; Nakaseko, C; Kuwabara, S

    2011-06-01

    POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare cause of demyelinating neuropathy with monoclonal plasma cell proliferation, and POEMS neuropathy is usually chronically progressive. Herein, the authors report a 34-year-old woman with POEMS syndrome presenting as acute polyneuropathy. Within 2 weeks of disease onset, she became unable to walk with electrodiagnostic features of demyelination and was initially diagnosed as having Guillan-Barré syndrome. Other systemic features (oedema and skin changes) developed later, and an elevated serum level of vascular endothelial growth factor led to the diagnosis of POEMS syndrome. She received high-dose chemotherapy with autologous peripheral blood stem cell transplantation, resulting in good recovery. The authors also reviewed patterns and speed of progression of neuropathy in the 30 patients with POEMS syndrome; 22 (73%) of them were unable to walk independently with the median period of 9.5 months from POEMS onset (range 0.5-51 months). Whereas the speed of neuropathy progression varies considerably among patients, some POEMS patients can show acute or subacute polyneuropathy. The early diagnosis and treatment could result in rapid improvement as shown in the present patient.

  18. 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

  19. Computer Models of Stress, Allostasis, and Acute and Chronic Diseases

    PubMed Central

    Goldstein, David S.

    2009-01-01

    The past century has seen a profound shift in diseases of humankind. Acute, unifactorial diseases are being replaced increasingly by multifactorial disorders that arise from complex interactions among genes, environment, concurrent morbidities and treatments, and time. According to the concept of allostasis, there is no single, ideal set of steady-state conditions in life. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators “homeostats.” Stress can be defined as a condition or state in which a sensed discrepancy between afferent information and a setpoint for response leads to activation of effectors, reducing the discrepancy. “Allostatic load” refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of a home temperature control system, the temperature can be maintained at any of a variety of levels (allostatic states) by multiple means (effectors), regulated by a comparator thermostat (homeostat). Stress might exert adverse health consequences via allostatic load. This presentation describes models of homeostatic systems that incorporate negative feedback regulation, multiple effectors, effector sharing, environmental influences, intrinsic obsolescence, and destabilizing positive feedback loops. These models can be used to predict effects of environmental and genetic alterations on allostatic load and therefore on the development of multi-system disorders and failures. PMID:19120114

  20. Viral epidemiology of acute exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Dimopoulos, G; Lerikou, M; Tsiodras, S; Chranioti, Aik; Perros, E; Anagnostopoulou, U; Armaganidis, A; Karakitsos, P

    2012-02-01

    The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation. The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD. Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited. Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses. A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected. The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%). A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients. Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2 ± 4.6 vs 7.6 ± 4.3, p < 0.01) while the severity of the disease was no related with significant differences among the groups of the study population. In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population. The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pathogen was not rare.

  1. MINIMAL RESIDUAL DISEASE QUANTITATION IN ACUTE MYELOID LEUKEMIA

    PubMed Central

    Shook, David; Coustan-Smith, Elaine; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Campana, Dario

    2009-01-01

    The prognosis for patients with acute myeloid leukemia (AML) is heterogeneous. A minority of patients has clinical and biologic features that are associated with a very high risk of relapse. For the remaining patients no clear prognostic factors can be identified at diagnosis. The degree of treatment response is likely to be an informative predictor of outcome for these patients. Modern assays to detect AML cells that are undetectable by conventional morphologic techniques, i.e. minimal residual disease (MRD), can potentially improve measurements of treatment response. It is plausible that modifications to treatment based on the results of these assays will improve clinical management and ultimately increase cure rates. Established MRD assays for AML are based on either polymerase chain reaction (PCR) amplification of genetic abnormalities or flow cytometric detection of abnormal immunophenotypes. Residual disease and treatment response can be measured by these assays in a manner that is much more sensitive and objective than that afforded by conventional morphologic examination. The expanding use of MRD testing is beginning to change the definition of treatment response and of remission. Other clinically informative uses of MRD testing include the detection of early relapse and the evaluation of the efficacy of new antileukemic agents. PMID:19778853

  2. [Acute diarrheal disease caused by enteropathogenic Escherichia coli in Colombia].

    PubMed

    Gómez-Duarte, Oscar G

    2014-10-01

    Intestinal Escherichia coli pathogens are leading causes of acute diarrheal disease in children less than 5 years in Latin America, Africa and Asia and a leading cause of death in children living in poorest communities in Africa and South East Asia. Studies on the role of E. coli pathogens in childhood diarrhea in Colombia and other countries in Latin America are limited due to the lack of detection assays in clinical laboratories at the main urban medical centers. Recent studies report that enterotoxigenic E. coli is the most common E. coli pathogens associated with diarrhea in children less than 5 years of age. Other E. coli pathotypes have been detected in children with diarrhea including enteropathogenic, enteroaggregative, shiga-toxin producing and diffusely adherent E. coli. It was also found that meat and vegetables at retail stores are contaminated with Shiga-toxin producing E. coli and enteroaggregative E. coli, suggesting that food products are involved in transmission and infection of the susceptible host. More studies are necessary to evaluate the mechanisms of transmission, the impact on the epidemiology of diarrheal disease, and management strategies and prevention of these pathogens affecting the pediatric population in Colombia.

  3. 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

  4. Review of Elephant Endotheliotropic Herpesviruses and Acute Hemorrhagic Disease.

    PubMed

    Long, Simon Y; Latimer, Erin M; Hayward, Gary S

    2016-01-01

    More than 100 young captive and wild Asian elephants are known to have died from a rapid-onset, acute hemorrhagic disease caused primarily by multiple distinct strains of two closely related chimeric variants of a novel herpesvirus species designated elephant endotheliotropic herpesvirus (EEHV1A and EEHV1B). These and two other species of Probosciviruses (EEHV4 and EEHV5) are evidently ancient and likely nearly ubiquitous asymptomatic infections of adult Asian elephants worldwide that are occasionally shed in trunk wash secretions. Although only a handful of similar cases have been observed in African elephants, they also have proved to harbor their own multiple and distinct species of Probosciviruses-EEHV2, EEHV3, EEHV6, and EEHV7-found in lung and skin nodules or saliva. For reasons that are not yet understood, approximately 20% of Asian elephant calves appear to be susceptible to the disease when primary infections are not controlled by normal innate cellular and humoral immune responses. Sensitive specific polymerase chain reaction (PCR) DNA blood tests have been developed, routine monitoring has been established, the complete large DNA genomes of each of the four Asian EEHV species have now been sequenced, and PCR gene subtyping has provided unambiguous evidence that this is a sporadic rather than epidemic disease that it is not being spread among zoos or other elephant housing facilities. Nevertheless, researchers have not yet been able to propagate EEHV in cell culture, determine whether or not human antiherpesvirus drugs are effective inhibitors, or develop serology assays that can distinguish between antibodies against the multiple different EEHV species. PMID:26912715

  5. Pathogenesis of acute hepatopancreatic necrosis disease (AHPND) in shrimp.

    PubMed

    Lai, Hung-Chiao; Ng, Tze Hann; Ando, Masahiro; Lee, Chung-Te; Chen, I-Tung; Chuang, Jie-Cheng; Mavichak, Rapeepat; Chang, Sheng-Hsiung; Yeh, Mi-De; Chiang, Yi-An; Takeyama, Haruko; Hamaguchi, Hiro-o; Lo, Chu-Fang; Aoki, Takashi; Wang, Han-Ching

    2015-12-01

    Acute hepatopancreatic necrosis disease (AHPND), also called early mortality syndrome (EMS), is a recently emergent shrimp bacterial disease that has resulted in substantial economic losses since 2009. AHPND is known to be caused by strains of Vibrio parahaemolyticus that contain a unique virulence plasmid, but the pathology of the disease is still unclear. In this study, we show that AHPND-causing strains of V. parahaemolyticus secrete the plasmid-encoded binary toxin PirAB(vp) into the culture medium. We further determined that, after shrimp were challenged with AHPND-causing bacteria, the bacteria initially colonized the stomach, where they started to produce PirAB(vp) toxin. At the same early time point (6 hpi), PirB(vp) toxin, but not PirA(vp) toxin, was detected in the hepatopancreas, and the characteristic histopathological signs of AHPND, including sloughing of the epithelial cells of the hepatopancreatic tubules, were also seen. Although some previous studies have found that both components of the binary PirAB(vp) toxin are necessary to induce a toxic effect, our present results are consistent with other studies which have suggested that PirB(vp) alone may be sufficient to cause cellular damage. At later time points, the bacteria and PirA(vp) and PirB(vp) toxins were all detected in the hepatopancreas. We also show that Raman spectroscopy "Whole organism fingerprints" were unable to distinguish between AHPND-causing and non-AHPND causing strains. Lastly, by using minimum inhibitory concentrations, we found that both virulent and non-virulent V. parahaemolyticus strains were resistant to several antibiotics, suggesting that the use of antibiotics in shrimp culture should be more strictly regulated. PMID:26549178

  6. Acute Hepatic Porphyria

    PubMed Central

    Bissell, D. Montgomery; Wang, Bruce

    2015-01-01

    The porphyrias comprise a set of diseases, each representing an individual defect in one of the eight enzymes mediating the pathway of heme synthesis. The diseases are genetically distinct but have in common the overproduction of heme precursors. In the case of the acute (neurologic) porphyrias, the cause of symptoms appears to be overproduction of a neurotoxic precursor. For the cutaneous porphyrias, it is photosensitizing porphyrins. Some types have both acute and cutaneous manifestations. The clinical presentation of acute porphyria consists of abdominal pain, nausea, and occasionally seizures. Only a small minority of those who carry a mutation for acute porphyria have pain attacks. The triggers for an acute attack encompass certain medications and severely decreased caloric intake. The propensity of females to acute attacks has been linked to internal changes in ovarian physiology. Symptoms are accompanied by large increases in delta-aminolevulinic acid and porphobilinogen in plasma and urine. Treatment of an acute attack centers initially on pain relief and elimination of inducing factors such as medications; glucose is administered to reverse the fasting state. The only specific treatment is administration of intravenous hemin. An important goal of treatment is preventing progression of the symptoms to a neurological crisis. Patients who progress despite hemin administration have undergone liver transplantation with complete resolution of symptoms. A current issue is the unavailability of a rapid test for urine porphobilinogen in the urgent-care setting. PMID:26357631

  7. Clinical and Virologic Characteristics May Aid Distinction of Acute Adenovirus Disease from Kawasaki Disease with Incidental Adenovirus Detection.

    PubMed

    Song, Eunkyung; Kajon, Adriana E; Wang, Huanyu; Salamon, Doug; Texter, Karen; Ramilo, Octavio; Leber, Amy; Jaggi, Preeti

    2016-03-01

    Incidental adenovirus detection in Kawasaki disease (KD) is important to differentiate from acute adenovirus disease. Twenty-four of 25 children with adenovirus disease and mimicking features of KD had <4 KD-like features, predominance of species B or E, and higher viral burden compared with those with KD and incidental adenovirus detection. PMID:26707621

  8. Cigarette smoke causes acute airway disease and exacerbates chronic obstructive lung disease in neonatal mice.

    PubMed

    Jia, Jie; Conlon, Thomas M; Ballester Lopez, Carolina; Seimetz, Michael; Bednorz, Mariola; Zhou-Suckow, Zhe; Weissmann, Norbert; Eickelberg, Oliver; Mall, Marcus A; Yildirim, Ali Önder

    2016-09-01

    Epidemiological evidence demonstrates a strong link between postnatal cigarette smoke (CS) exposure and increased respiratory morbidity in young children. However, how CS induces early onset airway disease in young children, and how it interacts with endogenous risk factors, remains poorly understood. We, therefore, exposed 10-day-old neonatal wild-type and β-epithelial sodium ion channel (β-ENaC)-transgenic mice with cystic fibrosis-like lung disease to CS for 4 days. Neonatal wild-type mice exposed to CS demonstrated increased numbers of macrophages and neutrophils in the bronchoalveolar lavage fluid (BALF), which was accompanied by increased levels of Mmp12 and Cxcl1 BALF from β-ENaC-transgenic mice contained greater numbers of macrophages, which did not increase following acute CS exposure; however, there was significant increase in airway neutrophilia compared with filtered air transgenic and CS-exposed wild-type controls. Interestingly, wild-type and β-ENaC-transgenic mice demonstrated epithelial airway and vascular remodeling following CS exposure. Morphometric analysis of lung sections revealed that CS exposure caused increased mucus accumulation in the airway lumen of neonatal β-ENaC-transgenic mice compared with wild-type controls, which was accompanied by an increase in the number of goblet cells and Muc5ac upregulation. We conclude that short-term CS exposure 1) induces acute airway disease with airway epithelial and vascular remodeling in neonatal wild-type mice; and 2) exacerbates airway inflammation, mucus hypersecretion, and mucus plugging in neonatal β-ENaC-transgenic mice with chronic lung disease. Our results in neonatal mice suggest that young children may be highly susceptible to develop airway disease in response to tobacco smoke exposure, and that adverse effects may be aggravated in children with underlying chronic lung diseases. PMID:27448665

  9. History of neurologic examination books

    PubMed Central

    2015-01-01

    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

  10. Viral epidemiology of acute exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Dimopoulos, G; Lerikou, M; Tsiodras, S; Chranioti, Aik; Perros, E; Anagnostopoulou, U; Armaganidis, A; Karakitsos, P

    2012-02-01

    The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation. The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD. Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited. Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses. A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected. The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%). A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients. Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2 ± 4.6 vs 7.6 ± 4.3, p < 0.01) while the severity of the disease was no related with significant differences among the groups of the study population. In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population. The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pat