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Sample records for spongiform encephalopathy electronic

  1. Transmissible spongiform encephalopathies.

    Science.gov (United States)

    Liemann, S; Glockshuber, R

    1998-09-18

    Scrapie, bovine spongiform encephalopathy (BSE), and the Creutzfeldt-Jakob disease (CJD) belong to a group of lethal neurodegenerative disorders in mammals. Prion diseases or transmissible spongiform encephalopathies (TSEs) are characterized by the accumulation of an abnormal isoform (PrPSc) of the host-encoded cellular prion protein (PrPC) in the brain. The infectious agent, the 'prion,' is believed to be devoid of informational nucleic acid and to consist largely, if not entirely, of PrPSc. The PrP isoforms contain identical amino acid sequences yet differ in their overall secondary structure with the PrPSc isoform possessing a higher beta-sheet and lower alpha-helix content than PrPC. Elucidation of the three-dimensional structure of PrPC has provided important clues on the molecular basis of inherited human TSEs and on the species barrier phenomenon of TSEs. Nevertheless, the molecular mechanism of the conformational rearrangement of PrPC into PrPSc is still unknown, mainly due to the lack of detailed structural information on PrPSc. Within the framework of the 'protein only' hypothesis, two plausible models for the self-replication of prions have been suggested, the conformational model and the nucleation-dependent polymerization model.

  2. IMMUNOLOGICAL STUDY OF SPONGIFORM ENCEPHALOPATHIES

    OpenAIRE

    J. Meenupriya

    2013-01-01

    Spongiform encephalopathies, categorized as a subclass of neuro-degenerative diseases and commonly known as prion diseases, are a group of progressive conditions that affect the brain and nervous system of many animals, including humans. Prion diseases are common among cannibalistic communities; further research has revealed that the infected or malformed prion protein (named PrPsc) spreads its virulence to the normal, healthy prion protein (named PrPc) when people consume...

  3. Mad Cow Disease-Bovine Spongiform Encephalopathy

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 4; Issue 4. Mad Cow Disease - Bovine Spongiform Encephalopathy. Ashutosh ... HP Agricultural University, Palampur 176 662, India. DES (Vety. Sei.) KVK (P A U) Old Gurunanak College Building Hardochhani Road Gurdaspur Punjab 143 521 India.

  4. Pathogenesis of bovine spongiform encephalopathy in sheep

    NARCIS (Netherlands)

    Keulen, van L.J.M.; Vromans, M.E.W.; Dolstra, C.H.; Bossers, A.; Zijderveld, van F.G.

    2008-01-01

    The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrPSc) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrPSc was

  5. [Update on transmissible spongiform subacute encephalopathies (TSSE)].

    Science.gov (United States)

    Brugère-Picoux, Jeanne; Adjou, Karim; Brugère, Henri

    2005-02-01

    This update concerns human and ruminant transmissible spongiform subacute encephalopathies (TSSE). The latest data on variant Creutzfeldt-Jakob disease confirm that new cases are less frequent than feared some years ago, but subclinical carriers could be a source of iatrogenic infection. The macaque is a good model of human oral transmission of bovine spongiform encephalopathy (BSE). The latest data on BSE in Europe confirm the effectiveness of precautionary measures taken in 1996 and 2000. Concerns in other ruminants include a chronic wasting disease of Cervidae in North America, the discovery of a BSE-like agent associated with natural scrapie in a French goat, maternal transmission of natural scrapie in sheep, with an exceptionally short incubation period (6.5 months), and doubts over the efficacy of genetic selection for combating ovine scrapie (atypical cases in " resistant " sheep, especially with the scrapie strain Nor 98 in Europe). These data demonstrate the value of active European surveillance of scrapie in small ruminants.

  6. Bovine Spongiform Encephalopathy (BSE, Mad Cow Disease

    Directory of Open Access Journals (Sweden)

    G. K. Bruckner

    1997-07-01

    Full Text Available Mad Cow Disease or BSE (Bovine Spongiform Encephalopathy became a household name internationally and also in South Africa. International hysteria resulted following reports of a possible link between a disease diagnosed in cattle in Britain and a variant of the disease diagnosed in humans after the presumed ingestion or contact with meat from infected cattle. The European Union instituted a ban on the importation of beef from the United Kingdom during March 1996 that had a severe effect on the beef industry in the UK and also resulted in a world wide consumer resistance against beef consumption.

  7. Prions and animal transmissible spongiform encephalopathies

    Directory of Open Access Journals (Sweden)

    Juntes Polona

    2017-01-01

    Full Text Available Background. Transmissible spongiform encephalopathies (TSEs or prion diseases are a unique group of neurodegenerative diseases of animals and humans, which always have a fatal outcome and are transmissible among animals of the same or different species. Scope and Approach. The aim of this work is to review some recent data about animal TSEs, with the emphasis on their causative agents and zoonotic potential, and to discuss why the surveillance and control measures over animal TSEs should remain in force. Key Findings and Conclusions. We still have incomplete knowledge of prions and prion diseases. Scrapie has been present for a very long time and controlled with varied success. Bovine spongiform encephalopathy (BSE emerged unnoticed, and spread within a few years to epidemic proportions, entailing enormous economic consequences and public concerns. Currently, the classical BSE epidemic is under control, but atypical cases do, and probably will, persist in bovine populations. The Chronic Wasting Disease (CWD of the cervids has been spreading in North America and has recently been detected in Europe. Preventive measures for the control of classical BSE remain in force, including the feed ban and removal of specified risk materials. However, active BSE surveillance has considerably decreased. In the absence of such preventive and control measures, atypical BSE cases in healthy slaughtered bovines might persist in the human food chain, and BSE prions might resurface. Moreover, other prion strains might emerge and spread undetected if the appropriate preventive and surveillance measures were to cease, leaving behind inestimable consequences.

  8. Quantitative Risk Assessment of Bovine Spongiform Encephalopathy

    Science.gov (United States)

    Tsutsui, Toshiyuki; Kasuga, Fumiko

    Bovine spongiform encephalopathy (BSE) is a progressive neurological disease of cattle affecting the central nervous system and was first diagnosed in the United Kingdom (UK) in 1986 (Wells et al., 1987). This disease is one of the transmissible spongiform encephalopathy (TSE) which includes Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep. The causative agent of TSE is considered to be an abnormal form of prion protein. However, the details of its pathogenic mechanism have not been fully identified. Scrapie, which causes neurological symptoms in sheep and goats, has existed in the UK for 200 years (Hoinville, 1996) and spread across the rest of the world in the 1900s (Detwiler & Baylis, 2003). There has been no report so far that scrapie can be transmitted to humans. Initially, BSE was also considered as a disease affecting only animals. However, a variant type of Creutzfeldt-Jakob disease (vCJD) was first reported in the UK, and exposure to a BSE agent was suspected (Collinge, Sidle, Meads, Ironside, & Hill, 1996). vCJD is clinically and pathologically different from the sporadic type of CJD, and age at clinical onset of vCJD is younger than sporadic type (Will et al., 1996). Since the UK government announced the possible association between BSE and vCJD in 1996, BSE has become a huge public health concern all over the world. Of particular concern about vCJD, the fatal disease in younger age, distorted consumer confidence in beef safety, and as a result reduced beef consumption has been seen in many BSE-affected countries.

  9. A quantitative risk assessment for bovine spongiform encephalopathy in Japan

    NARCIS (Netherlands)

    Kadohira, M.; Stevenson, M.A.; Hogasen, H.R.; Koeijer, de A.A.

    2012-01-01

    A predictive case-cohort model was applied to Japanese data to analyze the interaction between challenge and stability factors for bovine spongiform encephalopathy (BSE) for the period 1985–2020. BSE risk in cattle was estimated as the expected number of detectable cases per year. The model was

  10. Human transmissible spongiform encephalopathy: Case report

    OpenAIRE

    Duque Velásquez, Camilo; Garzón Álzate, Ánderson; Villegas Lanau, Andrés; Escobar Velásquez, Laura Marcela; Zea Lopera, Julián; Lopera, Francisco; Rodas González, Juan David

    2014-01-01

    We report the case of a 64 year-old woman with motor and cognitive deterioration that progressed rapidly during eight months. She was unsuccessfully treated with quinacrine, and died in a terminal status, by septic shock secondary to bronchopneumonia by broncho-aspiration. The brain was donated for research and the histopathological analysis showed spongiform changes, astrogliosis and prion protein (PrPRes) deposits, confirmed by Western blot (WB). These features are considered characteristic...

  11. Laboratory Examinations of Transmissible Spongiform Encephalopathies in Denmark during 2014

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre

    , Chapter 2.4.6 and Chapter 2.7.13) regarding diagnostic examinations. The DTU-VET is the national reference laboratory of bovine spongiform encephalopathy (BSE) and TSE/Scrapie, and therefore the results of all neuropathological examinations on BSE and Scrapie in Denmark are given in the present report......The aim of this report is to give detailed information on the diagnostic examination on transmissible spongiform encephalopathies (TSE) performed in Denmark during 2014. The present annual report is the 19th on this topic published by the National Veterinary Institute, Technical University...... of Denmark (DTU-VET). The report is made to fulfil the demands given by the EU Commission (Regulation No 999/2001 of the European Parliament and the Council of 22. May 2001) and the Office Inter-national des Epizooties (OIE) (Manual of Diagnostic Tests and Vaccines for Terrestrial Animals, 5th edition 2008...

  12. Laboratory Examinations of Transmissible Spongiform Encephalopathies in Denmark during 2012

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre

    , Chapter 2.4.6 and Chapter 2.7.13) regarding diagnostic examinations. The DTU-VET is the national reference laboratory of bovine spongiform encephalopathy (BSE) and TSE/Scrapie, and therefore the results of all neuropathological examinations on BSE and Scrapie in Denmark are given in the present report......The aim of this report is to give detailed information on the diagnostic examination on trans-missible spongiform encephalopathies (TSE) performed in Denmark during 2012. The present annual report is the 17th on this topic published by the National Veterinary Institute, Technical University...... of Denmark (DTU-VET). The report is made to fulfil the demands given by the EU Commission (Regulation No 999/2001 of the European Parliament and the Council of 22. May 2001) and the Office Inter-national des Epizooties (OIE) (Manual of Diagnostic Tests and Vaccines for Terrestrial Ani-mals, 5th edition 2008...

  13. Laboratory examinations of transmissible spongiform encephalopathies in Denmark during 2016

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre

    , Chapter 2.4.6 and Chapter 2.7.13) regarding diagnostic examinations.The DTU-VET is the national reference laboratory of bovine spongiform encephalopathy (BSE) and TSE/Scrapie, and therefore the results of all neuropathological examinations on BSE and Scrapie in Denmark are given in the present report......The aim of this report is to give detailed information on the diagnostic examination on trans-missible spongiform encephalopathies (TSE) performed in Denmark during 2016. The present annual report is the 21st on this topic published by the National Veterinary Institute, Technical University...... of Denmark (DTU-VET). The report is made to fulfil the demands given by the EU Commission (Regulation No 999/2001 of the European Parliament and the Council of 22. May 2001) and the Office Inter-national des Epizooties (OIE) (Manual of Diagnostic Tests and Vaccines for Terrestrial Ani-mals, 5th edition 2008...

  14. Laboratory Examinations of Transmissible Spongiform Encephalopathies in Denmark during 2013

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre

    , Chapter 2.4.6 and Chapter 2.7.13) regarding diagnostic examinations. The DTU-VET is the national reference laboratory of bovine spongiform encephalopathy (BSE) and TSE/Scrapie, and therefore the results of all neuropathological examinations on BSE and Scrapie in Denmark are given in the present report......The aim of this report is to give detailed information on the diagnostic examination on trans-missible spongiform encephalopathies (TSE) performed in Denmark during 2013. The present annual report is the 18th on this topic published by the National Veterinary Institute, Technical University...... of Denmark (DTU-VET). The report is made to fulfil the demands given by the EU Commission (Regulation No 999/2001 of the European Parliament and the Council of 22. May 2001) and the Office Inter-national des Epizooties (OIE) (Manual of Diagnostic Tests and Vaccines for Terrestrial Ani-mals, 5th edition 2008...

  15. Human transmissible spongiform encephalopathy: Case report

    Directory of Open Access Journals (Sweden)

    Duque Velásquez, Camilo

    2014-07-01

    Full Text Available We report the case of a 64 year-old woman with motor and cognitive deterioration that progressed rapidly during eight months. She was unsuccessfully treated with quinacrine, and died in a terminal status, by septic shock secondary to bronchopneumonia by broncho-aspiration. The brain was donated for research and the histopathological analysis showed spongiform changes, astrogliosis and prion protein (PrPRes deposits, confirmed by Western blot (WB. These features are considered characteristic of prion diseases, which are uncommon in Colombia. We highlight that its diagnosis was made for the first time in this country by the simultaneous use of immunohistochemistry and Western blot.

  16. Chronic wasting disease of captive mule deer: a spongiform encephalopathy.

    Science.gov (United States)

    Williams, E S; Young, S

    1980-01-01

    In the past 12 years (1967-79) a syndrome we identify as chronic wasting disease has been observed in 53 mule deer (Odocoileus hemionus hemionus) and one black-tailed deer (Odocoileus hemionus columbianus) held in captivity in several wildlife facilities in Colorado and more recently in Wyoming. Clinical signs were seen in adult deer and included behavioral alterations, progressive weight loss and death in 2 weeks to 8 months. Gross necropsy findings included emaciation and excess rumen fluid admixed with sand and gravel. Consistent histopathologic change was limited to the central nervous system and characterized by widespread spongiform transformation of the neuropil, single of multiple intracytoplasmic vacuoles in neuronal perikaryons and intense astrocytic hypertrophy and hyperplasia. Presented is a clinical characterization of chronic wasting disease and pathologic evidence supporting the conclusion that the disease is a specific spontaneously occurring form of spongiform encephalopathy.

  17. Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies

    Science.gov (United States)

    Transmissible Spongiform Encephalopathies (TSEs), including scrapie in sheep, chronic wasting disease (CWD) in cervids, and bovine spongiform encephalopathy (BSE), are fatal diseases of the nervous system associated with accumulation of misfolded prion protein (PrPSc). Different strains of BSE exist...

  18. Current status of transmissible spongiform encephalopathies in ruminants

    Directory of Open Access Journals (Sweden)

    Penders J.

    2004-01-01

    Full Text Available Transmissible spongiform encephalopathies (TSE encompass subacute neurological degenerative diseases for which the prototypes are scrapie in sheep and some forms of Creutzfeldt-Jakob disease in man. The emergence of a new form of TSE in cattle in United Kingdom (UK since 1986, namely bovine spongiform encephalopathy (BSE, sharply increased the interest for these diseases, especially because of the epidemic nature of BSE in UK, its subsequent spread in continental Europe and the later discovery of its zoonotic character. The number of measures of veterinary public health taken to control the disease and to prevent its spread to animals and human beings increased in time and culminated by the total feed ban. Indeed, since the beginning of 2001, feed containing proteins of animal origin is prohibited for the feeding of production animals, including ruminants and monogastric species. The effect of this total ban of mammalian meat and bone meal needs to be evaluated. The incidence of BSE has a trend to decrease in UK and in most of the other European member states. However, as BSE is a rare event distributed in a large bovine population, it is difficult to state unambiguously whether this trend is significant. Furthermore, the evaluation of this measure will be only effective at least five years after its introduction, since this period is the mean incubation time of BSE. The main concern is currently the eradication of BSE in the infected countries. Additionally, the control of scrapie is also carried out due to the possible contamination of sheep with the BSE agent. These actions must take into account several new facts: the recent discovery of BSE cases in countries with a low geographical BSE risk level as Japan, Canada and the United States of America (USA; the growing incidence of chronic wasting disease, a spongiform encephalopathy observed in deer in USA; the characterization of a new pattern of bovine amyloidotic spongiform encephalopathy in

  19. Cattle traceability system in Japan for bovine spongiform encephalopathy

    Directory of Open Access Journals (Sweden)

    Katsuaki Sugiura

    2008-09-01

    Full Text Available To promote consumer confidence in the safety of beef and to ensure the proper implementation of eradication measures against bovine spongiform encephalopathy (BSE, the Cattle Traceability Law was approved by the Diet in June 2003 and a cattle traceability system has been in operation in Japan since December 2003. The system enables tracing the cohort and offspring animals of a BSE case within 24 h of its detection. The traceability database system also provides distributors, restaurants and consumers with information on the cattle from which the beef that they sell, serve and consume originate.

  20. [Risk assessment for importing bovine spongiform encephalopathy (BSE)].

    Science.gov (United States)

    Hörnlimann, B; Guidon, D; Griot, C

    1994-07-01

    Since the occurrence of bovine spongiform encephalopathy (BSE) in Switzerland in 1990, extensive epidemiological investigations and risk factor analyses were carried out. In this study, statistical data on meat and bone meal traded from 1985 to 1989 were analysed addressing the following questions: i) what amount of meat and bone meal was exported from Great Britain (GB) and where to and ii) what amount of meat and bone meal was imported into Switzerland and where from? The findings led to the hypothesis that imported material potentially infected with scrapie-like agents was the cause for BSE in Switzerland.

  1. Bovine spongiform encephalopathy--some surprises for biochemists.

    Science.gov (United States)

    Campbell, Peter N

    2005-01-01

    Bovine Spongiform Encephalopathy (BSE) is typical of the dementias that affect both animals and man; Scrapie in sheep, Creutzfeldt-Jakob disease in man. Global efforts have been made to determine the nature of the active agents in these diseases. At present the 'protein only hypothesis' of Prusiner holds. It was a surprise that a protein could per se be the active agent but other surprises for our traditional teaching of biochemistry arose. These are explained in a brief summary of our present understanding of the biochemistry of the active agents that cause the diseases.

  2. Use of murine bioassay to resolve ovine transmissible spongiform encephalopathy cases showing a bovine spongiform encephalopathy molecular profile.

    Science.gov (United States)

    Beck, Katy E; Sallis, Rosemary E; Lockey, Richard; Vickery, Christopher M; Béringue, Vincent; Laude, Hubert; Holder, Thomas M; Thorne, Leigh; Terry, Linda A; Tout, Anna C; Jayasena, Dhanushka; Griffiths, Peter C; Cawthraw, Saira; Ellis, Richard; Balkema-Buschmann, Anne; Groschup, Martin H; Simmons, Marion M; Spiropoulos, John

    2012-05-01

    Two cases of unusual transmissible spongiform encephalopathy (TSE) were diagnosed on the same farm in ARQ/ARQ PrP sheep showing attributes of both bovine spongiform encephalopathy (BSE) and scrapie. These cases, UK-1 and UK-2, were investigated further by transmissions to wild-type and ovine transgenic mice. Lesion profiles (LP) on primary isolation and subpassage, incubation period (IP) of disease, PrP(Sc) immunohistochemical (IHC) deposition pattern and Western blot profiles were used to characterize the prions causing disease in these sheep. Results showed that both cases were compatible with scrapie. The presence of BSE was contraindicated by the following: LP on primary isolation in RIII and/or MR (modified RIII) mice; IP and LP after serial passage in wild-type mice; PrP(Sc) deposition pattern in wild-type mice; and IP and Western blot data in transgenic mice. Furthermore, immunohistochemistry (IHC) revealed that each case generated two distinct PrP(Sc) deposition patterns in both wild-type and transgenic mice, suggesting that two scrapie strains coexisted in the ovine hosts. Critically, these data confirmed the original differential IHC categorization that these UK-1 and UK-2 cases were not compatible with BSE. © 2011 The Authors. Brain Pathology © 2011 International Society of Neuropathology.

  3. Encefalopatías espongiformes transmisibles Transmissible spongiform encephalopathies

    Directory of Open Access Journals (Sweden)

    Jorge E Delgado-Hachmeister

    2002-01-01

    Full Text Available Las encefalopatías espongiformes transmisibles (EET han cobrado gran importancia en los últimos años. Principalmente por el surgimiento de la encefalopatía espongiforme del bovino (EEB y la nueva variante de la ermedad de Creutzfeldt-Jakob (nvECJ, esta última probablemente adquirida por la ingesta de carne de bovino contaminada. Hasta la fecha se ha informado de 109 casos de la nvECJ en el humano y la gran mayoría de los casos ha ocurrido en el Reino Unido. No se sabe la magnitud real que podrán tener las EET en el humano, sin embargo algunos piensan que nos encontramos en el principio de una pandemia de la nvECJ. En el presente artículo se discuten varios aspectos de las EET y métodos para la prevención de la transmisión de estas enfermedades, tanto en rumiantes como en el humano.Transmissible spongiform encephalopathies (TSE are a group of diseases which have received a lot of attention in recent years. The interest on these diseases has been stimulated by the appearance of bovine spongiform encephalopathy (BSE and the new variant of Creutzfeldt-Jakob disease (nvCJD; the latter is likely to be acquired by ingesting contaminated beef. Until now 109 cases of nvCJD have been reported, most of them occurring in the United Kingdom. Some experts think that this is the beginning of a nvCJD pandemic. Deep knowledge of the mechanisms of transmission of TSE is needed to prevent the emergence of a TSE pandemic in humans.We address various aspects of TSE and discuss prevention methods of TSE in ruminants and humans.

  4. Human transmissible spongiform encephalopathies in eleven countries: Diagnostic pattern across time, 1993-2002

    NARCIS (Netherlands)

    J. de Pedro-Cuesta (Jesús); M. Glatzel (Markus); J. Almazán (Javier); K. Stoeck (Katharina); V. Mellina (Vittorio); M. Puopolo (Maria); M. Pocchiari (Maurizio); I. Zerr (Inga); H.A. Kretszchmar (Hans); J-P. Brandel (Jean-Philippe); N. Delasnerie-Laupretre (Nicole); A. Alperovitch (Annick); C.M. van Duijn (Cornelia); P. Sanchez-Juan (Pascual); S.J. Collins (Steven); V. Lewis (Victoria); G.H. Jansen (Gerard); M.B. Coulthart (Michael); E. Gelpi (Ellen); H. Budka (Herbert); E. Mitrová (Eva)

    2006-01-01

    textabstractBackground: The objective of this study was to describe the diagnostic panorama of human transmissible spongiform encephalopathies across 11 countries. Methods: From data collected for surveillance purposes, we describe annual proportions of deaths due to different human transmissible

  5. Bovine spongiform encephalopathy in South America: a regional preventive approach.

    Science.gov (United States)

    van Gelderen, C; Gimeno, E J; Schudel, A A

    2003-04-01

    Bovine spongiform encephalopathy (BSE) is a neurodegenerative disease of cattle caused by prions that was first described in the United Kingdom (UK) in 1986. The BSE epizootic that commenced in the UK in the 1980s has since spread into other countries in Europe and Asia through exports of contaminated meat-and-bone meal or infected cattle. Over the past few years, other emerging or reemerging diseases have spread into previously free countries or regions through international trade. This negative effect of globalisation means that to implement successful preventive and strategic programmes to safeguard animal health, such programmes must, as a priority, take a regional approach. Global thinking, regional planning and local performance constitute the key factors for the successful control of animal diseases. In South America, initial preventive actions against BSE were adopted in 1989. Further measures adopted since then and based on new scientific and technical findings, have led to the demonstration that the region is free of BSE. These early preventive actions have reliably protected the region from importing BSE-infected material. An integral part of the project to determine the BSE status of South America was the training of personnel, the incorporation of technology and the provision of updated information through close relationships with international organisations and prominent international researcher workers. Regional activities aimed at harmonising BSE prevention programmes, producing objective and transparent data on the equivalence of regional BSE status and facilitating regional and international trade have recently been launched. Maintaining the BSE-free status of the region must be given high priority by the beef agro-industrial sectors.

  6. Immunohistochemical distinction between preclinical bovine spongiform encephalopathy and scrapie infection in sheep

    NARCIS (Netherlands)

    Thuring, C.M.A.; Keulen, van L.J.M.; Langeveld, J.P.M.; Vromans, M.E.W.; Zijderveld, van F.G.; Sweeney, T.

    2005-01-01

    Sheep are susceptible experimentally to bovine spongiform encephalopathy (BSE), the clinical signs being indistinguishable from those of scrapie. Because of the possibility of natural ovine BSE infection, laboratory tests are needed to distinguish between scrapie and BSE infection. The objectives of

  7. the role of mathematical modelling in understanding the epidemiology and control of sheep transmissible spongiform encephalopathies: a review

    NARCIS (Netherlands)

    Gubbins, S.; Touzeau, S.; Hagenaars, T.H.J.

    2010-01-01

    To deal with the incompleteness of observations and disentangle the complexities of transmission much use has been made of mathematical modelling when investigating the epidemiology of sheep transmissible spongiform encephalopathies (TSE) and, in particular, scrapie. Importantly, these modelling

  8. Risk analysis of Transmissible Spongiform Encephalopathies in animals: state-of-the-art

    DEFF Research Database (Denmark)

    Paisley, Larry; de Koeijer, Aline; Hagenaars, Thomas J.

    2008-01-01

    The Bovine Spongiform Encephalopathy (BSE) crisis of the last two decades has shown that proper interaction of risk assessment, risk management and risk communication is essential. Mathematical models and risk assessments have been used as a basis for BSE risk management options and much of the l......The Bovine Spongiform Encephalopathy (BSE) crisis of the last two decades has shown that proper interaction of risk assessment, risk management and risk communication is essential. Mathematical models and risk assessments have been used as a basis for BSE risk management options and much......). Nevertheless, the decline in the BSE epidemic in the UK and most European countries demonstrates that management has been, for the most part, sucessful. Literature pertaining to the three inter-related facets of risk analysis: risk assessment, risk management and risk communication of TSE's of animal origin...... was reviewed and used to describe the state-of-the-art of risk analysis for TSEs....

  9. [Bovine spongiform encephalopathy. Second update of data collected since the report of February 6, 1996].

    Science.gov (United States)

    Brugère-Picoux, J; Lasmézas, C; Deslys, J P; Adjou, K; Rérat, A; Dormont, D

    1996-01-01

    The observation in 1995 and 1996 of 12 cases of a new variant of Creutzfeldt-Jakob disease (V-CJD) in U.K. suggested a possible relation between this human cases and bovine spongiform encephalopathy (BSE). Recent papers about this topic are reviewed: BSE transmission to macaques, transmission of scrapie with embryo transfer, incidence of maternal transmission, PrP protein released by platelets, diagnostic test by detection of PrP protein in tissues of sheep, epidemiology of BSE, french regulations, identification of cattle in U.K.

  10. Monitoring and analysis of bovine spongiform encephalopathy (BSE) testing in Denmark using statistical models

    DEFF Research Database (Denmark)

    Paisley, Larry

    2002-01-01

    The evolution of monitoring and surveillance for bovine spongiform encephalopathy (BSE) from the phase of passive surveillance that began in the United Kingdom in 1988 until the present is described. Currently, surveillance for BSE in Europe consists of mass testing of cattle slaughtered for human...... consumption and cattle from certain groups considered to be at higher risk of having clinical or detectable BSE. The results of the ongoing BSE testing in Denmark have been analyzed using two statistical approaches: the "classical" fequuentist and the Bayesian that is widely used in quantitative risk analysis...

  11. Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control.

    Science.gov (United States)

    Seuberlich, Torsten; Heim, Dagmar; Zurbriggen, Andreas

    2010-11-01

    Since 1987, when bovine spongiform encephalopathy (BSE) emerged as a novel disease in cattle, enormous efforts were undertaken to monitor and control the disease in ruminants worldwide. The driving force was its high economic impact, which resulted from trade restrictions and the loss of consumer confidence in beef products, the latter because BSE turned out to be a fatal zoonosis, causing variant Creutzfeldt-Jakob disease in human beings. The ban on meat and bone meal in livestock feed and the removal of specified risk materials from the food chain were the main measures to successfully prevent infection in cattle and to protect human beings from BSE exposure. However, although BSE is now under control, previously unknown, so-called atypical transmissible spongiform encephalopathies (TSEs) in cattle and small ruminants have been identified by enhanced disease surveillance. This report briefly reviews and summarizes the current level of knowledge on the spectrum of TSEs in cattle and small ruminants and addresses the question of the extent to which such atypical TSEs have an effect on disease surveillance and control strategies.

  12. Control of bovine spongiform encephalopathy by genetic engineering: possible approaches and regulatory considerations

    International Nuclear Information System (INIS)

    Gavora, J.S.; Kochhar, H.P.S.; Gifford, G.A.

    2005-01-01

    Transmissible spongiform encephalopathies (TSE) include bovine spongiform encephalopathy (BSE), scrapie in sheep and Creutzfeldt-Jakob disease (CJD) in humans. A new CJD variant (nvCJD) is believed to be related to consumption of meat from BSE cattle. In TSE individuals, prion proteins (PrP) with approximately 250 amino acids convert to the pathogenic prion PrP Sc , leading to a dysfunction of the central neural system. Research elsewhere with mice has indicated a possible genetic engineering approach to the introduction of BSE resistance: individuals with amino acid substitutions at positions 167 or 218, inoculated with a pathogenic prion protein, did not support PrP Sc replication. This raises the possibility of producing prion-resistant cattle with a single PrP amino acid substitution. Since prion-resistant animals might still harbour acquired prion infectivity, regulatory assessment of the engineered animals would need to ascertain that such possible 'carriers' do not result in a threat to animal and human health. (author)

  13. Generation of a persistently infected MDBK cell line with natural bovine spongiform encephalopathy (BSE.

    Directory of Open Access Journals (Sweden)

    Dongseob Tark

    Full Text Available Bovine spongiform encephalopathy (BSE is a zoonotic transmissible spongiform encephalopathy (TSE thought to be caused by the same prion strain as variant Creutzfeldt-Jakob disease (vCJD. Unlike scrapie and chronic wasting disease there is no cell culture model allowing the replication of proteinase K resistant BSE (PrPBSE and the further in vitro study of this disease. We have generated a cell line based on the Madin-Darby Bovine Kidney (MDBK cell line over-expressing the bovine prion protein. After exposure to naturally BSE-infected bovine brain homogenate this cell line has shown to replicate and accumulate PrPBSE and maintain infection up to passage 83 after initial challenge. Collectively, we demonstrate, for the first time, that the BSE agent can infect cell lines over-expressing the bovine prion protein similar to other prion diseases. These BSE infected cells will provide a useful tool to facilitate the study of potential therapeutic agents and the diagnosis of BSE.

  14. Central nervous system gene expression changes in a transgenic mouse model for bovine spongiform encephalopathy

    Directory of Open Access Journals (Sweden)

    Tortosa Raül

    2011-10-01

    Full Text Available Abstract Gene expression analysis has proven to be a very useful tool to gain knowledge of the factors involved in the pathogenesis of diseases, particularly in the initial or preclinical stages. With the aim of finding new data on the events occurring in the Central Nervous System in animals affected with Bovine Spongiform Encephalopathy, a comprehensive genome wide gene expression study was conducted at different time points of the disease on mice genetically modified to model the bovine species brain in terms of cellular prion protein. An accurate analysis of the information generated by microarray technique was the key point to assess the biological relevance of the data obtained in terms of Transmissible Spongiform Encephalopathy pathogenesis. Validation of the microarray technique was achieved by RT-PCR confirming the RNA change and immunohistochemistry techniques that verified that expression changes were translated into variable levels of protein for selected genes. Our study reveals changes in the expression of genes, some of them not previously associated with prion diseases, at early stages of the disease previous to the detection of the pathological prion protein, that might have a role in neuronal degeneration and several transcriptional changes showing an important imbalance in the Central Nervous System homeostasis in advanced stages of the disease. Genes whose expression is altered at early stages of the disease should be considered as possible therapeutic targets and potential disease markers in preclinical diagnostic tool development. Genes non-previously related to prion diseases should be taken into consideration for further investigations.

  15. Possible case of maternal transmission of feline spongiform encephalopathy in a captive cheetah.

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    Anna Bencsik

    Full Text Available Feline spongiform encephalopathy (FSE is considered to be related to bovine spongiform encephalopathy (BSE and has been reported in domestic cats as well as in captive wild cats including cheetahs, first in the United Kingdom (UK and then in other European countries. In France, several cases were described in cheetahs either imported from UK or born in France. Here we report details of two other FSE cases in captive cheetah including a 2(nd case of FSE in a cheetah born in France, most likely due to maternal transmission. Complete prion protein immunohistochemical study on both brains and peripheral organs showed the close likeness between the two cases. In addition, transmission studies to the TgOvPrP4 mouse line were also performed, for comparison with the transmission of cattle BSE. The TgOvPrP4 mouse brains infected with cattle BSE and cheetah FSE revealed similar vacuolar lesion profiles, PrP(d brain mapping with occurrence of typical florid plaques. Collectively, these data indicate that they harbor the same strain of agent as the cattle BSE agent. This new observation may have some impact on our knowledge of vertical transmission of BSE agent-linked TSEs such as in housecat FSE, or vCJD.

  16. Bovine Spongiform Encephalopathy (BSE – Infectious, Contagious, Zoonotic or Production Disease?

    Directory of Open Access Journals (Sweden)

    Doherr Marcus G

    2003-03-01

    Full Text Available In 1986, a new progressive neurological condition similar to scrapie of sheep and goats was recognised in cattle in the United Kingdom (UK, and was named bovine spongiform encephalopathy (BSE. There is an ongoing discussion whether BSE should be classified as infectious, contagious, or zoonotic, and if it fits the definition of a production disease. The objective of this work is to briefly describe the main characteristics of transmissible spongiform encephalopathies (TSE, to review the epidemiology of BSE, and to address the question of how to classify BSE. TSEs are characterised as chronic wasting diseases with spongiform vacuolation and the accumulation of infectious prion protein (PrPSc in the central nervous system. TSE infectivity is very difficult to inactivate. Cattle BSE most likely originated from sheep scrapie, although this will remain to be an issue for debate. The disease can be transmitted from cattle to a range of species, and has resulted in smaller TSE epidemics in domestic cats, zoo cats and zoo ruminants, and in humans. Transmission in the field occurred through feed containing ruminant-derived protein, and measures to prevent the recycling of infectivity have proven effective to reduce the number of new infections. Mandatory reporting of clinical suspects combined with targeted screening of risk populations is needed to assess the BSE status of a country. Infection studies and the transmissibility to other species classify BSE as infectious and zoonotic. Absence of excretion of the agent, and therefor of horizontal transmission, categorise BSE as non-contagious. However, BSE is a multifactorial infectious disease that is dependent on management factors (mainly feeding, and therefore fits into the broader definition of production diseases.

  17. Sheep-passaged bovine spongiform encephalopathy agent exhibits altered pathobiological properties in bovine-PrP transgenic mice

    NARCIS (Netherlands)

    Espinosa, J.C.; Andreoletti, O.; Castilla, J.; Herva, M.E.; Morales, M.; Alamillo, E.; San-Segundo, F.D.; Lacroux, C.; Lugan, S.; Salguero, F.J.; Langeveld, J.P.M.; Torres, J.M.

    2007-01-01

    Sheep can be experimentally infected with bovine spongiform encephalopathy (BSE), and the ensuing disease is similar to scrapie in terms of pathogenesis and clinical signs. BSE infection in sheep is an animal and human health concern. In this study, the transmission in BoPrP-Tg110 mice of prions

  18. Animal feed controls implemented in Japan for the eradication of bovine spongiform encephalopathy

    Directory of Open Access Journals (Sweden)

    Katsuaki Sugiura

    2009-06-01

    Full Text Available After the detection of the first case of bovine spongiform encephalopathy (BSE in Japan in September 2001, the Japanese government introduced a series of animal feed control measures to reduce the risk of the spread of the disease from a feed source. To ensure the proper implementation of these measures, the Food and Agricultural Materials Inspection Centre conducted audit inspections of feed importers, producers, distributors and end-users. The audit inspections include on-site inspection of the feed plants, warehouses, farms and other related premises and the laboratory analysis of feed samples taken from these premises to check for the presence of animal protein. The results of inspections conducted in recent years indicate good compliance with the feed control measures.

  19. Reflexive modernization at the source: local media coverage of bovine spongiform encephalopathy in rural Alberta.

    Science.gov (United States)

    Davidson, Debra J; Bogdan, Eva

    2010-11-01

    The potential for reflexive modernization is defined by multiple factors, but the acknowledgment of risk is crucial, particularly among social groups that play a key role in risk minimization. This study offers an examination of the role of local media in response to the outbreak of bovine spongiform encephalopathy (BSE) in beef-producing communities in rural Alberta. BSE is one of several global risk issues that reflexive modernization theorists argue have the potential to trigger a transformation toward a critically reflexive society in which such risks are minimized. Content analysis of newspapers in beef-producing regions in Alberta, however, shows how local media framed BSE in a manner that maximized community cohesion and protection of local culture. This selective coverage of BSE in rural Alberta is quite likely to have contributed to, or at least reinforced, support for the current institutional structure of Canadian agriculture in beef-producing regions, through the constriction of discourse.

  20. Comparative evidence for a link between Peyer's patch development and susceptibility to transmissible spongiform encephalopathies

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    Rhind Susan M

    2006-01-01

    Full Text Available Abstract Background Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs reflect age-related risk of infection, however, the underlying mechanisms remain poorly understood. Using a comparative approach, we tested the hypothesis that, there is a significant correlation between risk of infection for scrapie, bovine spongiform encephalopathy (BSE and variant CJD (vCJD, and the development of lymphoid tissue in the gut. Methods Using anatomical data and estimates of risk of infection in mathematical models (which included results from previously published studies for sheep, cattle and humans, we calculated the Spearman's rank correlation coefficient, rs, between available measures of Peyer's patch (PP development and the estimated risk of infection for an individual of the corresponding age. Results There was a significant correlation between the measures of PP development and the estimated risk of TSE infection; the two age-related distributions peaked in the same age groups. This result was obtained for each of the three host species: for sheep, surface area of ileal PP tissue vs risk of infection, rs = 0.913 (n = 19, P s = 0.933 (n = 19, P s = 0.693 (n = 94, P s = 0.384 (n = 46, P = 0.008. In addition, when changes in exposure associated with BSE-contaminated meat were accounted for, the two age-related patterns for humans remained concordant: rs = 0.360 (n = 46, P = 0.014. Conclusion Our findings suggest that, for sheep, cattle and humans alike there is an association between PP development (or a correlate of PP development and susceptibility to natural TSE infection. This association may explain changes in susceptibility with host age, and differences in the age-susceptibility relationship between host species.

  1. Strain specific and common pathogenic events in murine models of scrapie and bovine spongiform encephalopathy.

    Science.gov (United States)

    Lasmézas, C I; Deslys, J P; Demaimay, R; Adjou, K T; Hauw, J J; Dormont, D

    1996-07-01

    The development of transmissible spongiform encephalopathies in experimental models depends on two major factors: the intracerebral accumulation of an abnormal, protease-resistant isoform of PrP (PrPres), which is a host protein mainly expressed in neurons; and the existence of different strains of agent. In order to make a distinction between pathogenic mechanisms depending upon the accumulation of host-derived PrPres and the strain-specific effects, we quantified and compared the sequence of molecular [PrPres and glial fibrillary acidic protein (GFAP) accumulation] and pathological events in the brains of syngeneic mice throughout the course of infection with two different strains of agent. The bovine spongiform encephalopathy (BSE) agent exhibits properties different from any known scrapie source and has been studied in comparison with a classical scrapie strain. Convergent kinetic data in both models confirmed the cause-effect relationship between PrPres and pathological changes and showed that PrPres accumulation is directly responsible for astrocyte activation in vivo. Moreover, we observed a threshold level of PrPres for this effect on astroglial cells. However, despite similar infectivity titres, the BSE model produced less PrPres than scrapie, and the relative importance of gliosis was higher. The comparison of the molecular and pathological features after intracerebral or intraperitoneal inoculation also revealed differences between the models. Therefore, the mechanisms leading to the targeting and the fine regulation of the molecular events seem to be independent of the host PrP and to depend upon the agent. The possible involvement of a regulatory molecule accounting for these specificities has to be considered.

  2. High-Throughput Screening of Compounds for Anti-Transmissible Spongiform Encephalopathy Activity Using Cell-Culture and Cell-Free Models and Infected Animals

    National Research Council Canada - National Science Library

    Caughey, Byron

    2004-01-01

    Transmissible spongiform encephalopathies (TSEs) are fatal untreatable neurodegenerative diseases associated with the accumulation of a disease-specific form of prion protein (prp(expSc)) in the brain...

  3. Detection and localisation of PrP(Sc in the liver of sheep infected with scrapie and bovine spongiform encephalopathy.

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    Sally J Everest

    Full Text Available Prions are largely contained within the nervous and lymphoid tissue of transmissible spongiform encephalopathy (TSE infected animals. However, following advances in diagnostic sensitivity, PrP(Sc, a marker for prion disease, can now be located in a wide range of viscera and body fluids including muscle, saliva, blood, urine and milk, raising concerns that exposure to these materials could contribute to the spread of disease in humans and animals. Previously we demonstrated low levels of infectivity in the liver of sheep experimentally challenged with bovine spongiform encephalopathy. In this study we show that PrP(Sc accumulated in the liver of 89% of sheep naturally infected with scrapie and 100% of sheep challenged with BSE, at both clinical and preclinical stages of the disease. PrP(Sc was demonstrated in the absence of obvious inflammatory foci and was restricted to isolated resident cells, most likely Kupffer cells.

  4. Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle ? an update

    OpenAIRE

    Konold, Timm; Arnold, Mark E; Austin, Anthony R; Cawthraw, Saira; Hawkins, Steve AC; Stack, Michael J; Simmons, Marion M; Sayers, A Robin; Dawson, Michael; Wilesmith, John W; Wells, Gerald AH

    2012-01-01

    Abstract Background To provide information on dose–response and aid in modelling the exposure dynamics of the BSE epidemic in the United Kingdom groups of cattle were exposed orally to a range of different doses of brainstem homogenate of known infectious titre from clinical cases of classical bovine spongiform encephalopathy (BSE). Interim data from this study was published in 2007. This communication documents additional BSE cases, which occurred subsequently, examines possible influence of...

  5. The evolution of risk perceptions related to bovine spongiform encephalopathy--Canadian consumer and producer behavior.

    Science.gov (United States)

    Yang, Jun; Goddard, Ellen

    2011-01-01

    In this study the dynamics of risk perceptions related to bovine spongiform encephalopathy (BSE) held by Canadian consumers and cow-calf producers were evaluated. Since the first domestic case of BSE in 2003, Canadian consumers and cow-calf producers have needed to make decisions on whether or not their purchasing/production behavior should change. Such changes in their behavior may relate to their levels of risk perceptions about BSE, risk perceptions that may be evolving over time and be affected by BSE media information available. An econometric analysis of the behavior of consumers and cow-calf producers might identify the impacts of evolving BSE risk perceptions. Risk perceptions related to BSE are evaluated through observed market behavior, an approach that differs from traditional stated preference approaches to eliciting risk perceptions at a particular point in time. BSE risk perceptions may be specified following a Social Amplification of Risk Framework (SARF) derived from sociology, psychology, and economics. Based on the SARF, various quality and quantity indices related to BSE media information are used as explanatory variables in risk perception equations. Risk perceptions are approximated using a predictive difference approach as defined by Liu et al. (1998). Results showed that Canadian consumer and cow-calf producer risk perceptions related to BSE have been amplified or attenuated by both quantity and quality of BSE media information. Government policies on risk communications need to address the different roles of BSE information in Canadian consumers' and cow-calf producers' behavior.

  6. Toward unfolding the prion misfolding mystery: protein free radical chemistry in transmissible spongiform encephalopathies

    International Nuclear Information System (INIS)

    Yang Chiming

    2003-01-01

    Owing to the high oxygen-respiration in the brain of mammals, oxidative damage to prion protein has been suggested to be an additional factor. A large body of intriguing features of scrapie and prion diseases have provided multiple lines of indirect chemistry evidence, suggesting that the infectious agents may be putative forms of sequence-specific prion radicals (SSPR) and/or their immediate precursors in the transmissible spongiform encephalopathies (TSE). Here a molecular mechanism corresponding to the self-replication of scrapie protein mediated by prion free-radical processes, consonant with 'protein-only' hypotheses is proposed. This new theory may not only aid our understanding of the occurrence of prions, but also provides new insight into the possible chemistry principles underlying the neutrodegenerative disorders. It is anticipated that future studies based on this suggestion and chemistry principles of genetic diseases may allow us to determine an effective approach to stop mad cow disease and its human version, new variant of Creutzfeldt-Jakob disease (v CJD)

  7. Infectivity in skeletal muscle of cattle with atypical bovine spongiform encephalopathy.

    Science.gov (United States)

    Suardi, Silvia; Vimercati, Chiara; Casalone, Cristina; Gelmetti, Daniela; Corona, Cristiano; Iulini, Barbara; Mazza, Maria; Lombardi, Guerino; Moda, Fabio; Ruggerone, Margherita; Campagnani, Ilaria; Piccoli, Elena; Catania, Marcella; Groschup, Martin H; Balkema-Buschmann, Anne; Caramelli, Maria; Monaco, Salvatore; Zanusso, Gianluigi; Tagliavini, Fabrizio

    2012-01-01

    The amyloidotic form of bovine spongiform encephalopathy (BSE) termed BASE is caused by a prion strain whose biological properties differ from those of typical BSE, resulting in a clinically and pathologically distinct phenotype. Whether peripheral tissues of BASE-affected cattle contain infectivity is unknown. This is a critical issue since the BASE prion is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible. We carried out bioassays in transgenic mice overexpressing bovine PrP (Tgbov XV) and found infectivity in a variety of skeletal muscles from cattle with natural and experimental BASE. Noteworthy, all BASE muscles used for inoculation transmitted disease, although the attack rate differed between experimental and natural cases (∼70% versus ∼10%, respectively). This difference was likely related to different prion titers, possibly due to different stages of disease in the two conditions, i.e. terminal stage in experimental BASE and pre-symptomatic stage in natural BASE. The neuropathological phenotype and PrP(res) type were consistent in all affected mice and matched those of Tgbov XV mice infected with brain homogenate from natural BASE. The immunohistochemical analysis of skeletal muscles from cattle with natural and experimental BASE showed the presence of abnormal prion protein deposits within muscle fibers. Conversely, Tgbov XV mice challenged with lymphoid tissue and kidney from natural and experimental BASE did not develop disease. The novel information on the neuromuscular tropism of the BASE strain, efficiently overcoming species barriers, underlines the relevance of maintaining an active surveillance.

  8. Brain and buffy coat transmission of bovine spongiform encephalopathy to the primate Microcebus murinus.

    Science.gov (United States)

    Bons, Nöelle; Lehmann, Sylvain; Mestre-Francès, Nadine; Dormont, Dominique; Brown, Paul

    2002-05-01

    More than 100 cases of variant CJD resulting from infections with bovine spongiform encephalopathy (BSE) have accumulated in the United Kingdom since 1995. Concern about the possibility of secondary transmissions via blood and blood components donated by infected individuals has prompted a variety of international donor deferral policies that will continue until laboratory and epidemiologic evidence provides a consensus about potential risk. BSE was passaged through macaque monkeys and then adapted to the prosimian microcebe (Microcebus murinus). Brain homogenate and buffy coat from an affected microcebe were separately inoculated intracerebrally into three healthy microcebes (two animals received brain and one received buffy coat). All three inoculated microcebes became ill after incubation periods of 16 to 18 months. Clinical, histopathologic, and immunocytologic features were similar in each of the recipients. Buffy coat from a symptomatic microcebe infected 17 months earlier with BSE contained the infectious agent. This observation represents the first documented transmission of BSE from the blood of an experimentally infected primate, which in view of rodent buffy coat infectivity precedents and the known host range of BSE is neither unexpected nor cause for alarm.

  9. In vitro prion protein conversion suggests risk of bighorn sheep (Ovis canadensis) to transmissible spongiform encephalopathies.

    Science.gov (United States)

    Morawski, Aaron R; Carlson, Christina M; Chang, Haeyoon; Johnson, Christopher J

    2013-08-09

    Transmissible spongiform encephalopathies (TSEs) affect both domestic sheep (scrapie) and captive and free-ranging cervids (chronic wasting disease; CWD). The geographical range of bighorn sheep (Ovis canadensis; BHS) overlaps with states or provinces that have contained scrapie-positive sheep or goats and areas with present epizootics of CWD in cervids. No TSEs have been documented in BHS, but the susceptibility of this species to TSEs remains unknown. We acquired a library of BHS tissues and found no evidence of preexisting TSEs in these animals. The prion protein gene (Prnp) in all BHS in our library was identical to scrapie-susceptible domestic sheep (A136R154Q171 genotype). Using an in vitro prion protein conversion assay, which has been previously used to assess TSE species barriers and, in our study appears to recollect known species barriers in mice, we assessed the potential transmissibility of TSEs to BHS. As expected based upon Prnp genotype, we observed BHS prion protein conversion by classical scrapie agent and evidence for a species barrier between transmissible mink encephalopathy (TME) and BHS. Interestingly, our data suggest that the species barrier of BHS to white-tailed deer or wapiti CWD agents is likely low. We also used protein misfolding cyclic amplification to confirm that CWD, but not TME, can template prion protein misfolding in A136R154Q171 genotype sheep. Our results indicate the in vitro conversion assay used in our study does mimic the species barrier of mice to the TSE agents that we tested. Based on Prnp genotype and results from conversion assays, BHS are likely to be susceptible to infection by classical scrapie. Despite mismatches in amino acids thought to modulate prion protein conversion, our data indicate that A136R154Q171 genotype sheep prion protein is misfolded by CWD agent, suggesting that these animals could be susceptible to CWD. Further investigation of TSE transmissibility to BHS, including animal studies, is warranted

  10. Whole Blood Gene Expression Profiling in Preclinical and Clinical Cattle Infected with Atypical Bovine Spongiform Encephalopathy.

    Directory of Open Access Journals (Sweden)

    Elena Xerxa

    Full Text Available Prion diseases, such as bovine spongiform encephalopathies (BSE, are transmissible neurodegenerative disorders affecting humans and a wide variety of mammals. Variant Creutzfeldt-Jakob disease (vCJD, a prion disease in humans, has been linked to exposure to BSE prions. This classical BSE (cBSE is now rapidly disappearing as a result of appropriate measures to control animal feeding. Besides cBSE, two atypical forms (named H- and L-type BSE have recently been described in Europe, Japan, and North America. Here we describe the first wide-spectrum microarray analysis in whole blood of atypical BSE-infected cattle. Transcriptome changes in infected animals were analyzed prior to and after the onset of clinical signs. The microarray analysis revealed gene expression changes in blood prior to the appearance of the clinical signs and during the progression of the disease. A set of 32 differentially expressed genes was found to be in common between clinical and preclinical stages and showed a very similar expression pattern in the two phases. A 22-gene signature showed an oscillating pattern of expression, being differentially expressed in the preclinical stage and then going back to control levels in the symptomatic phase. One gene, SEL1L3, was downregulated during the progression of the disease. Most of the studies performed up to date utilized various tissues, which are not suitable for a rapid analysis of infected animals and patients. Our findings suggest the intriguing possibility to take advantage of whole blood RNA transcriptional profiling for the preclinical identification of prion infection. Further, this study highlighted several pathways, such as immune response and metabolism that may play an important role in peripheral prion pathogenesis. Finally, the gene expression changes identified in the present study may be further investigated as a fingerprint for monitoring the progression of disease and for developing targeted therapeutic

  11. Recombinant PrP and Its Contribution to Research on Transmissible Spongiform Encephalopathies

    Directory of Open Access Journals (Sweden)

    Jorge M. Charco

    2017-12-01

    Full Text Available The misfolding of the cellular prion protein (PrPC into the disease-associated isoform (PrPSc and its accumulation as amyloid fibrils in the central nervous system is one of the central events in transmissible spongiform encephalopathies (TSEs. Due to the proteinaceous nature of the causal agent the molecular mechanisms of misfolding, interspecies transmission, neurotoxicity and strain phenomenon remain mostly ill-defined or unknown. Significant advances were made using in vivo and in cellula models, but the limitations of these, primarily due to their inherent complexity and the small amounts of PrPSc that can be obtained, gave rise to the necessity of new model systems. The production of recombinant PrP using E. coli and subsequent induction of misfolding to the aberrant isoform using different techniques paved the way for the development of cell-free systems that complement the previous models. The generation of the first infectious recombinant prion proteins with identical properties of brain-derived PrPSc increased the value of cell-free systems for research on TSEs. The versatility and ease of implementation of these models have made them invaluable for the study of the molecular mechanisms of prion formation and propagation, and have enabled improvements in diagnosis, high-throughput screening of putative anti-prion compounds and the design of novel therapeutic strategies. Here, we provide an overview of the resultant advances in the prion field due to the development of recombinant PrP and its use in cell-free systems.

  12. Quantitative analysis of wet-heat inactivation in bovine spongiform encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Matsuura, Yuichi; Ishikawa, Yukiko; Bo, Xiao; Murayama, Yuichi; Yokoyama, Takashi [Prion Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan); Somerville, Robert A. [The Roslin Institute and Royal (Dick) School of Veterinary Studies, Roslin, Midlothian, EH25 9PS (United Kingdom); Kitamoto, Tetsuyuki [Division of CJD Science and Technology, Department of Prion Research, Center for Translational and Advanced Animal Research on Human Diseases, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba, Sendai 980-8575 (Japan); Mohri, Shirou, E-mail: shirou@affrc.go.jp [Prion Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan)

    2013-03-01

    Highlights: ► We quantitatively analyzed wet-heat inactivation of the BSE agent. ► Infectivity of the BSE macerate did not survive 155 °C wet-heat treatment. ► Once the sample was dehydrated, infectivity was observed even at 170 °C. ► A quantitative PMCA assay was used to evaluate the degree of BSE inactivation. - Abstract: The bovine spongiform encephalopathy (BSE) agent is resistant to conventional microbial inactivation procedures and thus threatens the safety of cattle products and by-products. To obtain information necessary to assess BSE inactivation, we performed quantitative analysis of wet-heat inactivation of infectivity in BSE-infected cattle spinal cords. Using a highly sensitive bioassay, we found that infectivity in BSE cattle macerates fell with increase in temperatures from 133 °C to 150 °C and was not detected in the samples subjected to temperatures above 155 °C. In dry cattle tissues, infectivity was detected even at 170 °C. Thus, BSE infectivity reduces with increase in wet-heat temperatures but is less affected when tissues are dehydrated prior to the wet-heat treatment. The results of the quantitative protein misfolding cyclic amplification assay also demonstrated that the level of the protease-resistant prion protein fell below the bioassay detection limit by wet-heat at 155 °C and higher and could help assess BSE inactivation. Our results show that BSE infectivity is strongly resistant to wet-heat inactivation and that it is necessary to pay attention to BSE decontamination in recycled cattle by-products.

  13. Changes in retinal function and morphology are early clinical signs of disease in cattle with bovine spongiform encephalopathy.

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    M Heather West Greenlee

    Full Text Available Bovine spongiform encephalopathy (BSE belongs to a group of fatal, transmissible protein misfolding diseases known as transmissible spongiform encephalopathies (TSEs. All TSEs are caused by accumulation of misfolded prion protein (PrPSc throughout the central nervous system (CNS, which results in neuronal loss and ultimately death. Like other protein misfolding diseases including Parkinson's disease and Alzheimer's disease, TSEs are generally not diagnosed until the onset of disease after the appearance of unequivocal clinical signs. As such, identification of the earliest clinical signs of disease may facilitate diagnosis. The retina is the most accessible part of the central nervous system, and retinal pathology in TSE affected animals has been previously reported. Here we describe antemortem changes in retinal function and morphology that are detectable in BSE inoculated animals several months (up to 11 months prior to the appearance of any other signs of clinical disease. We also demonstrate that differences in the severity of these clinical signs reflect the amount of PrPSc accumulation in the retina and the resulting inflammatory response of the tissue. These results are the earliest reported clinical signs associated with TSE infection and provide a basis for understanding the pathology and evaluating therapeutic interventions.

  14. Transmissibility of H-Type Bovine Spongiform Encephalopathy to Hamster PrP Transgenic Mice.

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    Hiroyuki Okada

    Full Text Available Two distinct forms of atypical bovine spongiform encephalopathies (H-BSE and L-BSE can be distinguished from classical (C- BSE found in cattle based on biochemical signatures of disease-associated prion protein (PrPSc. H-BSE is transmissible to wild-type mice-with infected mice showing a long survival period that is close to their normal lifespan-but not to hamsters. Therefore, rodent-adapted H-BSE with a short survival period would be useful for analyzing H-BSE characteristics. In this study, we investigated the transmissibility of H-BSE to hamster prion protein transgenic (TgHaNSE mice with long survival periods. Although none of the TgHaNSE mice manifested the disease during their lifespan, PrPSc accumulation was observed in some areas of the brain after the first passage. With subsequent passages, TgHaNSE mice developed the disease with a mean survival period of 220 days. The molecular characteristics of proteinase K-resistant PrPSc (PrPres in the brain were identical to those observed in first-passage mice. The distribution of immunolabeled PrPSc in the brains of TgHaNSE mice differed between those infected with H-BSE as compared to C-BSE or L-BSE, and the molecular properties of PrPres in TgHaNSE mice infected with H-BSE differed from those of the original isolate. The strain-specific electromobility, glycoform profiles, and proteolytic cleavage sites of H-BSE in TgHaNSE mice were indistinguishable from those of C-BSE, in which the diglycosylated form was predominant. These findings indicate that strain-specific pathogenic characteristics and molecular features of PrPres in the brain are altered during cross-species transmission. Typical H-BSE features were restored after back passage from TgHaNSE to bovinized transgenic mice, indicating that the H-BSE strain was propagated in TgHaNSE mice. This could result from the overexpression of the hamster prion protein.

  15. Immunohistochemical studies of scrapie archival material from Irish ARQ/ARQ sheep for evidence of bovine spongiform encephalopathy-derived disease

    NARCIS (Netherlands)

    Sharpe, A.; McElroy, M.; Langeveld, J.P.M.; Bassett, H.; O'Donoghue, A.M.; Sweeney, T.

    2005-01-01

    Since scrapie and bovine spongiform encephalopathy (BSE) in sheep are clinicopathologically indistinguishable, BSE in sheep may have been misdiagnosed as scrapie. Disease-specific prion protein (PrPd) patterns in archival tissues of 38 Irish ARQ/ARQ sheep diagnosed as scrapie-affected were compared

  16. Trends in scientific activity addressing transmissible spongiform encephalopathies: a bibliometric study covering the period 1973–2002

    Directory of Open Access Journals (Sweden)

    Iribarren-Maestro Isabel

    2006-10-01

    Full Text Available Abstract Background The purpose of this study is to analyse the trends in scientific research on transmissible spongiform encephalopathies by applying bibliometric tools to the scientific literature published between 1973 and 2002. Methods The data for the study were obtained from Medline database, in order to determine the volume of scientific output in the above period, the countries involved, the type of document and the trends in the subject matters addressed. The period 1973–2002 was divided in three sub-periods. Results We observed a significant growth in scientific production. The percentage of increase is 871.7 from 1973 to 2002. This is more evident since 1991 and particularly in the 1996–2001 period. The countries found to have the highest output were the United States, the United Kingdom, Japan, France and Germany. The evolution in the subject matters was almost constant in the three sub-periods in which the study was divided. In the first and second sub-periods, the subject matters of greatest interest were more general, i.e Nervous system or Nervous system diseases, Creutzfeldt-Jakob disease, Scrapie, and Chemicals and Drugs, but in the last sub-period, some changes were observed because the Prion-related matters had the greatest presence. Collaboration among authors is small from 1973 to 1992, but increases notably in the third sub-period, and also the number of authors and clusters formed. Some of the authors, like Gajdusek or Prusiner, appear in the whole period. Conclusion The study reveals a very high increase in scientific production. It is related also with the beginnings of research on bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease, with the establishment of progressive collaboration relationships and a reflection of public health concerns about this problem.

  17. Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein.

    Science.gov (United States)

    Wilson, Rona; Plinston, Chris; Hunter, Nora; Casalone, Cristina; Corona, Cristiano; Tagliavini, Fabrizio; Suardi, Silvia; Ruggerone, Margherita; Moda, Fabio; Graziano, Silvia; Sbriccoli, Marco; Cardone, Franco; Pocchiari, Maurizio; Ingrosso, Loredana; Baron, Thierry; Richt, Juergen; Andreoletti, Olivier; Simmons, Marion; Lockey, Richard; Manson, Jean C; Barron, Rona M

    2012-07-01

    The association between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health and raises the possibility that other ruminant TSEs may be transmissible to humans. In recent years, several novel TSEs in sheep, cattle and deer have been described and the risk posed to humans by these agents is currently unknown. In this study, we inoculated two forms of atypical BSE (BASE and H-type BSE), a chronic wasting disease (CWD) isolate and seven isolates of atypical scrapie into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP). Upon challenge with these ruminant TSEs, gene-targeted Tg mice expressing human PrP did not show any signs of disease pathology. These data strongly suggest the presence of a substantial transmission barrier between these recently identified ruminant TSEs and humans.

  18. Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy.

    Science.gov (United States)

    Okada, Hiroyuki; Masujin, Kentaro; Miyazawa, Kohtaro; Iwamaru, Yoshihumi; Imamura, Morikazu; Matsuura, Yuichi; Arai, Shozo; Fukuda, Shigeo; Murayama, Yuichi; Yokoyama, Takashi

    2017-11-01

    H-type bovine spongiform encephalopathy (H-BSE) is an atypical form of BSE in cattle. During passaging of H-BSE in transgenic bovinized (TgBoPrP) mice, a novel phenotype of BSE, termed BSE-SW emerged and was characterized by a short incubation time and host weight loss. To investigate the biological and biochemical properties of the BSE-SW prion, a transmission study was conducted in cattle, which were inoculated intracerebrally with brain homogenate from BSE-SW-infected TgBoPrP mice. The disease incubation period was approximately 15 months. The animals showed characteristic neurological signs of dullness, and severe spongiform changes and a widespread, uniform distribution of disease-associated prion protein (PrP Sc ) were observed throughout the brain of infected cattle. Immunohistochemical PrP Sc staining of the brain revealed the presence of intraglial accumulations and plaque-like deposits. No remarkable differences were identified in vacuolar lesion scores, topographical distribution patterns, and staining types of PrP Sc in the brains of BSE-SW- vs H-BSE-infected cattle. PrP Sc deposition was detected in the ganglia, vagus nerve, spinal nerve, cauda equina, adrenal medulla, and ocular muscle. Western blot analysis revealed that the specific biochemical properties of the BSE-SW prion, with an additional 10- to 12-kDa fragment, were well maintained after transmission. These findings indicated that the BSE-SW prion has biochemical properties distinct from those of H-BSE in cattle, although clinical and pathologic features of BSW-SW in cattle are indistinguishable from those of H-BSE. The results suggest that the 2 infectious agents, BSE-SW and H-BSE, are closely related strains.

  19. Guinea Pig Prion Protein Supports Rapid Propagation of Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease Prions.

    Science.gov (United States)

    Watts, Joel C; Giles, Kurt; Saltzberg, Daniel J; Dugger, Brittany N; Patel, Smita; Oehler, Abby; Bhardwaj, Sumita; Sali, Andrej; Prusiner, Stanley B

    2016-11-01

    The biochemical and neuropathological properties of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) prions are faithfully maintained upon transmission to guinea pigs. However, primary and secondary transmissions of BSE and vCJD in guinea pigs result in long incubation periods of ∼450 and ∼350 days, respectively. To determine if the incubation periods of BSE and vCJD prions could be shortened, we generated transgenic (Tg) mice expressing guinea pig prion protein (GPPrP). Inoculation of Tg(GPPrP) mice with BSE and vCJD prions resulted in mean incubation periods of 210 and 199 days, respectively, which shortened to 137 and 122 days upon serial transmission. In contrast, three different isolates of sporadic CJD prions failed to transmit disease to Tg(GPPrP) mice. Many of the strain-specified biochemical and neuropathological properties of BSE and vCJD prions, including the presence of type 2 protease-resistant PrP Sc , were preserved upon propagation in Tg(GPPrP) mice. Structural modeling revealed that two residues near the N-terminal region of α-helix 1 in GPPrP might mediate its susceptibility to BSE and vCJD prions. Our results demonstrate that expression of GPPrP in Tg mice supports the rapid propagation of BSE and vCJD prions and suggest that Tg(GPPrP) mice may serve as a useful paradigm for bioassaying these prion isolates. Variant Creutzfeldt-Jakob disease (vCJD) and bovine spongiform encephalopathy (BSE) prions are two of the prion strains most relevant to human health. However, propagating these strains in mice expressing human or bovine prion protein has been difficult because of prolonged incubation periods or inefficient transmission. Here, we show that transgenic mice expressing guinea pig prion protein are fully susceptible to vCJD and BSE prions but not to sporadic CJD prions. Our results suggest that the guinea pig prion protein is a better, more rapid substrate than either bovine or human prion protein for

  20. Impact of potential changes to the current bovine spongiform encephalopathy surveillance programs for slaughter cattle and fallen stock in Japan.

    Science.gov (United States)

    Sugiura, Katsuaki; Murray, Noel; Shinoda, Naoki; Onodera, Takashi

    2009-07-01

    Cattle slaughtered in Japan for human consumption, regardless of their age, have been tested for bovine spongiform encephalopathy (BSE) since October 2001. Beginning in April 2004, all fallen stock from 24 months of age also have been tested. We evaluated the impact of potential changes to the current BSE surveillance programs for both slaughter cattle and fallen stock using a simple stochastic model. We calculated the probability that a BSE-infected dairy cow, Wagyu beef animal, Wagyu-Holstein cross steer or heifer, or Holstein steer slaughtered for human consumption or arising as fallen stock would be tested and detected. Four surveillance strategies were explored for cattle slaughtered for human consumption, with the minimum age at testing set at 0, 21, 31, or 41 months. Three surveillance strategies were explored for fallen stock, with the minimum age at testing set at 24, 31, or 41 months. Increasing the minimum age of testing from 0 to 21 months for both dairy cattle and Wagyu beef cattle had very little impact on the probability that a BSE-infected animal slaughtered for human consumption would be detected. Although increasing the minimum age at testing from 21 to 31 or 41 months would lead to fewer slaughtered animals being tested, the impact on the probability of detecting infected animals would be insignificant. The probability of infected Wagyu-Holstein crosses and Holstein steers being detected at slaughter or as fallen stock would be very low under all surveillance strategies.

  1. Protective Effect of Val129-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease.

    Science.gov (United States)

    Fernández-Borges, Natalia; Espinosa, Juan Carlos; Marín-Moreno, Alba; Aguilar-Calvo, Patricia; Asante, Emmanuel A; Kitamoto, Tetsuyuki; Mohri, Shirou; Andréoletti, Olivier; Torres, Juan María

    2017-09-01

    Bovine spongiform encephalopathy (BSE) is the only known zoonotic prion that causes variant Creutzfeldt-Jakob disease (vCJD) in humans. The major risk determinant for this disease is the polymorphic codon 129 of the human prion protein (Hu-PrP), where either methionine (Met 129 ) or valine (Val 129 ) can be encoded. To date, all clinical and neuropathologically confirmed vCJD cases have been Met 129 homozygous, with the exception of 1 recently reported Met/Val heterozygous case. Here, we found that transgenic mice homozygous for Val 129 Hu-PrP show severely restricted propagation of the BSE prion strain, but this constraint can be partially overcome by adaptation of the BSE agent to the Met 129 Hu-PrP. In addition, the transmission of vCJD to transgenic mice homozygous for Val 129 Hu-PrP resulted in a prion with distinct strain features. These observations may indicate increased risk for vCJD secondary transmission in Val 129 Hu-PrP-positive humans with the emergence of new strain features.

  2. Real-Time Quaking-Induced Conversion Detection of Bovine Spongiform Encephalopathy Prions in a Subclinical Steer

    Directory of Open Access Journals (Sweden)

    Soyoun Hwang

    2018-01-01

    Full Text Available Bovine spongiform encephalopathy (BSE belongs to a group of fatal prion diseases that result from the misfolding of the cellular prion protein (PrPC into a pathogenic form (PrPSc that accumulates in the brain. In vitro assays such as serial protein misfolding amplification and real-time quaking-induced conversion (RT-QuIC allow assessment of the conversion of PrPC to PrPSc. RT-QuIC can be used for the detection of prions in a variety of biological tissues from humans and animals. However, there is no such comparison of RT-QuIC data between BSE positive and presymptomatic cattle. Further, the current study assesses prion distribution in multiple brain regions of clinically ill or subclinical animals. Here, we compare RT-QuIC reactions seeded with brain samples collected from experimentally inoculated cattle that were clinically ill or subclinically affected with BSE. The results demonstrate RT-QuIC seeding in various brain regions of an animal with subclinical BSE despite being determined negative by immunohistochemistry. Bioassay of the subclinical animal and RT-QuIC of brainstem from inoculated knockout (PRNP−/− cattle were used to confirm infectivity in the subclinical animal and determine that RT-QuIC reactions were not the result of residual inoculum, respectively. These results confirm that RT-QuIC is a highly sensitive prion detection assay that can detect prions in a steer prior to the onset of clinical signs of BSE.

  3. Immunohistochemical study of PrPSc distribution in neural and extraneural tissues of two cats with feline spongiform encephalopathy

    Directory of Open Access Journals (Sweden)

    Wunderlin Sabina S

    2009-03-01

    Full Text Available Abstract Background Two domestic shorthair cats presenting with progressive hind-limb ataxia and increased aggressiveness were necropsied and a post mortem diagnosis of Feline Spongiform Encephalopathy (FSE was made. A wide spectrum of tissue samples was collected and evaluated histologically and immunohistologically for the presence of PrPSc. Results Histopathological examination revealed a diffuse vacuolation of the grey matter neuropil with the following areas being most severely affected: corpus geniculatum medialis, thalamus, gyrus dentatus of the hippocampus, corpus striatum, and deep layers of the cerebral and cerebellar cortex as well as in the brain stem. In addition, a diffuse glial reaction involving astrocytes and microglia and intraneuronal vacuolation in a few neurons in the brain stem was present. Heavy PrPSc immunostaining was detected in brain, retina, optic nerve, pars nervosa of the pituitary gland, trigeminal ganglia and small amounts in the myenteric plexus of the small intestine (duodenum, jejunum and slightly in the medulla of the adrenal gland. Conclusion The PrPSc distribution within the brain was consistent with that described in other FSE-affected cats. The pattern of abnormal PrP in the retina corresponded to that found in a captive cheetah with FSE, in sheep with scrapie and was similar to nvCJD in humans.

  4. High titers of transmissible spongiform encephalopathy infectivity associated with extremely low levels of PrPSc in vivo.

    Science.gov (United States)

    Barron, Rona M; Campbell, Susan L; King, Declan; Bellon, Anne; Chapman, Karen E; Williamson, R Anthony; Manson, Jean C

    2007-12-07

    Diagnosis of transmissible spongiform encephalopathy (TSE) disease in humans and ruminants relies on the detection in post-mortem brain tissue of the protease-resistant form of the host glycoprotein PrP. The presence of this abnormal isoform (PrP(Sc)) in tissues is taken as indicative of the presence of TSE infectivity. Here we demonstrate conclusively that high titers of TSE infectivity can be present in brain tissue of animals that show clinical and vacuolar signs of TSE disease but contain low or undetectable levels of PrP(Sc). This work questions the correlation between PrP(Sc) level and the titer of infectivity and shows that tissues containing little or no proteinase K-resistant PrP can be infectious and harbor high titers of TSE infectivity. Reliance on protease-resistant PrP(Sc) as a sole measure of infectivity may therefore in some instances significantly underestimate biological properties of diagnostic samples, thereby undermining efforts to contain and eradicate TSEs.

  5. Bovine spongiform encephalopathy induces misfolding of alleged prion-resistant species cellular prion protein without altering its pathobiological features.

    Science.gov (United States)

    Vidal, Enric; Fernández-Borges, Natalia; Pintado, Belén; Ordóñez, Montserrat; Márquez, Mercedes; Fondevila, Dolors; Torres, Juan María; Pumarola, Martí; Castilla, Joaquín

    2013-05-01

    Bovine spongiform encephalopathy (BSE) prions were responsible for an unforeseen epizootic in cattle which had a vast social, economic, and public health impact. This was primarily because BSE prions were found to be transmissible to humans. Other species were also susceptible to BSE either by natural infection (e.g., felids, caprids) or in experimental settings (e.g., sheep, mice). However, certain species closely related to humans, such as canids and leporids, were apparently resistant to BSE. In vitro prion amplification techniques (saPMCA) were used to successfully misfold the cellular prion protein (PrP(c)) of these allegedly resistant species into a BSE-type prion protein. The biochemical and biological properties of the new prions generated in vitro after seeding rabbit and dog brain homogenates with classical BSE were studied. Pathobiological features of the resultant prion strains were determined after their inoculation into transgenic mice expressing bovine and human PrP(C). Strain characteristics of the in vitro-adapted rabbit and dog BSE agent remained invariable with respect to the original cattle BSE prion, suggesting that the naturally low susceptibility of rabbits and dogs to prion infections should not alter their zoonotic potential if these animals became infected with BSE. This study provides a sound basis for risk assessment regarding prion diseases in purportedly resistant species.

  6. Ultra-sensitive detection of prion protein fibrils by flow cytometry in blood from cattle affected with bovine spongiform encephalopathy

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    Maas Elke

    2005-10-01

    Full Text Available Abstract Background The definite diagnosis of prion diseases such as Creutzfeldt-Jakob disease (CJD in humans or bovine spongiform encephalopathy (BSE in cattle currently relies on the post mortem detection of the pathological form of the prion protein (PrPSc in brain tissue. Infectivity studies indicate that PrPSc may also be present in body fluids, even at presymptomatic stages of the disease, albeit at concentrations well below the detection limits of currently available analytical methods. Results We developed a highly sensitive method for detecting prion protein aggregates that takes advantage of kinetic differences between seeded and unseeded polymerization of prion protein monomers. Detection of the aggregates was carried out by flow cytometry. In the presence of prion seeds, the association of labelled recombinant PrP monomers in plasma and serum proceeds much more efficiently than in the absence of seeds. In a diagnostic model system, synthetic PrP aggregates were detected down to a concentration of approximately 10-8 nM [0.24 fg/ml]. A specific signal was detected in six out of six available serum samples from BSE-positive cattle. Conclusion We have developed a method based on seed-dependent PrP fibril formation that shows promising results in differentiating a small number of BSE-positive serum samples from healthy controls. This method may provide the basis for an ante mortem diagnostic test for prion diseases.

  7. In situ formation of protease-resistant prion protein in transmissible spongiform encephalopathy-infected brain slices.

    Science.gov (United States)

    Bessen, R A; Raymond, G J; Caughey, B

    1997-06-13

    The transmissible spongiform encephalopathies (TSEs) comprise a group of fatal neurodegenerative diseases that are characterized by the conversion of the normal host cellular prion protein (PrPC), to the abnormal protease-resistant prion protein isoform (PrP-res). It has been proposed, though not proven, that the infectious TSE agent consists solely of PrP-res and that PrP-res-induced conformational conversion of PrPC to additional PrP-res represents agent replication. In this study we demonstrate in situ conversion of protease-sensitive PrPC to PrP-res in TSE-infected brain slices. One step in this process is the binding of soluble PrPC to endogenous PrP-res deposits. The newly formed PrP-res associated with the slices in a pattern that correlated with the pre-existing brain distribution of PrP-res. Punctate in situ PrP conversion was observed in brain regions containing PrP-res amyloid plaques, and a more dispersed conversion product was detected in areas containing diffuse PrP-res deposits. These studies provide direct evidence that PrP-res formation involves the incorporation of soluble PrPC into both nonfibrillar and fibrillar PrP-res deposits in TSE-infected brain. Our findings suggest that the in situ PrP conversion reaction leads to additional polymerization of endogenous PrP-res aggregates and is analogous to the process of PrP-res fibril and subfibril growth in vivo.

  8. Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie.

    Directory of Open Access Journals (Sweden)

    Fiona Houston

    Full Text Available Sheep are natural hosts of the prion disease, scrapie. They are also susceptible to experimental challenge with various scrapie strains and with bovine spongiform encephalopathy (BSE, which affects cattle and has been accidentally transmitted to a range of other species, including man. Incidence and incubation period of clinical disease in sheep following inoculation is controlled by the PRNP gene, which has different alleles defined on the basis of polymorphisms, particularly at codons 136, 154 and 171, although other codons are associated with survival time, and the exact responses of the sheep may be influenced by other breed-related differences. Here we report the results of a long term single study of experimental scrapie and BSE susceptibility of sheep of Cheviot, Poll Dorset and Suffolk breeds, originating from New Zealand and of a wide range of susceptible and resistant PRNP genotypes. Responses were compared with those of sheep from a closed Cheviot flock of UK origin (Roslin Cheviot flock. The unusually long observation period (6-8 years for most, but up to 12 years for others allows us to draw robust conclusions about rates of survival of animals previously regarded as resistant to infection, particularly PRNP heterozygotes, and is the most comprehensive such study reported to date. BSE inoculation by an intracerebral route produced disease in all genotype groups with differing incubation periods, although M112T and L141F polymorphisms seemed to give some protection. Scrapie isolate SSBP/1, which has the shortest incubation period in sheep with at least one VRQ PRNP allele, also produced disease following sub-cutaneous inoculation in ARQ/ARQ animals of New Zealand origin, but ARQ/ARQ sheep from the Roslin flock survived the challenge. Our results demonstrate that the links between PRNP genotype and clinical prion disease in sheep are much less secure than previously thought, and may break down when, for example, a different breed of

  9. PrP-C1 fragment in cattle brains reveals features of the transmissible spongiform encephalopathy associated PrPsc.

    Science.gov (United States)

    Serra, Fabienne; Müller, Joachim; Gray, John; Lüthi, Ramona; Dudas, Sandor; Czub, Stefanie; Seuberlich, Torsten

    2017-03-15

    Three different types of bovine spongiform encephalopathy (BSE) are known and supposedly caused by distinct prion strains: the classical (C-) BSE type that was typically found during the BSE epidemic, and two relatively rare atypical BSE types, termed H-BSE and L-BSE. The three BSE types differ in the molecular phenotype of the disease associated prion protein, namely the N-terminally truncated proteinase K (PK) resistant prion protein fragment (PrP res ). In this study, we report and analyze yet another PrP res type (PrP res-2011 ), which was found in severely autolytic brain samples of two cows in the framework of disease surveillance in Switzerland in 2011. Analysis of brain tissues from these animals by PK titration and PK inhibitor assays ruled out the process of autolysis as the cause for the aberrant PrP res profile. Immunochemical characterization of the PrP fragments present in the 2011 cases by epitope mapping indicated that PrP res-2011 corresponds in its primary sequence to the physiologically occurring PrP-C1 fragment. However, high speed centrifugation, sucrose gradient assay and NaPTA precipitation revealed biochemical similarities between PrP res-2011 and the disease-associated prion protein found in BSE affected cattle in terms of detergent insolubility, PK resistance and PrP aggregation. Although it remains to be established whether PrP res-2011 is associated with a transmissible disease, our results point out the need of further research on the role the PrP-C1 aggregation and misfolding in health and disease. Copyright © 2017. Published by Elsevier B.V.

  10. Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie

    Science.gov (United States)

    Houston, Fiona; Goldmann, Wilfred; Foster, James; González, Lorenzo; Jeffrey, Martin; Hunter, Nora

    2015-01-01

    Sheep are natural hosts of the prion disease, scrapie. They are also susceptible to experimental challenge with various scrapie strains and with bovine spongiform encephalopathy (BSE), which affects cattle and has been accidentally transmitted to a range of other species, including man. Incidence and incubation period of clinical disease in sheep following inoculation is controlled by the PRNP gene, which has different alleles defined on the basis of polymorphisms, particularly at codons 136, 154 and 171, although other codons are associated with survival time, and the exact responses of the sheep may be influenced by other breed-related differences. Here we report the results of a long term single study of experimental scrapie and BSE susceptibility of sheep of Cheviot, Poll Dorset and Suffolk breeds, originating from New Zealand and of a wide range of susceptible and resistant PRNP genotypes. Responses were compared with those of sheep from a closed Cheviot flock of UK origin (Roslin Cheviot flock). The unusually long observation period (6–8 years for most, but up to 12 years for others) allows us to draw robust conclusions about rates of survival of animals previously regarded as resistant to infection, particularly PRNP heterozygotes, and is the most comprehensive such study reported to date. BSE inoculation by an intracerebral route produced disease in all genotype groups with differing incubation periods, although M112T and L141F polymorphisms seemed to give some protection. Scrapie isolate SSBP/1, which has the shortest incubation period in sheep with at least one VRQ PRNP allele, also produced disease following sub-cutaneous inoculation in ARQ/ARQ animals of New Zealand origin, but ARQ/ARQ sheep from the Roslin flock survived the challenge. Our results demonstrate that the links between PRNP genotype and clinical prion disease in sheep are much less secure than previously thought, and may break down when, for example, a different breed of sheep is moved

  11. Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie.

    Science.gov (United States)

    Houston, Fiona; Goldmann, Wilfred; Foster, James; González, Lorenzo; Jeffrey, Martin; Hunter, Nora

    2015-01-01

    Sheep are natural hosts of the prion disease, scrapie. They are also susceptible to experimental challenge with various scrapie strains and with bovine spongiform encephalopathy (BSE), which affects cattle and has been accidentally transmitted to a range of other species, including man. Incidence and incubation period of clinical disease in sheep following inoculation is controlled by the PRNP gene, which has different alleles defined on the basis of polymorphisms, particularly at codons 136, 154 and 171, although other codons are associated with survival time, and the exact responses of the sheep may be influenced by other breed-related differences. Here we report the results of a long term single study of experimental scrapie and BSE susceptibility of sheep of Cheviot, Poll Dorset and Suffolk breeds, originating from New Zealand and of a wide range of susceptible and resistant PRNP genotypes. Responses were compared with those of sheep from a closed Cheviot flock of UK origin (Roslin Cheviot flock). The unusually long observation period (6-8 years for most, but up to 12 years for others) allows us to draw robust conclusions about rates of survival of animals previously regarded as resistant to infection, particularly PRNP heterozygotes, and is the most comprehensive such study reported to date. BSE inoculation by an intracerebral route produced disease in all genotype groups with differing incubation periods, although M112T and L141F polymorphisms seemed to give some protection. Scrapie isolate SSBP/1, which has the shortest incubation period in sheep with at least one VRQ PRNP allele, also produced disease following sub-cutaneous inoculation in ARQ/ARQ animals of New Zealand origin, but ARQ/ARQ sheep from the Roslin flock survived the challenge. Our results demonstrate that the links between PRNP genotype and clinical prion disease in sheep are much less secure than previously thought, and may break down when, for example, a different breed of sheep is moved

  12. Expenses connected with disposing of animals with bovine spongiform encephalopathy in selected rendering plant in the Czech Republic

    Directory of Open Access Journals (Sweden)

    Richard Pospíšil

    2009-01-01

    Full Text Available The first case of bovine spongiform encephalopathy (BSE in the Czech Republic appeared in 2001 and since that a total of 28 infected cows have been detected. Two outbreaks of BSE in 2007 and no di­sea­sed animal in 2008 confirms that, in the Czech Republic, the disease incidence has a decreasing trend, which is in an agreement with the situation in other EU countries. According to the Veterinary Act No. 166/1999, farmers with BSE disease are indemnified from the state budget. The state, therefore, significantly contributes to the prevention and mitigation of BSE and ensures epidemiologic health in our country. Between the outbreak in 2001 and 2008, a total of 1 311 473 cows were exa­mi­ned and, based on the finding of 28 BSE-positive animals, 4 022 cows were subsequently slaughtered. BSE examination, killing and decontamination costs amounted to 18.9 million CZK, compensation costs for killed animals reached almost 163.9 million CZK and compensation for unaccomplished production accounted for over 13.6 million CZK. Together with other additional costs, the total financial compensations paid out during the period of BSE presence were almost 198 million CZK. A se­pa­ra­te budget is proportioned to subsequent safe disposing of carcasses in rendering plants. The rendering plant “Asanace, spol. s r. o., Zichlinek“ was appointed by the State Veterinary Administration to perform the disposal of carcasses. Since the beginning of 2003 to 2008, 22 cases of BSE were reported and 3 572 cows were killed and destroyed there, what represents 2 221 tons of material . The cost of processing of 1 kg of waste material ranged from 3.50 CZK to 6.50 CZK, total costs reached 9.315 thousand CZK. The final product – meat and bone meal – was incinerated in a cement factories at a cost of 1 CZK per 1 kg between years 2003–2006, now it is free of charge. This study does not include costs of disposal of Specific Risk Material, because it is

  13. Progressive accumulation of the abnormal conformer of the prion protein and spongiform encephalopathy in the obex of nonsymptomatic and symptomatic Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease

    Science.gov (United States)

    Chronic wasting disease (CWD), a transmissible spongiform encephalopathy, has been reported in captive and free-ranging cervids. An abnormal isoform of a prion protein (PrP-CWD) has been associated with CWD in Rocky Mountain elk (Cervus elaphus nelsoni) and this prion protein can be detected with i...

  14. Risk of transmission of bovine spongiform encephalopathy to humans in the United States: report of the Council on Scientific Affairs. American Medical Association.

    Science.gov (United States)

    Tan, L; Williams, M A; Khan, M K; Champion, H C; Nielsen, N H

    The risk of possible transmission of bovine spongiform encephalopathy (BSE) in the United States is a substantial public health concern. To systematically review the current scientific literature and discuss legislation and regulations that have been implemented to prevent the disease. Literature review using the MEDLINE, EMBASE, and Lexis/Nexis databases for 1975 through 1997 on the terms bovine spongiform encephalopathy, prion diseases, prions, and Creutzfeldt-Jakob syndrome. The Internet was used to identify regulatory actions and health surveillance. MEDLINE, EMBASE, and Lexis/Nexis databases were searched from 1975 through 1997 for English-language articles that provided information on assessment of transmission risk. Unique circumstances in the United Kingdom caused the emergence and propagation of BSE in cattle, including widespread use of meat and bonemeal cattle feed derived from scrapie-infected sheep and the adoption of a new type of processing that did not reduce the amount of infectious prions prior to feeding. Many of these circumstances do not exist in the United States. In the United Kingdom, new variant Creutzfeldt-Jakob disease probably resulted from the ingestion of BSE-contaminated processed beef. The United Kingdom and the European Union now have strong regulations in place to stop the spread of BSE. While BSE has not been observed in the United States, the US government has surveillance and response plans in effect. Current risk of transmission of BSE in the United States is minimal because (1) BSE has not been shown to exist in this country; (2) adequate regulations exist to prevent entry of foreign sources of BSE into the United States; (3) adequate regulations exist to prevent undetected cases of BSE from uncontrolled amplification within the US cattle population; and (4) adequate preventive guidelines exist to prevent high-risk bovine materials from contaminating products intended for human consumption.

  15. Population-Level Retrospective Study of Neurologically Expressed Disorders in Ruminants before the Onset of Bovine Spongiform Encephalopathy (BSE) in Belgium, a BSE Risk III Country

    Science.gov (United States)

    Saegerman, C.; Berkvens, D.; Claes, L.; Dewaele, A.; Coignoul, F.; Ducatelle, R.; Cassart, D.; Brochier, B.; Costy, F.; Roels, S.; Deluyker, H.; Vanopdenbosch, E.; Thiry, E.

    2005-01-01

    A retrospective epidemiological study (n = 7,875) of neurologically expressed disorders (NED) in ruminants before the onset of the bovine spongiform encephalopathy epidemic (years studied, 1980 to 1997) was carried out in Belgium. The archives of all veterinary laboratories and rabies and transmissible spongiform encephalopathy (TSE) epidemiosurveillance networks were consulted. For all species, a significantly higher number of NED with virological causes (rabies) was reported south of the Sambre-Meuse Valley. During the period 1992 to 1997, for which the data were complete, (i) the predicted annual incidence of NED varied significantly as a function of species and area (higher numbers in areas where rabies was present) but was always above 100 cases per million, and (ii) the mean incidence of suspected TSE cases and, among them, those investigated by histopathological examination varied significantly as a function of species and area. The positive predictive value of a presumptive clinical diagnosis of NED ranged from 0.13 (game) to 0.63 (sheep). Knowledge of the positive predictive value permits the definition of a reference point before certain actions (e.g., awareness and training campaigns) are undertaken. It also shows the usefulness of a systematic necropsy or complementary laboratory tests to establish an etiological diagnosis. TSE analysis of a small, targeted historical sampling (n = 48) permitted the confirmation of one case and uncovered another case of scrapie. The results of the present study help to develop and maintain the quality of the worldwide clinical epidemiological networks for TSE, especially in countries that in the past imported live animals, animal products, and feedstuffs from countries with TSE cases. PMID:15695693

  16. Detection of PrP(Sc) in formalin-fixed, paraffin-embedded tissue by Western blot differentiates classical scrapie, Nor98 scrapie, and bovine spongiform encephalopathy.

    Science.gov (United States)

    Loiacono, Christina M; Beckwith, Nadine; Kunkle, Robert A; Orcutt, Dennis; Hall, S Mark

    2010-09-01

    Transmissible, spongiform encephalopathies including bovine spongiform encephalopathy (BSE) and scrapie are fatal neurodegenerative disorders associated with the presence of an infectious abnormal isoform of normal mammalian proteins called prions. Identification of the prion protein associated with scrapie (PrP(Sc)) in the central nervous system is typically based upon immunoassays including immunohistochemistry (IHC) using formalin-fixed tissues or Western blot (WB) assays using fresh and/or frozen, non-formalin-fixed tissues. Each assay can discriminate between BSE, classical scrapie, and a previously reported strain of scrapie recently identified in the United States named Nor98 scrapie. Different tissue samples are required from the same animal to run these 2 different immunoassays. This may result in inconsistent test results for the same animal. Sampling problems such as collecting insufficient volumes of fresh tissue or less than optimal anatomic location of brainstem for IHC can affect the ability of the test procedures to offer definitive and discriminatory results. Recently, a WB method using formalin-fixed, paraffin-embedded (FFPE) tissue to identify PrP(Sc) was developed that successfully identified PrP(Sc) in sheep affected by classical scrapie. In the current study, the use of this technique to produce discriminatory results identifying classical BSE in bovine tissue and both classical and Nor98 scrapie in ovine tissue using paraffin-embedded brain samples is described. Protein-banding patterns from WB using FFPE tissue were similar to protein-banding patterns produced by WB assays utilizing fresh tissues from the same animals, and results correlated well with the IHC PrP(Sc)-positive staining present in the cerebellum and obex regions of brain samples from these animals.

  17. Enhanced virulence of sheep-passaged bovine spongiform encephalopathy agent is revealed by decreased polymorphism barriers in prion protein conversion studies.

    Science.gov (United States)

    Priem, Jan; Langeveld, Jan P M; van Keulen, Lucien J M; van Zijderveld, Fred G; Andreoletti, Olivier; Bossers, Alex

    2014-03-01

    Bovine spongiform encephalopathy (BSE) can be efficiently transmitted to small ruminants (sheep and goats) with certain prion protein (PrP) genotypes. Polymorphisms in PrP of both the host and donor influence the transmission efficiency of transmissible spongiform encephalopathies (TSEs) in general. These polymorphisms in PrP also modulate the PrP conversion underlying TSE agent replication. Here we demonstrate that single-round protein misfolding cyclic amplification (PMCA) can be used to assess species and polymorphism barriers at the molecular level. We assessed those within and between the ovine and bovine species in vitro using a variety of natural scrapie and experimentally generated cross-species BSE agents. These BSE agents include ovBSE-ARQ isolates (BSE derived from sheep having the ARQ/ARQ PrP genotype), and two unique BSE-derived variants: BSE passaged in VRQ/VRQ sheep and a cow BSE agent isolate generated by back-transmission of ovBSE-ARQ into its original host. PMCA allowed us to quantitatively determine PrP conversion profiles that correlated with known in vivo transmissibility and susceptibility in the two ruminant species in which strain-specific molecular signatures, like its molecular weight after protease digestion, were maintained. Furthermore, both BSE agent isolates from ARQ and VRQ sheep demonstrated a surprising transmission profile in which efficient transmissions to both sheep and bovine variants was combined. Finally, all data support the notion that ARQ-derived sheep BSE points to a significant increase in virulence compared to all other tested scrapie- and BSE-derived variants reflected by the increased conversion efficiencies of previously inefficient convertible PrP variants (including the so-called "resistant" sheep ARR variant). Prion diseases such as scrapie in sheep and goats, BSE in cattle, and Creutzfeldt-Jakob disease (CJD) in humans are fatal neurodegenerative diseases caused by prions. BSE is known to be transmissible to a

  18. Comparison of the clinical course of Japanese MM1-type sporadic Creutzfeldt-Jakob disease between subacute spongiform encephalopathy and panencephalopathic-type.

    Science.gov (United States)

    Iwasaki, Yasushi; Tatsumi, Shinsui; Mimuro, Maya; Kitamoto, Tetsuyuki; Yoshida, Mari

    2014-06-01

    Approximately half of Japanese sporadic Creutzfeldt-Jakob disease (sCJD) cases show panencephalopathic-type (PE-type) pathology, which is a rare subtype in North Americans and Europeans. Until now, the differences in the clinical course between subacute spongiform encephalopathy (SSE) cases and PE-type cases have been unclear. To investigate the clinical course of both subtypes, clinical findings from 42 Japanese MM1-type sCJD cases (20 SSE cases and 22 PE-type cases) were retrospectively evaluated by statistical analysis. No significant differences could be found regarding age at disease onset, the period between disease onset and first observation of myoclonus, the period between disease onset and the first observation of periodic sharp-wave complexes on electroencephalogram, or the period between disease onset and progression to the akinetic mutism state - whereas total disease duration and the period between the akinetic mutism state and death were significantly longer in PE-type cases. The prolonged disease duration was induced by the extended survival period in the akinetic mutism state. There was a statistically significant difference between the two series regarding performance of tube-feeding, but no statistically significant difference regarding performance of tracheotomy or gastrostomy. None of the cases received mechanical ventilation. We speculate that the most crucial factor of the prolonged survival period of Japanese sCJD cases, particularly in the PE-type, is that the introduction of tube-feeding in the akinetic mutism state leads to the stabilization of the patient's general condition. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges

    Directory of Open Access Journals (Sweden)

    Konold Timm

    2012-03-01

    Full Text Available Abstract Background The majority of atypical bovine spongiform encephalopathy (BSE cases so far identified worldwide have been detected by active surveillance. Consequently the volume and quality of material available for detailed characterisation is very limiting. Here we report on a small transmission study of both atypical forms, H- and L-type BSE, in cattle to provide tissue for test evaluation and research, and to generate clinical, molecular and pathological data in a standardised way to enable more robust comparison of the two variants with particular reference to those aspects most relevant to case ascertainment and confirmatory diagnosis within existing regulated surveillance programmes. Results Two groups of four cattle, intracerebrally inoculated with L-type or H-type BSE, all presented with a nervous disease form with some similarities to classical BSE, which progressed to a more dull form in one animal from each group. Difficulty rising was a consistent feature of both disease forms and not seen in two BSE-free, non-inoculated cattle that served as controls. The pathology and molecular characteristics were distinct from classical BSE, and broadly consistent with published data, but with some variation in the pathological characteristics. Both atypical BSE types were readily detectable as BSE by current confirmatory methods using the medulla brain region at the obex, but making a clear diagnostic distinction between the forms was not consistently straightforward in this brain region. Cerebellum proved a more reliable sample for discrimination when using immunohistochemistry. Conclusions The prominent feature of difficulty rising in atypical BSE cases may explain the detection of naturally occurring cases in emergency slaughter cattle and fallen stock. Current confirmatory diagnostic methods are effective for the detection of such atypical cases, but consistently and correctly identifying the variant forms may require modifications to

  20. Removal of transmissible spongiform encephalopathy prion from large volumes of cell culture media supplemented with fetal bovine serum by using hollow fiber anion-exchange membrane chromatography.

    Science.gov (United States)

    Chou, Ming Li; Bailey, Andy; Avory, Tiffany; Tanimoto, Junji; Burnouf, Thierry

    2015-01-01

    Cases of variant Creutzfeldt-Jakob disease in people who had consumed contaminated meat products from cattle with bovine spongiform encephalopathy emphasize the need for measures aimed at preventing the transmission of the pathogenic prion protein (PrPSc) from materials derived from cattle. Highly stringent scrutiny is required for fetal bovine serum (FBS), a growth-medium supplement used in the production of parenteral vaccines and therapeutic recombinant proteins and in the ex vivo expansion of stem cells for transplantation. One such approach is the implementation of manufacturing steps dedicated to removing PrPSc from materials containing FBS. We evaluated the use of the QyuSpeed D (QSD) adsorbent hollow-fiber anion-exchange chromatographic column (Asahi Kasei Medical, Tokyo, Japan) for the removal of PrPSc from cell culture media supplemented with FBS. We first established that QSD filtration had no adverse effect on the chemical composition of various types of culture media supplemented with 10% FBS or the growth and viability characteristics of human embryonic kidney (HEK293) cells, baby hamster kidney (BHK-21) cells, African green monkey kidney (Vero) cells, and Chinese hamster ovary (CHO-k1) cells propagated in the various culture-medium filtrates. We used a 0.6-mL QSD column for removing PrPSc from up to 1000 mL of Dulbecco's modified Eagle's medium containing 10% FBS previously spiked with the 263K strain of hamster-adapted scrapie. The Western blot analysis, validated alongside an infectivity assay, revealed that the level of PrPSc in the initial 200mL flow-through was reduced by 2.5 to > 3 log10, compared with that of the starting material. These results indicate that QSD filtration removes PrPSc from cell culture media containing 10% FBS, and demonstrate the ease with which QSD filtration can be implemented in at industrial-scale to improve the safety of vaccines, therapeutic recombinant proteins, and ex vivo expanded stem cells produced using growth

  1. Subcritical Water Hydrolysis Effectively Reduces the In Vitro Seeding Activity of PrPSc but Fails to Inactivate the Infectivity of Bovine Spongiform Encephalopathy Prions.

    Science.gov (United States)

    Murayama, Yuichi; Yoshioka, Miyako; Okada, Hiroyuki; Takata, Eri; Masujin, Kentaro; Iwamaru, Yoshifumi; Shimozaki, Noriko; Yamamura, Tomoaki; Yokoyama, Takashi; Mohri, Shirou; Tsutsumi, Yuji

    2015-01-01

    The global outbreak of bovine spongiform encephalopathy (BSE) has been attributed to the recycling of contaminated meat and bone meals (MBMs) as feed supplements. The use of MBMs has been prohibited in many countries; however, the development of a method for inactivating BSE prions could enable the efficient and safe use of these products as an organic resource. Subcritical water (SCW), which is water heated under pressure to maintain a liquid state at temperatures below the critical temperature (374°C), exhibits strong hydrolytic activity against organic compounds. In this study, we examined the residual in vitro seeding activity of protease-resistant prion protein (PrPSc) and the infectivity of BSE prions after SCW treatments. Spinal cord homogenates prepared from BSE-infected cows were treated with SCW at 230-280°C for 5-7.5 min and used to intracerebrally inoculate transgenic mice overexpressing bovine prion protein. Serial protein misfolding cyclic amplification (sPMCA) analysis detected no PrPSc in the SCW-treated homogenates, and the mice treated with these samples survived for more than 700 days without any signs of disease. However, sPMCA analyses detected PrPSc accumulation in the brains of all inoculated mice. Furthermore, secondary passage mice, which inoculated with brain homogenates derived from a western blotting (WB)-positive primary passage mouse, died after an average of 240 days, similar to mice inoculated with untreated BSE-infected spinal cord homogenates. The PrPSc accumulation and vacuolation typically observed in the brains of BSE-infected mice were confirmed in these secondary passage mice, suggesting that the BSE prions maintained their infectivity after SCW treatment. One late-onset case, as well as asymptomatic but sPMCA-positive cases, were also recognized in secondary passage mice inoculated with brain homogenates from WB-negative but sPMCA-positive primary passage mice. These results indicated that SCW-mediated hydrolysis was

  2. Removal of transmissible spongiform encephalopathy prion from large volumes of cell culture media supplemented with fetal bovine serum by using hollow fiber anion-exchange membrane chromatography.

    Directory of Open Access Journals (Sweden)

    Ming Li Chou

    Full Text Available Cases of variant Creutzfeldt-Jakob disease in people who had consumed contaminated meat products from cattle with bovine spongiform encephalopathy emphasize the need for measures aimed at preventing the transmission of the pathogenic prion protein (PrPSc from materials derived from cattle. Highly stringent scrutiny is required for fetal bovine serum (FBS, a growth-medium supplement used in the production of parenteral vaccines and therapeutic recombinant proteins and in the ex vivo expansion of stem cells for transplantation. One such approach is the implementation of manufacturing steps dedicated to removing PrPSc from materials containing FBS. We evaluated the use of the QyuSpeed D (QSD adsorbent hollow-fiber anion-exchange chromatographic column (Asahi Kasei Medical, Tokyo, Japan for the removal of PrPSc from cell culture media supplemented with FBS. We first established that QSD filtration had no adverse effect on the chemical composition of various types of culture media supplemented with 10% FBS or the growth and viability characteristics of human embryonic kidney (HEK293 cells, baby hamster kidney (BHK-21 cells, African green monkey kidney (Vero cells, and Chinese hamster ovary (CHO-k1 cells propagated in the various culture-medium filtrates. We used a 0.6-mL QSD column for removing PrPSc from up to 1000 mL of Dulbecco's modified Eagle's medium containing 10% FBS previously spiked with the 263K strain of hamster-adapted scrapie. The Western blot analysis, validated alongside an infectivity assay, revealed that the level of PrPSc in the initial 200mL flow-through was reduced by 2.5 to > 3 log10, compared with that of the starting material. These results indicate that QSD filtration removes PrPSc from cell culture media containing 10% FBS, and demonstrate the ease with which QSD filtration can be implemented in at industrial-scale to improve the safety of vaccines, therapeutic recombinant proteins, and ex vivo expanded stem cells produced

  3. Transmissible Spongiform Encephalopathies (Prion Diseases)

    Science.gov (United States)

    ... when brain tissue is viewed under a microscope. Creutzfeldt-Jakob disease (CJD) is the most well-known of the ... when brain tissue is viewed under a microscope. Creutzfeldt-Jakob disease (CJD) is the most well-known of the ...

  4. Absence of Evidence for a Causal Link between Bovine Spongiform Encephalopathy Strain Variant L-BSE and Known Forms of Sporadic Creutzfeldt-Jakob Disease in Human PrP Transgenic Mice.

    Science.gov (United States)

    Jaumain, Emilie; Quadrio, Isabelle; Herzog, Laetitia; Reine, Fabienne; Rezaei, Human; Andréoletti, Olivier; Laude, Hubert; Perret-Liaudet, Armand; Haïk, Stéphane; Béringue, Vincent

    2016-12-01

    Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt-Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between the host cellular prion protein (PrP C ) and the infecting pathological PrP assemblies (PrP Sc ) constituting the prion. A BSE strain variant, designated L-BSE and responsible for atypical, supposedly spontaneous forms of prion diseases in aged cattle, demonstrates zoonotic potential, as evidenced by its capacity to propagate more easily than classical BSE in transgenic mice expressing human PrP C and in nonhuman primates. In humanized mice, L-BSE propagates without any apparent species barrier and shares similar biochemical PrP Sc signatures with the CJD subtype designated MM2-cortical, thus opening the possibility that certain CJD cases classified as sporadic may actually originate from L-type BSE cross-transmission. To address this issue, we compared the biological properties of L-BSE and those of a panel of CJD subtypes representative of the human prion strain diversity using standard strain-typing criteria in human PrP transgenic mice. We found no evidence that L-BSE causes a known form of sporadic CJD. Since the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD, and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  5. Detection of RNA in the Plasma of Patients with Sporadic Creutzfeldt–Jakob Disease, Gerstmann–Straüssler Syndrome and Other Non-Transmissible Spongiform Encephalopathy Brain Disorders

    Directory of Open Access Journals (Sweden)

    Kazuo Tsukui

    2010-01-01

    Full Text Available The infectious agent of transmissible spongiform encephalopathy (TSE was assumed to be the aggregate of abnormal prion protein isoform (PrPsc. We observed that lowering the pH of 3% SDS-inoculated plasma or brain homogenate after PK digestion to 4.5 (acidic SDS condition enabled to precipitate proteinase K-resistant prion protein (PrPres in plasma as well as PrPres in the brain with synthetic poly-A RNA as affinity aggregate. Therefore, we determined if RNA molecules could be used for discriminating TSE patients from healthy individuals. We also examined the plasma of patients with classical Creutzfeldt–Jakob disease (CJD and other brain disorders who were not diagnosed with TSE. The results indicated that RNA approximately 1.5–2.0 kb in length was commonly observed in the plasma of patients with brain disorders but was not detected in the plasma of healthy volunteers. Enhanced expression of RNA and its protection from endogenous nucleases might occur in the former group of patients. Moreover, we speculate that the non-transmissible neuronal disorders overlap with prion diseases.

  6. A comparison of classical and H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism in wild type and EK211 cattle following intracranial inoculation

    Directory of Open Access Journals (Sweden)

    Jo Moore

    2016-09-01

    Full Text Available In 2006, a case of H-type bovine spongiform encephalopathy (BSE-H was diagnosed in a cow that was associated with a heritable polymorphism in the bovine prion protein gene (PRNP resulting in a lysine for glutamine amino acid substitution at codon 211 (called E211K of the prion protein. Although the prevalence of this polymorphism is low, cattle carrying the K211 allele may be predisposed to rapid onset of BSE-H when exposed or to the potential development of a genetic BSE. This study was conducted to better understand the relationship between the K211 polymorphism and its effect on BSE phenotype. BSE-H from the US 2006 case was inoculated intracranially (IC in one PRNP wild type (EE211 calf and one EK211 calf. In addition, one wild type calf and one EK211 calf were inoculated IC with brain homogenate from a US 2003 classical BSE case. All cattle developed clinical disease. The survival times of the E211K BSE-H inoculated EK211 calf (10 months was shorter than the wild type calf (18 months. This genotype effect was not observed in classical BSE inoculated cattle (both 26 months. Significant changes in retinal function were observed in H-type BSE challenged cattle only. Cattle challenged with the same inoculum showed similar severity and neuroanatomical distribution of vacuolation and disease-associated prion protein deposition in the brain, though differences in neuropathology were observed between E211K BSE-H and classical BSE inoculated animals. Western blot results for brain tissue from challenged animals were consistent with the inoculum strains. This study demonstrates that the phenotype of E211K BSE-H remains stable when transmitted to cattle without the K211 polymorphism, and exhibits a number of features that differ from classical BSE in both wild type and heterozygous EK211 animals.

  7. A comparison of the risk of bovine spongiform encephalopathy infectivity in beef from cattle younger than 21 months in Japan with that in beef from the United States as assessed by the carcass maturity score.

    Science.gov (United States)

    Sugiura, Katsuaki; Smith, Gary C

    2008-04-01

    After the detection of the first case of bovine spongiform encephalopathy (BSE) in the United States in December 2003, the Japanese government halted all imports of U.S. beef. The BSE risk in beef is partly dependent on the slaughter age of the cattle from which it is derived. In Japan, all cattle 21 months old and older are screened using a rapid diagnostic test, while in the United States, routine BSE testing is not done at any age of slaughter cattle. In the United States, there is no nationally mandated cattle identification system that enables cattle younger than 21 months to be identified. Therefore, all beef potentially produced for export to Japan must be from cattle that are age verified as younger than 21 months old or be classified by the U.S. Department of Agriculture using a carcass maturity score, which in turn is related to the age of the animal from which the beef is derived. After consulting the Food Safety Commission, the Japanese government decided on 12 December 2005 to allow importation of beef from the United States derived from cattle with a carcass maturity score of < or =A40 and from which specified risk materials are removed. In this study, a stochastic model was used to simulate the interval of time from slaughter to the predicted clinical onset of BSE in an infected animal. A simulation result, based on the assumption that the BSE prevalence is equivalent in the two countries, revealed that there was no increased risk of BSE infectivity in beef coming from carcasses with a maturity score of < or =A40 in the United States, compared with beef from cattle younger than 21 months slaughtered in Japan.

  8. Transmissions of variant Creutzfeldt-Jakob disease from brain and lymphoreticular tissue show uniform and conserved bovine spongiform encephalopathy-related phenotypic properties on primary and secondary passage in wild-type mice.

    Science.gov (United States)

    Ritchie, Diane L; Boyle, Aileen; McConnell, Irene; Head, Mark W; Ironside, James W; Bruce, Moira E

    2009-12-01

    Prion strains are defined by their biological properties after transmission to wild-type mice, specifically by their incubation periods and patterns of vacuolar pathology ('lesion profiles'). Preliminary results from transmissions of variant Creutzfeldt-Jakob disease (vCJD) to wild-type mice provided the first compelling evidence for the close similarity of the vCJD agent to the agent causing bovine spongiform encephalopathy (BSE). Complete results from this investigation, including the transmission characteristics of vCJD from brain and peripheral tissues of 10 cases (after primary transmission and subsequent mouse-to-mouse passage), have now been analysed. All 10 vCJD sources resulted in consistent incubation periods and lesion profiles, suggesting that all 10 patients were infected with the same strain of agent. Incubation periods suggested that infectious titres may be subject to regional variation within the brain. Comparison of incubation periods and lesion profiles from transmission of brain and peripheral tissues showed no evidence of tissue-specific modification in the biological properties of the agent. Analysis of the protease-resistant prion protein (PrP(res)) by Western blotting from primary and subsequent passages in mice showed a glycosylation pattern closely resembling that of vCJD in humans, the so-called BSE 'glycoform signature'. Minor variations in PrP(res) fragment size were evident between mouse strains carrying different alleles of the gene encoding PrP both in primary transmissions and on further passages of vCJD brain. Overall, the results closely resembled those of previously reported transmissions of BSE in the same mouse strains, consistent with BSE being the origin of all of these vCJD cases.

  9. Modelling the trend of bovine spongiform encephalopathy prevalence in France: Use of restricted cubic spline regression in age-period-cohort models to estimate the efficiency of control measures.

    Science.gov (United States)

    Sala, Carole; Morignat, Eric; Ducrot, Christian; Calavas, Didier

    2009-07-01

    An age-period-cohort (APC) analysis was used to assess the trend in prevalence of bovine spongiform encephalopathy (BSE) in France over time in relation to the control measures adopted since onset of the epidemic. Restricted cubic regression splines were used to model the functional forms of the non-linear effects of age at screening, birth cohort and date of diagnosis of the tested animals. The data of the 2001-2007 period of surveillance was analysed using 1-year categorisation. A categorical analysis was performed as control to check the accuracy of the sets of knots in the spline models, which were selected according to the Akaike Information Criterion (AIC). Knot selection was based on a priori knowledge of the disease and the dates of implementation of the five main BSE control measures. It was assumed that disease prevalence was a function of exposure to BSE and that changes in the exposure of cattle to BSE were mainly due to the control measures. The effects of the five main control measures were discussed in relation to the trend in BSE risk for the successive birth cohorts. The six selected models confirmed that all measures participated in disease control. However, characterization of the respective effect of individual measures was not straightforward due to the very low disease prevalence, incompletely tested cohorts and probably cumulative and overlapping effects of successive measures. The ban of importation of meat and bone meal (MBM) from the UK and the ban of use of MBM in bovines were insufficient to control the epidemic. The decline in the BSE epidemic more likely originated from implementation of the ban of MBM use in all ruminants in 1994, whose effect was probably reinforced by the evolution in perception of the BSE risk following evidence of BSE transmission to humans. Finally, the respective effects of the last two measures (prohibition of the use of specific risk material in 1996 and total MBM ban in 2000) could not be characterized as

  10. Bovine Spongiform Encephalopathy: Production and Inspection

    Science.gov (United States)

    ... brain, skull, eyes trigeminal ganglia, spinal cord, vertebral column (excluding the vertebrae of the tail, the transverse processes of the thoracic and lumbar vertebrae, and the wings of the sacrum) and ...

  11. [Therapeutic prospects for subacute transmissible spongiform encephalopathies].

    Science.gov (United States)

    Seman, M; Adjou, K T

    1999-05-01

    There is currently no effective therapy available for Creutzfeldt-Jakob disease. However, a limited number of drugs such as polyanions, the amyloid-binding dye Congo red, amphotericin B and anthracyclines have been found to delay the appearance of the clinical signs in experimental prion diseases. Today, the most promising agent appears to be less toxic derivative the amphotericin B, MS-8209. Indeed this compound has a wide spectrum of anti-prion activity and constitute the unique molecule able to prolong survival time when treatment is performed at the late stages of infection. This result represents an important progress in therapeutical approaches of prion diseases and justify the development of new polyene antibiotic derivatives.

  12. Characterization of melanoma associated spongiform scleropathy

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish Jabur; Heegaard, Steffen; Prause, J.U.

    2002-01-01

    ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology......ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology...

  13. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Stages of Hepatic Encephalopathy? What Triggers or Can Cause HE to Get Worse? How is HE Diagnosed? ... portosystemic encephalopathy or PSE, is a condition that causes temporary worsening of brain function in people with ...

  14. Hepatic Encephalopathy

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    Full Text Available ... Get Worse? How is HE Diagnosed? Prior to Treatment Who treats HE? Preparing for your Medical Appointment Hepatic Encephalopathy Treatment Options Treatment Basics Treatment Medications Importance of Adhering ...

  15. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Hepatic Encephalopathy so you can tell your doctor right away if you think you may have it. ... American Liver Foundation © 2018 American Liver Foundation. All rights reserved. Funding for the HE123 - Diagnosis, Treatment and ...

  16. Hepatic Encephalopathy

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    Full Text Available ... Symptoms to look for Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is ... questions about HE, one step at a time. Home About Us Ways to Give Contact Us Privacy ...

  17. Hepatic Encephalopathy

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    Full Text Available ... Financial Assistance ALF HE Materials Suggested Reading Webinars Caregivers The Role of a Caregiver Signs and Symptoms to look for Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? ...

  18. Hepatic Encephalopathy

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    Full Text Available ... Hepatic Encephalopathy Treatment Options Treatment Basics Treatment Medications Importance of Adhering to Your Treatment Plan Long-Term Considerations Patient Support Finding Support Services Peer Support Groups Financial Assistance Support for My Loved Ones Resources Find ...

  19. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... your Medical Appointment Hepatic Encephalopathy Treatment Options Treatment Basics Treatment Medications Importance of Adhering to Your Treatment Plan Long-Term Considerations Patient Support Finding Support Services Peer Support Groups Financial Assistance ...

  20. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... to Treatment Who treats HE? Preparing for your Medical Appointment Hepatic Encephalopathy Treatment Options Treatment Basics Treatment ... treatment. Being a fully-informed participant in your medical care is an important factor in staying as ...

  1. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Reading Webinars Caregivers The Role of a Caregiver Signs and Symptoms to look for Caregiver Support Caregiver ... and your family to become familiar with the signs of Hepatic Encephalopathy so you can tell your ...

  2. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Encephalopathy often starts slowly, and at first you may not be aware you have it. The stages ... your doctor right away if you think you may have it. Prompt identification and treatment of HE ...

  3. Hashimoto's encephalopathy

    DEFF Research Database (Denmark)

    Montagna, Giacomo; Imperiali, Mauro; Agazzi, Pamela

    2016-01-01

    Hashimoto's encephalopathy (HE) is a rare not well understood, progressive and relapsing multiform disease, characterized by seizures, movement disorders, subacute cognitive dysfunction, psychiatric symptoms and responsiveness to steroid therapy. The disorder is generally associated with thyroid...... diseases and the most common feature is the presence of anti-thyroperoxidase antibodies (TPOAb). Patients are usually euthyroid or mildly hypothyroid at presentation. All age groups can be affected. The pathophysiology is still unclear, especially the link between elevated serum TPOAb...... and the encephalopathy. Most reported cases occurred in women and girls. Unspecific symptoms, non-pathognomonic laboratory neurophysiology and neuroimaging features make its diagnosis a real challenge for clinicians.The case of a 16 year old boy, with a clinical picture of HE associated with hypothyroidism...

  4. Toxic spongiform leucoencephalopathy after inhaling heroin vapour

    Energy Technology Data Exchange (ETDEWEB)

    Weber, W.; Henkes, H.; Kuehne, D. [Klinik fuer Allgemeine Roentgendiagnostik und Neuroradiologie, Alfried-Krupp-Krankenhaus, Alfried Krupp Strasse 21, D-45117, Essen (Germany); Moeller, P.; Bade, K. [Neurologische Klinik, Knappschafts-Krankenhaus, D-45657 Recklinghausen (Germany)

    1998-06-02

    This is a report of clinical, CT and MRI findings in a patient with toxic spongiform leucoencephalopathy after heroin ingestion. The disease is observed in drug addicts who inhale pre-heated heroin. The clinical onset, which usually occurs some days or even longer after the last heroin consumption, is characterized by a cerebellar syndrome. The cerebellar hemispheres, the cerebellar and cerebral peduncles and the pyramidal tract may be affected. Spongiform demyelination is the morphological substrate of the lesions, which are not contrast enhancing, hypodense on CT and hyperintense on T2-weighted MRI. The frequently perfect symmetry of the affection of functional systems points to a toxic and/or metabolic pathophysiological mechanism. (orig.) With 2 figs., 2 tabs., 26 refs.

  5. Toxic spongiform leucoencephalopathy after inhaling heroin vapour

    International Nuclear Information System (INIS)

    Weber, W.; Henkes, H.; Kuehne, D.; Moeller, P.; Bade, K.

    1998-01-01

    This is a report of clinical, CT and MRI findings in a patient with toxic spongiform leucoencephalopathy after heroin ingestion. The disease is observed in drug addicts who inhale pre-heated heroin. The clinical onset, which usually occurs some days or even longer after the last heroin consumption, is characterized by a cerebellar syndrome. The cerebellar hemispheres, the cerebellar and cerebral peduncles and the pyramidal tract may be affected. Spongiform demyelination is the morphological substrate of the lesions, which are not contrast enhancing, hypodense on CT and hyperintense on T2-weighted MRI. The frequently perfect symmetry of the affection of functional systems points to a toxic and/or metabolic pathophysiological mechanism. (orig.)

  6. Epileptic Encephalopathies: An Overview

    OpenAIRE

    Khan, Sonia; Al Baradie, Raidah

    2012-01-01

    Epileptic encephalopathies are an epileptic condition characterized by epileptiform abnormalities associated with progressive cerebral dysfunction. In the classification of the International League Against Epilepsy eight age-related epileptic encephalopathy syndromes are recognized. These syndromes include early myoclonic encephalopathy and Ohtahara syndrome in the neonatal period, West syndrome and Dravet syndrome in infancy, myoclonic status in nonprogressive encephalopathies, and Lennox-Ga...

  7. Pathogenesis of Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Irena Ciećko-Michalska

    2012-01-01

    Full Text Available Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy.

  8. Cross-seeding of prions by aggregated α-synuclein leads to transmissible spongiform encephalopathy.

    Directory of Open Access Journals (Sweden)

    Elizaveta Katorcha

    2017-08-01

    Full Text Available Aggregation of misfolded proteins or peptides is a common feature of neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's, prion and other diseases. Recent years have witnessed a growing number of reports of overlap in neuropathological features that were once thought to be unique to only one neurodegenerative disorder. However, the origin for the overlap remains unclear. One possibility is that diseases with mixed brain pathologies might arise from cross-seeding of one amyloidogenic protein by aggregated states of unrelated proteins. In the current study we examined whether prion replication can be induced by cross-seeding by α-synuclein or Aβ peptide. We found that α-synuclein aggregates formed in cultured cells or in vitro display cross-seeding activity and trigger misfolding of the prion protein (PrPC in serial Protein Misfolding Cyclic Amplification reactions, producing self-replicating PrP states characterized by a short C-terminal proteinase K (PK-resistant region referred to as PrPres. Non-fibrillar α-synuclein or fibrillar Aβ failed to cross-seed misfolding of PrPC. Remarkably, PrPres triggered by aggregated α-synuclein in vitro propagated in animals and, upon serial transmission, produced PrPSc and clinical prion disease characterized by spongiosis and astrocytic gliosis. The current study demonstrates that aggregated α-synuclein is potent in cross-seeding of prion protein misfolding and aggregation in vitro, producing self-replicating states that can lead to transmissible prion diseases upon serial passaging in wild type animals. In summary, the current work documents direct cross-seeding between unrelated amyloidogenic proteins associated with different neurodegenerative diseases. This study suggests that early interaction between unrelated amyloidogenic proteins might underlie the etiology of mixed neurodegenerative proteinopathies.

  9. 77 FR 29914 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Science.gov (United States)

    2012-05-21

    ...; ] DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service 9 CFR Parts 92, 93, 94, 95, 96, and 98...: Animal and Plant Health Inspection Service, USDA. ACTION: Proposed rule; reopening of comment period... 2012. Gregory L. Parham, Administrator, Animal and Plant Health Inspection Service. BILLING CODE 3410...

  10. 77 FR 15847 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Science.gov (United States)

    2012-03-16

    ... base importation conditions on the inherent risk of BSE infectivity in specified commodities, as well as on the BSE risk status of the region from which the commodities originate. We are proposing to establish a system for classifying regions as to BSE risk that is consistent with the system employed by the...

  11. 78 FR 72859 - Concurrence With OIE Risk Designations for Bovine Spongiform Encephalopathy

    Science.gov (United States)

    2013-12-04

    ... DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service [Docket No. APHIS-2013-0064... classifications of the following countries: Regions of negligible risk for BSE: Austria, Belgium, Brazil, Colombia....pdf (page 46). [[Page 72860

  12. 78 FR 72979 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Science.gov (United States)

    2013-12-04

    ... potentially contaminated with it, or is already present in the region. The elements considered include... cattle being exposed to the BSE agent by reviewing such elements as recycling and amplification of the... also require a permanent identification such as a brand or tattoo. For example, we require a C[square]N...

  13. Animal Meal: Production and Determination in Feedstuffs and the Origin of Bovine Spongiform Encephalopathy

    Science.gov (United States)

    Hahn, Heinz

    This contribution examines what animal meal is, how it is produced in rendering plants, and means of investigating feedstuff constituents. In addition to animal meal, numerous other products of animal origin are also on the market (e.g., blood meal, bone meal, feather meal, gelatin). Constituents of animal origin can be detected in feedstuffs by microscopy, but determining the animal species from which the constituents are derived, as required by law in Germany, requires methods such as enzyme-linked immunosorbent assay and polymerase chain reaction. We consider the problem of trace contamination being introduced accidentally during the production of ruminants' feedstuffs containing constituents of animal origin. The future of animal meal is discussed together with alternatives for disposing of animal carcasses and slaughtery offal, i.e., composting and incineration.

  14. 76 FR 38667 - Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-07-01

    ... Federal Register about last minute modifications that impact a previously announced advisory committee... check the Agency's Web site and call the appropriate advisory committee hot line/phone line to learn... blood and blood products and human cells, tissues and cellular and tissue-based products. FDA intends to...

  15. Investigation of metabolic encephalopathy

    African Journals Online (AJOL)

    , and. Table 1. Confirmed IMD cases associated with metabolic encephalopathy diagnosed at Red Cross Children's Hospital Metabolic Disease. Laboratory, 2006 - 2012. Name of disorder. Number of cases. Glutaric aciduria type 1 (GA1)*. 23.

  16. Treatment of Epileptic Encephalopathies.

    Science.gov (United States)

    Balestrini, Simona; Sisodiya, Sanjay M

    2017-01-01

    Epileptic encephalopathies represent the most severe epilepsies, with onset in infancy and childhood and seizures continuing in adulthood in most cases. New genetic causes are being identified at a rapid rate. Treatment is challenging and the overall outcome remains poor. Available targeted treatments, based on the precision medicine approach, are currently few. To provide an overview of the treatment of epileptic encephalopathies with known genetic determinants, including established treatment, anecdotal reports of specific treatment, and potential tailored precision medicine strategies. Genes known to be associated to epileptic encephalopathy were selected. Genes where the association was uncertain or with no reports of details on treatment, were not included. Although some of the genes included are associated with multiple epilepsy phenotypes or other organ involvement, we have mainly focused on the epileptic encephalopathies and their antiepileptic treatments. Most epileptic encephalopathies show genotypic and phenotypic heterogeneity. The treatment of seizures is difficult in most cases. The available evidence may provide some guidance for treatment: for example, ACTH seems to be effective in controlling infantile spams in a number of genetic epileptic encephalopathies. There are potentially effective tailored precision medicine strategies available for some of the encephalopathies, and therapies with currently unexplained effectiveness in others. Understanding the effect of the mutation is crucial for targeted treatment. There is a broad range of disease mechanisms underlying epileptic encephalopathies, and this makes the application of targeted treatments challenging. However, there is evidence that tailored treatment could significantly improve epilepsy treatment and prognosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Minimal hepatic encephalopathy

    OpenAIRE

    Stinton, Laura M; Jayakumar, Saumya

    2013-01-01

    Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy and can affect up to 80% of cirrhotic patients. By definition, it has no obvious clinical manifestation and is characterized by neurocognitive impairment in attention, vigilance and integrative function. Although often not considered to be clinically relevant and, therefore, not diagnosed or treated, MHE has been shown to affect daily functioning, quality of life, driving and overall mortality. The diagnosis o...

  18. [Encephalopathies caused by valproate].

    Science.gov (United States)

    Göbel, R; Görtzen, A; Bräunig, P

    1999-01-01

    Valproic acid (VPA)-induced encephalopathy is a rarely considered side effect, with somnolence, reduced motor activity and severe deterioration of cognitive and behavioural abilities. In accordance with the increasing clinical importance of valproate clinical symptoms, causes and possibilities of treatment are reviewed by reporting on two cases of valproate-induced encephalopathy. In comparison to VPA intoxication, which is associated to increased VPA blood levels, the mechanisms of encephalopathy may include interactions of the hepatic enzymes, a direct toxic effect on the cerebral receptors, as well as drug interactions, a paradoxical epileptogenic effect and metabolic interactions. In most cases withdrawal of VPA produces regression of the symptoms within a few days; the role of L-carnitin or citrullin supplementation in clinical treatment remains unclear.

  19. Management of Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    G. Wright

    2011-01-01

    Full Text Available Hepatic encephalopathy (HE, the neuropsychiatric presentation of liver disease, is associated with high morbidity and mortality. Reduction of plasma ammonia remains the central therapeutic strategy, but there is a need for newer novel therapies. We discuss current evidence supporting the use of interventions for both the general management of chronic HE and that necessary for more acute and advanced disease.

  20. GRIN2B encephalopathy

    DEFF Research Database (Denmark)

    Platzer, Konrad; Yuan, Hongjie; Schütz, Hannah

    2017-01-01

    treatment response in the respective patients still remains to be demonstrated. CONCLUSIONS: In addition to previously known features of intellectual disability, epilepsy and autism, we found evidence that GRIN2B encephalopathy is also frequently associated with movement disorder, cortical visual impairment...

  1. Evaluation of the Zoonotic Potential of Transmissible Mink Encephalopathy

    Directory of Open Access Journals (Sweden)

    Paul Brown

    2013-07-01

    Full Text Available Successful transmission of Transmissible Mink Encephalopathy (TME to cattle supports the bovine hypothesis for the still controversial origin of TME outbreaks. Human and primate susceptibility to classical Bovine Spongiform Encephalopathy (c-BSE and the transmissibility of L-type BSE to macaques indicate a low cattle-to-primate species barrier. We therefore evaluated the zoonotic potential of cattle-adapted TME. In less than two years, this strain induced in cynomolgus macaques a neurological disease similar to L-BSE but distinct from c-BSE. TME derived from another donor species (raccoon induced a similar disease with even shorter incubation periods. L-BSE and cattle-adapted TME were also transmissible to transgenic mice expressing human prion protein (PrP. Secondary transmissions to transgenic mice expressing bovine PrP maintained the features of the three tested bovine strains (cattle TME, c-BSE and L-BSE regardless of intermediate host. Thus, TME is the third animal prion strain transmissible to both macaques and humanized transgenic mice, suggesting zoonotic potentials that should be considered in the risk analysis of animal prion diseases for human health. Moreover, the similarities between TME and L-BSE are highly suggestive of a link between these strains, and therefore the possible presence of L-BSE for many decades prior to its identification in USA and Europe.

  2. Evaluation of the Zoonotic Potential of Transmissible Mink Encephalopathy

    Science.gov (United States)

    Comoy, Emmanuel E.; Mikol, Jacqueline; Ruchoux, Marie-Madeleine; Durand, Valérie; Luccantoni-Freire, Sophie; Dehen, Capucine; Correia, Evelyne; Casalone, Cristina; Richt, Juergen A.; Greenlee, Justin J.; Torres, Juan Maria; Brown, Paul; Deslys, Jean-Philippe

    2013-01-01

    Successful transmission of Transmissible Mink Encephalopathy (TME) to cattle supports the bovine hypothesis for the still controversial origin of TME outbreaks. Human and primate susceptibility to classical Bovine Spongiform Encephalopathy (c-BSE) and the transmissibility of L-type BSE to macaques indicate a low cattle-to-primate species barrier. We therefore evaluated the zoonotic potential of cattle-adapted TME. In less than two years, this strain induced in cynomolgus macaques a neurological disease similar to L-BSE but distinct from c-BSE. TME derived from another donor species (raccoon) induced a similar disease with even shorter incubation periods. L-BSE and cattle-adapted TME were also transmissible to transgenic mice expressing human prion protein (PrP). Secondary transmissions to transgenic mice expressing bovine PrP maintained the features of the three tested bovine strains (cattle TME, c-BSE and L-BSE) regardless of intermediate host. Thus, TME is the third animal prion strain transmissible to both macaques and humanized transgenic mice, suggesting zoonotic potentials that should be considered in the risk analysis of animal prion diseases for human health. Moreover, the similarities between TME and L-BSE are highly suggestive of a link between these strains, and therefore the possible presence of L-BSE for many decades prior to its identification in USA and Europe. PMID:25437205

  3. Minimal Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Laura M Stinton

    2013-01-01

    Full Text Available Minimal hepatic encephalopathy (MHE is the earliest form of hepatic encephalopathy and can affect up to 80% of cirrhotic patients. By definition, it has no obvious clinical manifestation and is characterized by neurocognitive impairment in attention, vigilance and integrative function. Although often not considered to be clinically relevant and, therefore, not diagnosed or treated, MHE has been shown to affect daily functioning, quality of life, driving and overall mortality. The diagnosis of MHE has traditionally been achieved through neuropsychological examination, psychometric tests or the newer critical flicker frequency test. A new smartphone application (EncephalApp Stroop Test may serve to function as a screening tool for patients requiring further testing. In addition to physician reporting and driving restrictions, medical treatment for MHE includes non-absorbable disaccharides (eg, lactulose, probiotics or rifaximin. Liver transplantation may not result in reversal of the cognitive deficits associated with MHE.

  4. Minimal hepatic encephalopathy.

    Science.gov (United States)

    Stinton, Laura M; Jayakumar, Saumya

    2013-10-01

    Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy and can affect up to 80% of cirrhotic patients. By definition, it has no obvious clinical manifestation and is characterized by neurocognitive impairment in attention, vigilance and integrative function. Although often not considered to be clinically relevant and, therefore, not diagnosed or treated, MHE has been shown to affect daily functioning, quality of life, driving and overall mortality. The diagnosis of MHE has traditionally been achieved through neuropsychological examination, psychometric tests or the newer critical flicker frequency test. A new smartphone application (EncephalApp Stroop Test) may serve to function as a screening tool for patients requiring further testing. In addition to physician reporting and driving restrictions, medical treatment for MHE includes non-absorbable disaccharides (eg, lactulose), probiotics or rifaximin. Liver transplantation may not result in reversal of the cognitive deficits associated with MHE.

  5. Metabolic Causes of Epileptic Encephalopathy

    OpenAIRE

    Yu, Joe Yuezhou; Pearl, Phillip L.

    2013-01-01

    Epileptic encephalopathy can be induced by inborn metabolic defects that may be rare individually but in aggregate represent a substantial clinical portion of child neurology. These may present with various epilepsy phenotypes including refractory neonatal seizures, early myoclonic encephalopathy, early infantile epileptic encephalopathy, infantile spasms, and generalized epilepsies which in particular include myoclonic seizures. There are varying degrees of treatability, but the outcome if u...

  6. Hashimoto encephalopathy: literature review.

    Science.gov (United States)

    Zhou, J Y; Xu, B; Lopes, J; Blamoun, J; Li, L

    2017-03-01

    Hashimoto encephalopathy (HE) presents as an encephalopathy without central nervous system infection or tumor. HE is associated with autoimmune thyroiditis and is thus considered to be an autoimmune disorder. The prevalence of HE is low, but death and status epilepticus have been reported. HE manifests with a wide range of symptoms that include behavioral changes and confusion. Elevated thyroid antibodies are present in the majority of cases and are required for the diagnosis of HE. Normal brain MRI findings are found in the majority of patients diagnosed with HE. The most consistent CSF abnormality noted in HE patients is the presence of elevated protein. Most HE patients respond well to steroid therapy. Clinical improvements are also observed with IV immunoglobulin and plasmapheresis. In conclusion, it is now generally accepted that the diagnosis of HE must include encephalopathy characterized by cognitive impairment associated with psychiatric features, such as hallucinations, delusions, and paranoia. Autoimmune encephalitis and prion disease should be considered in the differential diagnosis due to the similarity of the clinical features of these conditions to those of HE. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Melanoma-associated spongiform scleropathy: biochemical changes and possible relation to tumour extension

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish Jabur; Ribel-Madsen, S.; Heegaard, S.

    2003-01-01

    ophthalmology, melanoma-associated spongiform acleropathy (MASS), malignant melanoma, glycosaminoglycans (GAGs), collagen amino acids, tumour invasiveness, tumour extension, collagen degradation......ophthalmology, melanoma-associated spongiform acleropathy (MASS), malignant melanoma, glycosaminoglycans (GAGs), collagen amino acids, tumour invasiveness, tumour extension, collagen degradation...

  8. SCN2A encephalopathy

    Science.gov (United States)

    Howell, Katherine B.; McMahon, Jacinta M.; Carvill, Gemma L.; Tambunan, Dimira; Mackay, Mark T.; Rodriguez-Casero, Victoria; Webster, Richard; Clark, Damian; Freeman, Jeremy L.; Calvert, Sophie; Olson, Heather E.; Mandelstam, Simone; Poduri, Annapurna; Mefford, Heather C.; Harvey, A. Simon

    2015-01-01

    Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies. Herein, we define the phenotypic spectrum of SCN2A encephalopathy. Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping. Results: Patients were aged 0.7 to 22 years; 3 were deceased. Seizures commenced on day 1–4 in 8, week 2–6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset. Multifocal interictal epileptiform discharges were seen in all. Three of 12 patients had infantile spasms. The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment. Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms. Mutations arose de novo in 11 patients; paternal DNA was unavailable in one. Conclusions: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile–onset groups with severe and intermediate outcomes, and a childhood-onset group. Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome. Sodium channel blockers, particularly phenytoin, may improve seizure control. PMID:26291284

  9. Pathophysiology of epileptic encephalopathies.

    Science.gov (United States)

    Lado, Fred A; Rubboli, Guido; Capovilla, Giuseppe; Capovilla, Pippo; Avanzini, Giuliano; Moshé, Solomon L

    2013-11-01

    The application of metabolic imaging and genetic analysis, and now the development of appropriate animal models, has generated critical insights into the pathogenesis of epileptic encephalopathies. In this article we present ideas intended to move from the lesions associated with epileptic encephalopathies toward understanding the effects of these lesions on the functioning of the brain, specifically of the cortex. We argue that the effects of focal lesions may be magnified through the interaction between cortical and subcortical structures, and that disruption of subcortical arousal centers that regulate cortex early in life may lead to alterations of intracortical synapses that affect a critical period of cognitive development. Impairment of interneuronal function globally through the action of a genetic lesion similarly causes widespread cortical dysfunction manifesting as increased delta slow waves on electroencephalography (EEG) and as developmental delay or arrest clinically. Finally, prolonged focal epileptic activity during sleep (as occurring in the syndrome of continuous spike-wave in slow sleep, or CSWSS) might interfere with local slow wave activity at the site of the epileptic focus, thereby impairing the neural processes and, possibly, the local plastic changes associated with learning and other cognitive functions. Seizures may certainly add to these pathologic processes, but they are likely not necessary for the development of the cognitive pathology. Nevertheless, although seizures may be either a consequence or symptom of the underlying lesion, their effective treatment can improve outcomes as both clinical and experimental studies may suggest. Understanding their substrates may lead to novel, effective treatments for all aspects of the epileptic encephalopathy phenotype. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  10. DNM1 encephalopathy

    DEFF Research Database (Denmark)

    von Spiczak, Sarah; Helbig, Katherine L; Shinde, Deepali N

    2017-01-01

    evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations...... cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function. CONCLUSIONS: The phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one...

  11. Posterior Reversible Encephalopathy (PRES)

    International Nuclear Information System (INIS)

    Moron E, Fanny E; Diaz Marchan, Pedro

    2005-01-01

    The Posterior Reversible Encephalopathy Syndrome (PRES) is a clinical Syndrome composed of cephalea, alteration in vision and convulsions, usually observed in patients with sudden elevation of arterial pressure. The imagenologic evidence shows reversible vasogenic brain edema without stroke. Its location is predominantly posterior; it affects the cortex and the subcortical white matter of the occipital, parietal and temporal lobes. The treatment with antihypertensive drugs and the removing of immunosupressor medication are generally associated with complete neurological recovery; this is reflected also in the images which return to their basal condition. The untreated hypertension, on the other side, can result in a progressive defect of the autoregulation system of the central nervous system with cerebral hemorrhage, irreversible brain stroke, coma and death

  12. Diagnostic yield of genetic testing in epileptic encephalopathy in childhood.

    Science.gov (United States)

    Mercimek-Mahmutoglu, Saadet; Patel, Jaina; Cordeiro, Dawn; Hewson, Stacy; Callen, David; Donner, Elizabeth J; Hahn, Cecil D; Kannu, Peter; Kobayashi, Jeff; Minassian, Berge A; Moharir, Mahendranath; Siriwardena, Komudi; Weiss, Shelly K; Weksberg, Rosanna; Snead, O Carter

    2015-05-01

    Epilepsy is a common neurologic disorder of childhood. To determine the genetic diagnostic yield in epileptic encephalopathy, we performed a retrospective cohort study in a single epilepsy genetics clinic. We included all patients with intractable epilepsy, global developmental delay, and cognitive dysfunction seen between January 2012 and June 2014 in the Epilepsy Genetics Clinic. Electronic patient charts were reviewed for clinical features, neuroimaging, biochemical investigations, and molecular genetic investigations including targeted next-generation sequencing of epileptic encephalopathy genes. Genetic causes were identified in 28% of the 110 patients: 7% had inherited metabolic disorders including pyridoxine dependent epilepsy caused by ALDH7A1 mutation, Menkes disease, pyridox(am)ine-5-phosphate oxidase deficiency, cobalamin G deficiency, methylenetetrahydrofolate reductase deficiency, glucose transporter 1 deficiency, glycine encephalopathy, and pyruvate dehydrogenase complex deficiency; 21% had other genetic causes including genetic syndromes, pathogenic copy number variants on array comparative genomic hybridization, and epileptic encephalopathy related to mutations in the SCN1A, SCN2A, SCN8A, KCNQ2, STXBP1, PCDH19, and SLC9A6 genes. Forty-five percent of patients obtained a genetic diagnosis by targeted next-generation sequencing epileptic encephalopathy panels. It is notable that 4.5% of patients had a treatable inherited metabolic disease. To the best of our knowledge, this is the first study to combine inherited metabolic disorders and other genetic causes of epileptic encephalopathy. Targeted next-generation sequencing panels increased the genetic diagnostic yield from 25% in patients with epileptic encephalopathy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  13. Diabetic encephalopathy: a cerebrovascular disorder?

    NARCIS (Netherlands)

    Manschot, S.M.

    2006-01-01

    Animal study: The aim was to investigate the role of vascular disturbances in the development of experimental diabetic encephalopathy. We describe the effects of treatment with the Angiotensin Converting Enzyme(ACE)-inhibitor enalapril (treatment aimed at the

  14. Apnea in Acute Bilirubin Encephalopathy

    Science.gov (United States)

    Amin, Sanjiv B.; Bhutani, Vinod K.; Watchko, Jon F.

    2014-01-01

    Central apnea, defined as cessation of breathing for ≥ 20 seconds, is frequent in premature infants born apnea in neonates. This paper explores the reported association between acute bilirubin encephalopathy and symptomatic apneic events in newborns and the possible mechanisms involved in the pathogenesis of this phenomenon. The prevalence of symptomatic apneic events in reports of acute bilirubin encephalopathy suggests this clinical finding should be considered a sign of bilirubin neurotoxicity. PMID:25239473

  15. A quantitative assessment of the risk of transmission of bovine spongiform encephalopathy by tallow-based calf milk-replacer

    DEFF Research Database (Denmark)

    Paisley, Larry; Hostrup-Pedersen, J.

    2004-01-01

    A Monte Carlo simulation model was constructed to assess the risk of BSE transmission to calves by calf milk-replacer (CMR). We assumed that any BSE infectivity in the CMR would be associated with the allowable levels of impurities in tallow used to manufacture the milk-replacer. Simulations used...

  16. Chronic traumatic encephalopathy.

    Science.gov (United States)

    Yi, Juneyoung; Padalino, David J; Chin, Lawrence S; Montenegro, Philip; Cantu, Robert C

    2013-01-01

    Sports-related concussion has gained increased prominence, in part due to media coverage of several well-known athletes who have died from consequences of chronic traumatic encephalopathy (CTE). CTE was first described by Martland in 1928 as a syndrome seen in boxers who had experienced significant head trauma from repeated blows. The classic symptoms of impaired cognition, mood, behavior, and motor skills also have been reported in professional football players, and in 2005, the histopathological findings of CTE were first reported in a former National Football League (NFL) player. These finding were similar to Alzheimer's disease in some ways but differed in critical areas such as a predominance of tau protein deposition over amyloid. The pathophysiology is still unknown but involves a history of repeated concussive and subconcussive blows and then a lag period before CTE symptoms become evident. The involvement of excitotoxic amino acids and abnormal microglial activation remain speculative. Early identification and prevention of this disease by reducing repeated blows to the head has become a critical focus of current research.

  17. Sepsis Associated Encephalopathy

    Directory of Open Access Journals (Sweden)

    Neera Chaudhry

    2014-01-01

    Full Text Available Sepsis associated encephalopathy (SAE is a common but poorly understood neurological complication of sepsis. It is characterized by diffuse brain dysfunction secondary to infection elsewhere in the body without overt CNS infection. The pathophysiology of SAE is complex and multifactorial including a number of intertwined mechanisms such as vascular damage, endothelial activation, breakdown of the blood brain barrier, altered brain signaling, brain inflammation, and apoptosis. Clinical presentation of SAE may range from mild symptoms such as malaise and concentration deficits to deep coma. The evaluation of cognitive dysfunction is made difficult by the absence of any specific investigations or biomarkers and the common use of sedation in critically ill patients. SAE thus remains diagnosis of exclusion which can only be made after ruling out other causes of altered mentation in a febrile, critically ill patient by appropriate investigations. In spite of high mortality rate, management of SAE is limited to treatment of the underlying infection and symptomatic treatment for delirium and seizures. It is important to be aware of this condition because SAE may present in early stages of sepsis, even before the diagnostic criteria for sepsis can be met. This review discusses the diagnostic approach to patients with SAE along with its epidemiology, pathophysiology, clinical presentation, and differential diagnosis.

  18. Posterior reversible encephalopathy syndrome in the emergency ...

    African Journals Online (AJOL)

    Posterior reversible encephalopathy syndrome in the emergency service. ... The most common etiologies of PRES are hypertension and renal failure, and the most frequent pathophysiology is hyperperfusion. PRES is ... Keywords: Emergency service, hyperperfusion, posterior reversible encephalopathy, vasogenic edema ...

  19. MRI finding of ethylmalonic encephalopathy: case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Yong; Lee, Shi Kyung; Han, Chun Hwan; Rho, Eun Jin [Kangnam General Hospital Public Corporation, Seoul (Korea, Republic of)

    2002-12-01

    Ethylmalonic encephalopathy is a rare syndrom characterized by developmental delay, acrocyanosis, petechiae, chronic diarrhea, and ethylmalonic, lactic, and methylsuccinic aciduria. We report the MRI finding of ethylmalonic encephalopathy including previously unreported intracranial hematoma.

  20. Investigation of metabolic encephalopathy | van der Watt ...

    African Journals Online (AJOL)

    Encephalopathy may be a presenting sign in a wide range of medical conditions. This review focuses only on the diagnosis and initial management of those inherited metabolic diseases (IMDs) prevalent in South Africa that may present with encephalopathy in childhood. Metabolic encephalopathy is a medical emergency, ...

  1. Inflammation in Epileptic Encephalopathies.

    Science.gov (United States)

    Shandra, Oleksii; Moshé, Solomon L; Galanopoulou, Aristea S

    2017-01-01

    West syndrome (WS) is an infantile epileptic encephalopathy that manifests with infantile spasms (IS), hypsarrhythmia (in ~60% of infants), and poor neurodevelopmental outcomes. The etiologies of WS can be structural-metabolic pathologies (~60%), genetic (12%-15%), or of unknown origin. The current treatment options include hormonal treatment (adrenocorticotropic hormone and high-dose steroids) and the GABA aminotransferase inhibitor vigabatrin, while ketogenic diet can be given as add-on treatment in refractory IS. There is a need to identify new therapeutic targets and more effective treatments for WS. Theories about the role of inflammatory pathways in the pathogenesis and treatment of WS have emerged, being supported by both clinical and preclinical data from animal models of WS. Ongoing advances in genetics have revealed numerous genes involved in the pathogenesis of WS, including genes directly or indirectly involved in inflammation. Inflammatory pathways also interact with other signaling pathways implicated in WS, such as the neuroendocrine pathway. Furthermore, seizures may also activate proinflammatory pathways raising the possibility that inflammation can be a consequence of seizures and epileptogenic processes. With this targeted review, we plan to discuss the evidence pro and against the following key questions. Does activation of inflammatory pathways in the brain cause epilepsy in WS and does it contribute to the associated comorbidities and progression? Can activation of certain inflammatory pathways be a compensatory or protective event? Are there interactions between inflammation and the neuroendocrine system that contribute to the pathogenesis of WS? Does activation of brain inflammatory signaling pathways contribute to the transition of WS to Lennox-Gastaut syndrome? Are there any lead candidates or unexplored targets for future therapy development for WS targeting inflammation? © 2017 Elsevier Inc. All rights reserved.

  2. Inflammation in epileptic encephalopathies

    Science.gov (United States)

    Shandra, Oleksii; Moshé, Solomon L.; Galanopoulou, Aristea S.

    2017-01-01

    West syndrome (WS) is an infantile epileptic encephalopathy (EE) that manifests with infantile spasms, hypsarrhythmia (in ~60% of infants) and poor neurodevelopmental outcomes. The etiologies of WS can be structural-metabolic pathologies (~60%), genetic (12–15%) or of unknown origin. The current treatment options include hormonal treatment [adrenocorticotropic hormone (ACTH) and high dose steroids], the GABA aminotransferase inhibitor vigabatrin, while ketogenic diet can be given as add-on treatment in refractory IS. There is a need to identify new therapeutic targets and more effective treatments for WS. Theories about the role of inflammatory pathways in the pathogenesis and treatment of WS have emerged, being supported by both clinical and preclinical data from animal models of WS. Ongoing advances in genetics have revealed numerous genes involved in the pathogenesis of WS, including genes directly or indirectly involved in inflammation. Inflammatory pathways also interact with other signaling pathways implicated in WS, such as the neuroendocrine pathway. Furthermore, seizures may also activate pro-inflammatory pathways raising the possibility that inflammation can be a consequence of seizures and epileptogenic processes. With this targeted review we plan to discuss the evidence pro and against the following key questions. Does activation of inflammatory pathways in the brain cause epilepsy in WS and does it contribute to the associated comorbidities and progression? Can activation of certain inflammatory pathways be a compensatory or protective event? Are there interactions between inflammation and the neuroendocrine system that contribute to the pathogenesis of West syndrome? Does activation of brain inflammatory signaling pathways contribute to the transition of WS to Lennox-Gastaut syndrome? Are there any lead candidates or unexplored targets for future therapy development for WS targeting inflammation? PMID:28427564

  3. Some aspects of morphogenesis of diabetic encephalopathy

    Directory of Open Access Journals (Sweden)

    V. A. Tumanskiy

    2013-08-01

    Full Text Available On the basis of the literary data and conducted large-scale research it was ascertained that diabetes mellitus raises the risk of cerebral stroke in 2-6 times, the risk of transitional ischemic attacks in 3 times in comparison with the same risk in the general population [3]. Diabetic encephalopathy in its pure form can be found in 80.7% of patients with diabetes mellitus of the 1st type, its development is caused mainly by ineffective metabolic control of autoregulation of cerebral blood flow [4]. Mixed encephalopathy is prevailed among patients with diabetes mellitus of the 2nd type; lacunar heart attack is more often developed among this category of patients [5], multiple focus of ischemic affection of white substance – leukoaraiosis regarded as the areas of increased level of water, gliosis, and demyelination of white substance is often registered [6]. Pathogeny of diabetic encephalopathy hasn’t been studied properly. It is known that it is a multifactor effect in the development of which the main role is led by the vascular dysfunction with the reduction of blood supply and ischemia of brain tissue, as well as direct toxic influence of hyperglycemia and disorder of trophism of nerve tissue [7]. Microangiopathy and macroangiopathy acquire the special meaning in encephalopathy development among patients with diabetes mellitus. The evidence of microangiopathy and macroangiopathy is identified by the disease course and prognosis. On the ultrastructural level the changes of vessel microcircular movement are registered on the 1st month of the experimental alloxan diabetes. During electronic microscopy the thickening of basal membrane of capillaries as well as their dissection is observed. In micro vessels such phenomena as precipitation of lipoproteids, raising of the synthesis of collagen (the second type, dystrophic changes of endotheliocytes, and lowering of micropinocytosis can be found [11,12,13,14]. As the severity of diabetes mellitus

  4. Psychopathology and Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    João Gama Marques

    2013-12-01

    Full Text Available Since Hippocrates that neuropsychiatric illness secondary to liver disease fascinates physicians, but only in the XIX century Marcel Nencki and Ivan Pavlov suggested the relation between high concentrations of ammonia and Hepatic Encephalopathy (HE. The reaction of ammonia and glutamate (origins glutamine, “the Trojan Horse of neurotoxicity of ammonia continues to be the main responsible for the neurologic lesions, recently confirmed by neurochemistry and neuroimagiology studies. Glutamine starts the inflammatory reaction at the central nervous sys- tem but other important actors seem to be manganese and the neurotransmitters systems of GABA and endocanabinoids. Nowadays there are three different etiologic big groups for HE: type A associated with acute liver failure; type B associated with portosystemic bypass; and type C associated with cirrhosis of the liver. The staging of HE is still based on classic West Haven system, but a latent Grade 0 was introduced (the so called minimal HE; remaining the aggra- vating HE from Grade 1 (subtle changes at clinical examination to Grade 4 (coma. In this work a bibliographic review was made on 30 of the most pertinent and recent papers, focusing in psychopathology, physiopathology, etiology and staging of this clinical entity transversal to Psychiatry and Gastroenterology. Alterations are described in vigility and conscience like temporal, spatial and personal disorientation. Attention, concentration and memory are impaired very early, on latent phase and can be accessed through neuropsychological tests. Mood oscillates between euphoric and depressive. Personality changes begin obviously and abruptly or in a subtle and insidious way. There can be changes in perception like visual hallucinations or even of acoustic-verbal. The thought disorders can be of delusional type, paranoid, systematized or not, but also monothematic ala Capgras Syndrome. Speech can be accelerated, slowed down or completely in

  5. Dopamine agents for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Junker, Anders Ellekær; Als-Nielsen, Bodil; Gluud, Christian

    2014-01-01

    BACKGROUND: Patients with hepatic encephalopathy may present with extrapyramidal symptoms and changes in basal ganglia. These changes are similar to those seen in patients with Parkinson's disease. Dopamine agents (such as bromocriptine and levodopa, used for patients with Parkinson's disease) have...

  6. Genetics Home Reference: glycine encephalopathy

    Science.gov (United States)

    ... the brain. Glycine encephalopathy is caused by the shortage of an enzyme that normally breaks down glycine in the body. A lack of this enzyme allows excess glycine to build up in tissues and organs, particularly the brain, leading to serious medical problems. ...

  7. Amyloid Structure and Assembly: Insights from Scanning Transmission Electron Microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Goldsbury, C.; Wall, J.; Baxa, U.; Simon, M. N.; Steven, A. C.; Engel, A.; Aebi, U.; Muller, S. A.

    2011-01-01

    Amyloid fibrils are filamentous protein aggregates implicated in several common diseases such as Alzheimer's disease and type II diabetes. Similar structures are also the molecular principle of the infectious spongiform encephalopathies such as Creutzfeldt-Jakob disease in humans, scrapie in sheep, and of the so-called yeast prions, inherited non-chromosomal elements found in yeast and fungi. Scanning transmission electron microscopy (STEM) is often used to delineate the assembly mechanism and structural properties of amyloid aggregates. In this review we consider specifically contributions and limitations of STEM for the investigation of amyloid assembly pathways, fibril polymorphisms and structural models of amyloid fibrils. This type of microscopy provides the only method to directly measure the mass-per-length (MPL) of individual filaments. Made on both in vitro assembled and ex vivo samples, STEM mass measurements have illuminated the hierarchical relationships between amyloid fibrils and revealed that polymorphic fibrils and various globular oligomers can assemble simultaneously from a single polypeptide. The MPLs also impose strong constraints on possible packing schemes, assisting in molecular model building when combined with high-resolution methods like solid-state nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR).

  8. Genetics Home Reference: STXBP1 encephalopathy with epilepsy

    Science.gov (United States)

    ... Conditions STXBP1 encephalopathy with epilepsy STXBP1 encephalopathy with epilepsy Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description STXBP1 encephalopathy with epilepsy is a condition characterized by recurrent seizures (epilepsy), ...

  9. [Wernicke encephalopathy accompanying linitis plastica].

    Science.gov (United States)

    Soós, Zsuzsanna; Salamon, Mónika; Oláh, Roland; Czégeni, Anna; Salamon, Ferenc; Folyovich, András; Winkler, Gábor

    2014-01-05

    Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency. In the classical form it is characterized by a typical triad (confusion, oculomotor disturbance and ataxia), however, in the majority of the cases only confusion is present. It can be frequently observed in subjects with chronic alcohol consumption, but it may accompany different pathological states of which end stage malignant diseases are the most importants, where confusion may have different backgrounds. The authors present the case of an old male patient with advanced gastric cancer recognised and treated vitamin B1 deficiency, and they draw attention to difficulties of the diagnosis of Wernicke's disease.

  10. Ketogenic Diet in Epileptic Encephalopathies

    Directory of Open Access Journals (Sweden)

    Suvasini Sharma

    2013-01-01

    Full Text Available The ketogenic diet is a medically supervised high-fat, low-carbohydrate diet that has been found useful in patients with refractory epilepsy. It has been shown to be effective in treating multiple seizure types and epilepsy syndromes. In this paper, we review the use of the ketogenic diet in epileptic encephalopathies such as Ohtahara syndrome, West syndrome, Dravet syndrome, epilepsy with myoclonic atonic seizures, and Lennox-Gastaut syndrome.

  11. Ketogenic Diet in Epileptic Encephalopathies

    OpenAIRE

    Sharma, Suvasini; Tripathi, Manjari

    2013-01-01

    The ketogenic diet is a medically supervised high-fat, low-carbohydrate diet that has been found useful in patients with refractory epilepsy. It has been shown to be effective in treating multiple seizure types and epilepsy syndromes. In this paper, we review the use of the ketogenic diet in epileptic encephalopathies such as Ohtahara syndrome, West syndrome, Dravet syndrome, epilepsy with myoclonic atonic seizures, and Lennox-Gastaut syndrome.

  12. Comparison of MRI, CT, TCD and SPECT in patients with spongiform leukoencephalopathy after inhaling heroin vapor

    International Nuclear Information System (INIS)

    Wang Qun; Lu Bingxun; Yuan Huijuan

    2002-01-01

    Objective: To compare the characteristics of MRI, CT, single photon emission computed tomography (SPECT) and transcranial Doppler sonography (TCD) in patients with spongiform leukoencephalopathy after inhaling heroin vapor. Methods: Seventeen patients were investigated. MRI or CT was scanned in 17 patients, SPECT in 9 patients' and TCD in 11 patients. Results: MRI or CT: Brain MRI and CT revealed extensive symmetric white matter involvement of bilateral cerebral and cerebellar hemispheres and the brainstem. The lesions, which showed no contrast enhancement, were hypodense on CT and hypointense on T 1 -weighted and hyperintense on T 2 -weighted MRI. SPECT: The regional cerebral blood flows (rCBF) of white matter involvement on bilateral cerebral and cerebellar hemispheres was reduced obviously. The rCBF of temporal lobes, parietal lobes, occipital lobes, cerebellar hemispheres, and basal ganglion was reduced in varying degrees. TCD: The systolic peak became sharpened, and end-diastolic flow velocity and mean flow velocity were reduced obviously and pulsatile index was increased markedly in patients with spongiform leukoencephalopathy after inhaling heroin vapor. Conclusion: The characteristic manifestations of MRI and CT imaging may be regarded as the main foundation of diagnosing spongiform leukoencephalopathy after inhaling heroin vapor; SPECT and TCD can help comprehend the changes of hemodynamics of cerebral vessels and the degree of cerebral ischemia in patients with spongiform leukoencephalopathy after inhaling heroin vapor

  13. 9 CFR 98.15 - Health requirements.

    Science.gov (United States)

    2010-01-01

    ... evidence of the following diseases: (A) Ruminant: Bovine spongiform encephalopathy, brucellosis, contagious...: Bovine spongiform encephalopathy, brucellosis, contagious bovine pleuropneumonia, foot-and-mouth disease...: Bovine spongiform encephalopathy, contagious bovine pleuropneumonia, foot-and-mouth disease, Rift Valley...

  14. Clinical Characteristics and Outcomes Associated With High-Dose Intravenous Thiamine Administration in Patients With Encephalopathy.

    Science.gov (United States)

    Nakamura, Zev M; Tatreau, Jason R; Rosenstein, Donald L; Park, Eliza M

    2018-01-11

    Wernicke encephalopathy is a common neuropsychiatric syndrome due to thiamine deficiency. There is no consensus regarding thiamine dosing when Wernicke encephalopathy is suspected. A longstanding dosing strategy for Wernicke encephalopathy is 100mg daily, yet updated clinical guidelines suggest using high-dose intravenous (HDIV) thiamine. To describe thiamine prescribing practices at a large, public academic hospital and investigate clinical characteristics and outcomes associated with HDIV thiamine in patients with encephalopathy who received IV thiamine. Electronic medical records of hospitalized patients who received thiamine between 4/4/2014 and 11/1/2015 were reviewed. Chi-square tests, Wilcoxon Rank Sum tests, and logistic regression were used to compare clinical variables in patients with encephalopathy who received HDIV thiamine (≥ 200mg twice daily) vs lower doses of IV thiamine. Among the total of 5236 thiamine orders, 29% (n = 1531) were IV; 10% (n = 150) of IV orders met HDIV criteria. In patients with encephalopathy who received IV thiamine (n = 432), HDIV thiamine was administered to 20% (n = 86) and only 2.1% (n = 9) received dosing consistent with Royal College of Physicians guidelines. In bivariable analyses, HDIV thiamine was associated with surgical services (p = 0.001), psychiatric consultation (p < 0.001), and decreased mortality (p = 0.004). In multivariable models, the association between HDIV thiamine and decreased in-hospital mortality did not meet statistical significance (p = 0.061). In a large, public academic hospital, guideline-concordant thiamine supplementation is rare and HDIV thiamine is infrequently prescribed to patients with encephalopathy. Further studies are needed to confirm the possible benefits of HDIV thiamine for patients with suspected thiamine-deficient encephalopathy. Copyright © 2018 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  15. Wernicke's Encephalopathy in a Nigerian with Schizophrenia

    African Journals Online (AJOL)

    ANNALS

    irreversible Korsakoff psychosis, with confabulation and anterograde memory deficits, and with 17% mortality.9. Clinically, we most often associate. Wernicke's encephalopathy with alcohol consumption.1-5. Wernicke's encephalopathy producing an altered state may occur in malnourished psychiatric patients even in the ...

  16. Birth defects in children with newborn encephalopathy

    NARCIS (Netherlands)

    Felix, JF; Badawi, N; Kurinczuk, JJ; Bower, C; Keogh, JM; Pemberton, PJ

    2000-01-01

    This study was designed to investigate birth defects found in association with newborn encephalopathy. All possible birth defects were ascertained in a population-based study of 276 term infants with moderate or severe encephalopathy and 564 unmatched term control infants. A strong association

  17. Minimal hepatic encephalopathy: A review.

    Science.gov (United States)

    Nardone, Raffaele; Taylor, Alexandra C; Höller, Yvonne; Brigo, Francesco; Lochner, Piergiorgio; Trinka, Eugen

    2016-10-01

    Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy and can affect up to 80% of patients with liver cirrhosis. By definition, MHE is characterized by cognitive function impairment in the domains of attention, vigilance and integrative function, but obvious clinical manifestation are lacking. MHE has been shown to affect daily functioning, quality of life, driving and overall mortality. The diagnosis can be achieved through neuropsychological testing, recently developed computerized psychometric tests, such as the critical flicker frequency and the inhibitory control tests, as well as neurophysiological procedures. Event related potentials can reveal subtle changes in patients with normal neuropsychological performances. Spectral analysis of electroencephalography (EEG) and quantitative analysis of sleep EEG provide early markers of cerebral dysfunction in cirrhotic patients with MHE. Neuroimaging, in particular MRI, also increasingly reveals diffuse abnormalities in intrinsic brain activity and altered organization of functional connectivity networks. Medical treatment for MHE to date has been focused on reducing serum ammonia levels and includes non-absorbable disaccharides, probiotics or rifaximin. Liver transplantation may not reverse the cognitive deficits associated with MHE. We performed here an updated review on epidemiology, burden and quality of life, neuropsychological testing, neuroimaging, neurophysiology and therapy in subjects with MHE. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  18. MR findings of wernicke encephalopathy

    International Nuclear Information System (INIS)

    Yoon, Hyun Ki; Chang, Kee Hyun; Lee, Goo; Han, Moon Hee; Park, Sung Ho; Na, Duk Yull; Song, Chi Sung

    1991-01-01

    Seven patients (33 to 58 years old) with clinical diagnoses of Wernicke encephalopathy were examined with MR on either a 2.0T (5 cases) or a 0.5T scanner (2 cases) using spin-echo pulse sequences. In 2 patients, follow-up MR studies were performed 1 and 5 weeks after thiamine (vitamine B1) treatment. Five patients (4 chronic alcoholics and 1 with hyperemesis gravidarum) showed atrophy of both mamillary bodies, along with patchy lesions around the third ventricle, medial thalami, tectum of the midbrain, and periaqueductal gray matter. Another patient with hyperemesis of gravidrum demonstrated only slightly atrophic mamillary bodies, and the last patient with severe vomiting after gastrojejunostomy showed only diencephaic/mesencephalic lesions with apparently normal mamillary bodies. A follow-up MR showed a decrease in previously-noted diencephalic/-/mesencephalic lesions but no change in the size of the mamillary bodies. Diencephalic/mesencephalic lesions were well seen as a high-signal intensity on proton-and T2-weighted axial images, while atrophy of the mamillary bodies was seen best on T1-weighted sagittal images. MR imaging is very useful in demonstrating the characteristic lesions of Wernicke encephalopathy and in evaluating the result of treatment on follow-up study

  19. MR findings of wernicke encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hyun Ki; Chang, Kee Hyun; Lee, Goo; Han, Moon Hee [Seoul National University College of Medicine, Seoul (Korea, Republic of); Park, Sung Ho; Na, Duk Yull; Song, Chi Sung [Young-Deung-Po City Hospital, Seoul (Korea, Republic of)

    1991-07-15

    Seven patients (33 to 58 years old) with clinical diagnoses of Wernicke encephalopathy were examined with MR on either a 2.0T (5 cases) or a 0.5T scanner (2 cases) using spin-echo pulse sequences. In 2 patients, follow-up MR studies were performed 1 and 5 weeks after thiamine (vitamine B1) treatment. Five patients (4 chronic alcoholics and 1 with hyperemesis gravidarum) showed atrophy of both mamillary bodies, along with patchy lesions around the third ventricle, medial thalami, tectum of the midbrain, and periaqueductal gray matter. Another patient with hyperemesis of gravidrum demonstrated only slightly atrophic mamillary bodies, and the last patient with severe vomiting after gastrojejunostomy showed only diencephaic/mesencephalic lesions with apparently normal mamillary bodies. A follow-up MR showed a decrease in previously-noted diencephalic/-/mesencephalic lesions but no change in the size of the mamillary bodies. Diencephalic/mesencephalic lesions were well seen as a high-signal intensity on proton-and T2-weighted axial images, while atrophy of the mamillary bodies was seen best on T1-weighted sagittal images. MR imaging is very useful in demonstrating the characteristic lesions of Wernicke encephalopathy and in evaluating the result of treatment on follow-up study.

  20. Current understanding and neurobiology of epileptic encephalopathies.

    Science.gov (United States)

    Auvin, Stéphane; Cilio, Maria Roberta; Vezzani, Annamaria

    2016-08-01

    Epileptic encephalopathies are a group of diseases in which epileptic activity itself contributes to severe cognitive and behavioral impairments above and beyond what might be expected from the underlying pathology alone. These impairments can worsen over time. This concept has been continually redefined since its introduction. A few syndromes are considered epileptic encephalopathies: early myoclonic encephalopathy and Ohtahara syndrome in the neonatal period, epilepsy of infancy with migrating focal seizures, West syndrome or infantile spasms, Dravet syndrome during infancy, Lennox-Gastaut syndrome, epileptic encephalopathy with continuous spikes-and-waves during sleep, and Landau-Kleffner syndrome during childhood. The inappropriate use of this term to refer to all severe epilepsy syndromes with intractable seizures and severe cognitive dysfunction has led to confusion regarding the concept of epileptic encephalopathy. Here, we review our current understanding of those epilepsy syndromes considered to be epileptic encephalopathies. Genetic studies have provided a better knowledge of neonatal and infantile epilepsy syndromes, while neuroimaging studies have shed light on the underlying causes of childhood-onset epileptic encephalopathies such as Lennox-Gastaut syndrome. Apart from infantile spasm models, we lack animal models to explain the neurobiological mechanisms at work in these conditions. Experimental studies suggest that neuroinflammation may be a common neurobiological pathway that contributes to seizure refractoriness and cognitive involvement in the developing brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Wernicke encephalopathy: MR findings in two patients

    International Nuclear Information System (INIS)

    Opdenakker, G.; Gelin, G.; Palmers, Y.; Surgeloose, D. de

    1999-01-01

    Wernicke encephalopathy is a serious neurologic disorder caused by vitamin-B1 or thiamine deficiency. In the literature the characteristic symmetric paraventricular lesions of Wernicke encephalopathy are hyperintense on T2-weighted sequences spin-echo (SE) and enhance on T1-weighted SE sequences after intravenous gadolinium administration in the acute phase. We present two patients in the acute phase of Wernicke encephalopathy with special reference to the MR imaging. One of our reported cases is special because of the MR demonstration of a hemorrhagic focus in the caput of the right nucleus caudatus. The other case demonstrates no enhancement on SE T1-weighted sequences after intravenous gadolinium administration. (orig.)

  2. Encephalopathy

    Science.gov (United States)

    ... research is being done? The NINDS supports and conducts research on brain diseases. Much of this research is aimed at characterizing the agents that cause these disorders, clarifying the mechanisms underlying them, and, ...

  3. Fundus Findings in Wernicke Encephalopathy

    Directory of Open Access Journals (Sweden)

    Tal Serlin

    2017-07-01

    Full Text Available Wernicke encephalopathy (WE is an acute neuropsychiatric syndrome resulting from thiamine (vitamin B1 deficiency, classically characterized by the triad of ophthalmoplegia, confusion, and ataxia. While commonly associated with chronic alcoholism, WE may also occur in the setting of poor nutrition or absorption. We present a 37-year-old woman who underwent laparoscopic sleeve gastrectomy and presented with visual disturbance with bilateral horizontal nystagmus, confusion, and postural imbalance. Fundus examination revealed bilateral optic disc edema with a retinal hemorrhage in the left eye. Metabolic workup demonstrated thiamine deficiency. Her symptoms resolved after thiamine treatment. This case raises the awareness of the possibility of posterior segment findings in WE, which are underreported in WE.

  4. Wernicke's Encephalopathy following Hyperemesis Gravidarum

    Science.gov (United States)

    Kotha, V.K.; De Souza, A.

    2013-01-01

    Wernicke's encephalopathy (WE) due to causes other than chronic alcohol abuse is an uncommon and often misdiagnosed condition. In the setting of hyperemesis gravidarum, an acute deficiency of thiamine results from body stores being unable to meet increased metabolic demands. The condition produces typical clinical and radiological findings and when diagnosed early and treated promptly has a good prognosis. Magnetic resonance imaging (MRI) is sensitive and specific for diagnosis. We describe three patients with hyperemesis gravidarum who developed WE, and highlight a range of clinical and imaging features important for appropriate diagnosis. A high degree of clinical suspicion is essential. Treatment is often empirical pending results of investigation, and consists of parenteral repletion of thiamine stores. Reversal of MRI findings parallels clinical improvement. Neurologic outcomes are usually good, but half the pregnancies complicated by this condition do not produce healthy children. PMID:23859165

  5. Suicide and Chronic Traumatic Encephalopathy.

    Science.gov (United States)

    Iverson, Grant L

    2016-01-01

    For nearly 80 years, suicidality was not considered to be a core clinical feature of chronic traumatic encephalopathy (CTE). In recent years, suicide has been widely cited as being associated with CTE, and now depression has been proposed to be one of three core diagnostic features alongside cognitive impairment and anger control problems. This evolution of the clinical features has been reinforced by thousands of media stories reporting a connection between mental health problems in former athletes and military veterans, repetitive neurotrauma, and CTE. At present, the science underlying the causal assumption between repetitive neurotrauma, depression, suicide, and the neuropathology believed to be unique to CTE is inconclusive. Epidemiological evidence indicates that former National Football League players, for example, are at lower, not greater, risk for suicide than men in the general population. This article aims to discuss the critical issues and literature relating to these possible relationships.

  6. Functional neuroimaging in epileptic encephalopathies.

    Science.gov (United States)

    Siniatchkin, Michael; Capovilla, Giuseppe

    2013-11-01

    Epileptic encephalopathies (EEs) represent a group of severe epileptic disorders associated with cognitive and behavioral disturbances. The mechanisms of cognitive disability in EEs remain unclear. This review summarized neuroimaging studies that have tried to describe specific fingerprints of brain activation in EE. Although the epileptic activity can be generated individually in different brain regions, it seems likely that the activity propagates in a syndrome-specific way. In some EEs, the epileptiform discharges were associated with an interruption of activity in the default mode network. In another EE, other mechanisms seem to underlie cognitive disability associated with epileptic activity, for example, abnormal connectivity pattern or interfering activity in the thalamocortical network. Further neuroimaging studies are needed to investigate the short-term and long-term impact of epileptic activity on cognition and development. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  7. Chronic traumatic encephalopathy: The unknown disease.

    Science.gov (United States)

    Martínez-Pérez, R; Paredes, I; Munarriz, P M; Paredes, B; Alén, J F

    2017-04-01

    Chronic traumatic encephalopathy is a neurodegenerative disease produced by accumulated minor traumatic brain injuries; no definitive premortem diagnosis and no treatments are available for chronic traumatic encephalopathy. Risk factors associated with chronic traumatic encephalopathy include playing contact sports, presence of the apolipoprotein E4, and old age. Although it shares certain histopathological findings with Alzheimer disease, chronic traumatic encephalopathy has a more specific presentation (hyperphosphorylated tau protein deposited as neurofibrillary tangles, associated with neuropil threads and sometimes with beta-amyloid plaques). Its clinical presentation is insidious; patients show mild cognitive and emotional symptoms before progressing to parkinsonian motor signs and finally dementia. Results from new experimental diagnostic tools are promising, but these tools are not yet available. The mainstay of managing this disease is prevention and early detection of its first symptoms. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Immunolocalisation of PrPSc in scrapie-infected N2a mouse neuroblastoma cells by light and electron microscopy.

    Science.gov (United States)

    Veith, Nathalie M; Plattner, Helmut; Stuermer, Claudia A O; Schulz-Schaeffer, Walter J; Bürkle, Alexander

    2009-01-01

    The causative agent of transmissible spongiform encephalopathies (TSE) is PrPSc, an infectious, misfolded isoform of the cellular prion protein (PrPC). The localisation and trafficking of PrPSc and sites of conversion from PrPC to PrPSc are under debate, particularly since most published work did not discriminate between PrPC and PrPSc. Here we describe the localisation of PrPC and PrPSc in a scrapie-infected neuroblastoma cell line, ScN2a, by light and electron microscopic immunolocalisation. After eliminating PrPC with proteinase K, PrPSc was detected at the plasma membrane, endocytosed via clathrin-coated pits and delivered to early endosomes. Finally, PrPSc was detected in late endosomes/lysosomes. As we detected PrPSc at the cell surface, in early endosomes and in late endosomes/lysosomes, i.e. locations where PrPC is also present, our data imply that the conversion process could take place at the plasma membrane and/or along the endocytic pathway. Finally, we observed the release of PrPC/PrPSc via exocytotic pathways, i.e. via exosomes and as an opaque electron-dense mass which may represent a mechanism of intercellular spreading of infectious prions.

  9. STXBP1 encephalopathy

    DEFF Research Database (Denmark)

    Stamberger, Hannah; Nikanorova, Marina; Willemsen, Marjolein H.

    2016-01-01

    Objective: To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously reported patients. Methods: We recruited newly diagnosed patients with STXBP1 mutations through an international networ......, and the degree of ID. Accordingly, we hypothesize that seizure severity and ID present 2 independent dimensions of the STXBP1-E phenotype. STXBP1-E may be conceptualized as a complex neurodevelopmental disorder rather than a primary epileptic encephalopathy....

  10. The Structural Architecture of an Infectious Mammalian Prion Using Electron Cryomicroscopy.

    Directory of Open Access Journals (Sweden)

    Ester Vázquez-Fernández

    2016-09-01

    Full Text Available The structure of the infectious prion protein (PrPSc, which is responsible for Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, has escaped all attempts at elucidation due to its insolubility and propensity to aggregate. PrPSc replicates by converting the non-infectious, cellular prion protein (PrPC into the misfolded, infectious conformer through an unknown mechanism. PrPSc and its N-terminally truncated variant, PrP 27-30, aggregate into amorphous aggregates, 2D crystals, and amyloid fibrils. The structure of these infectious conformers is essential to understanding prion replication and the development of structure-based therapeutic interventions. Here we used the repetitive organization inherent to GPI-anchorless PrP 27-30 amyloid fibrils to analyze their structure via electron cryomicroscopy. Fourier-transform analyses of averaged fibril segments indicate a repeating unit of 19.1 Å. 3D reconstructions of these fibrils revealed two distinct protofilaments, and, together with a molecular volume of 18,990 Å3, predicted the height of each PrP 27-30 molecule as ~17.7 Å. Together, the data indicate a four-rung β-solenoid structure as a key feature for the architecture of infectious mammalian prions. Furthermore, they allow to formulate a molecular mechanism for the replication of prions. Knowledge of the prion structure will provide important insights into the self-propagation mechanisms of protein misfolding.

  11. Chronic Traumatic Encephalopathy: A Review

    Directory of Open Access Journals (Sweden)

    Michael Saulle

    2012-01-01

    Full Text Available Chronic traumatic encephalopathy (CTE is a progressive neurodegenerative disease that is a long-term consequence of single or repetitive closed head injuries for which there is no treatment and no definitive pre-mortem diagnosis. It has been closely tied to athletes who participate in contact sports like boxing, American football, soccer, professional wrestling and hockey. Risk factors include head trauma, presence of ApoE3 or ApoE4 allele, military service, and old age. It is histologically identified by the presence of tau-immunoreactive NFTs and NTs with some cases having a TDP-43 proteinopathy or beta-amyloid plaques. It has an insidious clinical presentation that begins with cognitive and emotional disturbances and can progress to Parkinsonian symptoms. The exact mechanism for CTE has not been precisely defined however, research suggest it is due to an ongoing metabolic and immunologic cascade called immunoexcitiotoxicity. Prevention and education are currently the most compelling way to combat CTE and will be an emphasis of both physicians and athletes. Further research is needed to aid in pre-mortem diagnosis, therapies, and support for individuals and their families living with CTE.

  12. Chronic traumatic encephalopathy: a review.

    Science.gov (United States)

    Saulle, Michael; Greenwald, Brian D

    2012-01-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that is a long-term consequence of single or repetitive closed head injuries for which there is no treatment and no definitive pre-mortem diagnosis. It has been closely tied to athletes who participate in contact sports like boxing, American football, soccer, professional wrestling and hockey. Risk factors include head trauma, presence of ApoE3 or ApoE4 allele, military service, and old age. It is histologically identified by the presence of tau-immunoreactive NFTs and NTs with some cases having a TDP-43 proteinopathy or beta-amyloid plaques. It has an insidious clinical presentation that begins with cognitive and emotional disturbances and can progress to Parkinsonian symptoms. The exact mechanism for CTE has not been precisely defined however, research suggest it is due to an ongoing metabolic and immunologic cascade called immunoexcitiotoxicity. Prevention and education are currently the most compelling way to combat CTE and will be an emphasis of both physicians and athletes. Further research is needed to aid in pre-mortem diagnosis, therapies, and support for individuals and their families living with CTE.

  13. Therapeutic approach to epileptic encephalopathies.

    Science.gov (United States)

    Vigevano, Federico; Arzimanoglou, Alexis; Plouin, Perrine; Specchio, Nicola

    2013-11-01

    Epileptic encephalopathies (EEs) are electroclinical entities with a peculiar course of disease; seizures and electroencephalographic (EEG) epileptiform abnormalities, ictal and interictal, contribute to progressive disturbance of cerebral functions. Frequently EEs are drug resistant, and consequences may be catastrophic. The main goal of treatment is to stop the peculiar course of epilepsy, operating on three parameters: seizure control, reduction of EEG abnormalities, and developmental outcome. For a correct therapeutic approach it is mandatory to have an as accurate as possible syndromic and etiologic diagnosis. Given the poor efficacy of conventional antiepileptic drugs (AEDs), the use of specific drugs for EEs, such as adrenocorticotropic hormone (ACTH) and corticosteroids or stiripentol is suggested. In some cases the choice of treatment is strictly related to the etiology: vigabatrin in tuberous sclerosis, ketogenic diet in glucose transporter type 1 (GLUT-1) deficiency, and pyridoxine in pyridoxine deficiency. Some AEDs combinations, such as sodium valproate with lamotrigine, have also provided interesting results, for example, in Lennox-Gastaut syndrome, although controlled studies are lacking. Finally, early surgery can be an option in children with focal structural abnormalities responsible for EEs preferably before irreversible damage on developmental outcome. Multispecialist support is recommended in EE. Management should be global from the onset, integrating not only seizure control but also all issues related to comorbidities, particularly neuropsychological and psychiatric. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  14. Genetics Home Reference: familial encephalopathy with neuroserpin inclusion bodies

    Science.gov (United States)

    ... Home Health Conditions FENIB Familial encephalopathy with neuroserpin inclusion bodies Printable PDF Open All Close All Enable ... expand/collapse boxes. Description Familial encephalopathy with neuroserpin inclusion bodies ( FENIB ) is a disorder that causes progressive ...

  15. Wernicke's encephalopathy as a complication of gastroparesis after ...

    African Journals Online (AJOL)

    Wernicke's encephalopathy is a common complication of malnutrition, alcohol abuse and gastric outlet obstruction. We describe a patient who developed Wernicke's encephalopathy secondary to gastroparesis, with no significant evidence of malnutrition, alcohol abuse, or gastric outlet obstruction.

  16. Hypertensive encephalopathy in a patient with neonatal thyrotoxicosis

    NARCIS (Netherlands)

    Pijnenburg, MWH; Zweens, MJ; Bink, MTE; Odink, RJ

    1999-01-01

    Neonatal hyperthyroidism may give rise to serious cardiovascular complications. A girl with severe thyrotoxicosis in whom hypertensive encephalopathy developed is described. Conclusion Neonatal thyrotoxicosis can give rise to hypertension and may lead to hypertensive encephalopathy.

  17. Branched-chain amino acids for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Koretz, R L; Kjaergard, L L

    2003-01-01

    Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy....

  18. Neuropsychological functioning in Wernicke's encephalopathy.

    Science.gov (United States)

    Behura, Sushree Sangita; Swain, Sarada Prasanna

    2015-01-01

    Wernicke's encephalopathy (WE) is caused by thiamine (Vitamin B1) deficiency and most commonly found in chronic alcoholism and malnutrition. Clinically, the key features are mental status disturbances (global confusion), oculomotor abnormalities, and gait disturbances (ataxia). Apart from these clinical features, we can find deficits in neuropsychological functioning in patients with WE, which is more prominent after the improvement in the physical conditions. Neuropsychological functioning includes both basic cognitive processes (i.e., attention-concentration) as well as higher order cognitive processes (i.e., memory, executive functioning, reasoning), which is much vital for the maintenance of quality of life of an individual. However, unfortunately, in most of the cases, neuropsychological functioning is ignored by the clinicians. In this study four case reports of WE have been presented. The patients were taken from the outdoor department of Mental Health Institute, S.C.B. Medical College, Cuttack, Odisha. Neuropsychological functioning was measured by administration of PGIBBD and Quality of Life was measured by WHO-QOL BREF Odia Version. As described in the literature, among the three cardinal signs (global confusion, ataxia, and ocular sings), the first two were present in all cases, but nystagmus was present in only two cases. Memory dysfunction was so disabling that the persons were unable to maintain a good Quality of Life and occupational impairment was prominent. There are disturbances in recent, remote memory, immediate recall, delayed recall, and attention and concentration, ultimately creating both physical and mental disability. PGI-BBD findings also suggest the overall impairment in neuropsychological functioning other than memory, that is, executive functioning, visual acuity, and depth perception. Findings of WHO-QOL BREF suggest the impairment of four domains of QOL in all the cases, but the severity level varies from person to person. Like the

  19. [Wernicke encephalopathy: Guiding thiamine prescription].

    Science.gov (United States)

    Boulanger, A S; Paquette, I; Létourneau, G; Richard-Devantoy, S

    2017-05-01

    Wernicke's encephalopathy (WE) is a medical emergency. The objective of this paper is to systematically review the literature published over the past 15 years pertaining to prophylactic and curative treatment of WE with thiamine. A systematic literature search was performed using Medline to include all studies published between January 1, 2000 and December 31, 2015. Of the 316 abstracts identified, 20 met the final inclusion criteria. The evidence on the use of prophylactic thiamine was quite heterogeneous. The use of thiamine in this context largely depended on the evaluation of an individual's risk of developing WE. Use of prophylactic thiamine in low-risk patients is not universally indicated. When prescribed in this sub-population, the oral route is suggested but may be insufficient owing to its limited intestinal absorption and the high risk of non-compliance. High-risk patients need parenteral treatment with a recommended posology of 250 mg daily for 3 to 5 days. Intramuscular route is preferred in the outpatient setting, whereas intravenous route is suggested for inpatients. In cases where the diagnosis of WE is suspected or confirmed, a curative treatment with high-dose IV thiamine is justified. The evidence widely accepted in the literature is much clearer in this condition, with treatment regimens consisting of 500 mg IV 3 times daily for 3 to 5 days, followed by 250 mg IV daily for a minimum of 3 to 5 additional days. The literature does indicate that thiamine should be prescribed at high dosages, with the parenteral routes indicated in hospital settings and in high-risk patients. Based on the current literature review, we suggest treatment algorithms guiding thiamine prescription for WE. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  20. Delayed encephalopathy after acute carbon monoxide poisoning

    Directory of Open Access Journals (Sweden)

    Mehmet İbrahim Turan

    2014-03-01

    Full Text Available Carbon monoxide poisoning is a major cause of death following attempted suicide and accidental exposures. Although clinical presentation depends on the duration and the intensity of exposure, the assessment of the severity of intoxication is difficult. A small percentage of patients who show complete initial recovery may develop delayed neurological deficits. Delayed encephalopathy after acute carbon monoxide poisoning is a rare and poor prognosis neurologic disorders and there is no specific treatment. We present a case with early onset of delayed encephalopathy after acute carbon monoxide poisoning with typical cranial imaging findings in a child with atypical history and clinical presentation.

  1. Time trends in exposure of cattle to bovine spongiform encephalopathy and cohort effect in France and Italy: value of the classical Age-Period-Cohort approach.

    Science.gov (United States)

    Sala, Carole; Ru, Giuseppe

    2009-09-18

    The Age-Period-Cohort (APC) analysis is routinely used for time trend analysis of cancer incidence or mortality rates, but in veterinary epidemiology, there are still only a few examples of this application. APC models were recently used to model the French epidemic assuming that the time trend for BSE was mainly due to a cohort effect in relation to the control measures that may have modified the BSE exposure of cohorts over time. We used a categorical APC analysis which did not require any functional form for the effect of the variables, and examined second differences to estimate the variation of the BSE trend. We also reanalysed the French epidemic and performed a simultaneous analysis of Italian data using more appropriate birth cohort categories for comparison. We used data from the exhaustive surveillance carried out in France and Italy between 2001 and 2007, and comparatively described the trend of the epidemic in both countries. At the end, the shape and irregularities of the trends were discussed in light of the main control measures adopted to control the disease. In Italy a decrease in the epidemic became apparent from 1996, following the application of rendering standards for the processing of specific risk material (SRM). For the French epidemic, the pattern of second differences in the birth cohorts confirmed the beginning of the decrease from 1995, just after the implementation of the meat and bone meal (MBM) ban for all ruminants (1994). The APC analysis proved to be highly suitable for the study of the trend in BSE epidemics and was helpful in understanding the effects of management and control of the disease. Additionally, such an approach may help in the implementation of changes in BSE regulations.

  2. High-Throughput Screening of Compounds for Anti-Transmissible Spongiform Encephalopathy Activity Using Cell-Culture and Cell-Free Models and Infected Animals

    Science.gov (United States)

    2007-07-01

    and Institute for Antiviral Research, Animal, Dairy and Veterinary Sciences Department, Utah State University, Logan, Utah Received March 2, 2006...Hamilton, Montana,1 and Institute for Antiviral Research, Animal, Dairy, and Veterinary Sciences Department, Utah State University, Logan, Utah2 Received 8

  3. High-Throughput Screening of Compounds for Anti-Transmissible Spongiform Encephalopathy Activity Using Cell-Culture and Cell-Free Models and Infected Animals

    Science.gov (United States)

    2008-07-01

    unconverted but bound 35S-labeled PrPC. The protein in the wells was eluted by boiling in sodium dodecyl sulfate sample buffer and scintillation counted...presumably due to the intramolecular quenching caused by the presence of the 2-O-methyl modification), with rh-Randomers 2 and 3 having intensities that...ligands such as hemin and metal ions can isolate PrPC from a macromolecular complex involved in neuronal plasticity and help organize PrPC into supramo

  4. High-Throughput Screening of Compounds for Anti-Transmissible Spongiform Encephalopathy Activity Using Cell-Culture and Cell-Free Models and Infected Animals

    National Research Council Canada - National Science Library

    Caughey, Byron; Kocisko, David

    2007-01-01

    .... To advance the rational basis for the search for anti-TSE therapeutics, we have developed a new unified mechanistic model for the activity of various classes of PrPSc inhibitors which is consistent...

  5. Hypoxic Ischaemic Encephalopathy among Asphyxiated Nigeran ...

    African Journals Online (AJOL)

    To compare the clinical presentation and immediate outcome of Hypoxic Ischaemic Encephalopathy among hospitalized asphyxiated newborns. Babies hospitalised with birth asphyxia in a Nigerian tertiary hospital were prospectively studied uding bivariate analysis. of 114 babies hospitalized with birth asphyxia, ...

  6. Hepatic encephalopathy: experimental studies on the pathogenesis

    NARCIS (Netherlands)

    R.J. de Knegt (Robert)

    1993-01-01

    textabstractAims of this thesis: 1. To study, in rabbits, the suitability of experimental acute liver failure and acute hyperammonemia simulating acute liver failure for the study of hepatic encephalopathy and ammonia toxicity. 2. To study glutamate neurotransmission in rabbits with acute liver

  7. Wernicke's Encephalopathy in a Nigerian with Schizophrenia ...

    African Journals Online (AJOL)

    While Wernicke's encephalopathy (WE) is a well-characterized syndrome in alcoholism and malnutrition, little is written of its prevalence or presentation in patients with psychiatric illness. We present a case of a 37-year-old Nigerian male with schizophrenia and malnutrition who presented with delirium and ophthalmoplegia ...

  8. Posterior reversible encephalopathy syndrome: Some novel ...

    African Journals Online (AJOL)

    Two cases occurred following cerebral anoxia due to accidental strangulation and near-drowning, respectively. The third patient, a child known to have E-β thalassaemia, presented with transient encephalopathy following blood transfusion but involving the anterior brain rather than the posterior part classically described in ...

  9. Wernicke encephalopathy in children and adolescents.

    Science.gov (United States)

    Lallas, Matt; Desai, Jay

    2014-11-01

    Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency. It is generally considered to be a disease of adult alcoholics. However, it is known to occur in the pediatric population and in non-alcoholic conditions. We searched PubMed with the key words Wernicke, thiamine, pediatric, children and adolescents and selected publications that were deemed appropriate. The global prevalence rates of hunger, poverty and resultant nutrient deprivation have decreased in the 21st century. However, several scenarios which may predispose to Wernicke encephalopathy may be increasingly prevalent in children and adolescents such as malignancies, intensive care unit stays and surgical procedures for the treatment of obesity. Other predisposing conditions include magnesium deficiency and defects in the SLC19A3 gene causing thiamine transporter-2 deficiency. The classic triad consists of encephalopathy, oculomotor dysfunction and gait ataxia but is not seen in a majority of patients. Treatment should be instituted immediately when the diagnosis is suspected clinically without waiting for laboratory confirmation. Common magnetic resonance findings include symmetric T2 hyperintensities in dorsal medial thalamus, mammillary bodies, periaqueductal gray matter, and tectal plate. Wernicke encephalopathy is a medical emergency. Delay in its recognition and treatment may lead to significant morbidity, irreversible neurological damage or even death. This article aims to raise the awareness of this condition among pediatricians.

  10. CT diagnosis of hypoxic ischemic encephalopathy

    International Nuclear Information System (INIS)

    Zhao Xiang; Ma Jiwei; Wu Lide

    2004-01-01

    Objective: To explore CT characteristics of hypoxic ischemic encephalopathy (HIE), and to improve the accuracy of CT diagnosis. Methods: 50 cases of neonatal asphyxia in perinatal period diagnosed as hypoxic ischemic encephalopathy by CT was analyzed. Results: The main manifestation of hypoxic ischemic encephalopathy is cerebral edema and intracranial hemorrhage. Focal or diffuse hypo-dense lesion and hyper-dense area in various location and morphology were seen on CT images. (1) Localized diffuse hypo-dense area in 1 or 2 cerebral lobe were found in 17 cases, and the lesions were localized in frontal lobe (n=6), in frontotemporal lobe (n=5), and in temporo-occipital lobe (n=6). (2) Hypo-density region involving more than three cerebral lobes were found in 18 cases, and abnormalities were found in frontotemporal and parietal lobe (n=8), accompanying with subarachnoid hemorrhage (n=2); in frontal, temporal and occipital lobe (n=6), in which cerebral hemorrhage was complicated (n=1); and in other cerebral lobe (n=4). (3) Diffuse low-density region in all cerebral lobe were found in 15 cases, in which subarachnoid hemorrhage was complicated in 4 cases, and ventricular hemorrhage was found in 2 case. Conclusion: CT imaging plays an important role in diagnosis of hypoxic ischemic encephalopathy and has shown its clinical value

  11. Post-infectious encephalopathy simulating functional psychosis.

    Science.gov (United States)

    Spihtle, B J; Fliegner, J; Faed, J A; Hannah, J B; James, B

    1977-03-09

    Three cases of post-infectious encephalopathy are presented in which behaviour changes occurred in the absence of neurological abnormality during convalescence from an influenza-like illness. The symptoms included aggresive behaviour, sleep reversal, sexual disinbition and a catatonic schizophrenia-like state. The prognosis was good.

  12. Diverse Neurological Manifestations of Lead Encephalopathy ...

    African Journals Online (AJOL)

    Three patients with lead encephalopathy due to industrial poisoning are presented. They all showed a wide spectrum of neurological manifestations, which mimic other neurological presentations. It is emphasised that lead poisoning still occurs in industry, despite efforts at prevention. S. Afr. Med. J., 48, 1721 (1974) ...

  13. Wernicke’s encephalopathy following hyperemesis gravidarum

    Directory of Open Access Journals (Sweden)

    Leila Pourali

    2016-06-01

    Full Text Available Background: ″Wernicke’s Korsakoff″ syndrome is the most important complication of severe thiamine deficiency. The term refers to two different syndromes, each representing a different stage of the disease. Wernicke’s encephalopathy (WE is an acute syndrome requiring emergent treatment to prevent death and neurologic morbidity. Korsakoff syndrome (KS refers to a chronic neurologic condition that usually occurs as a consequence of WE. It is a rare complication of hyperemesis gravidarum that confusion, ocular signs, and gait ataxia are the most prevalent symptoms, respectively. Typical brain lesions of wernicke’s encephalopathy (WE are observed at autopsy in 0.4 to 2.8 percent of the general population in the western world and the majority of affected patients are alcoholic. The prevalence of wernicke’s encephalopathy lesions seen on autopsy was 12.5% of alcohol abusers in one report. Among those who with alcohol-related death, it has been reported to be even higher, 29 to 59%. The aim of this study was to report a case of wernicke’s encephalopathy following hyperemesis gravidarum. Case Presentation: A 28-year-old-pregnant woman in 19th weeks of gestation referred to the hospital with hyperemesis, gait ataxia, and dysarthria before that she had hyperemesis gravidarum with weight loss and unresponsive to outpatient and inpatient medical therapy. MRI showed hyperdense lesion around thalamus which was characteristic of wernicke’s encephalopathy. Rapid improvement in patient’s condition occurred after high dose thiamine infusion. Conclusion: In hyperemesis gravidarum, presence of either symptoms of ocular or mental disorder or ataxia must be considered to rule out and appropriate treatment of Wernicke’s syndrome which can cause maternal and fetal death.

  14. Postinhibitory rebound neurons and networks are disrupted in retrovirus-induced spongiform neurodegeneration.

    Science.gov (United States)

    Li, Ying; Davey, Robert A; Sivaramakrishnan, Shobhana; Lynch, William P

    2014-08-01

    Certain retroviruses induce progressive spongiform motor neuron disease with features resembling prion diseases and amyotrophic lateral sclerosis. With the neurovirulent murine leukemia virus (MLV) FrCasE, Env protein expression within glia leads to postsynaptic vacuolation, cellular effacement, and neuronal loss in the absence of neuroinflammation. To understand the physiological changes associated with MLV-induced spongiosis, and its neuronal specificity, we employed patch-clamp recordings and voltage-sensitive dye imaging in brain slices of the mouse inferior colliculus (IC), a midbrain nucleus that undergoes extensive spongiosis. IC neurons characterized by postinhibitory rebound firing (PIR) were selectively affected in FrCasE-infected mice. Coincident with Env expression in microglia and in glia characterized by NG2 proteoglycan expression (NG2 cells), rebound neurons (RNs) lost PIR, became hyperexcitable, and were reduced in number. PIR loss and hyperexcitability were reversed by raising internal calcium buffer concentrations in RNs. PIR-initiated rhythmic circuits were disrupted, and spontaneous synchronized bursting and prolonged depolarizations were widespread. Other IC neuron cell types and circuits within the same degenerative environment were unaffected. Antagonists of NMDA and/or AMPA receptors reduced burst firing in the IC but did not affect prolonged depolarizations. Antagonists of L-type calcium channels abolished both bursts and slow depolarizations. IC infection by the nonneurovirulent isogenic virus Friend 57E (Fr57E), whose Env protein is structurally similar to FrCasE, showed no RN hyperactivity or cell loss; however, PIR latency increased. These findings suggest that spongiform neurodegeneration arises from the unique excitability of RNs, their local regulation by glia, and the disruption of this relationship by glial expression of abnormal protein. Copyright © 2014 the American Physiological Society.

  15. Autism spectrum disorder and epileptic encephalopathy: common causes, many questions.

    Science.gov (United States)

    Srivastava, Siddharth; Sahin, Mustafa

    2017-01-01

    Epileptic encephalopathies represent a particularly severe form of epilepsy, associated with cognitive and behavioral deficits, including impaired social-communication and restricted, repetitive behaviors that are the hallmarks of autism spectrum disorder (ASD). With the advent of next-generation sequencing, the genetic landscape of epileptic encephalopathies is growing and demonstrates overlap with genes separately implicated in ASD. However, many questions remain about this connection, including whether epileptiform activity itself contributes to the development of ASD symptomatology. In this review, we compiled a database of genes associated with both epileptic encephalopathy and ASD, limiting our purview to Mendelian disorders not including inborn errors of metabolism, and we focused on the connection between ASD and epileptic encephalopathy rather than epilepsy broadly. Our review has four goals: to (1) discuss the overlapping presentations of ASD and monogenic epileptic encephalopathies; (2) examine the impact of the epilepsy itself on neurocognitive features, including ASD, in monogenic epileptic encephalopathies; (3) outline many of the genetic causes responsible for both ASD and epileptic encephalopathy; (4) provide an illustrative example of a final common pathway that may be implicated in both ASD and epileptic encephalopathy. We demonstrate that autistic features are a common association with monogenic epileptic encephalopathies. Certain epileptic encephalopathy syndromes, like infantile spasms, are especially linked to the development of ASD. The connection between seizures themselves and neurobehavioral deficits in these monogenic encephalopathies remains open to debate. Finally, advances in genetics have revealed many genes that overlap in ties to both ASD and epileptic encephalopathy and that play a role in diverse central nervous system processes. Increased attention to the autistic features of monogenic epileptic encephalopathies is warranted for

  16. The Thompson Encephalopathy Score and Short-Term Outcomes in Asphyxiated Newborns Treated With Therapeutic Hypothermia

    NARCIS (Netherlands)

    Thorsen, Patricia; Jansen-van der Weide, Martine C.; Groenendaal, Floris; Onland, Wes; van Straaten, Henrika L. M.; Zonnenberg, Inge; Vermeulen, Jeroen R.; Dijk, Peter H.; Dudink, Jeroen; Rijken, Monique; van Heijst, Arno; Dijkman, Koen P.; Cools, Filip; Zecic, Alexandra; van Kaam, Anton H.; de Haan, Timo R.

    2016-01-01

    The Thompson encephalopathy score is a clinical score to assess newborns suffering from perinatal asphyxia. Previous studies revealed a high sensitivity and specificity of the Thompson encephalopathy score for adverse outcomes (death or severe disability). Because the Thompson encephalopathy score

  17. Epileptic encephalopathy as models of system epilepsy.

    Science.gov (United States)

    Capovilla, Giuseppe; Moshé, Solomon L; Wolf, Peter; Avanzini, Giuliano

    2013-11-01

    The pathophysiology of epileptic encephalopathies has long been debated. Recently, some authors proposed the new concept of so-called system epilepsies. This hypothesis postulates that system epilepsies are produced by the enduring propensity to generate seizures in different cerebral areas that, alone, are unable to create a specific electroclinical phenotype. This goes beyond the classical dichotomy between focal and generalized epilepsy. Epileptic encephalopathies, in general, have the ideal profile to be considered as system epilepsies, and West syndrome and Lennox-Gastaut syndrome are two of the best examples. Apart from the conventional neurophysiologic methods for studying brain activities and the pathophysiologic mechanisms underlying epileptic syndromes, other new methods of neuroimaging support this hypothesis. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  18. Encephalopathy Associated With Autoimmune Thyroid Disease

    OpenAIRE

    li A. Raouf; Gianluca Tamagno

    2014-01-01

    Autoimmune thyroid diseases (ATDs) are immune-endocrine disorders affecting the thyroid gland and, eventually, also a number of other systemic targets, including the brain and the nervous system. Encephalopathy associated with autoimmune thyroid disease (EAATD) is a rare, heterogeneous condition arising from the background of an ATD. It is characterised by neurological and/or psychiatric symptoms with acute or sub-acute onset, and virtually any neurological or psychiatric symptom can appear. ...

  19. Qualifying and quantifying minimal hepatic encephalopathy

    DEFF Research Database (Denmark)

    Morgan, Marsha Y; Amodio, Piero; Cook, Nicola A

    2016-01-01

    Minimal hepatic encephalopathy is the term applied to the neuropsychiatric status of patients with cirrhosis who are unimpaired on clinical examination but show alterations in neuropsychological tests exploring psychomotor speed/executive function and/or in neurophysiological variables......, liver-related mortality and morbidity. Patients will only benefit in this way if they can be effectively diagnosed. Corporate efforts and consensus agreements are needed to develop effective diagnostic algorithms....

  20. Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion

    Directory of Open Access Journals (Sweden)

    Adrienne Hughes

    2016-09-01

    Full Text Available Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects.

  1. Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion.

    Science.gov (United States)

    Hughes, Adrienne; Brown, Alisha; Valento, Matthew

    2016-09-01

    Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects.

  2. Wernicke's encephalopathy induced by hyperemesis gravidarum

    Science.gov (United States)

    Palacios-Marqués, Ana; Delgado-García, Silvia; Martín-Bayón, Tina; Martínez-Escoriza, Juan Carlos

    2012-01-01

    Wernicke's encephalopathy (WE) is a reversible neurological emergency caused by thiamine deficiency. Prolonged vomiting in pregnancy results in thiamine depletion. The early recognition of its clinical signs and symptoms is essential to establish the suspected diagnosis and can be confirmed by MRI. Prompt administration of thiamine is important for preventing the occurrence of sequelae in the mother and for improving the fetal prognostic. We report a case of WE induced by hyperemesis gravidarum with a good maternal and fetal outcome. PMID:22684836

  3. Pyridoxal phosphate-dependent neonatal epileptic encephalopathy

    OpenAIRE

    Bagci, S; Zschocke, J; Hoffmann, G F; Bast, T; Klepper, J; Müller, A; Heep, A; Bartmann, P; Franz, A R

    2009-01-01

    Pyridox(am)ine-5′-phosphate oxidase converts pyridoxine phosphate and pyridoxamine phosphate to pyridoxal phosphate, a cofactor in many metabolic reactions, including neurotransmitter synthesis. A family with a mutation in the pyridox(am)ine-5′-phosphate oxidase gene presenting with neonatal seizures unresponsive to pyridoxine and anticonvulsant treatment but responsive to pyridoxal phosphate is described. Pyridoxal phosphate should be considered in neonatal epileptic encephalopathy unrespons...

  4. Valproate-Induced Encephalopathy in Three Cases

    Directory of Open Access Journals (Sweden)

    Fatma Polat

    2010-12-01

    Full Text Available Valproic acid-induced encephalopathy is a serious complication of valproate, rarely observed, and can lead to death if early diagnosis is not made. It is clinically presented as mental status changes that range from drowsiness to lethargy and coma, focal or bilateral neurological deficits, seizure, vomiting, and marked electroencephalography (EEG background slowing, with or without hyperammonemia. It can also be properly managed by discontinuation of the drug. We present three cases who developed vomiting, disturbance in consciousness, EEG-slowing, and elevated serum ammonia levels. In all cases, symptoms resolved after termination of valproate. Most notably, these side effects occurred in the presence of normal liver enzymes and normal valproate concentrations. Development of unconsciousness and associated EEG slow waves are observed rarely in VPA-induced encephalopathy, and this is discussed together with a review of the literature. Serum ammonia level is an important parameter in the early diagnosis of this rare adverse event. The clinical symptomatology and EEG findings have significant importance in the differential diagnosis when encephalopathy occurs without hyperammonemia and with normal or slight increase in serum ammonia level

  5. Valproate-Induced Encephalopathy in Three Cases

    Directory of Open Access Journals (Sweden)

    Fatma Polat

    2010-12-01

    Full Text Available Valproic acid-induced encephalopathy is a serious complication of valproate, rarely observed, and can lead to death if early diagnosis is not made. It is clinically presented as mental status changes that range from drowsiness to lethargy and coma, focal or bilateral neurological deficits, seizure, vomiting, and marked electroencephalography (EEG background slowing, with or without hyperammonemia. It can also be properly managed by discontinuation of the drug. We present three cases who developed vomiting, disturbance in consciousness, EEG-slowing, and elevated serum ammonia levels. In all cases, symptoms resolved after termination of valproate. Most notably, these side effects occurred in the presence of normal liver enzymes and normal valproate concentrations. Development of unconsciousness and associated EEG slow waves are observed rarely in VPA-induced encephalopathy, and this is discussed together with a review of the literature. Serum ammonia level is an important parameter in the early diagnosis of this rare adverse event. The clinical symptomatology and EEG findings have significant importance in the differential diagnosis when encephalopathy occurs without hyperammonemia and with normal or slight increase in serum ammonia level.

  6. BLOOD BIOMARKERS FOR EVALUATION OF PERINATAL ENCEPHALOPATHY

    Directory of Open Access Journals (Sweden)

    Ernest Marshall Graham

    2016-07-01

    Full Text Available Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the liquid brain biopsy. A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment.

  7. Epileptic encephalopathies (including severe epilepsy syndromes).

    Science.gov (United States)

    Covanis, Athanasios

    2012-09-01

    Epileptic encephalopathies represent a group of devastating epileptic disorders that appear early in life and are characterized by pharmacoresistant generalized or focal seizures, persistent severe electroencephalography (EEG) abnormalities, and cognitive dysfunction or decline. The ictal and interictal epileptic discharges are age-specific and are the main etiologic factors causing cognitive deterioration. This is most obvious in the idiopathic group. In the symptomatic group, the most common causes are structural, congenital, or acquired and rarely some metabolic disorders. In certain cases, clinical and EEG abnormalities persist and may evolve from one type to another as the child grows older. Various factors trigger and sustain the underlying pathophysiologic process and the ongoing epileptic and epileptiform activity during the most critical periods of brain maturation, perpetuating their deleterious effect on the brain. Immune-mediated mechanisms may have a role, suggested by certain encephalopathies responding to immune-modulating treatments and by the finding of various autoimmune antibodies. The chance of a better cognitive outcome improves with early diagnosis and treatment that is appropriate and effective. Current antiepileptic drugs are, in general, not effective: we urgently need new trials in this very special epileptic category. This article briefly reviews the most common epileptic encephalopathies and analyzes the most important clinical issues. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  8. Genetics Home Reference: acute necrotizing encephalopathy type 1

    Science.gov (United States)

    ... induced acute encephalopathy 3 Related Information How are genetic conditions and genes named? ... National Institute of Allergy and Infectious Diseases: Flu (Influenza) National Institute of Neurological Disorders ...

  9. Intravenous methylprednisolone pulse therapy for children with epileptic encephalopathy

    OpenAIRE

    Pera, Maria Carmela; Randazzo, Giovanna; Masnada, Silvia; Dontin, Serena Donetti; De Giorgis, Valentina; Balottin, Umberto; Veggiotti, Pierangelo

    2015-01-01

    The aim of this retrospective study of children affected by epileptic encephalopathy was to evaluate seizure frequency, electroencephalographic pattern and neuropsychological status, before and after intravenous methylprednisolone therapy.

  10. A case of spongiform polioencephalomyelopathy in a cat with a history of behavioural problems

    Directory of Open Access Journals (Sweden)

    Tomàs Camps

    2015-08-01

    Full Text Available A 7-month-old, entire female, domestic shorthair cat was referred to our behavioural service owing to soiling in the house and a play-related problem. The owners’ complaints were that the cat had never used the litter tray, and it did not know how to play. After reviewing the behavioural history, a problem of substrate preferences acquisition was suspected with regard to the elimination problem. During the consultation, the physical examination was unremarkable, but the neurological examination revealed a moderate and hypermetric ataxic gait, and a bilateral lack of menace response. Some degree of visual impairment was suspected. The problem was located in the central nervous system (CNS; specifically, an intracranial and multifocal problem was diagnosed. After a complete work-up (complete ophthalmological examination, complete blood count and a complete biochemistry panel, feline immunodeficiency virus/feline leukaemia virus test, thorax radiographs, abdominal ultrasound, brain magnetic resonance imaging [0.2 T], cerebrospinal fluid analysis and a urinary metabolic screen test, a degenerative CNS problem was suspected. No treatment was prescribed for the neurological problem. Regarding the problem of soiling in the house, reward-based training with a clicker was used, and the cat partially improved in a few weeks. Three months later, the cat was referred to the neurology service in status epilepticus. A symptomatic treatment was prescribed, with a mild response. After 2 years of treatment and a progressive worsening, the cat was euthanased. Necropsy revealed spongiform polioencephalomyelopathy. In order to rule out prion aetiology a PrPsc inmunohistochemistry assay was performed, and the results were negative. Congenital spongiform polioencephalomyelopathy (CSP was diagnosed. We strongly suggest that the cat’s behavioural clinical signs were caused by the CSP, causing learning impairment. To the best of our knowledge, this would be the

  11. Sporadic fatal insomnia with spongiform degeneration in the thalamus and widespread PrPSc deposits in the brain.

    Science.gov (United States)

    Piao, Yue-Shan; Kakita, Akiyoshi; Watanabe, Hiroyuki; Kitamoto, Tetsuyuki; Takahashi, Hitoshi

    2005-06-01

    We report a case of human prion disease of 29 months duration in a 74-year-old Japanese man. The disease started with progressive sleeplessness and dementia. MRI showed gradually progressive cerebral atrophy. Neuronal loss, spongiform change and gliosis were evident in the thalamus and cerebral cortex, as well as in the striatum and amygdaloid nucleus. In the cerebellar cortex, mild-to-moderate depletion of Pukinje cells and spongiform change were observed. Mild neuronal loss in the inferior olivary nucleus was also seen. Immunohistochemistry revealed widespread perivacuolar deposits of abnormal prion protein (PrPsc) in the cerebral cortex, thalamus, basal ganglia, and brainstem, and minimal plaque-like deposits of PrPSc in the cerebellar cortex. In the cerebellar plaque-like deposits, the presence of amyloid fibrils was confirmed ultrastructurally. The entire pathology appeared to lie halfway between those of CJD and fatal insomnia, and further demonstrated the relationship between spongiform degeneration and PrPSc deposits, especially in the diseased thalamus. By immunoblotting, the thalamus was shown to contain the lowest amount of PrPSc among the brain regions examined. The PrPSc of type 2, in which the ratio of the three glycoforms was compatible with that of sporadic fatal insomnia (MM2-thalamic variant) reported previously, was also demonstrated. Analysis of the prion protein gene (PRNP) showed no mutation, and homozygosity for methionine at codon 129. In conclusion, we considered that this patient had been suffering from sporadic, pathologically atypical fatal insomnia.

  12. MRI features of patients with heroin spongiform leukoencephalopathy of different clinical stages

    International Nuclear Information System (INIS)

    Shi Zhu; Pan Suyue; Zhou Liang; Dong Zhao; Lu Bingxun

    2007-01-01

    Objective: To investigate radiological features of patients with heroin spongiform leukoencephalopathy (HSLE) of different clinical stages and discuss the evolutional characteristics of the disease. Methods: Thirty two patients with HSLE underwent precontrast MRI and postcontrast MRI. The history of addiction, clinical presentations, and brain MRI were analyzed and summarized according to the patient's clinical staging. There are 6 cases in I stage, 21 cases in II stage, 5 cases in III stage. Results: All patients had history of heroin vapor inhalation. Most of the cases developed subacute cerebellar impairment in earlier period. Brain MRI revealed symmetrical lesion within bilateral cerebellum in all patients. Splenium of the corpus callosum, posterior limb of the internal capsule, deep white matter of the occipital and parietal lobes, were gradually involved with progressive deterioration of HSLE. The brain stem and deep white matter of the frontal and temporal lobes were involved in some cases. Conclusions: The history of heated heroin vapor inhalation was the prerequisite for the diagnosis of HSLE. Brain MRI presented the characteristic lesion and its evolution of HSLE. Brain MRI was very important for accurate diagnosis and helpful to judge the clinical stages according to the involved brain region. (authors)

  13. Transient cardiac arrest in patient with left ventricular noncompaction (spongiform cardiomyopathy).

    Science.gov (United States)

    Yamazaki, Shinya; Ito, Hiroshi; Kawaai, Hiroyoshi

    2011-01-01

    Left ventricular noncompaction (LVNC), also known as spongiform cardiomyopathy, is a severe disease that has not previously been discussed with respect to general anesthesia. We treated a child with LVNC who experienced cardiac arrest. Dental treatment under general anesthesia was scheduled because the patient had a risk of endocarditis due to dental caries along with a history of being uncooperative for dental care. During sevoflurane induction, severe hypotension and laryngospasm resulted in cardiac arrest. Basic life support (cardiopulmonary resuscitation) was initiated to resuscitate the child, and his cardiorespiratory condition improved. Thereafter, an opioid-based anesthetic was performed, and recovery was smooth. In LVNC, opioid-based anesthesia is suggested to avoid the significant cardiac suppression seen with a volatile anesthetic, once intravenous access is established. Additionally, all operating room staff should master Advanced Cardiac Life Support/Pediatric Advanced Life Support (including intraosseous access), and more than 1 anesthesiologist should be present to induce general anesthesia, if possible, for this high-risk patient.

  14. Early onset epileptic encephalopathy or genetically determined encephalopathy with early onset epilepsy? Lessons learned from TSC.

    Science.gov (United States)

    Curatolo, Paolo; Aronica, Eleonora; Jansen, Anna; Jansen, Floor; Kotulska, Katarzyna; Lagae, Lieven; Moavero, Romina; Jozwiak, Sergiusz

    2016-03-01

    In tuberous sclerosis complex (TSC) a relationship has been shown between early and refractory seizures and intellectual disability. However, it is uncertain whether epilepsy in TSC is simply a marker in infants who are destined to develop an encephalopathic process or if seizures play a causal role in developing an encephalopathy. This paper summarizes the key points discussed during a European TSC workshop held in Rome, and reviews the experimental and clinical evidence in support of the two theories. There are many factors that influence the appearance of both early seizure onset and the encephalopathy resulting in neurodevelopmental deficits. Experimental studies show that as a consequence of the TSC genes mutation, mammalian target of Rapamycin (mTOR) overactivation determines an alteration in cellular morphology with cytomegalic neurons, altered synaptogenesis and an imbalance between excitation/inhibition, thus providing a likely neuroanatomical substrate for the early appearance of refractory seizures and for the encephalopathic process. At the clinical level, early signs of altered developmental trajectories are often unrecognized before 12 months of age. Evidence from experimental research shows that encephalopathy in TSC might have a genetic cause, and mTOR activation caused by TSC gene mutation can be directly responsible for the early appearance of seizures and encephalopathy. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  15. Normalization of the psychometric hepatic encephalopathy score for ...

    African Journals Online (AJOL)

    Aim: To construct normal values for the tests of the psychometric hepatic encephalopathy score (PHES) and evaluate the prevalence of minimal hepatic encephalopathy (MHE) among Turkish patients with liver cirrhosis. Materials and Methods: One hundred and eighty-five healthy subjects and sixty patients with liver ...

  16. Chronic liver disease and hepatic encephalopathy: Clinical profile ...

    African Journals Online (AJOL)

    Two patients had acute encephalopathy, while others had acute-on chronic encephalopathy. The risk factors for liver disease included significant alcohol ingestion, hepatitis B virus infection, and previous jaundice, while other complications of liver disease noted were deepening jaundice, ascites, bleeding tendencies, and ...

  17. Hashimoto’s Encephalopathy (A Review Article

    Directory of Open Access Journals (Sweden)

    M. Ghaffar Pour

    2008-10-01

    Full Text Available Background and ObjectivesHashimoto's encephalopathy (HE known as Steroid Responsive Encephalopathy associated with Autoimmune Thyroditis (SREAT is a rare nervous system disease. HE was originally described by Brain, et. al. in 1966, however its cause still remains unknown after about 40 years. Autoimmune vasculitis of CNS, brain edema, and anti-thyroid antibodies are considered some of the etiologies for HE. It is certain that HE is an autoimmune disease and not a thyroid system disease. HE patients may or may not have goiter. Some of the most common neurological manifestations of HE include: Confusion with altered consciousness, seizures, myoloclonus, and cognitive problems. Presence of high titers of anti-thyroid antibodies in blood serum and CSF of HE patients is considered the most common laboratory test for diagnosis of HE. EEG abnormalities such as diffuse slowing and atypical tri-phasic brain waves are the most common findings in about ¾ HE patients. Brain CT-Scan is normal in majority of HE patients. Global or local hypo perfusion may be seen in SPECT scanning of the brain. MRI findings are abnormal in about 40% of HE patients.Patients with sub acute or acute onset of confusion, seizure, myoloclonus, stroke-like episodes and amnesia whose laboratory serum and CSF tests indicate presence of high titers of anti- thyroid antibodies should be considered for having HE. Vascular myelopathies, CJD, HSP, Myelinoclastic disease like PML, SSPE, ADE, MS and DNL are some of the differential diagnosis of HE.Adrenal corticosteroids are the first line treatment for HE. Recurrent or steroid resistant HE cases may be treated by addition of other immunosuppressant drugs such as Azathioprine, Cyclophosphamide, or Methotrexate to the 1st line therapy.Keywords: Hashimoto Diseases; Encephalopathy; Thyroiditis, Autoimmune; Thyroiditis, Autoimmune, Diagnosis; Thyroiditis, Autoimmune, Therapy.

  18. Reversible cortical blindness in a case of hepatic encephalopathy

    Directory of Open Access Journals (Sweden)

    Amlan Kanti Biswas

    2016-01-01

    Full Text Available Hepatic encephalopathy is a frequent and often fatal manifestation of chronic liver disease. The pathogenesis of hepatic encephalopathy is believed to be multifactorial including impaired blood-brain barrier function, imbalance between the excitatory and inhibitory neurotransmitters in cortex, accumulation of various toxic and false neurotransmitters, and lack of nutrients like oxygen and glucose. Signs and symptoms of hepatic encephalopathy varies and commonly ranges from personality changes, disturbed consciousness, sleep pattern alternation, intellectual deterioration, speech disturbances, asterixis to frank coma and even death. Reversible or transient cortical blindness is rare manifestation of hepatic encephalopathy. It may even precede the phase of altered consciousness in such patients. Very few similar cases have been reported worldwide. Hence, we would like to report a case of transient cortical blindness in a patient of hepatic encephalopathy.

  19. Post-partum posterior reversible encephalopathy syndrome

    DEFF Research Database (Denmark)

    Aaen, Anne Albers; Jeppesen, Jørgen; Obaid, Hayder

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a complex clinical condition with vasogenic subcortical oedema caused by hypertension. Oedema is often seen on magnetic resonance imaging. The wide clinical spectrum ranges from headaches to vision loss and even death. Early diagnosis...... and treatment is important for the reversibility of the condition. In this case report we emphasize the importance of blood pressure control in a post-partum woman, who had a rather complicated pregnancy. The symptoms of PRES were not recognized immediately because of failure to use and acknowledge a blood...

  20. Cardiovascular dysfunction in infants with neonatal encephalopathy.

    LENUS (Irish Health Repository)

    Armstrong, Katey

    2012-04-01

    Severe perinatal asphyxia with hypoxic ischaemic encephalopathy occurs in approximately 1-2\\/1000 live births and is an important cause of cerebral palsy and associated neurological disabilities in children. Multiorgan dysfunction commonly occurs as part of the asphyxial episode, with cardiovascular dysfunction occurring in up to a third of infants. This narrative paper attempts to review the literature on the importance of early recognition of cardiac dysfunction using echocardiography and biomarkers such as troponin and brain type natriuretic peptide. These tools may allow accurate assessment of cardiac dysfunction and guide therapy to improve outcome.

  1. Probiotics for people with hepatic encephalopathy.

    Science.gov (United States)

    Dalal, Rohan; McGee, Richard G; Riordan, Stephen M; Webster, Angela C

    2017-02-23

    Hepatic encephalopathy is a disorder of brain function as a result of liver failure or portosystemic shunt or both. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient's quality of life and daily functioning, and represent a significant burden on healthcare resources. Probiotics are live micro-organisms, which when administered in adequate amounts, may confer a health benefit on the host. To determine the beneficial and harmful effects of probiotics in any dosage, compared with placebo or no intervention, or with any other treatment for people with any grade of acute or chronic hepatic encephalopathy. This review did not consider the primary prophylaxis of hepatic encephalopathy. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, conference proceedings, reference lists of included trials, and the World Health Organization International Clinical Trials Registry Platform until June 2016. We included randomised clinical trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in people with hepatic encephalopathy. We used standard methodological procedures expected by The Cochrane Collaboration. We conducted random-effects model meta-analysis due to obvious heterogeneity of participants and interventions. We defined a P value of 0.05 or less as significant. We expressed dichotomous outcomes as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). We included 21 trials with 1420 participants, of these, 14 were new trials. Fourteen trials compared a probiotic with placebo or no treatment, and seven trials compared a probiotic with lactulose. The trials used a variety of probiotics; the most commonly used group of probiotic was VSL#3, a proprietary name for a group of eight probiotics. Duration of administration

  2. Probiotics in management of hepatic encephalopathy.

    Science.gov (United States)

    Sharma, Barjesh Chander; Singh, Jatinderpal

    2016-12-01

    Gut microflora leads to production of ammonia and endotoxins which play important role in the pathogenesis of hepatic encephalopathy (HE). There is relationship between HE and absorption of nitrogenous substances from the intestines. Probiotics play a role in treatment of HE by causing alterations in gut flora by decreasing the counts of pathogen bacteria, intestinal mucosal acidification, decrease in production and absorption of ammonia, alterations in permeability of gut, decreased endotoxin levels and changes in production of short chain fatty acids. Role of gut microbiota using prebiotics, probiotics and synbiotics have been evaluated in the management of minimal hepatic encephalopathy (MHE), overt HE and prevention of HE. Many studies have shown efficacy of probiotics in reduction of blood ammonia levels, treatment of MHE and prevention of HE. However these trials have problems like inclusion of small number of patients, short treatment durations, variability in HE/MHE related outcomes utilized and high bias risk, errors of systematic and random types. Systematic reviews also have shown different results with one systematic review showing clinical benefits whereas another concluded that probiotics do not have any role in treatment of MHE or HE. Also practical questions on optimal dose, ideal combination of organisms, and duration of treatment and persistence of benefits on long term follow-up are still to be clarified. At present, there are no recommendations for use of probiotics in patients with HE.

  3. The why and wherefore of hepatic encephalopathy

    Directory of Open Access Journals (Sweden)

    Grover VPB

    2015-12-01

    Full Text Available Vijay PB Grover, Joshua M Tognarelli, Nicolas Massie, Mary ME Crossey, Nicola A Cook, Simon D Taylor-Robinson Liver Unit, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, UK Abstract: Hepatic encephalopathy is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease. It was probably first described by Hippocrates over 2000 years ago, who said that "those whose madness arises from phlegm are quiet and neither shout nor make a disturbance, while those whose madness arises from bile shout, play tricks and will not keep still, but are always up to some mischief". He was presumably describing the differences between patients with pneumonia and acute liver failure. Despite the fact that the syndrome was probably first recognized thousands of years ago, the exact pathogenesis still remains unclear. Furthermore, a precise definition of the syndrome is lacking, as are definitive methods of diagnosing this condition. It is important as both patients with cirrhosis and the general population with whom they interact may be affected as a consequence. At a minimum, the individual may be affected by impaired quality of life, impaired ability to work, and slowed reaction times, which are relevant to the population at large if affected individuals operate heavy machinery or drive a car. Pathogenic mechanisms, diagnostic tools, and treatment options are discussed. Keywords: hepatic encephalopathy, cirrhosis, ammonia, pathology, treatment, rifaximin, lactulose

  4. [Clinical Features and Treatment of Hashimoto Encephalopathy].

    Science.gov (United States)

    Maki, Yoshimitsu; Takashima, Hiroshi

    2016-09-01

    Hashimoto encephalopathy (HE) is characterized by heterogeneous neurological symptoms. HE is diagnosed based on three criteria-the presence of antithyroid antibodies, neurological symptoms from the cerebrum and/or cerebellum, and a positive response to immunotherapy. We clinically analyzed 18 patients (3 men, 15 women; age range, 38-81years) diagnosed with HE in our hospital from May 2013 to January 2016. Eleven patients showed sensory abnormalities such as strong pain, deep muscle pain, dysesthesia, paresthesia, or neuralgia. Surprisingly, the majority of the pain was distributed in a manner that was not explainable anatomically. Seventeen patients showed motor disturbances, such as weakness, paresis of extremities, or dexterity movement disorder, and eight patients showed give-way weakness, which is disruption of continuous muscle contraction. Other symptoms indicative of brain-related anomalies such as tremor, dystonia, involuntary movements, cerebellar ataxia, parkinsonism, memory loss, and chronic fatigue were also seen. In most patients, such motor, sensory, or higher brain functions were markedly improved with immunosuppressive therapies such as prednisolone, azathioprine, or immunoadsorption therapy. Although give-way weakness and anatomically unexplainable pain are typically considered as being psychogenic in origin, the presence of these symptoms is indicative of HE. HE exhibits diffuse involvement of the entire brain and thus, these symptoms are explainable. We propose that physicians should not diagnose somatoform disorders without first excluding autoimmune encephalopathy.

  5. [Clinical importance and diagnostic methods of minimal hepatic encephalopathy].

    Science.gov (United States)

    Stawicka, Agnieszka; Zbrzeźniak, Justyna; Świderska, Aleksandra; Kilisińska, Natalia; Świderska, Magdalena; Jaroszewicz, Jerzy; Flisiak, Robert

    2016-02-01

    Minimal hepatic encephalopathy (MHE) encompasses a number of neuropsychological and neurophysiological disorders in patients suffering from liver cirrhosis, who do not display abnormalities during a medical interview or physical examination. A negative influence of MHE on the quality of life of patients suffering from liver cirrhosis was confirmed, which include retardation of ability of operating motor vehicles and disruption of multiple health-related areas, as well as functioning in the society. The data on frequency of traffic offences and accidents amongst patients diagnosed with MHE in comparison to patients diagnosed with liver cirrhosis without MHE, as well as healthy persons is alarming. Those patients are unaware of their disorder and retardation of their ability to operate vehicles, therefore it is of utmost importance to define this group. The term minimal hepatic encephalopathy (formerly "subclinical" encephalopathy) erroneously suggested the unnecessity of diagnostic and therapeutic procedures in patients with liver cirrhosis. Diagnosing MHE is an important predictive factor for occurrence of overt encephalopathy - more than 50% of patients with this diagnosis develop overt encephalopathy during a period of 30 months after. Early diagnosing MHE gives a chance to implement proper treatment which can be a prevention of overt encephalopathy. Due to continuing lack of clinical research there exist no commonly agreed-upon standards for definition, diagnostics, classification and treatment of hepatic encephalopathy. This article introduces the newest findings regarding the importance of MHE, scientific recommendations and provides detailed descriptions of the most valuable diagnostic methods. © 2016 MEDPRESS.

  6. Harnessing gene expression networks to prioritize candidate epileptic encephalopathy genes.

    Science.gov (United States)

    Oliver, Karen L; Lukic, Vesna; Thorne, Natalie P; Berkovic, Samuel F; Scheffer, Ingrid E; Bahlo, Melanie

    2014-01-01

    We apply a novel gene expression network analysis to a cohort of 182 recently reported candidate Epileptic Encephalopathy genes to identify those most likely to be true Epileptic Encephalopathy genes. These candidate genes were identified as having single variants of likely pathogenic significance discovered in a large-scale massively parallel sequencing study. Candidate Epileptic Encephalopathy genes were prioritized according to their co-expression with 29 known Epileptic Encephalopathy genes. We utilized developing brain and adult brain gene expression data from the Allen Human Brain Atlas (AHBA) and compared this to data from Celsius: a large, heterogeneous gene expression data warehouse. We show replicable prioritization results using these three independent gene expression resources, two of which are brain-specific, with small sample size, and the third derived from a heterogeneous collection of tissues with large sample size. Of the nineteen genes that we predicted with the highest likelihood to be true Epileptic Encephalopathy genes, two (GNAO1 and GRIN2B) have recently been independently reported and confirmed. We compare our results to those produced by an established in silico prioritization approach called Endeavour, and finally present gene expression networks for the known and candidate Epileptic Encephalopathy genes. This highlights sub-networks of gene expression, particularly in the network derived from the adult AHBA gene expression dataset. These networks give clues to the likely biological interactions between Epileptic Encephalopathy genes, potentially highlighting underlying mechanisms and avenues for therapeutic targets.

  7. Minimal hepatic encephalopathy characterized by parallel use of the continuous reaction time and portosystemic encephalopathy tests

    DEFF Research Database (Denmark)

    Lauridsen, M M; Schaffalitzky de Muckadell, O B; Vilstrup, H

    2015-01-01

    based vs. paper and pencil). To compare results of the Continuous Reaction time (CRT) and the Portosystemic Encephalopathy (PSE) tests in a large unselected cohort of cirrhosis patients without clinically detectable brain impairment and to clinically characterize the patients according to their test...... results. The CRT method is a 10-minute computerized test of a patient's motor reaction time stability (CRTindex) to 150 auditory stimuli. The PSE test is a 20-minute paper-pencil test evaluating psychomotor speed. Both tests were performed at the same occasion in 129 patients. Both tests were normal......Minimal hepatic encephalopathy (MHE) is a frequent complication to liver cirrhosis that causes poor quality of life, a great burden to caregivers, and can be treated. For diagnosis and grading the international guidelines recommend the use of psychometric tests of different modalities (computer...

  8. Current concepts in the assessment and treatment of hepatic encephalopathy.

    LENUS (Irish Health Repository)

    Cash, W J

    2012-02-01

    Hepatic encephalopathy (HE) is defined as a metabolically induced, potentially reversible, functional disturbance of the brain that may occur in acute or chronic liver disease. Standardized nomenclature has been proposed but a standardized approach to the treatment, particularly of persistent, episodic and recurrent encephalopathy associated with liver cirrhosis has not been proposed. This review focuses on the pathogenesis and treatment of HE in patients with cirrhosis. The pathogenesis and treatment of hepatic encephalopathy in fulminant hepatic failure is quite different and is reviewed elsewhere.

  9. Dengue viral infections as a cause of encephalopathy

    Directory of Open Access Journals (Sweden)

    Malavige G

    2007-01-01

    Full Text Available The aim of this study was to determine the clinical characteristics and poor prognostic factors associated with high mortality in dengue encephalopathy. Fifteen patients with confirmed dengue infections, who developed encephalopathy, were recruited from two tertiary care hospitals in Colombo, Sri Lanka. Among the factors that contributed to encephalopathy were: Acute liver failure (73%, electrolyte imbalances (80% and shock (40%. Five (33.3% patients developed seizures. Disseminated intravascular coagulation was seen in five (33.3%. Secondary bacterial infections were observed in 8 (53.3% of our patients. The overall mortality rate was 47%.

  10. Excitotoxicity in encephalopathy associated with STEC O-157 infection.

    Science.gov (United States)

    Ishida, Shigenobu; Yasukawa, Kumi; Koizumi, Mai; Abe, Katsuhiro; Hirai, Nozomi; Honda, Takafumi; Sakuma, Hiroshi; Tada, Hiroko; Takanashi, Jun-Ichi

    2018-04-01

    Cytokines play an important role in the pathogenesis of the severe complications of Shiga toxin-producing Escherichia coli (STEC) infection, such as hemolytic uremic syndrome (HUS) and acute encephalopathy. A 3-year-old boy with acute encephalopathy associated with STEC O-157 HUS showed increased levels of IL-6 and IL-10, which normalized after methylprednisolone pulse therapy, and additionally exhibited a transient increase of glutamine on MR spectroscopy. This finding suggests that excitotoxicity, in addition to hypercytokinemia, may play an important role in the pathogenesis of HUS encephalopathy. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  11. Severe early onset ethylmalonic encephalopathy with West syndrome.

    Science.gov (United States)

    Papetti, Laura; Garone, Giacomo; Schettini, Livia; Giordano, Carla; Nicita, Francesco; Papoff, Paola; Zeviani, Massimo; Leuzzi, Vincenzo; Spalice, Alberto

    2015-12-01

    Ethylmalonic encephalopathy (EE) is a rare autosomal recessive disorder characterized by early onset encephalopathy, chronic diarrhoea, petechiae, orthostatic acrocyanosis and defective cytochrome c oxidase (COX) in muscle and brain. High levels of lactic, ethylmalonic and methylsuccinic acids are detected in body fluids. EE is caused by mutations in ETHE1 gene, a mitochondrial sulfur dioxygenase. Neurologic signs and symptoms include progressively delayed development, hypotonia, seizures, and abnormal movements. We report on the clinical, electroencephalographic and MRI findings of a baby with a severe early onset encephalopathy associated with novel ETHE1 gene mutation. This is the first case described in literature with an early pure epileptic onset, presenting with West syndrome.

  12. The history of the concept of epileptic encephalopathy.

    Science.gov (United States)

    Capovilla, Giuseppe; Wolf, Peter; Beccaria, Francesca; Avanzini, Giuliano

    2013-11-01

    The first description of epileptic encephalopathies dates back to Dr. West who, in 1857, described the syndrome that took his name. In addition to West syndrome, in the last century other epileptic syndromes entered into the chapter of epileptic encephalopathies. Henry Gastaut has the virtue of having created the modern concept of epileptic encephalopathy and entering it into the official terminology of the International League Against Epilepsy (ILAE). After the first proposal, it was further defined and refined over time. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  13. Chronic traumatic encephalopathy: contributions from the Boston University Center for the Study of Traumatic Encephalopathy.

    Science.gov (United States)

    Riley, David O; Robbins, Clifford A; Cantu, Robert C; Stern, Robert A

    2015-01-01

    Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease associated with repetitive brain trauma (RBT). Initially described in boxers, CTE has now been found in other contact sport athletes with a history of RBT. In recent years, there has been tremendous media attention regarding CTE, primarily because of the deaths of high profile American football players who were found to have CTE upon neuropathological examination. However, the study of CTE remains in its infancy. This review focuses on research from the Centre for the Study of Traumatic Encephalopathy (CSTE) at Boston University. This study reviews the formation of the CSTE, major CSTE publications and current ongoing research projects at the CSTE. The neuropathology of CTE has been well-described. Current research focuses on: methods of diagnosing the disease during life (including the development of biomarkers), examination of CTE risk factors (including genetic susceptibility and head impact exposure variables); description of the clinical presentation of CTE; development of research diagnostic criteria for Traumatic Encephalopathy Syndrome; and assessment of mechanism and pathogenesis. Current research at the BU CSTE is aimed at increasing understanding of the long-term consequences of repetitive head impacts and attempting to begin to answer several of the unanswered questions regarding CTE.

  14. No oxygen delivery limitation in hepatic encephalopathy

    DEFF Research Database (Denmark)

    Gjedde, Albert; Keiding, Susanne; Vilstrup, Hendrik

    2010-01-01

    Hepatic encephalopathy is a condition of reduced brain functioning in which both blood flow and brain energy metabolism declined. It is not known whether blood flow or metabolism is the primary limiting factor of brain function in this condition. We used calculations of mitochondrial oxygen tension...... declined in all gray matter regions of the brain in patients with HE but not significantly in patients with CL. Analysis of flow-metabolism coupling indicated that blood flow declined in HE as a consequence of reduced brain energy metabolism implied by the calculation of increased mitochondrial oxygen...... tensions that patients with HE were unable to utilize. We ascribe the inability to use the delivered oxygen of patients with HE to a specific inhibition associated with oxidative metabolism in mitochondria....

  15. Brain MRI findings in Wernicke encephalopathy.

    Science.gov (United States)

    Wicklund, Meredith R; Knopman, David S

    2013-08-01

    A 71-year-old woman with myelofibrosis on chemotherapy experienced an acute illness with nausea, vomiting, and diarrhea. Two weeks later, she developed an acute confusional state characterized by disorientation and fluctuating alertness with normal speech and language. Her neurologic examination demonstrated an upper motor neuron pattern of right hemiparesis. She reported double vision though ophthalmoparesis was not appreciated. Her gait was normal. While hospitalized, she developed generalized tonic-clonic seizures. Brain MRI revealed a small area of restricted diffusion of the left precentral gyrus (figure). She was diagnosed with a stroke with secondary seizures; however, as the confusional state resolved, she developed profound retrograde and anterograde amnesia. Review of the brain MRI showed high T2 signal in the medial thalamus and contrast enhancement of the mamillary bodies; a diagnosis of Wernicke-Korsakoff syndrome was entertained and she was started on thiamine replacement. The encephalopathy and hemiparesis resolved though she remains severely amnestic.

  16. Wernicke's encephalopathy: expanding the diagnostic toolbox.

    Science.gov (United States)

    Lough, Mary E

    2012-06-01

    Wernicke's encephalopathy (WE) is a life threatening neurological disorder that results from thiamine (Vitamin B1) deficiency. Clinical signs include mental status changes, ataxia, occulomotor changes and nutritional deficiency. The conundrum is that the clinical presentation is highly variable. WE clinical signs, brain imaging, and thiamine blood levels, are reviewed in 53 published case reports from 2001 to 2011; 81 % (43/53) were non-alcohol related. Korsakoff Syndrome or long-term cognitive neurological changes occurred in 28 % (15/53). Seven WE cases (13 %) had a normal magnetic resonance image (MRI). Four WE cases (8 %) had normal or high thiamine blood levels. Neither diagnostic tool can be relied upon exclusively to confirm a diagnosis of WE.

  17. Leucine metabolism in patients with Hepatic Encephalopathy

    International Nuclear Information System (INIS)

    McGhee, A.S.; Kassouny, M.E.; Matthews, D.E.; Millikan, W.

    1986-01-01

    A primed continuous infusion of [ 15 N, 1- 13 C]leucine was used to determine whether increased oxidation and/or protein synthesis of leucine occurs in patients with cirrhosis. Five controls and patients were equilibrated on a metabolic balance diet [0.6 g protein per kg ideal body weight (IBW)]. An additional four patients were equilibrated in the same manner with the same type of diet with a protein level of 0.75 g per kg IBW. Plasma leucine and breath CO 2 enrichments were measured by mass spectrometry. Protein synthesis and leucine metabolism were identical in controls and patients when both were fed a diet with 0.6 g protein/kg IBW. Results indicate that systemic derangements of leucine metabolism are not the cause of Hepatic Encephalopathy

  18. Transcranial electrostimulation in patients with alcoholic encephalopathy

    Directory of Open Access Journals (Sweden)

    Barylnik Yu.B.

    2010-09-01

    Full Text Available The method of transcranial electrostimulation (TES was used for treating patients with alcoholic encephalopathy against the background of the basic treatment, which includes nootropics, normotimics, soporifics, over-all strengthening therapy and other devices. The course of treatment consisted of 10 daily procedures lasting for 30 minutes. The TES influence was evaluated according to the clinical state, the neurologic status, including EEG (electroencephalogram, the psychometric scales were also used for evaluating the manifestation of depression, anxiety and working memory in comparison with appropriate indices in the control group of patients, who were being treated by the traditional method. TES led to normalization of health state, neurologic status and vegetative innervation, the reduction in pathologic inclination, which corresponded to general improvement of the state of patients, EEG indices and psychometric scales

  19. Neurological and Vascular Manifestations of Ethylmalonic Encephalopathy.

    Science.gov (United States)

    Tavasoli, Ali Reza; Rostami, Parastoo; Ashrafi, Mahmoud Reza; Karimzadeh, Parvaneh

    2017-01-01

    Objective Ethylmalonic encephalopathy (EE) is a severe mitochondrial disease of early infancy clinically characterized by a combination of developmental delay, progressive pyramidal signs, and vascular lesions including petechial purpura, orthostatic acrocyanosis, and chronic hemorrhagic diarrhea. Biochemical hallmarks of the disease are persistently high level of lactate, and C4-C5-acylcarnitines in blood, markedly elevated urinary excretion of methylsuccinic and ethylmalonic (EMA) acids. Here we report two patients with EE as a 16-months-old male infant and a 2-yr-old boy referred to Pediatric Neurology Clinic in Children's Medical Center, Tehran-Iran that in one patient genetic analysis revealed a homozygous mutation of the ETHE1 gene in favor of ethylmalonic acidemia.

  20. Is chronic traumatic encephalopathy a real disease?

    Science.gov (United States)

    Randolph, Christopher

    2014-01-01

    Chronic traumatic encephalopathy (CTE) has received widespread media attention and is treated in the lay press as an established disease, characterized by suicidality and progressive dementia. The extant literature on CTE is reviewed here. There currently are no controlled epidemiological data to suggest that retired athletes are at increased risk for dementia or that they exhibit any type of unique neuropathology. There remain no established clinical or pathological criteria for diagnosing CTE. Despite claims that CTE occurs frequently in retired National Football League (NFL) players, recent studies of NFL retirees report that they have an all-cause mortality rate that is approximately half of the expected rate, and even lower suicide rates. In addition, recent clinical studies of samples of cognitively impaired NFL retirees have failed to identify any unique clinical syndrome. Until further controlled studies are completed, it appears to be premature to consider CTE a verifiable disease.

  1. Posterior reversible encephalopathy syndrome: A case report

    Directory of Open Access Journals (Sweden)

    Kostić Dejan

    2015-01-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is characterized by the following symptoms: seizures, impaired consciousness and/or vision, vomiting, nausea, and focal neurological signs. Diagnostic imaging includes examination by magnetic resonance (MR and computed tomography (CT, where brain edema is visualized bi-laterally and symmetrically, predominantly posteriorly, parietally, and occipitally. Case report. We presented a 73-year-old patient with the years-long medical history of hipertension and renal insufficiency, who developed PRES with the symptomatology of the rear cranium. CT and MR verified changes in the white matter involving all lobes on both sides of the brain. After a two-week treatment (antihypertensive, hypolipemic and rehydration therapy clinical improvement with no complications occurred, with complete resolution of changes in the white matter observed on CT and MR. Conclusion. PRES is a reversible syndrome in which the symptoms withdraw after several days to several weeks if early diagnosis is made and appropriate treatment started without delay.

  2. Hashimoto’s Encephalopathy (A Review Article

    Directory of Open Access Journals (Sweden)

    M Ghaffar Pour

    2012-05-01

    Full Text Available

    Background and Objectives

    Hashimoto's encephalopathy (HE known as Steroid Responsive Encephalopathy associated with Autoimmune Thyroditis (SREAT is a rare nervous system disease. HE was originally described by Brain, et. al. in 1966, however its cause still remains unknown after about 40 years. Autoimmune vasculitis of CNS, brain edema, and anti-thyroid antibodies are considered some of the etiologies for HE. It is certain that HE is an autoimmune disease and not a thyroid system disease. HE patients may or may not have goiter.

    Some of the most common neurological manifestations of HE include: Confusion with altered consciousness, seizures, myoloclonus, and cognitive problems. Presence of high titers of anti-thyroid antibodies in blood serum and CSF of HE patients is considered the most common laboratory test for diagnosis of HE. EEG abnormalities such as diffuse slowing and atypical tri-phasic brain waves are the most common findings in about ¾ HE patients. Brain CT-Scan is normal in majority of HE patients. Global or local hypo perfusion may be seen in SPECT scanning of the brain. MRI findings are abnormal in about 40% of HE patients.

    Patients with sub acute or acute onset of confusion, seizure, myoloclonus, stroke-like episodes and amnesia whose laboratory serum and CSF tests indicate presence of high titers of anti- thyroid antibodies should be considered for having HE. Vascular myelopathies, CJD, HSP, Myelinoclastic disease like PML, SSPE, ADE, MS and DNL are some of the differential diagnosis of HE.

    Adrenal corticosteroids are the first line treatment for HE. Recurrent or steroid resistant HE cases may be treated by addition of other immunosuppressant drugs such as  Azathioprine, Cyclophosphamide, or Methotrexate to the 1st line therapy.

  3. Neuroimmunomodulators in neuroborreliosis and Lyme encephalopathy.

    Science.gov (United States)

    Eckman, Elizabeth A; Pacheco-Quinto, Javier; Herdt, Aimee R; Halperin, John J

    2018-01-11

    Lyme encephalopathy, characterized by non-specific neurobehavioral symptoms including mild cognitive difficulties, may occur in patients with systemic Lyme disease and is often mistakenly attributed to CNS infection. Identical symptoms occur in innumerable other inflammatory states and may reflect the effect of systemic immune mediators on the CNS. Multiplex immunoassays were used to characterize the inflammatory profile in serum and CSF from Lyme and non-Lyme patients with a range of symptoms to determine if there are specific markers of active CNS infection (neuroborreliosis), or systemic inflammatory mediators associated with neurobehavioral syndromes. CSF CXCL13 was elevated dramatically in confirmed neuroborreliosis (n=8) and to a lesser extent in possible neuroborreliosis (n=11) and other neuroinflammatory conditions (n=44). Patients with Lyme (n=63) or non-Lyme (n=8) encephalopathy had normal CSF findings, but had elevated serum levels of IL-7, TSLP, IL-17A, IL-17F, and MIP-1α/CCL3. CSF CXCL13 is a sensitive and specific marker of neuroborreliosis in individuals with Borrelia-specific intrathecal antibody (ITAb) production. However, CXCL13 does not distinguish individuals strongly suspected of having neuroborreliosis, but lacking confirmatory ITAb, from those with other neuroinflammatory conditions. Patients with mild cognitive symptoms occurring during acute Lyme disease, and/or following appropriate treatment, have normal CSF but elevated serum levels of T-helper 17 markers and T-cell growth factors. These markers are also elevated in non-Lyme disease patients experiencing similar symptoms. Our results support that in the absence of CSF abnormalities, neurobehavioral symptoms are associated with systemic inflammation, not CNS infection or inflammation, and are not specific to Lyme disease. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  4. Safety, efficacy, and patient acceptability of rifaximin for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Kimer, Nina; Krag, Aleksander; Gluud, Lise L

    2014-01-01

    Hepatic encephalopathy is a complex disease entity ranging from mild cognitive dysfunction to deep coma. Traditionally, treatment has focused on a reduction of ammonia through a reduced production, absorption, or clearance. Rifaximin is a nonabsorbable antibiotic, which reduces the production of ...... and safety of long-term treatment with rifaximin and evaluate effects of combination therapy with lactulose and branched-chain amino acids for patients with liver cirrhosis and hepatic encephalopathy....... of ammonia by gut bacteria and, to some extent, other toxic derivatives from the gut. Clinical trials show that these effects improve episodes of hepatic encephalopathy. A large randomized trial found that rifaximin prevents recurrent episodes of hepatic encephalopathy. Most patients were treated...

  5. Cerebral CT appearances of toxic encephalopathy of tetramine

    International Nuclear Information System (INIS)

    Zheng Wenlong; Wu Aiqin; Xu Chongyong; Ying Binyu; Hong Ruizhen

    2003-01-01

    Objective: To investigate the cerebral CT appearances of toxic encephalopathy of tetramine and improve the recognition on this disease. Methods: Four cases of toxic encephalopathy of tetramine were collected and their cerebral CT appearances were retrospectively analyzed. Results: Cerebral CT appearances in acute phase (within 8 days): (1) cerebral edema in different degree. CT abnormalities consisted of cortical hypodensities and complete loss of gray-white matter differentiation. The CT value were in 11-13 HU, and to be watery density in serious case, (2) subarachnoid hemorrhage. It demonstrated the signs of poisoning hypoxic ischemic encephalopathy in chronic phase. Conclusion: The cerebral CT appearances of toxic encephalopathy of tetramine had some character in acute phase and it can predict the serious degree of intoxication, but there was no characteristic findings in chronic phase

  6. Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies

    DEFF Research Database (Denmark)

    Møller, Rikke S.; Larsen, Line H.G.; Johannesen, Katrine M.

    2016-01-01

    to epileptic encephalopathies (EEs). Potentially causative variants were evaluated by literature and database searches, submitted to bioinformatic prediction algorithms, and validated by Sanger sequencing. If possible, parents were included for segregation analysis. We identified a presumed disease...

  7. Systematic review and meta-analysis of randomized trials on probiotics for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Holte, Kathrine; Krag, Aleksander; Gluud, Lise Lotte

    2012-01-01

    Aim:  The objective of this systematic review and meta-analysis was to assess the efficacy of probiotics and synbiotics in patients with hepatic encephalopathy. Methods:  Eligible trials were identified by searching electronic databases including MEDLINE, the Cochrane Library, Science Citation...... or synbiotics did not significantly affect the psychometric tests. Overall adverse events were reported in four trials with no difference between probiotics and placebo groups (RR = 0.32, 95% CI = 0.04-2.57; I(2)  = 59%). Regression analysis showed evidence of small-study effects. Conclusion:  The present meta...

  8. Early progressive encephalopathy in boys and MECP2 mutations.

    Science.gov (United States)

    Kankirawatana, P; Leonard, H; Ellaway, C; Scurlock, J; Mansour, A; Makris, C M; Dure, L S; Friez, M; Lane, J; Kiraly-Borri, C; Fabian, V; Davis, M; Jackson, J; Christodoulou, J; Kaufmann, W E; Ravine, D; Percy, A K

    2006-07-11

    MECP2 mutations mainly occur in females with Rett syndrome. Mutations have been described in 11 boys with progressive encephalopathy: seven of nine with affected sisters and two de novo. The authors report four de novo occurrences: three pathogenic and one potentially pathogenic. Common features include failure to thrive, respiratory insufficiency, microcephaly, and abnormal motor control. MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.

  9. Late onset arginase deficiency presenting with encephalopathy and midbrain hyperintensity

    Directory of Open Access Journals (Sweden)

    Boby Varkey Maramattom

    2016-01-01

    Full Text Available Urea cycle disorders (UCD are very rare metabolic disorders that present with encephalopathy and hyperammonemia. Of the UCDs, Arginase deficiency (ARD is the rarest and presents in childhood with a progressive spastic diplegia or seizures. Acute presentation in adulthood is extremely unusual. [1] We present the first case of adult onset ARD presenting with encephalopathy and diffusion weighted MRI findings that resembled a moustache in the midbrain.

  10. Lead encephalopathy treated by versenate (CA-EDTA)

    Energy Technology Data Exchange (ETDEWEB)

    Radwan, H.; Braun, H.; Kott, E.; Bar-Sela, S.

    1982-01-01

    A patient with generalised epileptic seizures, mental and psychotic signs was diagnosed as suffering from lead encephalopathy. He was a big consumer of home-made arrack, illicit alcohol prepared at home in secrecy, in tools containing copper and lead. Basophilic stippling increased the possibility of lead encephalopathy, which was soon proved. He was successfully treated with low doses of Versenate, a chelating factor, and totally recovered.

  11. EPILEPTIC ENCEPHALOPATHY WITH CONTINUOUS SPIKES-WAVES ACTIVITY DURING SLEEP

    OpenAIRE

    E. D. Belousova

    2012-01-01

    The author represents the review and discussion of current scientific literature devoted to epileptic encephalopathy with continuous spikes-waves activity during sleep — the special form of partly reversible age-dependent epileptic encephalopathy, characterized by triad of symptoms: continuous prolonged epileptiform (spike-wave) activity on EEG in sleep, epileptic seizures and cognitive disorders. The author describes the aspects of classification, pathogenesis and etiology, prevalence, clini...

  12. Branched-chain amino acids for people with hepatic encephalopathy

    DEFF Research Database (Denmark)

    Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo

    2017-01-01

    -chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. Objectives: To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. Search methods: We identified trials through...... included randomised clinical trials, irrespective of the bias control, language, or publication status. Data collection and analysis: The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update...

  13. Disease-associated prion protein in neural and lymphoid tissues of mink (Mustela vison) inoculated with transmissible mink encephalopathy.

    Science.gov (United States)

    Schneider, D A; Harrington, R D; Zhuang, D; Yan, H; Truscott, T C; Dassanayake, R P; O'Rourke, K I

    2012-11-01

    Transmissible spongiform encephalopathies (TSEs) are diagnosed by immunodetection of disease-associated prion protein (PrP(d)). The distribution of PrP(d) within the body varies with the time-course of infection and between species, during interspecies transmission, as well as with prion strain. Mink are susceptible to a form of TSE known as transmissible mink encephalopathy (TME), presumed to arise due to consumption of feed contaminated with a single prion strain of ruminant origin. After extended passage of TME isolates in hamsters, two strains emerge, HY and DY, each of which is associated with unique structural isoforms of PrP(TME) and of which only the HY strain is associated with accumulation of PrP(TME) in lymphoid tissues. Information on the structural nature and lymphoid accumulation of PrP(TME) in mink is limited. In this study, 13 mink were challenged by intracerebral inoculation using late passage TME inoculum, after which brain and lymphoid tissues were collected at preclinical and clinical time points. The distribution and molecular nature of PrP(TME) was investigated by techniques including blotting of paraffin wax-embedded tissue and epitope mapping by western blotting. PrP(TME) was detected readily in the brain and retropharyngeal lymph node during preclinical infection, with delayed progression of accumulation within other lymphoid tissues. For comparison, three mink were inoculated by the oral route and examined during clinical disease. Accumulation of PrP(TME) in these mink was greater and more widespread, including follicles of rectoanal mucosa-associated lymphoid tissue. Western blot analyses revealed that PrP(TME) accumulating in the brain of mink is structurally most similar to that accumulating in the brain of hamsters infected with the DY strain. Collectively, the results of extended passage in mink are consistent with the presence of only a single strain of TME, the DY strain, capable of inducing accumulation of PrP(TME) in the lymphoid

  14. Chronic traumatic encephalopathy and other neurodegenerative proteinopathies

    Directory of Open Access Journals (Sweden)

    Maria Carmela Tartaglia

    2014-01-01

    Full Text Available Chronic traumatic encephalopathy (CTE is described as a slowly progressive neurodegenerative disease believed to result from multiple concussions. Traditionally, concussions were considered benign events and although most people recover fully, about 10% develop a post-concussive syndrome with persisting neurological, cognitive and neuropsychiatric symptoms. CTE was once thought to be unique to boxers, but it has now been observed in many different athletes having suffered multiple concussions as well as in military personal after repeated blast injuries. Much remains unknown about the development of CTE but its pathological substrate is usually tau, similar to that seen in Alzheimer’s disease and frontotemporal lobar degeneration. The aim of this perspective is to compare and contrast clinical and pathological CTE with the other neurodegenerative proteinopathies and highlight that there is an urgent need for understanding the relationship between concussion and the development of CTE as it may provide a window into the development of a proteinopathy and thus new avenues for treatment.

  15. Pathogenetic aspects of alcoholic encephalopathy treatment

    Directory of Open Access Journals (Sweden)

    Shchetinin S.G.

    2010-12-01

    Full Text Available Alcohol is considered to be the most common exogenous toxins, causing encephalopathy. The defeat of almost all parts of the nervous system should be assigned to the special features of ethanol. Neurophysiological mechanisms of development of substance dependence are based in the stem and limbic structures of the brain that are involved in ensuring the regulation of emotional state, mood, motivation sphere, psychophysical tone of human behavior in general and its adaptation to the environment. Stress or disruption of the normal functioning of these structures can lead to the formation of abstinence syndrome, affective disorders in remission and craving for alcohol. Dopaminergic and opioid (endorphin system play an important role in the genesis of various mental and motor disorders. In some way alcohol dependence can be regarded as an endorfinodefitsitnoe disease with a pathogenetic point of view. Activating of opioidereal system by trans-cranial electrical stimulation promotes the restoration of disturbed emotional, cognitive and autonomic functions, reduces craving for alcohol and in that way increases the effectiveness of rehabilitation treatment

  16. Encephalopathy Associated With Autoimmune Thyroid Disease

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    li A. Raouf

    2014-07-01

    Full Text Available Autoimmune thyroid diseases (ATDs are immune-endocrine disorders affecting the thyroid gland and, eventually, also a number of other systemic targets, including the brain and the nervous system. Encephalopathy associated with autoimmune thyroid disease (EAATD is a rare, heterogeneous condition arising from the background of an ATD. It is characterised by neurological and/or psychiatric symptoms with acute or sub-acute onset, and virtually any neurological or psychiatric symptom can appear. However, EAATD often presents with confusion, altered consciousness, seizures, or myoclonus. The majority of cases are associated with Hashimoto’s thyroiditis, but a number of patients with Graves’ disease have also been described. EAATD is likely an immune-mediated disorder. Its exact prevalence has not been precisely elucidated, with an increasing number of cases reported in the last few years. Most EAATD patients respond in a dramatic manner to corticosteroids. However, the immunosuppressive treatment may require a long course (up to 12 months. The increasing number of EAATD cases reported in the literature demonstrates a growing interest of the scientific community about this condition, which still requires a better definition of its pathophysiology, the diagnostic criteria, and the most appropriate management, including the long-term follow-up of patients. The current clinical evidence about EAATD is mostly based on the report of single cases or small cohort studies. In this review, we present the current knowledge about EAATD, with a dedicated focus to the clinical management of the patients from a diagnostic and therapeutic perspective.

  17. Neuroimaging of Wernicke's encephalopathy and Korsakoff's syndrome.

    Science.gov (United States)

    Jung, Young-Chul; Chanraud, Sandra; Sullivan, Edith V

    2012-06-01

    There is considerable evidence that neuroimaging findings can improve the early diagnosis of Wernicke's encephalopathy (WE) in clinical settings. The most distinctive neuroimaging finding of acute WE are cytotoxic edema and vasogenic edema, which are represented by bilateral symmetric hyperintensity alterations on T2-weighted MR images in the periphery of the third ventricle, periaqueductal area, mammillary bodies and midbrain tectal plate. An initial bout of WE can result in Korsakoff's syndrome (KS), but repeated bouts in conjunction with its typical comorbidity, chronic alcoholism, can result in signs of tissue degeneration in vulnerable brain regions. Chronic abnormalities identified with neuroimaging enable examination of brain damage in living patients with KS and have expanded the understanding of the neuropsychological deficits resulting from thiamine deficiency, alcohol neurotoxicity, and their comorbidity. Brain structure and functional studies indicate that the interactions involving the thalamus, mammillary bodies, hippocampus, frontal lobes, and cerebellum are crucial for memory formation and executive functions, and the interruption of these circuits by WE and chronic alcoholism can contribute substantially to the neuropsychological deficits in KS.

  18. Resveratrol in Patients with Minimal Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Giulia Malaguarnera

    2018-03-01

    Full Text Available Background: Minimal Hepatic Encephalopathy (MHE is characterized by an impairment of social interaction, emotional behavior, sleep disorders, physical and mental symptoms, and diminished Quality of Life (QoL. The aim of our study is evaluating the potential liver health promoting a perspective of Resveratrol (RV activities and evaluate whether RV treatment may improve health related quality of life (HRQL and reduce depression and anxiety in patients with MHE. Methods: We evaluated depression using the Beck Depression Inventory test, anxiety with State-trait anxiety inventory test, quality of life through SF-36 test, and ammonia serum levels in 70 MHE patients that were randomized into two groups. Results: In the comparison between RV group and placebo group we observed a decrease in Back Depression Inventory (BDI (p < 0.001, in State-trait anxiety inventory (STAI (p < 0.001, and improve in physical function (p < 0.001, in role physical (p < 0.05, in body pain (p < 0.05, in general health (p < 0.001, in vitality (p < 0.05, and in social function (p < 0.001. Conclusions: Resveratrol showed efficacy in the treatment of depression, anxiety, and ammonia serum levels, and improved the quality of life Of MHE patients.

  19. The Thompson Encephalopathy Score and Short-Term Outcomes in Asphyxiated Newborns Treated With Therapeutic Hypothermia

    NARCIS (Netherlands)

    Thorsen, Patricia; Jansen-van der Weide, Martine C; Groenendaal, Floris; Onland, Wes; van Straaten, Henrika L M; Zonnenberg, Inge; Vermeulen, Jeroen R.; Dijk, Peter H; Dudink, Jeroen; Rijken, Monique; van Heijst, Arno; Dijkman, Koen P; Cools, Filip; Zecic, Alexandra; van Kaam, Anton H; de Haan, Timo R

    BACKGROUND: The Thompson encephalopathy score is a clinical score to assess newborns suffering from perinatal asphyxia. Previous studies revealed a high sensitivity and specificity of the Thompson encephalopathy score for adverse outcomes (death or severe disability). Because the Thompson

  20. Posterior reversible encephalopathy syndrome in a patient with lupus nephritis

    Directory of Open Access Journals (Sweden)

    Huseyin Kadikoy

    2012-01-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is characterized by acute onset of headache, nausea, focal neurological deficits or seizures along with radiological findings of white matter defects in the parietal and occipital lobes. Causes of PRES include uremia, hypertensive encephalopathy, eclampsia and immunosuppressive medications. Usually, the treat-ment of choice involves correcting the underlying abnormality. We describe an unusual case of recurrent PRES caused by uremia during a lupus flare in a patient with biopsy-proven Class IV Lupus Nephritis (LN with vasculitis. PRES in systemic lupus erythematosis (SLE is a rare clin-ical phenomenon and, when reported, it is associated with hypertensive encephalopathy. Our patient did not have hypertensive crisis, but had uremic encephalopathy. The patient′s PRES-related symptoms resolved after initiation of hemodialysis. The temporal correlation of the correc-tion of the uremia and the resolution of the symptoms of PRES show the etiology to be uremic encephalopathy, making this the first reported case of uremia-induced PRES in Class IV LN with vasculitis.

  1. Cerebellar Degeneration

    Science.gov (United States)

    ... and spinal cord transmissible spongiform encephalopathies (such as Creutzfeldt-Jakob disease) in which abnormal proteins cause inflammation in the ... and spinal cord transmissible spongiform encephalopathies (such as Creutzfeldt-Jakob disease) in which abnormal proteins cause inflammation in the ...

  2. The Effects of Probiotics and Symbiotics on Risk Factors for Hepatic Encephalopathy: A Systematic Review.

    Science.gov (United States)

    Viramontes Hörner, Daniela; Avery, Amanda; Stow, Ruth

    2017-04-01

    Alterations in the levels of intestinal microbiota, endotoxemia, and inflammation are novel areas of interest in the pathogenesis of hepatic encephalopathy (HE). Probiotics and symbiotics are a promising treatment option for HE due to possible beneficial effects in modulating gut microflora and might be better tolerated and more cost-effective than the traditional treatment with lactulose, rifaximin or L-ornithine-L-aspartate. A systematic search of the electronic databases PubMed, ISI Web of Science, EMBASE, and Cochrane Library was conducted for randomized controlled clinical trials in adult patients with cirrhosis, evaluating the effect of probiotics and symbiotics in changes on intestinal microflora, reduction of endotoxemia, inflammation, and ammonia, reversal of minimal hepatic encephalopathy (MHE), prevention of overt hepatic encephalopathy (OHE), and improvement of quality of life. Nineteen trials met the inclusion criteria. Probiotics and symbiotics increased beneficial microflora and decreased pathogenic bacteria and endotoxemia compared with placebo/no treatment, but no effect was observed on inflammation. Probiotics significantly reversed MHE [risk ratio, 1.53; 95% confidence interval (CI): 1.14, 2.05; P=0.005] and reduced OHE development (risk ratio, 0.62; 95% CI: 0.48, 0.80; P=0.0002) compared with placebo/no treatment. Symbiotics significantly decreased ammonia levels compared with placebo (15.24; 95% CI: -26.01, -4.47; P=0.006). Probiotics did not show any additional benefit on reversal of MHE and prevention of OHE development when compared with lactulose, rifaximin, and L-ornithine-L-aspartate. Only 5 trials considered tolerance with minimal side effects reported. Although further research is warranted, probiotics and symbiotics should be considered as an alternative therapy for the treatment and management of HE given the results reported in this systematic review.

  3. Electroencephalogram of Age-Dependent Epileptic Encephalopathies in Infancy and Early Childhood

    OpenAIRE

    Wong-Kisiel, Lily C.; Nickels, Katherine

    2013-01-01

    Epileptic encephalopathy syndromes are disorders in which the epileptiform abnormalities are thought to contribute to a progressive cerebral dysfunction. Characteristic electroencephalogram findings have an important diagnostic value in classification of epileptic encephalopathy syndromes. In this paper, we focus on electroencephalogram findings of childhood epileptic encephalopathy syndromes and provide sample illustrations.

  4. Clinical characteristics and prognosis in patients with hyponatremic encephalopathy

    Directory of Open Access Journals (Sweden)

    Jorge Cestari

    2015-01-01

    Full Text Available Introduction: Hyponatremic encephalopathy mortality rate reaches about 50% in some special groups of patients (pediatric, child-bearing age women, etc.. However, morbimortality seems to be much lower in men and elderly population. Methods: A retrospective and observational study on patients with hyponatremic encephalopathy diagnosis was carried out. Results: 47 patients with hyponatremic encephalopathy diagnosis were identified. It was an elderly population (age 69±15 years with women prevalence. In-hospital mortality was 19.1% and neurological aftermaths in the survivors were 27%. Charlson score and delay to initiate treatment were associated to larger in-hospital mortality. Conclusion: mortality rate observed in our population is less than the one observed in other cohorts, probably due to the fact of being a low risk population. In a logistic regression model, delay in initiating an adequate treatment is associated to larger mortality rate in the studied population.

  5. Research progress of BOLD-functional MRI of hepatic encephalopathy

    International Nuclear Information System (INIS)

    Ni Ling; Zhang Longjiang; Lu Guangming

    2013-01-01

    Hepatic encephalopathy (HE), characterized by a wide spectrum of clinical manifestations, ranging from behavior abnormality, conscious disorder and even coma, is a consequence of liver dysfunction in both acute and chronic hepatic diseases. Minimal hepatic encephalopathy (MHE) refers to a subgroup of cirrhotic patients without clinical overt hepatic encephalopathy symptoms hut with abnormalities in neuro -cognitive functions. HE/MHE can have a far-reaching impact on quality of life and prognosis. The exact neuropathology mechanism was still unclear. Recently, functional MRI (fMRI) has been increasingly applied for investigating the neuro-pathophysiological mechanism of HE. This paper will review the fMRI research applied on uncovering the neuropathology mechanism of HE. (authors)

  6. EPILEPTIC ENCEPHALOPATHY WITH CONTINUOUS SPIKES-WAVES ACTIVITY DURING SLEEP

    Directory of Open Access Journals (Sweden)

    E. D. Belousova

    2012-01-01

    Full Text Available The author represents the review and discussion of current scientific literature devoted to epileptic encephalopathy with continuous spikes-waves activity during sleep — the special form of partly reversible age-dependent epileptic encephalopathy, characterized by triad of symptoms: continuous prolonged epileptiform (spike-wave activity on EEG in sleep, epileptic seizures and cognitive disorders. The author describes the aspects of classification, pathogenesis and etiology, prevalence, clinical picture and diagnostics of this disorder, including the peculiar anomalies on EEG. The especial attention is given to approaches to the treatment of epileptic encephalopathy with continuous spikeswaves activity during sleep. Efficacy of valproates, corticosteroid hormones and antiepileptic drugs of other groups is considered. The author represents own experience of treatment this disorder with corticosteroids, scheme of therapy and assessment of efficacy.

  7. Wernicke’s Encephalopathy Complicating Hyperemesis during Pregnancy

    Directory of Open Access Journals (Sweden)

    Mohamed Adnane Berdai

    2016-01-01

    Full Text Available Wernicke’s encephalopathy is caused by severe thiamine deficiency; it is mostly observed in alcoholic patients. We report the case of a 28-year-old woman, at 17 weeks of gestational age, with severe hyperemesis gravidarum. She presented with disturbance of consciousness, nystagmus, ophthalmoplegia, and ataxia. The resonance magnetic imagery showed bilaterally symmetrical hyperintensities of thalamus and periaqueductal area. The case was managed with very large doses of thiamine. The diagnosis of Wernicke’s encephalopathy was confirmed later by a low thiamine serum level. The patient was discharged home on day 46 with mild ataxia and persistent nystagmus. Wernicke’s encephalopathy is a rare complication of hyperemesis gravidarum. It should be diagnosed as early as possible to prevent long-term neurological sequela or death. Thiamine supplementation in pregnant women with prolonged vomiting should be initiated, especially before parenteral dextrose infusion. Early thiamine replacement will reduce maternal morbidity and fetal loss rate.

  8. A Critical Case of Wernicke's Encephalopathy Induced by Hyperemesis Gravidarum

    Directory of Open Access Journals (Sweden)

    Byung Ju Kang

    2015-05-01

    Full Text Available Wernicke’s encephalopathy is a reversible but potentially critical disease caused by thiamine deficiency. Most patients complain of symptoms such as ophthalmoplegia, ataxia and confusion. Heavy alcohol drinking is commonly associated with the disease, but other clinical conditions also can provoke it. In pregnant women, hyperemesis gravidarum can lead to the depletion of body thiamine due to poor oral intake and a high metabolic demand. We report a case of Wernicke’s encephalopathy following hyperemesis gravidarum in a 36-year-old female at 20 weeks of pregnancy, who visited our hospital because of shock with vaginal bleeding. This case suggests that although the initial presentation may include atypical symptoms (e.g., shock or bleeding, Wernicke’s encephalopathy should be considered, and thiamine replacement should be performed in pregnant women with neurologic symptoms and poor oral intake.

  9. Magnetic resonance imaging in a case of Wernicke's encephalopathy

    International Nuclear Information System (INIS)

    Pagnan, L.; Pozzi-Mucelli, R.S.; Berlot, G.

    1998-01-01

    Wernicke's encephalopathy is an uncommon disorder caused by a thiamine deficiency which is clinically characterized by the triad of ophthalmoplegia, ataxia and disturbances of consciousness, each finding being variably present. The disease is caused by malnutrition or malabsorption, and is often associated with prolonged alcohol intake, neoplasm and extensive inflammatory processes of the digestive tract and parenteral hyperalimentation-induced gastrointestinal mucosal atrophy. Clinical diagnosis can be elusive and MRI may be the only imaging technique able to detect the cerebral lesions, whose type and distribution are characteristic of the Wernicke's encephalopathy, whereas CT is positive only in exceptional cases. We report a case of a 56-year-old woman who developed a Wernicke's encephalopathy 1 month after a colonic resection with signal intensity changes located in the mammillary bodies and in the medial thalamic nuclei. (orig.)

  10. Clinical and radiological features of hypertensive brainstem encephalopathy

    Directory of Open Access Journals (Sweden)

    Xiao-qiu LI

    2015-07-01

    Full Text Available Objective To discuss the diagnosis and treatment of hypertensive brainstem encephalopathy. Methods  The clinical and imaging data of 3 cases of hypertensive brainstem encephalopathy were summarized and analyzed for the purpose of improving the acumen in diagnosis and treatment. Results All the 3 patients showed relatively mild clinical symptoms, and they were misdiagnosed in different degrees during the treatment, but their clinical symptoms were improved by rapid and effective antihypertensive therapy. Cerebral CT and MRI scans revealed extensive abnormal signals in brain stem, with or without supratentorial lesions and brain stem hemorrhage. The lesions as revealed by imaging were improved significantly after treatment. Conclusions Clinical-radiographic dissociation is the classic feature of hypertensive brainstem encephalopathy. The clinical symptoms and lesions as shown by imaging could be improved after active treatment. DOI: 10.11855/j.issn.0577-7402.2015.06.03

  11. Intravenous methylprednisolone pulse therapy for children with epileptic encephalopathy.

    Science.gov (United States)

    Pera, Maria Carmela; Randazzo, Giovanna; Masnada, Silvia; Dontin, Serena Donetti; De Giorgis, Valentina; Balottin, Umberto; Veggiotti, Pierangelo

    2015-01-01

    The aim of this retrospective study of children affected by epileptic encephalopathy was to evaluate seizure frequency, electroencephalographic pattern and neuropsychological status, before and after intravenous methylprednisolone therapy. Eleven children with epileptic encephalopathy were administered one cycle of intravenous methylprednisolone (15-30 mg/kg/day for three consecutive days, once a month for four months) in addition to constant dosages of their regular antiepileptic drugs. The treatment resulted in statistically significant reductions of generalized slow spike-and-wave discharges (ptreatment regimen did not cause significant or persistent adverse effects. We suggest that children with epileptic encephalopathy without an underlying structural lesion could be the best candidates for intravenous methylprednisolone pulse therapy.

  12. Hippocampal sclerosis and chronic epilepsy following posterior reversible encephalopathy syndrome.

    Science.gov (United States)

    Kapina, Viktoria; Vargas, Maria-Isabel; Wohlrab, Gabriele; Vulliemoz, Serge; Fluss, Joel; Seeck, Margitta

    2013-12-01

    Chronic epilepsy has rarely been reported after posterior reversible encephalopathy syndrome (PRES) and the association with hippocampal sclerosis has been suggested only once before. We report the case of a girl admitted at the age of 8 years with idiopathic nephrotic syndrome. On the second day of admission, she presented with focal complex seizures and cerebral MRI showed posterior encephalopathy and no hippocampal sclerosis. MRI after one month confirmed the diagnosis of PRES. The seizures recurred and the girl developed pharmacoresistant epilepsy and was admitted to our hospital for further investigation. Cerebral MRI three years after the diagnosis of PRES showed hippocampal sclerosis which was not present on the initial MRI. We conclude that there is a triggering role of PRES in the development of hippocampal sclerosis. Hippocampal sclerosis may have resulted from seizure-associated damage, alternatively, hypertensive encephalopathy may have led to hippocampal damage via a vascular mechanism.

  13. Molecular chaperones and hypoxic-ischemic encephalopathy

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    Cong Hua

    2017-01-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway. Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century. Hypothermia, xenon gas treatment, the use of melatonin and erythropoietin, and hypoxic-ischemic preconditioning have proven effective in HIE patients. Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes. A large number of molecular chaperones are induced after brain ischemia and hypoxia, among which the heat shock proteins are the most important. Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects. Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations, assisting in the proper folding of newly synthesized polypeptides, regulating the degradation of misfolded proteins, inhibiting the aggregation of proteins, and by controlling the refolding of misfolded proteins. In addition, heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways, including the intrinsic pathway, the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway. Molecular chaperones play a key role in neuroprotection in HIE. In

  14. Wernicke encephalopathy: MR findings and clinical presentation

    International Nuclear Information System (INIS)

    Weidauer, Stefan; Lanfermann, Heinrich; Zanella, Friedhelm E.; Nichtweiss, Michael

    2003-01-01

    Wernicke encephalopathy (WE) is a severe neurological disorder caused by vitamin B1 deficiency. The aim of the study was to analyse MRI findings typical for this disease and to evaluate the significance of their correlations with clinical symptoms. Magnetic resonance images and clinical features of 12 patients with WE were analysed. The patients underwent MR imaging within 3-14 days after onset of clinical symptoms. In 7 of 12 patients MR imaging showed symmetrical diencephalic and midbrain lesions. Postcontrast T1-weighted images from 5 of 9 patients examined during the initial 6 days of acute WE showed a subtle enhancement of the mamillary bodies, the tectal plate, the periaqueductal area and the periventricular region of the third ventricle including the paramedian thalamic nuclei. In addition, T2-weighted and fluid-attenuated inversion recovery (FLAIR) images revealed hyperintense signals in these regions (except for 2 patients where the mamillary bodies were normal). Hyperintense lesions on T2-weighted images without any enhancement on postcontrast T1-weighted images were detected in 2 patients by MR imaging performed 11 or 14 days after onset of WE. Patients with hyperintensities on T2-weighted images of the periventricular region of the third ventricle and the paramedian thalamic nuclei had poor recovery from their mental dysfunction. The MR examination in case of WE shows a typical pattern of lesions in 58% of cases. Enhancement of the mamillary bodies, the periventricular region of the third ventricle including the paramedian thalamic nuclei, and the periaqueductal area on postcontrast T1-weighted images can be observed in the initial period after clinical onset of symptoms and are characteristic signs of the acute stage of WE. Hyperintense lesions in the periventricular region and the paramedian thalamic nuclei on T2-weighted and FLAIR images in the subacute stage of WE and enhancement on postcontrast T1-weighted images of the mamillary bodies and the

  15. Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy.

    Science.gov (United States)

    Lucke-Wold, Brandon P; Turner, Ryan C; Logsdon, Aric F; Nguyen, Linda; Bailes, Julian E; Lee, John M; Robson, Matthew J; Omalu, Bennet I; Huber, Jason D; Rosen, Charles L

    2016-03-01

    Chronic traumatic encephalopathy is a progressive neurodegenerative disease characterized by neurofibrillary tau tangles following repetitive neurotrauma. The underlying mechanism linking traumatic brain injury to chronic traumatic encephalopathy has not been elucidated. The authors investigate the role of endoplasmic reticulum stress as a link between acute neurotrauma and chronic neurodegeneration. The authors used pharmacological, biochemical, and behavioral tools to assess the role of endoplasmic reticulum stress in linking acute repetitive traumatic brain injury to the development of chronic neurodegeneration. Data from the authors' clinically relevant and validated rodent blast model were compared with those obtained from postmortem human chronic traumatic encephalopathy specimens from a National Football League player and World Wrestling Entertainment wrestler. The results demonstrated strong correlation of endoplasmic reticulum stress activation with subsequent tau hyperphosphorylation. Various endoplasmic reticulum stress markers were increased in human chronic traumatic encephalopathy specimens, and the endoplasmic reticulum stress response was associated with an increase in the tau kinase, glycogen synthase kinase-3β. Docosahexaenoic acid, an endoplasmic reticulum stress inhibitor, improved cognitive performance in the rat model 3 weeks after repetitive blast exposure. The data showed that docosahexaenoic acid administration substantially reduced tau hyperphosphorylation (t = 4.111, p < 0.05), improved cognition (t = 6.532, p < 0.001), and inhibited C/EBP homology protein activation (t = 5.631, p < 0.01). Additionally the data showed, for the first time, that endoplasmic reticulum stress is involved in the pathophysiology of chronic traumatic encephalopathy. Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy.

  16. Potentially modifiable factors contributing to sepsis-associated encephalopathy.

    Science.gov (United States)

    Sonneville, Romain; de Montmollin, Etienne; Poujade, Julien; Garrouste-Orgeas, Maïté; Souweine, Bertrand; Darmon, Michael; Mariotte, Eric; Argaud, Laurent; Barbier, François; Goldgran-Toledano, Dany; Marcotte, Guillaume; Dumenil, Anne-Sylvie; Jamali, Samir; Lacave, Guillaume; Ruckly, Stéphane; Mourvillier, Bruno; Timsit, Jean-François

    2017-08-01

    Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19-1.67], hypoglycemia 10 mmol/l (aOR = 1.37, 95% CI 1.09-1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53-2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48-3.57), and S. aureus (aOR = 1.54, 95% CI 1.05-2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13-14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09-1.76). Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

  17. De novo GABRG2 mutations associated with epileptic encephalopathies

    Science.gov (United States)

    Shen, Dingding; Hernandez, Ciria C; Shen, Wangzhen; Hu, Ningning; Poduri, Annapurna; Shiedley, Beth; Rotenberg, Alex; Datta, Alexandre N; Leiz, Steffen; Patzer, Steffi; Boor, Rainer; Ramsey, Kerri; Goldberg, Ethan; Helbig, Ingo; Ortiz-Gonzalez, Xilma R; Lemke, Johannes R; Marsh, Eric D; Macdonald, Robert L

    2017-01-01

    Abstract Epileptic encephalopathies are a devastating group of severe childhood onset epilepsies with medication-resistant seizures and poor developmental outcomes. Many epileptic encephalopathies have a genetic aetiology and are often associated with de novo mutations in genes mediating synaptic transmission, including GABAA receptor subunit genes. Recently, we performed next generation sequencing on patients with a spectrum of epileptic encephalopathy phenotypes, and we identified five novel (A106T, I107T, P282S, R323W and F343L) and one known (R323Q) de novo GABRG2 pathogenic variants (mutations) in eight patients. To gain insight into the molecular basis for how these mutations contribute to epileptic encephalopathies, we compared the effects of the mutations on the properties of recombinant α1β2γ2L GABAA receptors transiently expressed in HEK293T cells. Using a combination of patch clamp recording, immunoblotting, confocal imaging and structural modelling, we characterized the effects of these GABRG2 mutations on GABAA receptor biogenesis and channel function. Compared with wild-type α1β2γ2L receptors, GABAA receptors containing a mutant γ2 subunit had reduced cell surface expression with altered subunit stoichiometry or decreased GABA-evoked whole-cell current amplitudes, but with different levels of reduction. While a causal role of these mutations cannot be established directly from these results, the functional analysis together with the genetic information suggests that these GABRG2 variants may be major contributors to the epileptic encephalopathy phenotypes. Our study further expands the GABRG2 phenotypic spectrum and supports growing evidence that defects in GABAergic neurotransmission participate in the pathogenesis of genetic epilepsies including epileptic encephalopathies. PMID:27864268

  18. Risk factors and outcome of Shigella encephalopathy in Bangladeshi children.

    Directory of Open Access Journals (Sweden)

    Farzana Afroze

    2017-04-01

    Full Text Available Although, Shigella encephalopathy, a serious extra-intestinal complication of shigellosis, significantly increases the risks of death, data are very limited on predicting factors particularly related to electrolyte profiles in children below five years of age with Shigella encephalopathy. Our objective was to determine the clinical as well as laboratory predicting factors and outcome of children with Shigella encephalopathy.In this unmatched case-control design, children aged 2-59 months having a positive stool culture for Shigella and who had their serum electrolytes been done from July 2012 to June 2015 were studied. Children with Shigella encephalopathy, defined as having abnormal mentation, constituted the cases, and those without encephalopathy constituted the controls. During the study period, we identified a total of 541 children less than five years of age, who had Shigella in their stool culture. Only 139 children fulfilled the study criteria and among them 69 were cases and 70 were controls. The cases more often had fatal outcome compared to the controls (7% vs. 0%, P = 0.02. In logistic regression analysis, the cases were independently associated with shorter duration (1.2 ± 0.4 days of diarrhea prior to admission, dehydrating diarrhea, sepsis and hyponatremia (p<0.05 for all. Among 139 Shigella isolates, S. flexneri (88/139, 63% and S. sonnei(34/139, 24% were the dominant species. S. dysenteriae was not isolated throughout the study period. S.sonnei was more frequently isolated from the cases (24/69, 35% than the controls (10/70, 14%, whereas the isolation of S. flexneri was comparable between the groups (40/69, 58% vs 48/70, 69%. A total of 94 (67.6% isolates were resistant to trimethoprim-sulphamethoxazole, 84 (60.4% to ciprofloxacin, 66/138 (48% to ampicillin, 5 (3.5% to ceftriaxone, 17 (12.2% to mecillinum and 35 (25% to azithromycin.The case-fatality-rate was significantly higher among the children with Shigella encephalopathy

  19. [Value of MRI findings in Gayet-Wernicke encephalopathy].

    Science.gov (United States)

    Lenz, V; Vargas, M I; Bin, J F; Bogorin, A; Grebici-Guessoum, M; Jacques, C; Marin, H; Zöllner, G; Dietemann, J L

    2002-09-01

    Wernicke encephalopathy (Wernicke-Korsakoff encephalopathy) is related to thiamine deficiency. We report the MRI findings in four patients with visualization of bilateral and symmetrical hyperintense foci on T2W and FLAIR images involving the periaqueductal gray matter, the mamillary bodies and around the third ventricle. Diffusion weighted images obtained in two patients demonstrated mild hypersignal in the same areas. Contrast enhancement within the mamillary bodies was noted in one patient. Follow-up MRI obtained in three patients showed rapid regression of signal abnormalities without correlation with good clinical outcome.

  20. Acute necrotizing encephalopathy of childhood: a Turkish case

    Directory of Open Access Journals (Sweden)

    Olcay Unver

    2014-06-01

    Full Text Available Acute necrotizing encephalopathy of childhood (ANEC is a rare form of acute encephalopathy of unknown etiology characterized by typical symmetrical lesions in the thalami, with variable involvement of the white matter, brainstem and cerebellum. Clinically there is a rapid neurologic deterioration after a short period of a nonspecific viral-like illness associated with gastrointestinal or respiratory signs. Asian children are especially affected. Here we present a 3-year-old boy admitted to our hospital with fever and deterioration of consciousness. The diagnosis of ANEC was made by radiologic findings [Cukurova Med J 2014; 39(3.000: 641-645

  1. [Leigh's encephalopathy (subacute necrotizing encephalopathy). Documentation of its evolution through neuroimaging].

    Science.gov (United States)

    Pena, J A; González-Ferrer, S; Martínez, C; Prieto-Carrasquero, M; Delgado, W; Mora La Cruz, E

    1996-09-01

    A 30 months-old boy developed bilateral nistagmus, tremor, gait disturbance, hypotonia and disartria. The diagnose of Leigh encephalopathy was suggested on the basis of clinical, neuroimaging and laboratory findings. Computed tomography and magnetic resonance imaging (MRI) at an early stage revealed bilateral and symmetric lesions in the putamen, appearing as hyperintense signal on T2-weighted images. Twelve months later a relatively large hypertense area in the posterior brainstem was observed. At this stage, the patient exhibited marked deterioration, dystonic manifestations, rigidity and respiratory disturbances. He died 6 months later for respiratory arrest during bronconeumonic infection. We believe MRI is a valuable means to allow assessment of the evolution of the disease.

  2. Acute hyperammonemic encephalopathy with features on diffusion-weighted images: Report of two cases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ja Young; Yu, In Kyu [Dept. of Radiology, Eulji University Hospital, Daejeon (Korea, Republic of)

    2015-02-15

    Acute hyperammonemic encephalopathy is a rare toxic encephalopathy caused by accumulated plasma ammonia. A few literatures are reported about MRI findings of acute hyperammonemic encephalopathy. It is different from the well-known chronic hepatic encephalopathy. The clinical symptom and MRI findings of acute hyperammonemic encephalopathy can be reversible with proper treatment. Acute hepatic encephalopathy involves the cingulate cortex, diffuse cerebral cortices, insula, bilateral thalami on diffusion-weighted imaging (DWI), and fluid-attenuated inversion-recovery. Acute hepatic encephalopathy might mimic hypoxic-ischemic encephalopathy because of their similar predominant involving sites. We experienced 2 cases of acute hyperammonemic encephalopathy consecutively. They showed restricted diffusion at the cingulate cortex, cerebral cortices, insula, and bilateral dorsomedial thalami on DWI. One patient underwent acute fulminant hepatitis A, the other patient with underlying chronic liver disease had acute liver failure due to hepatotoxicity of tuberculosis medication. In this report, we presented the characteristic features of DWI in acute hyperammonemic encephalopathy. In addition, we reviewed articles on MRI findings of acute hyperammonemic encephalopathy.

  3. Neuropsychological functioning in Wernicke′s encephalopathy

    Directory of Open Access Journals (Sweden)

    Sushree Sangita Behura

    2015-01-01

    Full Text Available Context: Wernicke′s encephalopathy (WE is caused by thiamine (Vitamin B1 deficiency and most commonly found in chronic alcoholism and malnutrition. Clinically, the key features are mental status disturbances (global confusion, oculomotor abnormalities, and gait disturbances (ataxia. Apart from these clinical features, we can find deficits in neuropsychological functioning in patients with WE, which is more prominent after the improvement in the physical conditions. Neuropsychological functioning includes both basic cognitive processes (i.e., attention-concentration as well as higher order cognitive processes (i.e., memory, executive functioning, reasoning, which is much vital for the maintenance of quality of life of an individual. However, unfortunately, in most of the cases, neuropsychological functioning is ignored by the clinicians. Materials and Methods: In this study four case reports of WE have been presented. The patients were taken from the outdoor department of Mental Health Institute, S.C.B. Medical College, Cuttack, Odisha. Neuropsychological functioning was measured by administration of PGIBBD and Quality of Life was measured by WHO-QOL BREF Odia Version. Discussion: As described in the literature, among the three cardinal signs ( global confusion, ataxia, and ocular sings, the first two were present in all cases, but nystagmus was present in only two cases.Memory dysfunction was so disabling that the persons were unable to maintain a good Quality of Life and occupational impairment was prominent. There are disturbances in recent, remote memory, immediate recall, delayed recall, and attention and concentration, ultimately creating both physical and mental disability. PGI-BBD findings also suggest the overall impairment in neuropsychological functioning other than memory, that is, executive functioning, visual acuity, and depth perception. Findings of WHO-QOL BREF suggest the impairment of four domains of QOL in all the cases, but

  4. Intrapartum asphyxia and hypoxic ischaemic encephalopathy in a ...

    African Journals Online (AJOL)

    Objective: To determine the incidence of asphyxia and hypoxic ischaemic encephalopathy (HIE) and predictors of poor outcome in a hospital in a developing country. Methods: Neonates of birth weight ≥2 000 g who required bag-and-mask ventilation and were admitted with a primary diagnosis of asphyxia from January to ...

  5. HHV-6 symptoms in central nervous system. Encephalitis and encephalopathy

    International Nuclear Information System (INIS)

    Yoshinari, Satoshi; Hamano, Shinichiro

    2007-01-01

    Described is the present knowledge of central nervous symptoms, mainly encephalitis and encephalopathy, caused by the primary infection of human herpes virus-6 (HHV-6) in the pediatric field. Discovery of HHV-6 is in 1986, the virus, normally latent, has a high nervous affinity, and most infants are infected until the age of 3 years. Encephalitis and encephalopathy caused by the primary infection can be derived from direct viral invasion in nervous system or secondary like that through angitis. Most of early clinical symptoms are febrile convulsion. Imaging of the head by MRI particularly with diffusion weighted imaging and by cerebral blood flow SPECT with 123 I-infetamine (IMP) is important for classification of encephalitis and encephalopathy by HHV-6: Four types of them are defined according to the area of lesion observed in abnormal images, the basal nuclei-diencephalon-brainstem, frontal lobe-dominant one, cerebral hemisphere and diffusive one. Further reviewed are the diagnosis, treatment and prognosis together with other HHV-6 related problems like infection in neonate, temporal lobe epilepsy and drug-induced hypersensitivity syndrome. Current topics are related with activation of latent HHV-6. Despite numerous findings, many remain to be elucidated in acute encephalitis and encephalopathy which are most important in pediatrics. (R.T.)

  6. Hypothermia therapy for newborns with hypoxic ischemic encephalopathy.

    Science.gov (United States)

    Silveira, Rita C; Procianoy, Renato S

    2015-01-01

    Therapeutic hypothermia reduces cerebral injury and improves the neurological outcome secondary to hypoxic ischemic encephalopathy in newborns. It has been indicated for asphyxiated full-term or near-term newborn infants with clinical signs of hypoxic-ischemic encephalopathy (HIE). A search was performed for articles on therapeutic hypothermia in newborns with perinatal asphyxia in PubMed; the authors chose those considered most significant. There are two therapeutic hypothermia methods: selective head cooling and total body cooling. The target body temperature is 34.5 °C for selective head cooling and 33.5 °C for total body cooling. Temperatures lower than 32 °C are less neuroprotective, and temperatures below 30 °C are very dangerous, with severe complications. Therapeutic hypothermia must start within the first 6h after birth, as studies have shown that this represents the therapeutic window for the hypoxic-ischemic event. Therapy must be maintained for 72 h, with very strict control of the newborn's body temperature. It has been shown that therapeutic hypothermia is effective in reducing neurologic impairment, especially in full-term or near-term newborns with moderate hypoxic-ischemic encephalopathy. Therapeutic hypothermia is a neuroprotective technique indicated for newborn infants with perinatal asphyxia and hypoxic-ischemic encephalopathy. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  7. A novel encephalopathy in a thiamine-deficient dog resembling ...

    African Journals Online (AJOL)

    Thiamine is a water-soluble vitamin, which participates in several vital metabolic pathways involved in energy metabolism and neurotransmitter synthesis of mammals. In companion animals thiamine deficiency is classically associated with signs of diffuse encephalopathy and lesions on brainstem nuclei and ...

  8. About pathognomonic images: an infrequent case of acute encephalopathy

    Directory of Open Access Journals (Sweden)

    Alessandro Grasso

    2013-05-01

    Full Text Available BACKGROUND The occurrence of acute encephalopathy is a dramatic clinical dilemma when usual diagnostic techniques (blood tests, cerebral CT and cerebrospinal fluid analysis show no abnormalities. CLINICAL CASE We describe a case of a 73 years old man admitted in our Internal Medicine Unit for acute diarrhoea with vomiting and fever who developed a prolonged gastrointestinal dysmotility syndrome with poor nutritional intake. Although a parenteral support was provided, he developed acute encephalopathy followed by hypotension and lactic acidosis without evidence of renal and hepatic disease or glycemic alterations. Likewise, no cerebral CT and cerebrospinal fluid alterations were found. Conversely, cerebral MRI showed marked and diffuse DP-2 and FLAIR hyperintensity of the mesencephalic tectal plate, of the periaqueductal area, and of the periventricular region of the third ventricle including the median thalamic area. These MRI descriptions were considered pathognomonic of Wernicke encephalopathy. Thus, the immediate use of ev thiamine was followed by a prompt and complete recovery of neurological, hemodinamic and metabolic conditions. CONCLUSIONS Non-alcoholic Wernicke encephalopathy is a rare and dramatic clinical event with high mortality. In this context, brain MRI is the best diagnostic tool providing a typical picture.

  9. Chronic liver disease and hepatic encephalopathy: Clinical profile ...

    African Journals Online (AJOL)

    2011-03-08

    Mar 8, 2011 ... Background: Hepatic encephalopathy (HE) is an important neuropsychiatry complication of liver disease causing significant morbidity and mortality ... management given the background of new insights in the pathogenesis of this disease entity. .... maintenance with glutein and casein-free diet (GCFD),.

  10. A case of chronic Wernicke's encephalopathy: A neuropsychological study

    NARCIS (Netherlands)

    Oudman, Erik; Van der Stigchel, Stefan; Postma, Albert; Wijnia, Jan W.; Nijboer, Tanja C W

    2014-01-01

    A 54-year-old woman was referred to our Korsakoff Center because of extensive cognitive problems following acute Wernicke's encephalopathy (WE). She had a relatively short history of alcohol abuse and was found lying on the floor in her home by her son. After 5 days without treatment, she was

  11. Wernicke's encephalopathy: a preventable cause of maternal death.

    Science.gov (United States)

    Wedisinghe, Lilantha; Jayakody, Kaushadh; Arambage, Kirana

    2011-01-01

    Wernicke's encephalopathy is a rare cause of maternal death. It is a difficult diagnosis to make but prevention and treatment is straightforward. Severe thiamine deficiency causes Wernicke-Korsakoff syndrome. Correct diagnosis and treatment with thiamine will decrease the case fatality rate.

  12. Outcome Prediction of Neonatal Hypoxic-Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-12-01

    Full Text Available Data for 205 neonates from the multicenter National Institute of Child Health trial of hypothermia in hypoxic-ischemic encephalopathy (HIE were analyzed by using clinical and laboratory variables obtained in the NICUs within 6 hours of birth, with death or moderate/severe disability at 18-22 months or death as the outcomes.

  13. Posterior reversible encephalopathy syndrome in a adult female

    African Journals Online (AJOL)

    Oyinloye, et al.: Posterior reversible encephalopathy syndrome. Annals of African Medicine. Vol. 13, July-September, 2014. Page | 139. Classic neuroimaging applied to patients shows edema involving the white matter in the posterior portions of the cerebral hemispheres, especially bilaterally in the parieto‑occipital regions.

  14. Hypertensive encephalopathy with CT confirma- tion in four chil ...

    African Journals Online (AJOL)

    Kurt

    SA JOURNAL OF RADIOLOGY • February 2005. Abstract. Hypertensive encephalopathy (HE) is a clinical syndrome that occurs infre- quently in children and is often underdiagnosed. We review four patients with HE and describe their clinical presentation and radiological findings on computed tomography. (CT). Our cases ...

  15. Coenzyme Q-responsive Leigh's encephalopathy in two sisters.

    NARCIS (Netherlands)

    Maldergem, L. van; Trijbels, J.M.F.; Mauro, S. Di; Sindelar, P.J.; Musumeci, O.; Janssen, A.J.M.; Delberghe, X.; Martin, J.J.; Gillerot, Y.

    2002-01-01

    A 31-year-old woman had encephalopathy, growth retardation, infantilism, ataxia, deafness, lactic acidosis, and increased signals of caudate and putamen on brain magnetic resonance imaging. Muscle biochemistry showed succinate:cytochrome c oxidoreductase (complex II-III) deficiency. Both clinical

  16. The course of chronic solvent induced encephalopathy: A systematic review

    NARCIS (Netherlands)

    van Valen, Evelien; Wekking, Ellie; Van der Laan, Gert; Sprangers, Mirjam; van Dijk, Frank

    2009-01-01

    Background: Worldwide millions of workers; are exposed to organic solvents. Long term exposure leads in some workers to the development of Chronic Solvent induced Encephalopathy (CSE). The first reports about CSE came from the European Nordic countries in the 1970s. In spite of decades of experience

  17. Critical flicker frequency is diagnostic of minimal hepatic encephalopathy.

    Science.gov (United States)

    Esmat, Serag; Garem, Nouman El; Raslan, Hassan; Elfekki, Mohamed; Sleem, Gihan A

    2017-12-01

    Minimal hepatic encephalopathy may affect up to 80% of cirrhotic patients, in the absence of overt hepatic encephalopathy. The objective of the study is to evaluate the accuracy of diagnosis of minimal hepatic encephalopathy with critical flicker frequency (CFF). The study was conducted on 180 patients with post hepatitis C liver cirrhosis and on 60 healthy subjects as control. Patients and controls were divided into four groups: group 1 (60), healthy individuals as a control group; group 2 (60), patients with liver cirrhosis (Child class A); group 3 (60), patients with liver cirrhosis (Child class B); and group 4 (60), patients with liver cirrhosis (Child class C). All participants were subjected to estimation of CFF, line drawing test, complete blood picture, liver functions, viral markers, and abdominal ultrasound. CFF detected abnormality in 90% of patients. Accuracy of CFF in differentiation of Child A from normal is 100%, Child B from normal is 100%, Child C from normal is 100%, Child A from Child B is 80%, Child A from Child C is 100% and Child B from Child C is 100%, and it has higher accuracy than line drawing test. CFF is a simple, reliable and accurate method for the diagnosis of minimal hepatic encephalopathy. It is not influenced by the patient level of education. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Wernicke's encephalopathy and central pontine myelinolysis in hyperemesis gravidarum

    Science.gov (United States)

    Sutamnartpong, Panee; Muengtaweepongsa, Sombat; Kulkantrakorn, Kongkiat

    2013-01-01

    A pregnant woman, who had been suffering from hyperemesis gravidarum, presented with alteration of consciousness, ocular nystagmus and ataxia. Magnetic Resonance Imaging of the brain showed typical findings of Wernicke's encephalopathy and central pontine myelinolysis. The clinical features responded dramatically to thiamine supplementation. PMID:23546346

  19. Pathophysiological aspects of acute hepatic encephalopathy in the rat

    International Nuclear Information System (INIS)

    Deutz, N.E.P.

    1988-01-01

    The aim of the present thesis is to elucidate the pathogenesis of acute hepatic encephalopathy (HE). In order to study acute HE, plasma and brain concentrations were measured of ammonia, aminoacids, lactate and polyamines as well as brain energy rich phosphates. In addition new techniques of brain research were developed and applied. 277 refs.; 29 figs.; 18 tabs

  20. In vitro adsorption of possible aetiological factors of hepatic encephalopathy

    NARCIS (Netherlands)

    Chamuleau, R. A.; Schoemaker, L. P.; Smit, E. M.

    1979-01-01

    Four different adsorbents (activated charcoal, XAD-4, a strong base anion and a strong acid cation-exchange resin) were tested in vitro for their capacity to remove substances that may be important in the development of hepatic encephalopathy. Separate columns packed with one of these adsorbents

  1. Celiac crisis presenting with status epilepticus and encephalopathy.

    Science.gov (United States)

    Hijaz, Nadia M; Bracken, Julia M; Chandratre, Sonal R

    2014-12-01

    Celiac crisis is a life-threatening presentation of celiac disease which is described in the context of classic gastrointestinal (GI) symptoms of diarrhea, leading to dehydration and electrolyte imbalance. Neurologic manifestations are atypical symptoms of celiac crisis. To the best of our knowledge, there is no published report on seizure or encephalopathy as the presenting manifestation of celiac crisis. We describe a 2-year-old boy presenting with acute status epilepticus and lethargy. Prior to presentation, he had mild abdominal distention and intermittent diarrhea. Laboratory analysis revealed hyponatremia, anemia, hypocalcemia, transaminitis, and hyperglycemia. Electroencephalography revealed severe diffuse encephalopathy, and complete infectious work-up was negative. Initial brain magnetic resonance imaging was normal; however, repeat imaging showed osmotic demyelination syndrome. Given the history of GI symptoms and hyperglycemia, celiac serology was obtained revealing elevated tissue transglutaminase, and a diagnosis was confirmed by Marsh 3c lesions in the duodenum. He significantly improved with steroid therapy in addition to adequate nutrition, fluids, and initiation of a gluten-free diet. We report herein on the first case of celiac crisis presenting with status epilepticus and encephalopathy in the absence of profound GI symptoms. Our case suggests that celiac crisis should be considered in the differential of seizures and encephalopathy in children.

  2. Another cause of vaccine encephalopathy: a case of Angelman syndrome.

    Science.gov (United States)

    Novy, Jan; Catarino, Claudia B; Chinthapalli, Krishna; Smith, Shelagh M; Clayton-Smith, Jill; Hennekam, Raoul C M; Hammond, Peter; Sisodiya, Sanjay M

    2012-05-01

    Dravet syndrome has been found recently as an important underlying condition in cases of alleged vaccine encephalopathy after pertussis vaccination, where vaccination seemed to have precipitated the occurrence of the disease without modifying the long-term course. We report on a patient diagnosed with Angelman syndrome in her fifth decade, in whom the intellectual disability and epilepsy had been assumed to be caused by a vaccine encephalopathy following smallpox vaccination. Clinical features of Angelman syndrome had faded away. The history of the present patient suggests that genetic conditions other than Dravet syndrome can be associated with an alleged vaccine encephalopathy. A history of vaccine encephalopathy is rare among patients with learning disability and refractory epilepsy (1.4% in our cohort), but it should lead to consideration of a comprehensive genetic work-up if Dravet syndrome is excluded. The early history of the patient, when available, should guide the investigations. Medico-legal aspects are also discussed. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  3. Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Kjaergard, L L; Gluud, C

    2001-01-01

    The pathogenesis of hepatic encephalopathy is unknown. It has been suggested that liver failure leads to the accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition which may progress to coma. Several trials have assessed benzodiazepine receptor...

  4. Models for discovery of targeted therapy in genetic epileptic encephalopathies.

    Science.gov (United States)

    Maljevic, Snezana; Reid, Christopher A; Petrou, Steven

    2017-10-01

    Epileptic encephalopathies are severe disorders emerging in the first days to years of life that commonly include refractory seizures, various types of movement disorders, and different levels of developmental delay. In recent years, many de novo occurring variants have been identified in individuals with these devastating disorders. To unravel disease mechanisms, the functional impact of detected variants associated with epileptic encephalopathies is investigated in a range of cellular and animal models. This review addresses efforts to advance and use such models to identify specific molecular and cellular targets for the development of novel therapies. We focus on ion channels as the best-studied group of epilepsy genes. Given the clinical and genetic heterogeneity of epileptic encephalopathy disorders, experimental models that can reflect this complexity are critical for the development of disease mechanisms-based targeted therapy. The convergence of technological advances in gene sequencing, stem cell biology, genome editing, and high throughput functional screening together with massive unmet clinical needs provides unprecedented opportunities and imperatives for precision medicine in epileptic encephalopathies. © 2017 International Society for Neurochemistry.

  5. GRIN1 Mutations in Early-Onset Epileptic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Wenjuan Chen

    2015-06-01

    Full Text Available Investigators from Yokohama City University and other medical centers in Israel and Japan reported mutations on N-methyl-D-aspartate (NMDA receptors subunit GRIN1 (GluN1 identified in patients with nonsyndromic intellectual disability and early-onset epileptic encephalopathy.

  6. Another cause of vaccine encephalopathy: A case of Angelman syndrome

    NARCIS (Netherlands)

    Novy, Jan; Catarino, Claudia B.; Chinthapalli, Krishna; Smith, Shelagh M.; Clayton-Smith, Jill; Hennekam, Raoul C. M.; Hammond, Peter; Sisodiya, Sanjay M.

    2012-01-01

    Dravet syndrome has been found recently as an important underlying condition in cases of alleged vaccine encephalopathy after pertussis vaccination, where vaccination seemed to have precipitated the occurrence of the disease without modifying the long-term course. We report on a patient diagnosed

  7. CADASIL: Migraine, Encephalopathy, Stroke and Their Inter-Relationships.

    Science.gov (United States)

    Tan, Rhea Yan Ying; Markus, Hugh Stephen

    2016-01-01

    Migraine is common in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) but its treatment responses are not well described, and its relationship to stroke risk unknown. Encephalopathy is a less common presentation; it has been suggested it is related to migraine. We characterised migraine patterns and treatment responses in CADASIL, and examined associations between migraine and both stroke risk and encephalopathy. 300 symptomatic CADASIL patients were prospectively recruited from a national referral clinic over a nineteen year period, from 1996 to 2015. Data was collected using a standardised questionnaire. Migraine was classified according to the International Classification of Headache Disorders, 3rd edition (beta version). A cross-sectional analysis was carried out on the data collected. Migraine was present in 226 (75.3%), and the presenting feature in 203 (67.7%). It was usually accompanied by aura (89.8%). Patients showed variable responses to a variety of drugs for migraine. Of 24 given triptans, 45.5% had consistent or partial responses. None had complications following triptans. Thirty-three (11.0%) patients experienced encephalopathy lasting on average 8.1 ± 3.4 days. Patients with migraine with aura had higher odds of encephalopathy (OR = 5.4; 95%CI 1.6-28.4; p = 0.002). Patients with confusional aura had higher odds of encephalopathy than those with other aura types (OR = 2.5, 95%CI = 1.0-5.8, p = 0.04). There was also no increase in risk of encephalopathy with sex or age at onset of migraine. Migraineurs had a lower stroke risk than non-migraineurs (HR = 0.46, 95%CI 0.3-0.6, p = 2.1x10-6). Migraine with aura is a prominent feature of CADASIL. Treatment responses are similar to those seen in the general migraine population and no complications were observed with triptans. Migraine with aura was associated with increased risk of encephalopathy suggesting they may share pathophysiological mechanisms

  8. Metformin inhibits glutaminase activity and protects against hepatic encephalopathy.

    Directory of Open Access Journals (Sweden)

    Javier Ampuero

    Full Text Available AIM: To investigate the influence of metformin use on liver dysfunction and hepatic encephalopathy in a retrospective cohort of diabetic cirrhotic patients. To analyze the impact of metformin on glutaminase activity and ammonia production in vitro. METHODS: Eighty-two cirrhotic patients with type 2 diabetes were included. Forty-one patients were classified as insulin sensitizers experienced (metformin and 41 as controls (cirrhotic patients with type 2 diabetes mellitus without metformin treatment. Baseline analysis included: insulin, glucose, glucagon, leptin, adiponectin, TNFr2, AST, ALT. HOMA-IR was calculated. Baseline HE risk was calculated according to minimal hepatic encephalopathy, oral glutamine challenge and mutations in glutaminase gene. We performed an experimental study in vitro including an enzymatic activity assay where glutaminase inhibition was measured according to different metformin concentrations. In Caco2 cells, glutaminase activity inhibition was evaluated by ammonia production at 24, 48 and 72 hours after metformina treatment. RESULTS: Hepatic encephalopathy was diagnosed during follow-up in 23.2% (19/82: 4.9% (2/41 in patients receiving metformin and 41.5% (17/41 in patients without metformin treatment (logRank 9.81; p=0.002. In multivariate analysis, metformin use [H.R.11.4 (95% CI: 1.2-108.8; p=0.034], age at diagnosis [H.R.1.12 (95% CI: 1.04-1.2; p=0.002], female sex [H.R.10.4 (95% CI: 1.5-71.6; p=0.017] and HE risk [H.R.21.3 (95% CI: 2.8-163.4; p=0.003] were found independently associated with hepatic encephalopathy. In the enzymatic assay, glutaminase activity inhibition reached 68% with metformin 100 mM. In Caco2 cells, metformin (20 mM decreased glutaminase activity up to 24% at 72 hours post-treatment (p<0.05. CONCLUSIONS: Metformin was found independently related to overt hepatic encephalopathy in patients with type 2 diabetes mellitus and high risk of hepatic encephalopathy. Metformin inhibits glutaminase

  9. Metformin inhibits glutaminase activity and protects against hepatic encephalopathy.

    Science.gov (United States)

    Ampuero, Javier; Ranchal, Isidora; Nuñez, David; Díaz-Herrero, María del Mar; Maraver, Marta; del Campo, José Antonio; Rojas, Ángela; Camacho, Inés; Figueruela, Blanca; Bautista, Juan D; Romero-Gómez, Manuel

    2012-01-01

    To investigate the influence of metformin use on liver dysfunction and hepatic encephalopathy in a retrospective cohort of diabetic cirrhotic patients. To analyze the impact of metformin on glutaminase activity and ammonia production in vitro. Eighty-two cirrhotic patients with type 2 diabetes were included. Forty-one patients were classified as insulin sensitizers experienced (metformin) and 41 as controls (cirrhotic patients with type 2 diabetes mellitus without metformin treatment). Baseline analysis included: insulin, glucose, glucagon, leptin, adiponectin, TNFr2, AST, ALT. HOMA-IR was calculated. Baseline HE risk was calculated according to minimal hepatic encephalopathy, oral glutamine challenge and mutations in glutaminase gene. We performed an experimental study in vitro including an enzymatic activity assay where glutaminase inhibition was measured according to different metformin concentrations. In Caco2 cells, glutaminase activity inhibition was evaluated by ammonia production at 24, 48 and 72 hours after metformina treatment. Hepatic encephalopathy was diagnosed during follow-up in 23.2% (19/82): 4.9% (2/41) in patients receiving metformin and 41.5% (17/41) in patients without metformin treatment (logRank 9.81; p=0.002). In multivariate analysis, metformin use [H.R.11.4 (95% CI: 1.2-108.8); p=0.034], age at diagnosis [H.R.1.12 (95% CI: 1.04-1.2); p=0.002], female sex [H.R.10.4 (95% CI: 1.5-71.6); p=0.017] and HE risk [H.R.21.3 (95% CI: 2.8-163.4); p=0.003] were found independently associated with hepatic encephalopathy. In the enzymatic assay, glutaminase activity inhibition reached 68% with metformin 100 mM. In Caco2 cells, metformin (20 mM) decreased glutaminase activity up to 24% at 72 hours post-treatment (p<0.05). Metformin was found independently related to overt hepatic encephalopathy in patients with type 2 diabetes mellitus and high risk of hepatic encephalopathy. Metformin inhibits glutaminase activity in vitro. Therefore, metformin use seems

  10. Neonatal encephalopathy and the association to asphyxia in labor.

    Science.gov (United States)

    Jonsson, Maria; Ågren, Johan; Nordén-Lindeberg, Solveig; Ohlin, Andreas; Hanson, Ulf

    2014-12-01

    In cases with moderate and severe neonatal encephalopathy, we aimed to determine the proportion that was attributable to asphyxia during labor and to investigate the association between cardiotocographic (CTG) patterns and neonatal outcome. In a study population of 71,189 births from 2 Swedish university hospitals, 80 cases of neonatal encephalopathy were identified. Cases were categorized by admission CTG patterns (normal or abnormal) and by the presence of asphyxia (cord pH, asphyxia at birth were considered to experience asphyxia related to labor. CTG patterns were assessed for the 2 hours preceding delivery. Admission CTG patterns were normal in 51 cases (64%) and abnormal in 29 cases (36%). The rate of cases attributable to asphyxia (ie, hypoxic ischemic encephalopathy) was 48 of 80 cases (60%), most of which evolved during labor (43/80 cases; 54%). Both severe neonatal encephalopathy and neonatal death were more frequent with an abnormal, rather than with a normal, admission CTG pattern (13 [45%] vs 11 [22%]; P = .03), and 6 [21%] vs 3 [6%]; P = .04), respectively. Comparison of cases with an abnormal and a normal admission CTG pattern also revealed more frequently observed decreased variability (12 [60%] and 8 [22%], respectively) and more late decelerations (8 [40%] and 1 [3%], respectively). Moderate and severe encephalopathy is attributable to asphyxia in 60% of cases, most of which evolve during labor. An abnormal admission CTG pattern indicates a poorer neonatal outcome and more often is associated with pathologic CTG patterns preceding delivery. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. The burden of hepatic encephalopathy in Latin America.

    Science.gov (United States)

    Dávalos Moscol, Milagros; Bustios Sanchez, Carla

    2011-06-01

    Hepatic encephalopathy (HE) is a neuropsychiatric syndrome characterized by changes in cognitive function, behavior, and personality, as well as by transient neurological symptoms and electroencephalographic changes, which occur in the context of acute or chronic liver failure. Cirrhosis is the main disease associated to HE, and it is known that its incidence is increasing worldwide. As a cause of mortality, cirrhosis is ranked 14 worldwide, but 10 in developed countries. It has been demonstrated that the incidence of liver disease is increasing, in part because of the ascending prevalence of NAFLD, HCV, HCC, as well of alcohol consumption. The real incidence of cirrhosis in Latin America is unknown, although in some Latin American countries that provided national data, cirrhosis death rates were between 5 and 17/100,000 for men and 3 and 5/100,000 for women. Disability, quality of life, and social aspects should be considered when assessing the impact of a disease. In this context, preliminary estimates of the global burden of disease attributable to chronic liver disease seem to be substantial. Hepatic encephalopathy, a main complication of liver failure, occurs in 30-45% of patients as overt encephalopathy, but when subclinical or minimal hepatic encephalopathy (MHE) is considered, estimates of the incidence of encephalopathy vary from 20 to 60%. In USA, the 2009 NIH Report on the Costs of Digestive Diseases stated that liver disease was the second most costly disease in direct and indirect costs (13.1 billion dollars). Although the economic cost of HE has not been assessed, it is obvious that the economic impact of HE on daily activities of living is extremely high, as the costs of diminished work performance and lost wages are substantial.

  12. The epileptic encephalopathy jungle - from Dr West to the concepts of aetiology-related and developmental encephalopathies.

    Science.gov (United States)

    Kalser, Judith; Cross, J Helen

    2018-04-01

    We aim to further disentangle the jungle of terminology of epileptic encephalopathy and provide some insights into the current understanding about the aetiology and pathophysiology of this process. We cover also the key features of epilepsy syndromes of infancy and childhood which are considered at high risk of developing an epileptic encephalopathy. The concept of 'epileptic encephalopathy' has progressively been elaborated by the International League Against Epilepsy according to growing clinical and laboratory evidence. It defines a process of neurological impairment caused by the epileptic activity itself and, therefore, potentially reversible with successful treatment, although to a variable extent. Epileptic activity interfering with neurogenesis, synaptogenesis, and normal network organization as well as triggering neuroinflammation are among the possible pathophysiological mechanisms leading to the neurological compromise. This differs from the newly introduced concept of 'developmental encephalopathy' which applies to where the epilepsy and developmental delay are both because of the underlying aetiology and aggressive antiepileptic treatment may not be helpful. The understanding and use of correct terminology is crucial in clinical practice enabling appropriate expectations of antiepileptic treatment. Further research is needed to elucidate underlying pathophysiological mechanisms, define clear outcome predictors, and find new treatment targets.

  13. MRI and CT appearances in metabolic encephalopathies due to systemic diseases in adults

    International Nuclear Information System (INIS)

    Bathla, G.; Hegde, A.N.

    2013-01-01

    The term encephalopathy refers to a clinical scenario of diffuse brain dysfunction, commonly due to a systemic, metabolic, or toxic derangement. Often the clinical evaluation is unsatisfactory in this scenario and imaging plays an important role in the diagnosis, assessment of treatment response, and prognostication of the disorder. Hence, it is important for radiologists to be familiar with the imaging features of some relatively frequently acquired metabolic encephalopathies encountered in the hospital setting. This study reviews the computed tomography (CT) and magnetic resonance imaging (MRI) features of a number of metabolic encephalopathies that occur as part of systemic diseases in adults. The following conditions are covered in this review: hypoglycaemic encephalopathy, hypoxic ischaemic encephalopathy, non-ketotic hyperglycaemia, hepatic encephalopathy, uraemic encephalopathy, hyperammonaemic encephalopathy, and posterior reversible encephalopathy syndrome. MRI is the imaging method of choice in evaluating these conditions. Due to their high metabolic activity, bilateral basal ganglia changes are evident in the majority of cases. Concurrent imaging abnormalities in other parts of the central nervous system often provide useful diagnostic information about the likely underlying cause of the encephalopathy. Besides this, abnormal signal intensity and diffusion restriction patterns on MRI and MR spectroscopy features may provide important clues as to the diagnosis and guide further management. Frequently, the diagnosis is not straightforward and typical imaging features require correlation with clinical and laboratory data for accurate assessment

  14. A review of developmental outcomes of term infants with post-asphyxia neonatal encephalopathy.

    Science.gov (United States)

    Pin, Tamis W; Eldridge, Bev; Galea, Mary P

    2009-05-01

    Post-asphyxia neonatal encephalopathy (NE) is one of the main causes of disabilities in term-born infants. This review attempted to investigate the developmental outcomes of term-born infants with post-asphyxia NE. An electronic search on various databases identified 13 empirical studies against the selection criteria modified from the consensus statement from the International Cerebral Palsy Task Force. The overall quality of methodology of these studies was average. The random effect meta-estimate of the proportion of infants having adverse developmental outcomes such as death, cognitive impairment, sensory-motor impairments was 47% (95% CI 36-57%). Significant heterogeneity (I(2)=87.7%, pasphyxia and post-asphyxia NE, making the study samples heterogeneous. Clinicians and researchers are urged to make use of the recent consensus statement regarding diagnostic criteria for intrapartum asphyxia and to identify these high-risk infants for early intervention.

  15. Clinical manifestations and treatment response of steroid in pediatric Hashimoto encephalopathy.

    Science.gov (United States)

    Yu, Hee Joon; Lee, Jeehun; Seo, Dae Won; Lee, Munhyang

    2014-07-01

    Hashimoto encephalopathy is a steroid-responsive encephalopathy associated with elevated titers of antithyroid antibodies. Clinical symptoms are characterized by behavioral and cognitive changes, speech disturbance, seizures, myoclonus, psychosis, hallucination, involuntary movements, cerebellar signs, and coma. The standard treatment is the use of corticosteroids along with the treatment of any concurrent dysthyroidism. Other options are immunoglobulins and plasmapheresis. We described symptoms and outcomes on 3 teenage girls with Hashimoto encephalopathy. Presenting symptoms were seizure or altered mental status. One patient took levothyroxine due to hypothyroidism before presentation of Hashimoto encephalopathy. After confirmation of elevated antithyroid antibodies, all patients were treated with steroids. One patient needed plasmapheresis because of the lack of response to steroids and immunoglobulins. Hashimoto encephalopathy should be considered in any patient presenting with acute or subacute unexplained encephalopathy and seizures. Even though the use of steroids is the first line of treatment, plasmapheresis can rescue steroid-resistant patients. © The Author(s) 2013.

  16. Hepatic encephalopathy associated with hepatic lipidosis in llamas (Lama glama).

    Science.gov (United States)

    Pillitteri, C A; Craig, L E

    2013-01-01

    Hepatic encephalopathy has been listed as a differential for llamas displaying neurologic signs, but it has not been histopathologically described. This report details the neurologic histopathologic findings associated with 3 cases of hepatic lipidosis with concurrent neurologic signs and compares them to 3 cases of hepatic lipidosis in the absence of neurologic signs and 3 cases without hepatic lipidosis. Brain from all 3 llamas displaying neurologic signs contained Alzheimer type II cells, which were not detected in either subset of llamas without neurologic signs. Astrocytic immunohistochemical staining intensity for glial fibrillary acid protein was decreased in llamas with neurologic signs as compared to 2 of 3 llamas with hepatic lipidosis and without neurologic signs and to 2 of 3 llamas without hepatic lipidosis. Immunohistochemical staining for S100 did not vary between groups. These findings suggest that hepatic encephalopathy may be associated with hepatic lipidosis in llamas.

  17. Severe valproate induced hyperammonemic encephalopathy successfully managed with peritoneal dialysis.

    Science.gov (United States)

    Kumar, Amandeep; Suri, Ashish; Sharma, Bhawani S

    2014-07-01

    Valproic acid (VPA) is a commonly used drug for epilepsy, psychiatric disorders and migraine and is frequently used in neurosurgical intensive care units. Though most of its side-effects are mild and transient, certain idiosyncratic side-effects have been attributed to VPA. Valproate induced hyperammonemia (VIH) is one such side-effect. VIH can produce symptoms of encephalopathy known as valproate induced hyperammonemic encephalopathy (VHE). VIH and VHE usually respond to withdrawal of VPA. However, in some cases VHE can be unresponsive to supportive measures and severe enough to be life-threatening. In such cases, dialysis can be used to rapidly reverse hyperammonemia and VHE and can prove to be a lifesaving measure. We report such a case of VIH and life-threatening VHE in a postoperative neurosurgical patient that was managed successfully with peritoneal dialysis.

  18. Mutations of PTPN23 in developmental and epileptic encephalopathy

    KAUST Repository

    Sowada, Nadine

    2017-10-31

    Developmental and epileptic encephalopathies (DEE) are a heterogeneous group of neurodevelopmental disorders with poor prognosis. Recent discoveries have greatly expanded the repertoire of genes that are mutated in epileptic encephalopathies and DEE, often in a de novo fashion, but in many patients, the disease remains molecularly uncharacterized. Here, we describe a new form of DEE in patients with likely deleterious biallelic variants in PTPN23. The phenotype is characterized by early onset drug-resistant epilepsy, severe and global developmental delay, microcephaly, and sometimes premature death. PTPN23 encodes a tyrosine phosphatase with strong brain expression, and its knockout in mouse is embryonically lethal. Structural modeling supports a deleterious effect of the identified alleles. Our data suggest that PTPN23 mutations cause a rare severe form of autosomal-recessive DEE in humans, a finding that requires confirmation.

  19. [Current possibilities in the therapy of hepatic encephalopathy].

    Science.gov (United States)

    Meier, P J; Bansky, G

    1990-04-14

    Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome associated with acute or chronic liver disease. It is generally considered a metabolic and potentially reversible syndrome. An important component of HE is increased neuro-inhibition caused by reduced hepatic metabolism of gut-derived nitrogenous substances and by activation of the postsynaptic GABAA-receptor complex in the central nervous system. Effective conventional therapy of HE includes prevention of precipitating factors, restriction of dietary protein an administration of lactulose (or lactitol) and possibly also of antibiotics. In addition, animal studies and uncontrolled clinical studies indicate that the benzodiazepine antagonist flumazenil effectively diminishes the increased neuroinhibition in certain patients with HE. However, these favourable flumazenil effects must be confirmed in larger randomized and placebo-controlled multicenter studies before flumazenil can be regarded as a useful new addition to current management of patients with acute or chronic hepatic encephalopathy.

  20. Neurophysiological investigations of hepatic encephalopathy: ISHEN practice guidelines.

    Science.gov (United States)

    Guerit, Jean-Michel; Amantini, Aldo; Fischer, Catherine; Kaplan, Peter W; Mecarelli, Oriano; Schnitzler, Alfons; Ubiali, Emilio; Amodio, Piero

    2009-07-01

    By studying neuronal activity through neuronal electrogenesis, neurophysiological investigations provide a functional assessment of the nervous system and, therefore, has been used for quantitative assessment and follow-up of hepatic encephalopathy (HE). The different clinical neurophysiological approaches can be classified depending on the function to explore and their sensitivity to HE. The reliable techniques are those that reflect cortical function, i.e., cognitive-evoked potentials (EPs) (P300 paradigm), electroencephalogram (EEG), visual EPs (latency>100 ms) and somatosensory EPs (SEPs) (latency between 25 and 100 ms). Short-latency EPs (brainstem acoustic EPs, SEPs of a latencyreservation that the mildest degrees of encephalopathy might be associated with an EEG pattern similar to that induced by drugs; and (iii) to demonstrate the worsening or, conversely improvement, of HE in the follow-up period.

  1. [Wernicke's encephalopathy following sleeve gastrectomy for morbid obesity].

    Science.gov (United States)

    Landais, A; Saint-Georges, G

    2014-11-01

    Bariatric restrictive interventions, as sleeve gastrectomy or gastric banding can cause metabolic complications, especially when vomiting is present, such as thiamine deficiency that can lead to Wernicke's encephalopathy. A 31-year-old man with a 47kg/m(2) body mass index presented with Wernicke's encephalopathy, with ophtalmoplegia, nystagmus, ataxia and confusion, followed by a Korsakoff syndrome, occurring two months after a sleeve gastrectomy. MRI showed hyperintense signals on T2 and FLAIR image in both thalamus, periaqueducal area and mamillary bodies. A close clinical and biological monitoring is required in the first year after surgery, especially if vomiting occurs. Early diagnostic and treatment are needed to avoid severe sequelae. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  2. Iatrogenic Wernicke encephalopathy in a patient with severe hyperemesis gravidarum.

    Science.gov (United States)

    Giugale, Lauren E; Young, Omar M; Streitman, David C

    2015-05-01

    Hyperemesis gravidarum complicates 0.5-2.0% of pregnancies and may lead to substantial nutritional deficiencies. Total parenteral nutrition can be used in severe cases in an attempt to avoid such deficiencies. Rarely, thiamine deficiency resulting in Wernicke encephalopathy occurs, with significant maternal morbidity. We present the case of a 30-year-old woman with hyperemesis gravidarum at 13 4/7 weeks of gestation treated with prolonged total parenteral nutrition that lacked thiamine supplementation, resulting in iatrogenic Wernicke encephalopathy. After high-dose intravenous thiamine repletion, she experienced slow resolution of her symptoms. Pregnancies complicated by hyperemesis gravidarum treated with total parenteral nutrition represent potential high-risk clinical scenarios for thiamine deficiency. Compositions of total parenteral nutrition are not standardized. Thus, physicians must confirm repletion of all essential components to avoid significant morbidity.

  3. Wernicke’s encephalopathy following hyperemesis gravidarum: A case report

    Directory of Open Access Journals (Sweden)

    leila pourali

    2016-06-01

    Full Text Available Introduction: Wernicke’s Korsakoff syndrome is the most important complication of severe thiamine deficiency. Confusion and gait ataxia are the most prevalent symptoms, respectively. The aim of this study was report of a case of Wernicke’s encephalopathy following hyperemesis gravidarum. Case report: A 28-years-old pregnant woman in 19th weeks of gestation referred to the hospital with hyperemesis, gait ataxia, and dysarthria. MRI showed hyperdense lesion which was characteristic of wernicke’s encephalopathy. Rapid improvement in patient’s condition occurred after thiamine infusion. Conclusion: In hyperemesis gravidarum, presence of either symptoms of ocular or mental disorder or ataxia must be considered to rull out Wernicke’s syndrome which can cause maternal death.

  4. Branched-chain amino acids for people with hepatic encephalopathy

    DEFF Research Database (Denmark)

    Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo

    2015-01-01

    BACKGROUND: Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched...... control, language, or publication status. DATA COLLECTION AND ANALYSIS: The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic...... on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small...

  5. Epilepsy surgery for early infantile epileptic encephalopathy (ohtahara syndrome).

    Science.gov (United States)

    Malik, Saleem I; Galliani, Carlos A; Hernandez, Angel W; Donahue, David J

    2013-12-01

    Early infantile epileptic encephalopathy or Ohtahara syndrome is the earliest form of the age-dependent epileptic encephalopathies. Its manifestations include tonic spasms, focal motor seizures, suppression burst pattern, pharmaco-resistance, and dismal prognosis. The purpose of this study was to evaluate the effectiveness of epilepsy surgery in selected infants. We identified 11 patients, 9 from the literature and 2 from our institution that fulfilled diagnostic criteria of Ohtahara syndrome and had undergone epilepsy surgery in infancy. Seven of the 11 infants have remained seizure free (Engel class IA) and four are reportedly having rare to infrequent seizures (Engel class IIB). All patients experienced "catch up" development. In contrast to Ohtahara's15 pharmacotherapy managed patients, who had a mortality rate of approximately fifty percent, and those that survived continued to have seizures and were severely impaired, the outcome of selected surgically managed patients is much more favorable.

  6. Dextromethorphan in the treatment of early myoclonic encephalopathy evolving into migrating partial seizures in infancy

    OpenAIRE

    Yin-Hsuan Chien; Ming-I. Lin; Wen-Chin Weng; Jung-Chieh Du; Wang-Tso Lee

    2012-01-01

    Epileptic encephalopathy with suppression-burst in electroencephalography (EEG) can evolve into a few types of epileptic syndromes. We present here an unusual case of early myoclonic encephalopathy that evolved into migrating partial seizures in infancy. A female neonate initially had erratic myoclonus movements, hiccups, and a suppression-burst pattern in EEG that was compatible with early myoclonic encephalopathy. The seizures were controlled with dextromethorphan (20 mg/kg), and a suppress...

  7. Medical image of the week: MRI of Wernicke's encephalopathy

    Directory of Open Access Journals (Sweden)

    Reyes N

    2013-02-01

    Full Text Available A 61 year old male presented to the ED with altered mental status after being found down at home with several beer cans around him. He was noted to have horizontal nystagmus on hospital day 2 and a MRI was performed. MRI showed bilateral thalamic enhancement (Figure 1, arrows on flair imaging consistent with Wernicke’s encephalopathy. His thiamine dose was increased with improvement in his mental status.

  8. Approach to Clinical Syndrome of Jaundice and Encephalopathy in Tropics

    Science.gov (United States)

    Anand, Anil C.; Garg, Hitendra K.

    2015-01-01

    A large number of patients present with jaundice and encephalopathy in tropical country like India and acute liver failure is the usual cause. Clinical presentation like ALF is also a complication of many tropical infections, and these conditions may mimic ALF but may have subtle differences from ALF. Moreover, what hepatologists see as acute liver failure in tropics is different from what is commonly described in Western Textbooks. Paracetamol overdose, which is possibly the commonest cause of ALF in UK and USA, is hardly ever seen in India. Most common etiology here is viral hepatitis (hepatitis E > hepatitis B> hepatitis A). Apart from ALF, one may also come across subacute hepatic failure (SAHF) as well as acute-on-chronic liver failure (ACLF) due to viral hepatitis. Interestingly, a host of other conditions can mimic ALF because clinical presentation in these conditions can be dominated by jaundice and encephalopathy. Malarial hepatopathy is possibly the best-known condition out of these and is not an uncommon manifestation of severe malaria. A similar presentation can also be seen in other common infections in tropics such as dengue fever, typhoid fever, leptospirosis, scrub typhus, amoebic liver abscesses, tuberculosis and other bacterial and fungal infections with or without human immunodeficiency virus (HIV) related disease. In many of these conditions, liver failure may not be underlying pathophysiology. Some pregnancy related liver diseases could also present with jaundice and encephalopathy. This review summarizes the commonly seen presentations in tropical country like India, where jaundice and encephalopathy dominate the clinical picture. PMID:26041951

  9. Brainstem variant of posterior reversible encephalopathy syndrome: A case report.

    Science.gov (United States)

    Tortora, Fabio; Caranci, Ferdinando; Belfiore, Maria Paola; Manzi, Francesca; Pagliano, Pasquale; Cirillo, Sossio

    2015-12-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological condition, generally observed in conjunction with severe and acute hypertension, that involves mainly the posterior head areas (occipital and temporal lobes) and anterior "watershed" areas. In this syndrome it is rare to observe a predominant involvement of the brainstem. We describe the clinical and radiological findings in a patient with brainstem involvement, discussing its pathophysiological features and possible differential diagnosis. © The Author(s) 2015.

  10. Posterior reversible encephalopathy syndrome presenting as Balint syndrome.

    Science.gov (United States)

    Kumar, Sunil; Abhayambika, Archana; Sundaram, Arun N E; Sharpe, James A

    2011-09-01

    Balint syndrome is a disorder of inaccurate visually guided saccades, optic ataxia, and simultanagnosia that typically results from bilateral parieto-occipital lesions. Visual perception disturbances in the posterior reversible encephalopathy syndrome (PRES) include hemianopia, visual neglect, and cerebral blindness, but Balint syndrome had not been recognized. We report Balint syndrome associated with PRES in a 37-year-old woman with acute hypertension and systemic lupus erythematosus. Balint syndrome can be an initial presentation of PRES.

  11. Chronic traumatic encephalopathy: the dangers of getting "dinged"

    OpenAIRE

    Lakhan, Shaheen E; Kirchgessner, Annette

    2012-01-01

    Chronic traumatic encephalopathy (CTE) is a form of neurodegeneration that results from repetitive brain trauma. Not surprisingly, CTE has been linked to participation in contact sports such as boxing, hockey and American football. In American football getting "dinged" equates to moments of dizziness, confusion, or grogginess that can follow a blow to the head. There are approximately 100,000 to 300,000 concussive episodes occurring in the game of American football alone each year. It is beli...

  12. An Unusual Case of Posterior Reversible Encephalopathy Syndrome

    Directory of Open Access Journals (Sweden)

    Robert P. Zemple

    2017-07-01

    Full Text Available A 21-year-old pregnant female with no significant past medical history presented with acute onset headache and nausea as well as tonic-clonic seizures, then rapidly decompensated into a coma with complete absence of brainstem reflexes. The patient was ultimately diagnosed with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome and subsequent posterior reversible encephalopathy syndrome (PRES with brainstem involvement. Emergent delivery and blood pressure control resulted in rapid and complete neurologic recovery.

  13. STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy.

    Science.gov (United States)

    Stamberger, Hannah; Nikanorova, Marina; Willemsen, Marjolein H; Accorsi, Patrizia; Angriman, Marco; Baier, Hartmut; Benkel-Herrenbrueck, Ira; Benoit, Valérie; Budetta, Mauro; Caliebe, Almuth; Cantalupo, Gaetano; Capovilla, Giuseppe; Casara, Gianluca; Courage, Carolina; Deprez, Marie; Destrée, Anne; Dilena, Robertino; Erasmus, Corrie E; Fannemel, Madeleine; Fjær, Roar; Giordano, Lucio; Helbig, Katherine L; Heyne, Henrike O; Klepper, Joerg; Kluger, Gerhard J; Lederer, Damien; Lodi, Monica; Maier, Oliver; Merkenschlager, Andreas; Michelberger, Nina; Minetti, Carlo; Muhle, Hiltrud; Phalin, Judith; Ramsey, Keri; Romeo, Antonino; Schallner, Jens; Schanze, Ina; Shinawi, Marwan; Sleegers, Kristel; Sterbova, Katalin; Syrbe, Steffen; Traverso, Monica; Tzschach, Andreas; Uldall, Peter; Van Coster, Rudy; Verhelst, Helene; Viri, Maurizio; Winter, Susan; Wolff, Markus; Zenker, Martin; Zoccante, Leonardo; De Jonghe, Peter; Helbig, Ingo; Striano, Pasquale; Lemke, Johannes R; Møller, Rikke S; Weckhuysen, Sarah

    2016-03-08

    To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously reported patients. We recruited newly diagnosed patients with STXBP1 mutations through an international network of clinicians and geneticists. Furthermore, we performed a systematic literature search to review the phenotypes of all previously reported patients. We describe the phenotypic features of 147 patients with STXBP1-E including 45 previously unreported patients with 33 novel STXBP1 mutations. All patients have intellectual disability (ID), which is mostly severe to profound (88%). Ninety-five percent of patients have epilepsy. While one-third of patients presented with Ohtahara syndrome (21%) or West syndrome (9.5%), the majority has a nonsyndromic early-onset epilepsy and encephalopathy (53%) with epileptic spasms or tonic seizures as main seizure type. We found no correlation between severity of seizures and severity of ID or between mutation type and seizure characteristics or cognitive outcome. Neurologic comorbidities including autistic features and movement disorders are frequent. We also report 2 previously unreported adult patients with prominent extrapyramidal features. De novo STXBP1 mutations are among the most frequent causes of epilepsy and encephalopathy. Most patients have severe to profound ID with little correlation among seizure onset, seizure severity, and the degree of ID. Accordingly, we hypothesize that seizure severity and ID present 2 independent dimensions of the STXBP1-E phenotype. STXBP1-E may be conceptualized as a complex neurodevelopmental disorder rather than a primary epileptic encephalopathy. © 2016 American Academy of Neurology.

  14. Guillain-Barre syndrome with posterior reversible encephalopathy syndrome

    Directory of Open Access Journals (Sweden)

    Basavaraj F Banakar

    2014-01-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is a clinicoradiologic entity commonly associated with eclampsia, septicemia, chemotherapeutic drugs etc. Concurrent occurrence of Guillain-Barre syndrome (GBS with PRES is a rare entity. Dysautonomia is a proposed mechanism for such occurrence. Here we present a non-diabetic, non-hypertensive 63-year-old male patient, who came with acute onset flaccid quadriparesis, developing generalized seizures, altered sensorium and raised blood pressure on fifth day of illness. Magnetic resonance imaging (MRI of brain showed altered signal intensities involving the parieto-occipital areas suggestive of posterior reversible encephalopathy. Cerebrospinal fluid analysis showed albuminocytological dissociation, nerve conduction studies revealed demyelinating type of polyneuropathy. The patient was treated with antihypertensives and antiepileptics. After resolution of the encephalopathy, intravenous immunoglobulin (IVIg was given. The patient recovered gradually over few months. Our case concludes GBS as independent risk factor, for PRES may be secondary to dysautonomia and physicians should be aware of such rare coexistence so that early treatment can be done to reduce the mortality and morbidity.

  15. Ammonia levels and the severity of hepatic encephalopathy

    International Nuclear Information System (INIS)

    Qureshi, M.O.; Khokhar, N.; Shafqat, F.

    2014-01-01

    Objective: To evaluate the correlation between ammonia levels with the severity of HE in patients coming to the tertiary care hospital with liver cirrhosis and hepatic encephalopathy (HE). Study Design: Descriptive, analytical study. Place and Duration of Study: Shifa International Hospital, Islamabad, from January 2011 to February 2012. Methodology: A total of 135 patients with liver cirrhosis and HE had serum ammonia levels measured on admission. The diagnosis of HE was based on clinical criteria, and its severity was graded according to the West Haven Criteria for grading of mental status. Ammonia levels were correlated with the severity of HE using Spearman rank correlation. Results: Out of 20 patients with normal ammonia levels, 13 (65%) were in HE I-II, 6 (30%) were in grade-III, while 1 (5%) patient was in grade-IV HE. Out of 45 patients with mild hyperammonemia, 27 (60%) were in grade I-II, 12 (26%) were in grade-III and 6 (13%) were in grade-IV HE. Out of 34 patients with moderate hyperammonemia, 9 (26%) were in grade I-II, 18 (53%) were in grade-III, and 7 (20%) were in grade-IV HE. Out of 36 patients with severe hyperammonemia, 31 (86%) patients were in grade-IV HE (p < 0.001). Conclusion: Ammonia levels correlated with the severity of hepatic encephalopathy. Greater the ammonia level, severe is the grade of hepatic encephalopathy. (author)

  16. Hypoxic ischemic encephalopathy in children : CT findings related to prognosis

    International Nuclear Information System (INIS)

    Cho, Jae Min; Il, Yim Byung; Kim, Ok Hwa; Kang, Doo Kyoung; Suh, Jung Ho

    1997-01-01

    To evaluate prognosis-related CT findings in hypoxic ischemic encephalopathy. For the purpose of prognosis, 28 children with a clinical history and CT findings suggestive of hypoxic ischemic encephalopathy (HIE) were restrospectively reviewed. The diagnostic criteria for HIE, as seen on CT scanning, were as follows : 1, ventricular collapse;2, effacement of cortical sulci;3, prominent enhancement of cortical vessels;4, poor differentiation of gray and white matter;5, reversal sign;6, obliteration of perimesencephalic cistern;7, high density on tentorial edge, as seen on precontrast scans;and 8, low density in thalamus, brain stem and basal ganglia. On the basis of clinical outcome, we divided the patients into three groups, as follows:group I(good prognosis);group II(neurologic sequelae), and group III(vegetative state or expire), and among these, compared CT findings. There were thirteen patients in group I, six in group II, and nine in group III. Ventricular collapse, effacement of cortical sulci, and prominent enhancement of cortical vessels were noted in all groups, whereas poor differentiation of gray and white matter, reversal sign, obliteration of perimesencephalic cistern, high density on tentorial edge, on precontrast scan, and low density in brain stem and basal ganglia were observed only in groups II and III. CT findings showed distinct differences between groups in whom prognosis was good, and in whom it was poor. An awareness of poor prognostic CT findings may be clinically helpful in the evaluation of patients with hypoxic ischemic encephalopathy

  17. Metronidazole-induced encephalopathy in a patient with Crohn's disease

    Directory of Open Access Journals (Sweden)

    Jihye Kim

    2017-01-01

    Full Text Available Metronidazole is a widely used antibiotic for the treatment of anaerobic bacterial infections. Metronidazole-induced encephalopathy (MIEP is a rare but potentially reversible disease. The mechanism of MIEP remains unclear, and differences in the neurotoxic effects of oral versus intravenous (IV metronidazole administration have not yet been determined. We report the case of a Crohn's disease (CD patient who experienced encephalopathy immediately after a single IV dose of metronidazole following long-term exposure to the oral form of the drug. The 64-year-old man with intractable CD experienced a sudden change in mental status, aphasia, and muscle weakness after IV administration of metronidazole. He had previously taken metronidazole orally for 13 years and received intermittent IV metronidazole treatments for CD exacerbation. Brain magnetic resonance imaging (MRI showed high-intensity signals in the bilateral medial thalamus and the midbrain and pontine tegmentum on fluid-attenuated inversion recovery images. After discontinuation of metronidazole, the high-intensity brain MRI signals resolved and the patient's mental status dramatically improved; however, the patient exhibited mild cognitive dysfunction 2 months after the onset of encephalopathy.

  18. Comparative Neuroprotective Effects of Dexamethasone and Minocycline during Hepatic Encephalopathy

    Science.gov (United States)

    Gamal, Maha; Abdel Wahab, Zainab; Eshra, Mohamed; Rashed, Laila; Sharawy, Nivin

    2014-01-01

    Objective. Encephalopathy and brain edema are serious complications of acute liver injury and may lead to rapid death of patients. The present study was designed to investigate the role of the inflammatory mediators and oxidative stress in the cytotoxic brain oedema and the neuroprotective effects of both minocycline and dexamethasone. Methods. 48 male albino rats were divided into 4 groups: control group, acute liver injury (ALI) group, minocycline pretreated ALI group, and dexamethasone pretreated ALI group. 24 hours after acute liver injury serum ammonia, liver enzymes, brain levels of heme oxygenase-1 gene, iNOS gene expression, nitrite/nitrate, and cytokines were measured. In addition, the grades of encephalopathy and brain water content were assessed. Results. ALI was associated with significant increases in all measured inflammatory mediators, oxidative stress, iNOS gene expression, and nitrite/nitrate. Both minocycline and dexamethasone significantly modulated the inflammatory changes and the oxidative/nitrosative stress associated with ALI. However, only minocycline but not dexamethasone significantly reduced the cytotoxic brain oedema. Conclusion. Both minocycline and dexamethasone could modulate inflammatory and oxidative changes observed in brain after ALI and could be novel preventative therapy for hepatic encephalopathy episodes. PMID:24693424

  19. Systemic hypothermia after neonatal encephalopathy: outcomes of neo.nEURO.network RCT

    DEFF Research Database (Denmark)

    Simbruner, Georg; Mittal, Rashmi A; Rohlmann, Friederike

    2010-01-01

    Mild hypothermia after perinatal hypoxic-ischemic encephalopathy (HIE) reduces neurologic sequelae without significant adverse effects, but studies are needed to determine the most-efficacious methods....

  20. The ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies.

    Science.gov (United States)

    Ville, Dorothée; Chiron, Catherine; Laschet, Jacques; Dulac, Olivier

    2015-07-01

    Hormonal therapy or ketogenic diet often permits overcoming the challenging periods of many epileptic encephalopathies (West and Lennox-Gastaut syndromes and encephalopathy with continuous spike-waves in slow sleep), but relapse affects over 20% of patients. We report here a monocenter pilot series of 42 consecutive patients in whom we combined oral steroids with the ketogenic diet for corticosteroid-resistant or -dependent epileptic encephalopathy. We retrospectively evaluated the effect on seizure frequency, interictal spike activity, neuropsychological course, and steroid treatment course. Twenty-three patients had West syndrome (WS), 13 had encephalopathy with continuous spike-waves in slow sleep (CSWS), and six others had miscellaneous epileptic encephalopathies. All patients succeeded to reach 0.8 to 1.6g/l ketone bodies in the urine following the usual KD regimen. For at least 6 months, 14/42 responded to the addition of the ketogenic diet: 4/23 with WS, 8/13 with CSWS, and 2/6 with miscellaneous epileptic encephalopathies. The addition of the KD allowed withdrawing steroids in all responders. Among them, 10/15 had been patients with steroid-dependent epileptic encephalopathy and 4/27 patients with steroid-resistant epileptic encephalopathy. Therefore, the ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies. Patients presenting with steroid-dependent CSWS seem to be the best candidates. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. A Rare Case of Reversible Encephalopathy Syndrome Accompanying Late Postpartum Eclampsia or Hypertensive Encephalopathy-A Clinical Dilemma

    Directory of Open Access Journals (Sweden)

    Shakuntala PN

    2012-04-01

    Full Text Available Posterior Reversible Encephalopathy Syndrome (PRES refers to a clinic-radiologic diagnosis. Clinically it is characterized by non specific symptoms such as headache, confusion, visual disturbances and seizures. The radiological findings in PRES are thought to be due to vasogenic oedema, predominantly in the posterior cerebral hemispheres, and are reversible with appropriate management. We report a case of reversible encephalopathy diagnosed by MRI scan occurring in atypical areas like the caudate and lentiform nuclei of the brain following an uneventful lower segment caesarean section in a normotensive patient, who was successfully treated with antihypertensives, anticonvulsants and supportive treatment. The differential diagnosis of convulsions in the post-partum period is discussed.

  2. Performance of the hepatic encephalopathy scoring algorithm in a clinical trial of patients with cirrhosis and severe hepatic encephalopathy

    DEFF Research Database (Denmark)

    Hassanein, T.; Blei, A.T.; Perry, W.

    2009-01-01

    criteria (WHC) to provide an objective assessment of the cognitive parameters to complement the subjective clinical ratings for the performance of extracorporeal albumin dialysis (ECAD) using a molecular adsorption recirculating system in patients with cirrhosis and severe (grade III / IV) encephalopathy...... and not clinically useful. CONCLUSION: HESA extends the traditional WHC for grading HE. In the absence of a "gold" standard, the most useful indicators noted in this trial should be further validated Udgivelsesdato: 2009/6...

  3. Hypothyroidism-induced Reversible Encephalopathy as a Cause of Aggravation of Parkinsonism and Myoclonus in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Gwanhee Ehm

    2011-10-01

    Full Text Available Background: Myoclonus and encephalopathy are unusual in patients with Parkinson’s disease (PD.Case report: We describe the case of a 59-year-old male with PD who developed myoclonus and encephalopathy. Underlying hypothyroidism was revealed after admission and treated with levothyroxine. Myoclonus and encephalopathy were completely resolved following thyroid hormone replacement.Discussion: Hypothyroidism can cause reversible myoclonus and encephalopathy along with unusual aggravation of parkinsonism symptoms in patients with PD.

  4. Hypothyroidism-induced Reversible Encephalopathy as a Cause of Aggravation of Parkinsonism and Myoclonus in Parkinson's Disease.

    Science.gov (United States)

    Ehm, Gwanhee; Kim, Han-Joon; Jeon, Beomseok

    2017-01-01

    Myoclonus and encephalopathy are unusual in patients with Parkinson's disease (PD). We describe the case of a 59-year-old male with PD who developed myoclonus and encephalopathy. Underlying hypothyroidism was revealed after admission and treated with levothyroxine. Myoclonus and encephalopathy were completely resolved following thyroid hormone replacement. Hypothyroidism can cause reversible myoclonus and encephalopathy along with unusual aggravation of parkinsonism symptoms in patients with PD.

  5. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1

    DEFF Research Database (Denmark)

    Carvill, Gemma L; Heavin, Sinéad B; Yendle, Simone C

    2013-01-01

    Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify ...

  6. Localized Cerebral Energy Failure in DNA Polymerase Gamma-Associated Encephalopathy Syndromes

    Science.gov (United States)

    Tzoulis, Charalampos; Neckelmann, Gesche; Mork, Sverre J.; Engelsen, Bernt E.; Viscomi, Carlo; Moen, Gunnar; Ersland, Lars; Zeviani, Massimo; Bindoff, Laurence A.

    2010-01-01

    Mutations in the catalytic subunit of the mitochondrial DNA-polymerase gamma cause a wide spectrum of clinical disease ranging from infantile hepato-encephalopathy to juvenile/adult-onset spinocerebellar ataxia and late onset progressive external ophthalmoplegia. Several of these syndromes are associated with an encephalopathy that…

  7. A rare case of dengue encephalopathy complicating a term pregnancy.

    Science.gov (United States)

    Rajagopala, Lavanya; Satharasinghe, Ravindra L; Karunarathna, Madhava

    2017-02-02

    Dengue fever has an expanded clinical spectrum ranging from an asymptomatic infection to life threatening dengue hemorrhagic fever and refractory shock. Dengue infection in pregnancy can be a diagnostic dilemma, particularly considering the physiological changes in pregnancy and the obstetric complications encountered in clinical practice. Hence the knowledge of its diagnosis and management in its atypical presentations is of paramount importance. Here we report an unusual case of uncomplicated dengue encephalopathy in a term mother, probably the first to be reported from the Indian subcontinent. A 28 year old woman, 37 weeks of pregnancy presented with fever of four days duration. She eventually developed irritability, altered sensorium, somnolence, and unresponsiveness to commands by the 5th day of febrile illness without any circulatory compromise. Physical examination and investigations including serology confirmed dengue fever. After excluding all other possible causes, the transient neurological deterioration was finally attributed to dengue encephalopathy which is an uncommon manifestation of the disease, particularly in pregnancy. Her deteriorated neurological status which had lasted for 6 days improved spontaneously with the convalescence of dengue infection. Cautious fluid management was carried out in correlation to clinical and hematological parameters. The pregnancy was continued uncomplicated till the platelet count had risen to more than 50,000 cells/cumm. She delivered vaginally a healthy male baby. Dengue fever in pregnancy is increasingly being encountered due to its rising disease burden. Dengue encephalitis/encephalopathy must be suspected in the differential diagnosis of fever and altered sensorium, even in pregnancy, in the tropical countries where the infection is rampant. Management of dengue infection in term pregnancy is a challenge for both the clinician and obstetrician. Further discussion and research are mandatory to decide on

  8. Risk factor for hypoxic ischemic encephalopathy in children

    International Nuclear Information System (INIS)

    Butt, T.K.; Farooqui, R.; Khan, U.; Farooqui, R.

    2008-01-01

    To determine underlying risk factors in neonates with hypoxic ischemic encephalopathy. All neonates (153) with the diagnosis of Hypoxic Ischemic Encephalopathy (HIE) were included in the study. Controls (187) were selected from admissions on the same day. Possible risk factors such as maternal age, parity, antenatal monitoring, place of delivery, prolonged second stage of labour, type of delivery, type of attendant at delivery and the gestational age were noted and compared. Sixty one (39.9%) mothers of asphyxiated babies reported no antenatal visits compared to 24.1% in the control group (OR 2.1, 95% CI 1.3-3.2; p=0.002). Only 6.5% of cases were born in government hospitals (teaching and district) in comparison to 20.9% of controls (OR 3.8, 95% CI 1.9-7.6; p=0.001). In 28.1% of cases, mothers had history of prolonged 2nd stage of labour in comparison to 5.9% of controls (OR 6.3, 95% CI 3.3-11.9; p<0.001). Fifty five cases (35.9%) were delivered by unskilled birth attendants compared to 28 (14.9%) controls (OR 3.2, 95% CI 1.9-5.3; p<0.001). No significant difference was found in maternal age, maternal parity, gestational age and the mode of delivery between the two groups. Delivery by unskilled birth attendant, prolonged second stage of labour, birth in a non-government hospital setup and absence of antenatal care were significant risk factors for hypoxic ischemic encephalopathy in neonates. Improvement in antenatal and intrapartum care may be helpful in decreasing the frequency of this problem. (author)

  9. [Wernicke encephalopathy and Korsakoff's psychosis: clinical-pathophysiological correlation, diagnostics and treatment].

    Science.gov (United States)

    Sivolap, Iu P; Damulin, I V

    2013-01-01

    Wernicke's encephalopathy and Korsakoff's psychosis are severe unfavorable forms of alcoholic brain damage with poor prognosis. Thiamine deficiency represents a common cause of both diseases. In many cases, Korsakoff's psychosis develops in the outcome of Wernicke's encephalopathy, which, along with the general etiology, lets talk about a single disease - Wernicke-Korsakoff syndrome, acute (usually reversible) stage of which is Wernicke's encephalopathy and a chronic one (often irreversible) is Korsakoff psychosis. The dramatic paradox of Wernicke's encephalopathy is that in most cases it is difficult to detect, but early diagnosed cases are quite easy to cure. Unrecognized and therefore go untreated Wernicke's encephalopathy is a serious threat to the health and lives of patients, worsens the processes of brain aging and increases the risk of Alzheimer's disease in later life. The basic approach to the treatment of Wernicke-Korsakoff syndrome is long-term parenteral administration of thiamine, often in high doses. As an adjuvant means of therapy memantine is considered.

  10. Loss-of-function mutations of STXBP1 in patients with epileptic encephalopathy.

    Science.gov (United States)

    Yamamoto, Toshiyuki; Shimojima, Keiko; Yano, Tamami; Ueda, Yuki; Takayama, Rumiko; Ikeda, Hiroko; Imai, Katsumi

    2016-03-01

    Epileptic encephalopathy, which commences during early infancy, is a severe epileptic syndrome that manifests as age-dependent seizures and severe developmental delay. The syntaxin-binding protein 1 gene (STXBP1) is one of the genes responsible for epileptic encephalopathy. We conducted a cohort study to analyze STXBP1 in 42 patients with epileptic encephalopathy. We identified four novel mutations: two splicing mutations, a frameshift mutation, and a nonsense mutation. All of these mutations were predicted to cause loss-of-function. This result suggests loss-of-function is a common mechanism underlying STXBP1-related epileptic encephalopathy. The four patients showed epileptic features consistent with STXBP1-related epileptic encephalopathy, but showed variable radiological findings, including brain volume loss and myelination delay. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  11. Atypical presentation of posterior reversible encephalopathy syndrome: Two cases

    Directory of Open Access Journals (Sweden)

    Nishant Kumar

    2018-01-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is a clinico-neuroradiological entity, first described in 1996. It is commonly associated with systemic hypertension, intake of immunosuppressant drugs, sepsis and eclampsia and preeclampsia. Headache, alteration in consciousness, visual disturbances and seizures are common manifestations of PRES. Signs of pyramidal tract involvement and motor dysfunction are uncommon clinical findings. However, clinical presentation is not diagnostic. On neuroimaging, lesions are characteristically found in parieto occipital region of the brain due to vasogenic edema. We report two cases of PRES with atypical clinical presentation-one which was suggestive of neurocysticercosis and the other in which agitation and opisthotonic posture were predominant features.

  12. Hypercalcemic encephalopathy due to milk alkali syndrome and injection teriparatide

    Directory of Open Access Journals (Sweden)

    Sandeep Kharb

    2012-01-01

    Full Text Available An 82-year-old male, a known case of severe osteoporosis with vertebral fracture and prostatic carcinoma, was treated with gonadotropin releasing hormone analogue, calcium carbonate, cholecalciferol sachet and injection teriparatide. His diet consisted of milk and curd. He developed altered behavior and generalized weakness, and on investigation, hypercalcemia, hypokalemia, and metabolic alkalosis with low parathyroid hormone levels were detected. Injection teriparatide was stopped and he was managed with forced saline diuresis and injection zoledronic acid. He was diagnosed as a case of milk alkali syndrome in whom teriparatide and prolonged immobilization played a permissive role in the development of hypercalcemic encephalopathy.

  13. Posterior reversible encephalopathy syndrome associated with nephrotic syndrome.

    Science.gov (United States)

    Zhang, Hong-Liang; Yang, Yi; Wu, Jiang

    2010-01-01

    Kabicek and colleagues described a case of nephritic-syndrome-associated posterior reversible encephalopathy syndrome (PRES) (Kabicek, et al. 2010). This adds to the accumulating evidence that PRES can be associated with disorders other than hypertension. However, we wonder how the authors would explain the neuroimaging findings unsuggestive of vasogenic oedema. PRES (also named reversible posterior leukoencephalopathy syndrome, RPLS) represents a clinicoradiological syndrome characterized by vasogenic oedema as revealed by apparent diffusion coefficient (ADC) map of diffusion-weighted imaging (DWI) (Bartynski, 2008). The pathogenesis of PRES has been suggested to be autoregulation failure and endothelial dysfunction (Sharma, et al.). ...

  14. Chronic traumatic encephalopathy in sports: a historical and narrative review.

    Science.gov (United States)

    Solomon, Gary

    2018-03-13

    My objectives are to review: 1) a brief history of sport-related concussion (SRC) and chronic traumatic encephalopathy (CTE), 2) the evolution of CTE in American professional football, 3) the data regarding SRC/CTE as they relate to depression and suicide, 4) the data on the neurocognitive effects of subconcussion/repetitive head trauma (with emphases on heading the ball in soccer and early exposure to football), 5) the evidence related to SRC and neurodegenerative diseases, 6) the published studies of CTE, 7) the NINDS neuropathological criteria for CTE, 8) public beliefs about SRC/CTE, and 9) the scientific questions regarding CTE.

  15. The science and questions surrounding chronic traumatic encephalopathy.

    Science.gov (United States)

    Ban, Vin Shen; Madden, Christopher J; Bailes, Julian E; Hunt Batjer, H; Lonser, Russell R

    2016-04-01

    Recently, the pathobiology, causes, associated factors, incidence and prevalence, and natural history of chronic traumatic encephalopathy (CTE) have been debated. Data from retrospective case series and high-profile media reports have fueled public fear and affected the medical community's understanding of the role of sports-related traumatic brain injury (TBI) in the development of CTE. There are a number of limitations posed by the current evidence that can lead to confusion within the public and scientific community. In this paper, the authors address common questions surrounding the science of CTE and propose future research directions.

  16. The National Football League and chronic traumatic encephalopathy: legal implications.

    Science.gov (United States)

    Korngold, Caleb; Farrell, Helen M; Fozdar, Manish

    2013-01-01

    The growing awareness of chronic traumatic encephalopathy (CTE) has the potential to change the public perception and on-field rules of the National Football League (NFL). More than 3,000 ex-NFL players or their relatives are engaged in litigation alleging that the NFL failed to acknowledge and address the neuropsychiatric risks associated with brain injuries that result from playing in the NFL. This article explores the intersection between the medical and legal aspects of CTE in the NFL from a forensic psychiatry perspective.

  17. A Less Known Stroke Mimic: Posterior Reversible Encephalopathy Syndrome

    Directory of Open Access Journals (Sweden)

    Keneilwe Malomo

    2016-04-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is a clinico-neuro-radiological diagnosis, which can complicate a wide range of conditions. Clinical features include generalised and/or focal neurological deficits. These features are also present in neurovascular disorders, such as stroke. Currently, emphasis in the management of hyperacute stroke is thrombolysis, and it is important to bear in mind stroke mimics as a possible cause of clinical features. The Authors present the case of a 66-year-old man, who presented with acute focal neurological deficit. His brain imaging and history were consistent with PRES.

  18. The hunter and the pianist: two hepatic encephalopathy tales.

    Science.gov (United States)

    Montagnese, Sara; Cona, Giorgia; Schiff, Sami; Maresio, Giulio; Gatta, Angelo; Merkel, Carlo; Amodio, Piero

    2011-07-01

    Details of 2 patients with cirrhosis and hepatic encephalopathy whose hobby or job were possibly responsible for a selectively enhanced performance in 1 neuropsychiatric test are reported. Clinicians should be alert to the fact that personal inclinations and habits may impinge on both neuropsychological and psychophysic performance, thus producing a mismatch between the results of different mental status tests. A prospective study with accurate history taking, use of comprehensive assessment protocols, and modeling/critical interpretation of the test results is required to confirm this hypothesis.

  19. Genetic epileptic encephalopathies: is all written into the DNA?

    Science.gov (United States)

    Striano, Pasquale; de Jonghe, Peter; Zara, Federico

    2013-11-01

    Epileptic encephalopathy is a condition in which epileptic activity, clinical or subclinical, is thought to be responsible for any disturbance of cognition, behavior, or motor control. However, experimental evidence supporting this clinical observation are still poor and the causal relationship between pharmacoresistant seizures and cognitive outcome is controversial. In the past two decades, genetic studies shed new light onto complex mechanisms underlying different severe epileptic conditions associated with intellectual disability and behavioral abnormalities, thereby providing important clues on the relationship between seizures and cognitive outcome. Dravet syndrome is a childhood disorder associated with loss-of-function mutations in SCN1A and is characterized by frequent seizures and severe cognitive impairment, thus well illustrating the concept of epileptic encephalopathy. However, it is difficult to determine the causative role of the underlying sodium channel dysfunction and that of the consequent seizures in influencing cognitive outcome in these children. It is also difficult to demonstrate whether a recognizable profile of cognitive impairment or a definite behavioral phenotype exists. Data from the laboratory and the clinics may provide greater insight into the degree to which epileptic activity may contribute to cognitive impairment in individual syndromes. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  20. Therapeutic hypothermia for neonates with hypoxic ischemic encephalopathy

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    Ming-Chou Chiang

    2017-12-01

    Full Text Available Therapeutic hypothermia (TH is a recommended regimen for newborn infants who are at or near term with evolving moderate-to-severe hypoxic ischemic encephalopathy (HIE. The Task Force of the Taiwan Child Neurology Society and the Taiwan Society of Neonatology held a joint meeting in 2015 to establish recommendations for using TH on newborn patients with HIE. Based on current evidence and experts' experiences, this review article summarizes the key points and recommendations regarding TH for newborns with HIE, including: (1 selection criteria for TH; (2 choices of method and equipment for TH; (3 TH prior to and during transport; (4 methods for temperature maintenance, monitoring, and rewarming; (5 systemic care of patients during TH, including the care of respiratory and cardiovascular systems, management of fluids, electrolytes, and nutrition, as well as sedation and drug metabolism; (6 monitoring and management of seizures; (7 neuroimaging, prognostic factors, and outcomes; and (8 adjuvant therapy for TH. Key Words: hypoxic ischemic encephalopathy, neonate, patient care, perinatal asphyxia, therapeutic hypothermia

  1. Hepatic encephalopathy: Ever closer to its big bang.

    Science.gov (United States)

    Souto, Pablo A; Marcotegui, Ariel R; Orbea, Lisandro; Skerl, Juan; Perazzo, Juan Carlos

    2016-11-14

    Hepatic encephalopathy (HE) is a neuropsychiatric disorder that commonly complicates the course of patients with liver disease. Despite the fact that the syndrome was probably first recognized hundreds of years ago, the exact pathogenesis still remains unclear. Minimal hepatic encephalopathy (MHE) is the earliest form of HE and is estimated to affect more that 75% of patients with liver cirrhosis. It is characterized by cognitive impairment predominantly attention, reactiveness and integrative function with very subtle clinical manifestations. The development of MHE is associated with worsen in driving skills, daily activities and the increase of overall mortality. Skeletal muscle has the ability to shift from ammonia producer to ammonia detoxifying organ. Due to its large size, becomes the main ammonia detoxifying organ in case of chronic liver failure and muscular glutamine-synthase becomes important due to the failing liver and brain metabolic activity. Gut is the major glutamine consumer and ammonia producer organ in the body. Hepatocellular dysfunction due to liver disease, results in an impaired clearance of ammonium and in its inter-organ trafficking. Intestinal bacteria, can also represent an extra source of ammonia production and in cirrhosis, small intestinal bacterial overgrowth and symbiosis can be observed. In the study of HE, to get close to MHE is to get closer to its big bang; and from here, to travel less transited roads such as skeletal muscle and intestine, is to go even closer. The aim of this editorial is to expose this road for further and deeper work.

  2. Wernicke's Encephalopathy Mimicking Acute Onset Stroke Diagnosed by CT Perfusion

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    Alok Bhan

    2014-01-01

    Full Text Available Background. Metabolic syndromes such as Wernicke’s encephalopathy may present with a sudden neurological deficit, thus mimicking acute onset stroke. Due to current emphasis on rapid admission and treatment of acute stroke patients, there is a significant risk that these stroke mimics may end up being treated with thrombolysis. Rigorous clinical and radiological skills are necessary to correctly identify such metabolic stroke mimics, in order to avoid doing any harm to these patients due to the unnecessary use of thrombolysis. Patient. A 51-year-old Caucasian male was admitted to our hospital with suspicion of an acute stroke due to sudden onset dysarthria and unilateral facial nerve paresis. Clinical examination revealed confusion and dysconjugate gaze. Computed tomography (CT including a CT perfusion (CTP scan revealed bilateral thalamic hyperperfusion. The use of both clinical and radiological findings led to correctly diagnosing Wernicke’s encephalopathy. Conclusion. The application of CTP as a standard diagnostic tool in acute stroke patients can improve the detection of stroke mimics caused by metabolic syndromes as shown in our case report.

  3. Hypoxic-Ischemic Neonatal Encephalopathy: Animal Experiments for Neuroprotective Therapies

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    Hiroshi Sameshima

    2013-01-01

    Full Text Available Hypoxic-ischemic neonatal encephalopathy and ensuing brain damage is still an important problem in modern perinatal medicine. In this paper, we would like to share some of the results of our recent studies on neuroprotective therapies in animal experiments, as well as some literature reviews. From the basic animal studies, we have now obtained some possible candidates for therapeutic measures against hypoxic-ischemic neonatal encephalopathy. For example, they are hypothermia, rehabilitation, free radical scavenger, neurotrophic factors and growth factors, steroid, calcium channel blocker, vagal stimulation, some anti apoptotic agents, pre- and post conditioning, antioxidants, cell therapy with stem cells, modulators of K(+-ATP channels, and so on. Whether combination of these therapies may be more beneficial than any single therapy needs to be clarified. Hypoxia-ischemia is a complicated condition, in which the cause, severity, and time-course are different in each case. Likewise, each fetus has its own inherent potentials such as adaptation, preconditioning-tolerance, and intolerance. Therefore, further extensive studies are required to establish an individualized strategy for neuroprotection against perinatal hypoxic-ischemic insult.

  4. Sarcopenia predicts minimal hepatic encephalopathy in patients with liver cirrhosis.

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    Hanai, Tatsunori; Shiraki, Makoto; Watanabe, Satoshi; Kochi, Takahiro; Imai, Kenji; Suetsugu, Atsushi; Takai, Koji; Moriwaki, Hisataka; Shimizu, Masahito

    2017-12-01

    Minimal hepatic encephalopathy (MHE) and sarcopenia impair the health-related quality of life and prognosis of patients with liver cirrhosis; however, the relationship between MHE and sarcopenia remains unclear. The aim of this study was to investigate their relationship and to identify the predictors of MHE in cirrhotic patients. This retrospective study evaluated 120 cirrhotic patients who were tested for MHE and sarcopenia. Minimal hepatic encephalopathy was diagnosed by using the computer-aided neuropsychiatric test. Sarcopenia was diagnosed based on the assessment criteria recommended by the Japan Society of Hepatology. Muscle mass and muscle strength were measured by using bio-impedance analysis and digital grip strength dynamometer. Univariate and multivariate logistic regression analyses were carried out to identify the predictors of MHE. Of the 120 cirrhotic patients, 28 (23%) and 32 (27%) were diagnosed with MHE and sarcopenia, respectively. The prevalence of MHE was higher in patients with sarcopenia than in those without sarcopenia (P = 0.01). By the univariate analysis, MHE was significantly complicated with sarcopenia (P sarcopenia (odds ratio = 3.31, 95% confidence interval = 1.19-9.42; P = 0.02) and serum branched-chain amino acids levels Sarcopenia and serum branched-chain amino acids levels were predictors of MHE. The amelioration of sarcopenia and/or amino acids imbalance may improve MHE in patients with liver cirrhosis. © 2017 The Japan Society of Hepatology.

  5. CT and MR manifestations of acute methyl alcohol toxic encephalopathy

    International Nuclear Information System (INIS)

    Mao Xiaofen; Yang Bo; Ye Gengxin; Zhang Cheng

    2009-01-01

    Objective: To analyze the CT and MR manifestations of methyl alcohol toxic encephalopathy and to improve the diagnosing value of CT and MRI. Methods: 40 patients with methyl alcohol intoxication were collected in this study, in which CT scan was performed on 40 cases and MRI on 4 cases. All CT and MRI radiological data of brain were retrospectively studied. Results: 13 of 40 cases showed abnormal findings on brain CT and MRI. The most common manifestation (6/13, 46%)was hypodensity in frontal parietal white matter and external capsule-putamen on CT, which showed long or short T1 and long T2 on MR. Hemorrhage in right putamen was found only in 1 patient (1/13,7%). CT showed low density inbilateral external capsule in 4 cases (4/13,31%), in which MR showed long or short T1 and long T2. Low density lesions in subcortical white matter of bilateral frontal and parietal lobes, cingulate gyms and insular lobes were found in 2 patients (2/13,15%). The more severe clinic manifestation, the more obvious brain lesion CT and MRI showed. Conclusion: Brain CT and MR manifestations have great diagnostic value of acute methyl alcohol toxic encephalopathy. MRI was more sensitive and better than CT in finding early brain damage caused by methanol intoxication. (authors)

  6. Is Encephalopathy a Mechanism to Renew Sulfate in Autism?

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    Laurie Lentz-Marino

    2013-01-01

    Full Text Available This paper makes two claims: (1 autism can be characterized as a chronic low-grade encephalopathy, associated with excess exposure to nitric oxide, ammonia and glutamate in the central nervous system, which leads to hippocampal pathologies and resulting cognitive impairment, and (2, encephalitis is provoked by a systemic deficiency in sulfate, but associated seizures and fever support sulfate restoration. We argue that impaired synthesis of cholesterol sulfate in the skin and red blood cells, catalyzed by sunlight and nitric oxide synthase enzymes, creates a state of colloidal instability in the blood manifested as a low zeta potential and increased interfacial stress. Encephalitis, while life-threatening, can result in partial renewal of sulfate supply, promoting neuronal survival. Research is cited showing how taurine may not only help protect neurons from hypochlorite exposure, but also provide a source for sulfate renewal. Several environmental factors can synergistically promote the encephalopathy of autism, including the herbicide, glyphosate, aluminum, mercury, lead, nutritional deficiencies in thiamine and zinc, and yeast overgrowth due to excess dietary sugar. Given these facts, dietary and lifestyle changes, including increased sulfur ingestion, organic whole foods, increased sun exposure, and avoidance of toxins such as aluminum, mercury, and lead, may help to alleviate symptoms or, in some instances, to prevent autism altogether.

  7. A case of tacrolimus-induced encephalopathy after kidney transplantation

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    Myoung Uk Kim

    2011-01-01

    Full Text Available We present a case of tacrolimus-induced encephalopathy after successful kidney transplantation. An 11-year-old girl presented with sudden onset of neurologic symptoms, hypertension, and psychiatric symptoms, with normal kidney function, after kidney transplantation. The symptoms improved after cessation of tacrolimus. Magnetic resonance imaging (MRI showed acute infarction of the middle cerebral artery (MCA territory in the right frontal lobe. Three days later, she had normal mental function and maintained normal blood pressure with left hemiparesis. Follow-up MRI was performed on D19, showing new infarct lesions at both cerebral hemispheres. Ten days later, MRI showed further improvement, but brain single photon emission computed tomography (SPECT showed mild reduction of uptake in both the anterior cingulate gyrus and the left thalamus. One month after onset of symptoms, angiography showed complete resolution of stenosis. However, presenting as a mild fine motor disability of both hands and mild dysarthria, what had been atrophy at both centrum semiovale at 4 months now showed progression to encephalomalacia. There are two points of interest in this case. First, encephalopathy occurred after administration of tacrolimus and improved after discontinuation of the drug. Second, the development of right-side hemiplegia could not be explained by conventional MRI; but through diffusion tensor imaging (DTI and diffusion tensor tractography (DTT of white matter tract, visualization was possible.

  8. STXBP1 as a therapeutic target for epileptic encephalopathy.

    Science.gov (United States)

    Stamberger, Hannah; Weckhuysen, Sarah; De Jonghe, Peter

    2017-11-01

    STXBP1 is an essential protein for presynaptic vesicle release. Mutations in STXBP1 have been associated with a series of (epileptic) neurodevelopmental disorders collectively referred to as STXBP1-encephalopathy (STXBP1-E). In this review we hypothesize about the potential of STXBP1 as a therapeutic target in the field of epileptic encephalopathies. Areas covered: A state of the art overview on current understanding of the pathophysiologic mechanism underlying STXBP1-E is presented. Possibilities of different treatment modalities are discussed including unbiased compound screening, specific protein-protein interaction inhibition and gene therapy, consisting either of gene suppletion or upregulation of gene expression. Expert opinion: Current treatment for STXBP1-E is largely limited to seizure control and future therapies will need to target the developmental aspects of the disease as well. Both in vitro- and animal models used to study the pathophysiology of STXBP1-E could be further optimized as a model for compound screening. They should reflect both the hyper excitable state and the psychomotor delay of STXBP1-E. Specific protein-protein interaction and gene therapy are promising future treatment options that need to be investigated further. We suggest a parallel research strategy on basic pathophysiology and compound development with both fields working in close collaboration with the patient/clinical community.

  9. Need for early diagnosis of mental and mobility changes in Wernicke encephalopathy.

    Science.gov (United States)

    Wijnia, Jan W; Oudman, Erik; Bresser, Esmay L; Gerridzen, Ineke J; van de Wiel, Albert; Beuman, Carla; Mulder, Cornelis L

    2014-12-01

    Korsakoff syndrome is a chronic form of amnesia resulting from thiamine deficiency. The syndrome can develop from unrecognized or undertreated Wernicke encephalopathy. The intra-individual course of Wernicke-Korsakoff syndrome has not been studied extensively, nor has the temporal progression of gait disturbances and other symptoms of Wernicke encephalopathy. Here we present the detailed history of a patient whose acute symptoms of Wernicke encephalopathy were far from stable. We follow his mobility changes and the shifts in his mental status from global confusion and impaired consciousness to more selective cognitive deficits. His Wernicke encephalopathy was missed and left untreated, being labeled as "probable" Korsakoff syndrome. Patients with a history of self-neglect and alcohol abuse, at risk of or suffering with Wernicke encephalopathy, should receive immediate and adequate vitamin replacement. Self-neglecting alcoholics who are bedridden may have severe illness and probably active Wernicke encephalopathy. In these patients, mobility changes, delirium, or impaired consciousness can be an expression of Wernicke encephalopathy, and should be treated to prevent further damage from the neurologic complications of thiamine deficiency.

  10. Hashimoto encephalopathy in pediatric patients: Homogeneity in clinical presentation and heterogeneity in antibody titers.

    Science.gov (United States)

    Lee, Jiwon; Yu, Hee Joon; Lee, Jeehun

    2018-01-01

    Hashimoto encephalopathy is an autoimmune encephalopathy characterized by elevated antithyroid antibodies and a favorable response to corticosteroid. This study delineated the clinical characteristics of pediatric Hashimoto encephalopathy and the significance of low antithyroid antibody titers in diagnosis and treatment. Clinical manifestations, antibody titers, and treatment responses were retrospectively reviewed in six consecutive children diagnosed with Hashimoto encephalopathy between August 2008 and July 2016. Age at diagnosis was 10-17years. Presenting symptoms were seizures, altered consciousness, behavioral changes, psychosis, tremor, and dystonia. Thyroid function was normal in five patients, and one had hypothyroidism prior to the encephalopathy. Antithyroid antibody titer was increased at presentation in five patients and one week later in the other. Antibody levels were extremely varied (anti-thyroglobulin, 20.5-2318.0U/ml; anti-thyroid peroxidase, 12.5-2231.0U/ml; reference range, Hashimoto encephalopathy were similar, irrespective of antithyroid antibody titer. Because the initial antithyroid antibody titers can be normal or mildly-elevated, follow-up testing of antithyroid antibodies is required in patients who are clinically suspect for Hashimoto encephalopathy. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  11. Diagnostic Approach to Genetic Causes of Early-Onset Epileptic Encephalopathy.

    Science.gov (United States)

    Gürsoy, Semra; Erçal, Derya

    2016-03-01

    Epileptic encephalopathies are characterized by recurrent clinical seizures and prominent interictal epileptiform discharges seen during the early infantile period. Although epileptic encephalopathies are mostly associated with structural brain defects and inherited metabolic disorders, pathogenic gene mutations may also be involved in the development of epileptic encephalopathies even when no clear genetic inheritance patterns or consanguinity exist. The most common epileptic encephalopathies are Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, West syndrome and Dravet syndrome, which are usually unresponsive to traditional antiepileptic medication. Many of the diagnoses describe the phenotype of these electroclinical syndromes, but not the underlying causes. To date, approximately 265 genes have been defined in epilepsy and several genes including STXBP1, ARX, SLC25A22, KCNQ2, CDKL5, SCN1A, and PCDH19 have been found to be associated with early-onset epileptic encephalopathies. In this review, we aimed to present a diagnostic approach to primary genetic causes of early-onset epileptic encephalopathies. © The Author(s) 2015.

  12. Clinical subtypes of chronic traumatic encephalopathy: literature review and proposed research diagnostic criteria for traumatic encephalopathy syndrome.

    Science.gov (United States)

    Montenigro, Philip H; Baugh, Christine M; Daneshvar, Daniel H; Mez, Jesse; Budson, Andrew E; Au, Rhoda; Katz, Douglas I; Cantu, Robert C; Stern, Robert A

    2014-01-01

    The long-term consequences of repetitive head impacts have been described since the early 20th century. Terms such as punch drunk and dementia pugilistica were first used to describe the clinical syndromes experienced by boxers. A more generic designation, chronic traumatic encephalopathy (CTE), has been employed since the mid-1900s and has been used in recent years to describe a neurodegenerative disease found not just in boxers but in American football players, other contact sport athletes, military veterans, and others with histories of repetitive brain trauma, including concussions and subconcussive trauma. This article reviews the literature of the clinical manifestations of CTE from 202 published cases. The clinical features include impairments in mood (for example, depression and hopelessness), behavior (for example, explosivity and violence), cognition (for example, impaired memory, executive functioning, attention, and dementia), and, less commonly, motor functioning (for example, parkinsonism, ataxia, and dysarthria). We present proposed research criteria for traumatic encephalopathy syndrome (TES) which consist of four variants or subtypes (TES behavioral/mood variant, TES cognitive variant, TES mixed variant, and TES dementia) as well as classifications of 'probable CTE' and 'possible CTE'. These proposed criteria are expected to be modified and updated as new research findings become available. They are not meant to be used for a clinical diagnosis. Rather, they should be viewed as research criteria that can be employed in studies of the underlying causes, risk factors, differential diagnosis, prevention, and treatment of CTE and related disorders.

  13. Severe posterior reversible encephalopathy in pheochromocytoma: Importance of susceptibility-weighted MRI

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    Serter, Asil; Alkan, Alpay; Aralasmak, Ayse; Kocakoc, Ercan [Dept. of Radiology, Bezmialem Vakif University School of Medicine, Istanbul (Turkmenistan)

    2013-10-15

    Pheochromocytoma is a rare cause of hypertension in children. Hypertension is one of the common reasons of posterior reversible encephalopathy. Intracerebral hemorrhage is a serious and unexpected complication of hypertensive encephalopathy due to pheochromocytoma, and very rarely seen in the childhood. Intracerebral hemorrhages should be searched if there are hypertensive reversible signal changes on the brain. Susceptibility weighted imaging (SWI) is a more sensitive method than conventional MRI when demonstrating cerebral microhemorrhagic foci. This is the first report of SWI findings on intracerebral hemorrhages in basal ganglia, brain stem and periventricular white matter due to hypertensive encephalopathy in a child with pheochromocytoma.

  14. Uremic Encephalopathy with Atypical Magnetic Resonance Features on Diffusion-Weighted Images

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    Kang, Eu Gene; Jeon, Se Jeong; Choi, See Sung [Dept. of Radiology, Wonkwang University School of Medicine and Hospital, Iksan (Korea, Republic of)

    2012-11-15

    Uremic encephalopathy is a well-known disease with typical MR findings including bilateral vasogenic or cytotoxic edema at the cerebral cortex or basal ganglia. Involvement of the basal ganglia has been very rarely reported, typically occurring in uremic-diabetic patients. We recently treated a patient who had non-diabetic uremic encephalopathy with an atypical lesion distribution involving the supratentorial white matter, without cortical or basal ganglia involvement. To the best of our knowledge, this is only the second reported case of non-diabetic uremic encephalopathy with atypical MR findings.

  15. Bruxism Associated with Anoxic Encephalopathy: Successful Treatment with Baclofen

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    A. Bruce Janati

    2013-01-01

    Full Text Available Introduction. Bruxism is a movement disorder characterized by grinding and clenching of the teeth. Etiology of bruxism can be divided into three groups: psychosocial factors, peripheral factors, and pathophysiological factors. Methods. The clinical investigation was conducted at King Khaled Hospital in Hail, Saudi Arabia, in 2012. Results. A 16-year-old Saudi female was brought to the hospital in a comatose state and with generalized convulsive seizures secondary to acute anoxic encephalopathy. In the third week of hospitalization, while still in a state of akinetic mutism, she developed incessant bruxism which responded favorably to a GABA receptor agonist (baclofen. Conclusion. Our data support the hypothesis that bruxism emanates from imbalance or dysregulation of the neurotransmitter system. Larger scale studies will be needed to confirm this hypothesis.

  16. Quantitative EEG evaluation in patients with acute encephalopathy

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    Aline Souza Marques da Silva Braga

    2013-12-01

    Full Text Available Objective To investigate the use of quantitative EEG (qEEG in patients with acute encephalopathies (AEs and EEG background abnormalities. Method Patients were divided into favorable outcome (group A, 43 patients and an unfavorable outcome (group B, 5 patients. EEGLAB software was used for the qEEG analysis. A graphic of the spectral power from all channels was generated for each participant. Statistical comparisons between the groups were performed. Results In group A, spectral analysis revealed spectral peaks (theta and alpha frequency bands in 84% (38/45 of the patients. In group B, a spectral peak in the delta frequency range was detected in one patient. The remainder of the patients in both groups did not present spectral peaks. Statistical analysis showed lower frequencies recorded from the posterior electrodes in group B patients. Conclusion qEEG may be useful in the evaluations of patients with AEs by assisting with the prognostic determination.

  17. Saccadic dysfunction in patients with hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Teslenko, Elena L; Damyanovich, Elena V; Damjanović, Ilija; Gačić, Zoran; Baziyan, Boris K

    2017-10-25

    Electrophysiological monitoring of saccadic eye movements in patients with hypoxic-ischemic encephalopathy (HIE) was carried out. Externally guided saccades (prosaccades) were recorded using a patented hardware-software complex for studying the subject's physical activity. Recordings were performed in two independent experimental procedures - for saccades separately and when they were in coordination with the motion of head and hand. In both cases statistically significant differences in latent periods and durations of saccadic eye movements were noticed in HIE patients in comparison with healthy subjects of the same age group (peyes after fixing the gaze on a target were often present in HIE participants. In some cases saccades of patients were asymmetrical among themselves. We found HIE induced changes in the parameters of autosaccades as well, expressed through the instability of gaze fixation periods, sometimes asymmetric eye movements, slow gaze shift from one target to another and disturbance of gaze stabilization (as jerking of the eyeballs during the saccadic period).

  18. Posterior reversible encephalopathy syndrome: An atypical postpartum complication

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    Debashish Paul

    2016-01-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is presented by headache, altered mental status, blurring of vision, vomiting and seizure in conjunction with radiological finding of posterior cerebral white matter edema. Data suggest that most cases occur in young middle-aged with marked female preponderance, hypertension being the most common cause. In this case, it was diagnosed in a normotensive patient in the postnatal period that underwent cesarean section. The initial symptoms had misled toward a diagnosis of postdural puncture headache. Symptomatic treatment was started immediately in the ICU. This is an interesting case as the patient was a normotensive one without any other contributory factors and there was unanticipated delay in diagnosing the case until the time we could get a magnetic resonance imaging report.

  19. Refractory hypotension in a patient with Wernicke's encephalopathy.

    Science.gov (United States)

    Wang, Shi; Hou, Xiaojun; Ding, Suju; Guan, Yangtai; Zhen, Huimin; Tu, Laihui; Qiu, Yiqing

    2012-01-01

    A 57-year-old male patient with gastric carcinoma underwent radical distal gastrectomy type II + Braun anastomosis, and received total parenteral nutrition for 10 days after surgery, followed by small amounts of semi-liquid nutrition for 3 days and liquid nutrition for 2 days. The patient developed refractory hypotension for more than 1 week in the early course of disease, and on Day 15 after surgery presented with characteristic signs of Wernicke's encephalopathy, including diplopia and mental confusion. The hypotension did not improve despite appropriate fluid replacement soon after admission. Treatment with moderate dose of thiamine for 3 months partly relieved ophthalmoplegia and confusion, but not Korsakoff syndrome. This extraordinary presentation with refractory hypotension and the unusual course of the disease encouraged us to present this case.

  20. [Wernicke encephalopathy after subtotal gastrectomy for morbid obesity].

    Science.gov (United States)

    Gabaudan, C; La-Folie, T; Sagui, E; Soulier, B; Dion, A-M; Richez, P; Brosset, C

    2008-05-01

    Wernicke's encephalopathy (WE) is one of the potential complications of obesity surgery. It is an acute neuropsychiatric syndrome resulting from thiamine deficiency often associated with repeated vomiting. The classic triad is frequently reported in these patients (optic neuropathy, ataxia and confusion), associated with uncommon features. Cerebral impairment affects the dorsal medial nucleus of the thalamus and the periaqueductal grey area, appearing on MRI, as hyperintense signals on T2, Flair and Diffusion weighted imaging. Early diagnosis and parenteral thiamine are required to decrease morbidity and mortality. We report a case of WE and Korsakoff's syndrome in a young obese patient after subtotal gastrectomy, who still has substantial sequelae. The contribution of MRI with diffusion-weighted imaging is illustrated. The interest of nutritional supervision in the first weeks and preventive thiamine supplementation in case of repeated vomiting are of particular importance in these risky situations.

  1. [Hypertensive crisis and posterior reversible encephalopathy syndrome (PRES)].

    Science.gov (United States)

    Eberhardt, Olaf

    2018-02-28

    The urgency and intensity of therapeutic response to a hypertensive crisis are governed by the presence or absence of acute end-organ damage, which define hypertensive emergency and hypertensive urgency, respectively. In case of hypertensive urgency a slow and moderate lowering of blood pressure by oral antihypertensive agents seems adequate, while the approach to hypertensive emergency has to be tailored to the specific type of organ failure. Optimal blood pressure management in the context of neurovascular emergencies is made difficult by contradictory data from observational and interventional studies. It might prove advantageous to individualize treatment according to characteristics such as the location of persistent vessel occlusion or the presence of collaterals. Reversible posterior encephalopathy may present with atypical features that might make diagnosis difficult. Clevidipine might be a welcome supplement to current intravenous antihypertensive agents in neurological disease. Georg Thieme Verlag KG Stuttgart · New York.

  2. Chronic traumatic encephalopathy: historical origins and current perspective.

    Science.gov (United States)

    Montenigro, Philip H; Corp, Daniel T; Stein, Thor D; Cantu, Robert C; Stern, Robert A

    2015-01-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is most often identified in postmortem autopsies of individuals exposed to repetitive head impacts, such as boxers and football players. The neuropathology of CTE is characterized by the accumulation of hyperphosphorylated tau protein in a pattern that is unique from that of other neurodegenerative diseases, including Alzheimer's disease. The clinical features of CTE are often progressive, leading to dramatic changes in mood, behavior, and cognition, frequently resulting in debilitating dementia. In some cases, motor features, including parkinsonism, can also be present. In this review, the historical origins of CTE are revealed and an overview of the current state of knowledge of CTE is provided, including the neuropathology, clinical features, proposed clinical and pathological diagnostic criteria, potential in vivo biomarkers, known risk factors, and treatment options.

  3. Acute Pancreatitis and Posterior Reversible Encephalopathy Syndrome: A Case Report.

    Science.gov (United States)

    Magno Pereira, Vítor; Marote Correia, Luís; Rodrigues, Tiago; Serrão Faria, Gorete

    2016-09-01

    The posterior reversible encephalopathy syndrome is a neurological syndrome characterized by headache, confusion, visual disturbances and seizures associated with identifiable areas of cerebral edema on imaging studies. The authors report the case of a man, 33 years-old, leukodermic with a history of chronic alcohol and tobacco consumption, who is admitted to the emergency department for epigastric pain radiating to the back and vomiting with about six hours of evolution and an intense holocranial headache for two hours. His physical examination was remarkable for a blood pressure of 190/100 mmHg and tenderness in epigastrium. His analytical results revealed emphasis on amylase 193 U/L and lipase 934 U/L. During the observation in the emergency department,he presented a generalized tonic-clonic seizure. Abdominal ultrasonography was performed and suggestive of pancreatitis withoutgallstones signals. Head computed tomography showed subarachnoid haemorrhage and a small right frontal cortical haemorrhage. The brain magnetic resonance imaging done one week after admission showed areas of a bilateral and symmetrical T2 / FLAIR hyperintensities in the subcortical white matter of the parietal and superior frontal regions, suggesting a diagnosis of posterior reversible encephalopathy syndrome. Abdominal computed tomography (10 days after admission) demonstrated a thickened pancreas in connection with inflammation and two small hypodense foci in the anterior part of the pancreas body, translating small foci of necrosis. The investigation of a thrombophilic defect revealed a heterozygous G20210A prothrombin gene mutation. The patient was discharged without neurological sequelae and asymptomatic. The follow-up brain magnetic resonance imaging confirmed the reversal of the lesions, confirming the diagnosis.

  4. Hypertensive Encephalopathy: Isolated Pons Involvement Mimicking Central Pontine Myelinolysis

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    Gamanagatti, S.; Subramanian, S. [India Institute of Medical Sciences, New Delhi (India)

    2006-09-15

    MRI of the brain was performed, and it demonstrated an isolated high signal on the T2 weighted and fluid attenuated inversion recovery sequences that involved only the central pons with sparing the periphery. There was no restricted diffusion on diffusion weighted imaging. The differential diagnosis included posterior reversible syndrome and central pontine myelinolysis; however, the blood sodium on admission was normal. The pathogenesis of HE is that the auto-regulatory mechanisms that control the cerebral blood flow are exceeded, resulting in hyper-perfusion. The consequent over-distension of the cerebral vessels, the breakdown of the blood brain barrier and ultimately, the extravasation of fluid into the interstitium all cause vasogenic edema. In most cases, the changes of hypertensive encephalopathy represent reversible vasogenic edema, which can be seen on T2-weighted images, and restricted diffusion is not seen on the diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) maps. Hypertensive encephalopathy that manifests as a reversible increased signal isolated to the pons on T2-weighted images is extremely uncommon. The differential diagnosis for such pontine T2 hyperintensity includes pontine glioma, ischemic and radiation changes (generally irreversible conditions), as well as central pontine myelinolysis (CPM) and demyelinating disorders such as multiple sclerosis, acute disseminated encephalomyelitis and rhomb-encephalitis. In CPM electrolyte imbalances provide a clue for the diagnosis, where as for glioma, there will be an expansion and mass effect. In conclusion, clinical recognition of brainstem HE may be difficult. The features of a lack of correlation between the severity of the radiological abnormality and the clinical status, combined with the rapid resolution following antihypertensive treatment, should suggest the diagnosis. It is important for the radiologist to be familiar with the imaging abnormalities of this life

  5. Determinants of recovery from severe posterior reversible encephalopathy syndrome.

    Directory of Open Access Journals (Sweden)

    Stephane Legriel

    Full Text Available OBJECTIVE: Few outcome data are available about posterior reversible encephalopathy syndrome (PRES. We studied 90-day functional outcomes and their determinants in patients with severe PRES. DESIGN: 70 patients with severe PRES admitted to 24 ICUs in 2001-2010 were included in a retrospective cohort study. The main outcome measure was a Glasgow Outcome Scale (GOS of 5 (good recovery on day 90. MAIN RESULTS: Consciousness impairment was the most common clinical sign, occurring in 66 (94% patients. Clinical seizures occurred in 57 (81% patients. Median mean arterial pressure was 122 (105-143 mmHg on scene. Cerebral imaging abnormalities were bilateral (93% and predominated in the parietal (93% and occipital (86% white matter. Median number of brain areas involved was 4 (3-5. Imaging abnormalities resolved in 43 (88% patients. Ischaemic and/or haemorrhagic complications occurred in 7 (14% patients. The most common causes were drug toxicity (44% and hypertensive encephalopathy (41%. On day 90, 11 (16% patients had died, 26 (37% had marked functional impairments (GOS, 2 to 4, and 33 (56% had a good recovery (GOS, 5. Factors independently associated with GOS<5 were highest glycaemia on day 1 (OR, 1.22; 95%CI, 1.02-1.45, p = 0.03 and time to causative-factor control (OR, 3.3; 95%CI, 1.04-10.46, p = 0.04, whereas GOS = 5 was associated with toxaemia of pregnancy (preeclampsia/eclampsia (OR, 0.06; 95%CI, 0.01-0.38, p = 0.003. CONCLUSIONS: By day 90 after admission for severe PRES, 44% of survivors had severe functional impairments. Highest glycaemia on day 1 and time to causative-factor control were strong early predictors of outcomes, suggesting areas for improvement.

  6. Mitochondrial myopathy, encephalopathy, lactate acidosis with stroke-like episodes syndrome (MELAS: A case report

    Directory of Open Access Journals (Sweden)

    Petrović Igor N.

    2012-01-01

    Full Text Available Introduction. Mitochondrial encephalopathy, lactacidosis and stroke-like episodes (MELAS represent a multisystemic dysfunction due to various mutations in mitochondrial DNA. Here we report a patient with genetically confirmed MELAS. Case Outline. A patient is presented whose clinical features involved short stature, easy tendency to fatigue, recurrent seizures, progressive cognitive decline, myopathy, sensorineural deafness, diabetes mellitus as well as stroke-like episodes. The major clinical feature of migraine type headache was not present. Neuroimaging studies revealed signs of ischemic infarctions localized in the posterior regions of the brain cortex. Electron microscopy of the skeletal muscle biopsy showed subsarcolemmal accumulation of a large number of mitochondria with paracristal inclusions in the skeletal muscle cells. The diagnosis of MELAS was definitively confirmed by the detection of a specific point mutation A to G at nucleotide position 3243 of mitochondrial DNA. Conclusion. When a relatively young patient without common risk factors for ischemic stroke presents with signs of occipitally localized brain infarctions accompanied with multisystemic dysfunction, MELAS syndrome, it is necessary to conduct investigations in order to diagnose the disease.

  7. Suboptimal performance on neuropsychological tests in patients with suspected chronic toxic encephalopathy

    NARCIS (Netherlands)

    van Hout, MSE; Schmand, B; Wekking, EM; Hageman, G; Deelman, BG

    Suboptimal performance during neuropsychological testing can seriously complicate assessment in behavioral neurotoxicology. We present data on the prevalence of suboptimal performance in a group of Dutch patients with suspected chronic toxic encephalopathy (CTE) after long-term occupational exposure

  8. Suboptimal performance on neuropsychological tests in patients with suspected chronic toxic encephalopathy

    NARCIS (Netherlands)

    van Hout, Moniek S. E.; Schmand, Ben; Wekking, Ellie M.; Hageman, Gerard; Deelman, Betto G.

    2003-01-01

    Suboptimal performance during neuropsychological testing can seriously complicate assessment in behavioral neurotoxicology. We present data on the prevalence of suboptimal performance in a group of Dutch patients with suspected chronic toxic encephalopathy (CTE) after long-term occupational exposure

  9. Zonisamide eradicated paroxysmal headache with EEG abnormalities triggered by hypertensive encephalopathy due to purpura nephritic syndrome.

    Science.gov (United States)

    Anzai, Yuki; Hayashi, Masaharu; Ohya, Tatsuo

    2006-10-01

    Generally, prognosis of hypertensive encephalopathy in childhood is favorable. We reported a 5-year-old girl who presented with a headache attack and EEG abnormalities after hypertensive encephalopathy due to purpura nephritis. The patient had suffered from hypertensive encephalopathy due to purpura nephritis, which soon ameliorated. Five months later, she developed attacks of headache, vomiting and disturbed consciousness with left side-predominant EEG abnormalities. Although carbamazepine and sodium valproate failed to improve her condition, zonisamide eradicated both the symptoms and EEG abnormalities, and an attack has not reoccurred for 5 years since completion of her treatment. It is noteworthy that delayed-onset complications can occur in child hypertensive encephalopathy, cases of which should be followed up prudently. Zonisamide should be considered for treatment of attacks of headaches with an epileptic character.

  10. Compare Of the West Syndrome with Other Syndromes in the Epileptic Encephalopathy - Kosovo Experience

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    Naim Zeka

    2017-11-01

    CONCLUSION: WS is a frequent disease of the encephalopathies with the epileptogenic framework. The resistance in anticonvulsive therapy is huge, and psychomotoric retardation follows a big percentage of children with this syndrome.

  11. POETenceph - Automatic identification of clinical notes indicating encephalopathy using a realist ontology.

    Science.gov (United States)

    Doing-Harris, Kristina M; Weir, Charlene R; Igo, Sean; Shi, Jianlin; Shao, Yijun; Hurdle, John F

    2015-01-01

    Identifying inpatients with encephalopathy is important. The disorder is prevalent, often missed, and puts patients at risk. We describe POETenceph, natural language processing pipeline, which ranks clinical notes on the extent to which they indicate the patient had encephalopathy. We use a realist ontology of the entities and relationships indicative of encephalopathy in clinical notes. POETenceph includes a passage rank algorithm, which takes identified disorders; matches them to the ontology; calculates the diffuseness, centrality, and length of the matched entry; adds the scores; and returns the ranked documents. We evaluate it against a corpus of clinical documents annotated for evidence of delirium. Higher POETenceph are associated with increasing numbers of reviewer annotations. Detailed examination found that 65% of the bottom scoring documents contained little or no evidence and 70% of the top contained good evidence. POETenceph can effectively rank clinical documents for their evidence of encephalopathy as characterized by delirium.

  12. Thiamine in the treatment of Wernicke encephalopathy in patients with alcohol use disorders.

    Science.gov (United States)

    Latt, N; Dore, G

    2014-09-01

    Wernicke encephalopathy is an acute, reversible neuropsychiatric emergency due to thiamine deficiency. Urgent and adequate thiamine replacement is necessary to avoid death or progression to Korsakoff syndrome with largely irreversible brain damage. Wernicke Korsakoff syndrome refers to a condition where features of Wernicke encephalopathy are mixed with those of Korsakoff syndrome. Although thiamine is the cornerstone of treatment of Wernicke encephalopathy, there are no universally accepted guidelines with regard to its optimal dose, mode of administration, frequency of administration or duration of treatment. Currently, different dose recommendations are being made. We present recommendations for the assessment and treatment of Wernicke encephalopathy based on literature review and our clinical experience. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

  13. Wernicke’s encephalopathy associated with liver abscess.

    Science.gov (United States)

    Verma, Rajesh; Garg, Vipul

    2017-07-31

    Wernicke's encephalopathy is a rare neurological disorder caused by thiamine deficiency, characterised by ocular motor dysfunction, ataxia and impairment in consciousness. It predominantly affects brain regions with a high metabolic rate such as mammillary bodies, medial thalamic nuclei, the tectal region and the cerebellum. Although chronic alcoholism is the most common cause of Wernicke's encephalopathy, various other conditions not related to alcohol consumption such as bariatric surgery, acute pancreatitis, hyperemesis gravidarum, prolonged fasting and gastrointestinal surgery have been implicated in its aetiology. We report the case of a patient who underwent surgery for liver abscess and subsequently developed Wernicke's encephalopathy; he showed a positive response to thiamine supplementation. This is the first report describing liver abscess as the cause of Wernicke's encephalopathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Prognostic Value of Cytochrome C and Cytokines in Acute Viral Encephalopathy

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    J Gordon Millichap

    2006-06-01

    Full Text Available Serum cytochrome c and cytokines were evaluated as prognostic predictors in 29 children (ages 9 mos to 9 yrs 11 mos with viral acute encephalopathies and multiple organ failure at Fukushima Medical University School of Medicine, Japan.

  15. Long-term cognitive and behavioral consequences of neonatal encephalopathy following perinatal asphyxia: a review

    NARCIS (Netherlands)

    van Handel, M.; Swaab, H.; de Vries, L.S.; Jongmans, M.J.

    2007-01-01

    Neonatal encephalopathy (NE) following perinatal asphyxia (PA) is considered an important cause of later neurodevelopmental impairment in infants born at term. This review discusses long-term consequences for general cognitive functioning, educational achievement, neuropsychological functioning and

  16. Dutch patients with progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome

    NARCIS (Netherlands)

    Vanhatalo, S.; Somer, M.; Barth, P. G.

    2002-01-01

    PEHO syndrome (progressive encephalopathy, peripheral edema, hypsarrhythmia, and optic atrophy) is a neurodegenerative disorder first characterized in Finnish patients. Subsequent reports have occasionally identified cases of PEHO occurring in some other countries. We describe two Dutch children who

  17. Dextromethorphan in the treatment of early myoclonic encephalopathy evolving into migrating partial seizures in infancy

    Directory of Open Access Journals (Sweden)

    Yin-Hsuan Chien

    2012-05-01

    Full Text Available Epileptic encephalopathy with suppression-burst in electroencephalography (EEG can evolve into a few types of epileptic syndromes. We present here an unusual case of early myoclonic encephalopathy that evolved into migrating partial seizures in infancy. A female neonate initially had erratic myoclonus movements, hiccups, and a suppression-burst pattern in EEG that was compatible with early myoclonic encephalopathy. The seizures were controlled with dextromethorphan (20 mg/kg, and a suppression-burst pattern in EEG was reverted to relatively normal background activity. However, at 72 days of age, alternating focal tonic seizures, compatible with migrating partial seizures in infancy, were demonstrated by the 24-hour EEG recording. The seizures responded poorly to dextromethorphan. To our knowledge, this is the first reported case of early myoclonic encephalopathy evolving into migrating partial seizure in infancy. Whether it represents another age-dependent epilepsy evolution needs more clinical observation.

  18. GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders.

    Science.gov (United States)

    Ohba, Chihiro; Shiina, Masaaki; Tohyama, Jun; Haginoya, Kazuhiro; Lerman-Sagie, Tally; Okamoto, Nobuhiko; Blumkin, Lubov; Lev, Dorit; Mukaida, Souichi; Nozaki, Fumihito; Uematsu, Mitsugu; Onuma, Akira; Kodera, Hirofumi; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Miyake, Noriko; Tanaka, Fumiaki; Kato, Mitsuhiro; Ogata, Kazuhiro; Saitsu, Hirotomo; Matsumoto, Naomichi

    2015-06-01

    Recently, de novo mutations in GRIN1 have been identified in patients with nonsyndromic intellectual disability and epileptic encephalopathy. Whole exome sequencing (WES) analysis of patients with genetically unsolved epileptic encephalopathies identified four patients with GRIN1 mutations, allowing us to investigate the phenotypic spectrum of GRIN1 mutations. Eighty-eight patients with unclassified early onset epileptic encephalopathies (EOEEs) with an age of onset A) with a mutant allele frequency of 16% (in DNA of blood leukocytes) was detected in one patient. Three mutations were located in the transmembrane domain (3/4, 75%), and one in the extracellular loop near transmembrane helix 1. All the mutations were predicted to impair the function of the NMDA receptor. Clinical features of de novo GRIN1 mutations include infantile involuntary movements, seizures, and hand stereotypies, suggesting that GRIN1 mutations cause encephalopathy resulting in seizures and movement disorders. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  19. Steroid-Responsive Epilepsia Partialis Continua with Anti-Thyroid Antibodies: A Spectrum of Hashimoto's Encephalopathy

    OpenAIRE

    Hiroki Masuda; Masahiro Mori; Shoichi Ito; Toshiyuki Yagishita; Satoshi Kuwabara

    2014-01-01

    Background: When a neuropsychiatric symptom due to encephalopathy develops in a patient with anti-thyroid antibodies, especially when the symptom is steroid-responsive, Hashimoto's encephalopathy (HE) needs to be included in the differential diagnosis of the patient. Although HE is an elusive disease, it is thought to cause various clinical presentations including seizures, myoclonus, and epilepsia partialis continua (EPC). Case Report: We present the case of a 33-year-old Japanese woman who ...

  20. Pediatric posterior reversible encephalopathy syndrome presenting with isolated cerebellar edema and obstructive hydrocephalus.

    Science.gov (United States)

    Ettinger, Nicholas; Pearson, Matthew; Lamb, Fred S; Wellons, John C

    2014-10-01

    In this report, the authors describe the case of a teenage boy who presented with hypertensive emergency, posterior reversible encephalopathy syndrome, and hydrocephalus due to fourth ventricle outlet obstruction. Posterior reversible encephalopathy syndrome is a well-characterized but uncommon syndrome in children that is generally triggered by severe hypertension. The unusual clinical picture of this patient, who had isolated cerebellar edema leading to obstructive hydrocephalus, has been rarely described in children.

  1. Early Prediction and Outcome of Septic Encephalopathy in Acute Stroke Patients With Nosocomial Coma

    OpenAIRE

    Tong, Dao-Ming; Zhou, Ye-Ting; Wang, Guang-Sheng; Chen, Xiao-Dong; Yang, Tong-Hui

    2015-01-01

    Background Septic encephalopathy (SE) is the most common acute encephalopathy in ICU; however, little attention has been focused on risk of SE in the course of acute stroke. Our aim is to investigate the early prediction and outcome of SE in stroke patients with nosocomial coma (NC). Methods A retrospective cohort study was conducted in an ICU of the tertiary teaching hospital in China from January 2006 to December 2009. Ninety-four acute stroke patients with NC were grouped according to with...

  2. The thalamus in cirrhotic patients with and without hepatic encephalopathy: A volumetric MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Ran, E-mail: taoran1648@yahoo.cn [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Department of Radiology, Bethune International Peace Hospital of People' s Liberty Army, Shijiazhuang 050082, Hebei Province (China); Zhang, Jiuquan, E-mail: jiuquanzhang@yahoo.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); You, Zhonglan, E-mail: you_zhonglan@163.com [Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Wei, Luqing, E-mail: weiluqing@foxmail.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Fan, Yi, E-mail: fanyi1978@yahoo.cn [Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Cui, Jinguo, E-mail: cuijinguo2005@163.com [Department of Radiology, Bethune International Peace Hospital of People' s Liberty Army, Shijiazhuang 050082, Hebei Province (China); Wang, Jian, E-mail: wangjian_811@yahoo.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

    2013-11-01

    Background and aims: The thalamus is a major relay and filter station in the central neural system. Some previous studies have suggested that the thalamus maybe implicated in the pathogenesis of hepatic encephalopathy. The aim of our study was to investigate changing thalamic volumes in cirrhotic patients with and without hepatic encephalopathy. Methods: Neuropsychological tests and structural MR scanning were performed on 24 cirrhotic patients, 23 cirrhotic patients with minimal hepatic encephalopathy, 24 cirrhotic patients during their first episode of overt hepatic encephalopathy, and 33 healthy controls. Voxel-based morphometry analysis was performed to detect gray matter morphological changes. The thalamus and whole brain volume were extrapolated. A receiver operating characteristic curve analysis of thalamic volumes was used to discriminate patients with minimal hepatic encephalopathy from those with hepatic cirrhosis. Results: Thalamic volume increased in a stepwise manner in patients with progressively worse stages of hepatic encephalopathy compared to healthy subjects. Additionally, a comparison of gray matter morphometry between patients with Child–Pugh grades A, B, or C and controls revealed a progression in thalamic volumes in parallel with the degree of liver failure. Moreover, thalamic volume was significantly correlated with the number connection test A time and digit-symbol test score in cirrhotic patients with minimal hepatic encephalopathy (r = 0.659, P = 0.001; r = −0.577, P = 0.004; respectively). The area under the receiver operating characteristic curve was 0.827 (P = 0.001). Conclusions: A significantly increased thalamic volume may be provide an objective imaging measure for predicting seizures due to minimal hepatic encephalopathy in cirrhotic patients.

  3. Two Unusual Aspects of Posterior Reversible Encephalopathy Syndrome Mimicking Primary and Secondary Brain Tumor Lesions

    Directory of Open Access Journals (Sweden)

    Mazamaesso Tchaou

    2015-01-01

    Full Text Available The posterior reversible encephalopathy syndrome (PRES is a rare clinical-radiological entity well described with typical clinical and radiological manifestations. Atypical presentation, especially in imaging, exists. The authors report here two cases of posterior reversible encephalopathy in which imaging aspects were atypical, mimicking, in the first case, hemorrhagic cerebral metastasis of cholangiocarcinoma and, in the second case, a brain tumor. The diagnosis has been retrospectively rectified due to clinical and radiological outcome.

  4. Hypoxic-Ischemic Encephalopathy after Bee Sting and Treatment with Zolpidem: A Case Report

    Directory of Open Access Journals (Sweden)

    Turgay Demir

    2016-09-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE, a metabolic encephalopathy, develops as a result of cessation or reduction of oxygen and blood flow to the brain. The clinical picture may vary in severity from minimal neurologic deficits to coma. In living patients, permanent neuropsychological sequelae can develop. Herein, we present a case of HIE that occured after anaphylactic reaction due to bee sting, which was treatedm with zolpidem.

  5. Prodominant hypertensive brainstem encephalopathy with supratentorial involvement: Case report and literature review

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    Kim, Ji Hee; Park, Sung Tae; Lim, Hyun Kyung [Dept. of Radiology, Soonchunhyang University Hospital, Soonchunhyang University School of Medicine, Seoul (Korea, Republic of); Kim, Sung Tae; Cha, Ji Hoon [Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2014-12-15

    Hypertensive encephalopathy typically presents with bilateral parietooccipital vasogenic edema. Brainstem and cerebellar edema are uncommon in association with typical supratentorial changes. We experienced three cases of atypical hypertensive encephalopathy involving brainstem and cerebellum as well as cerebral white matter, which showed characteristic alternating linear bright and low signals in the pons, the so-called 'stripe sign'. We report these cases here with a brief literature review.

  6. More than meets the eye: infant presenting with hypoxic ischaemic encephalopathy.

    Science.gov (United States)

    Sen, Kuntal; Agarwal, Rajkumar

    2018-04-05

    We report a newborn infant who presented with poor Apgar scores and umbilical artery acidosis leading to the diagnosis of hypoxic ischaemic encephalopathy. During the course of the infant's hospitalisation, subsequent workup revealed an underlying genetic cause that masqueraded as hypoxic ischaemic encephalopathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Molecular and Genetic Investigation of Tau in Chronic Traumatic Encephalopathy (Log No. 13267017)

    Science.gov (United States)

    2017-10-01

    term goal is to identify molecular mechanisms regulating tau that can be used as diagnostics and to develop therapeutics for CTE. The immediate goal...AWARD NUMBER: W81XWH-14-1-0399 TITLE: Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy (Log No. 13267017) PRINCIPAL...INTRODUCTION: Repetitive mild traumatic brain injury leads to neurological symptoms and chronic traumatic encephalopathy (CTE). The molecular changes

  8. Posterior Reversible Encephalopathy Syndrome After Orthotopic Heart Transplantation: A Case Report

    OpenAIRE

    Ramirez, Rigoberto; Muskula, Preetham Reddy; Everley, Mark P.

    2017-01-01

    Patient: Female, 32 Final Diagnosis: Posterior reversible encephalopathy syndrome Symptoms: Seizures Medication: Tacrolimus Clinical Procedure: ? Specialty: Cardiology Objective: Rare disease Background: Calcineurin inhibitor-induced posterior reversible encephalopathy syndrome (PRES) is well described in liver and kidney transplant patients, but there is a paucity of data in heart transplant patients. PRES syndrome in the setting of heart transplantation can occur as early as 5 days followin...

  9. The role of epilepsy surgery in the treatment of childhood epileptic encephalopathy.

    Science.gov (United States)

    Kayyali, Husam R; Abdelmoity, Ahmed; Baeesa, Saleh

    2013-01-01

    Children with epileptic encephalopathy often have global impairment of brain function and frequent intractable seizures, which contribute further to their developmental disability. Many of these children have identifiable brain lesion on neurological imaging. In such cases, epilepsy surgery may be considered as a treatment option despite the lack of localized epileptic pattern on electroencephalogram (EEG). In this paper, we summarize the clinical features of epileptic encephalopathy syndromes and review the reported literature on the surgical approach to some of these disorders.

  10. Psychiatric presentation of voltage-gated potassium channel antibody-associated encephalopathy

    OpenAIRE

    PARTHASARATHI, U. D.; HARROWER, T.; TEMPEST, M.; HODGES, J. R.; WALSH, C.; McKENNA, P. J.; FLETCHER, P.C.

    2006-01-01

    Voltage-gated potassium channel antibody encephalopathy, a rare cause of limbic encephalopathy, typically presents with memory impairment and seizures. Psychiatric symptoms have not been emphasised in the literature. Here we describe a 58-year-old man who presented with panic attacks and psychogenic non-epileptic seizures and, later on, developed delusions and hallucinations and then confusion.He was found to have antibodies to voltage-gated potassium channels.Treatment with immuno-modulatory...

  11. The Role of Epilepsy Surgery in the Treatment of Childhood Epileptic Encephalopathy

    OpenAIRE

    Kayyali, Husam R.; Abdelmoity, Ahmed; Baeesa, Saleh

    2013-01-01

    Children with epileptic encephalopathy often have global impairment of brain function and frequent intractable seizures, which contribute further to their developmental disability. Many of these children have identifiable brain lesion on neurological imaging. In such cases, epilepsy surgery may be considered as a treatment option despite the lack of localized epileptic pattern on electroencephalogram (EEG). In this paper, we summarize the clinical features of epileptic encephalopathy syndrome...

  12. Psychometric hepatic encephalopathy score for the detection of minimal hepatic encephalopathy in Korean patients with liver cirrhosis.

    Science.gov (United States)

    Seo, Yeon Seok; Yim, Sun Young; Jung, Jin Yong; Kim, Chang Ha; Kim, Jin Dong; Keum, Bora; An, Hyonggin; Yim, Hyung Joon; Lee, Hong Sik; Kim, Chang Duck; Ryu, Ho Sang; Um, Soon Ho

    2012-11-01

    Although the Psychometric Hepatic Encephalopathy Score (PHES) for the diagnosis of minimal hepatic encephalopathy (MHE) has been validated in several countries, further validation is required for its use in different populations. The aims of this study were thus to standardize the PHES in a healthy Korean population and evaluate the prevalence of MHE among Korean patients with liver cirrhosis. Two-hundred healthy subjects without evidence of liver disease and 160 patients with liver cirrhosis without overt HE were included. Blood sampling for routine laboratory tests and determination of venous ammonia concentration was performed on the day of PHES neuropsychological testing. The age and education years of the control group were 41 ± 13 years and 13 ± 3 years, respectively; 100 of the subjects (50.0%) were men. The PHES for the control group was -0.31 ± 2.06 and the normal range was thus set at > -5 points. The age and education years of the liver cirrhosis group were 55 ± 8 and 11 ± 4 years, respectively; 102 of those in this group (63.8%) were men. Of the liver cirrhosis patients, 129 (80.6%), 21 (13.1%), and 10 (6.3%) had Child-Pugh grades A, B, and C, respectively. The PHES of the liver cirrhosis group was -2.94 ± 3.39. MHE was diagnosed in 41 patients (25.6%), of which 26 (20.2%), nine (42.9%), and six (60.0%) had Child-Pugh grades A, B, and C, respectively. The PHES was useful for detecting patients with MHE. A significant proportion of Korean patients with liver cirrhosis suffer from MHE. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  13. Post-streptococcal glomerulonephritis leading to posterior reversible encephalopathy syndrome: a case report.

    Science.gov (United States)

    Adikari, Madura; Priyangika, Dilani; Marasingha, Indika; Thamotheram, Sharmila; Premawansa, Gayani

    2014-09-13

    Posterior reversible encephalopathy syndrome is a clinical radiographic syndrome of heterogeneous etiologies. Developing hypertensive encephalopathy following post-streptococcal glomerulonephritis is a known but uncommon manifestation and developing posterior reversible encephalopathy syndrome in such a situation is very rare. We report a case with contrast-enhanced computed tomography and magnetic resonance imaging findings of posterior reversible encephalopathy syndrome in the background of acute post-streptococcal glomerulonephritis. A thirteen-year-old Sri Lankan boy presented with a focal fit by way of secondary generalization with duration of 10 minutes, and developed 2 similar fits subsequently following admission. He later developed severe hypertension with evidence of glomerulonephritis, which was diagnosed as acute post-streptococcal glomerulonephritis. A contrast-enhanced computed tomography imaging of brain done on day-3 revealed non-enhancing low-attenuating areas in fronto-parietal regions. A T2 weighted film of magnetic resonance imaging was done on day-10 of the admission and found to have linier sub-cortical hyper intensities in both parietal regions which were compatible with the radiological diagnosis of posterior reversible encephalopathy syndrome. Post-streptococcal glomerulonephritis is an important cause of acute nephritic syndrome especially in children. This case report illustrates a rare association of posterior reversible encephalopathy syndrome in a patient with post-streptococcal glomerulonephritis.

  14. Epileptic Encephalopathy in Childhood: A Stepwise Approach for Identification of Underlying Genetic Causes.

    Science.gov (United States)

    Patel, Jaina; Mercimek-Mahmutoglu, Saadet

    2016-10-01

    Epilepsy is one of the most common neurological disorders in childhood. Epilepsy associated with global developmental delay and cognitive dysfunction is defined as epileptic encephalopathy. Certain inherited metabolic disorders presenting with epileptic encephalopathy can be treated with disease specific diet, vitamin, amino acid or cofactor supplementations. In those disorders, disease specific therapy is successful to achieve good seizure control and improve long-term neurodevelopmental outcome. For this reason, intractable epilepsy with global developmental delay or history of developmental regression warrants detailed metabolic investigations for the possibility of an underlying treatable inherited metabolic disorder, which should be undertaken as first line investigations. An underlying genetic etiology in epileptic encephalopathy has been supported by recent studies such as array comparative genomic hybridization, targeted next generation sequencing panels, whole exome and whole genome sequencing. These studies report a diagnostic yield up to 70%, depending on the applied genetic testing as well as number of patients enrolled. In patients with epileptic encephalopathy, a stepwise approach for diagnostic work-up will help to diagnose treatable inherited metabolic disorders quickly. Application of detailed genetic investigations such as targeted next generation sequencing as second line and whole exome sequencing as third line testing will diagnose underlying genetic disease which will help for genetic counseling as well as guide for prenatal diagnosis. Knowledge of underlying genetic cause will provide novel insights into the pathogenesis of epileptic encephalopathy and pave the ground towards the development of targeted neuroprotective treatment strategies to improve the health outcome of children with epileptic encephalopathy.

  15. Syndrome of Electrical Status Epilepticus During Sleep: Epileptic Encephalopathy Related to Brain Development.

    Science.gov (United States)

    Chen, Xiao-Qiao; Zhang, Wei-Na; Hu, Lin-Yan; Liu, Meng-Jia; Zou, Li-Ping

    2016-03-01

    Epileptic encephalopathy with electrical status epilepticus during sleep is an age-related and self-limited disorder. The present study analyzed the etiology, demographics, and pathogenesis of patients with electrical status epilepticus during sleep to provide information on the diagnosis and therapy of this syndrome. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in patients admitted in Chinese People's Liberation Army General Hospital from 2009 to 2014 were retrospectively analyzed. Patients were classified into the genetic, structural-metabolic, and unknown groups according to the etiology. Demographics and clinical characteristics of all the patients were then analyzed and compared among groups. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in 75 patients mainly included benign childhood epilepsy with centrotemporal spikes, Landau-Kleffner syndrome, polymicrogyria, and migration disorders. Age at onset of epilepsy did not show a specific pattern, but age at onset of epileptic encephalopathy with electrical status epilepticus during sleep was concentrated at age 6-9 years. The mean age at onset of epilepsy in the genetic group was significantly older than that in the structural-metabolic group (P epileptic encephalopathy with electrical status epilepticus during sleep did not significantly differ between the two groups. Electrical status epilepticus during sleep is an epileptic encephalopathy related to brain development and presents an age-dependent occurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Modified-orientation log to assess hepatic encephalopathy.

    Science.gov (United States)

    Salam, M; Matherly, S; Farooq, I S; Stravitz, R T; Sterling, R K; Sanyal, A J; Gibson, D P; Wade, J B; Thacker, L R; Heuman, D M; Fuchs, M; Puri, P; Luketic, V; Bickston, S J; Bajaj, J S

    2012-04-01

    The subjectivity of the West-Haven criteria (WHC) hinders hepatic encephalopathy (HE) evaluation. The new HE classification has emphasised assessment of orientation. The modified-orientation log (MO-log, eight questions, scores 0-24; 24 normal) is adapted from a validated brain injury measure. To validate MO-log for HE assessment in cirrhosis. Cirrhotics admitted with/without HE were administered MO-log. We collected cirrhosis/HE details, admission/daily MO-logs and WHC (performed by different examiners), time to reach normal mentation (MO-log ≥23) and MO-log/WHC change (Δ) over day 1. Outcomes were in-hospital mortality, duration to normal mentation and length-of-stay (LOS). Regressions were performed for each outcome. MO-log inter-rater reliability was measured. Ninety-six HE (55 ± 8 years, MELD 21) and 20 non-HE (54 ± 5 years, MELD 19) in-patients were included. In HE patients, median admission WHC was 3 (range 1-4). Mean MO-log was 12 ± 8 (range 0-22). Their LOS was 6 ± 5 days and 13% died. Time to reach normal mentation was 2.4 ± 1.7 days. Concurrent validity: there was a significant negative correlation between admission MO-log and WHC (r = -0.79, P logs were significantly lower in those who died (7 vs. 12, P = 0.03) and higher in those admitted without HE (23.6 vs. 12, P log improved in 69% on day 1 (ΔMO-log 4 ± 8) which was associated with lower duration to normal mentation (2 vs. 3.5 days, P = 0.03) and mortality (3% vs.43%, P log but not WHC as a predictor. Inter-rater reliability: ICC for MO-log inter-rater observations was 0.991. Modified-orientation log is a valid tool for assessing severity and is better than West-Haven criteria in predicting outcomes in hospitalised hepatic encephalopathy patients. © 2012 Blackwell Publishing Ltd.

  17. Prolonged Toxic Encephalopathy following Accidental 4-Aminopyridine Overdose

    Directory of Open Access Journals (Sweden)

    Maria Ballesta Méndez

    2014-01-01

    Full Text Available Background. 4-Aminopyridine (4-AP is a drug that is used to improve motor fatigue in patients suffering from multiple sclerosis (MS. Medication error can occur, as commercial preparation may not be available in some countries. Case Presentation. A 58-year-old woman with progressive MS presented with status epilepticus. She was receiving 4-AP for more than 3 years. The symptoms started soon after the ingestion of a single pill that was supposed to contain 10 mg 4-AP, but further investigations revealed that each pill had been inadvertently prepared with an 100 mg 4-AP concentration. The patient was admitted to the intensive care unit (ICU for appropriate management (orotracheal intubation, sedation, and antiepileptic drugs. The first electroencephalogram (EEG showed abundant irregular spike-waves on the left central regions. Neurological condition gradually improved from day 7, while the EEG did not reveal any more electrical seizures but was still consistent with toxic encephalopathy. The patient stayed in the ICU until day 13. At discharge from the rehabilitation ward (2.5 months later, the patient had not yet recovered her previous cognitive and functional condition. Conclusion. A single 100 mg 4-AP accidental overdose may cause serious immediate complications, with a slow and incomplete neurological recovery.

  18. Mothball withdrawal encephalopathy: case report and review of paradichlorobenzene neurotoxicity.

    Science.gov (United States)

    Cheong, Raymond; Wilson, Robin K; Cortese, Irene C M; Newman-Toker, David E

    2006-12-01

    Paradichlorobenzene (PDB) is a common household deodorant and pesticide found in room deodorizers, toilet bowl fresheners, and some mothballs. Although human exposure to the compound is generally limited and harmless, PDB in larger doses can produce neurotoxic effects, including a chemical "high" similar to that seen with inhalants such as toluene. Although rare, frank addiction to PDB has been reported, and, in such cases, has been associated with gait ataxia, tremor, dysarthria, limb weakness, and bradyphrenia, in various combinations. In such cases, the adverse neurologic consequences have been presumed to result from a direct toxic effect of this small, organic molecule. We report a case of chronic mothball ingestion where profound encephalopathy with cognitive, pyramidal, extrapyramidal, and cerebellar features appears to have been largely the result of PDB withdrawal, rather than direct toxicity. This case raises important questions about the mechanism of PDB neurotoxicity and possible treatment options for PDB-addicted patients. We propose that in cases with clear clinical deterioration after abstinence, readministration and gradual taper of PDB might be considered a therapeutic option.

  19. Biomarkers of acute kidney injury in neonatal encephalopathy.

    LENUS (Irish Health Repository)

    Sweetman, D U

    2013-03-01

    Acute kidney injury (AKI) is a common complication of neonatal encephalopathy (NE). The accurate diagnosis of neonatal AKI, irrespective of the cause, relies on suboptimal methods such as identification of rising serum creatinine, decreased urinary output and glomerular filtration rate. Studies of AKI biomarkers in adults and children have shown that biomarkers can improve the early diagnosis of AKI. Hypoxia-ischaemia is the proposed aetiological basis of AKI in both NE and cardiopulmonary bypass (CPB). However, there is a paucity of studies examining the role of AKI biomarkers specifically in NE. Urinary cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18, kidney injury molecule-1, liver-type fatty acid-binding protein, serum CysC and serum NGAL all show good ability to predict early AKI in a heterogeneous critically ill neonatal population including infants post-CPB. Moreover, serum and urinary NGAL and urinary CysC are early predictors of AKI secondary to NE. These findings are promising and open up the possibility of biomarkers playing a significant role in the early diagnosis and treatment of NE-related AKI. There is an urgent need to explore the role of AKI biomarkers in infants with NE as establishing the diagnosis of AKI earlier may allow more timely intervention with potential for improving long-term outcome.

  20. MODELING CHRONIC TRAUMATIC ENCEPHALOPATHY: THE WAY FORWARD FOR FUTURE DISCOVERY

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    Ryan C. Turner

    2015-10-01

    Full Text Available Despite the extensive media coverage associated with the diagnosis of chronic traumatic encephalopathy (CTE, our fundamental understanding of the disease pathophysiology remains in its infancy. Only recently have scientific laboratories and personnel begun to explore CTE pathophysiology through the use of preclinical models of neurotrauma. Some studies have shown the ability to recapitulate some aspects of CTE in rodent models, through the use of various neuropathologic, biochemical, and/or behavioral assays. Many questions related to CTE development however remain unanswered. These include the role of impact severity, the time interval between impacts, the age at which impacts occur, and the total number of impacts sustained. Other important variables such as the location of impacts, character of impacts, and effect of environment/lifestyle and genetics also warrant further study. In this work we attempt to address some of these questions by exploring work previously completed using single and repetitive injury paradigms. Despite some models producing some deficits similar to CTE symptoms, it is clear that further studies are required to understand the development of neuropathological and neurobehavioral features consistent with CTE-like features in rodents. Specifically, acute and chronic studies are needed that characterize the development of tau-based pathology.

  1. Posterior reversible encephalopathy syndrome in children with kidney disease

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    D N Gera

    2014-01-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is a clinic-radiographic entity of heterogeneous etiologies that are grouped together because of similar findings on neuro-imaging and associated symptom complex of headache, vision loss, altered mentation, and seizures. Although usually considered benign and reversible, characteristics of this syndrome in pediatric patients remain obscure. This case series included 11 patients (8 males, 3 females, age 3-15 years of PRES during September 2010 to February 2012 out of a total 660 renal pediatric patients (1.66%. We studied their clinical profile, contributory factors, and outcome. Presenting symptoms were headache in 73%, dimness of vision or cortical blindness in 36%, seizures in 91%, and altered mentation in 55%. The associated renal diseases were acute renal failure (55%, chronic renal failure (9%, and 36% had normal renal function. The contributory factors were uncontrolled hypertension (100%, severe hypoproteinemia (9%, persistent hypocalcemia (9%, hemolytic uremic syndrome (36%, cyclosporine toxicity (9%, lupus nephritis (9%, high hematocrit (9%, and pulse methylprednisolone (9%. Brain imaging showed involvement of occipito-parietal area (100% and other brain areas (63%. All but one patient of hemolytic uremic syndrome had complete clinical neurological recovery in a week, and all had normal neurological imaging after 4-5 weeks. PRES is an underdiagnosed entity in pediatric renal disease patients. Associated hypertension, renal disease, and immunosuppressive treatment are important triggers. Early diagnosis and treatment of comorbid conditions is of prime importance for early reversal of syndrome.

  2. Radiotracer imaging studies in hepatic encephalopathy: ISHEN practice guidelines.

    Science.gov (United States)

    Berding, Georg; Banati, Richard B; Buchert, Ralph; Chierichetti, Franca; Grover, Vijay P B; Kato, Akinobu; Keiding, Susanne; Taylor-Robinson, Simon D

    2009-05-01

    There is lack of consensus on radiotracer usage in hepatic encephalopathy (HE). We have focused our attention on three main areas: (i) radiotracer imaging in animal models of HE, (ii) methodological issues of radiotracer imaging in HE and (iii) radiotracer imaging studies on the pathophysiology and (new) therapies in HE. We suggest the following: 1. Positron emission tomography (PET) and single photon emission computed tomography lend themselves to the study of animal models of HE, but the models that are suitable depend on the specific research question. Magnetic resonance imaging (MRI) may be a useful alternative technique. 2. Owing to the cost of the technique, there is a need for multicentre human PET studies to overcome the problem of underpowered small studies being undertaken in individual research centres. There should be a unified PET protocol with central, anonymised data analysis in one centre, using validated methodology, on behalf of all participating centres. Such studies would be useful for the assessment of early intervention in patients with subtle neuropsychiatric symptoms, or for clarification of the effect of liver transplantation on HE. 3. While radiotracer imaging modalities remain useful research tools for the study of pathogenesis and for the assessment of treatment effects, there is no consensus on the use of imaging in routine clinical practice for diagnosis and prognosis. The most promising objective tools appear to be magnetic resonance spectroscopy (MRS) and volumetric MRI, which can be performed in multiple centres without the difficulties that radiotracer imaging entail.

  3. The research of melatonin in hypoxic-ischemic encephalopathy

    International Nuclear Information System (INIS)

    Sun Bin; Feng Xing; Qian Zhihong; Shi Ming

    2006-01-01

    Objective: To elucidate the function of melatonin in the pathogenesis and the prognosis of hypoxic-ischemic encephalopathy (HIE) and provide the pathophysiology basis for therapying HIE with melatonin. Methods: The level of plasma melatonin of twenty normal term infants and twenty modest HIE and twenty middle-severity HIE in their acute phase and recovery phase were assayed respectively with radioimmunoassay (RIA). Then compare the difference of the melatonin level among these neonates. Results: (1) For modest HIE, the melatonin level was higher than that in the normal in the acute phase and there was no difference to the normal in the recovery phase. (2) There was no difference between the melatonin level in middle-severity HIE in the acute phase and that in the normal, but in the recovery phase it was higher than that in the normal. (3) For modest HIE, the melatonin level in acute phase was higher than that in the recovery phase, but for middle-severity HIE, it was adverse. (4) In the acute phase, the level in modest HIE was higher than that in the middle-severity HIE, but on the contrary in the recovery phase. Conclusion: Melatonin have protection action on HIE. The prognosis of modest HIE neonates with rising melatonin level in the acute phase is better than that with lower melatonin level of middle-severity HIE. (authors)

  4. Hexachlorophene storage in a burn patient associated with encephalopathy.

    Science.gov (United States)

    Chilcote, R; Curley, A; Loughlin, H H; Jupin, J A

    1977-03-01

    Hexachlorophene (HCP), a chlorinated phenolic hydrocarbon with bacteriostatic properties against Staphylococcus, is used in a number of topical products. Absorption through normal and damaged human skin has been appreciated and neurologic changes have been described in experimental animals, but instances of human toxicity have been reported infrequently. A 10-year-old boy who sustained a 25% burn did well initially but died in the second week of convalescence with hyperthermia, lower-extremity weakness, and cerebral edema. His treatment had included frequent applications of HCP. Analysis of post-mortem tissue revealed the presence of toxic levels of HCP in the blood (2.2 mug/gm) and brain (2.2 mug/gm), with storage in skin (25 mug/gm), liver (4.4 mug/gm), and fat (6.0 mug/gm). This case suggests that topical applications of HCP in man may result in an extensive absorption with fat storage and may cause fatal encephalopathy.

  5. Chronic Traumatic Encephalopathy and Suicide: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Hal S. Wortzel

    2013-01-01

    Full Text Available Traumatic brain injury (TBI is a global health concern, and the recent literature reports that a single mild TBI can result in chronic traumatic encephalopathy (CTE. It has been suggested that CTE may lead to death by suicide, raising important prevention, treatment, and policy implications. Thus, we conducted a systematic review of the medical literature to answer the key question: What is the existing evidence in support of a relationship between CTE and suicide? Systematic searches of CTE and suicide yielded 85 unique abstracts. Seven articles were identified for full text review. Only two case series met inclusion criteria and included autopsies from 17 unique cases, 5 of whom died by suicide. Neither studies used blinding, control cases, or systematic data collection regarding TBI exposure and/or medical/neuropsychiatric history. The identified CTE literature revealed divergent opinions regarding neuropathological elements of CTE and heterogeneity regarding clinical manifestations. Overall quality of evidence regarding a relationship between CTE and suicide was rated as very low using Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE criteria. Further studies of higher quality and methodological rigor are needed to determine the existence and nature of any relationship between CTE and suicide.

  6. [Oxidative stress in perinatal asphyxia and hypoxic-ischaemic encephalopathy].

    Science.gov (United States)

    Nuñez, Antonio; Benavente, Isabel; Blanco, Dorotea; Boix, Héctor; Cabañas, Fernando; Chaffanel, Mercedes; Fernández-Colomer, Belén; Fernández-Lorenzo, José Ramón; Loureiro, Begoña; Moral, María Teresa; Pavón, Antonio; Tofé, Inés; Valverde, Eva; Vento, Máximo

    2017-06-23

    Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways. A third phase has recently been described that includes persistent inflammation and epigenetic changes that would lead to a blockage of oligodendrocyte maturation, alteration of neurogenesis, axonal maturation, and synaptogenesis. In this scenario, oxidative stress plays a critical role causing direct damage to the central nervous system and activating metabolic cascades leading to apoptosis and inflammation. Moderate whole body hypothermia to preserve energy stores and to reduce the formation of oxygen reactive species attenuates the mechanisms that lead to the amplification of cerebral damage upon resuscitation. The combination of hypothermia with coadjuvant therapies may contribute to improve the prognosis. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Magnetic resonance reflects the pathological evolution of Wernicke encephalopathy.

    Science.gov (United States)

    Park, S H; Kim, M; Na, D L; Jeon, B S

    2001-10-01

    Wernicke encephalopathy (WE) is an acute phase of Wernicke-Korsakoff syndrome. Pathologic findings change between acute and chronic phases. Only a few magnetic resonance imaging (MRI) studies have been done to date. To correlate the MRI findings in acute and chronic stages of WE with the known pathologic information, 15 consecutive patients with WE were examined with MRI: 3 before thiamine treatment, 7 within 24 hours of thiamine treatment, 4 between the second and sixth day after thiamine treatment, and 1 fifty-five days after thiamine treatment. Nine of the patients had follow-up MRI between 2 days and 33 months. T1-weighted, proton, and T2-weighted axial images were obtained with additional 5-mm-thick T1-weighted sagittal and coronal images to better visualize the mammillary bodies. In the acute WE, MRI showed high signal intensityon T2-weighted images in periaqueduct and medial thalamic regions. In a few patients with alcoholism, vermian and mammillary body atrophies and third ventricular enlargements were noted. In the chronic phase of WE, T2 hyperintensity disappeared but mammillary bodies and cerebellar vermis became atrophic and third ventricular enlargements were evident. High signal intensity on T2-weighted images disappeared as early as 2 days, and atrophic changes appeared as early as 1 week. MRI is useful for in vivo monitoring and reflects the pathological evolution in acute and chronic phases of WE.

  8. Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy

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    Gabriel eGonzales-Portillo

    2014-08-01

    Full Text Available Treatments for neonatal hypoxic ischemic encephalopathy (HIE have been limited. The aim of this paper is to offer translational research guidance on stem cell therapy for neonatal HIE by examining clinically relevant animal models, practical stem cell sources, safety and efficacy of endpoint assays, as well as a general understanding of modes of action of this cellular therapy. In order to do so, we discuss the clinical manifestations of HIE, highlighting its overlapping pathologies with stroke providing insights on the potential of cell therapy, currently investigated in stroke, for HIE. To this end, we draw guidance from recommendations outlined in Stem cell Therapeutics as an Emerging Paradigm for Stroke or STEPS, which have been recently modified to Baby STEPS to cater for the neonatal symptoms of HIE. These guidelines recognized that neonatal HIE exhibits distinct disease symptoms from adult stroke in need of an innovative translational approach that facilitates the entry of cell therapy in the clinic. Finally, new information about recent clinical trials, and insights into combination therapy are provided with the vision that stem cell therapy may benefit from available treatments, such as hypothermia, already being tested in children diagnosed with HIE.

  9. Recurrent Wernicke's encephalopathy in pregnancy: A case report.

    Science.gov (United States)

    Stephens, Angela; Patel, Khilen; Rao, Ashwin; Browne, Paul; Raley, Susanna; Street, Linda

    2017-12-22

    Wernicke's encephalopathy (WE) is an acute neurologic syndrome resulting from a deficiency in thiamine, also known as Vitamin B1. Thiamine stores can be depleted rapidly in patients with severe hyperemesis. Treatment with thiamine typically results in complete resolution of the neurological abnormalities. A 15-year-old G2P0010 at 13.2 weeks gestation presented with altered mental status and transaminitis. She had a medical termination in her previous pregnancy following an admission for a similar clinical scenario. She was initially thought to have a postoperative surgical complication due to recent cholecystectomy, but further evaluation revealed thiamine depletion. Magnetic resonance imaging confirmed the diagnosis of WE. Repletion of thiamine and folic acid resulted in rapid clinical improvement. WE should be considered in the differential diagnosis of pregnant patients with hyperemesis and altered mental status. A prior history of WE increases the risk of recurrence during pregnancy. Severe hyperemesis during pregnancy increases the risk of thiamine deficiency and WE. Early thiamine supplementation may reduce the risk of WE in patients with a prior clinical history or in patients with severe hyperemesis gravidarum.

  10. Hepatic encephalopathy: An updated approach from pathogenesis to treatment

    Science.gov (United States)

    Toris, Giannakis T.; Bikis, Christos N.; Tsourouflis, Gerasimos S.; Theocharis, Stamatios E.

    2011-01-01

    Summary One of the most serious complications of chronic or fulminant liver failure is hepatic encephalopathy (HE), associated most commonly with cirrhosis. In the presence of chronic liver disease, HE is a sign of decompensation, while in fulminant liver failure its development represents a worrying sign and usually indicates that transplantation will be required. Despite the significance of HE in the course of liver disease, the progress in development of new therapeutic options has been unremarkable over the last 20 years. An up-to-date review regarding HE, including both research and review articles. HE is a serious and progressive, but potentially reversible, disorder with a wide spectrum of neuropsychiatric abnormalities and motor disturbances that ranges from mild alteration of cognitive and motor function to coma and death. Although a clear pathogenesis is yet to be determined, elevated ammonia in serum and the central nervous system is the mainstay for pathogenesis and treatment of HE. Management includes early diagnosis and prompt treatment of precipitating factors. Clinical trials and extensive clinical experience have established the efficacy of diverse substances in HE treatment. Novel therapies with clinical promise include: L-ornithine L-aspartate, sodium benzoate, phenylacetate, AST-120, and the molecular adsorbent recirculating system. Eventually, liver transplantation is often the most successful long-term therapy for HE. PMID:21278704

  11. Chronic traumatic encephalopathy and other long-term sequelae.

    Science.gov (United States)

    Jordan, Barry D

    2014-12-01

    Growing public health concern exists over the incidence of chronic traumatic brain injury (TBI) in athletes participating in contact sports. Chronic TBI represents a spectrum of disorders associated with long-term consequences of single or repetitive TBI and includes chronic traumatic encephalopathy (CTE), chronic postconcussion syndrome, and chronic neurocognitive impairment. Neurologists should be familiar with the different types of chronic TBI and their diagnostic criteria. CTE is the most severe chronic TBI and represents the neurologic consequences of repetitive mild TBI. It is particularly noted among boxers and football players. CTE presents with behavioral, cognitive, and motor symptoms, and can only be definitively diagnosed postmortem. Chronic postconcussion syndrome is defined as postconcussion symptoms that last longer than 1 year and do not appear to resolve; it may develop after a single concussive event. Chronic neurocognitive impairment is an all-encompassing clinical term denoting long-term neurologic sequelae secondary to sports-related trauma and can present either within the postconcussion syndrome or years after a symptom-free interval. This article discusses the diagnostic evaluation of chronic TBI, including clinical history, neurologic examination, neuropsychological testing, neuroimaging, and laboratory testing, as well as the distinctions between CTE, chronic postconcussion syndrome, and chronic neurocognitive impairment. Neurologic impairment among athletes exposed to repetitive brain injury appears to be a real phenomenon. Because CTE has no established treatment, prevention is of paramount importance for athletes participating in contact sports.

  12. Chronic traumatic encephalopathy and risk of suicide in former athletes.

    Science.gov (United States)

    Iverson, Grant L

    2014-01-01

    In the initial autopsy case studies of chronic traumatic encephalopathy (CTE), some researchers have concluded that the proteinopathy associated with CTE is the underlying cause of suicidality and completed suicide in former athletes. A review of the literature on contact sports and risk of completed suicide revealed only one epidemiological study with direct relevant data. There are no published cross-sectional, epidemiological or prospective studies showing a relation between contact sports and risk of suicide. One published epidemiological study suggests that retired National Football League players have lower rates of death by suicide than the general population. Outside of sports, there is a mature body of evidence suggesting that the causes of suicide are complex, multifactorial and difficult to predict in individual cases. Future research might establish a clear causal connection between the proteinopathy of CTE and suicide. At present, however, there is insufficient scientific evidence to conclude that there is a strong causal relationship between the presence of these proteinopathies and suicide in former athletes. Additional research is needed to determine the extent to which the neuropathology of CTE is a possible mediator or moderator variable associated with suicide.

  13. Chronic traumatic encephalopathy: the dangers of getting "dinged".

    Science.gov (United States)

    Lakhan, Shaheen E; Kirchgessner, Annette

    2012-01-01

    Chronic traumatic encephalopathy (CTE) is a form of neurodegeneration that results from repetitive brain trauma. Not surprisingly, CTE has been linked to participation in contact sports such as boxing, hockey and American football. In American football getting "dinged" equates to moments of dizziness, confusion, or grogginess that can follow a blow to the head. There are approximately 100,000 to 300,000 concussive episodes occurring in the game of American football alone each year. It is believed that repetitive brain trauma, with or possibly without symptomatic concussion, sets off a cascade of events that result in neurodegenerative changes highlighted by accumulations of hyperphosphorylated tau and neuronal TAR DNA-binding protein-43 (TDP-43). Symptoms of CTE may begin years or decades later and include a progressive decline of memory, as well as depression, poor impulse control, suicidal behavior, and, eventually, dementia similar to Alzheimer's disease. In some individuals, CTE is also associated with motor neuron disease similar to amyotrophic lateral sclerosis. Given the millions of athletes participating in contact sports that involve repetitive brain trauma, CTE represents an important public health issue. In this review, we discuss recent advances in understanding the etiology of CTE. It is now known that those instances of mild concussion or "dings" that we may have previously not noticed could very well be causing progressive neurodegenerative damage to a player's brain. In the future, focused and intensive study of the risk factors could potentially uncover methods to prevent and treat this disease.

  14. [Chronic traumatic encephalopathy: an old acquaintance in athletes].

    Science.gov (United States)

    Vijverberg, E G B; Pijnenburg, A C M; Scheltens, P; Pijnenburg, Y A L

    2017-01-01

    - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head injuries like those seen in sports such as boxing, American football and soccer.- The clinical features of CTE are a range of cognitive, psychiatric and motor symptoms, and histopathology involves deposits of hyperphosphorylated tau protein and the presence of TAR DNA-binding protein (TDP-43) with relatively little beta-amyloid.- CTE is difficult to differentiate clinically from Alzheimer's disease, frontotemporal dementia and psychiatric disorders because of the major symptom overlap between these conditions.- The most important risk factors for developing CTE are the cumulative effect of repetitive head injuries, with or without clinical symptoms, and the duration of exposure to the repetitive injuries (the sporting career).- There is no treatment for CTE at present and the strategy must be primarily geared to prevention.- In view of the large number of people, including those in the Netherlands, who take part in sports in which head injuries may occur, research into CTE is of major societal importance.

  15. Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers.

    Science.gov (United States)

    DeKosky, Steven T; Blennow, Kaj; Ikonomovic, Milos D; Gandy, Sam

    2013-04-01

    Over the past decade, public awareness of the long-term pathological consequences of traumatic brain injury (TBI) has increased. Such awareness has been stimulated mainly by reports of progressive neurological dysfunction in athletes exposed to repetitive concussions in high-impact sports such as boxing and American football, and by the rising number of TBIs in war veterans who are now more likely to survive explosive blasts owing to improved treatment. Moreover, the entity of chronic traumatic encephalopathy (CTE)--which is marked by prominent neuropsychiatric features including dementia, parkinsonism, depression, agitation, psychosis, and aggression--has become increasingly recognized as a potential late outcome of repetitive TBI. Annually, about 1% of the population in developed countries experiences a clinically relevant TBI. The goal of this Review is to provide an overview of the latest understanding of CTE pathophysiology, and to delineate the key issues that are challenging clinical and research communities, such as accurate quantification of the risk of CTE, and development of reliable biomarkers for single-incident TBI and CTE.

  16. Imaging Chronic Traumatic Encephalopathy: A Biomedical Engineering Perspective.

    Science.gov (United States)

    Polak, Paul; Tuyl, John Van; Engel, Robin

    2016-01-01

    A disease initially associated with boxers ninety years ago, chronic traumatic encephalopathy (CTE) is now recognized as a significant risk to boxers, American football players, ice hockey players, military personnel or anyone to whom recurrent head injuries are a distinct possibility. Diagnosis is currently confirmed at autopsy, although CTE's presumed sufferers have symptoms of depression, suicidal thoughts, mood and personality changes, and loss of memory. CTE sufferers also complain of losing cognitive ability, dysfunction in everyday activities, inability to keep regular employment, violent tendencies and marital strife. Dementia may develop over the long term. Unfortunately, there is no clear consensus in regards to pathology, with both number and severity of head injuries being linked to disease progression. Despite the slow advancement of this disease, there are no clinical methods to diagnose or monitor prognosis in presumed patients, limiting clinicians' efforts to symptom management. The lack of diagnostic tools fuels the need for biomedical engineers to develop techniques for in vivo detection of CTE. This review examines efforts made with various magnetic resonance and nuclear imaging techniques, with a view towards improving the sensitivity and specificity of diagnostic imaging for CTE.

  17. Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy.

    Science.gov (United States)

    Cherry, Jonathan D; Tripodis, Yorghos; Alvarez, Victor E; Huber, Bertrand; Kiernan, Patrick T; Daneshvar, Daniel H; Mez, Jesse; Montenigro, Philip H; Solomon, Todd M; Alosco, Michael L; Stern, Robert A; McKee, Ann C; Stein, Thor D

    2016-10-28

    The chronic effects of repetitive head impacts (RHI) on the development of neuroinflammation and its relationship to chronic traumatic encephalopathy (CTE) are unknown. Here we set out to determine the relationship between RHI exposure, neuroinflammation, and the development of hyperphosphorylated tau (ptau) pathology and dementia risk in CTE. We studied a cohort of 66 deceased American football athletes from the Boston University-Veteran's Affairs-Concussion Legacy Foundation Brain Bank as well as 16 non-athlete controls. Subjects with a neurodegenerative disease other than CTE were excluded. Counts of total and activated microglia, astrocytes, and ptau pathology were performed in the dorsolateral frontal cortex (DLF). Binary logistic and simultaneous equation regression models were used to test associations between RHI exposure, microglia, ptau pathology, and dementia. Duration of RHI exposure and the development and severity of CTE were associated with reactive microglial morphology and increased numbers of CD68 immunoreactive microglia in the DLF. A simultaneous equation regression model demonstrated that RHI exposure had a significant direct effect on CD68 cell density (p CTE. Inflammatory molecules may be important diagnostic or predictive biomarkers as well as promising therapeutic targets in CTE.

  18. [Epileptic encephalopathy associated with forced normalization after administration of levetiracetam].

    Science.gov (United States)

    Kikuchi, Takahiro; Kato, Mitsuhiro; Takahashi, Nobuya; Nakamura, Kazuyuki; Hayasaka, Kiyoshi

    2013-09-01

    Here we report a case of a 10-year-old female with unclassified epileptic encephalopathy who showed forced normalization after administration of levetiracetam (LEV). She initially presented with intractable tonic and myoclonic seizures that were observed about 10 times a day along with frequent multifocal sharp and slow wave complexes on electroencephalography (EEG). We were forced to decrease the topiramate dose because of the appearance of nystagmus, and her myoclonic seizures became worse. We added LEV (250 mg/day) and her tonic and myoclonic seizures disappeared one day after initiation of LEV administration. However, she showed hyporesponsiveness and akinesia. The disappearance of paroxysmal discharges on EEG confirmed the diagnosis of forced normalization. Despite continuous administration of LEV, tonic and myoclonic seizures relapsed within a month but her psychotic symptoms resolved simultaneously. To the best of our knowledge, this is the first reported case of forced normalization after LEV administration. It should be noted that LEV may cause forced normalization although it can be started at an adequate dosage.

  19. The role of neurosteroids in the pathogenesis of hepatic encephalopathy

    Directory of Open Access Journals (Sweden)

    Mladenović Dušan

    2016-01-01

    Full Text Available Hepatic Encephalopathy (HE represents a neuropsychiatric syndrome caused by acute or chronic liver failure. Hyperammonemia plays a pivotal role in the development of HE through modulation of neurotransmission, oxidative stress, neuroinflammation, mitochondrial dysfunction, and energy deficit. Neurosteroids contribute significantly to increased GABAergic tone in HE. Ammonia, in combination with manganese and proinflammatory cytokines, stimulate neurosteroid synthesis by up-regulation of translocator protein, a component of multiprotein complex that stimulate cholesterol transport into astrocytic mitochondria. Cholesterol serves as a substrate for the synthesis of neurosteroids allopregnanolone and tetrahydro-deoxycorticosterone. After release from astrocytes, allopregnanolone and tetrahydro-deoxycorticosterone potentiate GABAergic transmission by positive allosteric modulation of GABAA receptor, thus contributing to cognitive deficit and alterations in sleep-wake cycle. Additional potential mechanisms of neurosteroid action in HE include modulation of serotoninergic, cholinergic, glutamatergic, glycinergic, and opioid receptor activities, as well as modulation of gene expression. This review aimed to summarize current knowledge of the role of neurosteroids in the pathogenesis of HE.

  20. Outcomes of epilepsy surgery in childhood-onset epileptic encephalopathy.

    Science.gov (United States)

    Lee, Yun-Jin; Lee, Joon Soo; Kang, Hoon-Chul; Kim, Dong-Seok; Shim, Kyu-Won; Eom, Soyong; Kim, Heung Dong

    2014-06-01

    to evaluate the outcomes and role of epilepsy surgery in children with intractable epileptic encephalopathy (EE). ninety-five children (64 boys, 31 girls) with intractable EE were treated by epilepsy surgery at Severance Children's Hospital from 2003 to 2008. Surgical treatments included lobar resection, hemispherotomy and corpus callosotomy (CC). Seventy-six children were Lennox-Gastaut syndrome (LGS), and 19 had West syndrome. of the 76 patients with LGS, CC was performed in 37 patients (48.7%), lobar resection in 29 (38.2%) and hemispherotomy in 10 (13.2%). Of the 19 patients with West syndrome, respective surgery was performed in 15 patients (78.9%) and CC in 4 (21.1%). Of the patients receiving respective surgery, Engel's class I outcomes were achieved for 24 of 39 (61.5%) of LGS patients, and for 9 of 15 (60.0%) of West syndrome. Malformations of cortical development were commonly observed, appearing in 73.5% (36/49). In neuropsychiatric tests, 19 of 27 with LGS demonstrated improvement in postoperative cognitive function. More significant intellectual improvement correlated well with shorter epilepsy duration, good seizure outcomes, and decreased number of antiepileptic drugs. epilepsy surgery should be considered in treating childhood intractable EE with expectation of improvement of both seizure and cognitive outcomes, even in cases of LGS. Copyright © 2013. Published by Elsevier B.V.

  1. Sudden onset unexplained encephalopathy in infants: think of cannabis intoxication.

    Science.gov (United States)

    Lavi, Eran; Rekhtman, David; Berkun, Yackov; Wexler, Isaiah

    2016-03-01

    The use of cannabis as both a therapeutic agent and recreational drug is common, and its availability is increasing as a result of legalization in many countries. Among older children, the manifestations of cannabis intoxication are numerous and include both neurological and systemic manifestations that are frequently non-specific. There have been only a few reports detailing cannabis intoxication in infants and toddlers. We describe three infants who presented to the emergency department with encephalopathic signs without prominent systemic manifestations. During the initial interview of caregivers, no history of exposure to neurotoxic agents was obtained. All three patients were subsequently diagnosed with cannabis intoxication based on urine toxic screens for delta-9-tetrahydrocannabinol (THC). The infants recovered with supportive care that included fluids and monitoring. The non-specific symptomatology of cannabis intoxication in infants together with the wide differential for unexplained acute onset encephalopathy may delay diagnosis and lead to inappropriate procedures and interventions such as antimicrobial treatments and imaging studies. Healthcare personnel of emergency rooms, urgent care centers, and general clinics should be aware of the potential risk of cannabis ingestion in young infants. A thorough medical history and toxic screen are warranted in all infants with unexplained decreased sensorium.

  2. Neuroimaging findings in pediatric Wernicke encephalopathy: a review

    International Nuclear Information System (INIS)

    Zuccoli, Giulio; Siddiqui, Nasir; Bailey, Ariel; Bartoletti, Stefano C.

    2010-01-01

    Wernicke encephalopathy (WE) is an acute neurological disease resulting from dietary thiamine (vitamin B1) deficiency. WE is characterized by changes in consciousness, ocular dysfunction, and ataxia. Neuroradiologic findings usually show symmetric signal intensity alterations in the mammillary bodies, medial thalami, tectal plate, and periaqueductal area. Selective involvement of the cranial nerve nuclei, cerebellum, red nuclei, dentate nuclei, fornix, splenium, cerebral cortex, and basal ganglia characterize nonalcoholic WE patients. Furthermore, symmetric basal ganglia alterations with involvement of the putamen have only been observed in children. The incidence of WE is underestimated in both adult and pediatric patients. Interestingly, the frequency of WE in children appears to be similar to that observed in adults. The prognosis of the disease largely depends on the time from diagnosis to thiamine supplementation. The aim of this pediatric literature review is to provide an update on neuroradiologic findings in children affected by WE in an effort to determine pertinent clinical and imaging findings that can improve the detection and early identification of the disease. A thorough knowledge of the MRI findings of WE will assist in arriving at an early diagnosis, thereby reducing the morbidity and mortality associated with this disease in children. (orig.)

  3. Neuroimaging findings in pediatric Wernicke encephalopathy: a review

    Energy Technology Data Exchange (ETDEWEB)

    Zuccoli, Giulio [Children' s Hospital of Pittsburgh of UPMC, Children' s Hospital of Pittsburgh, Department of Radiology, Pittsburgh, PA (United States); University of Pittsburgh Medical Center, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh, Pittsburgh, PA (United States); Siddiqui, Nasir; Bailey, Ariel; Bartoletti, Stefano C. [Children' s Hospital of Pittsburgh of UPMC, Children' s Hospital of Pittsburgh, Department of Radiology, Pittsburgh, PA (United States)

    2010-06-15

    Wernicke encephalopathy (WE) is an acute neurological disease resulting from dietary thiamine (vitamin B1) deficiency. WE is characterized by changes in consciousness, ocular dysfunction, and ataxia. Neuroradiologic findings usually show symmetric signal intensity alterations in the mammillary bodies, medial thalami, tectal plate, and periaqueductal area. Selective involvement of the cranial nerve nuclei, cerebellum, red nuclei, dentate nuclei, fornix, splenium, cerebral cortex, and basal ganglia characterize nonalcoholic WE patients. Furthermore, symmetric basal ganglia alterations with involvement of the putamen have only been observed in children. The incidence of WE is underestimated in both adult and pediatric patients. Interestingly, the frequency of WE in children appears to be similar to that observed in adults. The prognosis of the disease largely depends on the time from diagnosis to thiamine supplementation. The aim of this pediatric literature review is to provide an update on neuroradiologic findings in children affected by WE in an effort to determine pertinent clinical and imaging findings that can improve the detection and early identification of the disease. A thorough knowledge of the MRI findings of WE will assist in arriving at an early diagnosis, thereby reducing the morbidity and mortality associated with this disease in children. (orig.)

  4. The Thompson Encephalopathy Score and Short-Term Outcomes in Asphyxiated Newborns Treated With Therapeutic Hypothermia.

    Science.gov (United States)

    Thorsen, Patricia; Jansen-van der Weide, Martine C; Groenendaal, Floris; Onland, Wes; van Straaten, Henrika L M; Zonnenberg, Inge; Vermeulen, Jeroen R; Dijk, Peter H; Dudink, Jeroen; Rijken, Monique; van Heijst, Arno; Dijkman, Koen P; Cools, Filip; Zecic, Alexandra; van Kaam, Anton H; de Haan, Timo R

    2016-07-01

    The Thompson encephalopathy score is a clinical score to assess newborns suffering from perinatal asphyxia. Previous studies revealed a high sensitivity and specificity of the Thompson encephalopathy score for adverse outcomes (death or severe disability). Because the Thompson encephalopathy score was developed before the use of therapeutic hypothermia, its value was reassessed. The purpose of this study was to assess the association of the Thompson encephalopathy score with adverse short-term outcomes, defined as death before discharge, development of severe epilepsy, or the presence of multiple organ failure in asphyxiated newborns undergoing therapeutic hypothermia. The study period ranged from November 2010 to October 2014. A total of 12 tertiary neonatal intensive care units participated. Demographic and clinical data were collected from the "PharmaCool" multicenter study, an observational cohort study analyzing pharmacokinetics of medication during therapeutic hypothermia. With multiple logistic regression analyses the association of the Thompson encephalopathy scores with outcomes was studied. Data of 142 newborns were analyzed (male: 86; female: 56). Median Thompson score was 9 (interquartile range: 8 to 12). Median gestational age was 40 weeks (interquartile range 38 to 41), mean birth weight was 3362 grams (standard deviation: 605). All newborns manifested perinatal asphyxia and underwent therapeutic hypothermia. Death before discharge occurred in 23.9% and severe epilepsy in 21.1% of the cases. In total, 59.2% of the patients had multiple organ failure. The Thompson encephalopathy score was not associated with multiple organ failure, but a Thompson encephalopathy score ≥12 was associated with death before discharge (odds ratio: 3.9; confidence interval: 1.3 to 11.2) and with development of severe epilepsy (odds ratio: 8.4; confidence interval: 2.5 to 27.8). The Thompson encephalopathy score is a useful clinical tool, even in cooled asphyxiated

  5. Effects of the benzodiazepine receptor antagonist flumazenil in hepatic encephalopathy in humans.

    Science.gov (United States)

    Bansky, G; Meier, P J; Riederer, E; Walser, H; Ziegler, W H; Schmid, M

    1989-09-01

    If increased gamma-aminobutyric acid (GABA)-mediated neurotransmission contributes to the mediation of hepatic encephalopathy, it may be possible to induce ameliorations of the syndrome by pharmacologically antagonizing a component of the GABA/benzodiazepine receptor complex. To test this possibility we administered the benzodiazepine receptor antagonist flumazenil by intravenous injection to 14 patients with hepatic encephalopathy complicating cirrhosis. Flumazenil administration induced variable and transient, but distinct, improvements of the mental status in 71% of the patients. The degree of encephalopathy improved from stage IV to stage II in 4 patients and from stage IV to stage III in 2 patients. The mental status of all patients with less advanced encephalopathy (3 with stage III, 1 with stage II) also improved, but these responses were clinically less impressive. The arousal effect occurred within minutes after the injection and lasted for 1 to 2 h. Furthermore, it was associated with a significant increase of the mean electroencephalographic frequency from 4.2 to 5.2 cycle/s. Of the 8 patients who were ultimately discharged from the hospital, 7 had responded to flumazenil. No patient who died within 48 h of receiving flumazenil had shown any arousal effect. These findings strongly favor a prominent pathogenetic role of increased GABAergic tone in hepatic encephalopathy in humans and suggest that a positive response to flumazenil might be of prognostic value in predicting short-term survival in encephalopathic patients with liver disease.

  6. Non-alcoholic Korsakoff syndrome in psychiatric patients with a history of undiagnosed Wernicke's encephalopathy.

    Science.gov (United States)

    Nikolakaros, Georgios; Ilonen, Tuula; Kurki, Timo; Paju, Janina; Papageorgiou, Sokratis G; Vataja, Risto

    2016-11-15

    Wernicke's encephalopathy is often undiagnosed, particularly in non-alcoholics. There are very few reports of non-alcoholic patients diagnosed with Korsakoff syndrome in the absence of a prior diagnosis of Wernicke's encephalopathy and no studies of diffusion tensor imaging in non-alcoholic Korsakoff syndrome. We report on three non-alcoholic psychiatric patients (all women) with long-term non-progressive memory impairment that developed after malnutrition accompanied by at least one of the three Wernicke's encephalopathy manifestations: ocular abnormalities, ataxia or unsteadiness, and an altered mental state or mild memory impairment. In neuropsychological examination, all patients had memory impairment, including intrusions. One patient had mild cerebellar vermis atrophy in MRI taken after the second episode of Wernicke's encephalopathy. The same patient had mild hypometabolism in the lateral cortex of the temporal lobes. Another patient had mild symmetrical atrophy and hypometabolism of the superior frontal lobes. Two patients were examined with diffusion tensor imaging. Reduced fractional anisotropy values were found in the corona radiata in two patients, and the uncinate fasciculus and the inferior longitudinal fasciculus in one patient. Our results suggest that non-alcoholic Korsakoff syndrome is underdiagnosed. Psychiatric patients with long-term memory impairment may have Korsakoff syndrome and, therefore, they should be evaluated for a history of previously undiagnosed Wernicke's encephalopathy. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Structural and functional cerebral impairments in cirrhotic patients with a history of overt hepatic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Hua-Jun [Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Zhu, Xi-Qi [Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Department of Radiology, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing 210002 (China); Shu, Hao [Department of Neurology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Yang, Ming; Zhang, Yi; Ding, Jie; Wang, Yu [Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Teng, Gao-Jun, E-mail: gjteng@vip.sina.com [Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China)

    2012-10-15

    Objective: Diffuse brain atrophy has been observed in cirrhotic patients and recent reports have revealed the persistence of cognitive impairment after clinical resolution of overt hepatic encephalopathy. We sought to explore the continued influence of overt hepatic encephalopathy on neurological function by measuring brain resting-state inherent connectivity, based on an investigation of structural abnormalities. Methods: Neuropsychological tests and structural and functional magnetic resonance scanning were conducted in 20 healthy controls and 21 cirrhotic patients with a history of overt hepatic encephalopathy. The analysis of voxel-based morphometry and functional connectivity were performed to detect the alterations in brain structure and function, respectively. Results: Patients showed significantly worse performance in neuropsychological tests as compared with controls, despite apparently normal mental status. Analysis of voxel-based morphometry revealed a decrease in gray matter volume primarily in the midline regions, bilateral insular cortex and caudates, left parahippocampal gyrus, and right cerebellum posterior lobe, while the volume of the bilateral thalamus showed an increase. Of these regions, the posterior cingulate cortex with peak atrophy was selected as the origin for the analysis of functional connectivity. Typical patterns of a default mode network were identified in both groups. Decreased functional connectivity was found in the medial prefrontal gyrus, left inferior parietal lobule, and left middle temporal gyrus in the patients. Conclusions: Both functional and structural impairments were evident after apparent recovery from overt hepatic encephalopathy, demonstrating that brain dysfunction induced by hepatic encephalopathy persisted after clinical resolution and provided a basis for further evolution of the disease.

  8. Epilepsy surgery in pediatric epileptic encephalopathy: when interictal EEG counts the most.

    Science.gov (United States)

    Shahwan, Amre; O'Halloran, Philip J; Madigan, Cathy; King, Mary D; O'Brien, Donncha

    2016-07-01

    Traditionally, seizure onset localization in ictal electro-encephalography (EEG) is the main factor guiding resective epilepsy surgery. The situation is often different in infantile epileptic encephalopathy. We demonstrate the importance of the underrated interictal (rather than ictal) surface EEG in informing decision-making in epilepsy surgery for children with epileptic encephalopathy caused by subtle focal cortical dysplasia (FCD). We present a small case series of three children who had an epileptic encephalopathy with either epileptic spasms or tonic seizures. All three were thought initially to have normal neuroimaging. Ictal EEG localizing features were seen in none and lateralizing features were seen only clinically in one of the three. However, the interictal EEG showed persistent and consistent focal irregular slowing in all, particularly after medically resolving the diffuse encephalopathy. Subtle FCDs were uncovered in all. Surgery was performed in all with excellent outcome. In infantile epileptic encephalopathy caused by subtle FCD, the often underrated interictal surface EEG (particularly persistent foal irregular slowing) informs the most; not only to the target area for surgical resection but also to its extent. This may negate the need for unnecessary and sometimes non-informative invasive monitoring in these cases. A matter of "zooming out" to define the extent of a resectable abnormality rather than "zooming in" to define a seemingly localized epileptic focus that may change with time.

  9. Risks and Benefits of Rituximab in the Treatment of Hashimoto Encephalopathy in Children : Two Case Reports and a Mini Review

    NARCIS (Netherlands)

    Maas, Annemieke; Braun, Kees P J|info:eu-repo/dai/nl/207237239; Geleijns, Karin|info:eu-repo/dai/nl/275854965; Jansen, Floor E.|info:eu-repo/dai/nl/304815640; van Royen-Kerkhof, Annet|info:eu-repo/dai/nl/288270770

    2017-01-01

    Hashimoto encephalopathy is a rare condition, characterized by the association of encephalopathy with a variety of neurological symptoms and autoantibodies to the thyroid gland. Its etiology is unknown, and symptoms are usually treated with immune suppressive therapy, e.g., high doses of

  10. Autoimmune encephalopathy associated with thyroid autoantibodies as the cause of reversible cognitive impairment

    Directory of Open Access Journals (Sweden)

    Robert Dobbin Chow

    2012-04-01

    Full Text Available We herewith describe a patient with acute confusion, expressive aphasia and generalized seizures. A through workup excluded most causes of encephalopathy. He was, however, found to have TSH = 18.6 MIU/ml, T3reverse = 0.44nmol/L, T4 = 0.8ng/dl and Anti-Thyroid-Peroxidase AB titer >1000 IU/ml. Based on the above findings the patient was diagnosed with Hashimoto's encephalopathy and his mental status showed dramatic improvement (MMS 30/30 with high dose prednisone. Hashimoto's encephalopathy is rare disorder of presumed autoimmune origin characterized by cognitive decline, seizures, neuro-psychiatric symptoms, high titers of Anti-Thyroid-Peroxidase AB, and a positive response to steroids.

  11. Modeling the Encephalopathy of Prematurity in Animals: The Important Role of Translational Research

    Directory of Open Access Journals (Sweden)

    Hannah C. Kinney

    2012-01-01

    Full Text Available Translational research in preterm brain injury depends upon the delineation of the human neuropathology in order that animal models faithfully reiterate it, thereby ensuring direct relevance to the human condition. The major substrate of human preterm brain injury is the encephalopathy of prematurity that is characterized by gray and white matter lesions reflecting combined acquired insults, altered developmental trajectories, and reparative phenomena. Here we highlight the key features of human preterm brain development and the encephalopathy of prematurity that are critical for modeling in animals. The complete mimicry of the complex human neuropathology is difficult in animal models. Many models focus upon mechanisms related to a specific feature, for example, loss of premyelinating oligodendrocytes in the cerebral white matter. Nevertheless, animal models that simultaneously address oligodendrocyte, neuronal, and axonal injury carry the potential to decipher shared mechanisms and synergistic treatments to ameliorate the global consequences of the encephalopathy of prematurity.

  12. Correlation of Hyponatremia with Hepatic Encephalopathy and Severity of Liver Disease

    International Nuclear Information System (INIS)

    Qureshi, M. O.; Khokhar, N.; Saleem, A.; Niazi, T. K.

    2014-01-01

    Objective: To assess the frequency of low serum sodium levels and to correlate it with the severity of liver disease and hepatic encephalopathy (HE) in patients coming to the tertiary care hospital. Study Design: Observational study. Place and Duration of Study: Shifa International Hospital, Islamabad, from January 2011 to January 2012. Methodology: A total of 202 patients with hepatic encephalopathy and chronic liver disease had serum sodium measured. The HE was graded according to the West Haven classification (4 grades). Relationship of hyponatremia was correlated with severity grade of encephalopathy using Spearman rank correlation test. Results: Out of 202 patients, 62 (30.7%) patients had serum sodium less than 130 meq/l. Out of 202, HE was present in 69 (34.15%) patients and out of these, 38 had grade III-IV HE and 31 had grade I - II HE. Out of 69 patients with HE 57 had sodium less than 135 (p 135 mmol/L. (author)

  13. Palatal-Myoclonus as a Presentation of Hashimoto Encephalopathy: an Interesting case Report

    Directory of Open Access Journals (Sweden)

    Esmaeel Ghoreishi

    2013-09-01

    Full Text Available Objective: Hashimoto encephalopathy (HE is known as a steroid-responsive encephalopathy associated with autoimmune thyroiditis or nonvascular inflammation-related autoimmune meningoencephalitis. The average age of onset of HE is approximately 50 years; and it is more common in women. The onset of HE may be acute or subacute. The course of most HE cases is relapsing and remitting, which is similar to that of vasculitis and stroke.Methods: In this article, we present a previously healthy 32 years old; veterinarian male with palatal myoclonus, as a rare presentation of this disorder, and review the neurologic aspects of hashimoto encephalitis . Results:The clinical presentation of HE is characterized by progressive cognitive decline tremor, transient aphasia, seizures, abnormal gait, sleep disorder and stroke-like episodes .Myoclonus, either generalized or multifocal, and tremor, often of the bilateral upper extremities, is the most frequently observed involuntary movements in HE.Conclusion:The rapidly progressive cognitive dysfunction and encephalopathies observed.

  14. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management.

    Science.gov (United States)

    Sechi, Gianpietro; Serra, Alessandro

    2007-05-01

    Wernicke's encephalopathy is an acute neuropsychiatric syndrome resulting from thiamine deficiency, which is associated with significant morbidity and mortality. According to autopsy-based studies, the disorder is still greatly underdiagnosed in both adults and children. In this review, we provide an update on the factors and clinical settings that predispose to Wernicke's encephalopathy, and discuss the most recent insights into epidemiology, pathophysiology, genetics, diagnosis, and treatment. To facilitate the diagnosis, we classify the common and rare symptoms at presentation and the late-stage symptoms. We emphasise the optimum dose of parenteral thiamine required for prophylaxis and treatment of Wernicke's encephalopathy and prevention of Korsakoff's syndrome associated with alcohol misuse. A systematic approach helps to ensure that patients receive a prompt diagnosis and adequate treatment.

  15. Wernicke's encephalopathy in a malnourished surgical patient: clinical features and magnetic resonance imaging.

    Science.gov (United States)

    Nolli, M; Barbieri, A; Pinna, C; Pasetto, A; Nicosia, F

    2005-11-01

    We report a clinical and neuroradiological description of a severe case of Wernicke's encephalopathy in a surgical patient. After colonic surgery for neoplasm, he was treated for a long time with high glucose concentration total parenteral nutrition. In the early post-operative period, the patient showed severe encephalopathy with ataxia, ophthalmoplegia and consciousness disorders. We used magnetic resonance imaging (MRI) to confirm the clinical suspicion of Wernicke's encephalopathy. The radiological feature showed hyperintense lesions which were symmetrically distributed along the bulbo-pontine tegmentum, the tectum of the mid-brain, the periacqueductal grey substance, the hypothalamus and the medial periventricular parts of the thalamus. This progressed to typical Wernicke-Korsakoff syndrome with ataxia and memory and cognitive defects. Thiamine deficiency is a re-emerging problem in non-alcoholic patients and it may develop in surgical patients with risk factors such as malnutrition, prolonged vomiting and long-term high glucose concentration parenteral nutrition.

  16. Wernicke Encephalopathy in Adolescents After Bariatric Surgery: Case Report and Review.

    Science.gov (United States)

    Armstrong-Javors, Amy; Pratt, Janey; Kharasch, Sigmund

    2016-12-01

    Roughly 1% of all weight loss surgery is performed in adolescents. There is strong evidence demonstrating significant postsurgical weight loss, improvement in quality of life, and reduction in comorbidities such as hypertension and diabetes. Reports of postoperative complications in adolescents are few because of the small sample size in most series. Despite vitamin supplementation, nutritional deficiencies requiring hospitalization occur occasionally after Roux-en-Y gastric bypass. Wernicke encephalopathy, a triad of ophthalmoplegia, ataxia, and altered mental status, is a serious consequence of thiamine (vitamin B 1 ) deficiency. Few cases of Wernicke encephalopathy after weight loss surgery have been reported in the literature and even fewer in the pediatric population. Here we describe a teenage girl who develops vomiting after Roux-en-Y gastric bypass and presented with nystagmus, irritability, and ataxia. The clinical presentation, diagnosis, and treatment of Wernicke encephalopathy in adolescents after bariatric surgery are discussed. Copyright © 2016 by the American Academy of Pediatrics.

  17. Posterior reversible encephalopathy syndrome and acute post-streptococcal glomerulonephritis mimicking breakthrough seizures

    Directory of Open Access Journals (Sweden)

    Kamille Abdool

    2015-05-01

    Full Text Available We report the case of a 14-year-old boy with a past history of primary generalized seizures, who had been seizure-free for 2 years on sodium valproate and presented with generalized tonic clonic seizures suggestive of breakthrough seizures. Examination revealed hypertension, impetiginous lesions of the lower limbs, microscopic hematuria, elevated antistreptolysin O titre and low complement levels consistent with acute post-streptococcal glomerulonephritis. Cranial magnetic resonance imaging (MRI demonstrated changes consistent with posterior reversible encephalopathy syndrome. Hypertension was controlled with intravenous nitroglycerin followed by oral captopril and amlodipine. Brain MRI changes returned normal within 2 weeks. The nephritis went in to remission within 2 months and after 8 months the patient has been seizure free again. Posterior reversible encephalopathy syndrome appeared to have neither short nor intermediate effect on seizure control in this patient. The relationship between posterior reversible encephalopathy syndrome and seizures is reviewed.

  18. Single-photon emission computed tomography in human immunodeficiency virus encephalopathy: A preliminary report

    International Nuclear Information System (INIS)

    Masdeu, J.C.; Yudd, A.; Van Heertum, R.L.; Grundman, M.; Hriso, E.; O'Connell, R.A.; Luck, D.; Camli, U.; King, L.N.

    1991-01-01

    Depression or psychosis in a previously asymptomatic individual infected with the human immunodeficiency virus (HIV) may be psychogenic, related to brain involvement by the HIV or both. Although prognosis and treatment differ depending on etiology, computed tomography (CT) and magnetic resonance imaging (MRI) are usually unrevealing in early HIV encephalopathy and therefore cannot differentiate it from psychogenic conditions. Thirty of 32 patients (94%) with HIV encephalopathy had single-photon emission computed tomography (SPECT) findings that differed from the findings in 15 patients with non-HIV psychoses and 6 controls. SPECT showed multifocal cortical and subcortical areas of hypoperfusion. In 4 cases, cognitive improvement after 6-8 weeks of zidovudine (AZT) therapy was reflected in amelioration of SPECT findings. CT remained unchanged. SPECT may be a useful technique for the evaluation of HIV encephalopathy

  19. Posterior Reversible Encephalopathy Syndrome and Acute Post-Streptococcal Glomerulonephritis Mimicking Breakthrough Seizures.

    Science.gov (United States)

    Abdool, Kamille; Ramcharan, Kanterpersad; Bhagwandass, Neal; Persad, Navindra; Temull, Vasant; Seegobin, Karan; Mike, Cassie

    2015-03-23

    We report the case of a 14-year-old boy with a past history of primary generalized seizures, who had been seizure-free for 2 years on sodium valproate and presented with generalized tonic clonic seizures suggestive of breakthrough seizures. Examination revealed hypertension, impetiginous lesions of the lower limbs, microscopic hematuria, elevated anti-streptolysin O titre and low complement levels consistent with acute post-streptococcal glomerulonephritis. Cranial magnetic resonance imaging (MRI) demonstrated changes consistent with posterior reversible encephalopathy syndrome. Hypertension was controlled with intravenous nitroglycerin followed by oral captopril and amlodipine. Brain MRI changes returned normal within 2 weeks. The nephritis went in to remission within 2 months and after 8 months the patient has been seizure free again. Posterior reversible encephalopathy syndrome appeared to have neither short nor intermediate effect on seizure control in this patient. The relationship between posterior reversible encephalopathy syndrome and seizures is reviewed.

  20. RECENT THEORIES OF PATHOGENESIS OF HEPATIC ENCEPHALOPATHY IN HEPATITIS C VIRAL INFECTION

    Directory of Open Access Journals (Sweden)

    Lidija Popović Dragonjić

    2013-01-01

    Full Text Available Hepatic encephalopathy is potentially reversible, or progressive neuropsychiatric syndrome characterized by changes in cognitive function, behavior and personality changes, and transient neurologic symptoms and characteristic electroencephalographic patterns associated with acute and chronic liver failure. For some time, there has been controversy regarding the origin of toxins responsible for the change of mental state. It was found that the occurrence of hepatic encephalopathy is responsible for multiple organ peripheral changes (intestinal changes, abnormalities of portal-systemic circulation, liver failure, loss of muscle tissue, changes in brain intracellular communication (osmotic changes, astrocytes and axonal abnormalities in communication, changes in cerebral perfusion and ammonia, endogenous benzodiazepines, gamma amino butyric acid, derivatives of methionine and false neurotransmitters. The aforementioned metabolic factors that contribute to the development of hepatic encephalopathy are not mutually exclusive and multiple factors may be present at the same time.

  1. Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy

    DEFF Research Database (Denmark)

    Elo, Jenni M; Yadavalli, Srujana S; Euro, Liliya

    2012-01-01

    the mitochondrial phenylalanyl transfer RNA (tRNA) synthetase (mtPheRS) in two patients with fatal epileptic mitochondrial encephalopathy. The mutations affected highly conserved amino acids, p.I329T and p.D391V. Recently, a homozygous FARS2 variant p.Y144C was reported in a Saudi girl with mitochondrial...... encephalopathy, but the pathogenic role of the variant remained open. Clinical features, including postnatal onset, catastrophic epilepsy, lactic acidemia, early lethality and neuroimaging findings of the patients with FARS2 variants, resembled each other closely, and neuropathology was consistent with Alpers...... was impaired. Our results imply that the three FARS2 mutations directly impair aminoacylation function and stability of mtPheRS, leading to a decrease in overall tRNA charging capacity. This study establishes a new genetic cause of infantile mitochondrial Alpers encephalopathy and reports a new mitochondrial...

  2. Infantile Epileptic Encephalopathy Associated With SCN2A Mutation Responsive to Oral Mexiletine.

    Science.gov (United States)

    Foster, Laura A; Johnson, Maria R; MacDonald, John T; Karachunski, Peter I; Henry, Thomas R; Nascene, David R; Moran, Brian P; Raymond, Gerald V

    2017-01-01

    Genetic alterations are significant causes of epilepsy syndromes; especially early-onset epileptic encephalopathies and voltage-gated sodium channelopathies are among the best described. Mutations in the SCN2A subunit of voltage-gated sodium channels have been associated with benign familial neonatal-infantile seizures, generalized epilepsy febrile seizures plus, and an early-onset infantile epileptic encephalopathy. We describe two infants with medically refractory seizures due to a de novo SCN2A mutation. The first child responded to intravenous lidocaine with significant reduction in seizure frequency and was successfully transitioned to enteral mexiletine. Mexiletine was subsequently used in a second infant with reduction in seizure frequency. Class 1b antiarrhythmic agents, lidocaine and mexiletine, may be useful in infants with medically refractory early infantile epileptic encephalopathy secondary to mutations in SCN2A. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Brain Training with Video Games in Covert Hepatic Encephalopathy.

    Science.gov (United States)

    Bajaj, Jasmohan S; Ahluwalia, Vishwadeep; Thacker, Leroy R; Fagan, Andrew; Gavis, Edith A; Lennon, Michael; Heuman, Douglas M; Fuchs, Michael; Wade, James B

    2017-02-01

    Despite the associated adverse outcomes, pharmacologic intervention for covert hepatic encephalopathy (CHE) is not the standard of care. We hypothesized that a video game-based rehabilitation program would improve white matter integrity and brain connectivity in the visuospatial network on brain magnetic resonance imaging (MRI), resulting in improved cognitive function in CHE subjects on measures consistent with the cognitive skill set emphasized by the two video games (e.g., IQ Boost-visual working memory, and Aim and Fire Challenge-psychomotor speed), but also generalize to thinking skills beyond the focus of the cognitive training (Hopkins verbal learning test (HVLT)-verbal learning/memory) and improve their health-related quality of life (HRQOL). The trial included three phases over 8 weeks; during the learning phase (cognitive tests administered twice over 2 weeks without intervening intervention), training phase (daily video game training for 4 weeks), and post-training phase (testing 2 weeks after the video game training ended). Thirty CHE patients completed all visits with significant daily achievement on the video games. In a subset of 13 subjects that underwent brain MRI, there was a significant decrease in fractional anisotropy, and increased radial diffusivity (suggesting axonal sprouting or increased cross-fiber formation) involving similar brain regions (i.e., corpus callosum, internal capsule, and sections of the corticospinal tract) and improvement in the visuospatial resting-state connectivity corresponding to the video game training domains. No significant corresponding improvement in HRQOL or HVLT performance was noted, but cognitive performance did transiently improve on cognitive tests similar to the video games during training. Although multimodal brain imaging changes suggest reductions in tract edema and improved neural network connectivity, this trial of video game brain training did not improve the HRQOL or produce lasting improvement in

  4. Elevated cerebrospinal fluid tau protein levels in Wernicke's encephalopathy.

    Science.gov (United States)

    Matsushita, Sachio; Miyakawa, Tomohiro; Maesato, Hitoshi; Matsui, Toshifumi; Yokoyama, Akira; Arai, Hiroyuki; Higuchi, Susumu; Kashima, Haruo

    2008-06-01

    Limited neuronal cell loss is seen in the neuropathology of Wernicke's encephalopathy (WE), but the extent of neuronal damage has not been well studied. Moreover, there is still a debate as to whether alcohol itself causes brain damage in humans. Although, it is difficult to examine the extent of neuronal damage in living patients, recent studies have revealed that total tau protein levels in the cerebrospinal fluid (CSF) reflect the rate of neuronal degeneration. Therefore, we hypothesized that the elevated CSF total tau in patients with WE was due to neuronal damage and thus we examined CSF total tau protein in patients with WE, as well as in those with alcohol withdrawal delirium (WD) and Korsakoff syndrome (KS). We also examined CSF total tau in nonalcohol dependent patients with Alzheimer's disease (AD) as a disease control. CSF samples were obtained from 13 acute WE patients with alcohol dependence, 9 WD patients with alcohol dependence and 16 KS patients with alcohol dependence, and from 20 nonalcohol dependent AD patients. CSF was also obtained from 10 of the WE patients after their disease had progressed to the chronic stage. CSF tau protein levels in all samples were determined by sandwich enzyme-linked immunosorbent assay. Tau phosphorylated at threonine 181 (p-tau(181)) and amyloid beta-protein ending at amino acid 42 (A beta 42) in CSF were also determined for comparison between acute WE with AD. Total tau was significantly elevated in acute WE and decreased on long-term follow-up, but was not elevated in WD or KS. The patterns of p-tau(181) and A beta 42 differed between acute WE and AD. Intense neuronal cell death occurs transiently in WE, and the mechanism differs from that in AD. Neuronal damage is generally unaccompanied in WD. These results suggest that CSF total tau is a useful biological marker for WE.

  5. Limonene in exhaled breath is elevated in hepatic encephalopathy.

    Science.gov (United States)

    O'Hara, M E; Fernández Del Río, R; Holt, A; Pemberton, P; Shah, T; Whitehouse, T; Mayhew, C A

    2016-11-21

    Breath samples were taken from 31 patients with liver disease and 30 controls in a clinical setting and proton transfer reaction quadrupole mass spectrometry (PTR-Quad-MS) used to measure the concentration of volatile organic compounds (VOCs). All patients had cirrhosis of various etiologies, with some also suffering from hepatocellular cancer (HCC) and/or hepatic encephalopathy (HE). Breath limonene was higher in patients with No-HCC than with HCC, median (lower/upper quartile) 14.2 (7.2/60.1) versus 3.6 (2.0/13.7) and 1.5 (1.1/2.3) nmol mol -1 in controls. This may reflect disease severity, as those with No-HCC had significantly higher UKELD (United Kingdom model for End stage Liver Disease) scores. Patients with HE were categorized as having HE symptoms presently, having a history but no current symptoms and having neither history nor current symptoms. Breath limonene in these groups was median (lower/upper quartile) 46.0 (14.0/103), 4.2 (2.6/6.4) and 7.2 (2.0/19.1) nmol mol -1 , respectively. The higher concentration of limonene in those with current symptoms of HE than with a history but no current symptoms cannot be explained by disease severity as their UKELD scores were not significantly different. Longitudinal data from two patients admitted to hospital with HE show a large intra-subject variation in breath limonene, median (range) 18 (10-44) and 42 (32-58) nmol mol -1 .

  6. Clustering of tau-immunoreactive pathology in chronic traumatic encephalopathy.

    Science.gov (United States)

    Armstrong, Richard A; McKee, Ann C; Alvarez, Victor E; Cairns, Nigel J

    2017-02-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder which may result from repetitive brain injury. A variety of tau-immunoreactive pathologies are present, including neurofibrillary tangles (NFT), neuropil threads (NT), dot-like grains (DLG), astrocytic tangles (AT), and occasional neuritic plaques (NP). In tauopathies, cellular inclusions in the cortex are clustered within specific laminae, the clusters being regularly distributed parallel to the pia mater. To determine whether a similar spatial pattern is present in CTE, clustering of the tau-immunoreactive pathology was studied in the cortex, hippocampus, and dentate gyrus in 11 cases of CTE and 7 cases of Alzheimer's disease neuropathologic change (ADNC) without CTE. In CTE: (1) all aspects of tau-immunoreactive pathology were clustered and the clusters were frequently regularly distributed parallel to the tissue boundary, (2) clustering was similar in two CTE cases with minimal co-pathology compared with cases with associated ADNC or TDP-43 proteinopathy, (3) in a proportion of cortical gyri, estimated cluster size was similar to that of cell columns of the cortico-cortical pathways, and (4) clusters of the tau-immunoreactive pathology were infrequently spatially correlated with blood vessels. The NFT and NP in ADNC without CTE were less frequently randomly or uniformly distributed and more frequently in defined clusters than in CTE. Hence, the spatial pattern of the tau-immunoreactive pathology observed in CTE is typical of the tauopathies but with some distinct differences compared to ADNC alone. The spread of pathogenic tau along anatomical pathways could be a factor in the pathogenesis of the disease.

  7. Mozart's music in children with drug-refractory epileptic encephalopathies.

    Science.gov (United States)

    Coppola, Giangennaro; Toro, Annacarmela; Operto, Francesca Felicia; Ferrarioli, Giuseppe; Pisano, Simone; Viggiano, Andrea; Verrotti, Alberto

    2015-09-01

    Mozart's sonata for two pianos in D major, K448, has been shown to decrease interictal EEG discharges and recurrence of clinical seizures in both adults and young patients. In this prospective, open-label study, we evaluated the effect of listening to a set of Mozart's compositions, according to the Tomatis method, on sleep quality and behavioral disorders, including auto-/hetero-aggression, irritability, and hyperactivity, in a group of children and adolescents with drug-resistant epilepsy. The study group was composed of 11 outpatients (7 males and 4 females), between 1.5years and 21years of age (mean age: 11.9years), all suffering from drug-resistant epileptic encephalopathy (n=11). All of them had a severe/profound intellectual disability associated with cerebral palsy. During the study period, each patient had to listen to a set of Mozart's compositions 2h per day for fifteen days for a total of 30h, which could be distributed over the day depending on the habits and compliance of each patient. The music was filtered by a device preferably delivering higher sound frequencies (>3000Hz) according to the Tomatis principles. The antiepileptic drug therapy remained unchanged throughout the study period. During the 15-day music therapy, 2 out of 11 patients had a reduction of 50-75% in seizure recurrence, and 3 out of 12 patients had a reduction of 75-89%. Overall, 5 (45.4%) out of 11 patients had a ≥50% reduction in the total number of seizures, while the percentage decrease of the total seizure number (11/11) compared with baseline was -51.5% during the 15-day music therapy and -20.7% in the two weeks after the end of treatment. All responders also had an improvement in nighttime sleep and daytime behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Emerging histomorphologic phenotypes of chronic traumatic encephalopathy in American athletes.

    Science.gov (United States)

    Omalu, Bennet; Bailes, Julian; Hamilton, Ronald L; Kamboh, M Ilyas; Hammers, Jennifer; Case, Mary; Fitzsimmons, Robert

    2011-07-01

    We define chronic traumatic encephalopathy (CTE) as a progressive neurodegenerative syndrome caused by single, episodic, or repetitive blunt force impacts to the head and transfer of acceleration-deceleration forces to the brain. We present emerging histomorphologic phenotypes of CTE that we identified in our cohort of CTE cases with apolipoprotein E genotyping and causes and manners of death. Autopsy brain tissue of 14 professional athletes and 3 high school football players was examined after unexpected deaths. Histochemical and immunohistochemical tissue staining was performed with apolipoprotein E genotyping. Ten of 14 professional athletes (71%) were positive for CTE: 7 of 8 football players, 2 of 4 wrestlers, and 1 boxer. One of 3 high school players manifested incipient CTE. The age range of those with CTE was 18 to 52 years; they were all male athletes. In all cases of CTE, Alzheimer-type cerebral cortical atrophy was absent; negligible to mild neocortical neuronal dropout was present. The fundamental neuropathologic feature of CTE was the topographic distribution of sparse, moderate, and frequent band-shaped, flame-shaped, small and large globose neurofibrillary tangles and neuritic threads in the cerebral cortex, subcortical nuclei/basal ganglia, hippocampus, and brainstem nuclei. Sparse to frequent diffuse amyloid plaques may accompany tauopathy and was seen in only 2 CTE cases. No α-synucleinopathy was present. All 7 CTE-positive professional athletes with known apolipoprotein E genotypes had at least 1 E3 allele comprising 5 E3/E3 (71%) and 2 E3/E4 (29%). Alcohol- and drug-related deaths, suicides, and accidental deaths were overrepresented in our CTE cohort. The emerging histomorphologic features of our CTE cohort may specify histologic criteria for CTE diagnosis, may identify emerging histologic variants of CTE and may facilitate more objective surveillance and accurate identification of sentinel CTE cases.

  9. [Corrected QT interval during therapeutic hypothermia in hypoxic ischaemic encephalopathy].

    Science.gov (United States)

    Vega, Laia; Boix, Héctor; Albert, Dimpna; Delgado, Ignacio; Castillo, Félix

    2016-12-01

    Therapeutic hypothermia is the standard treatment for hypoxic ischaemic encephalopathy (HIE), despite not knowing all its effects and complications. Sinus bradycardia is one of the consequences of cooling that has been previously documented in the literature, but little is known about the cardiac electrical activity in these patients. To determine the corrected QT (QTc) interval in newborns treated with therapeutic hypothermia for HIE. A prospective observational study was conducted in all patients treated with hypothermia for HIE that were admitted to our Unit between November 2012 and October 2013. ECGs were performed during hypothermia (every 24h), during the re-warming period (at 34.5°C, 35.5°C, 36.5°C), and on the 7th day of life. A total of 19 patients were included. A prolonged QTc was observed in all patients during hypothermia, and 84% (n=16) had prolonged QTc in all the ECGs during treatment. In 3 patients, one of the ECGs did not have a prolonged QTc. After re-warming, the QTc interval returned to normal in all patients. No statistically significant differences were seen when the degree of HIE (P=.192) or the use of inotropic support (P=.669) were considered. Therapeutic hypothermia applied to asphyxiated newborns with HIE seems to induce a QTc prolongation that resolves when the patient regains physiological temperature. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Compare Of the West Syndrome with Other Syndromes in the Epileptic Encephalopathy - Kosovo Experience

    Science.gov (United States)

    Zeka, Naim; Gërguri, Abdurrahim; Bejiqi, Ramush; Retkoceri, Ragip; Vuciterna, Armend

    2017-01-01

    BACKGROUND: West Syndrome (WS) represents as a specific epileptic encephalopathy characterised with a unique type of attacks, called infantile spasms, severe forms of abnormalities in electroencephalographic (EEG) records as a hypsarythmias and delays in the psychomotoric development. The characteristics of the disease, mostly affecting male gender, are infantile spasms and typical findings in EEG as a hypsarythmia. Infantile spasms are a consequence of many factors in the undeveloped brain. AIM: We aimed: (1) to see the incidence of the illness and the spreading out because of gender in rapport with other syndromes in the epileptic encephalopathies group; (2) to show principles of the treatment for the illness; and (3) to present the effects of the disease in the psycho-motoric development of affected children. METHODS: The study was designed as a cross-sectional study of the patients with epileptic encephalopathies, treated in Paediatric Clinic in Prishtina, from 1st of January 2013 until the 31st of December 2015. RESULTS: From the cohort group of 97 children diagnosed with epileptic encephalopathies, in 14 of them clinical and EEG signs of WS were noted. The earliest age of disease manifestation was 74 days (± 63.8 days). On the group of children with WS, 13 of them with Natrium Valpropat were treated, with the doses of 301.9 mg (± 64.1). From the cohort group, in 89 children (91.8%) psychomotoric retardation was documented, within the higher reoccurrence in the undifferentiated epileptic encephalopathies (96%) and the WS (78.6%). CONCLUSION: WS is a frequent disease of the encephalopathies with the epileptogenic framework. The resistance in anticonvulsive therapy is huge, and psychomotoric retardation follows a big percentage of children with this syndrome. PMID:29362620

  11. Low Apgar score, neonatal encephalopathy and epidural analgesia during labour: a Swedish registry-based study.

    Science.gov (United States)

    Törnell, S; Ekéus, C; Hultin, M; Håkansson, S; Thunberg, J; Högberg, U

    2015-04-01

    Maternal intrapartum fever (MF) is associated with neonatal sequelae, and women in labour who receive epidural analgesia (EA) are more likely to develop hyperthermia. The aims of this study were to investigate if EA and/or a diagnosis of MF were associated to adverse neonatal outcomes at a population level. Population-based register study with data from the Swedish Birth Register and the Swedish National Patient Register, including all nulliparae (n=294,329) with singleton pregnancies who gave birth at term in Sweden 1999-2008. Neonatal outcomes analysed were Apgar score (AS)neonatal encephalopathy (e.g. convulsions or neonatal cerebral ischaemia). Multivariate logistic regression was used to calculate adjusted odds ratios (AOR) with 95% confidence intervals (CI). EA was used in 44% of the deliveries. Low AS or encephalopathy was found in 1.26% and 0.39% of the children in the EA group compared with 0.80% and 0.29% in the control group. In multivariate analysis, EA was associated with increased risk with low AS, AOR 1.27 (95% CI 1.16-1.39), but not with diagnosis of encephalopathy, 1.11 (0.96-1.29). A diagnosis of MF was associated with increased risk for both low AS, 2.27 (1.71-3.02), and of neonatal encephalopathy, 1.97 (1.19-3.26). Diagnosis of MF was associated with low AS and neonatal encephalopathy, whereas EA was only associated with low AS and not with neonatal encephalopathy. The found associations might be a result of confounding by indication, which is difficult to assess in a registry-based population study. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  12. Compare Of the West Syndrome with Other Syndromes in the Epileptic Encephalopathy - Kosovo Experience.

    Science.gov (United States)

    Zeka, Naim; Gërguri, Abdurrahim; Bejiqi, Ramush; Retkoceri, Ragip; Vuciterna, Armend

    2017-12-15

    West Syndrome (WS) represents as a specific epileptic encephalopathy characterised with a unique type of attacks, called infantile spasms, severe forms of abnormalities in electroencephalographic (EEG) records as a hypsarythmias and delays in the psychomotoric development. The characteristics of the disease, mostly affecting male gender, are infantile spasms and typical findings in EEG as a hypsarythmia. Infantile spasms are a consequence of many factors in the undeveloped brain. We aimed: (1) to see the incidence of the illness and the spreading out because of gender in rapport with other syndromes in the epileptic encephalopathies group; (2) to show principles of the treatment for the illness; and (3) to present the effects of the disease in the psycho-motoric development of affected children. The study was designed as a cross-sectional study of the patients with epileptic encephalopathies, treated in Paediatric Clinic in Prishtina, from 1st of January 2013 until the 31st of December 2015. From the cohort group of 97 children diagnosed with epileptic encephalopathies, in 14 of them clinical and EEG signs of WS were noted. The earliest age of disease manifestation was 74 days (± 63.8 days). On the group of children with WS, 13 of them with Natrium Valpropat were treated, with the doses of 301.9 mg (± 64.1). From the cohort group, in 89 children (91.8%) psychomotoric retardation was documented, within the higher reoccurrence in the undifferentiated epileptic encephalopathies (96%) and the WS (78.6%). WS is a frequent disease of the encephalopathies with the epileptogenic framework. The resistance in anticonvulsive therapy is huge, and psychomotoric retardation follows a big percentage of children with this syndrome.

  13. Wernicke-korsakoff encephalopathy and polyneuropathy after gastroplasty for morbid obesity: report of a case.

    Science.gov (United States)

    Cirignotta, F; Manconi, M; Mondini, S; Buzzi, G; Ambrosetto, P

    2000-09-01

    Gastric partitioning is a surgical procedure for the treatment of morbid obesity that may engender neurological complications, such as Wernicke encephalopathy and polyneuropathy. A specialist hospital. A 36-year-old woman developed Wernicke-Korsakoff encephalopathy and polyneuropathy 3 months after gastroplasty for morbid obesity. A magnetic resonance scan documented the diagnosis, and a clear improvement occurred after parenteral thiamine treatment. In our patient and in previously described cases of the literature, postsurgical vomiting is a constant finding that seems to be the precipitating factor of neurological complications of gastric partitioning. Persistent vomiting after gastroplasty for morbid obesity should be considered an alarming symptom to treat immediately with appropriate measures.

  14. Posterior Reversible Encephalopathy Syndrome in a Postpartum Preeclamptic Woman without Seizure

    Directory of Open Access Journals (Sweden)

    Ülkü Mete Ural

    2014-01-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is a cliniconeuroradiological entity presenting with headache, confusion, visual disturbances or blindness, and seizures. Parieto-occipital white matter changes due to vasogenic oedema can be observed on imaging modalities. It rarely occurs without seizures and after delivery. We report a 33-year-old multigravida with a history of preeclampsia in term pregnancy complicated by PRES without seizures at the postpartum period. Clinical improvement with complete resolution without any complications was observed on the 6th day after delivery. Posterior reversible encephalopathy syndrome is reversible when early diagnosis is established and appropriate treatment is started without delay.

  15. Good outcome after posterior reversible encephalopathy syndrome (PRES) despite elevated cerebral lactate

    DEFF Research Database (Denmark)

    Ewertsen, Caroline; Kondziella, Daniel; Danielsen, Else R

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) may cause irreversible brain damage. The diagnosis is confirmed by magnetic resonance imaging (MRI), where vasogenic edema may be seen especially in the posterior parts of the brain. MR spectroscopy (MRS) may be included to help predict the outc......Posterior reversible encephalopathy syndrome (PRES) may cause irreversible brain damage. The diagnosis is confirmed by magnetic resonance imaging (MRI), where vasogenic edema may be seen especially in the posterior parts of the brain. MR spectroscopy (MRS) may be included to help predict...

  16. A Rare Case of Wernicke’s Encephalopathy Due to Hyperemesis Gravidarum

    Directory of Open Access Journals (Sweden)

    Bellad AV

    2015-04-01

    Full Text Available A young pregnant woman with hyperemesis gravidarum presented to casualty with ataxia, confusion and diplopia. Examination revealed nystagmus and bilateral retinal haemorrhages. Characteristic brain MRI findings and rapid response to thiamine was suggestive of Wernicke’s encephalopathy due to hyperemesis gravidarum. Wernicke’s encephalopathy is a potentially reversible condition caused by thiamine deficiency. It is usually suspected in the setting of chronic alcoholosim and might not be recognised when associated with other conditions. A high index of suspicion is required since lack or delay of treatment may lead to high morbidity and mortality.

  17. Intravenous Poison Hemlock Injection Resulting in Prolonged Respiratory Failure and Encephalopathy.

    Science.gov (United States)

    Brtalik, Douglas; Stopyra, Jason; Hannum, Jennifer

    2017-06-01

    Poison hemlock (Conium maculatum) is a common plant with a significant toxicity. Data on this toxicity is sparse as there have been few case reports and never a documented poisoning after intravenous injection. We present a case of intravenous poison hemlock injection encountered in the emergency department. We describe a 30-year-old male who presented to the emergency department after a brief cardiac arrest after injecting poison hemlock. The patient had return of spontaneous circulation in the emergency department but had prolonged muscular weakness and encephalopathy later requiring tracheostomy. Intravenous injection of poison hemlock alkaloids can result in significant toxicity, including cardiopulmonary arrest, prolonged weakness, and encephalopathy.

  18. Dental management of bilirubin encephalopathy patient: A case report and review

    Directory of Open Access Journals (Sweden)

    Poornima Parameswarappa

    2017-01-01

    Full Text Available Patients with special health care needs often present with compromised oral health for which they need dental treatment. Such patients and often their guardians find it difficult to maintain oral health due to various reasons such as decreased manual dexterity and preference for soft diet. Bilirubin encephalopathy is a condition occurring as a result of neonatal jaundice/hyperbilirubinemia. Elevated levels of unconjugated bilirubin at birth often leads to brain damage manifesting as auditory and motor defects such as athetoid cerebral palsy. This paper reports one such case of dental management of a known case of bilirubin encephalopathy.

  19. Assessment of minimal hepatic encephalopathy (with emphasis on computerized psychometric tests).

    Science.gov (United States)

    Kappus, Matthew R; Bajaj, Jasmohan S

    2012-02-01

    Minimal hepatic encephalopathy (MHE) is associated with a high risk of development of overt hepatic encephalopathy, impaired quality of life, and driving accidents. The detection of MHE requires specialized testing because it cannot, by definition, be diagnosed on standard clinical examination. Psychometric and neurophysiologic techniques are often used to test for MHE. Paper-pencil psychometric batteries and computerized tests have proved useful in diagnosing MHE and predicting its outcomes. Neurophysiologic tests also provide useful information. The diagnosis of MHE is an important issue for clinicians and patients alike. Testing strategies depend on the normative data available, patient comfort, and local expertise. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Clinical characteristics of acute encephalopathies associated with influenza H1N1-2009 in children

    International Nuclear Information System (INIS)

    Watanabe, Yashihiro; Tsuji, Megumi; Sameshima, Kiyoko; Wada, Takahito; Iai, Mizue; Yamashita, Sumimasa; Hayashi, Takuya; Aida, Noriko; Osaka, Hiroshi

    2012-01-01

    We report 12 cases of acute encephalopathy associated with influenza H1N1-2009 treated according to Japanese guideline (2009). In all 12 cases, electroencephalogram presented diffuse or localized high-amplitude slow waves. Brain CT and MRI showed abnormalities in 4 and 6 cases, respectively. We used hypothermia therapy for 5 patients. One patient showed impairment in short term memory, while the rest of the patients showed no sequelae. These 12 cases presented here suggest the early recognition and therapy according to the newly proposed guideline may reduce severe sequelae and mortality by acute encephalopathy associated with influenza H1N1-2009. (author)

  1. Brain Inflammation in an Infant With Hemimegalencephaly, Escalating Seizures, and Epileptic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Se Hee Kim MD

    2016-03-01

    Full Text Available Hemimegalencephaly, a congenital brain malformation typically characterized by enlargement of one hemisphere, is frequently associated with intractable epilepsy. The authors report a case of a 12-month-old girl with hemimegalencephaly who underwent semiurgent hemispherectomy because of rapidly escalating seizures, arrested development, and associated encephalopathy. The brain tissue was examined and evaluated for neuroinflammation. Immunohistochemical analysis of the brain tissue revealed the presence of abundant activated CD68-positive microglia and reactive astrogliosis. Detection of active inflammatory changes in the brain of a patient with hemimegalencephaly complicated by intractable epilepsy suggests a potential role of ongoing brain inflammation in seizure exacerbation and epileptic encephalopathy.

  2. Ketogenic diet - A novel treatment for early epileptic encephalopathy due to PIGA deficiency.

    Science.gov (United States)

    Joshi, Charuta; Kolbe, Diana L; Mansilla, M Adela; Mason, Sara; Smith, Richard J H; Campbell, Colleen A

    2016-10-01

    We describe the presentation and workup of two brothers with early-onset epileptic encephalopathy who became seizure-free on a ketogenic diet. Extensive testing culminated in whole exome sequencing, which led to the diagnosis of phosphatidyl inositol glycan biosynthesis class A protein (PIGA) deficiency. This familial case highlights the importance of genetic testing for early-onset epileptic encephalopathies and underscores the potential value of a ketogenic diet in the treatment of this condition. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  3. Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy.

    Science.gov (United States)

    Puvenna, Vikram; Engeler, Madeline; Banjara, Manoj; Brennan, Chanda; Schreiber, Peter; Dadas, Aaron; Bahrami, Ashkon; Solanki, Jesal; Bandyopadhyay, Anasua; Morris, Jacqueline K; Bernick, Charles; Ghosh, Chaitali; Rapp, Edward; Bazarian, Jeffrey J; Janigro, Damir

    2016-01-01

    Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six postmortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (PCTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy

    Science.gov (United States)

    Puvenna, Vikram; Engeler, Madeline; Banjara, Manoj; Brennan, Chanda; Schreiber, Peter; Dadas, Aaron; Bahrami, Ashkon; Solanki, Jesal; Bandyopadhyay, Anasua; Morris, Jacqueline K.; Bernick, Charles; Ghosh, Chaitali; Bazarian, Jeffrey J.; Janigro, Damir

    2016-01-01

    Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six post mortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (Pepileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. PMID:26556772

  5. Cost-effective therapeutic hypothermia treatment device for hypoxic ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Allen RH

    2013-01-01

    Full Text Available John J Kim,1,2 Nathan Buchbinder,1,† Simon Ammanuel,1,4,5,† Robert Kim,1,† Erika Moore,1 Neil O'Donnell,1 Jennifer K Lee,3 Ewa Kulikowicz,3 Soumyadipta Acharya,1 Robert H Allen,1,9 Ryan W Lee,6,7 Michael V Johnston4–81Department of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, 2The James Buchanan Brady Urological Institute, Department of Urology, The Johns Hopkins University School of Medicine, 3Department of Anesthesia and Critical Care Medicine, Johns Hopkins University, 4Kennedy Krieger Institute, 5Hugo W Moser Research Institute, 6Department of Neurology, 7Department of Pediatrics, 8Department of Physical Medicine and Rehabilitation Johns Hopkins University School of Medicine, Baltimore, MD; 9Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA†These authors contributed equally to this workAbstract: Despite recent advances in neonatal care and monitoring, asphyxia globally accounts for 23% of the 4 million annual deaths of newborns, and leads to hypoxic-ischemic encephalopathy (HIE. Occurring in five of 1000 live-born infants globally and even more in developing countries, HIE is a serious problem that causes death in 25%–50% of affected neonates and neurological disability to at least 25% of survivors. In order to prevent the damage caused by HIE, our invention provides an effective whole-body cooling of the neonates by utilizing evaporation and an endothermic reaction. Our device is composed of basic electronics, clay pots, sand, and urea-based instant cold pack powder. A larger clay pot, lined with nearly 5 cm of sand, contains a smaller pot, where the neonate will be placed for therapeutic treatment. When the sand is mixed with instant cold pack urea powder and wetted with water, the device can extract heat from inside to outside and maintain the inner pot at 17°C for more than 24 hours with monitoring by LED lights and thermistors

  6. A look at the hepatic encephalopathy in cirrhosis

    Directory of Open Access Journals (Sweden)

    Giacomo Zaccherini

    2013-01-01

    Full Text Available Hepatic encephalopathy (HE is a neuropsychiatric syndrome complicating acute and chronic liver failure and characterized by a wide range of manifestations, in absence of other brain disease. HE is very frequent in course of cirrhosis and even mild forms involve a great additional burden on patients, their families and health-care resources. Its onset affects subsequent survival of patients. Historically, pathophysiology of HE was connected to several substances (mostly ammonia produced in the gut and normally metabolized by the liver, but more recently other factors such as inflammation, bacterial translocation and oxidative stress have shown a crucial role. Symptoms are often overt (confusion, asterixis, disorientation, ataxia or coma but can also be subtle (sleep disturbances, cognitive impairment, mood alterations, impairment of executive decision-making, and psychomotor speed – Minimal HE; the West Haven Criteria are most often used to grade Overt HE (OHE, with grade ranging from 0 to 4 (4 corresponding to coma. Since both Minimal HE and grade 1 HE cannot be diagnosed by clinical examination and need for specific tests, it results practical to combine these entities and name them "Covert" HE (CHE to aid clinical use. Diagnosis is based on evidence of neurological impairment in presence of liver cirrhosis, only after the exclusion of other brain diseases. Measurement of serum ammonia and electroencephalography are little specific, while brain magnetic resonance and search for portosystemic shunts are important in complex cases. Diagnosis of OHE is often just clinical, while that of CHE requires dedicated psychometric and neurophysiological tests. Although these tests are difficult to be performed in the clinical practice, detection and treatment of CHE are cost-effective and important; indeed, CHE affects patients’ quality of life, socioeconomic status and driving skills, and increases the risk for falls, car accidents, development of OHE

  7. Morphological changes in the brain in diabetic encephalopathy

    Directory of Open Access Journals (Sweden)

    Т.Е. Mikhaylichenko

    2017-10-01

    Full Text Available Background. The purpose of this work was to study the morphological characteristics of brain changes in patients with diabetic encephalopathy (DE on the basis of autopsy material research. Materials and methods. The paper presents the results of 14 postmortem observations. The mean age of the patients was 51.0 ± 3.4 years. The pieces of the brain were fixed in a solution of IHC Zinc Fixative, serial paraffin sections were made with a thickness of 10 ± 1 μm. The preparations were stained with hematoxylin and eosin, Congo red, thionin according to the Nissl method, Schick test was applied, with silver nitrate impregnation according to the Bielschowsky method and gold chloride — by Cajal, morphometric examination was performed according to G.G. Avtandilov. The study of the preparations was carried out on the Olympus AX70 microscope with a digital camera Olympus DP50. Microphotography of the preparations was performed using the program Pro 3.2. Results. The main cyto-angioarchitectonic manifestations of DE are: diffuse alteration of basal membranes and vascular endothelium of the microcirculatory bed, and to a lesser extent — arterioles, intracerebral arteries and veins. High density (specific volume of the capillary network at DE morphologically reflects the pattern of capillary paralytic stagnation. Capillary stagnation is accompanied by a stasis of the blood, an increase in the perivascular capillary space (Virchow-Robin space, the width of which is the morphological equivalent of lymphatic dyscirculation. Early morphological damage to the capillary walls is thickening and cleft of the main membrane with the accumulation of Schick-positive substan­ces, focal proliferation of endotheliocytes. Late injuries include capillary fibrosis and hyalinosis, proliferation of pericytes, which is accompanied by a sharp violation of transcapillary transport. Violation of striatal and radial cytoarchitectonics in the I–IV layers of the brain, prolapse

  8. Effects of common chronic medical conditions on psychometric tests used to diagnose minimal hepatic encephalopathy

    DEFF Research Database (Denmark)

    Lauridsen, M M; Poulsen, L; Rasmussen, C K

    2016-01-01

    Many chronic medical conditions are accompanied by cognitive disturbances but these have only to a very limited extent been psychometrically quantified. An exception is liver cirrhosis where hepatic encephalopathy is an inherent risk and mild forms are diagnosed by psychometric tests. The preferred...

  9. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kuzmanić Šamija, R. [Department of Pediatrics, University Hospital Split, Split (Croatia); Primorac, D. [School of Medicine Split, University of Split, Split (Croatia); Department of Pediatrics, School of Medicine, University of Osijek, Osijek (Croatia); Eberly College of Science, Penn State University, University Park, PA (United States); St. Catherine Speciality Hospital, Zabok (Croatia); Rešić, B. [School of Medicine Split, University of Split, Split (Croatia); Pavlov, V. [Department of Neonatology, University Hospital Split, Split (Croatia); Čapkun, V. [Department of Nuclear Medicine, University Hospital Split, Split (Croatia); Punda, H. [School of Medicine Split, University of Split, Split (Croatia); Lozić, B. [Department of Pediatrics, University Hospital Split, Split (Croatia); Zemunik, T. [Department of Medical Biology, School of Medicine Split, University of Split, Split (Croatia)

    2014-08-15

    The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

  10. Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data

    NARCIS (Netherlands)

    Allen, Andrew S.; Berkovic, Samuel F.; Bridgers, Joshua; Cossette, Patrick; Dlugos, Dennis; Epstein, Michael P.; Glauser, Tracy; Goldstein, David B.; Heinzen, Erin L.; Jiang, Yu; Johnson, Michael R.; Kuzniecky, Ruben; Lowenstein, Daniel H.; Marson, Anthony G.; Mefford, Heather C.; O'Brien, Terence J.; Ottman, Ruth; Petrou, Steven; Petrovski, Slavé; Poduri, Annapurna; Ren, Zhong; Scheffer, Ingrid E.; Sherr, Elliott; Wang, Quanli; Balling, Rudi; Barisic, Nina; Baulac, Stéphanie; Caglayan, Hande; Craiu, Dana; De Jonghe, Peter; Depienne, Christel; Guerrini, Renzo; Helbig, Ingo; Hjalgrim, Helle; Hoffman-Zacharska, Dorota; Jähn, Johanna A.; Klein, Karl Martin; Koeleman, Bobby; Komarek, Vladimir; Krause, Roland; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes R.; Lerche, Holger; Linnankivi, Tarja; Marini, Carla; May, Patrick; Møller, Rikke S.; Muhle, Hiltrud; Pal, Deb; Palotie, Aarno; Rosenow, Felix; Selmer, Kaja; Serratosa, Jose M.; Sisodiya, Sanjay M.; Stephani, Ulrich; Sterbova, Katalin; Striano, Pasquale; Suls, Arvid; Talvik, Tiina; von Spiczak, Sarah; Weber, Yvonne G.; Weckhuysen, Sarah; Zara, Federico; Abou-Khalil, Bassel; Alldredge, Brian K.; Amrom, Dina; Andermann, Eva; Andermann, Frederick; Bautista, Jocelyn F.; Bluvstein, Judith; Cascino, Gregory D.; Consalvo, Damian; Crumrine, Patricia; Devinsky, Orrin; Fiol, Miguel E.; Fountain, Nathan B.; French, Jacqueline; Friedman, Daniel; Haas, Kevin; Haut, Sheryl R.; Hayward, Jean; Joshi, Sucheta; Kanner, Andres; Kirsch, Heidi E.; Kossoff, Eric H.; Kuperman, Rachel; McGuire, Shannon M.; Motika, Paul V.; Novotny, Edward J.; Paolicchi, Juliann M.; Parent, Jack; Park, Kristen; Shellhaas, Renée A; Sirven, Joseph; Smith, Michael C.; Sullivan, Joseph; Thio, Liu Lin; Venkat, Anu; Vining, Eileen P. G.; Von Allmen, Gretchen K.; Weisenberg, Judith L.; Widdess-Walsh, Peter; Winawer, Melodie R.

    2017-01-01

    The classic epileptic encephalopathies, including infantile spasms (IS) and Lennox-Gastaut syndrome (LGS), are severe seizure disorders that usually arise sporadically. De novo variants in genes mainly encoding ion channel and synaptic proteins have been found to account for over 15% of patients

  11. A machine learning approach to automated structural network analysis: application to neonatal encephalopathy.

    Directory of Open Access Journals (Sweden)

    Etay Ziv

    Full Text Available Neonatal encephalopathy represents a heterogeneous group of conditions associated with life-long developmental disabilities and neurological deficits. Clinical measures and current anatomic brain imaging remain inadequate predictors of outcome in children with neonatal encephalopathy. Some studies have suggested that brain development and, therefore, brain connectivity may be altered in the subgroup of patients who subsequently go on to develop clinically significant neurological abnormalities. Large-scale structural brain connectivity networks constructed using diffusion tractography have been posited to reflect organizational differences in white matter architecture at the mesoscale, and thus offer a unique tool for characterizing brain development in patients with neonatal encephalopathy. In this manuscript we use diffusion tractography to construct structural networks for a cohort of patients with neonatal encephalopathy. We systematically map these networks to a high-dimensional space and then apply standard machine learning algorithms to predict neurological outcome in the cohort. Using nested cross-validation we demonstrate high prediction accuracy that is both statistically significant and robust over a broad range of thresholds. Our algorithm offers a novel tool to evaluate neonates at risk for developing neurological deficit. The described approach can be applied to any brain pathology that affects structural connectivity.

  12. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

    International Nuclear Information System (INIS)

    Kuzmanić Šamija, R.; Primorac, D.; Rešić, B.; Pavlov, V.; Čapkun, V.; Punda, H.; Lozić, B.; Zemunik, T.

    2014-01-01

    The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children

  13. High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies

    NARCIS (Netherlands)

    Hamdan, Fadi F.; Myers, Candace T.; Cossette, Patrick; Lemay, Philippe; Spiegelman, Dan; Laporte, Alexandre Dionne; Nassif, Christina; Diallo, Ousmane; Monlong, Jean; Cadieux-Dion, Maxime; Dobrzeniecka, Sylvia; Meloche, Caroline; Retterer, Kyle; Cho, Megan T.; Rosenfeld, Jill A.; Bi, Weimin; Massicotte, Christine; Miguet, Marguerite; Brunga, Ledia; Regan, Brigid M.; Mo, Kelly; Tam, Cory; Schneider, Amy; Hollingsworth, Georgie; FitzPatrick, David R.; Donaldson, Alan; Canham, Natalie; Blair, Edward; Kerr, Bronwyn; Fry, Andrew E.; Thomas, Rhys H.; Shelagh, Joss; Hurst, Jane A.; Brittain, Helen; Blyth, Moira; Lebel, Robert Roger; Gerkes, Erica H.; Davis-Keppen, Laura; Stein, Quinn; Chung, Wendy K.; Dorison, Sara J.; Benke, Paul J.; Fassi, Emily; Corsten-Janssen, Nicole; Kamsteeg, Erik-Jan; Mau-Them, Frederic T.; Bruel, Ange-Line; Verloes, Alain; Ounap, Katrin; Wojcik, Monica H.; Albert, Dara V. F.; Venkateswaran, Sunita; Ware, Tyson; Jones, Dean; Liu, Yu-Chi; Mohammad, Shekeeb S.; Bizargity, Peyman; Bacino, Carlos A.; Leuzzi, Vincenzo; Martinelli, Simone; Dallapiccola, Bruno; Tartaglia, Marco; Blumkin, Lubov; Wierenga, Klaas J.; Purcarin, Gabriela; O'Byrne, James J.; Stockler, Sylvia; Lehman, Anna; Keren, Boris; Nougues, Marie-Christine; Mignot, Cyril; Auvin, Stephane; Nava, Caroline; Hiatt, Susan M.; Bebin, Martina; Shao, Yunru; Scaglia, Fernando; Lalani, Seema R.; Frye, Richard E.; Jarjour, Imad T.; Jacques, Stephanie; Boucher, Renee-Myriam; Riou, Emilie; Srour, Myriam; Carmant, Lionel; Lortie, Anne; Major, Philippe; Diadori, Paola; Dubeau, Francois; D'Anjou, Guy; Bourque, Guillaume; Berkovic, Samuel F.; Sadleir, Lynette G.; Campeau, Philippe M.; Kibar, Zoha; Lafreniere, Ronald G.; Girard, Simon L.; Mercimek-Mahmutoglu, Saadet; Boelman, Cyrus; Rouleau, Guy A.; Scheffer, Ingrid E.; Mefford, Heather C.; Andrade, Danielle M.; Rossignol, Elsa; Minassian, Berge A.; Michaud, Jacques L.

    2017-01-01

    Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. The cause of DEE remains unknown in the

  14. White matter lesions and encephalopathy in patients treated for primary central nervous system lymphoma

    NARCIS (Netherlands)

    Wassenberg, MWM; Bromberg, JEC; Witkamp, TD; Terhaard, CHJ; Taphoorn, MJB

    A retrospective analysis of the clinical presentations and neuroimaging characteristics of 33 patients with a primary central nervous system lymphoma (PCNL) who received cranial radiotherapy was performed to assess incidence of and risk factors for radiation-induced encephalopathy. CT and MRI scans

  15. BNF Recommendations for the treatment of Wernicke's encephalopathy : Lost in translation?

    NARCIS (Netherlands)

    Oudman, Erik; Wijnia, Jan W.

    2014-01-01

    We agree with Thomson and Marshall (2013) that the current prescribing of thiamine replacement therapy for Wernicke's Encephalopathy (WE) is ambiguous. In response to their article, we also advocate that any consensus on accurate thiamine treatment for WE should receive sufficient international

  16. Benzodiazepines and risk for hepatic encephalopathy in patients with cirrhosis and ascites

    DEFF Research Database (Denmark)

    Grønbæk, Lisbet; Watson, Hugh; Vilstrup, Hendrik

    2018-01-01

    Background: There is limited evidence to support the belief that benzodiazepines increase cirrhosis patients’ risk of hepatic encephalopathy (HE). Objective: We aimed to examine the association between benzodiazepine use and HE development in cirrhosis patients. Methods: We used data on 865 cirrh...

  17. The ketogenic diet is effective for refractory epilepsy associated with acquired structural epileptic encephalopathy.

    Science.gov (United States)

    Villaluz, Mel Michel; Lomax, Lysa Boissé; Jadhav, Trupti; Cross, J Helen; Scheffer, Ingrid E

    2018-02-16

    Ketogenic diet therapies have proven efficacy for refractory epilepsy. There are many reports of their use in the genetic developmental and epileptic encephalopathies; however, little attention has been paid as to whether the diet is also effective in individuals with an acquired structural aetiology. We observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic encephalopathy. We then analysed our cases with refractory structural epilepsies of acquired origin to characterize their response to the ketogenic diet. The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1. Seizure frequency at 1 month, 3 months, 6 months, 1 year, and 2 years was ascertained. A responder was defined as greater than 50% seizure reduction compared to baseline. Seven of the nine patients were responders at 3 months. Somewhat surprisingly we found that the ketogenic diet was effective in patients with a developmental and epileptic encephalopathy due to an acquired structural aetiology. This cohort may not be routinely considered for the ketogenic diet because of their structural and acquired, rather than genetic, basis. The ketogenic diet should be considered early in the management of patients with acquired structural encephalopathies as it can improve seizure control with the potential to improve developmental outcome. The ketogenic diet was effective in children with epilepsy associated with an acquired structural aetiology. © 2018 Mac Keith Press.

  18. Clinical spectrum and genotype-phenotype associations of KCNA2-related encephalopathies

    DEFF Research Database (Denmark)

    Masnada, Silvia; Hedrich, Ulrike B S; Gardella, Elena

    2017-01-01

    Recently, de novo mutations in the gene KCNA2, causing either a dominant-negative loss-of-function or a gain-of-function of the voltage-gated K+ channel Kv1.2, were described to cause a new molecular entity within the epileptic encephalopathies. Here, we report a cohort of 23 patients (eight prev...

  19. Progressive Encephalopathy in Boys with Symptoms of Rett Syndrome and MECP2 Mutations

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-08-01

    Full Text Available Four young boys with neonatal onset of encephalopathy, a progressive course, and MECP2 mutations are reported from the University of Alabama, Birmingham, AL Symptoms suggestive of Rett syndrome included failure to thrive, respiratory insufficiency, microcephaly, hypotonia, movement disorder, with myoclonic, dyskinetic, and choreiform patterns, and repetitive face scratching or nose rubbing stereotypies.

  20. Wernicke′s encephalopathy and central pontine myelinolysis in hyperemesis gravidarum

    Directory of Open Access Journals (Sweden)

    Panee Sutamnartpong

    2013-01-01

    Full Text Available A pregnant woman, who had been suffering from hyperemesis gravidarum, presented with alteration of consciousness, ocular nystagmus and ataxia. Magnetic Resonance Imaging of the brain showed typical findings of Wernicke′s encephalopathy and central pontine myelinolysis. The clinical features responded dramatically to thiamine supplementation.