Liemann, S; Glockshuber, R
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.
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...
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.
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.
Keulen, van L.J.M.; Vromans, M.E.W.; Dolstra, C.H.; Bossers, A.; Zijderveld, van F.G.
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
Brugère-Picoux, Jeanne; Adjou, Karim; Brugère, Henri
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.
G. K. Bruckner
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.
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.
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
Kadohira, M.; Stevenson, M.A.; Hogasen, H.R.; Koeijer, de A.A.
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
Paisley, Larry; de Koeijer, Aline; Hagenaars, Thomas J.
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....
Duque Velásquez, Camilo; Garzón Álzate, Ánderson; Villegas Lanau, Andrés; Escobar Velásquez, Laura Marcela; Zea Lopera, Julián; Lopera, Francisco; Rodas González, Juan David
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...
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...
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...
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...
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...
Duque Velásquez, Camilo
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.
Williams, E S; Young, S
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.
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...
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.
Hörnlimann, B; Guidon, D; Griot, C
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.
Campbell, Peter N
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.
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
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...
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
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.
Jorge E Delgado-Hachmeister
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.
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)
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
Doherr Marcus G
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.
van Gelderen, C; Gimeno, E J; Schudel, A A
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.
Thuring, C.M.A.; Keulen, van L.J.M.; Langeveld, J.P.M.; Vromans, M.E.W.; Zijderveld, van F.G.; Sweeney, T.
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
Gubbins, S.; Touzeau, S.; Hagenaars, T.H.J.
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
Brugère-Picoux, J; Lasmézas, C; Deslys, J P; Adjou, K; Rérat, A; Dormont, D
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.
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...
Seuberlich, Torsten; Heim, Dagmar; Zurbriggen, Andreas
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.
Gavora, J.S.; Kochhar, H.P.S.; Gifford, G.A.
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)
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.
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.
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.
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.
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
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.
Davidson, Debra J; Bogdan, Eva
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.
Rhind Susan M
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.
Lasmézas, C I; Deslys, J P; Demaimay, R; Adjou, K T; Hauw, J J; Dormont, D
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.
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...
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.
Serra, Fabienne; Müller, Joachim; Gray, John; Lüthi, Ramona; Dudas, Sandor; Czub, Stefanie; Seuberlich, Torsten
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 Â© 2017. Published by Elsevier B.V.
Yang, Jun; Goddard, Ellen
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.
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)
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
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.
Bons, Nöelle; Lehmann, Sylvain; Mestre-Francès, Nadine; Dormont, Dominique; Brown, Paul
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.
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.
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
Morawski, Aaron R; Carlson, Christina M; Chang, Haeyoon; Johnson, Christopher J
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
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
Jorge M. Charco
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.
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: firstname.lastname@example.org [Prion Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan)
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.
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.
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.
Sharpe, A.; McElroy, M.; Langeveld, J.P.M.; Bassett, H.; O'Donoghue, A.M.; Sweeney, T.
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
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.
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
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.
Okada, Hiroyuki; Masujin, Kentaro; Miyazawa, Kohtaro; Iwamaru, Yoshihumi; Imamura, Morikazu; Matsuura, Yuichi; Arai, Shozo; Fukuda, Shigeo; Murayama, Yuichi; Yokoyama, Takashi
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.
Watts, Joel C; Giles, Kurt; Saltzberg, Daniel J; Dugger, Brittany N; Patel, Smita; Oehler, Abby; Bhardwaj, Sumita; Sali, Andrej; Prusiner, Stanley B
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
Sugiura, Katsuaki; Murray, Noel; Shinoda, Naoki; Onodera, Takashi
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.
Fernández-Borges, Natalia; Espinosa, Juan Carlos; Marín-Moreno, Alba; Aguilar-Calvo, Patricia; Asante, Emmanuel A; Kitamoto, Tetsuyuki; Mohri, Shirou; Andréoletti, Olivier; Torres, Juan María
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.
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.
Wunderlin Sabina S
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.
Barron, Rona M; Campbell, Susan L; King, Declan; Bellon, Anne; Chapman, Karen E; Williamson, R Anthony; Manson, Jean C
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.
Vidal, Enric; Fernández-Borges, Natalia; Pintado, Belén; Ordóñez, Montserrat; Márquez, Mercedes; Fondevila, Dolors; Torres, Juan María; Pumarola, Martí; Castilla, Joaquín
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.
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.
Bessen, R A; Raymond, G J; Caughey, B
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.
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
Houston, Fiona; Goldmann, Wilfred; Foster, James; González, Lorenzo; Jeffrey, Martin; Hunter, Nora
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
Houston, Fiona; Goldmann, Wilfred; Foster, James; González, Lorenzo; Jeffrey, Martin; Hunter, Nora
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
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
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
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...
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.
Loiacono, Christina M; Beckwith, Nadine; Kunkle, Robert A; Orcutt, Dennis; Hall, S Mark
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.
Priem, Jan; Langeveld, Jan P M; van Keulen, Lucien J M; van Zijderveld, Fred G; Andreoletti, Olivier; Bossers, Alex
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
Sala, Carole; Morignat, Eric; Ducrot, Christian; Calavas, Didier
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
Iwasaki, Yasushi; Tatsumi, Shinsui; Mimuro, Maya; Kitamoto, Tetsuyuki; Yoshida, Mari
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.
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
Chou, Ming Li; Bailey, Andy; Avory, Tiffany; Tanimoto, Junji; Burnouf, Thierry
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
Murayama, Yuichi; Yoshioka, Miyako; Okada, Hiroyuki; Takata, Eri; Masujin, Kentaro; Iwamaru, Yoshifumi; Shimozaki, Noriko; Yamamura, Tomoaki; Yokoyama, Takashi; Mohri, Shirou; Tsutsumi, Yuji
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
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
... 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 ...
Jaumain, Emilie; Quadrio, Isabelle; Herzog, Laetitia; Reine, Fabienne; Rezaei, Human; Andréoletti, Olivier; Laude, Hubert; Perret-Liaudet, Armand; Haïk, Stéphane; Béringue, Vincent
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.
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.
Sala, Carole; Ru, Giuseppe
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.
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.
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.
Sugiura, Katsuaki; Smith, Gary C
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.
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.
Ritchie, Diane L; Boyle, Aileen; McConnell, Irene; Head, Mark W; Ironside, James W; Bruce, Moira E
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.
... 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 ...
Seman, M; Adjou, K T
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.
Alyahya, Ghassan Ayish Jabur; Heegaard, Steffen; Prause, J.U.
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...
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 ...
Full Text Available A food-poisoning outbreak due to enterohemorrhagic Escherichia coli (EHEC occurred in Toyama, Japan. The case of a 26-year-old pregnant woman with hemolytic–uremic syndrome who developed acute encephalopathy due to EHEC infection after eating raw meat is presented herein. On day 2 following admission, a cesarean section was performed because of a non-reassuring fetal status. Fecal bacterial culture confirmed an O111/O157 superinfection. Intensive care therapies including continuous hemodiafiltration and plasma exchange were performed. After the operation, the patient developed encephalopathy for which steroid pulse therapy was added. Her condition improved gradually and she was discharged 55 days after delivery.
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 ...
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 ...
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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? ...
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 ...
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 ...
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 ...
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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 ...
Montagna, Giacomo; Imperiali, Mauro; Agazzi, Pamela
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...
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)
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.
Weber, W.; Henkes, H.; Kuehne, D.; Moeller, P.; Bade, K.
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.)
Khan, Sonia; Al Baradie, Raidah
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...
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.
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.
...; ] 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...
... 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...
... 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
... 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...
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.
... 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...
, 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.
Balestrini, Simona; Sisodiya, Sanjay M
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 email@example.com.
Stinton, Laura M; Jayakumar, Saumya
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...
Göbel, R; Görtzen, A; Bräunig, P
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.
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.
Platzer, Konrad; Yuan, Hongjie; Schütz, Hannah
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...
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.
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
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
Laura M Stinton
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.
Stinton, Laura M; Jayakumar, Saumya
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.
Yu, Joe Yuezhou; Pearl, Phillip L.
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...
Zhou, J Y; Xu, B; Lopes, J; Blamoun, J; Li, L
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.
Alyahya, Ghassan Ayish Jabur; Ribel-Madsen, S.; Heegaard, S.
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...
Bechah, Yassina; Capo, Christian; Mege, Jean-Louis; Raoult, Didier
Epidemic typhus is transmitted to human beings by the body louse Pediculus humanus corporis. The disease is still considered a major threat by public-health authorities, despite the efficacy of antibiotics, because poor sanitary conditions are conducive to louse proliferation. Until recently, Rickettsia prowazekii, the causal agent, was thought to be confined to human beings and their body lice. Since 1975, R prowazekii infection in human beings has been related to contact with the flying squirrel Glaucomys volans in the USA. Moreover, Brill-Zinsser disease, a relapsed form of epidemic typhus that appears as sporadic cases many years after the initial infection, is unrelated to louse infestation. Stress or a waning immune system are likely to reactivate this earlier persistent infection, which could be the source of new epidemics when conditions facilitate louse infestation. Finally, R prowazekii is a potential category B bioterrorism agent, because it is stable in dried louse faeces and can be transmitted through aerosols. An increased understanding of the pathogenesis of epidemic typhus may be useful for protection against this bacterial threat.
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
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
Lado, Fred A; Rubboli, Guido; Capovilla, Giuseppe; Capovilla, Pippo; Avanzini, Giuliano; Moshé, Solomon L
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.
von Spiczak, Sarah; Helbig, Katherine L; Shinde, Deepali N
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...
Moron E, Fanny E; Diaz Marchan, Pedro
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
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
Amin, Sanjiv B.; Bhutani, Vinod K.; Watchko, Jon F.
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
Paisley, Larry; Hostrup-Pedersen, J.
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...
Yi, Juneyoung; Padalino, David J; Chin, Lawrence S; Montenegro, Philip; Cantu, Robert C
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.
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.
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 ...
Kim, Jin Yong; Lee, Shi Kyung; Han, Chun Hwan; Rho, Eun Jin [Kangnam General Hospital Public Corporation, Seoul (Korea, Republic of)
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.
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, ...
Shandra, Oleksii; Moshé, Solomon L; Galanopoulou, Aristea S
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.
Shandra, Oleksii; Moshé, Solomon L.; Galanopoulou, Aristea S.
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
João Gama Marques
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
Junker, Anders Ellekær; Als-Nielsen, Bodil; Gluud, Christian
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...
... 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. ...
Ingrosso, Loredana; Novoa, Beatriz; Valle, Andrea Z Dalla; Cardone, Franco; Aranguren, Raquel; Sbriccoli, Marco; Bevivino, Simona; Iriti, Marcello; Liu, Quanguo; Vetrugno, Vito; Lu, Mei; Faoro, Franco; Ciappellano, Salvatore; Figueras, Antonio; Pocchiari, Maurizio
Abstract Background Scrapie and bovine spongiform encephalopathy (BSE) belongs to the group of animal transmissible spongiform encephalopathy (TSE). BSE epidemic in the UK and elsewhere in Europe has been linked to the use of bovine meat and bone meals (MBM) in the feeding of cattle. There is concern that pigs, poultry and fish bred for human consumption and fed with infected MBM would eventually develop BSE or carry residual infectivity without disease. Although there has been no evidence of...
Soós, Zsuzsanna; Salamon, Mónika; Oláh, Roland; Czégeni, Anna; Salamon, Ferenc; Folyovich, András; Winkler, Gábor
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.
Ruepp, Sarah Renée; Fagertun, Anna Manolova
This paper presents the implementation of a failure propagation model for transport networks when multiple failures occur resulting in an epidemic. We model the Susceptible Infected Disabled (SID) epidemic model and validate it by comparing it to analytical solutions. Furthermore, we evaluate...... to evaluate multiple epidemic scenarios in various network types....
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.
Sharma, Suvasini; Tripathi, Manjari
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.
Wang Qun; Lu Bingxun; Yuan Huijuan
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
... 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...
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 ...
Felix, JF; Badawi, N; Kurinczuk, JJ; Bower, C; Keogh, JM; Pemberton, PJ
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
Nardone, Raffaele; Taylor, Alexandra C; Höller, Yvonne; Brigo, Francesco; Lochner, Piergiorgio; Trinka, Eugen
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.
Yoon, Hyun Ki; Chang, Kee Hyun; Lee, Goo; Han, Moon Hee; Park, Sung Ho; Na, Duk Yull; Song, Chi Sung
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
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)
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.
Auvin, Stéphane; Cilio, Maria Roberta; Vezzani, Annamaria
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.
Opdenakker, G.; Gelin, G.; Palmers, Y.; Surgeloose, D. de
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.)
... 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, ...
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.
Kotha, V.K.; De Souza, A.
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
Iverson, Grant L
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.
Siniatchkin, Michael; Capovilla, Giuseppe
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.
Martínez-Pérez, R; Paredes, I; Munarriz, P M; Paredes, B; Alén, J F
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.
Stamberger, Hannah; Nikanorova, Marina; Willemsen, Marjolein H.
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....
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.
Saulle, Michael; Greenwald, Brian D
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.
Vigevano, Federico; Arzimanoglou, Alexis; Plouin, Perrine; Specchio, Nicola
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.
... 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 ...
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.
Pijnenburg, MWH; Zweens, MJ; Bink, MTE; Odink, RJ
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.
Als-Nielsen, B; Koretz, R L; Kjaergard, L L
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....
Seeberg, Jens; Christensen, Fie Lund Lindegaard
is skewed in favour of boys, and girls with autism tend to be diagnosed much later than boys. Building and further developing the notion of ‘configuration’ of epidemics, this article explores the configuration of autism in Denmark, with a particular focus on the health system and social support to families...... with children diagnosed with autism, seen from a parental perspective. The article points to diagnostic dynamics that contribute to explaining why girls with autism are not diagnosed as easily as boys. We unfold these dynamics through the analysis of a case of a Danish family with autism.......Autism has been described as an epidemic, but this claim is contested and may point to an awareness epidemic, i.e. changes in the definition of what autism is and more attention being invested in diagnosis leading to a rise in registered cases. The sex ratio of children diagnosed with autism...
Brauer, Fred; Feng, Zhilan; Castillo-Chavez, Carlos
The mathematical theory of single outbreak epidemic models really began with the work of Kermack and Mackendrick about decades ago. This gave a simple answer to the long-standing question of why epidemics woould appear suddenly and then disappear just as suddenly without having infected an entire population. Therefore it seemed natural to expect that theoreticians would immediately proceed to expand this mathematical framework both because the need to handle recurrent single infectious disease outbreaks has always been a priority for public health officials and because theoreticians often try to push the limits of exiting theories. However, the expansion of the theory via the inclusion of refined epidemiological classifications or through the incorporation of categories that are essential for the evaluation of intervention strategies, in the context of ongoing epidemic outbreaks, did not materialize. It was the global threat posed by SARS in that caused theoreticians to expand the Kermack-McKendrick single-outbreak framework. Most recently, efforts to connect theoretical work to data have exploded as attempts to deal with the threat of emergent and re-emergent diseases including the most recent H1N1 influenza pandemic, have marched to the forefront of our global priorities. Since data are collected and/or reported over discrete units of time, developing single outbreak models that fit collected data naturally is relevant. In this note, we introduce a discrete-epidemic framework and highlight, through our analyses, the similarities between single-outbreak comparable classical continuous-time epidemic models and the discrete-time models introduced in this note. The emphasis is on comparisons driven by expressions for the final epidemic size.
Behura, Sushree Sangita; Swain, Sarada Prasanna
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
Boulanger, A S; Paquette, I; Létourneau, G; Richard-Devantoy, S
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.
Mehmet İbrahim Turan
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.
Learn about obesity and the community initiatives taking place to prevent and reduce this epidemic. Created: 7/18/2011 by National Center for Chronic Disease Prevention and Health Promotion, Division of Nutrition, Physical Activity and Obesity. Date Released: 7/18/2011.
The first peak was related to water contamination which began in December 1990. The second peak was related to failure of municipal authorities to chlorinate water during the 2nd week of February 1991. The epidemic came under control quickly after water contamination was controlled, providing confirmation for role of ...
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
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
Caughey, Byron; Kocisko, David
.... 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...
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, ...
R.J. de Knegt (Robert)
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
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 ...
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 ...
Lallas, Matt; Desai, Jay
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.
Zhao Xiang; Ma Jiwei; Wu Lide
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
Spihtle, B J; Fliegner, J; Faed, J A; Hannah, J B; James, B
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.
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) ...
The first well recorded epidemic was in 1955-56 here in Delhi with nearly 30000 cases. Large outbreaks occurred in 1978 in Kashmir. My interest in this disease began in 1991 during investigations into a large epidemic of hepatitis E in Kanpur that my mentor, later Prof SR Naik, and I undertook. I will use this epidemic as an ...
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.
Li, Ying; Davey, Robert A; Sivaramakrishnan, Shobhana; Lynch, William P
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.
Auger, P.; Pouliot, B.; De Grace, M.; Milot, C.; Lafortune, M.; Bergeron, Z.
An outbreak of bacillary dysentery in 1978 affecting 928 persons, most of whom were living in the village of St-Jacques, PQ, is described. An epidemiologic study suggested the water supply as the source of the infection, and it was established that the water carried by the municipal aqueduct was contaminated by feces containing the causal agent, Shigella sonnei. This epidemic, the largest mentioned in he Canadian medical literature, demonstrates how contagious this infection is.
Srivastava, Siddharth; Sahin, Mustafa
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
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.
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
Capovilla, Giuseppe; Moshé, Solomon L; Wolf, Peter; Avanzini, Giuliano
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.
li A. Raouf; Gianluca Tamagno
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. ...
Morgan, Marsha Y; Amodio, Piero; Cook, Nicola A
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....
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.
Hughes, Adrienne; Brown, Alisha; Valento, Matthew
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.
Palacios-Marqués, Ana; Delgado-García, Silvia; Martín-Bayón, Tina; Martínez-Escoriza, Juan Carlos
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
Bagci, S; Zschocke, J; Hoffmann, G F; Bast, T; Klepper, J; Müller, A; Heep, A; Bartmann, P; Franz, A R
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...
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
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.
Ernest Marshall Graham
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.
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.
... 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 ...
Pera, Maria Carmela; Randazzo, Giovanna; Masnada, Silvia; Dontin, Serena Donetti; De Giorgis, Valentina; Balottin, Umberto; Veggiotti, Pierangelo
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.
Vos, de C.J.; Heres, L.
The total ban on use of meat and bone meal (MBM) in livestock feed has been very successful in reducing bovine spongiform encephalopathy (BSE) spread, but also implies a waste of high-quality proteins resulting in economic and ecological loss. Now that the BSE epidemic is fading out, a partial
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
Piao, Yue-Shan; Kakita, Akiyoshi; Watanabe, Hiroyuki; Kitamoto, Tetsuyuki; Takahashi, Hitoshi
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.
Notes: We compiled this slide in 1992. It shows dates, locations and number of cases for various epidemics reported from different parts of India till that time. The first well recorded epidemic was in 1955-56 here in Delhi with nearly 30000 cases. Large outbreaks occurred in 1978 in Kashmir. My interest in this disease began ...
Shi Zhu; Pan Suyue; Zhou Liang; Dong Zhao; Lu Bingxun
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)
Yamazaki, Shinya; Ito, Hiroshi; Kawaai, Hiroyoshi
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.
Curatolo, Paolo; Aronica, Eleonora; Jansen, Anna; Jansen, Floor; Kotulska, Katarzyna; Lagae, Lieven; Moavero, Romina; Jozwiak, Sergiusz
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.
Schwensen, Jakob F; Uter, Wolfgang; Bruze, Magnus
BACKGROUND: The use of methylisothiazolinone (MI) in cosmetic products has caused an unprecedented epidemic of MI contact allergy. Current data concerning exposures at a European level are required. OBJECTIVES: To describe demographics and MI exposures for European patients with MI contact allergy....... METHODS: Eleven European dermatology departments from eight European countries prospectively collected data between 1 May and 31 October 2015 among consecutive patients who had positive patch test reactions to MI (2000 ppm aq.). RESULTS: A total of 6.0% (205/3434; range 2.6-13.0%) of patients had positive...... patch test reactions to MI. Dermatitis most frequently affected the hands (43.4%), face (32.7%), arms (14.6%), and eyelids (11.7%); 12.7% had widespread dermatitis. For 72.7% (149/205), MI contact allergy was currently relevant mainly because of exposure to cosmetic products (83.2%; 124...
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 ...
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 ...
Ben Achour, N; Benrhouma, H; Rouissi, A; Touaiti, H; Kraoua, I; Turki, I; Gouider-Khouja, N
Rubella is a mild viral illness in children. Rubella encephalitis is an extremely uncommon complication of rubella affecting unvaccinated children, aged between 5 and 14 years. From May to June 2011, we observed 9 cases of rubella encephalitis diagnosed during an epidemic of rubella. All were previously healthy (8 boys and 1 girl). None of them had received rubella vaccine. The mean age was 11.6 years. The onset of neurological symptoms occurred within 1-5 days after the typical rush and was associated with seizures and altered consciousness in all cases. The presence of serum immunoglobulin M antibody against rubella virus was demonstrated in all patients. EEGs showed slow wave activity in all patients and brain MRI was normal in the 9 cases. Full recovery was obtained in all patients. However, 4 of them required intensive care unit referral. Acute encephalitis is an extremely rare complication of rubella. The main neurological findings are headache, ataxia, and hemiplegia. Epileptic seizure and altered consciousness are rarely observed. Rubella encephalitis is generally self-limiting with about 80% recovery rate with no sequelae. However, severe courses have been reported. These cases illustrated the potential severity of rubella and they should be prevented by encouraging widespread early childhood vaccination. In Tunisia, rubella encephalitis has been reported once previously and vaccination against rubella virus has only recently been included in the national vaccination program, prescribed only for adolescent females. Following this rubella epidemic, vaccination strategies in Tunisia have been revised. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
V. A. Tumanskiy
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 . 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 . 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 , 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 . 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 . 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
M. Ghaffar Pour
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.
Amlan Kanti Biswas
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.
Aaen, Anne Albers; Jeppesen, Jørgen; Obaid, Hayder
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...
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.
Dalal, Rohan; McGee, Richard G; Riordan, Stephen M; Webster, Angela C
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
Sharma, Barjesh Chander; Singh, Jatinderpal
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.
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
Maki, Yoshimitsu; Takashima, Hiroshi
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.
Stawicka, Agnieszka; Zbrzeźniak, Justyna; Świderska, Aleksandra; Kilisińska, Natalia; Świderska, Magdalena; Jaroszewicz, Jerzy; Flisiak, Robert
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.
Oliver, Karen L; Lukic, Vesna; Thorne, Natalie P; Berkovic, Samuel F; Scheffer, Ingrid E; Bahlo, Melanie
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.
Roy, Manojit; Zinck, Richard D.; Bouma, Menno J.; Pascual, Mercedes
Cholera is on the rise globally, especially epidemic cholera which is characterized by intermittent and unpredictable outbreaks that punctuate periods of regional disease fade-out. These epidemic dynamics remain however poorly understood. Here we examine records for epidemic cholera over both contemporary and historical timelines, from Africa (1990-2006) and former British India (1882-1939). We find that the frequency distribution of outbreak size is fat-tailed, scaling approximately as a power-law. This pattern which shows strong parallels with wildfires is incompatible with existing cholera models developed for endemic regions, as it implies a fundamental role for stochastic transmission and local depletion of susceptible hosts. Application of a recently developed forest-fire model indicates that epidemic cholera dynamics are located above a critical phase transition and propagate in similar ways to aggressive wildfires. These findings have implications for the effectiveness of control measures and the mechanisms that ultimately limit the size of outbreaks.
Lauridsen, M M; Schaffalitzky de Muckadell, O B; Vilstrup, H
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...
Cash, W J
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.
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%.
Ishida, Shigenobu; Yasukawa, Kumi; Koizumi, Mai; Abe, Katsuhiro; Hirai, Nozomi; Honda, Takafumi; Sakuma, Hiroshi; Tada, Hiroko; Takanashi, Jun-Ichi
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.
Papetti, Laura; Garone, Giacomo; Schettini, Livia; Giordano, Carla; Nicita, Francesco; Papoff, Paola; Zeviani, Massimo; Leuzzi, Vincenzo; Spalice, Alberto
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.
Capovilla, Giuseppe; Wolf, Peter; Beccaria, Francesca; Avanzini, Giuliano
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.
Riley, David O; Robbins, Clifford A; Cantu, Robert C; Stern, Robert A
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.
Gjedde, Albert; Keiding, Susanne; Vilstrup, Hendrik
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....
Wicklund, Meredith R; Knopman, David S
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.
Lough, Mary E
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.
McGhee, A.S.; Kassouny, M.E.; Matthews, D.E.; Millikan, W.
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
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
Tavasoli, Ali Reza; Rostami, Parastoo; Ashrafi, Mahmoud Reza; Karimzadeh, Parvaneh
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.
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.
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.
M Ghaffar Pour
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.
Eckman, Elizabeth A; Pacheco-Quinto, Javier; Herdt, Aimee R; Halperin, John J
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: firstname.lastname@example.org.
Kimer, Nina; Krag, Aleksander; Gluud, Lise L
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...
Zheng Wenlong; Wu Aiqin; Xu Chongyong; Ying Binyu; Hong Ruizhen
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
Møller, Rikke S.; Larsen, Line H.G.; Johannesen, Katrine M.
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...
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
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.
Boby Varkey Maramattom
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.  We present the first case of adult onset ARD presenting with encephalopathy and diffusion weighted MRI findings that resembled a moustache in the midbrain.
Radwan, H.; Braun, H.; Kott, E.; Bar-Sela, S.
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.
E. D. Belousova
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...
Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo
-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...
Pastor-Satorras, Romualdo; Castellano, Claudio; Van Mieghem, Piet; Vespignani, Alessandro
In recent years the research community has accumulated overwhelming evidence for the emergence of complex and heterogeneous connectivity patterns in a wide range of biological and sociotechnical systems. The complex properties of real-world networks have a profound impact on the behavior of equilibrium and nonequilibrium phenomena occurring in various systems, and the study of epidemic spreading is central to our understanding of the unfolding of dynamical processes in complex networks. The theoretical analysis of epidemic spreading in heterogeneous networks requires the development of novel analytical frameworks, and it has produced results of conceptual and practical relevance. A coherent and comprehensive review of the vast research activity concerning epidemic processes is presented, detailing the successful theoretical approaches as well as making their limits and assumptions clear. Physicists, mathematicians, epidemiologists, computer, and social scientists share a common interest in studying epidemic spreading and rely on similar models for the description of the diffusion of pathogens, knowledge, and innovation. For this reason, while focusing on the main results and the paradigmatic models in infectious disease modeling, the major results concerning generalized social contagion processes are also presented. Finally, the research activity at the forefront in the study of epidemic spreading in coevolving, coupled, and time-varying networks is reported.
We study a susceptible-infected-susceptible epidemic process over a static contact network where the nodes have partial information about the epidemic state. They react by limiting their interactions with their neighbors when they believe the epidemic is currently prevalent. A node\\'s awareness is weighted by the fraction of infected neighbors in their social network, and a global broadcast of the fraction of infected nodes in the entire network. The dynamics of the benchmark (no awareness) and awareness models are described by discrete-time Markov chains, from which mean-field approximations (MFAs) are derived. The states of the MFA are interpreted as the nodes\\' probabilities of being infected. We show a sufficient condition for the existence of a
Azaele, Sandro; Maritan, Amos; Bertuzzo, Enrico; Rodriguez-Iturbe, Ignacio; Rinaldo, Andrea
We describe the predictions of an analytically tractable stochastic model for cholera epidemics following a single initial outbreak. The exact model relies on a set of assumptions that may restrict the generality of the approach and yet provides a realm of powerful tools and results. Without resorting to the depletion of susceptible individuals, as usually assumed in deterministic susceptible-infected-recovered models, we show that a simple stochastic equation for the number of ill individuals provides a mechanism for the decay of the epidemics occurring on the typical time scale of seasonality. The model is shown to provide a reasonably accurate description of the empirical data of the 2000/2001 cholera epidemic which took place in the Kwa Zulu-Natal Province, South Africa, with possibly notable epidemiological implications.
Jutla, Antarpreet; Whitcombe, Elizabeth; Hasan, Nur; Haley, Bradd; Akanda, Ali; Huq, Anwar; Alam, Munir; Sack, R. Bradley; Colwell, Rita
Cholera outbreak following the earthquake of 2010 in Haiti has reaffirmed that the disease is a major public health threat. Vibrio cholerae is autochthonous to aquatic environment, hence, it cannot be eradicated but hydroclimatology-based prediction and prevention is an achievable goal. Using data from the 1800s, we describe uniqueness in seasonality and mechanism of occurrence of cholera in the epidemic regions of Asia and Latin America. Epidemic regions are located near regional rivers and are characterized by sporadic outbreaks, which are likely to be initiated during episodes of prevailing warm air temperature with low river flows, creating favorable environmental conditions for growth of cholera bacteria. Heavy rainfall, through inundation or breakdown of sanitary infrastructure, accelerates interaction between contaminated water and human activities, resulting in an epidemic. This causal mechanism is markedly different from endemic cholera where tidal intrusion of seawater carrying bacteria from estuary to inland regions, results in outbreaks. PMID:23897993
Ben-Naim, E.; Krapivsky, P. L.
We study the classic Susceptible-Infected-Recovered (SIR) model for the spread of an infectious disease. In this stochastic process, there are two competing mechanism: infection and recovery. Susceptible individuals may contract the disease from infected individuals, while infected ones recover from the disease at a constant rate and are never infected again. Our focus is the behavior at the epidemic threshold where the rates of the infection and recovery processes balance. In the infinite population limit, we establish analytically scaling rules for the time-dependent distribution functions that characterize the sizes of the infected and the recovered sub-populations. Using heuristic arguments, we also obtain scaling laws for the size and duration of the epidemic outbreaks as a function of the total population. We perform numerical simulations to verify the scaling predictions and discuss the consequences of these scaling laws for near-threshold epidemic outbreaks.
Mitchell, Nia; Catenacci, Vicki; Wyatt, Holly R.; Hill, James O.
Despite growing recognition of the problem, the obesity epidemic continues in the U.S., and obesity rates are increasing around the world. The latest estimates are that approximately 34% of adults and 15–20% of children and adolescents in the U.S. are obese. Obesity affects every segment of the U.S. population. Obesity increases the risk of many chronic diseases in children and adults. The epidemic of obesity arose gradually over time, apparently from a small, consistent degree of positive en...
Wetzel, Eunike; Brown, Anna; Hill, Patrick; Chung, J.M.H.; Robins, R.W.; Roberts, B.W.
Are recent cohorts of college students more narcissistic than their predecessors? To address debates about the so-called “narcissism epidemic,” we used data from three cohorts of students (N1990s = 1,166; N2000s = 33,647; N2010s = 25,412) to test whether narcissism levels (overall and specific
Aug 26, 2014 ... Method: 'Know your epidemic' synthesis suggests that HIV prevalence is rising in older age groups and falling in younger people. Using secondary data analyses of population-based and antenatal care surveillance (ANC) surveys, we explored trends and patterns in HIV prevalence in KwaZulu-Natal and ...
Schneider, D A; Harrington, R D; Zhuang, D; Yan, H; Truscott, T C; Dassanayake, R P; O'Rourke, K I
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
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
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.
Lefèvre, Claude; Picard, Philippe
This collection of papers gives a representative cross-selectional view of recent developments in the field. After a survey paper by C. Lefèvre, 17 other research papers look at stochastic modeling of epidemics, both from a theoretical and a statistical point of view. Some look more specifically at a particular disease such as AIDS, malaria, schistosomiasis and diabetes.
Schiøler, Henrik; Nielsen, Jens Frederik Dalsgaard; Ngo, Trung Dung
Clock synchronization in swarms of networked mobile robots is studied in a probabilistic, epidemic framework. In this setting communication and synchonization is considered to be a randomized process, taking place at unplanned instants of geographical rendezvous between robots. In combination...... as an infinite-dimensional optimal controlproblem. Illustrative numerical examples are given and commented....
Courtwright, David T.
Discusses the wave of cocaine abuse that followed the drug's recommendation by the late nineteenth-century medical community as a cure all. Details drug addiction among ethnic and social groups at the turn of the century. Warns that drug epidemics have important social and legal consequences. Suggests legal pressure may alter the form of drug…
Maria Carmela Tartaglia
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.
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
li A. Raouf
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.
Jung, Young-Chul; Chanraud, Sandra; Sullivan, Edith V
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.
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.
... About the Epidemic Help, Resources and Information National Opioids Crisis Search Search National Helpline SAMHSA’s National Helpline ... 1-800-662-4357 Visit Helpline Website THE OPIOID EPIDEMIC IN NUMBERS 80% Nearly 80% of heroin ...
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
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.
... 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 ...
Wong-Kisiel, Lily C.; Nickels, Katherine
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.
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.
Ni Ling; Zhang Longjiang; Lu Guangming
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)
E. D. Belousova
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.
Mohamed Adnane Berdai
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.
Byung Ju Kang
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.
Pagnan, L.; Pozzi-Mucelli, R.S.; Berlot, G.
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.)
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
Pera, Maria Carmela; Randazzo, Giovanna; Masnada, Silvia; Dontin, Serena Donetti; De Giorgis, Valentina; Balottin, Umberto; Veggiotti, Pierangelo
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.
Kapina, Viktoria; Vargas, Maria-Isabel; Wohlrab, Gabriele; Vulliemoz, Serge; Fluss, Joel; Seeck, Margitta
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.
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
Weidauer, Stefan; Lanfermann, Heinrich; Zanella, Friedhelm E.; Nichtweiss, Michael
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
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
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.
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
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.
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
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
Hernández, D. G.; Risau-Gusman, S.
It is well known that sexually transmitted diseases (STD) spread across a network of human sexual contacts. This network is most often bipartite, as most STD are transmitted between men and women. Even though network models in epidemiology have quite a long history now, there are few general results about bipartite networks. One of them is the simple dependence, predicted using the mean field approximation, between the epidemic threshold and the average and variance of the degree distribution of the network. Here we show that going beyond this approximation can lead to qualitatively different results that are supported by numerical simulations. One of the new features, that can be relevant for applications, is the existence of a critical value for the infectivity of each population, below which no epidemics can arise, regardless of the value of the infectivity of the other population.
Zhao, Dawei; Li, Lixiang; Peng, Haipeng; Luo, Qun; Yang, Yixian
This letter investigates the multiple routes transmitted epidemic process on multiplex networks. We propose detailed theoretical analysis that allows us to accurately calculate the epidemic threshold and outbreak size. It is found that the epidemic can spread across the multiplex network even if all the network layers are well below their respective epidemic thresholds. Strong positive degree–degree correlation of nodes in multiplex network could lead to a much lower epidemic threshold and a relatively smaller outbreak size. However, the average similarity of neighbors from different layers of nodes has no obvious effect on the epidemic threshold and outbreak size. -- Highlights: •We studies multiple routes transmitted epidemic process on multiplex networks. •SIR model and bond percolation theory are used to analyze the epidemic processes. •We derive equations to accurately calculate the epidemic threshold and outbreak size. •ASN has no effect on the epidemic threshold and outbreak size. •Strong positive DDC leads to a lower epidemic threshold and a smaller outbreak size.
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
Lenz, V; Vargas, M I; Bin, J F; Bogorin, A; Grebici-Guessoum, M; Jacques, C; Marin, H; Zöllner, G; Dietemann, J L
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.
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
Full Text Available The contact structure between hosts shapes disease spread. Most network-based models used in epidemiology tend to ignore heterogeneity in the weighting of contacts between two individuals. However, this assumption is known to be at odds with the data for many networks (e.g. sexual contact networks and to have a critical influence on epidemics' behavior. One of the reasons why models usually ignore heterogeneity in transmission is that we currently lack tools to analyze weighted networks, such that most studies rely on numerical simulations. Here, we present a novel framework to estimate key epidemiological variables, such as the rate of early epidemic expansion (r0 and the basic reproductive ratio (R0, from joint probability distributions of number of partners (contacts and number of interaction events through which contacts are weighted. These distributions are much easier to infer than the exact shape of the network, which makes the approach widely applicable. The framework also allows for a derivation of the full time course of epidemic prevalence and contact behaviour, which we validate with numerical simulations on networks. Overall, incorporating more realistic contact networks into epidemiological models can improve our understanding of the emergence and spread of infectious diseases.
Barrais, Robert; Faucher, Benoît; Haus, Rachel; Piarroux, Martine; Gaudart, Jean; Magloire, Roc; Raoult, Didier
After onset of a cholera epidemic in Haiti in mid-October 2010, a team of researchers from France and Haiti implemented field investigations and built a database of daily cases to facilitate identification of communes most affected. Several models were used to identify spatiotemporal clusters, assess relative risk associated with the epidemic’s spread, and investigate causes of its rapid expansion in Artibonite Department. Spatiotemporal analyses highlighted 5 significant clusters (p<0.001): 1 near Mirebalais (October 16–19) next to a United Nations camp with deficient sanitation, 1 along the Artibonite River (October 20–28), and 3 caused by the centrifugal epidemic spread during November. The regression model indicated that cholera more severely affected communes in the coastal plain (risk ratio 4.91) along the Artibonite River downstream of Mirebalais (risk ratio 4.60). Our findings strongly suggest that contamination of the Artibonite and 1 of its tributaries downstream from a military camp triggered the epidemic. PMID:21762567
Pena, J A; González-Ferrer, S; Martínez, C; Prieto-Carrasquero, M; Delgado, W; Mora La Cruz, E
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.
Rojek, Amanda M; Horby, Peter W
Emerging and epidemic infectious disease outbreaks are a significant public health problem and global health security threat. As an outbreak begins, epidemiological investigations and traditional public health responses are generally mounted very quickly. However, patient-centred research is usually not prioritised when planning and enacting the response. Instead, the clinical research response occurs subsequent to and separate from the public health response, and is inadequate for evidence-based decision-making at the bedside or in the offices of public health policymakers. The deficiencies of the clinical research response to severe acute respiratory syndrome, pandemic influenza, Middle East respiratory syndrome coronavirus and Ebola virus demonstrate that current research models do not adequately inform and improve the quality of clinical care or public health response. Three suggestions for improvements are made. First, integrate the data and sample collection needs for clinical and public health decision-making within a unified framework, combined with a risk-based, rather than a discipline-based, approach to ethical review and consent. Second, develop clinical study methods and tools that are specifically designed to meet the epidemiological and contextual challenges of emerging and epidemic infectious diseases. Third, invest in investigator-led clinical research networks that are primed and incentivised to respond to outbreak infections, and which can call on the support and resources of a central centre of excellence. It is crucial that the field of epidemic science matures to place patients at the heart of the response. This can only be achieved when patient-centred research is integrated in the outbreak response from day one and practical steps are taken to reduce the barriers to the generation of reliable and useful evidence.
Kim, Ja Young; Yu, In Kyu [Dept. of Radiology, Eulji University Hospital, Daejeon (Korea, Republic of)
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.
Sushree Sangita Behura
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
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 ...
Yoshinari, Satoshi; Hamano, Shinichiro
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.)
Silveira, Rita C; Procianoy, Renato S
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.
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 ...
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.
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),.
Oudman, Erik; Van der Stigchel, Stefan; Postma, Albert; Wijnia, Jan W.; Nijboer, Tanja C W
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
Wedisinghe, Lilantha; Jayakody, Kaushadh; Arambage, Kirana
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.
J Gordon Millichap
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.
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.
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 ...
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.
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
van Valen, Evelien; Wekking, Ellie; Van der Laan, Gert; Sprangers, Mirjam; van Dijk, Frank
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
Esmat, Serag; Garem, Nouman El; Raslan, Hassan; Elfekki, Mohamed; Sleem, Gihan A
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.
Sutamnartpong, Panee; Muengtaweepongsa, Sombat; Kulkantrakorn, Kongkiat
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
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
Chamuleau, R. A.; Schoemaker, L. P.; Smit, E. M.
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
Hijaz, Nadia M; Bracken, Julia M; Chandratre, Sonal R
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.
Novy, Jan; Catarino, Claudia B; Chinthapalli, Krishna; Smith, Shelagh M; Clayton-Smith, Jill; Hennekam, Raoul C M; Hammond, Peter; Sisodiya, Sanjay M
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.
Als-Nielsen, B; Kjaergard, L L; Gluud, C
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...
Maljevic, Snezana; Reid, Christopher A; Petrou, Steven
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.
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.
Novy, Jan; Catarino, Claudia B.; Chinthapalli, Krishna; Smith, Shelagh M.; Clayton-Smith, Jill; Hennekam, Raoul C. M.; Hammond, Peter; Sisodiya, Sanjay M.
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
Tan, Rhea Yan Ying; Markus, Hugh Stephen
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
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
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
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
Jonsson, Maria; Ågren, Johan; Nordén-Lindeberg, Solveig; Ohlin, Andreas; Hanson, Ulf
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.
Dávalos Moscol, Milagros; Bustios Sanchez, Carla
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.
Bodó, Ágnes; Katona, Gyula Y; Simon, Péter L
Mathematical modelling of epidemic propagation on networks is extended to hypergraphs in order to account for both the community structure and the nonlinear dependence of the infection pressure on the number of infected neighbours. The exact master equations of the propagation process are derived for an arbitrary hypergraph given by its incidence matrix. Based on these, moment closure approximation and mean-field models are introduced and compared to individual-based stochastic simulations. The simulation algorithm, developed for networks, is extended to hypergraphs. The effects of hypergraph structure and the model parameters are investigated via individual-based simulation results.
Thyssen, Jacob Pontoppidan; Johansen, Jeanne Duus; Menné, Torkil
Contact dermatitis can be severe and lead to sick leave as well as significant healthcare expenses. The aim of this review is to present the published knowledge on 6 historical epidemics of contact allergy to apply this knowledge on the prevention and control of future contact allergy epidemics...... to prevent contact allergy epidemics. It is essential that dermatologist, scientists, administrators, and consumers organize and structure known methods to accelerate the control of emerging contact allergens....
Kalser, Judith; Cross, J Helen
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.
Manzano, Marc; Calle, Eusebi; Ripoll, Jordi
in telecommunication networks has not been extensively considered, nowadays, with the increasing computation capacity and complexity of operating systems of modern network devices (routers, switches, etc.), the study of possible epidemic-like failure scenarios must be taken into account. When epidemics occur......, such as in other multiple failure scenarios, identifying the level of vulnerability offered by a network is one of the main challenges. In this paper, we present epidemic survivability, a new network measure that describes the vulnerability of each node of a network under a specific epidemic intensity. Moreover......, this metric is able to identify the set of nodes which are more vulnerable under an epidemic attack. In addition, two applications of epidemic survivability are provided. First, we introduce epidemic criticality, a novel robustness metric for epidemic failure scenarios. A case study shows the utility...
Manzano, Marc; Calle, Eusebi; Ripoll, Jordi
Epidemics theory has been used in different contexts in order to describe the propagation of diseases, human interactions or natural phenomena. In computer science, virus spreading has been also characterized using epidemic models. Although in the past the use of epidemic models in telecommunicat......Epidemics theory has been used in different contexts in order to describe the propagation of diseases, human interactions or natural phenomena. In computer science, virus spreading has been also characterized using epidemic models. Although in the past the use of epidemic models...... in telecommunication networks has not been extensively considered, nowadays, with the increasing computation capacity and complexity of operating systems of modern network devices (routers, switches, etc.), the study of possible epidemic-like failure scenarios must be taken into account. When epidemics occur...
Dong, Chao; Yin, Qiuju; Liu, Wenyang; Yan, Zhijun; Shi, Tianyu
Relation existed in the social contact network can affect individuals' behaviors greatly. Considering the diversity of relation intimacy among network nodes, an epidemic propagation model is proposed by incorporating the link-breaking threshold, which is normally neglected in the rewiring strategy. The impact of rewiring strategy on the epidemic spreading in the weighted adaptive network is explored. The results show that the rewiring strategy cannot always control the epidemic prevalence, especially when the link-breaking threshold is low. Meanwhile, as well as strong links, weak links also play a significant role on epidemic spreading.
Bathla, G.; Hegde, A.N.
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
Full Text Available Influenza-associated encephalopathy (IAE is a serious complication of influenza and is reported most frequently in Japan. This paper presents an assessment of the epidemiological characteristics of influenza A (H1N1 2009-associated encephalopathy in comparison to seasonal IAE, based on Japanese national surveillance data of influenza-like illness (ILI and IAE during flu seasons from 2004-2005 through 2009-2010. In each season before the pandemic, 34-55 IAE cases (mean 47.8; 95% confidence interval: 36.1-59.4 were reported, and these cases increased drastically to 331 during the 2009 pandemic (6.9-fold the previous seasons. Of the 331 IAE cases, 322 cases were reported as influenza A (H1N1 2009-associated encephalopathy. The peaks of IAE were consistent with the peaks of the influenza epidemics and pandemics. A total of 570 cases of IAE (seasonal A, 170; seasonal B, 50; influenza A (H1N1 2009, 322; unknown, 28 were reported over six seasons. The case fatality rate (CFR ranged from 4.8 to 18.2% before the pandemic seasons and 3.6% in the 2009 pandemic season. The CFR of pandemic-IAE was 3.7%, which is lower than that of influenza A-/B-associated encephalopathy (12.9%, p<0.001; 14.0%, p = 0.002; respectively. The median age of IAE was 7 years during the pandemic, which is higher than that of influenza A-/B-associated encephalopathy (4, p<0.001; 4.5, p = 0.006; respectively. However, the number of pandemic-IAE cases per estimated ILI outpatients peaked in the 0-4-year age group and data both before and during the pandemic season showed a U-shape pattern. This suggests that the high incidence of influenza infection in the 0-4 year age group may lead to a high incidence of IAE in the same age group in a future influenza season. Further studies should include epidemiologic case definitions and clinical details of IAE to gain a more accurate understanding of the epidemiologic status of IAE.
This paper aims to study corruption as an epidemic phenomenon using the epidemic diffusion model of Kermack and Mc-Kendrick (1927). We seek to determine the dynamics of corruption and its impact on the composition of the population at a given time. We determine a threshold epidemiological corruption based on the approximation of the honest population.
Ruepp, Sarah Renée; Katsikas, Dimitrios; Fagertun, Anna Manolova
This paper presents a failure propagation model for transport networks which are affected by epidemic failures. The network is controlled using the GMPLS protocol suite. The Susceptible Infected Disabled (SID) epidemic model is investigated and new signaling functionality of GMPLS to support...
Mokrani, K; Fournier, P E; Dalichaouche, M; Tebbal, S; Aouati, A; Raoult, D
We report a case of epidemic typhus in a patient from the Batna region of Algeria, who presented with generalized febrile exanthema. The clinical diagnosis was confirmed by serological cross-adsorption followed by Western blotting. Our report emphasizes the threat of epidemic typhus in the highlands of Algeria.
Yu, Hee Joon; Lee, Jeehun; Seo, Dae Won; Lee, Munhyang
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.
Houston, F.; McCutcheon, S.; Goldmann, W.; Chong, A.; Foster, J.; Siso, S.; Gonzalez, L.; Jeffrey, M.; Hunter, N.
The emergence of variant Creutzfeld-Jakob disease, following on from the bovine spongiform encephalopathy (BSE) epidemic, led to concerns about the potential risk of iatrogenic transmission of disease by blood transfusion and the introduction of costly control measures to protect blood supplies. We previously reported preliminary data demonstrating the transmission of BSE and natural scrapie by blood transfusion in sheep. The final results of this experiment, reported here, give unexpectedly ...
Peter, McDonald AM
Since the end of the cold war the world economy has become dominated by Western [largely US] interests. In this period there have developed several pandemics or epidemics of infectious diseases that have affected most nations. HIV, SARS, Avian Influenza, Hepatitis-C, Bovine Spongiform Encephalopathy, drug-resistant TB, viral zoonoses, are specific examples that will be discussed in terms of their genesis, economic impact and consequences for ways of life in the range of economies – developed,...
Visscher, T L S; Heitmann, B L; Rissanen, A
epidemic. However, follow-ups of short duration may, in part, explain the apparent break or decrease in the obesity epidemic. On the other hand, a single focus on body mass index (BMI) ⩾25 or ⩾30 kg m(-)(2) is likely to mask a real increase in the obesity epidemic. And, in both children and adults, trends......Recent epidemiologic papers are presenting prevalence data suggesting breaks and decreases in obesity rates. However, before concluding that the obesity epidemic is not increasing anymore, the validity of the presented data should be discussed more thoroughly. We had a closer look...... into the literature presented in recent reviews to address the major potential biases and distortions, and to develop insights about how to interpret the presented suggestions for a potential break in the obesity epidemic. Decreasing participation rates, the use of reported rather than measured data and small sample...
Smilović, V; Vrbanec-Megla, L; Payerl-Pal, M; Puntarić, D; Baklaić, Z
Two closely related boys from the same house hold (Home 1), aged two and three, were affected with fulminant meningococcal sepsis known as Waterhouse-Friderichsen syndrome. Neisseria meningitidis serogorup B was isolated from their blood and cerebrospinal fluid. The two-year-old boy died one day after the onset of the disease. Epidemiological examination of contacts and pharyngeal swabs were performed in 14 persons from the household, all of them relatives of the affected children, as well as in a number of other contacts. Chemoprophylaxis with cotrimoxazole was simultaneously administered to all contacts. Family histories revealed that two contacts from the household where the patients did not live (Home 2) were inadvertently omitted. Subsequent examinations, following a report of another contagious disease (salmonelosis), revealed that these two persons were Neisseria meningitidis carriers, together with another one in the same household. The carriers most probably caused the infection of a third, five-year-old boy, the deceased boy's brother (Home 1) who also developed fulminant meningococcal sepsis. The failure to take the appropriate prophylaxis led to a prolonged carrier state in the carrier from the second household. Repeated pharyngeal swab sampling revealed two more carriers from both households that had previously been negative. Control of the epidemic was achieved after 5 weeks by repeated and controlled chemoprophylaxis with ciprofloxacin, and by repeated epidemiological examinations, disinfection, and daily health surveillance by the Sanitary Inspectorate. This extremely rare instance of a familial epidemic with three infected persons emphasizes the need for consistent chemoprophylaxis in meningococcal disease contacts.
Vega, Tomás; Lozano, Jose Eugenio; Meerhoff, Tamara; Snacken, René; Mott, Joshua; Ortiz de Lejarazu, Raul; Nunes, Baltazar
Please cite this paper as: Vega et al. (2012) Influenza surveillance in Europe: establishing epidemic thresholds by the moving epidemic method. Influenza and Other Respiratory Viruses 7(4), 546–558. Background Timely influenza surveillance is important to monitor influenza epidemics. Objectives (i) To calculate the epidemic threshold for influenza‐like illness (ILI) and acute respiratory infections (ARI) in 19 countries, as well as the thresholds for different levels of intensity. (ii) To evaluate the performance of these thresholds. Methods The moving epidemic method (MEM) has been developed to determine the baseline influenza activity and an epidemic threshold. False alerts, detection lags and timeliness of the detection of epidemics were calculated. The performance was evaluated using a cross‐validation procedure. Results The overall sensitivity of the MEM threshold was 71·8% and the specificity was 95·5%. The median of the timeliness was 1 week (range: 0–4·5). Conclusions The method produced a robust and specific signal to detect influenza epidemics. The good balance between the sensitivity and specificity of the epidemic threshold to detect seasonal epidemics and avoid false alerts has advantages for public health purposes. This method may serve as standard to define the start of the annual influenza epidemic in countries in Europe. PMID:22897919
Pillitteri, C A; Craig, L E
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.
Kumar, Amandeep; Suri, Ashish; Sharma, Bhawani S
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.
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.
Meier, P J; Bansky, G
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.
Guerit, Jean-Michel; Amantini, Aldo; Fischer, Catherine; Kaplan, Peter W; Mecarelli, Oriano; Schnitzler, Alfons; Ubiali, Emilio; Amodio, Piero
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.
Landais, A; Saint-Georges, G
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.
Giugale, Lauren E; Young, Omar M; Streitman, David C
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.
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.
Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo
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...
Malik, Saleem I; Galliani, Carlos A; Hernandez, Angel W; Donahue, David J
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.
Yin-Hsuan Chien; Ming-I. Lin; Wen-Chin Weng; Jung-Chieh Du; Wang-Tso Lee
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...
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.
Anand, Anil C.; Garg, Hitendra K.
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
Tortora, Fabio; Caranci, Ferdinando; Belfiore, Maria Paola; Manzi, Francesca; Pagliano, Pasquale; Cirillo, Sossio
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.
Kumar, Sunil; Abhayambika, Archana; Sundaram, Arun N E; Sharpe, James A
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.
Lakhan, Shaheen E; Kirchgessner, Annette
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...
Robert P. Zemple
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.
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
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.
Basavaraj F Banakar
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.
Qureshi, M.O.; Khokhar, N.; Shafqat, F.
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)
Cho, Jae Min; Il, Yim Byung; Kim, Ok Hwa; Kang, Doo Kyoung; Suh, Jung Ho
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
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.
Gamal, Maha; Abdel Wahab, Zainab; Eshra, Mohamed; Rashed, Laila; Sharawy, Nivin
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
Simbruner, Georg; Mittal, Rashmi A; Rohlmann, Friederike
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....
Ville, Dorothée; Chiron, Catherine; Laschet, Jacques; Dulac, Olivier
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.
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.
Hassanein, T.; Blei, A.T.; Perry, W.
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...
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.
Ehm, Gwanhee; Kim, Han-Joon; Jeon, Beomseok
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.
Zhang, Zhaoyang; Wang, Honggang; Wang, Chonggang; Fang, Hua
Social contact networks and the way people interact with each other are the key factors that impact on epidemics spreading. However, it is challenging to model the behavior of epidemics based on social contact networks due to their high dynamics. Traditional models such as susceptible-infected-recovered (SIR) model ignore the crowding or protection effect and thus has some unrealistic assumption. In this paper, we consider the crowding or protection effect and develop a novel model called improved SIR model. Then, we use both deterministic and stochastic models to characterize the dynamics of epidemics on social contact networks. The results from both simulations and real data set conclude that the epidemics are more likely to outbreak on social contact networks with higher average degree. We also present some potential immunization strategies, such as random set immunization, dominating set immunization, and high degree set immunization to further prove the conclusion.
Seeberg, Jens; Meinert, Lotte
This article argues that the concept of communicability that is central to the distinction between communicable diseases (CDs) and noncommunicable diseases (NCDs) is poorly conceptualized. The epidemic spread of NCDs such as diabetes, depression, and eating disorders demonstrates...
Eng, Thomas R; Butler, William T
.... In addition, STDs increase the risk of HIV transmission. The Hidden Epidemic examines the scope of sexually transmitted infections in the United States and provides a critical assessment of the nation's response to this public health crisis...
Sun, Ye [Institute of Information Economy, Hangzhou Normal University, Hangzhou 311121 (China); Alibaba Research Center of Complexity Science, Hangzhou Normal University, Hangzhou 311121 (China); Liu, Chuang, E-mail: email@example.com [Institute of Information Economy, Hangzhou Normal University, Hangzhou 311121 (China); Alibaba Research Center of Complexity Science, Hangzhou Normal University, Hangzhou 311121 (China); Zhang, Chu-Xu [Institute of Information Economy, Hangzhou Normal University, Hangzhou 311121 (China); Alibaba Research Center of Complexity Science, Hangzhou Normal University, Hangzhou 311121 (China); Zhang, Zi-Ke, E-mail: firstname.lastname@example.org [Institute of Information Economy, Hangzhou Normal University, Hangzhou 311121 (China); Alibaba Research Center of Complexity Science, Hangzhou Normal University, Hangzhou 311121 (China)
Nowadays, the emergence of online services provides various multi-relation information to support the comprehensive understanding of the epidemic spreading process. In this Letter, we consider the edge weights to represent such multi-role relations. In addition, we perform detailed analysis of two representative metrics, outbreak threshold and epidemic prevalence, on SIS and SIR models. Both theoretical and simulation results find good agreements with each other. Furthermore, experiments show that, on fully mixed networks, the weight distribution on edges would not affect the epidemic results once the average weight of whole network is fixed. This work may shed some light on the in-depth understanding of epidemic spreading on multi-relation and weighted networks.
Sun, Ye; Liu, Chuang; Zhang, Chu-Xu; Zhang, Zi-Ke
Nowadays, the emergence of online services provides various multi-relation information to support the comprehensive understanding of the epidemic spreading process. In this Letter, we consider the edge weights to represent such multi-role relations. In addition, we perform detailed analysis of two representative metrics, outbreak threshold and epidemic prevalence, on SIS and SIR models. Both theoretical and simulation results find good agreements with each other. Furthermore, experiments show that, on fully mixed networks, the weight distribution on edges would not affect the epidemic results once the average weight of whole network is fixed. This work may shed some light on the in-depth understanding of epidemic spreading on multi-relation and weighted networks.
Information propagation through peer-to-peer systems, online social systems, wireless mobile ad hoc networks and other modern structures can be modelled as an epidemic on a network of contacts. Understanding how epidemic processes interact with network topology allows us to predict ultimate course, understand phase transitions and develop strategies to control and optimise dissemination. This book is a concise introduction for applied mathematicians and computer scientists to basic models, analytical tools and mathematical and algorithmic results. Mathematical tools introduced include coupling
Ellner, S.; Gallant, A.R. [North Carolina State Univ., Raleigh, NC (United States). Dept. of Statistics; Theiler, J. [Santa Fe Inst., NM (United States)]|[Los Alamos National Lab., NM (United States)
Historical data on recurrent epidemics have been central to the debate about the prevalence of chaos in biological population dynamics. Schaffer and Kot who first recognized that the abundance and accuracy of disease incidence data opened the door to applying a range of methods for detecting chaos that had been devised in the early 1980`s. Using attractor reconstruction, estimates of dynamical invariants, and comparisons between data and simulation of SEIR models, the ``case for chaos in childhood epidemics`` was made through a series of influential papers beginning in the mid 1980`s. The proposition that the precise timing and magnitude of epidemic outbreaks are deterministic but chaotic is appealing, since it raises the hope of finding determinism and simplicity beneath the apparently stochastic and complicated surface of the data. The initial enthusiasm for methods of detecting chaos in data has been followed by critical re-evaluations of their limitations. Early hopes of a ``one size fits all`` algorithm to diagnose chaos vs. noise in any data set have given way to a recognition that a variety of methods must be used, and interpretation of results must take into account the limitations of each method and the imperfections of the data. Our goals here are to outline some newer methods for detecting nonlinearity and chaos that have a solid statistical basis and are suited to epidemic data, and to begin a re-evaluation of the claims for nonlinear dynamics and chaos in epidemics using these newer methods. We also identify features of epidemic data that create problems for the older, better known methods of detecting chaos. When we ask ``are epidemics nonlinear?``, we are not questioning the existence of global nonlinearities in epidemic dynamics, such as nonlinear transmission rates. Our question is whether the data`s deviations from an annual cyclic trend (which would reflect global nonlinearities) are described by a linear, noise-driven stochastic process.
Carvill, Gemma L; Heavin, Sinéad B; Yendle, Simone C
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 ...
Tzoulis, Charalampos; Neckelmann, Gesche; Mork, Sverre J.; Engelsen, Bernt E.; Viscomi, Carlo; Moen, Gunnar; Ersland, Lars; Zeviani, Massimo; Bindoff, Laurence A.
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…
Real-time HIV genotyping and breaking down local HIV epidemics into phylogenetically distinct sub-epidemics may help to reveal the structure and dynamics of HIV transmission networks in communities, and aid in the design of targeted interventions for members of the acute sub-epidemics that likely fuel local HIV/AIDS epidemics.
Rajagopala, Lavanya; Satharasinghe, Ravindra L; Karunarathna, Madhava
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
Butt, T.K.; Farooqui, R.; Khan, U.; Farooqui, R.
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)
Sivolap, Iu P; Damulin, I V
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.
Yamamoto, Toshiyuki; Shimojima, Keiko; Yano, Tamami; Ueda, Yuki; Takayama, Rumiko; Ikeda, Hiroko; Imai, Katsumi
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.
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.
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.
Zhang, Hong-Liang; Yang, Yi; Wu, Jiang
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.). ...
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.
Ban, Vin Shen; Madden, Christopher J; Bailes, Julian E; Hunt Batjer, H; Lonser, Russell R
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.
Korngold, Caleb; Farrell, Helen M; Fozdar, Manish
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.
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.
Montagnese, Sara; Cona, Giorgia; Schiff, Sami; Maresio, Giulio; Gatta, Angelo; Merkel, Carlo; Amodio, Piero
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.
Striano, Pasquale; de Jonghe, Peter; Zara, Federico
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.
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
Souto, Pablo A; Marcotegui, Ariel R; Orbea, Lisandro; Skerl, Juan; Perazzo, Juan Carlos
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.
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.
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.
Hanai, Tatsunori; Shiraki, Makoto; Watanabe, Satoshi; Kochi, Takahiro; Imai, Kenji; Suetsugu, Atsushi; Takai, Koji; Moriwaki, Hisataka; Shimizu, Masahito
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.
Mao Xiaofen; Yang Bo; Ye Gengxin; Zhang Cheng
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)
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.
Myoung Uk Kim
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.
Stamberger, Hannah; Weckhuysen, Sarah; De Jonghe, Peter
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.
Full Text Available Men who have sex with men (MSM and heterosexuals are the populations with the fastest growing HIV infection rates in China. We characterize the epidemic growth and age patterns between these two routes from 2004 to 2015 in Chongqing and Shenzhen, China.Data were downloaded from the National HIV/ AIDS Comprehensive Response Information Management System. For the new HIV diagnoses of heterosexuals and MSM in both cities, we estimated the growth rates by fitting different sub-exponential models. Heat maps are used to show their age patterns. We used histograms to compare these patterns by birth cohort.The MSM epidemics grew significantly in both cities. Chongqing experienced quadratic growth in HIV reported cases with an estimated growth rate of 0.086 per week and a "deceleration rate" of 0.673. HIV reported cases of MSM in Shenzhen grew even more drastically with a growth rate of 0.033 per week and "deceleration rate" of 0.794. The new infections are mainly affecting the ages of 18 to 30 in Chongqing and ages of 20 to 35 in Shenzhen. They peaked in early 1990's and mid-1990's birth cohorts in Chongqing and Shenzhen respectively. The HIV epidemic among heterosexuals grew rapidly in both cities. The growth rates were estimated as 0.02 and 0.028 in Chongqing and Shenzhen respectively whereas the "deceleration rates" were 0.878 and 0.790 in these two places. It affected mostly aged 18 to 75 in males and 18 to 65 in females in Chongqing and aged 18 to 45 in males and 18 to 50 in females in Shenzhen in 2015. In Chongqing, the heterosexual female epidemics display two peaks in HIV diagnoses in the birth cohorts of early 1950's and early 1980's, with heterosexual male epidemics peaked in early 1940's and early 1960's. The heterosexual male and female epidemics display higher rates in the birth cohort 1940-1960, than the birth cohort 1960-1990. It peaked in birth cohorts of 1950's and 1980's in Shenzhen.We revealed striking differences in epidemic growth
Full Text Available Systemic sclerosis (SSc is an autoimmune connective tissue disease involving the skin and internal organs and characterized pathologically by microvascular damage and increased deposition of connective tissue. Skin changes seen in SSc include edema, inflammation, induration, thickening, and progressive skin fibrosis. Histologically, skin fibrosis, accumulation of compact collagen in the dermis, effacement of rete pegs, infiltration by CD4+ T cells, and skin atrophy are observed. The “toxic oil syndrome” reported from Spain caused an outbreak of a scleroderma-like illness and was caused by ingestion of contaminated rapeseed cooking oil. Epidemic dropsy is caused by ingestion of mustard oil contaminated with the oil of Argemone mexicana. The major alkaloids in Argemone oil are sanguinarine and dihydrosanguinarine. These alkaloids produce widespread capillary dilatation, increased capillary permeability, and endothelial proliferation, akin to the toxic oil syndrome. Cutaneous manifestations include erythematous and tender bilaterally symmetrical pitting edema usually involving lower limbs, skin thickening and tethering, pigmentation, and presence of telangiectasias. The dermatopathology observed in epidemic dropsy includes atrophy and flattening of rete pegs, hypertrophy of and deposition of collagen, vascular dilatation and proliferation, and subcutaneous inflammation and fibrosis. Epidemic dropsy usually presents with subacute multisystem involvement, which may mimic a connective tissue disease. Skin involvement in epidemic dropsy may closely mimic cutaneous manifestations in SSc, both clinically and histologically. Thus, the clinician needs to be aware that epidemic dropsy with cutaneous involvement, especially if encountered sporadically, may be mistakenly diagnosed as scleroderma.
Frasca, M.; Rizzo, A.; Gallo, L.; Fortuna, L.; Porfiri, M.
Complex dynamical systems often exhibit collective dynamics that are well described by a reduced set of key variables in a low-dimensional space. Such a low-dimensional description offers a privileged perspective to understand the system behavior across temporal and spatial scales. In this work, we propose a data-driven approach to establish low-dimensional representations of large epidemic datasets by using a dimensionality reduction algorithm based on isometric features mapping (ISOMAP). We demonstrate our approach on synthetic data for epidemic spreading in a population of mobile individuals. We find that ISOMAP is successful in embedding high-dimensional data into a low-dimensional manifold, whose topological features are associated with the epidemic outbreak. Across a range of simulation parameters and model instances, we observe that epidemic outbreaks are embedded into a family of closed curves in a three-dimensional space, in which neighboring points pertain to instants that are close in time. The orientation of each curve is unique to a specific outbreak, and the coordinates correlate with the number of infected individuals. A low-dimensional description of epidemic spreading is expected to improve our understanding of the role of individual response on the outbreak dynamics, inform the selection of meaningful global observables, and, possibly, aid in the design of control and quarantine procedures.
Wijnia, Jan W; Oudman, Erik; Bresser, Esmay L; Gerridzen, Ineke J; van de Wiel, Albert; Beuman, Carla; Mulder, Cornelis L
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.
Lee, Jiwon; Yu, Hee Joon; Lee, Jeehun
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.
Gürsoy, Semra; Erçal, Derya
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.
Syahrini, Intan; Sriwahyuni; Halfiani, Vera; Meurah Yuni, Syarifah; Iskandar, Taufiq; Rasudin; Ramli, Marwan
Tuberculosis is an infectious disease which has caused a large number of mortality in Indonesia. This disease is caused by Mycrobacterium tuberculosis. Besides affecting lung, this disease also affects other organs such as lymph gland, intestine, kidneys, uterus, bone, and brain. This article discusses the epidemic of tuberculosis through employing the SEIR model. Here, the population is divided into four compartments which are susceptible, exposed, infected and recovered. The susceptible population is further grouped into two which are vaccinated group and unvaccinated group. The behavior of the epidemic is investigated through analysing the equilibrium of the model. The result shows that administering vaccine to the susceptible population contributes to the reduction of the tuberculosis epidemic rate.
Nagatani, Takashi; Ichinose, Genki; Tainaka, Kei-ichi
We present an epidemic model combined with a traffic cellular automaton. Each agent or individual is either susceptible (S) or infected (I). An agent with a certain density moves to a fixed direction on one-dimensional lattice. Simulations for SIS model show that the epidemic spreads via migration. We find a dynamical phase transition between infectious and non-infectious phases. If the density exceeds the critical limit ρC, the epidemic spreads into the population. The value of ρC decreases along with the recovery rate as predicted by mean-field theory. However, this theory cannot explain the simulation result that a traffic jam strongly affects the phase transition. It is found that the minimum value of ρC corresponds to the critical value of the jamming transition.
Manzano, Marc; Calle, Eusebi; Ripoll, Jordi
Our society nowadays is governed by complex networks, examples being the power grids, telecommunication networks, biological networks, and social networks. It has become of paramount importance to understand and characterize the dynamic events (e.g. failures) that might happen in these complex...... networks. For this reason, in this paper, we propose two measures to evaluate the vulnerability of complex networks in two different dynamic multiple failure scenarios: epidemic-like and cascading failures. Firstly, we present epidemic survivability ( ES ), a new network measure that describes...... the vulnerability of each node of a network under a specific epidemic intensity. Secondly, we propose cascading survivability ( CS ), which characterizes how potentially injurious a node is according to a cascading failure scenario. Then, we show that by using the distribution of values obtained from ES and CS...
Zhang Haifeng; Small, Michael; Fu Xinchu
Models for diseases spreading are not just limited to SIS or SIR. For instance, for the spreading of AIDS/HIV, the susceptible individuals can be classified into different cases according to their immunity, and similarly, the infected individuals can be sorted into different classes according to their infectivity. Moreover, some diseases may develop through several stages. Many authors have shown that the individuals' relation can be viewed as a complex network. So in this paper, in order to better explain the dynamical behavior of epidemics, we consider different epidemic models on complex networks, and obtain the epidemic threshold for each case. Finally, we present numerical simulations for each case to verify our results.
Shi, Hong-Jing; Duan, Zhi-Sheng; Chen, Guan-Rong; Li, Rong
In this paper, a new susceptible-infected-susceptible (SIS) model on complex networks with imperfect vaccination is proposed. Two types of epidemic spreading patterns (the recovered individuals have or have not immunity) on scale-free networks are discussed. Both theoretical and numerical analyses are presented. The epidemic thresholds related to the vaccination rate, the vaccination-invalid rate and the vaccination success rate on scale-free networks are demonstrated, showing different results from the reported observations. This reveals that whether or not the epidemic can spread over a network under vaccination control is determined not only by the network structure but also by the medicine's effective duration. Moreover, for a given infective rate, the proportion of individuals to vaccinate can be calculated theoretically for the case that the recovered nodes have immunity. Finally, simulated results are presented to show how to control the disease prevalence.
In the current century, the highly developed transportation system can not only boost the economy, but also greatly accelerate the spreading of epidemics. While some epidemic diseases may infect quite a number of people ahead of our awareness, the health care resources such as vaccines and the medical staff are usually locally or even globally insufficient. In this research, with the network of major aviation routes as an example, we present a method to determine the optimal locations to allocate the medical service in order to minimize the impact of the infectious disease with limited resources. Specifically, we demonstrate that when the medical resources are insufficient, we should concentrate our efforts on the travelers with the objective of effectively controlling the spreading rate of the epidemic diseases. © 2011 Springer-Verlag Berlin Heidelberg.
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
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.
Serter, Asil; Alkan, Alpay; Aralasmak, Ayse; Kocakoc, Ercan [Dept. of Radiology, Bezmialem Vakif University School of Medicine, Istanbul (Turkmenistan)
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.
Kang, Eu Gene; Jeon, Se Jeong; Choi, See Sung [Dept. of Radiology, Wonkwang University School of Medicine and Hospital, Iksan (Korea, Republic of)
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.
A. Bruce Janati
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.
Aline Souza Marques da Silva Braga
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.
Teslenko, Elena L; Damyanovich, Elena V; Damjanović, Ilija; Gačić, Zoran; Baziyan, Boris K
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).
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.
Wang, Shi; Hou, Xiaojun; Ding, Suju; Guan, Yangtai; Zhen, Huimin; Tu, Laihui; Qiu, Yiqing
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.
Gabaudan, C; La-Folie, T; Sagui, E; Soulier, B; Dion, A-M; Richez, P; Brosset, C
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.
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.
Montenigro, Philip H; Corp, Daniel T; Stein, Thor D; Cantu, Robert C; Stern, Robert A
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.
Full Text Available . 2005. Climate Drives the Meningitis Epidemics Onset in West Africa. PLoS Medicine, 2: 0043-0049. TAMPLIN, M.L., GAUZENS, A.L., HUQ,A., SACK, D.A. & COLWELL, R.R. 1990. COLWELL. Attachment of Vibrio cholerae Serogroup 01 to Zooplankton...
Sandoval, Ruben; Martinez, Douglas R.
Recently, incidents of police abuse against Hispanics have increased so rapidly that the phenomenon has been called an epidemic. Of special concern to Hispanic leaders is the lack of Federal intervention in these police brutality cases. A list of 56 documented cases involving police brutality against Hispanics is included. (Author/NQ)
Audelin, Anne Margrethe; Cowan, Susan A; Obel, Niels
BACKGROUND:: In Denmark 300 new individuals are diagnosed with HIV every year, despite decades of public health campaigns aimed to raise awareness of potential risk behaviour for HIV transmission. It is important to identify the driving forces of the epidemic, to enable more targeted campaigns...
Overdose related to prescription opioids has become an epidemic. This podcast discusses the risks of this type of drug sometimes used to treat pain, and how to protect yourself. . Created: 4/19/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP). Date Released: 4/19/2016.
An epidemic of acute conjunctivitis in Dar es Salaam in 2010 demonstrated the importance of a strong infectious diseases epidemiological surveillance network to minimise disease outbreaks. Misunderstanding of the causes and management of diseases explains the repetitive nature of acute haemorrhagic conjunctivitis ...
Carton, H; Kayembe, K; Kabeya; Odio; Billiau, A; Maertens, K
Epidemiological findings of twenty sporadic cases of epidemic spastic paraparesis (buka-buka) in three areas of Bandundu (Zaire) are reported. These findings suggest the involvement of an infectious agent and do not support the hypothesis of a dietary cyanide intoxication, which has been advanced to explain the outbreak of a very similar disease (Mantakassa) in Mozambique.
Argues that public perceptions of an epidemic of school violence are media-induced; asserts that violence in schools declined during the 1990s; supports assertion with evidence from the National School Safety Center; states the estimates of bullying in school are exaggerated. (PKP)
Malawi Medical Journal. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 13, No 1 (2001) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Cholera Epidemic Control. R Zachariah. Full Text: EMAIL FREE ...
Issue/problem: After disasters, terrorist attacks and wars social epidemics of medically unexplained physical symptoms/syndromes (ups) are often seen. In modern times people feel more vulnerable and especially under pressure of those incidents, everyday symptoms are interpreted as disease and
Magno Pereira, Vítor; Marote Correia, Luís; Rodrigues, Tiago; Serrão Faria, Gorete
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.
Gamanagatti, S.; Subramanian, S. [India Institute of Medical Sciences, New Delhi (India)
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
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.
First page Back Continue Last page Overview Graphics. Epidemics can be prevented with a Doctor on Call. A potential epidemic of Chicken Pox was halted by a simple email to the right people. Instant response from the Government Doctors.
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
van Hout, Moniek S. E.; Schmand, Ben; Wekking, Ellie M.; Hageman, Gerard; Deelman, Betto G.
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
Anzai, Yuki; Hayashi, Masaharu; Ohya, Tatsuo
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.
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.
Doing-Harris, Kristina M; Weir, Charlene R; Igo, Sean; Shi, Jianlin; Shao, Yijun; Hurdle, John F
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.
Latt, N; Dore, G
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.
Verma, Rajesh; Garg, Vipul
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.
J Gordon Millichap
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.
van Handel, M.; Swaab, H.; de Vries, L.S.; Jongmans, M.J.
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
Vanhatalo, S.; Somer, M.; Barth, P. G.
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
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.
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
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.
Osaka, Shunsuke; Okuzumi, Katsuko; Koide, Shota; Tamai, Kiyoko; Sato, Tomoaki; Tanimoto, Koichi; Tomita, Haruyoshi; Suzuki, Masahiro; Nagano, Yukiko; Shibayama, Keigo; Arakawa, Yoshichika; Nagano, Noriyuki
The decline in methicillin-resistant Staphylococcus aureus (MRSA) isolation rates has become a general observation worldwide, including Japan. We hypothesized that some genetic shift in MRSA might cause this phenomenon, and therefore we investigated the genetic profiles among MRSA clinical isolates obtained from three different epidemic phases in Japan. A total of 353 MRSA isolates were selected from 202 medical facilities in 1990 (pre-epidemic phase), 2004 (epidemic phase) and 2016 (post-epidemic phase). Molecular typing was performed by PCR detection of 22 genes using the polymerase chain reaction (PCR)-based ORF typing (POT) system, including an additional eight genes including small genomic islets and seven toxin genes. Isolates with a POT1 of score 93, identified as presumed clonal complex (pCC)5-staphylococcal cassette chromosome mec (SCCmec) type II including ST5-SCCmec type II New York/Japan clone, represented the major epidemic MRSA lineage in 1990 and 2004. In 2016, however, a marked decrease in isolates with a POT1 score of 93, along with changes in the epidemiology of toxin genes carried, was noted, where the carriers of tst genes including the tst-sec combination were markedly reduced, and those possessing the seb gene alone were markedly increased. Rather, isolates with a POT1 score of 106, including pCC1 or pCC8 among the isolates with SCCmec type IV, which often links to community-associated MRSA, were predominant. Interestingly, the pCC1 and pCC8 lineages were related to sea and tst-sec carriage, respectively. Over time, a transition in MRSA genetic profiles from a POT1 score of 93 in 1990 and 2004 to 106 in 2014 was found in Japan.
Hiroki Masuda; Masahiro Mori; Shoichi Ito; Toshiyuki Yagishita; Satoshi Kuwabara
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 ...
Ettinger, Nicholas; Pearson, Matthew; Lamb, Fred S; Wellons, John C
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.
Tong, Dao-Ming; Zhou, Ye-Ting; Wang, Guang-Sheng; Chen, Xiao-Dong; Yang, Tong-Hui
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...
Nakamura, Zev M; Tatreau, Jason R; Rosenstein, Donald L; Park, Eliza M
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.
Tao, Ran, E-mail: email@example.com [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: firstname.lastname@example.org [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); You, Zhonglan, E-mail: email@example.com [Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Wei, Luqing, E-mail: firstname.lastname@example.org [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Fan, Yi, E-mail: email@example.com [Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Cui, Jinguo, E-mail: firstname.lastname@example.org [Department of Radiology, Bethune International Peace Hospital of People' s Liberty Army, Shijiazhuang 050082, Hebei Province (China); Wang, Jian, E-mail: email@example.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)
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.
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.
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.
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)
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.
Sen, Kuntal; Agarwal, Rajkumar
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.
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
Ramirez, Rigoberto; Muskula, Preetham Reddy; Everley, Mark P.
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...
Kayyali, Husam R; Abdelmoity, Ahmed; Baeesa, Saleh
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.
PARTHASARATHI, U. D.; HARROWER, T.; TEMPEST, M.; HODGES, J. R.; WALSH, C.; McKENNA, P. J.; FLETCHER, P.C.
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...
Kayyali, Husam R.; Abdelmoity, Ahmed; Baeesa, Saleh
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...
Chiyori T Urabe
Full Text Available In recent years, serious infectious diseases tend to transcend national borders and widely spread in a global scale. The incidence and prevalence of epidemics are highly influenced not only by pathogen-dependent disease characteristics such as the force of infection, the latent period, and the infectious period, but also by human mobility and contact patterns. However, the effect of heterogeneous mobility of individuals on epidemic outcomes is not fully understood. Here, we aim to elucidate how spatial mobility of individuals contributes to the final epidemic size in a spatial susceptible-exposed-infectious-recovered (SEIR model with mobile individuals in a square lattice. After illustrating the interplay between the mobility parameters and the other parameters on the spatial epidemic spreading, we propose an index as a function of system parameters, which largely governs the final epidemic size. The main contribution of this study is to show that the proposed index is useful for estimating how parameter scaling affects the final epidemic size. To demonstrate the effectiveness of the proposed index, we show that there is a positive correlation between the proposed index computed with the real data of human airline travels and the actual number of positive incident cases of influenza B in the entire world, implying that the growing incidence of influenza B is attributed to increased human mobility.
Gesser-Edelsburg, Anat; Shir-Raz, Yaffa; Bar-Lev, Oshrat Sassoni; James, James J; Green, Manfred S
Our aim was to examine in what terms leading newspapers' online sites described the current Ebola crisis. We employed a quantitative content analysis of terms attributed to Ebola. We found and analyzed 582 articles published between March 23 and September 30, 2014, on the online websites of 3 newspapers: The New York Times, Daily Mail, and Ynet. Our theoretical framework drew from the fields of health communication and emerging infectious disease communication, including such concepts as framing media literacy, risk signatures, and mental models. We found that outbreak and epidemic were used interchangeably in the articles. From September 16, 2014, onward, epidemic predominated, corresponding to when President Barack Obama explicitly referred to Ebola as an epidemic. Prior to Obama's speech, 86.8% of the articles (323) used the term outbreak and only 8.6% (32) used the term epidemic. Subsequently, both terms were used almost the same amount: 53.8% of the articles (113) used the term outbreak and 53.3% (112) used the term epidemic. Effective communication is crucial during public health emergencies such as Ebola, because language framing affects the decision-making process of social judgments and actions. The choice of one term (outbreak) over another (epidemic) can create different conceptualizations of the disease, thereby influencing the risk signature. (Disaster Med Public Health Preparedness. 2016;10:669-673).
Transferring the Malaria Epidemic Prediction Model to Users in East Africa. In the highlands of East Africa, epidemic malaria is an emerging climate-related hazard that urgently needs addressing. Malaria incidence increased by 337% during the 1987 epidemic in Rwanda. In Tanzania, Uganda and Kenya, malaria incidence ...
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
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.
Adikari, Madura; Priyangika, Dilani; Marasingha, Indika; Thamotheram, Sharmila; Premawansa, Gayani
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.
Patel, Jaina; Mercimek-Mahmutoglu, Saadet
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.
Chen, Xiao-Qiao; Zhang, Wei-Na; Hu, Lin-Yan; Liu, Meng-Jia; Zou, Li-Ping
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.
Pastor-Satorras, Romualdo; Vespignani, Alessandro
We study by analytical methods and large scale simulations a dynamical model for the spreading of epidemics in complex networks. In networks with exponentially bounded connectivity we recover the usual epidemic behavior with a threshold defining a critical point below that the infection prevalence is null. On the contrary, on a wide range of scale-free networks we observe the absence of an epidemic threshold and its associated critical behavior. This implies that scale-free networks are prone to the spreading and the persistence of infections whatever spreading rate the epidemic agents might possess. These results can help understanding computer virus epidemics and other spreading phenomena on communication and social networks
Yoshioka, Eiji; Hanley, Sharon J B; Kawanishi, Yasuyuki; Saijo, Yasuaki
The charcoal burning suicide epidemics in both Hong Kong and Taiwan have been well documented. However, little is known about the situation in Japan. To examine the impact of charcoal burning suicide on the overall and other method-specific suicide rates between 1998 and 2007 in Japan. Using data obtained from the Vital Statistics of Japan, negative binomial regression analyses were performed to investigate the impact of the charcoal burning method. In males and females aged 15-24 and 25-44 years, the charcoal burning epidemic led to a substantial increase in overall suicides, without a decrease in other methods. In all other age groups, no such trend was observed. In young Japanese, the charcoal burning method may have appealed to individuals who might not have chosen other highly or relatively lethal methods, and consequently led to an increase in overall suicides.
van der Feltz-Cornelis, Christina M
There has been much discussion in the media about the question of the existence of a depression epidemic. This leads on to the questions of whether the social and economic approaches are adequate, and what the alternatives are. The concept of the disease 'depression' can be defined using a medical model, or from a patient's or a societal perspective. From a medical perspective, indeed a depression epidemic has ensued from the increased prosperity and the associated decompression of the mortality rate. Society responded with preventative measures and policies aimed at improving functioning in the workplace. However, patients with a major depressive disorder (MDD) who are eligible for treatment are often not motivated to take it up, or are undertreated. Research is necessary in order to explore what patients think about the identification and treatment of depression. The confusion regarding the concept of depression found in the media, needs to be cleared.
Full Text Available Networks offer a fertile framework for studying the spread of infection in human and animal populations. However, owing to the inherent high-dimensionality of networks themselves, modelling transmission through networks is mathematically and computationally challenging. Even the simplest network epidemic models present unanswered questions. Attempts to improve the practical usefulness of network models by including realistic features of contact networks and of host–pathogen biology (e.g. waning immunity have made some progress, but robust analytical results remain scarce. A more general theory is needed to understand the impact of network structure on the dynamics and control of infection. Here we identify a set of challenges that provide scope for active research in the field of network epidemic models.
Zusman, Mara B.
Methamphetamine abuse has become an epidemic in the United States. As methamphetamine becomes increasingly available, more and more people are trying â€“ and becoming addicted to â€“ this potent drug. But although methamphetamine is made using over-the-counter (OTC) drugs containing pseudoephedrine, shifting OTC drugs containing pseudoephedrine to prescription status is not the solution to the methamphetamine crisis. Rather, society must adopt a comprehensive...
Obesity and metabolic syndromes are major threats to health in both developed and developing countries. This opinion article is a holistic attempt to understand the obesity epidemic, by connecting it to the widespread narcissism in society. The narcissism epidemic refers to an increased prevalence of status-striving individualism and a decreased sense of community, observed in Westerns populations and spreading worldwide. Based on social personality and evolutionary psychology approaches, I speculate that this rise of narcissism underlies a steep social hierarchy resulting in increase of social stress. This social stress markedly affects individuals who are sensitive to social hierarchy dominance due to their personality, yet are relegated at a lower social position. I speculate that over-eating is one major mechanism for coping with this stress, and discuss the possibility that visceral fat may constitute an adaptive behaviour to the lower social hierarchy position, which is perceived as unjust. Connecting the prevalence of obesity to the narcissism epidemic allows for a more thorough examination of factors, which contribute to obesity, which includes early difficult childhood experience, lower rank, and the overall competitive framework of the society. Copyright © 2016 The Author. Published by Elsevier Ltd.. All rights reserved.
Full Text Available The transmission of infectious diseases can be affected by many or even hidden factors, making it difficult to accurately predict when and where outbreaks may emerge. One approach at the moment is to develop and deploy surveillance systems in an effort to detect outbreaks as timely as possible. This enables policy makers to modify and implement strategies for the control of the transmission. The accumulated surveillance data including temporal, spatial, clinical, and demographic information, can provide valuable information with which to infer the underlying epidemic networks. Such networks can be quite informative and insightful as they characterize how infectious diseases transmit from one location to another. The aim of this work is to develop a computational model that allows inferences to be made regarding epidemic network topology in heterogeneous populations. We apply our model on the surveillance data from the 2009 H1N1 pandemic in Hong Kong. The inferred epidemic network displays significant effect on the propagation of infectious diseases.
This paper explores the historical context of the dramatic rise in surgery for glue ear in the mid-20th century, and questions the published assertion that this represented a manufactured 'epidemic'. In examining historical sources, the reader's theoretical viewpoint greatly influences their conclusions: the sustained rise in treatment for glue ear may be seen as the advance of science in a golden age or the resistance of insular professionals to reason in the light of new scientific study methods. Current views on the practice of medicine, consumerism, science and standardisation, rationing and the nature of 'truth' all affect the way that we see this period. Technological advances clearly allowed better diagnosis and more effective treatment, but these did not appear to drive an 'epidemic', rather they were developed to meet the pre-existing challenges of otological practice. The proposition that an 'epidemic' was created does not appear to have any solid grounding. Society's perception of what constitutes disease and what needs treatment may have evolved, but the prevalence of other important diseases changed dramatically over this time period, and a real change in the epidemiology of glue ear cannot be dismissed. In defining the case for and against surgical treatment, a solely positivist, quantitative worldview cannot give us a complete picture of benefit and risk to individuals, families and society at large.
Fofana, Abdou Moutalab; Hurford, Amy
An overlooked aspect of disease ecology is considering how and why animals come into contact with one and other resulting in disease transmission. Mathematical models of disease spread frequently assume mass-action transmission, justified by stating that susceptible and infectious hosts mix readily, and foregoing any detailed description of host movement. Numerous recent studies have recorded, analysed and modelled animal movement. These movement models describe how animals move with respect to resources, conspecifics and previous movement directions and have been used to understand the conditions for the occurrence and the spread of infectious diseases when hosts perform a type of movement. Here, we summarize the effect of the different types of movement on the threshold conditions for disease spread. We identify gaps in the literature and suggest several promising directions for future research. The mechanistic inclusion of movement in epidemic models may be beneficial for the following two reasons. Firstly, the estimation of the transmission coefficient in an epidemic model is possible because animal movement data can be used to estimate the rate of contacts between conspecifics. Secondly, unsuccessful transmission events, where a susceptible host contacts an infectious host but does not become infected can be quantified. Following an outbreak, this enables disease ecologists to identify 'near misses' and to explore possible alternative epidemic outcomes given shifts in ecological or immunological parameters.This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'. © 2017 The Author(s).
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
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.
Saeedian, M.; Khalighi, M.; Azimi-Tafreshi, N.; Jafari, G. R.; Ausloos, M.
Memory has a great impact on the evolution of every process related to human societies. Among them, the evolution of an epidemic is directly related to the individuals' experiences. Indeed, any real epidemic process is clearly sustained by a non-Markovian dynamics: memory effects play an essential role in the spreading of diseases. Including memory effects in the susceptible-infected-recovered (SIR) epidemic model seems very appropriate for such an investigation. Thus, the memory prone SIR model dynamics is investigated using fractional derivatives. The decay of long-range memory, taken as a power-law function, is directly controlled by the order of the fractional derivatives in the corresponding nonlinear fractional differential evolution equations. Here we assume "fully mixed" approximation and show that the epidemic threshold is shifted to higher values than those for the memoryless system, depending on this memory "length" decay exponent. We also consider the SIR model on structured networks and study the effect of topology on threshold points in a non-Markovian dynamics. Furthermore, the lack of access to the precise information about the initial conditions or the past events plays a very relevant role in the correct estimation or prediction of the epidemic evolution. Such a "constraint" is analyzed and discussed.
Sadun, A A; Martone, J F; Muci-Mendoza, R; Reyes, L; DuBois, L; Silva, J C; Roman, G; Caballero, B
To characterize and establish a clinical definition of the optic neuropathy that appeared in epidemic form in Cuba in 1992 and 1993. At the invitation of the Cuban Ministry of Health, Havana, members of ORBIS International and the Pan American Health Organization, assembled teams that traveled to Cuba in May 1993. We were initially briefed by Cuban national experts in the areas of virology, nutrition, toxicology, ophthalmology, neurology, and public health. We then examined 20 patients on our own. Thirteen of these patients underwent a comprehensive neuro-ophthalmologic examination, including neurologic examination, ophthalmologic examination, visual fields, optic nerve function studies, contrast sensitivity studies, and funduscopy. We returned 4 months later to perform an additional 12 comprehensive neuro-ophthalmologic and follow-up examinations. Only seven of the 13 patients who were alleged to have the optic form of the epidemic and who were rigorously and systematically examined on the first visit demonstrated a bilateral optic neuropathy. These seven patients had several features that included decreased visual acuity, poor color vision, central scotomas, decreased contrast sensitivity, saccadic eye movements, and most prominent and distinctive of all, nerve fiber layer wedge defects of the papillomacular bundle. Our clinical definition was then implemented by the Cuban ophthalmologists and epidemiologists. On returning 4 months later, we found that all newly presented patients were correctly diagnosed to have the epidemic disease. With the new case definition and the application of a few simple psychophysical tests, the false-positive rate of diagnosis became much lower. After vitamin therapy, we reexamined the patients seen on our initial visit, and all showed marked improvement. The Cuban epidemic was characterized by an optic neuropathy with features that were similar to those of tobacco/alcohol amblyopia and Leber's optic atrophy. Recent political
Maria Ballesta Méndez
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.
Cheong, Raymond; Wilson, Robin K; Cortese, Irene C M; Newman-Toker, David E
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.