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...
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.
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.
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.
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.
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...
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.
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
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
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 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.
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
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.
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...
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...
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.
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
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.
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...
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.
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.
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
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.
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
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....
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.
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.
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.
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.
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
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.
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.
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)
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.
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.
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
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.
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.
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
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.
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
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.
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.
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.
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 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
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...
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.
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
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.
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
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
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
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.
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.
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.
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.
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.
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.
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.
... 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 ...
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
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.)
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
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.
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.
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.
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.
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.
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.
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
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.
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
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.
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.
... 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.
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.
Full Text Available Hashimoto's encephalopathy (HE is a rare condition characterized by atypical psychiatric and heterogeneous neurological manifestations such as acute cerebral ischemia, seizure, tremors, myoclonus, psychosis, depression, cognitive disorders, and fluctuating loss of consciousness. Here, a case of 28 year-old man was reported who referred to the emergency department (ED with different acute neurologic disorders and final diagnose of HE.
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.
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.
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
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.
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
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.
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.
Full Text Available Patients with special health care needs often present with compromised oral health for which they need dental treatment. Such patients and often their guardians find it difficult to maintain oral health due to various reasons such as decreased manual dexterity and preference for soft diet. Bilirubin encephalopathy is a condition occurring as a result of neonatal jaundice/hyperbilirubinemia. Elevated levels of unconjugated bilirubin at birth often leads to brain damage manifesting as auditory and motor defects such as athetoid cerebral palsy. This paper reports one such case of dental management of a known case of bilirubin encephalopathy.
Cirignotta, F; Manconi, M; Mondini, S; Buzzi, G; Ambrosetto, P
Gastric partitioning is a surgical procedure for the treatment of morbid obesity that may engender neurological complications, such as Wernicke encephalopathy and polyneuropathy. A specialist hospital. A 36-year-old woman developed Wernicke-Korsakoff encephalopathy and polyneuropathy 3 months after gastroplasty for morbid obesity. A magnetic resonance scan documented the diagnosis, and a clear improvement occurred after parenteral thiamine treatment. In our patient and in previously described cases of the literature, postsurgical vomiting is a constant finding that seems to be the precipitating factor of neurological complications of gastric partitioning. Persistent vomiting after gastroplasty for morbid obesity should be considered an alarming symptom to treat immediately with appropriate measures.
Full Text Available Objective: Hashimoto encephalopathy (HE is known as a steroid-responsive encephalopathy associated with autoimmune thyroiditis or nonvascular inflammation-related autoimmune meningoencephalitis. The average age of onset of HE is approximately 50 years; and it is more common in women. The onset of HE may be acute or subacute. The course of most HE cases is relapsing and remitting, which is similar to that of vasculitis and stroke.Methods: In this article, we present a previously healthy 32 years old; veterinarian male with palatal myoclonus, as a rare presentation of this disorder, and review the neurologic aspects of hashimoto encephalitis . Results:The clinical presentation of HE is characterized by progressive cognitive decline tremor, transient aphasia, seizures, abnormal gait, sleep disorder and stroke-like episodes .Myoclonus, either generalized or multifocal, and tremor, often of the bilateral upper extremities, is the most frequently observed involuntary movements in HE.Conclusion:The rapidly progressive cognitive dysfunction and encephalopathies observed.
Armstrong-Javors, Amy; Pratt, Janey; Kharasch, Sigmund
Roughly 1% of all weight loss surgery is performed in adolescents. There is strong evidence demonstrating significant postsurgical weight loss, improvement in quality of life, and reduction in comorbidities such as hypertension and diabetes. Reports of postoperative complications in adolescents are few because of the small sample size in most series. Despite vitamin supplementation, nutritional deficiencies requiring hospitalization occur occasionally after Roux-en-Y gastric bypass. Wernicke encephalopathy, a triad of ophthalmoplegia, ataxia, and altered mental status, is a serious consequence of thiamine (vitamin B 1 ) deficiency. Few cases of Wernicke encephalopathy after weight loss surgery have been reported in the literature and even fewer in the pediatric population. Here we describe a teenage girl who develops vomiting after Roux-en-Y gastric bypass and presented with nystagmus, irritability, and ataxia. The clinical presentation, diagnosis, and treatment of Wernicke encephalopathy in adolescents after bariatric surgery are discussed. Copyright © 2016 by the American Academy of Pediatrics.
Carl, David; Grüllich, Carsten; Hering, Steffen; Schabet, Martin
Ipilimumab is a cytotoxic T-lymphocyte-associated protein 4 receptor antibody used for immunotherapy in cancer. Several immune-related adverse events are known. Steroid responsive encephalopathy associated with autoimmune thyroiditis is an autoimmune encephalopathy associated with Hashimoto's Disease and elevated serum levels of the related antibodies (anti-thyroid-peroxidase antibody or anti-thyroglobulin antibody). Our case implies that steroid responsive encephalopathy associated with autoimmune thyroiditis may be another previously unreported side effect of ipilimumab therapy. We report the case of a 64 years old caucasian patient with prostatic cancer who received ipilimumab therapy in a clinical trial. He presented with aphasia, tremor and ataxia, myocloni, hallucinations, anxiety and agitation in turns with somnolence. Cranial nerves, deep tendon reflexes, motor and sensory functions were normal. Electroencephalography showed background slowing but no epileptic discharges. Brain magnetic resonance imaging was normal and showed no signs of hypophysitis. Cerebrospinal fluid findings ruled out infection and neoplastic meningitis. Anti-thyroid antibodies (anti-thyroid-peroxidase antibody and anti-thyroglobulin antibody) were heavily increased. Assuming steroid responsive encephalopathy associated with autoimmune thyroiditis the patient was treated with 1,000 mg methylprednisolone i.v. for 3 days and continued with 1 mg/kg orally. On the 3rd day of treatment the patient's condition started to improve. Within the next few days he gradually returned to his previous state, and electroencephalography eventually showed only slight slowing. Seven months later the patient's condition was stable, and anti-thyroid antibodies were no more detectable. Steroid responsive encephalopathy associated with autoimmune thyroiditis may be a hitherto unrecognized complication of ipililumab treatment and should be taken into consideration in patients developing central nervous
Stephens, Angela; Patel, Khilen; Rao, Ashwin; Browne, Paul; Raley, Susanna; Street, Linda
Wernicke's encephalopathy (WE) is an acute neurologic syndrome resulting from a deficiency in thiamine, also known as Vitamin B1. Thiamine stores can be depleted rapidly in patients with severe hyperemesis. Treatment with thiamine typically results in complete resolution of the neurological abnormalities. A 15-year-old G2P0010 at 13.2 weeks gestation presented with altered mental status and transaminitis. She had a medical termination in her previous pregnancy following an admission for a similar clinical scenario. She was initially thought to have a postoperative surgical complication due to recent cholecystectomy, but further evaluation revealed thiamine depletion. Magnetic resonance imaging confirmed the diagnosis of WE. Repletion of thiamine and folic acid resulted in rapid clinical improvement. WE should be considered in the differential diagnosis of pregnant patients with hyperemesis and altered mental status. A prior history of WE increases the risk of recurrence during pregnancy. Severe hyperemesis during pregnancy increases the risk of thiamine deficiency and WE. Early thiamine supplementation may reduce the risk of WE in patients with a prior clinical history or in patients with severe hyperemesis gravidarum.
Variava, Ebrahim; Sigauke, Farai R; Norman, Jennifer; Rakgokong, Modiehi; Muchichwa, Petudzai; Mochan, Andre; Maartens, Gary; Martinson, Neil A
WHO treatment guidelines recommend efavirenz in first-line antiretroviral therapy (ART). Efavirenz commonly causes early transient neuropsychiatric adverse events. We present 20 cases with severe encephalopathy accompanied by ataxia due to efavirenz toxicity. Consecutive HIV-infected adults taking efavirenz-containing ART admitted to Tshepong hospital, Klerksdorp, South Africa with ataxia and encephalopathy were included in this case series. We identified 20 women admitted to hospital with severe ataxia. All received efavirenz-based ART for a median of 2 years. All had severe ataxia and none had nystagmus. Eleven had features of encephalopathy. Median weight was 34 kg [interquartile range (IQR): 29.7-35.3]; median CD4 count 299 cells/mm (IQR: 258-300) and most (18 of 19) were virally suppressed. Eight patients had a record of prior weights and 7 of 8 showed significant weight loss with a median weight loss of 10.8 kg (IQR: 8-11.6). All cases had plasma efavirenz assays, 19 were supratherapeutic (more than twice the upper level of therapeutic range), and 15 had concentrations above the upper limit of assay detection. Ataxia resolved after withdrawal of efavirenz at a median time of 2 months (IQR: 1.25-4) and recurred in 2 of 3 patients when rechallenged. Admissions before diagnosis were frequent with 10 cases admitted previously. Three women died. Efavirenz toxicity may present with severe reversible ataxia often with encephalopathy years after its initiation, likely in genetic slow metabolizers. We recommend that patients whose weight is ataxia. Eight patients had a record of prior subsequent weights and 7 of 8 showed significant weight loss gain; median gain of 10.8 kg (IQR: 8-11.6).
Full Text Available Tacrolimus is an immunosuppressive drug mainly used to lower the risk of transplant rejection in individuals who are post solid organ or hematopoietic transplantation. It is a macrolide which reduces peptidyl-propyl isomerase activity and inhibits calcineurin, thus inhibiting T-lymphocyte signal transduction and interleukin-2 (IL-2 transcription. It has been associated with Posterior Reversible Encephalopathy Syndrome (PRES, a disease of sudden onset that can present as a host of different symptoms, depending on the affected area of the brain. While infectious causes of encephalopathy must always be entertained, the differential diagnosis should also include PRES in the appropriate context. We report three cases of PRES in patients with acute myeloid leukemia (AML placed on tacrolimus after receiving a bone marrow transplant (BMT. The focus of this review is to enhance clinical recognition of PRES as it is related to an adverse effect of Tacrolimus in the setting of hematopoietic transplantation.
Meiron, Oded; Gale, Rena; Namestnic, Julia; Bennet-Back, Odeya; David, Jonathan; Gebodh, Nigel; Adair, Devin; Esmaeilpour, Zeinab; Bikson, Marom
Early onset epileptic encephalopathy is characterized by high daily seizure-frequency, multifocal epileptic discharges, severe psychomotor retardation, and death at infancy. Currently, there are no effective treatments to alleviate seizure frequency and high-voltage epileptic discharges in these catastrophic epilepsy cases. The current study examined the safety and feasibility of High-Definition transcranial direct current stimulation (HD-tDCS) in reducing epileptiform activity in a 30-month-old child suffering from early onset epileptic encephalopathy. HD-tDCS was administered over 10 intervention days spanning two weeks including pre- and post-intervention video-EEG monitoring. There were no serious adverse events or side effects related to the HD-tDCS intervention. Frequency of clinical seizures was not significantly reduced. However, interictal sharp wave amplitudes were significantly lower during the post-intervention period versus baseline. Vital signs and blood biochemistry remained stable throughout the entire study. These exploratory findings support the safety and feasibility of 4 × 1 HD-tDCS in early onset epileptic encephalopathy and provide the first evidence of HD-tDCS effects on paroxysmal EEG features in electroclinical cases under the age of 36 months. Extending HD-tDCS treatment may enhance electrographic findings and clinical effects.
Caspar Godthaab Sørensen
Full Text Available Introduction: Encephalopathy and convulsive seizures are rare manifestations of metronidazole toxicity. The incidence is unknown, but the condition has most frequently been reported in patients in their fifth to sixth decades. Usually, this condition is regarded as reversible, but permanent deficits and even death have been reported. Case Report: A 66-year-old female patient undergoing metronidazole treatment for pleural empyema was admitted to our institution after her second episode of seizure. Over the course of 1 week after admittance, the patient developed several convulsive seizures along with progressive cerebellar dysfunction and cognitive impairment. MRI revealed bilateral, symmetrical hyperintense signal changes in the pons and dentate nuclei. EEG, ECG, lumbar puncture, and blood samples were normal. The patient improved already 2–3 days after discontinuation of metronidazole and was discharged fully recovered after 17 days. Follow-up clinical assessment and MRI were unremarkable. Conclusion: Metronidazole-induced encephalopathy is a rare condition, and due to a general lack of awareness the diagnosis is often delayed. This condition should be considered in metronidazole-treated patients presenting with unprovoked seizures, myoclonus, cerebellar signs, and encephalopathy. Characteristic MRI lesions may support the clinical suspicion.
Rener-Primec, Zvonka; Balkovec, Valerija
Cutaneous adverse reactions to antiepileptic drugs (AEDs) are usually easily recognized in daily clinical practice when they manifest as a morbilliform or maculopapular rash within the first few weeks after introducing an AED. Valproate (VPA)-induced encephalopathy is a rare but serious complication, presenting with impaired consciousness, with or without hyperammonemia, normal liver enzymes, and normal serum level of VPA. A 2-year-old Caucasian boy with severe developmental disability and pharmacoresistant epilepsy presented with fever, generalized erythrodermia, and encephalopathy, which resolved after discontinuation of valproate. Sodium valproate (30 mg/kg/day) was introduced 5 months previously, as the third drug in combination with vigabatrin and levetiracetam, due to frequent daily seizures. The clinical condition of generalized erythrodermia and encephalopathy was recognized by the treating physician as a possible adverse reaction to VPA: with the Naranjo scale it was probably associated with VPA (six points) and possibly associated with vigabatrin and levetiracetam (three and two points, respectively). After valproate withdrawal, the patient recovered completely. This case is of interest because erythrodermia was a clue to the recognition of valproate-related adverse reaction with severe central nervous system involvement without hyperammonemia and with normal liver enzymes--a very rare occurrence.
Full Text Available Posterior reversible encephalopathy syndrome (PRES is a rare entity involving brainstem in very rare reported cases. We describe here the case of a boy who presented to the emergency department for headaches and strabismus. Diagnosis of PRES was retained by magnetic resonance imaging. The causes were blood pressure urgency and renal failure. Location of lesions was very rarely reported in literature and neurological troubles were persistent. Emergency physicians should evocate PRES each time there is a clinical context associated with neurological troubles by a normal brain CT scan. Early diagnosis is very important to treat its causes and improve prognosis.
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...
Dr Shital Turakhia
Full Text Available Hypernatremia is defined as increased serum sodium concentration more than 145mEq/L. It occurs most commonly in pediatric patients, geriatric patients and patients with debilitated conditions in ICU who suffers from severe water losses. Newborns and toddlers are at high risk as they have poor thirst control and regulatory mechanism. It occurs when patient is suffering from diarrhea and then mismanagement by over treating the patient with sodium containing fluids. CNS complications and radiological findings are rarely recognized and reported. We hereby report cases of two such pediatric patients who were referred to our hospital from primary health care centers with complain of convulsions and diarrhea.
Full Text Available Abstract Introduction Hepatic encephalopathy may be initiated by many factors such as gastrointestinal bleeding, infections, fluid and electrolyte disturbances. Hypokalemia is one of the most commonly encountered electrolyte abnormalities causing hepatic encephalopathy in patients with cirrhosis. Case presentation We present the case of a 62-year-old Caucasian man with decompensated liver cirrhosis having multiple episodes of hepatic encephalopathy precipitated by vomiting. He had an incisional hernia at the right lumbar region. A barium contrast study of the small intestine and magnetic resonance imaging showed that the hernial sac included gastric antrum and bowel. We observed that hepatic encephalopathy coincided with hypokalemia as a result of a large volume of vomiting triggered by the collapsed hernial sac. Hepatic encephalopathy was resolved by administration of intravenous potassium. Conclusion This case illustrates that a hernia causing a large volume of vomiting may be a precipitant factor in the development of hepatic encephalopathy.
Hirose, Hisaaki; Suzuki, Koh-ichirou; Nakamura, Yoshihiro; Kido, Kun-ichi; Sato, Masaharu; Fujii, Chiho; Kohama, Akitsugu
We present an interesting case of burn encephalopathy. The patient is a three-year-old girl with second to third degree and 30 % scald burn. She developed central nervous symptom on the second day with high fever and systemic convulsions and was transferred to our clinic on the third day from a local hospital. Her level of consciousness was 30 to 100 (3-3-9 formula) and she developed extra-pyramidal involuntary movement; these neurological signs persisted untill 66th day when she spoke for the first time since admission. Her EEG showed diffuse brain dysfunction and CT showed marked brain atrophy. She began to improve after around 50 days systematically as well as neurologically and was discharged after four months. EEG, CT findings and neurological signs were normal 1.5 years later. We could not find a case of reversible brain atrophy in the reports on burn encephalopathy or other neurological disorders except for the cases of long-term steroid administration on autoimmune diseases or ACTH therapy on infantile spasm. In our case, the reversible brain atrophy might be caused by the rise of endogenous steroid under burn stress, or transient malfunction of cerebro-spinal fluid absorption, or some other causes. (author)
Full Text Available We present an original case report of a bladder explosion during a TURP intervention for benign prostatic hypertrophy, that was brought on by the absorption of about 5 liters of glycine 1.5% and then onset of a severe hyponatremia. The quick and inappropriate correction of this electrolyte imbalance led the onset of encephalopathy and the death of the patient. The authors discuss the pathogenesis of these uncommon diseases and, considering the most recent Italian Legislation, they highlight the importance to respect good clinical practice standards and guidelines to ensure the most appropriate treatments for the patient and remove any assumptions of medical liability.
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...
Shodeinde A Coker
Full Text Available Background/Objectives: Neurotoxicity is a serious and sometimes fatal adverse effect that can occur following methotrexate treatment. We describe two adult patients with hematological malignancies with methotrexate encephalopathy who recovered with dextromethorphan therapy. Results: Case 1: A 24-year-old male with acute lymphoblastic leukemia developed the acute onset of bilateral facial weakness and slurred speech after his first treatment with high-dose intravenous methotrexate. The clinical scenario and a head magnetic resonance imaging supported a diagnosis of methotrexate encephalopathy. Treatment with dextromethorphan was coincident with recovery. Case 2: A 65-year-old female with recurrent diffuse large B-cell lymphoma was treated with high-dose intravenous methotrexate. Two weeks after a cycle, she developed hypoactive delirium, marked lethargy, ocular ataxia, and a right-sided facial weakness. Within 2 days of starting dextromethorphan, there was improvement with clinical recovery. Conclusions: These two cases suggest that N-methyl d-aspartate receptor activation by homocysteine may play an important role in the pathogenesis of methotrexate neurotoxicity.
Elefante, Andrea, E-mail: email@example.com [Department of Neuroradiology, University of Naples “Federico II”, Naples (Italy); Puoti, Gianfranco [I Division of Neurology, General Medicine Department, Second University of Naples, Naples (Italy); Senese, Rossana [Department of Neuroradiology, University of Naples “Federico II”, Naples (Italy); Coppola, Cinzia [I Division of Neurology, General Medicine Department, Second University of Naples, Naples (Italy); Russo, Carmela [Department of Neuroradiology, University of Naples “Federico II”, Naples (Italy); Tortora, Fabio [Department of Neuroradiology, Second University of Naples, Naples (Italy); Divitiis, Oreste de [Department of Neurosurgery, University of Naples “Federico II”, Naples (Italy); Brunetti, Arturo [Department of Neuroradiology, University of Naples “Federico II”, Naples (Italy)
Aim: Acute Wernicke's encephalopathy (WE) is a severe neurological disorder caused by thiamine deficiency, most commonly found in chronic alcoholics. It is not so easy to suspect acute WE when the clinical picture does not include all the typical symptoms and alcohol abuse is not reported. Three rare cases of Wernicke's encephalopathy (WE) in non-alcoholic patients are reported. Cases presentation: Two patients developed the disease following prolonged intravenous feeding, the third was carrying a gastric lymphoma. None of them presented with the classic clinical triad of WE (ophtalmoplegia/nystagmus, ataxia and consciousness disturbance), showing just one or two of the typical symptoms. Brain Magnetic Resonance Imaging (MRI) represented the key tool to suspect and define WE diagnosis, showing a picture characterized by bilaterally altered signal of the thalamic pulvinar, mesencephalic cup, mammillary bodies, periaqueductal grey matter and floor of fourth ventricle. All patients dramatically improved within 48 h after administration of thiamine. Conclusion: We emphasize that WE should be suspected in all patients showing typical MRI features presenting with at least one of the clinical triad of WE.
Elefante, Andrea; Puoti, Gianfranco; Senese, Rossana; Coppola, Cinzia; Russo, Carmela; Tortora, Fabio; Divitiis, Oreste de; Brunetti, Arturo
Aim: Acute Wernicke's encephalopathy (WE) is a severe neurological disorder caused by thiamine deficiency, most commonly found in chronic alcoholics. It is not so easy to suspect acute WE when the clinical picture does not include all the typical symptoms and alcohol abuse is not reported. Three rare cases of Wernicke's encephalopathy (WE) in non-alcoholic patients are reported. Cases presentation: Two patients developed the disease following prolonged intravenous feeding, the third was carrying a gastric lymphoma. None of them presented with the classic clinical triad of WE (ophtalmoplegia/nystagmus, ataxia and consciousness disturbance), showing just one or two of the typical symptoms. Brain Magnetic Resonance Imaging (MRI) represented the key tool to suspect and define WE diagnosis, showing a picture characterized by bilaterally altered signal of the thalamic pulvinar, mesencephalic cup, mammillary bodies, periaqueductal grey matter and floor of fourth ventricle. All patients dramatically improved within 48 h after administration of thiamine. Conclusion: We emphasize that WE should be suspected in all patients showing typical MRI features presenting with at least one of the clinical triad of WE.
Full Text Available Posterior reversible encephalopathy syndrome (PRES is associated with various clinical manifestations such as headache, blurred vision, confusion and tonic-clonic convulsion. Some of the predisposing factors for PRES include hypertensive encephalopathy, preeclampsia and eclampsia, lupus erythematosus, thrombotic thrombocytopenic purpura and long-term use of immunosuppressive drugs. This condition rarely occurs after normotensive and uneventful pregnancies. Several theories have been proposed on the etiology of PRES. For instance, endothelial injury and brain edema have been reported as possible causes of PRES. Although PRES is a temporary condition, proper and timely management of the disorder in the acute phase is critical for the prevention of permanent neurological complications. During pregnancy, PRES is normally accompanied with hypertension. In this paper, we present a rare case of PRES in a normotensive pregnancy in a 25-year-old parturient woman (Gravida 2, Ab 1. The patient unexpectedly manifested symptoms of tonic-clonic convulsion one hour after an uneventful vaginal delivery, which were successfully managed. According to our observations, PRES has various clinical manifestations with unexpected occurrence in some cases. Therefore, it is recommended that maternity centers be well-equipped with resuscitation tools, emergency drugs and expert staff so as to manage unforeseen PRES efficiently and prevent permanent maternal neurological complications and mortality.
Mastroyianni, Sotiria D; Gionnis, Dimitrios; Voudris, Konstantinos; Skardoutsou, Angeliki; Mizuguchi, Masashi
Acute necrotizing encephalopathy of childhood is a novel type of parainfectious encephalopathy with a racial and geographic predilection, rarely reported from other than East Asian areas. The objective was to describe the clinical, imaging, and other laboratory findings of non-Asian patients with acute necrotizing encephalopathy. Data were collected from three patients diagnosed in Athens over a 4-year period plus 16 cases reported from other European and North American countries. One of the Greek children died, and the other two had a normal outcome. A neuropathologic examination in the fatal case showed edematous necrosis without inflammatory, reactive, or proliferative changes. Data from Greek and other non-Asian patients support the homogeneity of the disease worldwide.
, 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.
Full Text Available Hashimoto’s encephalopathy (HE is a rare, poorly understood, autoimmune disease characterized by symptoms of acute or subacute encephalopathy associated with increased anti-thyroid antibody levels. Here, we report a case of a 14-year-old girl with HE and briefly review the literature. The patient presented with acute mental changes and seizures, but no evidence of infectious encephalitis. In the acute stage, the seizures did not respond to conventional antiepileptic drugs, including valproic acid, phenytoin, and topiramate. The clinical course was complicated by the development of acute psychosis, including bipolar mood, insomnia, agitation, and hallucinations. The diagnosis of HE was supported by positive results for antithyroperoxidase and antithyroglobulin antibodies. Treatment with methylprednisolone was effective; her psychosis improved and the number of seizures decreased. HE is a serious but curable, condition, which might be underdiagnosed if not suspected. Anti-thyroid antibodies must be measured for the diagnosis. HE should be considered in patients with diverse neuropsychiatric manifestations.
Watanabe, Seiji; Yamakura, Shinji; Hirano, Keiko; Okumura, Yoshinori; Aiba, Hideo
Wernicke's encephalopathy (WE) or thiamine deficiency is fatal if left untreated. We report a case of a 3-year-old boy with infantile autism and a severe eating disorder who developed WE after 3 weeks of starvation without thiamine supplementation. The eating disorder started when he entered preschool. He presented with unconsciousness and a cluster of seizures. Cranial magnetic resonance imaging (MRI) showed high-intensity signal changes in the basal ganglia on T2-weighted images and fluid-attenuated inversion recovery (FLAIR). Treatment with high-dose intravenous thiamine was effective. Pediatric patients with WE tends to show no typical symptoms or brain lesions on MRI as seen in adult WE patients typically along alcoholics. Brain lesions similar to those in hypoxia or mitochondrial diseases such as Leigh's encephalopathy, are observed in patients with pediatric WE, and this makes diagnosis difficult. WE should be considered when patients with severe eating disorders present with unconsciousness and/or frequent seizures, and show basal ganglia lesions on MRI, differential diagnosis should include WE.
Full Text Available 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 five days without treatment she was diagnosed with WE in a general hospital. During the course of the disease minimal change to the acute situation occurred, with chronic confusion, attention deficits and incoherent behavior symptoms most notable unlike classical Korsakoff's Syndrome (KS. Neuropsychological assessment after four and sixteen months after admission to the hospital revealed global cognitive decline, with striking impairments in attentional, executive and memory functions. The present case study suggests that the state of confusion and the neuropsychological symptoms in WE can become chronic in case of very late treatment. We therefore recommend that confused alcoholics should receive appropriate parenteral thiamine according to the current clinical standards.
Kaneko, Yuji; Tsurutani, Yuya; Sagawa, Naoko; Kondo, Mai; Sata, Akira; Miyao, Mariko; Azuma, Reo; Orimo, Satoshi; Mizuno, Yuzo
A 70-year-old man with a 28-year history of type 2 diabetes mellitus was admitted due to persistent vomiting and neurological abnormalities in Nov 2012. He had developed gait disturbance and diplopia for six months during antiplatelet therapy, which was initiated following the diagnosis of a cerebellar infarction in June 2012. He had nystagmus, truncal ataxia and an ocular motility disorder, and the MRI study showed increased FLAIR and DWI signals in the peri-third ventricle and periaqueductal region, in addition to the cerebellar vermis. Wernicke encephalopathy was suspected according to his symptoms, and thiamine administration dramatically improved his condition. He did not have a history of alcohol abuse or poor eating habits; however, various coexisting factors, including diabetes mellitus, pyloric stenosis and the use of antiulcer drugs and insulin, were considered to be responsible for Wernicke encephalopathy. This case demonstrates the importance of distinguishing Wernicke encephalopathy from cerebrovascular disease in elderly patients.
Tozzo, Pamela; Caenazzo, Luciana; Rodriguez, Daniele; Bolcato, Matteo
Introduction: Wernicke’s encephalopathy (WE) is a neurological syndrome caused by thiamine deficiency, and clinically characterized by ophthalmoplegia, ataxia and acute confusion. In developed countries, most cases of WE have been seen in alcohol misusers. Other reported causes are gastrointestinal tract surgery, hyperemesis gravidarum, chronic malnutrition, prolonged total parenteral nutrition without thiamine supplementation, and increased nutrient requirements as in trauma or septic shock....
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 This report presents the case of a 60-year-old woman who was diagnosed with stage IV lung adenocarcinoma with asymptomatic brain metastases and commenced chemotherapy with cisplatin/pemetrexed (CDDP/Pem. She experienced tonic-clonic convulsions on day 9 of the first cycle, which were accompanied by increased blood pressure (173/69 mm Hg and headache. Therefore, brain MRI was performed to check for stroke or progression of brain metastatic foci. T2-weighted, FLAIR, and ADC map images showed high-intensity areas in the subcortical region of the bilateral parieto-occipital lobes, leading to a diagnosis of posterior reversible encephalopathy syndrome (PRES. The symptoms improved after treatment with antihypertensive and antiepileptic drugs. Clinicians should keep it in mind that central nervous system symptoms during anticancer therapy containing Pem may indicate possible PRES.
Hasbun H, Jorge; Rodriguez G, Marcelo; Miranda G, Gonzalo
The Posterior Reversible Encephalopathy Syndrome is a neurological condition described on 1996, developed in patients with complex systemic conditions, especially pregnant women with pre eclampsia that at the same time presented neurological signs as seizures, headache, visual loss, and vomiting in addition to posterior brain edema, visible on neuroimaging and located in parietal and occipital lobes, that usually reverses completely. We present two clinical cases with Pres and eclampsia, antenatal and post-partum, both with seizure and confirmed brain edema with Nuclear Magnetic Resonance. Both had a favorable evolution after the anticonvulsant and anti-hypertensive therapy were done. We discuss the controversy over pathophysiological mechanisms, the new methods for diagnosis and management and the importance of multidisciplinary approach
Wong, Virginia Chun-Nei; Kwong, Anna Ka-Yee
A Chinese boy presented at 18 months with intractable epilepsy, developmental delay and autistic features. He had multiple seizure types, including absence, myoclonic seizures, limb spasm and tonic seizures. His seizures were finally controlled at 3 years of age with clonazepam and a short course of chloral hydrate incidentally given for his insomnia. Subsequently, he had improvement in his communication skills. A novel hemizygous missense variant (c.1649G>A; p.R550Q) in exon 12 of CDKL5 gene was detected for him, his asymptomatic mother and elder sister. His phenotype is less severe than other male cases. We recommend screening CDKL5 for boys with pharmarco-resistant epilepsy and a trial of benzodiazepines for Infantile Epileptic Encephalopathy (IEE). Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Timothy R. Larsen
Full Text Available Introduction. Wernicke’s encephalopathy is a well-described syndrome characterized by the classic triad of confusion, ataxia, and ophthalmoplegia. Wernicke’s encephalopathy results from thiamine (vitamin B1 deficiency. Common causes include alcoholism and gastric disorders. Wernicke’s has been described in patients with acquired immune deficiency syndrome (AIDS; however, given these patients’ immunosuppressed state, the diagnosis of Wernicke’s encephalopathy is not apparent. Case Presentation. A 31-year-old previously healthy male presented to the ER complaining of progressive dyspnea. Workup revealed HIV/AIDS and PCP pneumonia. He was treated and improved. On day 14 he became confused and developed nystagmus and ataxia. Considering his immunocompromised state, infectious and neoplastic etiologies topped the differential diagnosis. CT head was negative. Lumbar puncture was unremarkable. Brain MRI revealed increased T2 signal in the medial thalamus bilaterally. Intravenous thiamine was administered resulting in resolution of symptoms. Discussion. The classic triad of Wernicke’s encephalopathy occurs in 10% of cases. When immunosuppressed patients develop acute neurologic symptoms infectious or neoplastic etiologies must be excluded. However, given the relative safety of thiamine supplementation, there should be a low threshold for initiating therapy in order to reverse the symptoms and prevent progression to Korsakoff dementia, which is permanent.
Maas, Annemieke; Braun, Kees P J; Geleijns, Karin; Jansen, Floor E; van Royen-Kerkhof, Annet
Hashimoto encephalopathy is a rare condition, characterized by the association of encephalopathy with a variety of neurological symptoms and autoantibodies to the thyroid gland. Its etiology is unknown, and symptoms are usually treated with immune suppressive therapy, e.g., high doses of corticosteroids. Here, we report the long-term outcome in two steroid-refractory adolescents with Hashimoto encephalopathy who were treated with rituximab, a monoclonal antibody directed against CD20. In addition, we reviewed the literature regarding treatment strategies in Hashimoto encephalopathy. Anti-B-cell therapy can be of value in the treatment of Hashimoto encephalopathy, especially in steroid refractory cases, but side effects due to low levels of immunoglobulins warrant careful monitoring. Copyright © 2016 Elsevier Inc. All rights reserved.
Joseph C Maroon
Full Text Available Chronic traumatic encephalopathy (CTE is a neurodegenerative disease associated with head trauma. Although initially believed to affect only boxers, the at-risk population has expanded to encompass a much wider demographic, including American football players, hockey players, wrestlers, and military veterans. This expansion has garnered considerable media attention and public concern for the potential neurodegenerative effects of head trauma. The main aim of this systematic review is to give a complete overview of the common findings and risk factors for CTE as well as the status quo regarding the incidence and prevalence of CTE. This systematic review was performed using PubMed and MEDLINE and includes all neuropathologically confirmed cases of CTE in the medical literature to date, from the first published case in 1954 to August 1, 2013 (n = 153. The demographics, including the primary source of mTBI (mild Traumatic Brain Injury, age and cause of death, ApoE genotype, and history of substance abuse, when listed, were obtained from each case report. The demographics of American football players found to have CTE are also presented separately in order to highlight the most prevalent group of CTE cases reported in recent years. These 153 case reports of CTE represent the largest collection to date. We found that a history of mTBI was the only risk factor consistently associated with CTE. In addition, we found no relationships between CTE and age of death or abnormal ApoE allele. Suicide and the presence of premorbid dementia was not strongly associated with CTE. We conclude that the incidence of CTE remains unknown due to the lack of large, longitudinal studies. Furthermore, the neuropathological and clinical findings related to CTE overlap with many common neurodegenerative diseases. Our review reveals significant limitations of the current CTE case reporting and questions the widespread existence of CTE in contact sports.
Maroon, Joseph C; Winkelman, Robert; Bost, Jeffrey; Amos, Austin; Mathyssek, Christina; Miele, Vincent
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with head trauma. Although initially believed to affect only boxers, the at-risk population has expanded to encompass a much wider demographic, including American football players, hockey players, wrestlers, and military veterans. This expansion has garnered considerable media attention and public concern for the potential neurodegenerative effects of head trauma. The main aim of this systematic review is to give a complete overview of the common findings and risk factors for CTE as well as the status quo regarding the incidence and prevalence of CTE. This systematic review was performed using PubMed and MEDLINE and includes all neuropathologically confirmed cases of CTE in the medical literature to date, from the first published case in 1954 to August 1, 2013 (n = 153). The demographics, including the primary source of mTBI (mild Traumatic Brain Injury), age and cause of death, ApoE genotype, and history of substance abuse, when listed, were obtained from each case report. The demographics of American football players found to have CTE are also presented separately in order to highlight the most prevalent group of CTE cases reported in recent years. These 153 case reports of CTE represent the largest collection to date. We found that a history of mTBI was the only risk factor consistently associated with CTE. In addition, we found no relationships between CTE and age of death or abnormal ApoE allele. Suicide and the presence of premorbid dementia was not strongly associated with CTE. We conclude that the incidence of CTE remains unknown due to the lack of large, longitudinal studies. Furthermore, the neuropathological and clinical findings related to CTE overlap with many common neurodegenerative diseases. Our review reveals significant limitations of the current CTE case reporting and questions the widespread existence of CTE in contact sports.
Vergura, Michele; Prencipe, Michele; Del Giudice, Antonio Maria; Grifa, Rachele; Miscio, Filomena; Pennelli, Anna Maria; Popolizio, Teresa; Simeone, Anna; Ferrara, Mariangela; Leone, Maurizio; Aucella, Filippo
Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiological syndrome, usually reversible, characterized by vasogenic oedema in cerebral posterior regions in patients with autoimmune diseases, nephropathies, hypertensive crisis, eclampsia and exposure to cytotoxic drugs. The main symptoms are: headache, nausea, vomiting, seizures, visual disturbance and altered consciousness. Complications as cerebral hemorrhage and recurrences are rare. We describe a case of a 65 years old woman, affected by chronic kidney disease, recently exacerbated, diabetes and hypertension in treatment, who showed an heterogeneous clinical presentation with vomiting, headache, blurred vision and impaired consciousness during an episode of acute hypertension. After an adjustement of the antihypertensive treatment we observed a regression of symptoms in one week. FLAIR sequences on MRI showed cerebral bilateral vasogenic oedema in posterior regions, typical for PRES. This case was suggestive for PRES and a prompt adjustement of the antihypertensive treatment was critical for clinical recovery. Brain MRI was crucial for diagnosis. It is important for clinicians to recognize PRES as a possible complication of renal disease and hypertensive crisis. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.
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...
Petrović Igor N.
Full Text Available Introduction. Mitochondrial encephalopathy, lactacidosis and stroke-like episodes (MELAS represent a multisystemic dysfunction due to various mutations in mitochondrial DNA. Here we report a patient with genetically confirmed MELAS. Case Outline. A patient is presented whose clinical features involved short stature, easy tendency to fatigue, recurrent seizures, progressive cognitive decline, myopathy, sensorineural deafness, diabetes mellitus as well as stroke-like episodes. The major clinical feature of migraine type headache was not present. Neuroimaging studies revealed signs of ischemic infarctions localized in the posterior regions of the brain cortex. Electron microscopy of the skeletal muscle biopsy showed subsarcolemmal accumulation of a large number of mitochondria with paracristal inclusions in the skeletal muscle cells. The diagnosis of MELAS was definitively confirmed by the detection of a specific point mutation A to G at nucleotide position 3243 of mitochondrial DNA. Conclusion. When a relatively young patient without common risk factors for ischemic stroke presents with signs of occipitally localized brain infarctions accompanied with multisystemic dysfunction, MELAS syndrome, it is necessary to conduct investigations in order to diagnose the disease.
Lukiana, Tuna; Mandina, Madone; Situakibanza, Nanituma H; Mbula, Marcel M; Lepira, Bompeka F; Odio, Wobin T; Kamgno, Joseph; Boussinesq, Michel
It is well known that renal and neurological complications may occur after antifilarial treatment of patients infected with Loa loa. Conversely, spontaneous cases of visceral complications of loiasis have been rarely reported. A 31-year-old Congolese male patient who had not received any antifilarial drug developed oedema of the lower limbs, and then transient swellings of upper limbs. Two months after, he developed troubles of consciousness within several hours. At hospital, the patient was comatose with mild signs of localization. Laboratory tests and an abdominal echography revealed a chronic renal failure due to a glomerulopathy. Three weeks after admission, Loa microfilariae were found in the cerebrospinal fluid, and a calibrated blood smear revealed a Loa microfilaraemia of 74,200 microfilariae per ml. The level of consciousness of the patient improved spontaneously, without any specific treatment, but several days after becoming completely lucid, the patient died suddenly, from an undetermined cause. Unfortunately, no biopsy or autopsy could be performed. The role of Loa loa in the development of the renal and neurological troubles of this patient is questionable. But the fact that such troubles, which are known complications of Loa infection, were found concomitantly in a person harbouring a very high microfilarial load suggests that they might have been caused by the filarial parasite. In areas endemic for loiasis, examinations for a Loa infection should be systematically performed in patients presenting an encephalopathy or a glomerulopathy.
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 firstname.lastname@example.org.
Full Text Available ABstract Introduction Influenza virus-associated encephalitis/encephalopathy is a severe childhood illness with a poor prognosis. Adult case reports are rare and, to date, there have been no reports of adults with a mild subcortical encephalopathy with reversible lesions of the corpus callosum splenium. Case presentation A previously healthy 35-year-old man presented with acute progressive tetraplegia, transcortical motor aphasia and a mild decrease in his consciousness during his recovery after receiving oseltamivir phosphate treatment, and influenza type A antiviral medication. The initial magnetic resonance imaging study at day 1 showed symmetrical diffuse lesions in the white matter and a lesion on the central portion of the corpus callosum splenium. These findings had resolved on follow-up studies at day 8 and day 146. His neurological deficits mostly recovered within 12 hours following methylprednisolone pulse therapy. The levels of interleukin-6 and interleukin-10 in his blood and cerebrospinal fluid were initially elevated, but rapidly decreased to normal levels by day 8. Conclusion It is important for clinicians to recognize that even in adulthood, the subcortical encephalopathy observed during the therapeutic treatment for influenza type A infection can occur in conjunction with a reversible lesion of the corpus callosum, which may recover quickly. In addition, the cytokine storm in the blood system and the corticospinal cavity may play an important role in the etiology of the disease process.
Ugurel, Mehmet Sahin; Hayakawa, Minako
Background: There is a relative lack of definitive information about the contrast-enhancement characteristics of lesions in posterior reversible encephalopathy syndrome (PRES). Objective: Evaluation of contrast-enhanced MRI findings in PRES with a special emphasis on pathophysiology of post-gadolinium behavior of these lesions. Materials and methods: Contrast-enhanced 1.5 T MRI findings and relevant clinical data of the patients were retrospectively reviewed on 13 cases (six males, seven females; age range: 22-78; mean age 47). Although fluid attenuated inversion recovery (FLAIR) and diffusion-weighted MR images were considered for identification of the entity, primarily post-contrast T1-weighted MR images were searched for traces of enhancement in the lesions. Results: No definitely enhancing lesion was identified in the MR images obtained in 6-48 h after onset of symptoms (mostly headaches, seizures and cortical visual field deficits) in this series. Severity of disease indicated by small hemorrhages, confluence of lesions or progression to cytotoxic edema did not seem to alter this result. Typical lesion characteristics were consistent with vasogenic edema on FLAIR and diffusion MR images. Acute elevation of blood pressure on chronic hypertensive background was responsible in four, eclampsia in three, uremia with blood pressure fluctuations in three, and cyclosporine-toxicity in three cases. Conclusion: Although occasional enhancing brain lesions have been reported in the literature on PRES, contrast-enhancement of lesions may be a factor of scan timing and underlying etiology. Prospective studies with larger series on PRES are required for better evaluation of contrast-enhancement in MRI with respect to scan timing, which in turn may help understand its pathophysiology better
Infante, Maria Teresa; Fancellu, Roberto; Murialdo, Alessandra; Barletta, Laura; Castellan, Lucio; Serrati, Carlo
Wernicke encephalopathy (WE) is a medical emergency caused by thiamine deficiency, characterized by cerebellar ataxia, ophthalmoplegia, and cognitive disturbances that may progress to Korsakoff amnesia. We describe 2 patients with WE who needed high-dose and long-term treatment with thiamine to obtain neurological improvement and recovery. The first patient was a woman diagnosed with non-Hodgkin lymphoma. After a gastrointestinal infection, she developed depression, memory loss, disorientation, behavioral changes, and ataxic paraplegia. Brain magnetic resonance imaging (MRI) showed bilateral alterations in thalamic, frontal, and periaqueductal regions, suggestive of WE. The second patient was a man who lost 10 kg after surgical gastrectomy; he developed diplopia, ophthalmoplegia, cerebellar ataxia, lower limb paresthesias, and amnesia. A brain MRI demonstrated contrast enhancement of mammillary bodies, compatible with WE. The patients were treated with intramuscular (IM) thiamine (1200 mg/d for 2 months and 900 mg/d for a month, respectively) with gradual cognitive and behavioral improvement and brain MRI normalization, while ataxia and oculomotion improved in following months. In both patients, thiamine was gradually reduced to IM 200 mg/d and continued for a year, without clinical relapses. There is no consensus about dosage, frequency, route, and duration of thiamine administration in WE treatment. Based on our cases, we recommend treating patients with WE with higher doses of IM thiamine for a longer time than suggested (900-1200 mg/d for 1-2 months, in our cases) and to gradually reduce dosage after clinical and radiological improvement, maintaining IM 200 mg/d dosage for at least 1 year. © 2016 American Society for Parenteral and Enteral Nutrition.
Full Text Available A young pregnant woman with hyperemesis gravidarum presented to casualty with ataxia, confusion and diplopia. Examination revealed nystagmus and bilateral retinal haemorrhages. Characteristic brain MRI findings and rapid response to thiamine was suggestive of Wernicke’s encephalopathy due to hyperemesis gravidarum. Wernicke’s encephalopathy is a potentially reversible condition caused by thiamine deficiency. It is usually suspected in the setting of chronic alcoholosim and might not be recognised when associated with other conditions. A high index of suspicion is required since lack or delay of treatment may lead to high morbidity and mortality.
Giovagnoli, Anna Rita; Oliveri, Serena; Schifano, Letizia; Raglio, Alfredo
This study describes the effects of active music therapy (AMT) on cognition and behaviour in chronic vascular encephalopathy. A single case study investigated different cognitive and psycho-behavioural changes after AMT. An adult patient with memory, attention, and verbal fluency deficits associated with Vascular Cognitive Impairment-No Dementia (VCI-ND) was treated. A four-months AMT course was based on creative and interactive music playing. Sixteen sessions were conducted simultaneously to the pharmacological therapy. Cognitive performances, mood, interpersonal interactions, and perceived abilities were assessed using standardized neuropsychological and psycho-behavioural measurements. At baseline, the patient reported a tendency to feel tense, nervous, and angry and difficulties in memory and visuospatial performances, frequently accompanied by attention drops. The social network was a habitual component of the patient's life, but not a source of sharing of personal experiences, safety or comfort. Neuropsychological tests showed deficits in object and figure naming, verbal fluency, short and long-term verbal memory, short-term spatial memory, selective attention, and visuomotor coordination. After AMT, the cognitive profile significantly improved in attention, visuomotor coordination, and verbal and spatial memory. Such positive changes were confirmed at the three-months follow-up. An increase of the interpersonal interactions and consistent reduction of anxiety were also observed. In selected patients with VCI-ND, a well-structured AMT intervention added to standard therapy may contribute in determining a stable improvement of cognitive and psycho-behavioural aspects. Controlled studies are needed to confirm these promising results. Copyright © 2013 Elsevier Ltd. All rights reserved.
Namitha Rachel Mathew
Full Text Available Wernicke's Encephalopathy (WE is a potentially devastating disorder, which if not diagnosed and treated at the earliest, could lead to dangerous neurological and ophthalmological complications. We report the ocular manifestations of WE in a pregnant woman with hyperemesis gravidarum.
Patrícia, Coral; Germiniani, Francisco M. B.; Silvado, Carlos E.
Creuzfeldt-Jakob’s Disease is a rare neurodegenerative disorder that is included among the transmissible spongiform encephalopathies. The clinical features are those of a rapid progressive dementia with mioclonic jerks, which progresses to death in less than one year. We report the case of a 79 years old woman, with initial complaints of vertigo, visual and gait compromise, with an initial brain MRI, EEG and CSF that had no specific features of CJD. After 12 days she was again admitted to the...
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Vrielynck, P; Marique, P; Ghariani, S; Lienard, F; de Borchgrave, V; van Rijckevorsel, K; Bonnier, C
Encephalopathy with continuous spike-wave during sleep (CSWS) is a particularly difficult-to-treat childhood epileptic syndrome. This study sought to present the EEG improvement and clinical efficacy of topiramate (TPM), a broad spectrum antiepileptic drug (AED), in a series of 21 children with CSWS encephalopathy. We retrospectively reviewed the EEG results and clinical data of children with CSWS followed-up in our institution and treated with TPM. Sleep EEGs were performed 0-3 months prior to TPM introduction and then at 3 and 12 months. The exclusion criteria were (1) introduction of another AED and (2) withdrawal of a potentially aggravating AED during the first 3 months of treatment. In addition to spike index (SI), the severity of EEG abnormalities was rated using an original scale that also considered the spatial extent of interictal epileptiform discharges. 21 patients were included (18 males, 4-14y, three symptomatic cases). At 3 months, sleep EEG was improved in 14 and normalized in four (TPM doses: 2-5.5 mg/kg/day). Among these 18 patients, 16 manifested cognitive or behavioural improvement. In a subgroup of seven patients with frequent seizures, five became seizure-free and one had over 75% decrease in seizure frequency. At the one-year follow-up, 20 children were still on TPM and 10 exhibited persistent EEG improvement without any other AED being introduced, most of them with clinical benefits. TPM can decrease EEG abnormalities in epileptic encephalopathy with CSWS, achieving clinical improvement in the majority of patients. However, relapse may occur in the long-term in nearly half of cases. Otherwise, TPM has proven particularly useful in reducing seizure frequency in refractory cases. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
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 Background: The essential features of Posterior Reversible Encephalopathy Syndrome (PRES are headache, mental changes, seizures, visual symptoms and often arterial hypertension. Brain RMN typically shows cortico-sottocortical parieto-occipital edema, with a bilateral and symmetric distribution. PRES develops in clinical conditions as hypertensive encephalopathy, preeclampsia/ eclampsia, autoimmune diseases, after transplantation, infections and as an adverse effect of immunosuppressive drugs or chemotherapy. It usually completely reverses with treatment, although permanent sequelae are possible in case of delayed or missed diagnosis. Case report: We describe the case of a transsexual (M!F and tetraplegic patient, admitted for neck and low back pain. She suddenly developed headache, confusion, seizures and severe hypertension with normal blood tests. RMN showed multiple cortico-sottocortical areas of vasogenic and citotoxic edema in temporo-occipital, parietal, frontal, and cerebellar regions. Soon after the beginning of the antihypertensive therapy, clinical recovery was observed, as well as the disappearance of edema at RMN. Discussion and conclusions: Although PRES is usually associated with definite pathological conditions, it is not always the case, as was for the patient here described, who had no predisposing factors in her past clinical history, and presented hypertension only in the acute phase of the syndrome. Since, moreover, PRES usually presents with acute non specific features and it can be misdiagnosed with other serious diseases, the clinician will be helped by the knowledge of this syndrome to promptly start diagnostic workup and treatments, and avoid permanent neurological deficits.
Full Text Available The JC virus ( JCV is well known for causing progressive multifocal leukoencephalopathy (PML, a potentially fatal, demyelinating disease of the central nervous system (CNS. PML almost exclusively affects immunosuppressed patients, whereas it is rare in immunocompetent subjects. Recently, a new clinical entity, named JCV encephalopathy ( JCVE, has been observed. We present the case of a 62-year-old male, with no identifiable immunosuppression, who developed aphasia and progressive reduction in consciousness. He had a six months insidious history of psychiatric symptoms. He passed away 3 weeks after onset of symptoms. On admission, brain MRI demonstrated a prominent grey matter involvement. Serological tests and cerebrospinal fluid analysis were all negative for infectious diseases. A whole-body CT scan was negative for cancer. Several EEGs showed a diffuse anterior theta activity with bilateral parietal epileptic periodic discharges. A second MRI imaging showed a more prominent non-enhancing grey and white matter involvement, compatible with PML. Finally, CSF- PCR for JCV was performed and resulted positive. To the best of our knowledge, our report is the second case of JCVE described so far. Similarly to our patient, the previous case developed symptoms consistent with a CNS disease with progressive clinical course. MRI abnormalities were initially restricted to the hemispheric grey matter and only later extended to the subcortical regions. Our case suggests that JCV infection should be considered even in immunocompetent patients presenting with unexplained cortical lesions and rapidly progressive encephalopathy.
Cissé, A F; Camara, N; Diallo, L L; Morel, Y; Koné, S; Camara, M I; Koumbassa, M L; Tafsir, D; Soumah, D; Djigué, B S; Camara, O B; Barry, M; Bangoura, S A; Kourouma, S; Da Silva, L; Cissé, A
The authors report 13 cases of Gayet-Wernicke's encephalopathy observed in 13 patients of a refugee population. 11 presented the classical triad: oculomotor signs, cerebral ataxia and state of confusion and in 2 patients, only 2 symptoms were noted. The etiological factors: chronic alcoholism, malnutrition, uncontrollable vomiting, HIV and tuberculosis were identified. The outcome was evaluated on the basis of the disappearance of symptoms after treatment with 500 mg of thiamine in 7 patients, 1 death and 5 patients progressed toward Korsakoff amnesic syndrome.
Sakurai, Keita; Sasaki, Shigeru; Hara, Masaki; Yamawaki, Takemori; Shibamoto, Yuta
To investigate clinical and magnetic resonance imaging (MRI) features of Wernicke's encephalopathy with cortical abnormalities (WEc). We retrospectively evaluated the clinical features and MRI findings in 3 cases of WEc in comparison with those of 7 previously reported cases. Besides the classical triad of ocular abnormalities, ataxia and global confusion, muscular weakness of all extremities was frequently recognized (5 of 6 evaluable cases; 83%). During the clinical courses, 2 patients (20%) died and 1 fell into a vegetative state. The cortical abnormalities were distributed in the frontal and parietal lobes, especially around the bilateral central sulcus, in all cases. In 1 case, the cortical abnormality was irreversible, and the abnormal lesion, similar to that seen in laminar necrosis, persisted. Bilateral frontal cortical abnormalities around the central sulcus and muscular weakness of all extremities might be the characteristic features of WEc. Copyright 2009 S. Karger AG, Basel.
Full Text Available Delayed encephalopathy (DE is a neuropsychiatric syndrome that can arise generally within 20 days of acute carbon monoxide (CO intoxication after apparent recovery and involves variable degrees of cognitive deficits, personality changes, movement disorders and focal neurologic deficits. We report a 35-year-old female patient with delayed encephalopathy due to CO intoxication, presenting with cognitive impairment and mild parkinsonism despite receiving hyberbaric oxigen therapy (HBO. Magnetic resonance imaging showed abnormal signal intensity and decreased diffusivity at both caudate nuclei and globus pallidus. She continued to receive additional HBO therapy and complete recovery was reached within six months. The positive effect of early HBO therapy of selected patients in reversing the acute effects of CO intoxication is appearant. We here also review the beneficial effect of HBO in preventing or limitating the late neurocognitive deficits associated with severe CO intoxication
Susmitha Apuri; Kristin Carlin; Edward Bass; Phuong Thuy Nguyen; John Norman Greene
Tacrolimus is an immunosuppressive drug mainly used to lower the risk of transplant rejection in individuals who are post solid organ or hematopoietic transplantation. It is a macrolide which reduces peptidyl-propyl isomerase activity and inhibits calcineurin, thus inhibiting T-lymphocyte signal transduction and interleukin-2 (IL-2) transcription. It has been associated with Posterior Reversible Encephalopathy Syndrome (PRES), a disease of sudden onset ...
Kim, Carole H; Syed, Saba
Although altered consciousness and other neurologic manifestations are frequently seen in hypertensive encephalopathy, behavioral and psychotic symptoms are rarely seen. We describe a patient with no previous psychiatric history who was admitted for hypertensive crisis. A few days after admission, his blood pressure remained uncontrolled and he started to exhibit episodes of confusion, agitation, and psychosis. During one particular episode, he overcame multiple staff members and physical res...
Maroon, Joseph C.; Winkelman, Robert; Bost, Jeffrey; Amos, Austin; Mathyssek, Christina; Miele, Vincent
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with head trauma. Although initially believed to affect only boxers, the at-risk population has expanded to encompass a much wider demographic, including American football players, hockey players, wrestlers, and military veterans. This expansion has garnered considerable media attention and public concern for the potential neurodegenerative effects of head trauma. The main aim of this systematic review is to give...
Full Text Available Posterior reversible encephalopathy syndrome (PRES is a neurotoxic state accompanied by a unique brain imaging pattern. This cliniconeuroradiological entity usually presents with visual disturbances (cortical blindness, homonymous hemianopia, visual neglect, and blurred vision along with neurotoxic manifestations. Only a few cases of PRES have previously been reported in patients with advanced HIV disease. The authors describe a case of posterior reversible encephalopathy syndrome (PRES in a patient with advanced HIV/TBC infection who developed a neurotoxic state following TB and ART therapy initiation. They present a comprehensive review of the literature and discuss the pathogenetic hypotheses.
Choi, Hye Mi; Jung, Gum Mo; Lee, Woong Ki; Lee, Hyeuk Soo; Kim, Byung Sun; Seong, Choong Sil; Yoon, So Hee; Cho, Yong Keun
Cryptococcus neoformans, an encapsulated fungus, is an important opportunistic pathogen that can cause meningitis in im-munocompromised patients. Since patients with cryptococcemia have high mortality, it is essential to make an early diagnosis and promptly initiate antifungal therapy. However, it is often very difficult to differentiate between cryptococcal meningitis and hepatic encephalopathy in patients with liver cirrhosis, and there is delay in making the diagnosis. Therefore, these patients have a particularly grave prognosis and consequently many patients die before culture results become available. In one study, starting antifungal therapy within 48 hours of the blood culture was associated with improved survival, but patients with liver cirrhosis were significantly less likely to receive antifungal therapy within 48 hours compared to those without liver cirrhosis. Recently, the authors experience a case of a 68-year-old woman with liver cirrhosis who presented with fever and a drowsy mental status. She had a previous history of having been admitted for infection-associated hepatic encephlopathy. Cryptococcal meningitis and cryptococcemia were diagnosed by spinal puncture and culture of cerebrospinal fluid. In spite of adequate treatment, the patient developed multi-system organ failure and eventually expired. Herein, we report a case of cryptococcal meningitis mimicking hepatic encephalopathy in a patient with liver cirrhosis.
Full Text Available Abstract Introduction Patients with clinically mild encephalitis/encephalopathy with a reversible splenial lesion present with relatively mild central nervous system disturbances. Although the exact etiology of the condition remains poorly understood, it is thought to be associated with infective agents. We present a case of a patient with mild encephalitis/encephalopathy with a reversible splenial lesion, who had the unusual feature of acute urinary retention. Case presentation A 23-year-old Japanese woman developed mild confusion, gait ataxia, and urinary retention seven days after onset of fever and headache. Magnetic resonance imaging demonstrated T2 prolongation in the splenium of the corpus callosum and bilateral cerebral white matter. These magnetic resonance imaging abnormalities disappeared two weeks later, and all of the symptoms resolved completely within four weeks. Except for the presence of acute urinary retention (due to underactive detrusor without hyper-reflexia, the clinical and radiologic features of our patient were consistent with those of previously reported patients with mild encephalitis/encephalopathy with a reversible splenial lesion. To the best of our knowledge, this is the first report of acute urinary retention recognized in a patient with mild encephalitis/encephalopathy with a reversible splenial lesion. Conclusion Our findings suggest that mild encephalitis/encephalopathy with a reversible splenial lesion can be associated with impaired bladder function and indicate that acute urinary retention in this benign disorder should be treated immediately to avoid bladder injury.
Full Text Available Introduction The appearance of neurological disorders in a patient with liver cirrhosis initially suggests hepatic encephalopathy, but other causes should be considered, including bacterial infections.Materials and methods An 80-year-old woman suffering from HCV-related cirrhosis was admitted for fever, confusion, and stupor. No improvement was seen after treatment with cephalosporins, lactulose, and fluids.Results Listeria monocytogenes was isolated from blood cultures and subsequently from a cerebrospinal fluid specimen as well. On the basis of the antibiogram, the antibiotic therapy was modified to include ampicillin, but shock and multiorgan failure developed and the patient died one week later.Discussion Bacterial infections are more common and more aggressive in patients with liver cirrhosis, probably because of the immune dysfunction associated with this disorder. The presence of neurological disorders in a patient with liver cirrhosis may be a sign of hepatic encephalopathy, but it is important to recall that there are other potential causes as well, including bacterial infections. In this case, it is possible that the patient's symptoms were the result of the CNS infection with L. monocytogenes, which was particularly aggressive as a result of her cirrhosis.
Kang, Kyung-Sik; Heo, Sang Taek
Some herbal medications induce acute kidney injury. The acute kidney injuries caused by herbal medications are mild and commonly treated by palliative care. A 51-years-old man who drank the juice squeezed from the raw tubers of Dioscorea quinqueloba (D. quinqueloba) was admitted with nausea, vomiting and chilling. He developed a seizure with decreased level of consciousness. He was diagnosed with acute kidney injury, which was cured by continuous venovenous hemodialfiltration. Non-detoxified D. quinqueloba can cause severe acute kidney injury with toxic encephalopathy. It is critical to inform possible adverse effects of the medicinal herbs and to implement more strict regulation of these products.
Endo, Ayumi; Fuchigami, Tatsuo; Hasegawa, Maki; Hashimoto, Koji; Fujita, Yukihiko; Inamo, Yasuji; Mugishima, Hideo
Posterior reversible encephalopathy syndrome (PRES) is a recently described disorder with typical radiological findings of bilateral gray and white matter abnormalities in the posterior regions of the cerebral hemispheres and cerebellum. Its clinical symptoms include headache, decreased alertness, mental abnormalities such as confusion, diminished spontaneity of speech, and changed behavior ranging from drowsiness to stupor, seizures, vomiting, and abnormalities of visual perception such as cortical blindness. In this study, the clinical and radiological findings of 4 children with this syndrome due to a variety of conditions are reported. The records of 4 children with a diagnosis of PRES were retrospectively analyzed. PRES is associated with a disorder of cerebrovascular autoregulation of multiple etiologies. Four patients with PRES who had primary diagnoses of severe aplastic anemia, nephritic syndrome, Henoch-Schönlein purpura, and acute poststreptococcal glomerulonephritis are presented. This syndrome has been described in numerous medical conditions, including hypertensive encephalopathy, eclampsia, and with the use of immunosuppressive drugs. Early recognition of PRES as a complication during different diseases and therapies in childhood may facilitate precise diagnosis and appropriate treatment.
Valduga, Mylène; Philippe, Christophe; Lambert, Laetitia; Bach-Segura, Pascale; Schmitt, Emmanuelle; Masutti, Jean Pierre; François, Bénédicte; Pinaud, Patrick; Vibert, Mireille; Jonveaux, Philippe
WWOX has been recently implicated in autosomal recessive spinocerebellar ataxia type 12 (SCAR12) and severe early-onset epileptic encephalopathy (EOEE). By array comparative genomic hybridization, we identified a 0.6 Mb homozygous deletion in 16q23.1 in a fetus presenting with brain anomalies. His older sister who died at the age of 22 months from an EOEE was also homozygous for the copy number variations in 16q23.1. This deletion includes the first six exons of WWOX and results in a null genotype in homozygous patients. This family gives additional support for the implication of WWOX in severe EOEEs. We report for the first time prenatal ultrasound findings in a fetus with a WWOX-null genotype. Our study expands the range of brain abnormalities in WWOX-related EOEEs. This additional family confirms the genotype-phenotype correlation with WWOX-null alleles associated with the most severe form of WWOX-related epileptic encephalopathy with premature death.
ARZANIAN, Mohammad Thaghi; SHAMSIAN, Bibi Shahin; KARIMZADEH, Parvaneh; KAJIYAZDI, Mohammad; MALEK, Fatima; HAMMOUD, Mohammad
Objective Posterior reversible encephalopathy syndrome (PRES) is a cliniconeuroradiological disease entity, which is represented by characteristic magnetic resonance imaging (MRI) findings of subcortical/cortical hyperintensity in T2-weighted sequences. It is more often seen in parietaloccipital lobes, and is accompanied by clinical neurological changes. PRES is a rare central nervous system (CNS) complication in patients with childhood hematologic-oncologic disese and shows very different neurological symptoms between patients, ranging from numbness of extremities to generalized seizure. In this article, we will review PRES presentation in hematologic-oncologic patients. Then, we will present our patient, a 7-year-old boy with Evans syndrome on treatment with cyclosporine, mycophenolate mofetil (MMF) and prednisone, with seizure episodes and MRI finding in favour of PRES. PMID:24949044
Francine Judith Freitas Fernandes
therarapy. Diffusion-weighted images would not show hyperintense signal because of the presence of interstitial rather than cytotoxic edema. We report a case of PRES due to hipertensive encephalopathy studied by CT and MRI.
Maas, Annemieke; Braun, Kees P J|info:eu-repo/dai/nl/207237239; Geleijns, Karin|info:eu-repo/dai/nl/275854965; Jansen, Floor E.|info:eu-repo/dai/nl/304815640; van Royen-Kerkhof, Annet|info:eu-repo/dai/nl/288270770
Hashimoto encephalopathy is a rare condition, characterized by the association of encephalopathy with a variety of neurological symptoms and autoantibodies to the thyroid gland. Its etiology is unknown, and symptoms are usually treated with immune suppressive therapy, e.g., high doses of
Omalu, Bennet I; Hamilton, Ronald L; Kamboh, M Ilyas; DeKosky, Steven T; Bailes, Julian
We present a case of chronic traumatic encephalopathy (CTE) in a retired National Football League (NFL) Player with autopsy findings, apolipoprotein E genotype, and brain tissue evidence of chronic brain damage. This 44-year-old retired NFL player manifested a premortem history of cognitive and neuropsychiatric impairment, which included in part, chronic depression, suicide attempts, insomnia, paranoia, and impaired memory before he finally committed suicide. A full autopsy was performed with Polymerase Chain Reaction-based analyses of his blood to determine the apolipoprotein genotype. Histochemical and immunohistochemical analyses were performed on topographical gross sections of the brain. Autopsy confirmed a fatal gunshot wound of the head. The apolipoprotein E genotype was E3/E3 and the brain tissue revealed diffuse cerebral taupathy (Neurofibrillary Tangles and Neuritic Threads). This will be the third case of CTE in a national football player, which has been reported in the medical literature. Omalu et al., reported the first two cases in 2005 and 2006. This case series manifested similar premortem history of neuropsychiatric impairment with autopsy evidence of cerebral taupathy without any neuritic amyloidopathy. For a definitive diagnosis of CTE to be made, and for medicolegal purposes, a full autopsy must be performed with histochemical and immunohistochemical analyses of the brain to identify the presence of Neurofibrillary Tangles (NFTs) and Neuritic Threads (NTs). Further longitudinal prospective studies are required to confirm the common denominators and epidemiology of CTE in professional American football players, which have been identified by this case series.
Zhang, Yi; Lian, Yajun; Xie, Nanchang
Early onset epileptic encephalopathy (EOEE) is one of the most serious early onset epilepsies. The etiopathology of this condition remains unclear, and recent evidence indicated that gamma-aminobutyric acid (GABA) A receptor, subunit beta 3 (GABRB3) gene mutations might be associated with EOEE. Furthermore, the therapeutic regimen for EOEE has yet to be well elucidated. Herein, we reported the clinical and genetic features of a case with GABRB3-related EOEE. A 6-year-old girl developed epileptic seizures 3 days after birth. She presented with multiple seizure types including myoclonic seizures, spasms, and absence seizures. Serial electroencephalographic examinations showed variable abnormalities, and intellectual evaluation revealed significant development retardation. Conventional antiepileptic drugs were ineffective for the seizure controlling. Genetic screening identified a novel nonsense mutation (C.5G > A, p.W2X) in the GABRB3 gene. Early onset epileptic encephalopathy. We changed the antiepileptic strategy to oral clonazepam (0.5mg twice daily). The patient was followed up once a week and significant declining in the attack frequency was noted 1 week later (2-3 times daily). Subsequently, the dosage was doubled (1mg twice daily), and complete cessation of seizures was achieved 20 days later. Through a 9-month follow up,the girl remained seizure-free. This study identified a novel nonsensemutation (C.5G>A) in the exon 1 of GABRB3 Gene, which may be associated with EOEE. To our knowledge, this is the first report to use clonazepam in the patient with GABRB3-related EOEE with favorable outcome. Our finding suggested that clonazepam might be a choice for patient with GABRB3-related EOEE. The remarkable efficacy of clonazepam in the control of seizures indicated a potential GABRB3- or GABA-related mechanism involved in the development of EOEE. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
Azad, Tej D; Li, Amy; Pendharkar, Arjun V; Veeravagu, Anand; Grant, Gerald A
Few neurologic diseases have captured the nation's attention more completely than chronic traumatic encephalopathy (CTE), which has been discovered in the autopsies of professional athletes, most notably professional football players. The tragic case of Junior Seau, a Hall of Fame, National Football League linebacker, has been the most high-profile confirmed case of CTE. Here we describe Seau's case, which concludes an autopsy conducted at the National Institutes of Health that confirmed the diagnosis. Since 1990, Junior Seau had a highly distinguished 20-year career playing for the National Football League as a linebacker, from which he sustained multiple concussions. He committed suicide on May 2, 2012, at age 43, after which an autopsy confirmed a diagnosis of CTE. His clinical history was significant for a series of behavioral disturbances. Seau's history and neuropathologic findings were used to better understand the pathophysiology, diagnosis, and possible risk factors for CTE. This high-profile case reflects an increasing awareness of CTE as a long-term consequence of multiple traumatic brain injuries. The previously unforeseen neurologic risks of American football have begun to cast doubt on the safety of the sport. Copyright © 2016 Elsevier Inc. All rights reserved.
Guerin, Andrea; Aziz, Aly S; Mutch, Carly; Lewis, Jillian; Go, Cristina Y; Mercimek-Mahmutoglu, Saadet
Pyridox(am)ine-5-phosphate oxidase deficiency is an autosomal recessive disorder of pyridoxine metabolism. Intractable neonatal epileptic encephalopathy is the classical presentation. Pyridoxal-5-phosphate or pyridoxine supplementation improves symptoms. We report a patient with myoclonic and tonic seizures at the age of 1 hour. Pyridoxal-5-phosphate was started on the first day of life and seizures stopped at the age of 3 days, but encephalopathy persisted for 4 weeks. She had normal neurodevelopmental outcome at the age of 12 months on pyridoxal-5-phosphate monotherapy. She had novel homozygous pathogenic frameshift mutation (c.448_451del;p.Pro150Argfs*27) in the PNPO gene. Long-lasting encephalopathy despite well-controlled clinical seizures does neither confirm nor exclude pyridox(am)ine-5-phosphate oxidase deficiency. Normal neurodevelopmental outcome of our patient emphasizes the importance of pyridoxal-5-phosphate treatment. Pyridox(am)ine-5-phosphate oxidase deficiency should be included in the differential diagnosis of Ohtahara syndrome and neonatal myoclonic encephalopathy as a treatable underlying cause. In addition, we reviewed the literature for pyridox(am)ine-5-phosphate oxidase deficiency and summarized herein all confirmed cases. © The Author(s) 2014.
Akamine, Satoshi; Ishizaki, Yoshito; Sakai, Yasunari; Torisu, Hiroyuki; Fukai, Ryoko; Miyake, Noriko; Ohkubo, Kazuhiro; Koga, Hiroshi; Sanefuji, Masafumi; Sakata, Ayumi; Kimura, Masahiko; Yamaguchi, Seiji; Sakamoto, Osamu; Hara, Toshiro; Saitsu, Hirotomo; Matsumoto, Naomichi; Ohga, Shouichi
Mutations in the X-linked gene CDKL5 cause early-onset epileptic encephalopathy and severe developmental delay. Because this disorder predominantly affects females, the full clinical spectrum of male patients remains elusive. We herein report a 16-year-old boy, who suffered from intractable seizures 20 days after birth. Serial electroencephalograms detected recurrent focal epileptiform discharges from age 4 months, which evolved to hypsarrhythmia later in infancy. Mass-spectrometric analyses revealed increase in urinary excretion of methylmalonic acid without perturbed concentrations of propionic acid, homocystein and methionine. Whole-exome sequencing identified a de novo, truncating mutation in CDKL5 (NM_003159.2:c.419dupA, p.Asn140Lysfs*8). Targeted sequencing excluded concomitant mutations in methylmalonic academia-associated genes. No methylmalonic acidemia has been reported in children with CDKL5 disorder. Extensive analyses on organic acid metabolism for males with CDKL5 mutations will gain more insight into their biochemical profiles in infancy. Copyright © 2018. Published by Elsevier Masson SAS.
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...
Saito, Nobuo; Kitashouji, Emi; Kojiro, Maiko; Furumoto, Akitugu; Morimoto, Konosuke; Morita, Kouichi; Ariyoshi, Koya
Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) has been recently proposed as a clinical-radiological syndrome. Several causes of MERS have been reported including infectious diseases. We present herein on a case of MERS induced by dengue fever in a Japanese traveler. A 48-year-old male returning from Thailand and Cambodia was admitted for an unknown fever. Following admission, the dengue virus was diagnosed with a positive RT-PCR result. On day 5 of the illness, regardless of reduced fever, weakness suddenly developed in both upper limbs. A cerebral MRI showed hyperintensities in the splenium of the corpus callosum on T2-weighted and diffusion-weighted images. The symptoms resolved completely within two days of onset. The patient was diagnosed as having MERS due to the MRI features and the mild clinical course. Although only a few cases of MERS caused by dengue fever have been reported, the condition is possibly underdiagnosed. It is hypothesized that dengue fever can induce MERS as dengue fever can cause increased endothelium permeability and hypo-sodium which have been proposed in the pathogenesis of MERS. However, there is currently limited evidence for this. Further research is recommended to demonstrate a causal association between dengue fever and MERS.
Neurotoxicity from iodinated contrast agents is a known but rare complication of angiography and neurovascular intervention. Neurotoxicity results from contrast penetrating the blood-brain barrier with resultant cerebral oedema and altered neuronal excitability. Clinical effects include encephalopathy, seizures, cortical blindness and focal neurological deficits. Contrast induced encephalopathy is extensively reported as a transient and reversible phenomenon. We describe a patient with a persistent motor deficit due to an encephalopathy from iodinated contrast media administered during cerebral aneurysm coiling. This observation and a review of the literature highlights that contrast-induced encephalopathy may not always have a benign outcome and can cause permanent deficits. This potential harmful effect should be recognised by the angiographer and the interventionalist.
Graham, Brett R; Shiff, Natalie; Nour, Munier; Hasal, Simona; Huntsman, Richard; Almubarak, Salah
Hashimoto encephalopathy is a rare form of encephalopathy thought to be of autoimmune etiology. Cognitive changes and seizures are the most commonly reported presenting manifestation. Stroke-like episodes have also been documented in these individuals. We describe a rare adolescent with Hashimoto encephalopathy who presented with stroke-like symptoms. A previously well 15-year-old girl experienced sudden-onset language disturbance and right hemiparesis. Her symptoms resolved, but weeks later, she began experiencing refractory seizures, episodes of status epilepticus, and cognitive decline. An extensive evaluation was unremarkable, but thyroid peroxidase antibodies were elevated, and a diagnosis of Hashimoto encephalitis was made. Steroid therapy was initiated, and her symptoms resolved with return to baseline cognitive function. Hashimoto encephalopathy is a highly treatable condition that may be considered in the differential diagnosis of children and adolescents presenting with stroke-like symptoms. Copyright © 2016 Elsevier Inc. All rights reserved.
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.
Tozzo, Pamela; Caenazzo, Luciana; Rodriguez, Daniele; Bolcato, Matteo
Wernicke's encephalopathy (WE) is a neurological syndrome caused by thiamine deficiency, and clinically characterized by ophthalmoplegia, ataxia and acute confusion. In developed countries, most cases of WE have been seen in alcohol misusers. Other reported causes are gastrointestinal tract surgery, hyperemesis gravidarum, chronic malnutrition, prolonged total parenteral nutrition without thiamine supplementation, and increased nutrient requirements as in trauma or septic shock. WE is a well-known postoperative complication of gastric restrictive surgery for morbid obesity, after which patients often experience protracted nausea and vomiting, leading to malnutrition and massive weight loss. This case report concerns WE occurring in a patient who underwent Roux-en-Y subtotal gastrectomy for gastric cancer, and subsequently experienced neurological symptoms that proved irreversible probably due to the lengthy time elapsing between their clinical presentation and the diagnosis of WE. There have been some reports of WE occurring after total or subtotal gastrectomy for gastric cancer in non-obese patients with no history of alcoholism, but monitoring for WE has yet to be recommended in the clinical guidelines in this setting (as it has for bariatric surgery). Because of its rarity and variable clinical presentation, WE is often under-diagnosed and under-treated, and confused with other neurological problems. There is an urgent need for the specific guidelines to take into account not only the neoplastic follow-up of such patients, but also the possible side effects of necessary surgery, since this could help to ensure the timely diagnosis and management of WE in this setting, and to avoid, when possible, claims for medical malpractice that may cause enormous costs both in economical and professional terms. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Park, Seung Hyun; Kang, Hyun Koo; Yu, Hyeon; Lee, Sang Chun
Creutzfeldt-Jakob disease (DJD) is one of the transmissible spongiform encephalopathies, which is mediated by what has been known as 'prion'. It is a rare and fatal progressive neurodegenerative disease that affects the middle and old aged. There are a number of subtypes of CJD, one of which is the sporadic type characterized by rapidly progressing clinical symptoms, including progressive dementia, myoclonic jerk, and pyramidal or extrapyramidal syndrome. Patients usually end up dying within 1 to 2 years of contacting the disease. We report an autopsy-proven case of sporadic CJD with clinical symptoms that progressed within several days, along with dramatic changes on diffusion weighted magnetic resonance images
Azevedo, M F; Nascimento, F; Quintella, L; Rosso, A L; Maranhão Filho, P A; Corrêa, R B; Chimelli, L; Vincent, M; Novis, S A
Creutzfeldt-Jakob disease (CJD) is the most common subacute transmissible spongiform encephalopathy. Approximately 85% of the cases are sporadic. The remaining 15% consist of genetic and iatrogenic forms. We report a sporadic form of CJD with spinal cord involvement and a clinical manifestation characterized by dementia and cerebellar syndrome, myofasciculation with absent reflexes and seizures. The two last manifestations are rare. The clinical hypothesis was probable CJD which was confirmed with autopsy and immunohistochemistry. We conclude that CJD should always be suspected when rapidly progressive dementia occurs and the absence of pyramidal or extrapyramidal signs suggest a spinal cord and/or peripheral nerve involvement.
Dirzius, Edgaras; Balnyte, Renata; Steibliene, Vesta; Gleizniene, Rymante; Gudinaviciene, Inga; Radziunas, Andrius; Petrikonis, Kestutis
Creutzfeldt - Jakob disease (CJD) is a rapidly progressive and fatal neurodegenerative prion disease. MRI findings are included in diagnostic criteria for probable CJD, giving a sensitivity and specificity more than 90%, but the atypical radiological presentations in the early stage of the disease could cause the diagnostic difficulties. CJD can be definitively diagnosed by histopathological confirmation, brain biopsy or at autopsy. We present a case of 53-year-old woman with a history of a rapidly progressive dementia with symptoms of visual impairment, increased extrapyramidal type muscle tonus, stereotypical movements and ataxic gait resulting in the patient's death after13 months. The clinical symptoms deteriorated progressively to myoclonus and akinetic mutism already on the 14th week. The series of diagnostic examinations were done to exclude the possible causes of dementia. Initial MRI evaluation as posterior reversible encephalopathy syndrome (PRES) on the 9th week after the onset of symptoms created us a diagnostic conundrum. Subsequent MRI findings of symmetrical lesions in the basal ganglia (nucleus caudatus, putamen) on the 13th week and EEG with periodic sharp wave complexes (PSWC) in frontal regions on the 18th week allowed us to diagnose the probable sCJD. The histopathological findings after brain biopsy on the 14th week demonstrated the presence of the abnormal prion protein deposits in the grey matter by immunohistochemistry with ICSM35, KG9 and 12 F10 antibodies and confirmed the diagnosis of sCJD. In this article we focus our attention on a rare association between radiological PRES syndrome and early clinical stage of sCJD. Although concurrent manifestation of these conditions can be accidental, but the immunogenic or neuropeptide mechanisms could explain such radiological MRI findings. A thorough knowledge of differential diagnostic of PRES may be especially useful in earlier diagnosis of sCJD.
Tsironis, Theocharis; Tychalas, Athanasios; Kiourtidis, Dimitrios; Kountouras, Jannis; Xiromerisiou, Georgia; Rudolf, Jobst; Deretzi, Georgia
Thyrotoxic periodic paralysis (TPP) is an uncommon complication of Graves' disease, characterized by the triad of acute hypokalemia without total body potassium deficit, episodic muscle paralysis, and thyrotoxicosis. Graves' encephalopathy is an extremely rare form of encephalopathy associated with autoimmune thyroid disease (EAATD), characterized by neuropsychiatric symptoms, increased antithyroid antibodies and cerebrospinal fluid protein concentration, nonspecific electroencephalogram abnormalities, and cortico-responsiveness. Coexistence of both these complications in the same patient has not been reported before. We herein present a 48-year-old white male patient with TPP and encephalopathy as initial presentations of Graves' disease. Flaccid tetraparesis was reversed a few hours after potassium level correction and the patient did not suffer any relapse with the successful pharmaceutical management of the thyroid function. One month later, the patient presented with dizziness and behavioral symptoms, such as inappropriate laughter and anger. Brain magnetic resonance imaging revealed meningeal enhancement and cerebrospinal fluid analysis showed a mild protein increase, with a blood-brain barrier disruption. With the suspicion of EAATD, the patient was treated with high doses of corticosteroids and improved dramatically. To our knowledge this is the first reported coexistence of potentially treatable TPP and EAATD as initial neurological manifestations of Graves' disease, thereby underscoring the necessity of suspicion of possible underlying Graves' disease in patients with acute paralysis and encephalopathy of unclear origin.
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.)
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.
Caulo, M; Tampieri, D; Brassard, R; Christine Guiot, M; Melanson, D
A case of cerebral amyloid angiopathy is presented with MR imaging findings of high intense signal on T2-weighted sequences at the level of the white and gray matter of both hemispheres in the absence of neuroradiologic signs of cerebral hemorrhage. The biopsy specimen revealed deposition of amyloid in the walls of the intracranial arterial branches and focal ischemic changes and gliosis in the gray and white matter. We consider this presentation to be very unusual in patients affected by cerebral amyloid angiopathy.
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
Okanishi, Tohru; Fujimoto, Ayataka; Motoi, Hirotaka; Kanai, Sotaro; Nishimura, Mitsuyo; Yamazoe, Tomohiro; Takagi, Atsushi; Yamamoto, Takamichi; Enoki, Hideo
Corpus callosotomy is a palliative therapy for refractory epilepsy, including West syndrome, without a resectable epileptic focus. The surgical outcome of corpus callosotomy is relatively favorable in cryptogenic (non-lesional) West syndrome. Tuberous sclerosis complex (TSC) is a disorder that frequently leads to the development of refractory seizures by multiple cortical tubers. The multiple cortical tubers cause multiple or wide epileptic networks in these cases. Most of West syndrome cases in TSC with multiple tubers need additional resective surgery after corpus callosotomy. We describe a case of TSC in a boy aged 4years and 8months. He had multiple cortical tubers on his brain and developed epileptic spasms. The seizures were controlled with valproate. At the age of 1year and 4months, he presented with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), and had relapsed epileptic spasms one month after the onset of the encephalopathy. The seizures were refractory to multiple antiepileptic drugs. A total corpus callosotomy was performed at the age of 3years and 8months. The patient did not show any seizures after the surgery. During 12months of the follow-up, the patient was free from any seizures. Even in cases of symptomatic WS with multiple lesions, total corpus callosotomy may be a good strategy if the patients have secondary diffuse brain insults. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Wernicke's encephalopathy revisited. Translation of the case history section of the original manuscript by Carl Wernicke 'Lehrbuch der Gehirnkrankheiten fur Aerzte and Studirende' (1881) with a commentary.
Thomson, Allan D; Cook, Christopher C H; Guerrini, Irene; Sheedy, Donna; Harper, Clive; Marshall, E Jane
A translation into English of the case history section of Carl Wernicke's original manuscript of 1881, with a discussion on its relevance for clinicians today. A copy of Carl Wernicke's original German text was obtained by one of the authors (CCHC) and translated into English from the old German by a professional translator. The translation was subsequently agreed by native German speaking referees, and minor changes made. The authors studied the translation in detail and concluded that Wernicke's description had stood the test of time. The diagnosis of Wernicke's Encephalopathy remains a clinical one.
Dong, Kai; Zhang, Qian; Ding, Jianping; Ren, Liankun; Zhang, Zhen; Wu, Longfei; Feng, Wuwei; Song, Haiqing
Reversible splenial lesion syndrome (RESLES) is a newly recognized syndrome, and a reversible progress associated with transiently reduced diffusion lesion in the splenium of the corpus callosum (SCC) is the typical pathological finding. The routine clinical symptoms include mildly altered states of consciousness, delirium, and seizures. We presented a 14-year-old patient with signs suggestive of transient ischemic attack (TIA), including triple episodic weakness on the right upper limb, slurred speech, and bucking, lasting several hours in each time 2 days ago. She just had a slight cold 2 weeks ago. No evidence of abnormality was found in laboratory examinations except an elevated percentage of lymphocyte. Magnetic resonance imaging revealed lesions in splenium of the corpus callosum and frontal-parietal subcortex on both cerebral hemispheres. Cerebrovascular examination was also unremarkable. The patient recovered to baseline within 25 hours. No treatment was given to her in hospital. In addition, the follow-up brain magnetic resonance imaging scan showed reduced lesions. TIA-like symptoms did not occur during a 30-day follow-up period. This young patient with RESLES type II exhibited TIA-like symptoms, which was not previously reported in literature. This case extends the recognized clinical phenotypes for this disorder.
Full Text Available Introduction: Children having hemolytic anemias who have received multiple blood transfusions exhibit a rare complication of development of hypertension and seizures following transfusion, which may or may not be associated with intracranial hemorrhage. Case description: A 9-year-old boy presented with history of progressive paleness of body and weakness for the 30 days. There was a history of blood transfusion one week ago and multiple transfusions for one year of age. Examination revealed tachycardia, tachypnea, severe pallor and splenohepatomegaly. Blood work revealed a hemoglobin level of 4.0 grams with peripheral smear findings suggestive of hemolytic anemia. After blood transfusion, child complained of difficulty in breathing, vomiting and visual loss, followed by convulsions. Blood pressure was 180/110 mmHg. Seizure was controlled with intravenous midazolam and hypertension with furosemide and labetalol. CT brain was normal. As hypertension got under control, child gradually gained consciousness. Conclusion: A less intensive transfusion regimen among such patients along with prompt management of hypertension can prevent this potentially fatal syndrome.
Full Text Available Abstract Introduction A combination therapy of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been used to control proteinuria, following initial demonstration of its efficacy. However, recently concerns about the safety of this therapy have emerged, prompting several authors to urge for caution in its use. In the following case report, we describe the occurrence of a serious and unexpected adverse drug reaction after administration of a combination of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to a patient with nephrotic syndrome and liver cirrhosis with severe portal hypertension. Case presentation We administered this combination therapy to a 40-year-old Caucasian man with liver cirrhosis in our Hepatology Clinic, given the concomitant presence of glomerulopathy associated with severe proteinuria. While the administration of one single drug appeared to be well-tolerated, our patient developed severe acute encephalopathy after the addition of the second one. Discontinuation of the therapy led to the disappearance of the side-effect. A tentative rechallenge with the same drug combination led to a second episode of acute severe encephalopathy. Conclusion We speculate that this adverse reaction may be directly related to the effect of angiotensin II on the excretion of blood ammonia. Therefore, we suggest that patients with liver cirrhosis and portal hypertension are at risk of developing clinically relevant encephalopathy when angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker combination therapy is administered, thus indicating the need for a careful clinical follow-up. In addition, the incidence of this serious side-effect should be rigorously evaluated in all patients with liver cirrhosis administered with this common treatment combination.
Covelli, Vincent; Khanapara, Dipen B; Naut, Edgar R
Penicillin encephalopathy is a rare, potentially reversible phenomenon of drug-induced neurotoxicity. A 65-year-old female with a history of HIV was admitted with a three-day history of worsening headache, confusion, and lethargy. On examination she was awake but confused. Cerebrospinal fluid (CSF) and serum venereal disease research laboratory (VDRL) test returned positive and the patient was started on intravenous penicillin G with probenecid. On the second day of therapy, she developed myoclonic jerking, consistent with penicillin neurotoxicity. Repeat labs also showed new onset renal failure. Penicillin and probenecid therapy were stopped with a resolution of symptoms. Subsequently, therapy without probenecid was reinstituted uneventfully. Herein, we describe a female who developed penicillin neurotoxicity after initiation of intravenous penicillin therapy with probenecid for neurosyphilis. It is important that penicillin-induced toxicity be considered if characteristic myoclonic movements accompany encephalopathy. The presence of coexistent renal compromise should heighten the vigilance of clinicians.
Adachi, Masao; Abe, Yu; Aoki, Yoko; Matsubara, Yoichi
We report two individual cases of cardio-facio-cutaneous (CFC) syndrome with severe neurological impairment consisting of infantile spasms with hypsarrhythmia and refractory epilepsy with multifocal epileptic paroxysms such as modified hypsarrhythmia. Both cases shared diffuse brain atrophy and severely delayed myelination on neuroimaging. Genetic analysis revealed individual heterozygous mutations in the KRAS (phenotype of CFC/Noonan syndrome) and BRAF genes (phenotype of CFC syndrome). Neurological impairment in cases with mutations in the RAS/MAPK (mitogen activated protein kinase) signal pathway may be more severe, and could be linked to some forms of refractory epilepsy, especially epileptic encephalopathy that includes infantile spasms. Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Neilson, Derek E.; Adams, Mark D.; Orr, Caitlin M.D.; Schelling, Deborah K.; Eiben, Robert M.; Kerr, Douglas S.; Anderson, Jane; Bassuk, Alexander G.; Bye, Ann M.; Childs, Anne-Marie; Clarke, Antonia; Crow, Yanick J.; Di Rocco, Maja; Dohna-Schwake, Christian; Dueckers, Gregor; Fasano, Alfonso E.; Gika, Artemis D.; Gionnis, Dimitris; Gorman, Mark P.; Grattan-Smith, Padraic J.; Hackenberg, Annette; Kuster, Alice; Lentschig, Markus G.; Lopez-Laso, Eduardo; Marco, Elysa J.; Mastroyianni, Sotiria; Perrier, Julie; Schmitt-Mechelke, Thomas; Servidei, Serenella; Skardoutsou, Angeliki; Uldall, Peter; van der Knaap, Marjo S.; Goglin, Karrie C.; Tefft, David L.; Aubin, Cristin; de Jager, Philip; Hafler, David; Warman, Matthew L.
Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait. We now report that all affected individuals and obligate carriers in this family are heterozygous for a missense mutation (c.1880C→T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2). To determine whether this mutation is the susceptibility allele, we screened controls and other patients with ANE who are unrelated to the index family. Patients from 9 of 15 additional kindreds with familial or recurrent ANE had the identical mutation. It arose de novo in two families and independently in several other families. Two other patients with familial ANE had different RANBP2 missense mutations that altered conserved residues. None of the three RANBP2 missense mutations were found in 19 patients with isolated ANE or in unaffected controls. We conclude that missense mutations in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE. PMID:19118815
Paghera, Barbara; Caobelli, Federico; Nisa, Lutfun; Puta, Erinda; Borroni, Barbara; Premi, Enrico; Padovani, Alessandro; Giubbini, Raffaele
Creutzfeldt-Jakob disease (CJD) is a subacute spongiform encephalopathy characterized by rapidly progressive dementia, hard to diagnose during life. We present a case of a patient with pathologically confirmed sporadic form of CJD in whom initial diagnostic tests were negative. Two sequential brain single-photon emission computed tomography with Tc-99m ethyl-cysteinate dimer were performed, the first one was performed few days after the admission into hospital and the second, 1 month later. Both studies revealed a decrease in regional cerebral blood flow indicative of neuronal dysfunction, more pronounced in the second study. Current radionuclide scintigraphy can be an useful tool for the investigation of CJD.
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.
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...
Pugnet, G; Pagnoux, C; Bézanahary, H; Ly, K H; Vidal, E; Guillevin, L
Progressive multifocal encephalopathy (PML) is a rare demyelinating disorder targeting the central nervous system and resulting from JC virus reactivation. PML occurs in patients immunocompromised because of haematological malignancies, HIV infection or treatment with cytotoxic drugs. Herein, we describe PML occurring in 2 granulomatosis with polyangiitis (Wegener) patients treated with steroids and cyclophosphamide. The outcome was progressively favourable after immunosuppressant discontinuation for 1 patient and fatal for the other. Four previously reported GPA patients developed PML in the course of their disease. One of them improved gradually after immunosuppressant withdrawal. PML should be strongly suspected whenever unusual central neurological manifestations appear in this context. No effective treatment is available, but immunosuppressants should be discontinued if possible.
Neilson, Derek E; Adams, Mark D; Orr, Caitlin M D
Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a ...
Neilson, Derek E.; Adams, Mark D.; Orr, Caitlin M. D.; Schelling, Deborah K.; Eiben, Robert M.; Kerr, Douglas S.; Anderson, Jane; Bassuk, Alexander G.; Bye, Ann M.; Childs, Anne-Marie; Clarke, Antonia; Crow, Yanick J.; Di Rocco, Maja; Dohna-Schwake, Christian; Dueckers, Gregor; Fasano, Alfonso E.; Gika, Artemis D.; Gionnis, Dimitris; Gorman, Mark P.; Grattan-Smith, Padraic J.; Hackenberg, Annette; Kuster, Alice; Lentschig, Markus G.; Lopez-Laso, Eduardo; Marco, Elysa J.; Mastroyianni, Sotiria; Perrier, Julie; Schmitt-Mechelke, Thomas; Servidei, Serenella; Skardoutsou, Angeliki; Uldall, Peter; van der Knaap, Marjo S.; Goglin, Karrie C.; Tefft, David L.; Aubin, Cristin; de Jager, Philip; Hafler, David; Warman, Matthew L.
Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a
Kobayakawa, Yuko; Tateishi, Takahisa; Kawamura, Nobutoshi; Doi, Hikaru; Ohyagi, Yasumasa; Kira, Jun-ichi
We reported a patient with immune-mediated encephalopathy showing refractory epilepsy and multiple brain lesions on MRI. The patient had high titers of anti-glutamic acid decarboxylase (GAD) antibody in sera and cerebrospinal fluid (CSF). A 36-year-old previously healthy woman was admitted to our hospital with onset of sudden generalized seizure that then persisted for one month. She had repeated epileptic attacks accompanied with loss of consciousness, and was refractory to valproic acid, zonisamide (200 mg/day) and phenobarbital (200 mg/day). Brain MRI showed multiple hyperintense lesions in predominantly bilateral frontal lobes, parietal lobes, occipital lobes and cingulate cortices. EEG showed epileptic activities (frequent sharp waves) in bilateral frontal regions. After admission, attacks disappeared through the administration of clonazepam (1.5 mg/day), though the patient remained slightly disoriented. As titers of anti-GAD antibody in sera and CSF were extremely high, we implemented plasma exchanges. After treatment, titers of anti-GAD antibody in sera and CSF decreased. The patient completely recovered to an alert state and the abnormal MRI lesions almost disappeared. Since GAD catalyzes production of gamma-aminobutyric acid (GABA), it is proposed that anti-GAD antibodies reduce synthesis of GABA or interferes with exocytosis of GABA in the nervous system. Anti-GAD antibodies are detected in some rare neurological disorders such as stiff-person syndrome. Recently, anti-GAD antibodies have been reported as implicated in cerebellar ataxia, palatal myoclonus, refractory epilepsy and limbic encephalitis. Epilepsy associated with the anti-GAD antibody is mostly pharmacoresistant temporal lobe epilepsy; with brain MRI showing no abnormality or only hippocampal sclerosis. It is very rare that brain MRI shows extensive abnormal lesions except in the hippocampus. This case suggests that anti-GAD antibodies could contribute to unexplained encephalopathy with
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...
Full Text Available Immune checkpoint inhibitors are antibodies, which enhance cellular and humoral immune responses and are approved for the treatment of various tumors. Immune-related adverse events (irAE involving different organs and systems are, however, among the side-effects. Recent reports of severe persistent neurological deficits and even fatal cases underpin the need for better understanding of the exact pathomechanisms of central nervous system (CNS toxicity. To our knowledge, we report the first biopsy-proven case of fatal necrotizing encephalopathy after treatment with nivolumab. Nivolumab targets the immune-check point inhibitor programmed cell death-1 and was used for squamous non-small cell lung cancer. Partly reversible neurologic and psychiatric symptoms and unremarkable brain magnetic resonance imaging (MRI were observed after the first course. Neurological symptoms progressed and recurrent seizures developed after the second course. Brain MRI disclosed multiple edematous and confluent supra- and infratentorial lesions, partly with contrast-enhancement. We excluded autoimmune and paraneoplastic causes and performed ancillary investigations to rule out common and opportunistic infections. Eventually, postmortem histopathological analysis of the brain revealed a necrotizing process, which contrasts previous cases reporting parenchymal immune cell infiltration or demyelination. Appropriate diagnostic pathways and treatment algorithms need to be implemented for the work-up of CNS toxicity and irAEs related to immune checkpoint inhibitor treatment.
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
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.
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 ...
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.
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.
Full Text Available Reena Shah, Agnieszka Kubisz-Pudelko, Jeremy Reid Yeovil District Hospital, Yeovil, UK Abstract: Posterior reversible encephalopathy syndrome (PRES is a clinico-neuroradiological syndrome characterized by various symptoms of neurological disease. It has commonly been reported in association with acute hypertension, pre-eclampsia, eclampsia, sepsis, and exposure to immunosuppressants. Here, we report on a normotensive woman who developed a severe frontal headache, visual disturbances, and hypertension 3 days after undergoing an emergency laparotomy for ischemic colitis during which she suffered an inadvertent dural puncture. Neuro-imaging revealed features consistent with PRES. The patient went on to make a good recovery, being discharged 21 days postoperatively, with only minor visual disturbances and memory problems. This case highlights the importance of awareness of PRES to all specialties. On reviewing the literature, we feel that PRES may be a potential differential diagnosis to post-procedural neurological symptoms in those patients undergoing routine procedures such as spinal anesthetics or lumbar punctures. Keywords: PRES, neurological disease, lumbar puncture, spinal anesthetic
Lilles, Stella; Talvik, Inga; Noormets, Klari; Vaher, Ulvi; Õunap, Katrin; Reimand, Tiia; Sander, Valentin; Ilves, Pilvi; Talvik, Tiina
Cyclin-dependent kinase-like 5 ( CDKL5 ) gene mutations have mainly been found in females with early infantile epileptic encephalopathy (EIEE), severe intellectual disability, and Rett-like features. To date, only 22 boys have been reported, presenting with far more severe phenotypic features. We report the first cases of CDKL5 gene-related EIEE in Estonia diagnosed using panels of epilepsy-associated genes and describe the phenotype-genotype correlations in three male and one female patient. One of the mutations, identified in a male patient, was a novel de novo hemizygous frameshift mutation (NM_003159.2:c.2225_2228del (p.Glu742Afs*41)) in exon 15 of CDKL5. All boys have a more severe phenotype than the female patient. In boys with early onset of seizures and poor development with absent or poor eye contact, CDKL5 gene-related EIEE can be suspected and epilepsy-associated genes should be analyzed for early etiological diagnosis. Early genetic diagnosis would be the cornerstone in personalized treatment in the future. Georg Thieme Verlag KG Stuttgart · New York.
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.
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...
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.
Management of transjugular intrahepatic portosystemic shunt (TIPS)-associated refractory hepatic encephalopathy by shunt reduction using the parallel technique: outcomes of a retrospective case series.
Cookson, Daniel T; Zaman, Zubayr; Gordon-Smith, James; Ireland, Hamish M; Hayes, Peter C
To investigate the reproducibility and technical and clinical success of the parallel technique of transjugular intrahepatic portosystemic shunt (TIPS) reduction in the management of refractory hepatic encephalopathy (HE). A 10-mm-diameter self-expanding stent graft and a 5-6-mm-diameter balloon-expandable stent were placed in parallel inside the existing TIPS in 8 patients via a dual unilateral transjugular approach. Changes in portosystemic pressure gradient and HE grade were used as primary end points. TIPS reduction was technically successful in all patients. Mean ± standard deviation portosystemic pressure gradient before and after shunt reduction was 4.9 ± 3.6 mmHg (range, 0-12 mmHg) and 10.5 ± 3.9 mmHg (range, 6-18 mmHg). Duration of follow-up was 137 ± 117.8 days (range, 18-326 days). Clinical improvement of HE occurred in 5 patients (62.5%) with resolution of HE in 4 patients (50%). Single episodes of recurrent gastrointestinal hemorrhage occurred in 3 patients (37.5%). These were self-limiting in 2 cases and successfully managed in 1 case by correction of coagulopathy and blood transfusion. Two of these patients (25%) died, one each of renal failure and hepatorenal failure. The parallel technique of TIPS reduction is reproducible and has a high technical success rate. A dual unilateral transjugular approach is advantageous when performing this procedure. The parallel technique allows repeat bidirectional TIPS adjustment and may be of significant clinical benefit in the management of refractory HE.
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.
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.
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
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.
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
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
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...
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.
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.
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...
Maheshwari, Atul; Fischer, Michael; Gambetti, Pierluigi; Parker, Alicia; Ram, Aarthi; Soto, Claudio; Concha-Marambio, Luis; Cohen, Yvonne; Belay, Ermias D; Maddox, Ryan A; Mead, Simon; Goodman, Clay; Kass, Joseph S; Schonberger, Lawrence B; Hussein, Haitham M
Variant Creutzfeldt-Jakob disease (vCJD) is a rare, fatal prion disease resulting from transmission to humans of the infectious agent of bovine spongiform encephalopathy. We describe the clinical presentation of a recent case of vCJD in the United States and provide an update on diagnostic testing. The location of this patient's exposure is less clear than those in the 3 previously reported US cases, but strong evidence indicates that exposure to contaminated beef occurred outside the United States more than a decade before illness onset. This case exemplifies the persistent risk for vCJD acquired in unsuspected geographic locations and highlights the need for continued global surveillance and awareness to prevent further dissemination of vCJD.
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 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
Isenberg-Grzeda, Elie; Alici, Yesne; Hatzoglou, Vaios; Nelson, Christian; Breitbart, William
Wernicke-Korsakoff Syndrome (WKS) is a neuropsychiatric syndrome caused by thiamine deficiency. Cancer predisposes to thiamine deficiency through various mechanisms. Although many case reports exist on nonalcoholic WKS in cancer, larger qualitative studies are lacking. Retrospective study of patients admitted to a cancer hospital and diagnosed with WKS during routine care on a psychiatric consultation service. Only patients with at least 1 additional supporting feature (magnetic resonance imaging findings, low serum thiamine concentrations, or response to treatment) were included. Data pertaining to demographics, risk factors, phenomenology, and outcomes were abstracted from medical records by chart review. In all, 18 patients were included. All patients developed WKS during cancer treatment. Hematologic malignancy, gastrointestinal tract tumors, low oral intake, and weight loss were common risk factors. All patients presented with cognitive dysfunction, most commonly impaired alertness, attention, and short-term memory. All were diagnosed by operational criteria proposed by Caine et al., 1997 (where 2 of the following are required: nutritional deficiency, ocular signs, cerebellar signs, and either altered mental status or mild memory impairment). Few exhibited Wernicke's classic triad. Diagnostic and treatment delay were common. Only 3 patients recovered fully. Nonalcoholic WKS can occur during cancer treatment and manifests clinically as delirium. Diagnosis should be made using operational criteria, not Wernicke's triad. Most patients were not underweight and had normal serum concentration of vitamin B12 and folate. A variety of mechanisms might predispose to thiamine deficiency and WKS in cancer. Given the high frequency of residual morbidity, studies should focus on decreasing diagnostic and treatment delay. Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.
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
Park, Seung Hyun; Kang, Hyun Koo; Yu, Hyeon; Lee, Sang Chun [Seoul Veterans Hospital, Seoul (Korea, Republic of)
Creutzfeldt-Jakob disease (DJD) is one of the transmissible spongiform encephalopathies, which is mediated by what has been known as 'prion'. It is a rare and fatal progressive neurodegenerative disease that affects the middle and old aged. There are a number of subtypes of CJD, one of which is the sporadic type characterized by rapidly progressing clinical symptoms, including progressive dementia, myoclonic jerk, and pyramidal or extrapyramidal syndrome. Patients usually end up dying within 1 to 2 years of contacting the disease. We report an autopsy-proven case of sporadic CJD with clinical symptoms that progressed within several days, along with dramatic changes on diffusion weighted magnetic resonance images.
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...
Coulthart, Michael B; Geschwind, Michael D; Qureshi, Shireen; Phielipp, Nicolas; Demarsh, Alex; Abrams, Joseph Y; Belay, Ermias; Gambetti, Pierluigi; Jansen, Gerard H; Lang, Anthony E; Schonberger, Lawrence B
As of mid-2016, 231 cases of variant Creutzfeldt-Jakob disease-the human form of a prion disease of cattle, bovine spongiform encephalopathy-have been reported from 12 countries. With few exceptions, the affected individuals had histories of extended residence in the UK or other Western European countries during the period (1980-96) of maximum global risk for human exposure to bovine spongiform encephalopathy. However, the possibility remains that other geographic foci of human infection exist, identification of which may help to foreshadow the future of the epidemic. We report results of a quantitative analysis of country-specific relative risks of infection for three individuals diagnosed with variant Creutzfeldt-Jakob disease in the USA and Canada. All were born and raised in Saudi Arabia, but had histories of residence and travel in other countries. To calculate country-specific relative probabilities of infection, we aligned each patient's life history with published estimates of probability distributions of incubation period and age at infection parameters from a UK cohort of 171 variant Creutzfeldt-Jakob disease cases. The distributions were then partitioned into probability density fractions according to time intervals of the patient's residence and travel history, and the density fractions were combined by country. This calculation was performed for incubation period alone, age at infection alone, and jointly for incubation and age at infection. Country-specific fractions were normalized either to the total density between the individual's dates of birth and symptom onset ('lifetime'), or to that between 1980 and 1996, for a total of six combinations of parameter and interval. The country-specific relative probability of infection for Saudi Arabia clearly ranked highest under each of the six combinations of parameter × interval for Patients 1 and 2, with values ranging from 0.572 to 0.998, respectively, for Patient 2 (age at infection × lifetime) and
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.
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 ...
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)
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.
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
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS: diagnostic criteria, features of epileptic seizures, and treatment approaches by the example of a clinical case
M. A. Yamin
Full Text Available The paper describes a patient with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS. The features of the course and therapy of epilepsy in MELAS are discussed. The disease is known for its late diagnosis when years elapse from the onset of the clinical manifestations to diagnosis. The paper presents clinical criteria for the diagnosis of MELAS and the specific features of brain neuroimaging changes that allow identification of the disease at an early stage.
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
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
Bisiacchi, Patrizia; Cona, Giorgia; Tarantino, Vincenza; Schiff, Sami; Montagnese, Sara; Amodio, Piero; Capizzi, Giovanna
Recent evidence reveals that inter- and intra-individual variability significantly affects cognitive performance in a number of neuropsychological pathologies. We applied a flexible family of statistical models to elucidate the contribution of inter- and intra-individual variables on cognitive functioning in healthy volunteers and patients at risk for hepatic encephalopathy (HE). Sixty-five volunteers (32 patients with cirrhosis and 33 healthy volunteers) were assessed by means of the Inhibitory Control Task (ICT). A Generalized Additive Model for Location, Scale and Shape (GAMLSS) was fitted for jointly modeling the mean and the intra-variability of Reaction Times (RTs) as a function of socio-demographic and task related covariates. Furthermore, a Generalized Linear Mixed Model (GLMM) was fitted for modeling accuracy. When controlling for the covariates, patients without minimal hepatic encephalopathy (MHE) did not differ from patients with MHE in the low-demanding condition, both in terms of RTs and accuracy. Moreover, they showed a significant decline in accuracy compared to the control group. Compared to patients with MHE, patients without MHE showed faster RTs and higher accuracy only in the high-demanding condition. The results revealed that the application of GAMLSS and GLMM models are able to capture subtle cognitive alterations, previously not detected, in patients' subclinical pathologies.
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.
Atalay, Fatma Öz; Tolunay, Şahsine; Özgün, Gonca; Bekar, Ahmet; Zarifoğlu, Mehmet
Creutzfeldt-Jakob disease is a very rare, progressive neurodegenerative disorder that is incurable and always fatal. It is one of the transmissible spongiform encephalopathies caused by prions. Multiple vacuoles in neuropil and neuronal loss in the gray matter gives the classical sponge-like appearance of brain and are responsible for the typical clinical symptoms. In this report, we present 4 cases referred to the neurology department of Uludağ University with neurological symptoms. Patients were evaluated with electroencephalogram and magnetic resonance imaging, and performed brain biopsies for further investigation. For definitive diagnosis of Creutzfeldt-Jakob disease, accumulation of prion protein in brain was detected immunohistochemically. Patients died within weeks in consequence of rapid progression of the disease. Although Creutzfeldt-Jakob disease is an infrequent disorder, when a patient presents with characteristic clinical symptoms such as rapidly progressive dementia with myoclonus, the diagnosis of Creutzfeldt-Jakob disease should be taken into consideration.
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.
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
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.
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.
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.
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...
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 ...
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
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 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.
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, ...
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.
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 ...
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
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.
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.
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
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 ...
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.
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. ...
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.
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.
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.
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.
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.
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.
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.
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...
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
High-resolution nuclear magnetic resonance imaging and single photon emission computerized tomography--cerebral blood flow in a case of pure sensory stroke and mild dementia owing to subcortical arteriosclerotic encephalopathy (Binswanger's disease)
De Chiara, S.; Lassen, N.A.; Andersen, A.R.; Gade, A.; Lester, J.; Thomsen, C.; Henriksen, O.
Pure sensory stroke (PSS) is typically caused by a lacunar infarct located in the ventral-posterior (VP) thalamic nucleus contralateral to the paresthetic symptoms. The lesion is usually so small that it cannot be seen on computerized tomography (CT), as illustrated by our case. In our moderately hypertensive, 72-year-old patient with PSS, CT scanning and conventional nuclear magnetic resonance imaging (NMRI) scanning using a 7-mm-thick slice on a 1.5 Tesla instrument all failed to visualize the thalamic infarct. Using the high-resolution mode with 2-mm slice thickness it was, however, clearly seen. In addition, NMRI unexpectedly showed diffuse periventricular demyelinization as well as three other lacunar infarcts, i.e., findings characteristic of subcortical arteriosclerotic encephalopathy (SAE). This prompted psychometric testing, which revealed signs of mild (subclinical) dementia, in particular involving visiospatial apraxia; this pointed to decreased function of the right parietal cortex, which was structurally intact on CT and NMRI. Single photon emission computerized tomography by Xenon-133 injection and by hexamethyl-propyleneamine-oxim labeled with Technetium-99m showed asymmetric distribution of cerebral blood flow (CBF), with an 18% lower value in the right parietal cortex compared to the left side; this indicated asymmetric disconnection of the cortex by the SAE. Thus, the tomograms of the functional parameter, CBF, correlated better with the deficits revealed by neuropsychological testing than by CT or NMRI.
Síndrome da encefalopatia posterior reversível (PRES e lúpus eritematoso sistêmico: relato de dois casos Posterior reversible encephalopathy syndrome (PRES and systemic lupus erythematosus: report of two cases
Aline de Souza Streck
Full Text Available A síndrome da encefalopatia posterior reversível (PRES é uma entidade nova clinicamente caracterizada por cefaleia, alterações sensoriais, convulsões e perda visual. A patogenia da PRES ainda não foi esclarecida. A PRES pode estar associada a uma variedade de condições clínicas, principalmente hipertensão, insuficiência renal e terapia imunossupressora. Uma possível associação de doenças autoimunes com PRES foi recentemente sugerida. Aqui descrevemos dois casos de lúpus eritematoso sistêmico nos quais a PRES foi deflagrada por diferentes fatores.The posterior reversible encephalopathy syndrome (PRES is a novel entity clinically manifested by headache, changes of sensorium, seizures, and visual loss. PRES pathogenesis has not been fully clarified. The entity can be associated to a variety of clinical conditions, mainly hypertension, renal insufficiency and immunosuppressive therapy. A possible link of autoimmune disorders with PRES has been recently hypothesized. We herein describe two cases of systemic lupus erythematosus whereby PRES was triggered by different factors.
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.
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.
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.
... 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
Zhang, Zhentao; Moreno, Alejandro
Paradichlorobenzene (PDB) is an aromatic compound found in several household insect repellents and deodorizers. Paradichlorobenzene may cause dependence and damage when inhaled or ingested. Prior cases of PDB neurotoxicity involved ingestion or inhalation of mothballs or occupational exposure. We report the first case of PDB neurotoxicity from chronic toilet bowl deodorizers ("toilet cake") sniffing. A 19-year-old woman, 4 weeks postpartum, presented with gradual mental status deterioration, lethargy, and general weakness for 2 weeks. On physical examination, the patient was found to have a strong odor of deodorizer and diffuse hyperpigmented skin lesions, with scratch marks in neck, axillae, trunk, and 4 limbs. She was alert but unable to communicate or follow commands. Ataxia, hyporeflexia, cogwheel rigidity, and decreased muscle tone were also noted. Laboratory tests revealed only normocytic anemia. A brain magnetic resonance imaging scan showed enhancement within the splenium of the corpus callosum. Postpartum depression, psychosis, and panhypopituitarism were excluded. Family members reported on further questioning that the patient was a habitual "toilet cake" sniffer for an unknown period. A urine test for 2,5-dichlorophenol (a PDB metabolite) level was 620 mg/L (3100 times higher than the average concentration with household exposure). Her clinical condition and body odor remained unchanged during the 30-day hospitalization and the skin findings improved.
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.
Watanabe, Yashihiro; Tsuji, Megumi; Sameshima, Kiyoko; Wada, Takahito; Iai, Mizue; Yamashita, Sumimasa; Hayashi, Takuya; Aida, Noriko; Osaka, Hiroshi
We report 12 cases of acute encephalopathy associated with influenza H1N1-2009 treated according to Japanese guideline (2009). In all 12 cases, electroencephalogram presented diffuse or localized high-amplitude slow waves. Brain CT and MRI showed abnormalities in 4 and 6 cases, respectively. We used hypothermia therapy for 5 patients. One patient showed impairment in short term memory, while the rest of the patients showed no sequelae. These 12 cases presented here suggest the early recognition and therapy according to the newly proposed guideline may reduce severe sequelae and mortality by acute encephalopathy associated with influenza H1N1-2009. (author)
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.
Hélio Araújo Oliveira
Full Text Available Os autores apresentam um caso de encefalopatia de Wernicke em um paciente com síndrome de obstrução pilórica por adenocarcinoma gástrico, sem história de alcoolismo e desnutrição. Comentam aspectos fisiológicos da importância da tiamina como co-enzima da transcetolase e da piruvato-descarboxilase na rota metabólica para produção de ATP e a possibilidade da existência de interação de fatores genéticos e ambientais no surgimento do quadro clínico. Chamam a atenção para a importância do diagnóstico clínico, que deve ser precoce para que a terapêutica específica com tiamina possa surtir efeito, principalmente em pacientes sem história prévia de alcoolismo e desnutrição.The authors present one case of Wernicke's encephalopathy in a patient with obstructive pyloric syndrome caused by gastric adenocarcinoma, wihout previous history of alcoholism or malnutrition. They comment on the importance of physiological aspects of thiamine as a co-enzyme of transketolase and pyruvate-decarboxilase in the metabolic pathway for ATP production and the possibility of existing an interaction between genetical and environmental factors in the onset the symptoms. They draw attention for the clinical diagnosis, which should be precocious for the therapy with thiamine to be efective, especially in patients without previous history of alcoholism or malnutrition.
Koolmees, P A; Tersteeg, M H G; Keizer, G; van den Broek, J; Bradley, R
The natural sausage casings industry is large and worldwide, and casings prepared from the small intestine of sheep form a large part of it. Food safety authorities in several countries have been concerned about the risk to consumers from the bovine spongiform encephalopathy (BSE) agent. Although this agent could enter the European small ruminant population via infected feed, there is no evidence that it has. Because the BSE agent introduced experimentally into sheep and goats has a tissue distribution very similar to that found in animals with natural cases of scrapie, the agent would likely be found in the intestine and lymph nodes of some infected sheep from an early age. When natural casings are prepared from the intestine, the ileum (known to be infected in animals with natural cases of scrapie) is removed and the intestine is cleaned such that the inner (tunica mucosa) and outer (tunica serosa and tunica muscularis) layers are removed, leaving only the submucosa. There are two main methods for cleaning the intestine: manual and mechanical. The cleaning efficiency of these two methods was examined in the commercial environment as practiced on healthy sheep considered fit for human consumption in Turkey and Great Britain. The investigation involved a qualitative and quantitative histological approach. There was no significant difference in cleaning efficiency between the two methods, although there was some variation. No Peyer's patches or residues of them were found in any part of the cleaned casings. This finding is important because in sheep infected with transmissible spongiform encephalopathies (TSEs) Peyer's patches are likely to contain a major part of the intestinal infectivity. No serosa was found in any casing, but some residual mucosa and muscularis was retained, with more of the former than the latter. The results indicate that the cleaning efficiency of the two methods was broadly equivalent, that there was significant removal of tissue that could
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.
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.
Markus Leitinger; Mihael V. Varosanec; Slaven Pikija; Romana E. Wass; Dave Bandke; Serge Weis; Michael Studnicka; Susanne Grinzinger; Mark R. McCoy; Larissa Hauer; Johann Sellner; Johann Sellner
Immune checkpoint inhibitors are antibodies, which enhance cellular and humoral immune responses and are approved for the treatment of various tumors. Immune-related adverse events (irAE) involving different organs and systems are, however, among the side-effects. Recent reports of severe persistent neurological deficits and even fatal cases underpin the need for better understanding of the exact pathomechanisms of central nervous system (CNS) toxicity. To our knowledge, we report the first b...
Siegler, Anne; Rosner, Zachary; MacDonald, Ross; Ford, Elizabeth; Venters, Homer
Abstract Because there is no standard reporting of injuries in jails and prisons, the national burden of head trauma during incarceration is unclear. We report on a case of repeated head trauma in the New York City (NYC) jail system, data on the incidence of head trauma and mild traumatic brain injury (mTBI), and compare those findings with national estimates. The case report revealed 64 injurious events over two years, 44% resulting in a head injury and 25% resulting in emergency hospitalization. During the 42 months of this analysis, 10,286 incidents of head trauma occurred in the NYC jail system. Mild TBI occurred in 1,507 of these instances. The rate of head trauma and mTBI was 269.0 and 39.4 per 1,000 person-years, respectively. The lack of reporting head trauma in correctional settings means that national prevalence estimates of these critical health outcomes miss the vulnerable cohort of incarcerated individuals.
... 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, ...
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.
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.
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.
Wijnker, Joris J; Tersteeg, M H G; Berends, B R; Vernooij, J C M; Koolmees, P A
A histological study was undertaken to determine the efficiency in the removal of the mucosa and Peyer's patches by standard processing of bovine intestines into natural sausage casings. The second objective was to calculate the quantity of lymphoid and nervous tissue per consumable sausage. For the histological analysis, intestinal samples were collected from 80 beef cattle during the slaughter process. Fresh and cleaned intestines were compared in analyzing the thickness of the intestinal wall, weight reduction during cleaning, removal of the mucosal layer, and the presence of lymphoid and neural tissue after cleaning. The obtained data indicate a weight reduction of about 50% during standard cleaning procedures, as 90% of the mucosa and 48% of the lymphoid tissue are removed. Based on the quantitative histological image analysis, it was calculated that 1 m of cleaned casings, weighing on average 64 g, contains about 2.8 g of mucosa, 0.3 g of lymphoid tissue, and 0.1 g of neural tissue. Assuming, in a worst-case scenario, that the sausage casing is ingested when consuming 200 g of sausage at one meal, this consumption includes 0.09 g of lymphoid tissue and 0.02 g of neural tissue as part of the sausage casing. These data can be included in a risk assessment on the potentialexposure of consumers to bovine spongiform encephalopathy infectivity after eating sausages in beef casings.
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.
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.
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....
Brtalik, Douglas; Stopyra, Jason; Hannum, Jennifer
Poison hemlock (Conium maculatum) is a common plant with a significant toxicity. Data on this toxicity is sparse as there have been few case reports and never a documented poisoning after intravenous injection. We present a case of intravenous poison hemlock injection encountered in the emergency department. We describe a 30-year-old male who presented to the emergency department after a brief cardiac arrest after injecting poison hemlock. The patient had return of spontaneous circulation in the emergency department but had prolonged muscular weakness and encephalopathy later requiring tracheostomy. Intravenous injection of poison hemlock alkaloids can result in significant toxicity, including cardiopulmonary arrest, prolonged weakness, and encephalopathy.
Shahwan, Amre; O'Halloran, Philip J; Madigan, Cathy; King, Mary D; O'Brien, Donncha
Traditionally, seizure onset localization in ictal electro-encephalography (EEG) is the main factor guiding resective epilepsy surgery. The situation is often different in infantile epileptic encephalopathy. We demonstrate the importance of the underrated interictal (rather than ictal) surface EEG in informing decision-making in epilepsy surgery for children with epileptic encephalopathy caused by subtle focal cortical dysplasia (FCD). We present a small case series of three children who had an epileptic encephalopathy with either epileptic spasms or tonic seizures. All three were thought initially to have normal neuroimaging. Ictal EEG localizing features were seen in none and lateralizing features were seen only clinically in one of the three. However, the interictal EEG showed persistent and consistent focal irregular slowing in all, particularly after medically resolving the diffuse encephalopathy. Subtle FCDs were uncovered in all. Surgery was performed in all with excellent outcome. In infantile epileptic encephalopathy caused by subtle FCD, the often underrated interictal surface EEG (particularly persistent foal irregular slowing) informs the most; not only to the target area for surgical resection but also to its extent. This may negate the need for unnecessary and sometimes non-informative invasive monitoring in these cases. A matter of "zooming out" to define the extent of a resectable abnormality rather than "zooming in" to define a seemingly localized epileptic focus that may change with time.
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)
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)
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.). ...
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.
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.
... 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.
Se Hee Kim MD
Full Text Available Hemimegalencephaly, a congenital brain malformation typically characterized by enlargement of one hemisphere, is frequently associated with intractable epilepsy. The authors report a case of a 12-month-old girl with hemimegalencephaly who underwent semiurgent hemispherectomy because of rapidly escalating seizures, arrested development, and associated encephalopathy. The brain tissue was examined and evaluated for neuroinflammation. Immunohistochemical analysis of the brain tissue revealed the presence of abundant activated CD68-positive microglia and reactive astrogliosis. Detection of active inflammatory changes in the brain of a patient with hemimegalencephaly complicated by intractable epilepsy suggests a potential role of ongoing brain inflammation in seizure exacerbation and epileptic encephalopathy.
Joshi, Charuta; Kolbe, Diana L; Mansilla, M Adela; Mason, Sara; Smith, Richard J H; Campbell, Colleen A
We describe the presentation and workup of two brothers with early-onset epileptic encephalopathy who became seizure-free on a ketogenic diet. Extensive testing culminated in whole exome sequencing, which led to the diagnosis of phosphatidyl inositol glycan biosynthesis class A protein (PIGA) deficiency. This familial case highlights the importance of genetic testing for early-onset epileptic encephalopathies and underscores the potential value of a ketogenic diet in the treatment of this condition. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Nolli, M; Barbieri, A; Pinna, C; Pasetto, A; Nicosia, F
We report a clinical and neuroradiological description of a severe case of Wernicke's encephalopathy in a surgical patient. After colonic surgery for neoplasm, he was treated for a long time with high glucose concentration total parenteral nutrition. In the early post-operative period, the patient showed severe encephalopathy with ataxia, ophthalmoplegia and consciousness disorders. We used magnetic resonance imaging (MRI) to confirm the clinical suspicion of Wernicke's encephalopathy. The radiological feature showed hyperintense lesions which were symmetrically distributed along the bulbo-pontine tegmentum, the tectum of the mid-brain, the periacqueductal grey substance, the hypothalamus and the medial periventricular parts of the thalamus. This progressed to typical Wernicke-Korsakoff syndrome with ataxia and memory and cognitive defects. Thiamine deficiency is a re-emerging problem in non-alcoholic patients and it may develop in surgical patients with risk factors such as malnutrition, prolonged vomiting and long-term high glucose concentration parenteral nutrition.
Full Text Available We report the case of a 14-year-old boy with a past history of primary generalized seizures, who had been seizure-free for 2 years on sodium valproate and presented with generalized tonic clonic seizures suggestive of breakthrough seizures. Examination revealed hypertension, impetiginous lesions of the lower limbs, microscopic hematuria, elevated antistreptolysin O titre and low complement levels consistent with acute post-streptococcal glomerulonephritis. Cranial magnetic resonance imaging (MRI demonstrated changes consistent with posterior reversible encephalopathy syndrome. Hypertension was controlled with intravenous nitroglycerin followed by oral captopril and amlodipine. Brain MRI changes returned normal within 2 weeks. The nephritis went in to remission within 2 months and after 8 months the patient has been seizure free again. Posterior reversible encephalopathy syndrome appeared to have neither short nor intermediate effect on seizure control in this patient. The relationship between posterior reversible encephalopathy syndrome and seizures is reviewed.
Masdeu, J.C.; Yudd, A.; Van Heertum, R.L.; Grundman, M.; Hriso, E.; O'Connell, R.A.; Luck, D.; Camli, U.; King, L.N.
Depression or psychosis in a previously asymptomatic individual infected with the human immunodeficiency virus (HIV) may be psychogenic, related to brain involvement by the HIV or both. Although prognosis and treatment differ depending on etiology, computed tomography (CT) and magnetic resonance imaging (MRI) are usually unrevealing in early HIV encephalopathy and therefore cannot differentiate it from psychogenic conditions. Thirty of 32 patients (94%) with HIV encephalopathy had single-photon emission computed tomography (SPECT) findings that differed from the findings in 15 patients with non-HIV psychoses and 6 controls. SPECT showed multifocal cortical and subcortical areas of hypoperfusion. In 4 cases, cognitive improvement after 6-8 weeks of zidovudine (AZT) therapy was reflected in amelioration of SPECT findings. CT remained unchanged. SPECT may be a useful technique for the evaluation of HIV encephalopathy
Abdool, Kamille; Ramcharan, Kanterpersad; Bhagwandass, Neal; Persad, Navindra; Temull, Vasant; Seegobin, Karan; Mike, Cassie
We report the case of a 14-year-old boy with a past history of primary generalized seizures, who had been seizure-free for 2 years on sodium valproate and presented with generalized tonic clonic seizures suggestive of breakthrough seizures. Examination revealed hypertension, impetiginous lesions of the lower limbs, microscopic hematuria, elevated anti-streptolysin O titre and low complement levels consistent with acute post-streptococcal glomerulonephritis. Cranial magnetic resonance imaging (MRI) demonstrated changes consistent with posterior reversible encephalopathy syndrome. Hypertension was controlled with intravenous nitroglycerin followed by oral captopril and amlodipine. Brain MRI changes returned normal within 2 weeks. The nephritis went in to remission within 2 months and after 8 months the patient has been seizure free again. Posterior reversible encephalopathy syndrome appeared to have neither short nor intermediate effect on seizure control in this patient. The relationship between posterior reversible encephalopathy syndrome and seizures is reviewed.
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....
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 was developed before the use of therapeutic hypothermia, its value was reassessed. The purpose of this study was to assess the association of the Thompson encephalopathy score with adverse short-term outcomes, defined as death before discharge, development of severe epilepsy, or the presence of multiple organ failure in asphyxiated newborns undergoing therapeutic hypothermia. The study period ranged from November 2010 to October 2014. A total of 12 tertiary neonatal intensive care units participated. Demographic and clinical data were collected from the "PharmaCool" multicenter study, an observational cohort study analyzing pharmacokinetics of medication during therapeutic hypothermia. With multiple logistic regression analyses the association of the Thompson encephalopathy scores with outcomes was studied. Data of 142 newborns were analyzed (male: 86; female: 56). Median Thompson score was 9 (interquartile range: 8 to 12). Median gestational age was 40 weeks (interquartile range 38 to 41), mean birth weight was 3362 grams (standard deviation: 605). All newborns manifested perinatal asphyxia and underwent therapeutic hypothermia. Death before discharge occurred in 23.9% and severe epilepsy in 21.1% of the cases. In total, 59.2% of the patients had multiple organ failure. The Thompson encephalopathy score was not associated with multiple organ failure, but a Thompson encephalopathy score ≥12 was associated with death before discharge (odds ratio: 3.9; confidence interval: 1.3 to 11.2) and with development of severe epilepsy (odds ratio: 8.4; confidence interval: 2.5 to 27.8). The Thompson encephalopathy score is a useful clinical tool, even in cooled asphyxiated
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
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.
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
González-Duarte, Alejandra; Medina, Zaira; Balaguer, Rainier Rodriguez; Calleja, Jesus Higuera
The subacute spongiform encephalopathies are prion diseases characterized by acute and rapid neurodegeneration that lead to the death of the patient within months to a few years. The epidemiology of CJD is complicated and the frequency in Mexico is unknown. We aim to describe the cases of prion disease in Mexico. Consecutive patients who met the diagnostic criteria by the WHO were enrolled. We describe 26 patients with clinical manifestations, imaging and laboratory studies compatible with prion disease. The mean age at onset was 52 years old. The main clinical manifestations were cognitive alterations (69%) followed by extrapyramidal movements (50%), abnormal cerebellar function (46%), behavioral alterations (46%), myoclonus (46%), and mood depression (23%), among other features. Half of the patients progressed rapidly to a state of akinetic mutism (53%). Only 2 (7.6%) patients had a family history of a similar disease. Time interval between onset and diagnosis varied between 71 days to 24 months, with a median of 6 months. The classical bilateral basal ganglia hyperintensities were present in the very early stage of the disease. Protein 14-3-3 immuneassay in the CSF was positive in all measured cases. Bilateral basal ganglia hyperintensities was the most important early finding, while protein 14-3-3 was a late finding and the results were usually obtained after the patient was discharged. Around 1.5 cases of CJD cases per year are reported in our country. When suspected, MRI can support the diagnosis earlier than other studies.
Myae, Aye C.; Goddard, Ellen W.
Prion diseases have raised concerns in consumer’s minds about food safety associated with meat world-wide. Bovine Spongiform Encephalopathy (BSE) and Chronic Wasting Disease (CWD) both exist in Canada and consumer markets for beef, bison, elk and deer may have been affected by the diseases. While numerous studies have examined Canadian consumer beef purchasing behavior in the presence of BSE (Lomeli (2005), John(2007)), no examination of the impact of the animal diseases on consumer behavior ...
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.
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
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.
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) ...
Sunny Oteikwu Ochigbo
Full Text Available Background: Bilirubin encephalopathy is a clinical syndrome, associated with bilirubin toxicity in the central nervous system, resulting in chronic and permanent sequelae. It has been estimated that approximately 60% and 80% of term and preterm newborns develop jaundice in the first week of life, respectively. In the present study, we aimed to determine the prevalence, morbidity, and mortality of bilirubin encephalopathy in the neonatal unit of the University of Calabar Teaching Hospital, Calabar, Nigeria. Methods: In this retrospective, descriptive review, medical records of all newborns, diagnosed with bilirubin encephalopathy over the past five years (from January 2010 to December 2014, were studied. Information retrieved from the medical records included age, sex, presence of fever, duration of disease, place of delivery, causes of the disease, and selected treatments. Variables such as hospital discharge, discharge against medical advice, and mortality were also evaluated. Results: Out of 2,820 newborns, 21 (0.74% cases were admitted on account of bilirubin encephalopathy. Among these affected cases, 17 (81% were male and 4 (19% were female (male-to-female ratio of 5:1. Based on the findings, 18 newborns (85.7% had pyrexia, while 8 (38.1% and 6 (28.6% cases were hypertonic and hypotonic, respectively upon admission. Only 33.3% of deliveries took place in healthcare facilities. The established factors responsible for jaundice included infection, i.e., septicemia (n=15, 71.4%, ABO incompatibility (n=4, 19.1%, and glucose-6-phosphate-dehydrogenase (G6PD deficiency (n=2, 9.5%. The mean maximum total bilirubin level in subjects was 321.3 μmol/L (range: 242.5–440.3 μmol/L. Also, mortality was reported in 4 (19% out of 21 cases. Conclusion: Based on the findings, neonatal septicemia is associated with bilirubin encephalopathy. Therefore, identification and prompt treatment are of utmost importance in preventing the associated morbidity and
Bastian, Frank O
The question whether Alzheimer's disease is infectious as brought up in the recent editorial published in the Journal of Alzheimer's Disease is complicated by the controversy whether the causal agent is a microbe or a misfolded host protein (amyloid). The replicating amyloid (prion) theory, based upon data from studies of Creutzfeldt-Jakob disease (CJD) and other transmissible spongiform encephalopathies (TSEs), has been challenged since the prion can be separated from TSE infectivity, and spiroplasma, a wall-less bacterium, has been shown to be involved in the pathogenesis of CJD. Further support for a microbial cause for AD comes from occurrence of mixed CJD/AD cases involving up to 15% of AD brains submitted to brain banks. The association of CJD with AD suggests a common etiology rather than simply being a medical curiosity. A co-infection with the transmissible agent of CJD, which we propose to be a Spiroplasma sp., would explain the diversity of bacteria shown to be associated with cases of AD.
Simpson, Ewan; Andronikou, Savvas; Vedajallam, Schadie; Chacko, Anith; Thai, Ngoc Jade
Hypoxic-ischaemic encephalopathy is optimally imaged with brain MRI in the neonatal period. However neuroimaging is often also performed later in childhood (e.g., when parents seek compensation in cases of alleged birth asphyxia). We describe a standardised technique for creating two curved reconstructions of the cortical surface to show the characteristic surface changes of hypoxic-ischaemic encephalopathy in children imaged after the neonatal period. The technique was applied for 10 cases of hypoxic-ischaemic encephalopathy and also for age-matched healthy children to assess the visibility of characteristic features of hypoxic-ischaemic encephalopathy. In the abnormal brains, fissural or sulcal widening was seen in all cases and ulegyria was identifiable in 7/10. These images could be used as a visual aid for communicating MRI findings to clinicians and other interested parties.
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.
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.
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
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).
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.
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.
Villaluz, Mel Michel; Lomax, Lysa Boissé; Jadhav, Trupti; Cross, J Helen; Scheffer, Ingrid E
Ketogenic diet therapies have proven efficacy for refractory epilepsy. There are many reports of their use in the genetic developmental and epileptic encephalopathies; however, little attention has been paid as to whether the diet is also effective in individuals with an acquired structural aetiology. We observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic encephalopathy. We then analysed our cases with refractory structural epilepsies of acquired origin to characterize their response to the ketogenic diet. The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1. Seizure frequency at 1 month, 3 months, 6 months, 1 year, and 2 years was ascertained. A responder was defined as greater than 50% seizure reduction compared to baseline. Seven of the nine patients were responders at 3 months. Somewhat surprisingly we found that the ketogenic diet was effective in patients with a developmental and epileptic encephalopathy due to an acquired structural aetiology. This cohort may not be routinely considered for the ketogenic diet because of their structural and acquired, rather than genetic, basis. The ketogenic diet should be considered early in the management of patients with acquired structural encephalopathies as it can improve seizure control with the potential to improve developmental outcome. The ketogenic diet was effective in children with epilepsy associated with an acquired structural aetiology. © 2018 Mac Keith Press.
Kale, Alok; Joshi, Priscilla; Kelkar, A B
Restricted diffusion within the splenium of the corpus callosum has been described by other authors in various conditions, however, restricted diffusion in the entire corpus callosum or isolated involvement of the splenium, genu, or body has been infrequently reported on magnetic resonance imaging (MRI) in neonatal hypoxic-ischemic encephalopathy. We report a series of cases showing different patterns of involvement. Perinatal imaging with MRI including diffusion-weighted imaging was performed in 40 neonates with hypoxic-ischemic encephalopathy, including 11 premature neonates. Sixteen out of 40 patients demonstrated restricted diffusion within the corpus callosum. Out of 16 patients, 9 showed restricted diffusion in the entire corpus callosum, 4 had isolated splenium involvement, 2 had body and splenium signal abnormality, and 1 showed diffusion restriction only in the genu. Changes in the corpus callosum were also associated with more severe clinical presentation of encephalopathy. Restricted diffusion within the corpus callosum in infants with hypoxic-ischemic encephalopathy is often associated with extensive brain injury and appears to be an early neuroradiologic marker of adverse neurologic outcome.
Irfan Ahmad Shah
Full Text Available Objective: The objective of this study was to describe the demographic features, clinical presentation, and management and outcome of fifty cases of nonalcoholic Wernicke's encephalopathy from a tertiary care hospital of a region with reported incidence of thiamine deficiency disorders. Materials and Methods: In a retrospective study, fifty adult cases of Wernicke's encephalopathy were analyzed. The diagnosis of Wernicke's encephalopathy was made according to the European federation of neurological societies guidelines 2010. Response to thiamine replacement and associated brain magnetic resonance imaging (MRI findings were also considered as supportive evidence. Results: The mean age of patients was 50.38 years with 20 males and 30 females. The most common clinical manifestations were alteration in sensorium in 30 (60%, ataxia in 18 (36%, memory impairment in 15 (30%, nystagmus in 35 (70%, ophthalmoparesis in 11 (22%, and seizures in 4 (8%. A total of 42 patients had a history of recurrent vomiting. All patients had polished rice as their staple diet. Thirty-five patients had associated polyneuropathy and 15 had a gastrointestinal disorder. Twenty patients underwent MRI which showed both typical and atypical lesions. Majority of patients showed partial or complete response to intravenous thiamine. On discharge, the most common residual symptoms were lower limb weakness, ataxia, and memory impairment. Conclusion: The study shows high incidence of nonalcoholic Wernicke's encephalopathy in the region with predominant causative factor being a thiamine deficient diet. Recurrent vomiting can be a prominent early symptom of thiamine deficiency and its recognition can help in the early diagnosis of Wernicke's encephalopathy and related thiamine deficiency disorders. Thiamine fortification of food should be done in areas with reported incidence of thiamine deficiency disorders.
Romaniello, Romina; Zucca, Claudio; Tenderini, Erika; Arrigoni, Filippo; Ragona, Francesca; Zorzi, Giovanna; Bassi, Maria Teresa; Borgatti, Renato
Mutations in STXBP1 gene, encoding the syntaxin binding protein 1, have been recently described in Ohtahara syndrome, or early infantile epileptic encephalopathy with suppression-burst pattern, and in other early-onset epileptic encephalopathies. A 3-year-old boy affected by epileptic encephalopathy started at 8 months of age is described. Focal epilepsy was characterized by drug resistance seizures with multifocal interictal and ictal electroencephalographic (EEG) features and variable EEG focus. Direct sequencing of the STXBP1 gene showed a novel de novo mutation (c.751G>A), leading to a p.Ala251Thr substitution. Based on reported data, treatment with vigabatrin was attempted and patient became immediately seizure free for 4 months. The present case further expands the clinical spectrum of "STXBP1-related encephalopathy" suggesting molecular analysis of STXBP1 in early onset epileptic encephalopathies of unknown etiology (with onset within the first year of life). In addition, the case provides valuable suggestions on seizures treatment in STXBP1 mutated subjects.
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....
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...
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.
... 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.
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.
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 Background. Hyperammonemia resulting from chronic liver disease (CLD can potentially challenge and damage any organ system of the body, particularly the brain. However, there is still some controversy regarding the diagnostic or prognostic values of serum ammonia in patients with over hepatic encephalopathy, especially in the setting of acute-on-chronic or chronic liver failure. Moreover, the association of serum ammonia with worsening Child-Pugh grade of liver cirrhosis has not been studied. Objective. This study was conducted to solve the controversy regarding the association between hyperammonemia and cirrhosis, especially hepatic encephalopathy in chronically failed liver. Material and Methods. In this study, 171 cirrhotic patients had their serum ammonia measured and analyzed by SPSS version 16. Chi-squared test and one-way ANOVA were applied. Results. The study had 110 male and 61 female participants. The mean age of all the participants in years was 42.33±7.60. The mean duration (years of CLD was 10.15±3.53 while the mean Child-Pugh (CP score was 8.84±3.30. Chronic viral hepatitis alone was responsible for 71.3% of the cases. Moreover, 86.5% of participants had hepatic encephalopathy (HE. The frequency of hyperammonemia was 67.3%, more frequent in males (N=81, z-score = 2.4, and P<0.05 than in females (N=34, z-score = 2.4, and P<0.05, and had a statistically significant relationship with increasing CP grade of cirrhosis (χ2(2 = 27.46, P<0.001, Phi = 0.40, and P<0.001. Furthermore, serum ammonia level was higher in patients with hepatic encephalopathy than in those without it; P<0.001. Conclusion. Hyperammonemia is associated with both increasing Child-Pugh grade of liver cirrhosis and hepatic encephalopathy.
Gano, Dawn; Sargent, Michael A; Miller, Steven P; Connolly, Mary B; Wong, Peter; Glass, Hannah C; Poskitt, Kenneth J; Chau, Vann
To evaluate the predominant pattern of brain injury and the anatomic areas of injury in children with infantile spasms following neonatal hypoxic-ischemic encephalopathy. A nested case-control study of infantile spasms in children with term neonatal hypoxic-ischemic encephalopathy was performed. All patients had T1/T2-weighted magnetic resonance imaging with diffusion-weighted imaging performed on the third day of life. Using a validated scoring system, the magnetic resonance imaging was classified as: normal, watershed, basal ganglia/thalamus, total, or focal-multifocal. Two study investigators scored additional anatomic areas of injury (cortical extent, levels of the brainstem, hypothalamus) on T1/T2-weighted magnetic resonance imaging and diffusion-weighted imaging blinded to the outcome. The predominant pattern of brain injury and anatomic areas of injury were compared between patients who developed infantile spasms and randomly selected controls. Eight patients who developed infantile spasms were identified among a cohort of 176 term newborns with hypoxic-ischemic encephalopathy (4.5%). There were no significant differences in the perinatal and neonatal course between newborns who developed infantile spasms and controls who did not. The development of infantile spasms after neonatal hypoxic-ischemic encephalopathy was significantly associated with basal ganglia/thalamus and total brain injury (P = 0.001), extent of cortical injury greater than 50% (odds ratio = 11.7, 95% confidence interval = 1.1-158.5, P = 0.01), injury to the midbrain (odds ratio = 13, 95% confidence interval = 1.3-172, P = 0.007) and hypothalamic abnormalities (P = 0.01). The development of infantile spasms after hypoxic-ischemic encephalopathy is associated with injury to the basal ganglia and thalami on neonatal magnetic resonance imaging, particularly when extensive cortical injury and/or injury to the midbrain is present. Copyright © 2013 Elsevier Inc. All rights reserved.
Objective: To evaluate spiral CT imaging in the diagnosis of hypoxic-ischemic encephalopathy (HIE) in the neonates and infants. Methods: 112 children with history of asphyxia in peri-natal period and evident clinical symptoms were evaluated with Spiral CT. CT findings were studied. Results: 46 minor cases, 57 moderate cases and 9 severe cases were found out of 112 patients. Intracranial hemorrhage was revealed in 38 cases. Mortality occurred in 1 case. Conclusion: Spiral CT is helpful for evaluating brain damage and predicting prognosis in neonates with HIE. (authors)
Full Text Available Infection with Epstein–Barr virus (EBV is very common and usually occurs in childhood or early adulthood. Encephalitis/encephalopathy is an uncommon but serious neurological complication of EBV. A case of EBV-associated encephalitis/encephalopathy with involvement of reversible widespread cortical and splenial lesions is presented herein. An 8-year-old Chinese girl who presented with fever and headache, followed by seizures and drowsiness, was admitted to the hospital. Magnetic resonance imaging revealed high signal intensities on diffusion-weighted imaging in widespread cortical and splenial lesions. The clinical and laboratory examination results together with the unusual radiology findings suggested acute encephalitis/encephalopathy due to primary EBV infection. After methylprednisolone pulse therapy together with ganciclovir, the patient made a full recovery without any brain lesions. The hallmark clinical–radiological features of this patient included severe encephalitis/encephalopathy at onset, the prompt and complete recovery, and rapidly reversible widespread involvement of the cortex and splenium. Patients with EBV encephalitis/encephalopathy who have multiple lesions, even with the widespread involvement of cortex and splenium of the corpus callosum, may have a favorable outcome with complete disappearance of all brain lesions.
M F Devine
Full Text Available We report a case of a 36-year-old man with a medical history of human immunodeficiency virus (HIV infection who presented with hypomimia, hypophonia, bradykinesia, rigidity, and freezing of gait. His clinical presentation and magnetic resonance imaging were consistent with HIV encephalopathy with involvement of the bilateral basal ganglia and diffuse leukoencephalopathy. We initiated a trial of carbidopa-levodopa. The dose was escalated to 1050 mg levodopa daily. Amantadine was also started. The patient was closely monitored for behavioral, neurological, or systemic side effects. He tolerated therapy well without adverse effects. The patient's neurological status significantly improved with levodopa, including hypomimia, hypophonia, bradykinesia, and fluidity of gait. This case demonstrates that carbidopa-levodopa can be safely utilized to manage parkinsonism in an adult patient with HIV encephalopathy.
Full Text Available Thorsten Gerstner, Nellie Bell, Stephan A KoenigUniversity Children’s Hospital, Mannheim, GermanyAbstract: Valproic acid (VPA is considered to be a drug of first choice for the therapy of generalized and focal epilepsies, including special epileptic syndromes. The drug is usually well tolerated, rare serious complications may occur in some patients, including hemorrhagic pancreatitis, coagulapathies, bone marrow suppression, VPA-induced hepatotoxicity and encephalopathy. We report a case of VPA-associated encephalopathy without hyperammonemia in a 3-year-old girl with Pallister-Killian-Syndrom, combined with a mild hepatopathy and thrombopathy. After withdrawal of VPA, the clinical symptoms and the electroencephalography-alterations vanished rapidly.Keywords: pallister-killian, valproate, encephalopathy, EEG, ammonia
Pavlidis, Elena; Rubboli, Guido; Nikanorova, Marina
Encephalopathy with status epilepticus during sleep (ESES) is an age-related disorder characterized by neuropsychological regression, epilepsy and a typical EEG pattern of continuous epileptiform activity (> 85%) during NREM sleep. Cases of worsening or induction of ESES with phenytoin......, carbamazepine and phenobarbital have been reported. We describe a child with benign epilepsy with centrotemporal spikes (BECTS) in whom treatment with oxcarbazepine (OXC) induced ESES. The patient was studied through repeated clinical-neuropsychological evaluations and 24-hour EEG recordings. He was treated...
Sengupta, Pratim; Biswas, Sumanta
Dialysis disequilibrium syndrome is a neurological adverse effect of acute hemodialysis in advanced uremic patients. Dialysis disequilibrium has a wide spectrum of clinical manifestations starting from subtle uneasiness, confusion, to florid and complex life threatening neurological deficit. In this case study, we present a patient who developed sudden cortical blindness following hemodialysis due to posterior reversible encephalopathy, which is a rare presentation of dialysis disequilibrium ...
McKee, Ann C.; Cantu, Robert C.; Nowinski, Christopher J.; Hedley-Whyte, E. Tessa; Gavett, Brandon E.; Budson, Andrew E.; Santini, Veronica E.; Lee, Hyo-Soon; Kubilus, Caroline A.; Stern, Robert A.
Since the 1920s, it has been known that the repetitive brain trauma associated with boxing may produce a progressive neurological deterioration, originally termed “dementia pugilistica” and more recently, chronic traumatic encephalopathy (CTE). We review the 47 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 professional athletes: one football player and 2 boxers. Clinically, CTE is associated with memory disturbances, behavi...
McKee, Ann C.; Cantu, Robert C.; Nowinski, Christopher J.; Hedley-Whyte, E. Tessa; Gavett, Brandon E.; Budson, Andrew E.; Santini, Veronica E.; Lee, Hyo-Soon; Kubilus, Caroline A.; Stern, Robert A.
Since the 1920s, it has been known that the repetitive brain trauma associated with boxing may produce a progressive neurological deterioration, originally termed “dementia pugilistica” and more recently, chronic traumatic encephalopathy (CTE). We review the 47 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 professional athletes: one football player and 2 boxers. Clinically, CTE is associated with memory disturbances, behavi...
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.
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 ...
Sadler, Lynn C; Farquhar, Cynthia M; Masson, Vicki L; Battin, Malcolm R
The recently published monograph, Neonatal encephalopathy and neurologic outcome, from the American College of Obstetricians and Gynecologists calls for a root cause analysis to identify components of care that contributed to cases of neonatal encephalopathy to design better practices, surveillance mechanisms, and systems. All cases of infants born in New Zealand with moderate and severe neonatal encephalopathy were reported to the New Zealand Perinatal and Maternal Mortality Review Committee from 2010. A national clinical review of these individual cases has not previously been undertaken. The objective of the study was to undertake a multidisciplinary structured review of all cases of neonatal encephalopathy that arose following the onset of labor in the absence of acute peripartum events in 2010-2011 to determine the frequency of contributory factors, the proportion of potentially avoidable morbidity and mortality and to identify themes for quality improvement. National identification of, and collection of clinical records on, cases of moderate or severe neonatal encephalopathy occurring after the onset of labor in the absence of an acute peripartum event, excluding those with normal gases and Apgar scores at 1 minute, among all cases of moderate and severe neonatal encephalopathy at term in New Zealand in 2010-2011 was undertaken. Cases were included if they had abnormal gases as defined by any of pH of ≤ 7.2, base excess of ≤ -10, or lactate of ≥ 6 or if there were no cord gases, an Apgar score at 1 minute of ≤ 7. A clinical case review was undertaken by a multidisciplinary team using a structured tool to record contributory factors (organization and/or management, personnel, and barriers to access and/or engagement with care), potentially avoidable morbidity and mortality and to identify themes to guide quality improvement. Eighty-three babies fulfilled the inclusion criteria for the review, 56 moderate (67%) and 27 severe (33%), 21 (25%) of whom were
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
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
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.
Full Text Available Hepatic encephalopathy due to intrahepatic portosystemic venous shunts (IPSVS in a non-cirrhotic condition is rare. Here we report a rare case of a patient with congenital multiple IPSVS successfully treated by percutaneous transhepatic obliteration. The patient was a 67-year-old woman who presented to our hospital with progressive episodes of consciousness disorder and vomiting. Laboratory tests revealed hyperammonemia (192.0 μg/dL, and computed tomography revealed multiple IPSVS in both lobes. There was no evidence of underlying liver disease or hepatic trauma. Transcatheter embolization for IPSVS was performed because conservative therapy was not sufficiently effective. After endovascular shunt closure, hepatic encephalopathy improved. The serum ammonia level normalized during the 5-year follow-up period. Thus, transcatheter embolization may be an effective therapy for patients with symptomatic and refractory IPSVS. Careful follow-up is necessary for portal hypertension-related complications after transcatheter embolization for IPSVS.
Jones, Rachel; Redler, Kasey; Witherick, Jonathan; Fuller, Geraint; Mahajan, Tripti; Wakerley, Benjamin R
Development of acute neurological symptoms secondary to cerebral oedema is well described in diabetic ketoacidosis (DKA) and often has a poor prognosis. We present the clinical and radiological data of a 17-yr-old girl who developed cortical blindness, progressive encephalopathy, and seizures caused by posterior reversible encephalopathy syndrome (PRES) that developed after her DKA had resolved. Vasogenic oedema in PRES resolves if the underlying trigger is identified and eliminated. In this case, hypertension was identified as the likely precipitating factor and following treatment her vision and neurological symptoms rapidly improved. We suggest how recent DKA may have contributed to the development of PRES in this patient. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Jang, Jae-Won; Park, So Young; Park, Young Ho; Kim, Jung E; Kim, SangYun
Creutzfeldt-Jakob disease and Hashimoto's encephalopathy often show similar clinical presentation. Among Creutzfeldt-Jakob disease mimics, Hashimoto's encephalopathy is particularly important as it is treatable with corticosteroids. Thus, in cases of middle-aged woman diagnosed with probable Creutzfeldt-Jakob disease and who exhibit high titers of antithyroid antibodies, corticosteroid pulse therapy is typically performed with expectations of near complete recovery from Hashimoto's encephalopathy. Herein, we provide the first case report that exhibited a negative effect of corticosteroid pulse therapy for a patient with Creutzfeldt-Jakob disease with features of Hashimoto's encephalopathy. We report a case of 59-year-old Asian woman with blurred vision, dysarthria, myoclonus, and rapidly progressive dementia. Cerebrospinal fluid showed 14-3-3 protein positive. Electroencephalogram showed periodic sharp waves (1.5 Hz) at the bilateral frontal or occipital areas. Magnetic resonance imaging showed high signal intensities at the bilateral cerebral cortex, caudate nucleus, and putamen. The patient was diagnosed with probable Creutzfeldt-Jakob disease. However, serum analysis showed a high titer of antithyroid antibodies. We started corticosteroid pulse therapy with subsequent aggravation of seizure activity including generalized myoclonus, epilepsia parialis continua, and ballistic dyskinesia, which was effectively treated with clonazepam. We provide evidence of a case of Creutzfeldt-Jakob disease that exhibited clinical deterioration after corticosteroid therapy. Although histopathological confirmation with brain biopsy is not easily available in Creutzfeldt-Jakob disease patients, selective initiation of corticosteroid pulse therapy should be considered in cases of uncertain diagnosis for differentiation with Hashimoto's encephalopathy.
Kim, Boaz; Yoo, Patrick; Sutherland, Tom; Boyd, Alison; Stehmann, Christiane; McLean, Catriona
Objective: To report a rare case of leucine-rich, glioma inactivated 1 (LGI1) antibody–mediated autoimmune encephalopathy clinically overlapping with pathologically confirmed sporadic Creutzfeldt-Jakob disease (CJD). Methods: The patient was investigated with repeated brain MRI, EEG, CSF examination, whole-body fluorodeoxy-glucose positron emission tomography, genetic analysis of the prion protein gene (PRNP), and extensive serologic screening for paraneoplastic and autoimmune encephalopathy markers. Written informed consent was obtained from the patient's next of kin for access to clinical files for research purposes and for publication. Results: The patient was a 77-year-old man who presented with faciobrachial dystonic seizures (FBDS) secondary to LGI1 antibody–mediated autoimmune encephalopathy, with suggestive MRI findings and a complete response to treatment with combinatorial immunosuppression. Stereotactic biopsy of a nonenhancing T1 hyperintense basal ganglia lesion during the initial FBDS phase, albeit following immunosuppression, did not disclose evidence of lymphocytic inflammation. Following full remission of the FBDS, the patient manifested a rapidly progressive dementia associated with gross motor decline confirmed to be CJD at autopsy (molecular subtype VV3), with no evidence of a pathogenic PRNP mutation. Conclusions: Our patient highlights that these rare diseases are not invariably mutually exclusive and underscores the benefits of comprehensive neuropathologic examination of the brain to achieve an accurate diagnosis, especially in complex cases when the clinical trajectory dramatically deviates and a concomitant disease may need to be conscientiously considered to best explain the new clinical course. PMID:27354985
Dilena, Robertino; Striano, Pasquale; Gennaro, Elena; Bassi, Laura; Olivotto, Sara; Tadini, Laura; Mosca, Fabio; Barbieri, Sergio; Zara, Federico; Fumagalli, Monica
Recent clinical evidence supports a targeted therapeutic approach for genetic epileptic encephalopathies based on the molecular dysfunction. A 2-day-old male infant presented with epileptic encephalopathy characterized by burst-suppression EEG background and tonic-clonic migrating partial seizures. The condition was refractory to phenobarbital, pyridoxine, pyridoxal phosphate and levetiracetam, but a dramatic response to an intravenous loading dose of phenytoin was documented by video-EEG monitoring. Over weeks phenytoin was successfully switched to carbamazepine to prevent seizure relapses associated with difficulty in maintaining proper blood levels of phenytoin. Genetic analysis identified a novel de novo heterozygous mutation (c.[4633A>G]p.[Met1545Val]) in SCN2A. At two years and three months of age the patient is still seizure-free on carbamazepine, although a developmental delay is evident. Sodium channel blockers represent the first-line treatment for confirmed or suspected SCN2A-related epileptic encephalopathies. In severe cases with compatible electro-clinical features we propose a treatment algorithm based on a test trial with high dose intravenous phenytoin followed in case of a positive response by carbamazepine, more suitable for long-term maintenance treatment. Because of their rarity, collaborative studies are needed to delineate shared therapeutic protocols for EIEE based on the electro-clinical features and the presumed underlying genetic substrate. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
В. Г. Постнов
Full Text Available Reviewed in this paper are modern approaches in the intensive therapy of acute hypoxic encephalopathy developing in a number of occasions after the heart valve replacement surgery. The study is based on the results of neurological, neuropsychological and neurophysiological (EEG examinations of 240 patients who underwent heart valve replacement surgery under cardiopulmonary bypass conditions complicated later by the development of hypoxic encephalopathies of varying severity and who received complex intensive care. Relying on many years of experience in the treatment of heart surgery patients in whom manifestations of encephalopathy developed in the early postoperative period, or were delayed, we have formulated the following algorithms of therapy. (1 Maintenance of normal blood gas: Hb>100 g/L, pH 7.45, PaCO2 35 mmHg. (2 Maintenance of hemodynamics: ABPsystolic>90 mmHg. (3 Supplying fluids and electrolytes: isoosmolar infusion solutions, adding of KCl and MgSO4 to the infusion. (4 Antiedemic therapy: 15% mannitol or 40% glycerol solution. (5 If necessary (in case of psychomotor agitation, seizures, short-acting barbiturates (sodium thiopental, neuroleptics (haloperidol, propofol. No benzodiazepines in case of psychoses (6 Cerebral metabolism stimulation (not earlier than 48 hours after surgery with cholinomimetics, nootropics, cerebral blood flow protectors. Cholinomimetics are allowed on the first day after surgery. This algorithm and the above-mentioned groups of drugs, especially central cholinomimetics, allow for correcting the neurocognitive impairment in the discussed group of patients quickly and effectively.
Papandreou, Apostolos; McTague, Amy; Trump, Natalie; Ambegaonkar, Gautam; Ngoh, Adeline; Meyer, Esther; Scott, Richard H; Kurian, Manju A
The gamma-aminobutyric acid type A receptor β3 gene (GABRB3) encodes the β3-subunit of the gamma-aminobutyric acid type A (GABAA ) receptor, which mediates inhibitory signalling within the central nervous system. Recently, GABRB3 mutations have been identified in a few patients with infantile spasms and Lennox-Gastaut syndrome. We report the clinical and electrographic features of a novel case of GABRB3-related early-onset epileptic encephalopathy. Our patient presented with neonatal hypotonia and feeding difficulties, then developed pharmacoresistant epileptic encephalopathy, characterized by multiple seizure types from 3 months of age. Electroencephalography demonstrated ictal generalized and interictal multifocal epileptiform abnormalities. Using a SureSelectXT custom multiple gene panel covering 48 early infantile epileptic encephalopathy/developmental delay genes, a novel de novo GABRB3 heterozygous missense mutation, c.860C>T (p.Thr287Ile), was identified and confirmed on Sanger sequencing. GABRB3 is an emerging cause of early-onset epilepsy. Novel genetic technologies, such as whole-exome/genome sequencing and multiple gene panels, will undoubtedly identify further cases, allowing more detailed electroclinical delineation of the GABRB3-related genotypic and phenotypic spectra. © 2015 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.
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.
Ziada, Dina H; Soliman, Hanan H; El Yamany, Saher A; Hamisa, Manal F; Hasan, Azza M
Minimal hepatic encephalopathy (MHE) is diagnosed when hepatic patients perform worse on psychometric tests compared to healthy controls. This study aimed to evaluate probiotics as alternative therapy in MHE. This is an open-label randomised controlled trial, performed in the Department of Tropical Medicine and Infectious Diseases, Tanta University Hospitals, from March 2010 to January 2012. A total of 90 patients with MHE were allocated by simple randomisation to three parallel equal groups. Group A received lactulose, group B a probiotic (Lactobacillus acidophilus) and group C served as the control. After informed consent, patients were tested for gut micrecology, fasting blood ammonia, liver functions and magnetic resonance spectroscopy (MRS) examination to study brain metabolites, mainly choline (Cho), myo-inositol (mI), glutamine+glutamate (Glx) and creatinin (Cre). Patients who developed overt encephalopathy were excluded from analysis. The whole battery of investigations was repeated in the same order after 4weeks. The probiotic was better tolerated than lactulose. The relative risk reduction (RRR) of developing overt encephalopathy was 60% in the case of lactulose and 80% in the case of probiotic, with a number needed to treat (NNT) of 2.4 and 2.3, respectively. The differential but not total microecology count was significantly shifted towards saccharolytic rather than proteolytic bacteria. The mI/Cre and (Cho+mI)/Glx ratios were significantly increased and the Glx/Cre ratio was significantly reduced after 1month-follow-up in the probiotic group compared to the lactulose group and in both treatment groups compared to the control group. Both probiotic and lactulose therapy can improve blood ammonia and psychometric tests in MHE and reduce the risk of developing overt encephalopathy. MRS showed more improvement in the levels of brain neurometabolites in the probiotic group. Copyright © 2013 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All
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.
Hal S. Wortzel
Full Text Available Traumatic brain injury (TBI is a global health concern, and the recent literature reports that a single mild TBI can result in chronic traumatic encephalopathy (CTE. It has been suggested that CTE may lead to death by suicide, raising important prevention, treatment, and policy implications. Thus, we conducted a systematic review of the medical literature to answer the key question: What is the existing evidence in support of a relationship between CTE and suicide? Systematic searches of CTE and suicide yielded 85 unique abstracts. Seven articles were identified for full text review. Only two case series met inclusion criteria and included autopsies from 17 unique cases, 5 of whom died by suicide. Neither studies used blinding, control cases, or systematic data collection regarding TBI exposure and/or medical/neuropsychiatric history. The identified CTE literature revealed divergent opinions regarding neuropathological elements of CTE and heterogeneity regarding clinical manifestations. Overall quality of evidence regarding a relationship between CTE and suicide was rated as very low using Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE criteria. Further studies of higher quality and methodological rigor are needed to determine the existence and nature of any relationship between CTE and suicide.
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.
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.
Simpson, Ewan [Bristol Royal Hospital for Children, Department of Pediatric Radiology, Bristol (United Kingdom); Andronikou, Savvas [Bristol Royal Hospital for Children, Department of Pediatric Radiology, Bristol (United Kingdom); University of Bristol, CRICBristol, Bristol (United Kingdom); Vedajallam, Schadie; Chacko, Anith; Thai, Ngoc Jade [University of Bristol, CRICBristol, Bristol (United Kingdom)
Hypoxic-ischaemic encephalopathy is optimally imaged with brain MRI in the neonatal period. However neuroimaging is often also performed later in childhood (e.g., when parents seek compensation in cases of alleged birth asphyxia). We describe a standardised technique for creating two curved reconstructions of the cortical surface to show the characteristic surface changes of hypoxic-ischaemic encephalopathy in children imaged after the neonatal period. The technique was applied for 10 cases of hypoxic-ischaemic encephalopathy and also for age-matched healthy children to assess the visibility of characteristic features of hypoxic-ischaemic encephalopathy. In the abnormal brains, fissural or sulcal widening was seen in all cases and ulegyria was identifiable in 7/10. These images could be used as a visual aid for communicating MRI findings to clinicians and other interested parties. (orig.)
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.
Ghaly, Ramsis F; Haroutunian, Armen; Candido, Kenneth D; Knezevic, Nebojsa Nick
Altered mental status describes impaired mental functioning ranging from confusion to coma and indicates an illness, either metabolic or structural in nature. Metabolic causes include hypothyroidism, hyperuremia, hypo/hyperglycemia, hypo/hypernatremia, and encephalopathy. The structural causes include tumors, brain hemorrhage, infection, and stroke. To our knowledge, this is the first case in which a patient presented with altered mental status from both metabolic (myxedema coma) and structural diseases (frontal meningioma) with vasogenic edema and midline shift. A 55-year-old female presented with progressive coma. The clinical features included bradycardia and hypothermia. The imaging demonstrated a large frontal meningioma with a significant midline shift with laboratory findings suggestive of severe hypothyroidism and myxedema coma. Hypothyroidism was treated aggressively with intravenous T3 and T4 with close neurosurgical observation. Osmodiuretics and steroids were administered as temporizing agents prior to craniotomy. Craniotomy was successfully undertaken after using these appropriate pre-emptive measures. Management of concomitant metabolic encephalopathy and meningioma with vasogenic edema and impending herniation can be challenging. Correction of the encephalopathy is crucial to minimize perioperative morbidity and mortality. Awareness of metabolic causes of acute decompensation is critical for perioperative management, so a high index of clinical suspicion can make an important timely diagnosis for treatment initiation. Severely hypothyroid patients are sensitive to anesthetic agents and are at a high risk for perioperative complications. Prompt treatment prior to surgical intervention can help minimize perioperative complications.
Olson, Heather E.; Kelly, McKenna; LaCoursiere, Christopher M.; Pinsky, Rebecca; Tambunan, Dimira; Shain, Catherine; Ramgopal, Sriram; Takeoka, Masanori; Libenson, Mark H.; Julich, Kristina; Loddenkemper, Tobias; Marsh, Eric D.; Segal, Devorah; Koh, Susan; Salman, Michael S.; Paciorkowski, Alex R.; Yang, Edward; Bergin, Ann M.; Sheidley, Beth Rosen; Poduri, Annapurna
Objective We sought to identify genetic causes of early onset epileptic encephalopathies with burst suppression (Ohtahara syndrome and early myoclonic encephalopathy) and evaluate genotype-phenotype correlations. Methods We enrolled 33 patients with a referral diagnosis of Ohtahara syndrome or early myoclonic encephalopathy without malformations of cortical development. We performed detailed phenotypic assessment including seizure presentation, EEG, and MRI. We confirmed burst suppression in 28 out of 33 patients. Research-based exome sequencing was performed for patients without a previously identified molecular diagnosis from clinical evaluation or research-based epilepsy gene panel. Results In 17/28 (61%) patients with confirmed early burst suppression, we identified variants predicted to be pathogenic in KCNQ2 (n=10), STXBP1 (n=2), SCN2A (n=2), PNPO (n=1), PIGA (n=1), and SEPSECS (n=1). In 3/5 (60%) patients without confirmed early burst suppression, we identified variants predicted to be pathogenic in STXBP1 (n=2) and SCN2A (n=1). The patient with the homozygous PNPO variant had a low CSF pyridoxal-5-phosphate level. Otherwise, no early laboratory or clinical features distinguished the cases associated with pathogenic variants in specific genes from each other or from those with no prior genetic cause identified. Interpretation We characterize the genetic landscape of epileptic encephalopathy with burst suppression, without brain malformations, and demonstrate feasibility of genetic diagnosis with clinically available testing in over 60% of our cohort with KCNQ2 implicated in one third. This electroclinical syndrome is associated with pathogenic variation in SEPSECS. PMID:28133863
Mann, Theresa N; Donald, Kirsten A; Walker, Kathleen G; Langerak, Nelleke G
This short report arose from a follow-up study of children previously diagnosed with human immunodeficiency virus (HIV) encephalopathy and spastic diplegia and is among the first to describe that increased lower limb muscle tone in children with a confirmed HIV encephalopathy diagnosis may resolve over time in some cases. Of 19 children previously diagnosed with HIV encephalopathy and increased lower limb muscle tone, some were found to have resolved muscle tone abnormalities during a follow-up physical examination [resolved group, n = 13, median age 9 years 7 months (interquartile range 7 years 3 months-10 years 9 months)] whereas others continued to show increased lower limb muscle tone at follow-up [unresolved group, n = 6 median age 8 years 6 months (interquartile range 7 years 9 months-9 years 7 months)]. A review of clinical records showed no significant differences in age or follow-up time between the resolved and unresolved groups. However, the unresolved group appeared to have severe disease at an earlier age than the resolved group, based on the age at antiretroviral treatment initiation [median age at start of treatment 2 years 3 months (interquartile range 7 months-5 years 3 months) vs. 8 months (interquartile range 6-12 months), p = 0.08] and had more severe neurological signs at the initial assessment. It is anticipated that this information may be of immediate value to those involved in the treatment of children with HIV encephalopathy and increased lower limb muscle tone whilst awaiting the outcome of future controlled clinical trials.
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.
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.
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: email@example.com.
Iverson, Grant L
In the initial autopsy case studies of chronic traumatic encephalopathy (CTE), some researchers have concluded that the proteinopathy associated with CTE is the underlying cause of suicidality and completed suicide in former athletes. A review of the literature on contact sports and risk of completed suicide revealed only one epidemiological study with direct relevant data. There are no published cross-sectional, epidemiological or prospective studies showing a relation between contact sports and risk of suicide. One published epidemiological study suggests that retired National Football League players have lower rates of death by suicide than the general population. Outside of sports, there is a mature body of evidence suggesting that the causes of suicide are complex, multifactorial and difficult to predict in individual cases. Future research might establish a clear causal connection between the proteinopathy of CTE and suicide. At present, however, there is insufficient scientific evidence to conclude that there is a strong causal relationship between the presence of these proteinopathies and suicide in former athletes. Additional research is needed to determine the extent to which the neuropathology of CTE is a possible mediator or moderator variable associated with suicide.
Kikuchi, Takahiro; Kato, Mitsuhiro; Takahashi, Nobuya; Nakamura, Kazuyuki; Hayasaka, Kiyoshi
Here we report a case of a 10-year-old female with unclassified epileptic encephalopathy who showed forced normalization after administration of levetiracetam (LEV). She initially presented with intractable tonic and myoclonic seizures that were observed about 10 times a day along with frequent multifocal sharp and slow wave complexes on electroencephalography (EEG). We were forced to decrease the topiramate dose because of the appearance of nystagmus, and her myoclonic seizures became worse. We added LEV (250 mg/day) and her tonic and myoclonic seizures disappeared one day after initiation of LEV administration. However, she showed hyporesponsiveness and akinesia. The disappearance of paroxysmal discharges on EEG confirmed the diagnosis of forced normalization. Despite continuous administration of LEV, tonic and myoclonic seizures relapsed within a month but her psychotic symptoms resolved simultaneously. To the best of our knowledge, this is the first reported case of forced normalization after LEV administration. It should be noted that LEV may cause forced normalization although it can be started at an adequate dosage.
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...
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...
Grinberg, Lea T; Anghinah, Renato; Nascimento, Camila Fernandes; Amaro, Edson; Leite, Renata P; Martin, Maria da Graça M; Naslavsky, Michel S; Takada, Leonel T; Filho, Wilson Jacob; Pasqualucci, Carlos A; Nitrini, Ricardo
The relationship between soccer and chronic traumatic encephalopathy (CTE) is not well established. We report clinicopathological correlations in an 83-year-old retired center-back soccer player, with no history of concussion, manifesting typical Alzheimer-type dementia. Examination revealed mixed pathology including widespread CTE, moderate Alzheimer's disease, hippocampal sclerosis, and TDP-43 proteinopathy. This case adds to a few CTE cases described in soccer players. Furthermore, it corroborates that CTE may present clinically as typical Alzheimer-type dementia. Further studies investigating the extent to which soccer is a risk for CTE are needed.
Khan, M.R.; Maheshwari, P.K.; Haque, A.
Acute necrotizing encephalopathy of childhood (ANEC) is a rare condition characterized by the presence of multifocal symmetrical brain lesions involving mainly thalami, brainstem, cerebellum and white matter. ANEC is a serious and life threatening complication of simple viral infections. We present a case of a young child who developed this condition with classical clinical and radiological findings consistent with ANEC, secondary to swine flu (H1N1). He needed ventilatory support and had profound motor and intellectual deficit on discharge. We report this case with aim of raising awareness about this fatal complication of swine flu which has become a global health care issue these days. (author)
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.
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...
Hundallah, Khaled; Alenizi, Asma'a; AlHashem, Amal; Tabarki, Brahim
Recently, de novo loss- or gain-of-function mutations in the KCNA2 gene; have been described in individuals with epileptic encephalopathy, ataxia or intellectual disability. In this report, we describe a further case of KCNA2-early-onset epileptic encephalopathy. The patient presented since birth with intractable seizures, progressive microcephaly, developmental delay, and progressive brain atrophy. Whole-exome sequencing showed a novel de novo mutation in the KCNA2 gene: c.1120A > G (p.Thr374Ala). This case expands the genotypic and phenotypic disease spectrum of this genetic form of KCNA2-early onset epileptic encephalopathy. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Armstrong, Richard A; McKee, Ann C; Alvarez, Victor E; Cairns, Nigel J
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder which may result from repetitive brain injury. A variety of tau-immunoreactive pathologies are present, including neurofibrillary tangles (NFT), neuropil threads (NT), dot-like grains (DLG), astrocytic tangles (AT), and occasional neuritic plaques (NP). In tauopathies, cellular inclusions in the cortex are clustered within specific laminae, the clusters being regularly distributed parallel to the pia mater. To determine whether a similar spatial pattern is present in CTE, clustering of the tau-immunoreactive pathology was studied in the cortex, hippocampus, and dentate gyrus in 11 cases of CTE and 7 cases of Alzheimer's disease neuropathologic change (ADNC) without CTE. In CTE: (1) all aspects of tau-immunoreactive pathology were clustered and the clusters were frequently regularly distributed parallel to the tissue boundary, (2) clustering was similar in two CTE cases with minimal co-pathology compared with cases with associated ADNC or TDP-43 proteinopathy, (3) in a proportion of cortical gyri, estimated cluster size was similar to that of cell columns of the cortico-cortical pathways, and (4) clusters of the tau-immunoreactive pathology were infrequently spatially correlated with blood vessels. The NFT and NP in ADNC without CTE were less frequently randomly or uniformly distributed and more frequently in defined clusters than in CTE. Hence, the spatial pattern of the tau-immunoreactive pathology observed in CTE is typical of the tauopathies but with some distinct differences compared to ADNC alone. The spread of pathogenic tau along anatomical pathways could be a factor in the pathogenesis of the disease.
Omalu, Bennet; Bailes, Julian; Hamilton, Ronald L; Kamboh, M Ilyas; Hammers, Jennifer; Case, Mary; Fitzsimmons, Robert
We define chronic traumatic encephalopathy (CTE) as a progressive neurodegenerative syndrome caused by single, episodic, or repetitive blunt force impacts to the head and transfer of acceleration-deceleration forces to the brain. We present emerging histomorphologic phenotypes of CTE that we identified in our cohort of CTE cases with apolipoprotein E genotyping and causes and manners of death. Autopsy brain tissue of 14 professional athletes and 3 high school football players was examined after unexpected deaths. Histochemical and immunohistochemical tissue staining was performed with apolipoprotein E genotyping. Ten of 14 professional athletes (71%) were positive for CTE: 7 of 8 football players, 2 of 4 wrestlers, and 1 boxer. One of 3 high school players manifested incipient CTE. The age range of those with CTE was 18 to 52 years; they were all male athletes. In all cases of CTE, Alzheimer-type cerebral cortical atrophy was absent; negligible to mild neocortical neuronal dropout was present. The fundamental neuropathologic feature of CTE was the topographic distribution of sparse, moderate, and frequent band-shaped, flame-shaped, small and large globose neurofibrillary tangles and neuritic threads in the cerebral cortex, subcortical nuclei/basal ganglia, hippocampus, and brainstem nuclei. Sparse to frequent diffuse amyloid plaques may accompany tauopathy and was seen in only 2 CTE cases. No α-synucleinopathy was present. All 7 CTE-positive professional athletes with known apolipoprotein E genotypes had at least 1 E3 allele comprising 5 E3/E3 (71%) and 2 E3/E4 (29%). Alcohol- and drug-related deaths, suicides, and accidental deaths were overrepresented in our CTE cohort. The emerging histomorphologic features of our CTE cohort may specify histologic criteria for CTE diagnosis, may identify emerging histologic variants of CTE and may facilitate more objective surveillance and accurate identification of sentinel CTE cases.
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
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.
D N Gera
Full Text Available Posterior reversible encephalopathy syndrome (PRES is a clinic-radiographic entity of heterogeneous etiologies that are grouped together because of similar findings on neuro-imaging and associated symptom complex of headache, vision loss, altered mentation, and seizures. Although usually considered benign and reversible, characteristics of this syndrome in pediatric patients remain obscure. This case series included 11 patients (8 males, 3 females, age 3-15 years of PRES during September 2010 to February 2012 out of a total 660 renal pediatric patients (1.66%. We studied their clinical profile, contributory factors, and outcome. Presenting symptoms were headache in 73%, dimness of vision or cortical blindness in 36%, seizures in 91%, and altered mentation in 55%. The associated renal diseases were acute renal failure (55%, chronic renal failure (9%, and 36% had normal renal function. The contributory factors were uncontrolled hypertension (100%, severe hypoproteinemia (9%, persistent hypocalcemia (9%, hemolytic uremic syndrome (36%, cyclosporine toxicity (9%, lupus nephritis (9%, high hematocrit (9%, and pulse methylprednisolone (9%. Brain imaging showed involvement of occipito-parietal area (100% and other brain areas (63%. All but one patient of hemolytic uremic syndrome had complete clinical neurological recovery in a week, and all had normal neurological imaging after 4-5 weeks. PRES is an underdiagnosed entity in pediatric renal disease patients. Associated hypertension, renal disease, and immunosuppressive treatment are important triggers. Early diagnosis and treatment of comorbid conditions is of prime importance for early reversal of syndrome.
Chilcote, R; Curley, A; Loughlin, H H; Jupin, J A
Hexachlorophene (HCP), a chlorinated phenolic hydrocarbon with bacteriostatic properties against Staphylococcus, is used in a number of topical products. Absorption through normal and damaged human skin has been appreciated and neurologic changes have been described in experimental animals, but instances of human toxicity have been reported infrequently. A 10-year-old boy who sustained a 25% burn did well initially but died in the second week of convalescence with hyperthermia, lower-extremity weakness, and cerebral edema. His treatment had included frequent applications of HCP. Analysis of post-mortem tissue revealed the presence of toxic levels of HCP in the blood (2.2 mug/gm) and brain (2.2 mug/gm), with storage in skin (25 mug/gm), liver (4.4 mug/gm), and fat (6.0 mug/gm). This case suggests that topical applications of HCP in man may result in an extensive absorption with fat storage and may cause fatal encephalopathy.
Lee, Yun-Jin; Lee, Joon Soo; Kang, Hoon-Chul; Kim, Dong-Seok; Shim, Kyu-Won; Eom, Soyong; Kim, Heung Dong
to evaluate the outcomes and role of epilepsy surgery in children with intractable epileptic encephalopathy (EE). ninety-five children (64 boys, 31 girls) with intractable EE were treated by epilepsy surgery at Severance Children's Hospital from 2003 to 2008. Surgical treatments included lobar resection, hemispherotomy and corpus callosotomy (CC). Seventy-six children were Lennox-Gastaut syndrome (LGS), and 19 had West syndrome. of the 76 patients with LGS, CC was performed in 37 patients (48.7%), lobar resection in 29 (38.2%) and hemispherotomy in 10 (13.2%). Of the 19 patients with West syndrome, respective surgery was performed in 15 patients (78.9%) and CC in 4 (21.1%). Of the patients receiving respective surgery, Engel's class I outcomes were achieved for 24 of 39 (61.5%) of LGS patients, and for 9 of 15 (60.0%) of West syndrome. Malformations of cortical development were commonly observed, appearing in 73.5% (36/49). In neuropsychiatric tests, 19 of 27 with LGS demonstrated improvement in postoperative cognitive function. More significant intellectual improvement correlated well with shorter epilepsy duration, good seizure outcomes, and decreased number of antiepileptic drugs. epilepsy surgery should be considered in treating childhood intractable EE with expectation of improvement of both seizure and cognitive outcomes, even in cases of LGS. Copyright © 2013. Published by Elsevier B.V.
Marco Aurélio Lana-peixoto
Full Text Available Eleven out of 36 autopsied cases of Wernicke's encephalopathy had developed coma. None of these patients had the diagnosis during life. There were six men and five women with ages ranging from 36 to 50 years (mean 36.6. Seven of these patients were heavy drinkers, three exhibited signs of severe malnutrition, whereas one was being evaluated for a disseminated gastric cancer and one was in treatment of hyperemesis gravidarum. Two patients were brought to the hospital after found unconscious at home. Neuropatholo-gical examination disclosed gross changes in the mammillary bodies in eight cases and microscopic changes in all cases. In one case there was atrophy of the anterior superior part of the vermis. Petechial hemorrhages were observed particularly in the walls of the third ventricle. Microscopically there were in addition to hemorrhages, glial proliferation, endothelial hypertrophy and necrosis of nerve cells and myelin. Central pontine myelmolysis was observed in one case. Wernicke's encephalopathy is a clinically underdiagnosed condition. Coma may mask its classical clinical picture or even be the sole manifestation. Although coma points to a poor outlook it may be reversed by thiamine administration. Any patient with Coma of unknown etiology should be given parenteral thiamine.
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.
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
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.
Di Gangi, Stefania; Gizzo, Salvatore; Patrelli, Tito Silvio; Saccardi, Carlo; D'Antona, Donato; Nardelli, Giovanni Battista
Wernicke's encephalopathy (WE) is a neuropsychiatric syndrome due to thiamine deficiency, which is potentially fatal but preventable. In Obstetrics, it can complicate hyperemesis gravidarum because of major daily requirement. Nowadays there is no consensus on early diagnosis, treatment and prevention of this disorder. We present a case report of hyperemesis gravidarum which degenerated into WE and Korsakoff's syndrome. It highlights that the clinical suspicion is necessary to recognize signs and symptoms, to apply the available effective preventive measures in situations at risk and to begin urgent treatment in presence of characteristic clinical features.
Larsen, Jan; Carvill, Gemma L; Gardella, Elena
of the SCN8A gene in 683 patients with a range of epileptic encephalopathies. In addition, we ascertained cases with SCN8A mutations from other centers. A detailed clinical history was obtained together with a review of EEG and imaging data. RESULTS: Seventeen patients with de novo heterozygous mutations...... refractory to antiepileptic therapy. Development was normal in 12 patients and slowed after seizure onset, often with regression; 5 patients had delayed development from birth. All patients developed intellectual disability, ranging from mild to severe. Motor manifestations were prominent including hypotonia...
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
... 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 ...
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 Abstract Background Transmissible spongiform encephalopathies (TSEs, a group of neurodegenerative diseases, are thought to be caused by an abnormal isoform of a naturally occurring protein known as cellular prion protein, PrPC. The abnormal form of prion protein, PrPSc accumulates in the brain of affected individuals. Both isoforms are encoded by the same prion protein gene (PRNP, and the structural changes occur post-translationally. Certain mutations in the PRNP gene result in genetic TSEs or increased susceptibility to TSEs. Case presentation A 70 year old woman was admitted to the hospital with severe confusion and inability to walk. Relatives recognized memory loss, gait and behavioral disturbances over a six month period prior to hospitalization. Neurological examination revealed Creutzfeldt-Jakob disease (CJD related symptoms such as incontinence, Babinski sign and myoclonus. EEG showed periodic sharp waves typical of sporadic CJD and cerebrospinal fluid analysis (CSF was positive for the presence of the 14-3-3-protein. As the disease progressed the patient developed akinetic mutism and died in the tenth month after onset of the disease symptoms. Unfortunately, no autopsy material was available. PRNP sequencing showed the occurrence of a point mutation on one allele at codon 193, which is altered from ACC, coding for a threonine, to ATC, encoding an isoleucine (T193I. Conclusion Here we report a novel mutation of the PRNP gene found in an elderly female patient resulting in heterozygosity for isoleucine and threonine at codon 193, in which normally homozygosity for threonine is expected (T193. The patient presented typical clinical symptoms of CJD. EEG findings and the presence of the 14-3-3 protein in the CSF, contributed to CJD diagnosis, allowing the classification of this case as a probable CJD according to the World Health Organization (WHO accepted criteria.
Zimering, Jeffrey H; Mesfin, Addisu
Increasing the mean arterial pressure (MAP) is an accepted treatment modality to minimize the risk for irreversible neurologic damage secondary to spinal cord ischemia. Posterior reversible encephalopathy syndrome (PRES) is a rare complication occurring after transplantation surgery, in persons having an autoimmune disorder or after abrupt increases in blood pressure of various etiologies. Case report. Retrospective evaluation of medical records. A 68-year-old female with long-standing diabetes, and rheumatoid arthritis (treated with methotrexate) presented with bilateral upper extremity weakness and numbness developing several days after a motor vehicle accident. Physical examination confirmed decreased upper extremity motor strength and decreased sensation to light touch and pinprick in the C5-C6 dermatomal distribution. Magnetic resonance imaging (MRI) demonstrated C5-C6 subluxation with spinal cord compression. The patient had traction applied and mean arterial pressures were elevated greater than 85 mmg. The following day the patient underwent anterior and posterior cervical spine fusion and decompression. Immediately post-operatively, the patient developed status epilepticus. Head MRI revealed areas of high T2 signal intensity in the bilateral occipital lobes, consistent with a diagnosis of PRES. Two weeks later, the patient had resolution of her symptoms and resolution of PRES on imaging. This is the first report of posterior reversible encephalopathy syndrome secondary to therapeutic blood pressure increase in the setting of cervical spine fracture with neurological deficits. The patients had resolution of symptoms following discontinuation of the MAP goals. Posterior reversible encephalopathy syndrome (PRES) is a life-threatening condition characterized by seizures, confusion, visual disturbance, and headaches alongside neuroradiological findings indicative of posterior cerebral hemispheric white matter edema. 1,2 PRES has been described in association
Guo, Xiaopeng; Wei, Junji; Gao, Lu; Xing, Bing; Xu, Zhiqin
Abstract Rationale: Postoperative coma is not uncommon in patients after craniotomy. It generally presents as mental state changes and is usually caused by intracranial hematoma, brain edema, or swelling. Hyperammonemia can also result in postoperative coma; however, it is rarely recognized as a potential cause in coma patients. Hyperammonemic coma is determined through a complicated differential diagnosis, and although it can also be induced as a side effect of valproate (VPA), this cause is frequently unrecognized or confused with upper gastrointestinal hemorrhage (UGH)-induced hepatic encephalopathy. We herein present a case of valproate-induced hyperammonemic encephalopathy (VHE) to illustrate the rarity of such cases and emphasize the importance of correct diagnosis and proper treatment. Patient concerns and diagnoses: A 61-year-old woman with meningioma was admitted into our hospital. Radical resection of the tumor was performed, and the patient recovered well as expected. After administration of valproate for 7 days, the patient was suddenly found in a deep coma, and her mental state deteriorated rapidly. The diagnoses of hepatic encephalopathy was confirmed. However, whether it origins from upper gastrointestinal hemorrhage or valproate side effect is uncertain. Interventions and outcomes: The patient's condition fluctuated without improvement during the subsequent 3 days under the treatment of reducing ammonia. With the discontinuation of valproate treatment, the patient regained complete consciousness within 48 hours, and her blood ammonia decreased to the normal range within 4 days. Lessons subsections: VHE is a rare but serious complication in patients after craniotomy and is diagnosed by mental state changes and elevated blood ammonia. Thus, the regular perioperative administration of VPA, which is frequently neglected as a cause of VHE, should be emphasized. In addition, excluding UGH prior to providing a diagnosis and immediately discontinuing VPA
de Kovel, Carolien G F; Meisler, Miriam H; Brilstra, Eva H; van Berkestijn, Frederique M C; van 't Slot, Ruben; van Lieshout, Stef; Nijman, Isaac J; O'Brien, Janelle E; Hammer, Michael F; Estacion, Mark; Waxman, Stephen G; Dib-Hajj, Sulayman D; Koeleman, Bobby P C
Recently, de novo SCN8A missense mutations have been identified as a rare dominant cause of epileptic encephalopathies (EIEE13). Functional studies on the first described case demonstrated gain-of-function effects of the mutation. We describe a novel de novo mutation of SCN8A in a patient with epileptic encephalopathy, and functional characterization of the mutant protein. Whole exome sequencing was used to discover the variant. We generated a mutant cDNA, transfected HEK293 cells, and performed Western blotting to assess protein stability. To study channel functional properties, patch-clamp experiments were carried out in transfected neuronal ND7/23 cells. The proband exhibited seizure onset at 6 months of age, diffuse brain atrophy, and more profound developmental impairment than the original case. The mutation p.Arg233Gly in the voltage sensing transmembrane segment D1S4 was present in the proband and absent in both parents. This mutation results in a temperature-sensitive reduction in protein expression as well as reduced sodium current amplitude and density and a relative increased response to a slow ramp stimulus, though this did not result in an absolute increased current at physiological temperatures. The new de novo SCN8A mutation is clearly deleterious, resulting in an unstable protein with reduced channel activity. This differs from the gain-of-function attributes of the first SCN8A mutation in epileptic encephalopathy, pointing to heterogeneity of mechanisms. Since Nav1.6 is expressed in both excitatory and inhibitory neurons, a differential effect of a loss-of-function of Nav1.6 Arg223Gly on inhibitory interneurons may underlie the epilepsy phenotype in this patient. Copyright © 2014 Elsevier B.V. All rights reserved.
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 Abstract Introduction Transmissible spongiform encephalopathies are a group of neurodegenerative diseases of humans and animals. Genetic Creutzfeldt-Jakob diseases, in which mutations in the PRNP gene predispose to disease by causing the expression of abnormal PrP protein, include familial Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome and fatal familial insomnia. Case presentation A 47-year-old Han-Chinese woman was hospitalized with a 2-year history of progressive dementia, tiredness, lethargy and mild difficulty in falling asleep. On neurological examination, there was severe apathy, spontaneous myoclonus of the lower limbs, generalized hyperreflexia and bilateral Babinski signs. A missense mutation (T to G was identified at the position of nt 341 in one PRNP allele, leading to a change from glycine (Gly to valine (Val at codon 114. PK-resistant PrPSc was detected in brain tissues by Western blotting and immunohistochemical assays. Information on pedigree was collected notably by interviews with family members. A further four suspected patients in five consecutive generations of the family have been identified. One of them was hospitalized for progressive memory impairment at the age of 32. On examination, he had impairment of memory, calculation and comprehension, mild ataxia of the limbs, tremor and a left Babinski sign. He is still alive. Conclusion This family with G114V inherited prion disease is the first to be described in China and represents the second family worldwide in which this mutation has been identified. Three other suspected cases have been retrospectively identified in this family, and a further case with suggestive clinical manifestations has been shown by gene sequencing to have the causal mutation.
Full Text Available 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 acutely developed EPC in the right hand as an isolated manifestation. A thyroid ultrasound showed an enlarged hypoechogenic gland, and a thyroid status assessment showed euthyroid with high titers of thyroid antibodies. A brain MRI revealed a nodular lesion in the left precentral gyrus. Corticosteroid treatment resulted in a cessation of the symptom. Conclusions: A precentral nodular lesion can be responsible for steroid-responsive EPC in a patient with anti-thyroid antibodies and may be caused by HE. The serial MRI findings of our case suggest the presence of primary demyelination, with ischemia possibly due to vasculitis around the demyelinating lesion.
Masuda, Hiroki; Mori, Masahiro; Ito, Shoichi; Yagishita, Toshiyuki; Kuwabara, Satoshi
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 acutely developed EPC in the right hand as an isolated manifestation. A thyroid ultrasound showed an enlarged hypoechogenic gland, and a thyroid status assessment showed euthyroid with high titers of thyroid antibodies. A brain MRI revealed a nodular lesion in the left precentral gyrus. Corticosteroid treatment resulted in a cessation of the symptom. Conclusions A precentral nodular lesion can be responsible for steroid-responsive EPC in a patient with anti-thyroid antibodies and may be caused by HE. The serial MRI findings of our case suggest the presence of primary demyelination, with ischemia possibly due to vasculitis around the demyelinating lesion. PMID:24932178