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  1. Hepatic Encephalopathy

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    ... is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy or PSE, is a condition that ... medical care is an important factor in staying as healthy as possible. The American Liver Foundation is ...

  2. Hepatic Encephalopathy

    PubMed Central

    Bleibel, Wissam; Al-Osaimi, Abdullah M. S.

    2012-01-01

    Chronic liver disease and cirrhosis affect hundreds of millions of patients all over the world. The majority of patients with cirrhosis will eventually develop complications related to portal hypertension. One of these recurrent and difficult to treat complications is hepatic encephalopathy. Studies have indicated that overt hepatic encephalopathy affects 30 to 45% of patients with cirrhosis and a higher percentage may be affected by minimal degree of encephalopathy. All of these factors add to the impact of hepatic encephalopathy on the healthcare system and presents a major challenge to the gastroenterologist, hospitalist and primary care physician. PMID:23006457

  3. Hepatic encephalopathy.

    PubMed

    Córdoba, Juan; Mínguez, Beatriz

    2008-02-01

    Hepatic encephalopathy is a severe complication of cirrhosis that is related to the effects of ammonia. Analysis of interorgan ammonia trafficking has identified an important role of skeletal muscle in ammonia removal and has highlighted the importance of the nutritional status. Ammonia causes neurotransmitter abnormalities and induces injury to astrocytes that is partially mediated by oxidative stress. These disturbances lead to astrocyte swelling and brain edema, which appear to be involved in the pathogenesis of neurological manifestations. Inflammatory mediators worsen brain disturbances. New methods for assessing hepatic encephalopathy include clinical scales, neuropsychological tests, imaging of portal-systemic circulation, and magnetic resonance of the brain. Reappraisal of current therapy indicates the need for performing placebo-controlled trials and the lack of evidence for administering diets with restricted protein content. Liver transplant should be considered in selected patients with hepatic encephalopathy. Future prospects include new drugs that decrease plasma ammonia, measures to reduce brain edema, and liver-support devices. PMID:18293278

  4. [Hepatic encephalopathy].

    PubMed

    Jacques, Jérémie; Carrier, Paul; Debette-Gratien, Marilyne; Sobesky, Rodolphe; Loustaud-Ratti, Véronique

    2016-01-01

    Hepatic encephalopathy is a severe complication of liver cirrhosis and is an important therapeutic challenge, with a social and economic issue. If, now, the pathophysiology is not totally understood (main role of ammonia, but a better understanding of cerebral mechanisms), the clinical presentation is well-known. Some treatments are useful (disaccharides, treatment of the trigger) but their efficiency is limited. Nevertheless, the emergence of new treatments, such as non-absorbable antibiotics (rifaximin essentially), is an interesting therapeutic tool. PMID:26597584

  5. [Hepatic encephalopathy].

    PubMed

    Córdoba, Juan; Mur, Rafael Esteban

    2014-07-01

    Hepatic encephalopathy (EH) is a severe complication of hepatic cirrhosis that is characterized by multiple neuropsychiatric manifestations. EH is usually triggered by a precipitating factor and occurs in patients with severely impaired hepatic function. Minimal EH is characterized by minor cognitive impairments that are difficult to specify but represent a risk for the patients. The primary pathophysiological mechanism of EH is considered to be an increase in blood ammonia with an impairment in the patency of the blood-brainbarrier and its metabolism to glutamine in astrocytes. The diagnosis is clinical and neuroimaging techniques can be complementary. The diagnosis of minimal EH requires specific neurocognitive tests. The clinical evaluation should be directed towards identifying the trigger. Nonabsorbable disaccharides and rifaximin constitute the treatment of choice, along with prophylaxis for new episodes. PMID:25087716

  6. [Hepatic encephalopathy].

    PubMed

    Festi, Davide; Marasco, Giovanni; Ravaioli, Federico; Colecchia, Antonio

    2016-07-01

    Hepatic encephalopathy (HE) is a common complication of liver cirrhosis and it can manifest with a broad spectrum of neuropsychiatric abnormalities of varying severity, acuity and time course with important clinical implications. According to recent guidelines, HE has been classified into different types, depending on the severity of hepatic dysfunction, the presence of porto-systemic shunts and the number of previous episodes or persistent manifestations. From a clinical point of view, HE can be recognized as unimpaired, covert (that deals with minimal and grade 1 according to the grading of mental state), and overt (that is categorized from grade 2 to grade 4). Different and only partially known pathogenic mechanisms have been identified, comprising ammonia, inflammatory cytokines, benzodiazepine-like compounds and manganese deposition. Different therapeutic strategies are available for treating HE, in particular the overt HE, since covert HE needs to be managed case by case. Recognition and treatment of precipitating factors represent fundamental part of the management. The more effective treatments, which can be performed separately or combined, are represented by non-absorbable disaccharides (lactulose and lactitol) and the topic antibiotic rifaximin; other possible therapies, mainly used in patients non responders to previous treatments, are represented by branched chain amino acids and metabolic ammonia scavengers. PMID:27571468

  7. Pathogenesis of Hepatic Encephalopathy

    PubMed Central

    Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

    2012-01-01

    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. PMID:23316223

  8. Hepatic encephalopathy: a review.

    PubMed

    Lizardi-Cervera, Javier; Almeda, Paloma; Guevara, Luis; Uribe, Misael

    2003-01-01

    Hepatic encephalopathy (HE) is a complication that presents in as many as 28% of patients with cirrhosis, and reported up to ten years after the diagnosis of cirrhosis. Commonly, it is observed in patients with severe hepatic failure and is characterized by neuropsychiatric manifestations that can range in severity from a mild alteration in mental state to a coma; additionally, some neuromuscular symptoms can be observed. This complication of either acute or chronic hepatic disease is the result of a diminished hepatic reservoir and inability to detoxify some toxins that originate in the bowel. Today, the role of astrocytes, specifically the Alzheimer type II cells, is known to be very important in the pathogenesis of the hepatic encephalopathy, and will be reviewed later. In conclusion, the objectives of this review are: To understand the pathogenesis of hepatic encephalopathy, To recognize the precipitating factors, as well as preventive measures for the development of the hepatic encephalopathy, To describe the new classification of hepatic encephalopathy and its clinical implications, To recognize the clinical manifestations and stages of the disease, To understand the main diagnostic tests used to detect the hepatic encephalopathy, To describe the main therapeutic treatments of hepatic encephalopathy. PMID:15115963

  9. [Prevention of hepatic encephalopathy].

    PubMed

    Morillas, Rosa M; Sala, Marga; Planas, Ramon

    2014-06-01

    Hepatic encephalopathy (HE) is a frequent complication of cirrhosis which, in addition to producing a great social impact, deteriorates the quality of life of patients and is considered a sign of advanced liver disease and therefore a clinical indication for liver transplant evaluation. Patients who have had episodes of HE have a high risk of recurrence. Thus, after the HE episode resolves, it is recommended: control and prevention of precipitating factors (gastrointestinal bleeding, spontaneous bacterial peritonitis, use of diuretics with caution, avoid nervous system depressant medications), continued administration of non-absorbable disaccharides such as lactulose or lactitol, few or non-absorbable antibiotics such as rifaximin and assess the need for a liver transplant as the presence of a HE episode carries a poor prognosis in cirrhosis. PMID:24480288

  10. Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy

    PubMed Central

    Cichoż-Lach, Halina; Michalak, Agata

    2013-01-01

    Hepatic encephalopathy is a medical phenomenon that is described as a neuropsychiatric manifestation of chronic or acute liver disease that is characterized by psychomotor, intellectual and cognitive abnormalities with emotional/affective and behavioral disturbances. This article focuses on the underlying mechanisms of the condition and the differences between hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. Hepatic encephalopathy is a serious condition that can cause neurological death with brain edema and intracranial hypertension. It is assumed that approximately 60%-80% of patients with liver cirrhosis develop hepatic encephalopathy. This review explores the complex mechanisms that lead to hepatic encephalopathy. However, noncirrhotic hyperammonemic encephalopathy is not associated with hepatic diseases and has a completely different etiology. Noncirrhotic hyperammonemic encephalopathy is a severe occurrence that is connected with multiple pathogeneses. PMID:23326159

  11. Pharmacotherapy for hepatic encephalopathy.

    PubMed

    Phongsamran, Paula V; Kim, Jiwon W; Cupo Abbott, Jennifer; Rosenblatt, Angela

    2010-06-18

    Hepatic encephalopathy (HE) is a challenging clinical complication of liver dysfunction with a wide spectrum of neuropsychiatric abnormalities that range from mild disturbances in cognitive function and consciousness to coma and death. The pathogenesis of HE in cirrhosis is complex and multifactorial, but a key role is thought to be played by circulating gut-derived toxins of the nitrogenous compounds, most notably ammonia. Therapeutic treatment options for HE are currently limited and have appreciable risks and benefits associated with their use. Management of HE primarily involves avoidance of precipitating factors, limitation of dietary protein intake, and administration of various ammonia-lowering therapies such as non-absorbable disaccharides and select antimicrobial agents. Non-absorbable disaccharides, such as lactulose, have traditionally been regarded as first-line pharmacotherapy for patients with HE. However, multiple adverse events have been associated with their use. In addition, recent literature has questioned the true efficacy of the disaccharides for this indication. Neomycin, metronidazole and vancomycin may be used as alternative treatments for patients intolerant or unresponsive to non-absorbable disaccharides. Antimicrobials reduce bacterial production of ammonia and other bacteria-derived toxins through suppression of intestinal flora. Neomycin has been reported to be as effective as lactulose, and similar efficacy has been reported with vancomycin and metronidazole for the management of HE. However, the adverse effects frequently associated with these antimicrobials limit their use as first-line pharmacological agents. Neomycin is the most commonly used antimicrobial for HE and, although poorly absorbed, systemic exposure to the drug in sufficient amounts causes hearing loss and renal toxicity. Long-term neomycin therapy requires annual auditory testing and continuous monitoring of renal function. Long-term use of metronidazole has been

  12. Diagnosis of minimal hepatic encephalopathy.

    PubMed

    Weissenborn, Karin

    2015-03-01

    Minimal hepatic encephalopathy (mHE) has significant impact upon a liver patient's daily living and health related quality of life. Therefore a majority of clinicians agree that mHE should be diagnosed and treated. The optimal means for diagnosing mHE, however, is controversial. This paper describes the currently most frequently used methods-EEG, critical flicker frequency, Continuous Reaction time Test, Inhibitory Control Test, computerized test batteries such as the Cognitive Drug Research test battery, the psychometric hepatic encephalopathy score (PHES) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)-and their pros and cons. PMID:26041959

  13. Hepatic Encephalopathy-the Old and the New.

    PubMed

    Kandiah, Prem A; Kumar, Gagan

    2016-07-01

    Hepatic encephalopathy occurs ubiquitously in all causes of advanced liver failure, however, its implications on mortality diverge and vary depending upon acuity and severity of liver failure. This associated mortality has decreased in subsets of liver failure over the last 20 years. Aside from liver transplantation, this improvement is not attributable to a single intervention but likely to a combination of practical advances in critical care management. Misconceptions surrounding many facets of hepatic encephalopathy exists due to heterogeneity in presentation, pathophysiology and outcome. This review is intended to highlight the important concepts, rationales and strategies for managing hepatic encephalopathy. PMID:27339673

  14. Rifaximin in the treatment of hepatic encephalopathy

    PubMed Central

    Iadevaia, Maddalena Diana; Prete, Anna Del; Cesaro, Claudia; Gaeta, Laura; Zulli, Claudio; Loguercio, Carmelina

    2011-01-01

    Hepatic encephalopathy is a challenging complication in patients with advanced liver disease. It can be defined as a neuropsychiatric syndrome caused by portosystemic venous shunting, ranging from minimal to overt hepatic encephalopathy or coma. Its pathophysiology is still unclear, although increased levels of ammonia play a key role. Diagnosis of hepatic encephalopathy is currently based on specific tests evaluating the neuropsychiatric state of patients and their quality of life; the severity of hepatic encephalopathy is measured by the West Haven criteria. Treatment of hepatic encephalopathy consists of pharmacological and corrective measures, as well as nutritional interventions. Rifaximin received approval for the treatment of hepatic encephalopathy in 2010 because of its few side effects and pharmacological benefits. The aim of this work is to review the use and efficacy of rifaximin both in acute and long-term management of hepatic encephalopathy. Treatment of overt hepatic encephalopathy involves management of the acute episode as well as maintenance of remission in those patients who have previously experienced an episode, in order to improve their quality of life. The positive effect of rifaximin in reducing health care costs is also discussed. PMID:24367227

  15. Rifaximin in the treatment of hepatic encephalopathy.

    PubMed

    Iadevaia, Maddalena Diana; Prete, Anna Del; Cesaro, Claudia; Gaeta, Laura; Zulli, Claudio; Loguercio, Carmelina

    2011-01-01

    Hepatic encephalopathy is a challenging complication in patients with advanced liver disease. It can be defined as a neuropsychiatric syndrome caused by portosystemic venous shunting, ranging from minimal to overt hepatic encephalopathy or coma. Its pathophysiology is still unclear, although increased levels of ammonia play a key role. Diagnosis of hepatic encephalopathy is currently based on specific tests evaluating the neuropsychiatric state of patients and their quality of life; the severity of hepatic encephalopathy is measured by the West Haven criteria. Treatment of hepatic encephalopathy consists of pharmacological and corrective measures, as well as nutritional interventions. Rifaximin received approval for the treatment of hepatic encephalopathy in 2010 because of its few side effects and pharmacological benefits. The aim of this work is to review the use and efficacy of rifaximin both in acute and long-term management of hepatic encephalopathy. Treatment of overt hepatic encephalopathy involves management of the acute episode as well as maintenance of remission in those patients who have previously experienced an episode, in order to improve their quality of life. The positive effect of rifaximin in reducing health care costs is also discussed. PMID:24367227

  16. Management of Hepatic Encephalopathy in the Hospital

    PubMed Central

    Leise, Michael D.; Poterucha, John J.; Kamath, Patrick S.; Kim, W. Ray

    2014-01-01

    Hepatic encephalopathy (HE) develops in about 50% of patients with cirrhosis and is one of the features of decompensated cirrhosis. The inpatient incidence of HE is approximately 23,000/year and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails two phases, induction and maintenance of remission. Most cases of significant hepatic encephalopathy are precipitated by infection, gastrointestinal bleeding, medications or other culprits. All patients should be evaluated for secondary triggers of HE and treatment should be initiated with a non-absorbable disaccharide (i.e. lactulose) in most cases. Rifaximin (off-label) can be added in patients not responding to lactulose. Neomycin is a less preferable alternative to rifaximin, due to its side effect profile. Other therapies including zinc, LOLA, and branch chain amino acids can be considered for patients not responding to a disaccharide and non-absorbable antibiotic. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe hepatic encephalopathy who do not respond to medical therapy. It is critically important that patients hospitalized with significant hepatic encephalopathy continue a maintenance medication(s) at the time of dismissal to prevent further episodes. Patients with a 1st time episode of HE can be placed on lactulose and careful instruction should be provided to patient and caregiver about titration of dose to achieve 3 bowel movements per day. Patients with recurrent HE episodes despite lactulose benefit from the addition of rifaximin which decreases the frequency of recurrent HE episodes and related hospitalizations. Lastly, patients and their families should be counselled about the risk of motor vehicle accidents which

  17. Treatment of Overt Hepatic Encephalopathy.

    PubMed

    Sussman, Norman L

    2015-08-01

    Hepatic encephalopathy (HE) is defined by an altered mental status in the setting of portosystemic shunting, with or without cirrhosis. The basis of HE is probably multi-factorial, but increased ammonia delivery to the brain is thought to play a pivotal role. Medical therapies have typically focused on reducing blood ammonia concentrations. These measures are moderately effective, but further improvements will require identification of new therapeutic targets. Two medications, lactulose and rifaximin, are currently approved for the treatment of HE in the USA - new compounds are available off-label, and are in clinical trials. The presence of HE is associated with a higher risk of death in cirrhotic patients. Liver transplantation typically cures HE, but HE does not increase the MELD score, and therefore does not contribute to the likelihood of liver transplantation. PMID:26195208

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

    PubMed

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

    2016-02-01

    Minimal hepatic encephalopathy (MHE) encompasses a number of neuropsychological and neurophysiological disorders in patients suffering from liver cirrhosis, who do not display abnormalities during a medical interview or physical examination. A negative influence of MHE on the quality of life of patients suffering from liver cirrhosis was confirmed, which include retardation of ability of operating motor vehicles and disruption of multiple health-related areas, as well as functioning in the society. The data on frequency of traffic offences and accidents amongst patients diagnosed with MHE in comparison to patients diagnosed with liver cirrhosis without MHE, as well as healthy persons is alarming. Those patients are unaware of their disorder and retardation of their ability to operate vehicles, therefore it is of utmost importance to define this group. The term minimal hepatic encephalopathy (formerly "subclinical" encephalopathy) erroneously suggested the unnecessity of diagnostic and therapeutic procedures in patients with liver cirrhosis. Diagnosing MHE is an important predictive factor for occurrence of overt encephalopathy - more than 50% of patients with this diagnosis develop overt encephalopathy during a period of 30 months after. Early diagnosing MHE gives a chance to implement proper treatment which can be a prevention of overt encephalopathy. Due to continuing lack of clinical research there exist no commonly agreed-upon standards for definition, diagnostics, classification and treatment of hepatic encephalopathy. This article introduces the newest findings regarding the importance of MHE, scientific recommendations and provides detailed descriptions of the most valuable diagnostic methods. PMID:27000818

  19. CLIF–SOFA score and SIRS are independent prognostic factors in patients with hepatic encephalopathy due to alcoholic liver cirrhosis

    PubMed Central

    Jeong, Jin Hee; Park, In Sung; Kim, Dong Hoon; Kim, Seong Chun; Kang, Changwoo; Lee, Soo Hoon; Kim, Tae Yun; Lee, Sang Bong

    2016-01-01

    Abstract Hepatic encephalopathy (HE) is a complication associated with worst prognosis in decompensated liver cirrhosis (LC) patients. Previous studies have identified prognostic factors for HE, and recent studies reported an association between systemic inflammatory response syndrome (SIRS) and liver disease. This study aimed to identify prognostic factors for 30-day mortality in alcoholic LC patients with HE who visited the emergency department (ED). This was a retrospective study of alcoholic LC patients with HE from January 1, 2010, to April 30, 2015. The baseline characteristics, complications of portal hypertension, laboratory values, Child–Pugh class, Model for End-stage Liver Disease (MELD) score, chronic liver failure-sequential organ failure assessment (CLIF–SOFA) score, and SIRS criteria were assessed. The presence of 2 or more SIRS criteria was considered SIRS. The primary outcomes were 30-day mortality and prognostic factors for patients with HE visiting the ED. In total, 105 patients who met the inclusion criteria were analyzed. Overall, the 30-day mortality rate was 6.7% (7 patients). Significant variables were hepatorenal syndrome, international normalized ratio, white blood cell count, total bilirubin level, MELD score CLIF–SOFA score, and SIRS in univariate analysis. CLIF–SOFA score and SIRS were the significant factors in the multivariate analysis (hazard ratio 5.56, 15.98; 95% confidence interval 1.18–26.18, 1.58–161.37; P = 0.03, P = 0.02). The mortality rates differed according to the CLIF–SOFA score (P < 0.01). The CLIF–SOFA score and SIRS in alcoholic LC patients with HE visiting the ED are independent predictors of 30-day mortality. PMID:27367990

  20. Useful Tests for Hepatic Encephalopathy in Clinical Practice

    PubMed Central

    Nabi, Eiman; Bajaj, Jasmohan S

    2014-01-01

    Hepatic encephalopathy (HE) is a serious complication of liver disease and portosystemic shunting that represents a continuum of neuropsychiatric changes and altered consciousness. It is classified as overt hepatic encephalopathy (OHE) when clinically apparent or as covert hepatic encephalopathy (CHE) in its mildest form. Progression of CHE to OHE and its impact of quality of life make its early diagnosis imperative. Several diagnostic techniques ranging from simple clinical scales to sophisticated computerized tests exist yet diagnosis remains a challenge due to the time, cost and personnel involved. Psychometric tests appear promising due to their high sensitivity and low cost but results are variable depending on age and education. The pros and cons of current diagnostic methods for overt and covert HE are reviewed along with strategy to CHE testing. PMID:24357348

  1. Gut microbiota and hepatic encephalopathy.

    PubMed

    Dhiman, Radha K

    2013-06-01

    There is a strong relationship between liver and gut; while the portal venous system receives blood from the gut, and its contents may affect liver functions, liver in turn, affects intestinal functions through bile secretion. There is robust evidence that the pathogenesis of hepatic encephalopathy (HE) is linked to alterations in gut microbiota and their by-products such as ammonia, indoles, oxindoles, endotoxins, etc. In the setting of intestinal barrier and immune dysfunction, these by-products are involved in the pathogenesis of complications of liver cirrhosis including HE and systemic inflammation plays an important role. Prebiotics, probiotics and synbiotics may exhibit efficacy in the treatment of HE by modulating the gut flora. They improve derangement in flora by decreasing the counts of pathogenic bacteria and thus improving the endotoxemia, HE and the liver disease. Current evidence suggest that the trials evaluating the role of probiotics in the treatment of HE are of not high quality and all trials had high risk of bias and high risk of random errors. Therefore, the use of probiotics for patients with HE cannot be currently recommended. Further RCTs are required. This review summarizes the main literature findings about the relationships between gut flora and HE, both in terms of the pathogenesis and the treatment of HE. PMID:23463489

  2. Clinical Neurophysiology of Hepatic Encephalopathy

    PubMed Central

    Amodio, Piero; Montagnese, Sara

    2015-01-01

    Background/Objectives Hepatic encephalopathy (HE) has relevant impact on the quality of life of patients and their caregivers and causes relevant costs because of hospitalizations and work days lost. Its quantification is important to perform adequate clinical trials on this relevant complication of cirrhosis and portal-systemic shunting. Clinical neurophysiology, which detects functional alterations of the nervous system, has been applied to the study of HE for over 60 years. This review aims at summarizing and clarifying the role of neurophysiologic techniques in the study of HE. Methods A narrative review was performed aiming at interpreting the cited papers and the techniques on the basis of their physiological and pathophysiological meaning. Results The potential role of EEG, quantified EEG, evoked potentials—both exogenous, endogenous and motor—have been clarified to the reader that may be unfamiliar with neurophysiology. Conclusions The EEG, reflecting the oscillatory changes of neural network is the preferable tool to detect and monitor HE, with the exception of its most severe stage, when EEG flattens. SSEP and MEP have indication to detect and monitor transmission alterations that are likely related to myelin changes and microedema. PMID:26041960

  3. Minimal Hepatic Encephalopathy Impairs Quality of Life

    PubMed Central

    Agrawal, Swastik; Umapathy, Sridharan; Dhiman, Radha K.

    2015-01-01

    Minimal hepatic encephalopathy (MHE) is the mildest form of the spectrum of neurocognitive impairment in cirrhosis. It is a frequent occurrence in patients of cirrhosis and is detectable only by specialized neurocognitive testing. MHE is a clinically significant disorder which impairs daily functioning, driving performance, work capability and learning ability. It also predisposes to the development of overt hepatic encephalopathy, increased falls and increased mortality. This results in impaired quality of life for the patient as well as significant social and economic burden for health providers and care givers. Early detection and treatment of MHE with ammonia lowering therapy can reverse MHE and improve quality of life. PMID:26041957

  4. Minimal hepatic encephalopathy impairs quality of life.

    PubMed

    Agrawal, Swastik; Umapathy, Sridharan; Dhiman, Radha K

    2015-03-01

    Minimal hepatic encephalopathy (MHE) is the mildest form of the spectrum of neurocognitive impairment in cirrhosis. It is a frequent occurrence in patients of cirrhosis and is detectable only by specialized neurocognitive testing. MHE is a clinically significant disorder which impairs daily functioning, driving performance, work capability and learning ability. It also predisposes to the development of overt hepatic encephalopathy, increased falls and increased mortality. This results in impaired quality of life for the patient as well as significant social and economic burden for health providers and care givers. Early detection and treatment of MHE with ammonia lowering therapy can reverse MHE and improve quality of life. PMID:26041957

  5. Subclinical hepatic encephalopathy: the diagnostic value of evoked potentials.

    PubMed

    Kullmann, F; Hollerbach, S; Holstege, A; Schölmerich, J

    1995-01-01

    Brainstem auditory (BAEPs) and somatosensory evoked potentials (SEPs) have been shown to be useful in detecting brainstem or cortical dysfunction in neurological diseases and in combination with other methods to diagnose brain death (37,38). These neurophysiological methods are simple and easy to perform. BAEPs and SEPs can even be easily recorded in intensive care units and guarantee a standardized examination. Moreover, these methods require no extensive patient cooperation and are not heavily influenced by learning effects. The role of BAEPs in the evaluation and diagnosis of hepatic encephalopathy is not clear. BAEPs are obviously strongly influenced by the etiology of liver disease and are normal in viral hepatitis, but prolonged in alcoholic liver disease, Wilson's disease or in hepatic coma (8,12). Unfortunately, BAEPs were not compared to psychometric tests. There was no clear-cut differentiation between various hepatic encephalopathy-gradings. At present, the use of BAEPs in the detection of subclinical hepatic encephalopathy cannot be recommended, whereas in comatose patients BAEPs can be useful as a prognostic marker and for follow-up examinations (12). Recently, Pozessere et al. (12) examined 13 comatose patients with advanced coma stages (Glasgow coma scale 5-10) and recorded unspecific changes in their EEG tracings. In all cases of hepatic coma and in one intoxicated patient they found prolongation of interpeak latencies. In addition, in this small study the interpeak latencies correlated well with the clinical outcome of the patients. Only two studies were performed using SEPs to detect neurophysiological alterations in hepatic encephalopathy (32,33). The design as well as the results of these studies are quite different. Despite the small number of patients (n = 10), the prolongation of late components in 50% of patients with hepatic encephalopathy stage 0 could be a promising result (32). The value of SEPs in detecting subclinical hepatic

  6. Hepatic Encephalopathy: From the Pathogenesis to the New Treatments

    PubMed Central

    Cordoba, Juan

    2014-01-01

    Hepatic encephalopathy is a frequent and serious complication of liver cirrhosis; the pathophysiology of this complication is not fully understood although great efforts have been made during the last years. There are few prospective studies on the epidemiology of this complication; however, it is known that it confers with high short-term mortality. Hepatic encephalopathy has been classified into different groups depending on the degree of hepatic dysfunction, the presence of portal-systemic shunts, and the number of episodes. Due to the large clinical spectra of overt EH and the complexity of cirrhotic patients, it is very difficult to perform quality clinical trials for assessing the efficacy of the treatments proposed. The physiopathology, clinical manifestation, and the treatment of HE is a challenge because of the multiple factors that converge and coexist in an episode of overt HE. PMID:27335836

  7. Disaccharides in the treatment of hepatic encephalopathy.

    PubMed

    Sharma, Praveen; Sharma, Barjesh Chander

    2013-06-01

    Management of hepatic encephalopathy (HE) primarily involves avoidance of precipitating factors and administration of various ammonia-lowering therapies such as nonabsorbable disaccharides and antimicrobial agents like rifaximin. The nonabsorbable disaccharides which include lactulose and lactitol are considered the first-line therapy for the treatment of HE and minimal hepatic encephalopathy (MHE). Lactulose significantly improves cognitive function and health-related quality of life in patients with MHE. Lactitol is comparable to lactulose in the treatment of HE with fewer side effects. Lactulose has also shown to be effective in primary and secondary prophylaxis of HE. Disaccharides were found to be comparable to rifaximin in recent systemic reviews in the treatment of HE however conclusion was based on inclusion of some poor quality trials. Combination therapy of disaccharides either with rifaximin, L-ornithine L-aspartate,probiotics for the treatment of HE needs further validation in large studies. PMID:23456517

  8. NMDA receptors in hyperammonemia and hepatic encephalopathy.

    PubMed

    Llansola, Marta; Rodrigo, Regina; Monfort, Pilar; Montoliu, Carmina; Kosenko, Elena; Cauli, Omar; Piedrafita, Blanca; El Mlili, Nisrin; Felipo, Vicente

    2007-12-01

    The NMDA type of glutamate receptors modulates learning and memory. Excessive activation of NMDA receptors leads to neuronal degeneration and death. Hyperammonemia and liver failure alter the function of NMDA receptors and of some associated signal transduction pathways. The alterations are different in acute and chronic hyperammonemia and liver failure. Acute intoxication with large doses of ammonia (and probably acute liver failure) leads to excessive NMDA receptors activation, which is responsible for ammonia-induced death. In contrast, chronic hyperammonemia induces adaptive responses resulting in impairment of signal transduction associated to NMDA receptors. The function of the glutamate-nitric oxide-cGMP pathway is impaired in brain in vivo in animal models of chronic liver failure or hyperammonemia and in homogenates from brains of patients died in hepatic encephalopathy. The impairment of this pathway leads to reduced cGMP and contributes to impaired cognitive function in hepatic encephalopathy. Learning ability is reduced in animal models of chronic liver failure and hyperammonemia and is restored by pharmacological manipulation of brain cGMP by administering phosphodiesterase inhibitors (zaprinast or sildenafil) or cGMP itself. NMDA receptors are therefore involved both in death induced by acute ammonia toxicity (and likely by acute liver failure) and in cognitive impairment in hepatic encephalopathy. PMID:17701332

  9. Experimental models of hepatic encephalopathy: ISHEN guidelines.

    PubMed

    Butterworth, Roger F; Norenberg, Michael D; Felipo, Vicente; Ferenci, Peter; Albrecht, Jan; Blei, Andres T

    2009-07-01

    Objectives of the International Society for Hepatic Encephalopathy and Nitrogen Metabolism Commission were to identify well-characterized animal models of hepatic encephalopathy (HE) and to highlight areas of animal modelling of the disorder that are in need of development. Features essential to HE modelling were identified. The best-characterized animal models of HE in acute liver failure, the so-called Type A HE, were found to be the hepatic devascularized rat and the rat with thioacetamide-induced toxic liver injury. In case of chronic liver failure, surgical models in the rat involving end-to-side portacaval anastomosis or bile duct ligation were considered to best model minimal/mild (Type B) HE. Unfortunately, at this time, there are no satisfactory animal models of Type C HE resulting from end-stage alcoholic liver disease or viral hepatitis, the most common aetiologies encountered in patients. The commission highlighted the urgent need for such models and of improved models of HE in chronic liver failure in general as well as a need for models of post-transplant neuropsychiatric disorders. Studies of HE pathophysiology at the cellular and molecular level continue to benefit from in vitro and or ex vivo models involving brain slices or exposure of cultured cells (principally cultured astrocytes) to toxins such as ammonia, manganese and pro-inflammatory cytokines. More attention could be paid in the future to in vitro models involving the neurovascular unit, microglia and neuronal co-cultures in relation to HE pathogenesis. PMID:19638106

  10. Using saccades to diagnose covert hepatic encephalopathy.

    PubMed

    Cunniffe, Nicholas; Munby, Henry; Chan, Shona; Saatci, Defne; Edison, Eric; Carpenter, R H S; Massey, Dunecan

    2015-06-01

    Covert Hepatic Encephalopathy (CHE), previously known as Minimal Hepatic Encephalopathy, is a subtle cognitive defect found in 30-70 % of cirrhosis patients. It has been linked to poor quality of life, impaired fitness to drive, and increased mortality: treatment is possible. Despite its clinical significance, diagnosis relies on psychometric tests that have proved unsuitable for use in a clinical setting. We investigated whether measurement of saccadic latency distributions might be a viable alternative. We collected data on 35 cirrhosis patients at Addenbrooke's Hospital, Cambridge, with no evidence of clinically overt encephalopathy, and 36 age-matched healthy controls. Performance on standard psychometric tests was evaluated to determine those patients with CHE as defined by the World Congress of Gastroenterology. We then compared visually-evoked saccades between those with CHE and those without, as well as reviewing blood test results and correlating saccadic latencies with biochemical parameters and prognostic scores. Cirrhosis patients have significantly longer median saccadic latencies than healthy controls. Those with CHE had significantly prolonged saccadic latencies when compared with those without CHE. Analysis of a cirrhosis patient's saccades can diagnose CHE with a sensitivity of 75 % and a specificity of 75 %. We concluded that analysis of a cirrhosis patient's saccadic latency distributions is a fast and objective measure that can be used as a diagnostic tool for CHE. This improved early diagnosis could direct avoidance of high-risk activities such as driving, and better inform treatment strategies. PMID:25586511

  11. [Rifaximin for hepatic encephalopathy in children. Case report].

    PubMed

    Malla, Ivone; Torres Cerino, Verónica; Villa, Andrés; Cheang, Yu; Giacove, Gisela; Pedreira, Alejandra; Silva, Marcelo

    2011-12-01

    Rifaximin is an antibiotic recently approved for the treatment of hepatic encephalopathy in adults. In children more than 12 year-old, it has been approved for travelers' diarrhea and it is also widely used in inflammatory bowel disease. We report, to our knowledge, the first case of a pediatric patient who received rifaximin for hepatic encephalopathy with good clinical outcome. PMID:22231877

  12. Resolution of Hepatic Encephalopathy Following Hepatic Artery Embolization in a Patient with Well-Differentiated Neuroendocrine Tumor Metastatic to the Liver

    SciTech Connect

    Erinjeri, Joseph P. Deodhar, Ajita; Thornton, Raymond H.; Allen, Peter J.; Getrajdman, George I.; Brown, Karen T.; Sofocleous, Constantinos T.; Reidy, Diane L.

    2010-06-15

    Hepatic encephalopathy is considered a contraindication to hepatic artery embolization. We describe a patient with a well-differentiated neuroendocrine tumor metastatic to the liver with refractory hepatic encephalopathy and normal liver function tests. The encephalopathy was refractory to standard medical therapy with lactulose. The patient's mental status returned to baseline after three hepatic artery embolization procedures. Arteriography and ultrasound imaging before and after embolization suggest that the encephalopathy was due to arterioportal shunting causing hepatofugal portal venous flow and portosystemic shunting. In patients with a primary or metastatic well-differentiated neuroendocrine tumor whose refractory hepatic encephalopathy is due to portosystemic shunting (rather than global hepatic dysfunction secondary to tumor burden), hepatic artery embolization can be performed safely and effectively.

  13. A neurotoxic alcohol exposure paradigm does not induce hepatic encephalopathy.

    PubMed

    Hashimoto, Joel G; Wiren, Kristine M; Wilhelm, Clare J

    2016-01-01

    Alcohol abuse is associated with neurological dysfunction, brain morphological deficits and frank neurotoxicity. Although these disruptions may be a secondary effect due to hepatic encephalopathy, no clear evidence of causality is available. This study examined whether a 72h period of alcohol intoxication known to induce physical dependence, followed by a single withdrawal, was sufficient to induce signs of hepatic encephalopathy in male and female mice. Animals were continuously intoxicated via alcohol vapor inhalation, a procedure previously shown to induce significant neurotoxicity in female mice. At peak synchronized withdrawal (8h following the end of alcohol exposure), blood samples were taken and levels of several liver-regulated markers and brain swelling were characterized. Glutathione levels were also determined in the medial frontal cortex (mFC) and hippocampus. Results revealed elevated levels of cholesterol, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and decreased levels of blood urea nitrogen and total bilirubin in alcohol-exposed male and female groups compared to controls. Brain water weight was not affected by alcohol exposure, though males tended to have slightly more water weight overall. Alcohol exposure led to reductions in tissue levels of glutathione in both the hippocampus and mFC which may indicate increased oxidative stress. Combined, these results suggest that hepatic encephalopathy does not appear to play a significant role in the neurotoxicity observed following alcohol exposure in this model. PMID:27268733

  14. Hepatic Encephalopathy and Sleepiness: An Interesting Connection?

    PubMed Central

    Montagnese, Sara; Turco, Matteo; Amodio, Piero

    2015-01-01

    Sleep-wake abnormalities in patients with cirrhosis have been traditionally associated with hepatic encephalopathy (HE). In recent years, a certain amount of work has been devoted to the study of this relationship. This has lead to a modified picture, with weakening of the association between HE and poor night sleep, and the emergence of stronger links between HE and excessive daytime sleepiness. This brief review focuses on the evidence in favor of the interpretation of HE as a sleepiness syndrome, and on the diagnostic, therapeutic and social implications of such an interpretation. PMID:26041958

  15. Management options for minimal hepatic encephalopathy.

    PubMed

    Bajaj, Jasmohan S

    2008-12-01

    Minimal hepatic encephalopathy (MHE) is a neurocognitive dysfunction that is present in the majority of patients with cirrhosis. MHE has a characteristic cognitive profile that cannot be diagnosed clinically. This cognitive dysfunction is independent of sleep dysfunction or problems with overall intelligence. MHE has a significant impact on quality of life, the ability to function in daily life and progression to overt hepatic encephalopathy. Driving ability can be impaired in MHE and this may be a significant factor behind motor vehicle accidents. A crucial aspect of the clinical care of MHE patients is their driving history, which is often ignored during routine care and can add a vital dimension to the overall disease assessment. Driving history should be an integral part of the care of patients with MHE. The preserved communication skills and lack of specific signs and insight make MHE difficult to diagnose. The predominant strategies for MHE diagnosis are psychometric or neurophysiological testing. These are usually limited by financial, normative or time constraints. Studies into inhibitory control, cognitive drug research and critical flicker frequency tests are encouraging. These tests do not require a psychologist for administration and interpretation. Lactulose and probiotics have been studied for their potential use as therapies for MHE, but these are not standard-of-care practices at this time. Therapy can improve the quality of life in MHE patients but the natural history, specific diagnostic strategies and treatment options are still being investigated. PMID:19090738

  16. Management of hepatic encephalopathy in the hospital.

    PubMed

    Leise, Michael D; Poterucha, John J; Kamath, Patrick S; Kim, W Ray

    2014-02-01

    Hepatic encephalopathy (HE) develops in up to 50% of patients with cirrhosis and is a feature of decompensated cirrhosis. With the goal of reviewing the evidence for treatment and prevention of overt hepatic encephalopathy, pubmed was searched using search terms hepatic encephalopathy AND treatment, limited to human studies from January 1, 2003, through December 1, 2013, and supplemented by key references. The inpatient incidence of HE is approximately 23,000 annually, and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails 2 phases: induction and maintenance of remission. Most cases of significant HE are precipitated by infection, gastrointestinal bleeding, medications, or other culprits. All patients should be evaluated for secondary triggers of HE, and treatment should be initiated with a nonabsorbable disaccharide (ie, lactulose) in most patients. Rifaximin (off label) can be added in patients not responding to lactulose. Neomycin is a less preferred alternative to rifaximin owing to its adverse effect profile. Other therapies, including zinc, L-ornithine-L-aspartate, and branched-chain amino acids, can be considered for patients not responding to disaccharides and nonabsorbable antibiotics. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well-compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe HE who do not respond to medical therapy. It is critically important that patients hospitalized with significant HE continue maintenance therapy at the time of dismissal to prevent further episodes. Patients with a first-time episode of HE can be administered lactulose, and careful instructions should be provided to patients and caregivers about dose titration to achieve 3 bowel movements daily. Patients with recurrent HE episodes

  17. Hepatic Encephalopathy: Pharmacological Therapies Targeting Ammonia.

    PubMed

    Rahimi, Robert S; Rockey, Don C

    2016-02-01

    Hepatic encephalopathy (HE) is a major complication in patients with decompensated cirrhosis, leading to higher readmission rates causing a profound burden of disease and considerable health care costs. Because ammonia is thought to play a crucial role in the pathogenesis of HE, therapies directed at reducing ammonia levels are now being aggressively developed. Ammonia scavengers such as AST-120 (spherical carbon adsorbent), glycerol phenylbutyrate, sodium phenylacetate or sodium benzoate, and ornithine phenylacetate have been used to improve HE symptoms. A new approach, bowel cleansing with polyethylene glycol 3350, appears to be a promising therapy, with a recent study demonstrating a more rapid improvement in overt HE (at 24 hours after treatment) than lactulose. Extracorporeal devices, although now used primarily in research settings, have also been utilized in patients with refractory HE, but are not approved for clinical management. PMID:26870932

  18. Leucine metabolism in patients with Hepatic Encephalopathy

    SciTech Connect

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

    1986-03-01

    A primed continuous infusion of (/sup 15/N, 1-/sup 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/sub 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.

  19. Pathogenesis, Diagnosis, and Treatment of Hepatic Encephalopathy

    PubMed Central

    Atluri, Dileep K; Prakash, Ravi; Mullen, Kevin D

    2011-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric disorder seen in patients with advanced liver disease or porto-systemic shunts. Based on etiology and severity of HE, the World Congress of Gastroenterology has divided HE into categories and sub-categories. Many user-friendly computer-based neuropsychiatric tests are being validated for diagnosing covert HE. Currently, emphasis is being given to view HE deficits as a continuous spectrum rather than distinct stages. Ammonia is believed to play crucial role in pathogenesis of HE via astrocyte swelling and cerebral edema. However, evidence has been building up which supports the synergistic role of oxidative stress, inflammation and neurosteroids in pathogenesis of HE. At present, treatment of HE aims at decreasing the production and intestinal absorption of ammonia. But as the role of new pathogenetic mechanisms becomes clear, many potential new treatment strategies may become available for clinician. PMID:25755319

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

    PubMed

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

    2014-01-01

    Hepatic encephalopathy is a complex disease entity ranging from mild cognitive dysfunction to deep coma. Traditionally, treatment has focused on a reduction of ammonia through a reduced production, absorption, or clearance. Rifaximin is a nonabsorbable antibiotic, which reduces the production of 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 concurrently with lactulose. Trials have varied greatly in design, outcomes, and duration of treatment regimes. Although a number of retrospective studies have indicated that long-term treatment with rifaximin is safe and possibly beneficial, high quality trials are needed to further clarify efficacy 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. PMID:24672227

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

    PubMed Central

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

    2014-01-01

    Hepatic encephalopathy is a complex disease entity ranging from mild cognitive dysfunction to deep coma. Traditionally, treatment has focused on a reduction of ammonia through a reduced production, absorption, or clearance. Rifaximin is a nonabsorbable antibiotic, which reduces the production of 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 concurrently with lactulose. Trials have varied greatly in design, outcomes, and duration of treatment regimes. Although a number of retrospective studies have indicated that long-term treatment with rifaximin is safe and possibly beneficial, high quality trials are needed to further clarify efficacy 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. PMID:24672227

  2. Coagulopathy and encephalopathy in a dog with acute hepatic necrosis.

    PubMed

    Strombeck, D R; Krum, S; Rogers, Q

    1976-10-15

    Disseminated intravascular coagulation developed secondary to hepatic necrosis in a 5-year-old Saint Bernard. Although the coagulopathy responded to treatment with heparin, the dog died from the combined effects of gastric hemorrhage and encephalopathy, both of which are complications of hepatic necrosis. PMID:977448

  3. Hepatic encephalopathy: An approach to its multiple pathophysiological features.

    PubMed

    Perazzo, Juan Carlos; Tallis, Silvina; Delfante, Amalia; Souto, Pablo Andrés; Lemberg, Abraham; Eizayaga, Francisco Xavier; Romay, Salvador

    2012-03-27

    Hepatic encephalopathy (HE) is a neuropsychiatric complex syndrome, ranging from subtle behavioral abnormalities to deep coma and death. Hepatic encephalopathy emerges as the major complication of acute or chronic liver failure. Multiplicity of factors are involved in its pathophysiology, such as central and neuromuscular neurotransmission disorder, alterations in sleep patterns and cognition, changes in energy metabolism leading to cell injury, an oxidative/nitrosative state and a neuroinflammatory condition. Moreover, in acute HE, a condition of imminent threat of death is present due to a deleterious astrocyte swelling. In chronic HE, changes in calcium signaling, mitochondrial membrane potential and long term potential expression, N-methyl-D-aspartate-cGMP and peripheral benzodiazepine receptors alterations, and changes in the mRNA and protein expression and redistribution in the cerebral blood flow can be observed. The main molecule indicated as responsible for all these changes in HE is ammonia. There is no doubt that ammonia, a neurotoxic molecule, triggers or at least facilitates most of these changes. Ammonia plasma levels are increased two- to three-fold in patients with mild to moderate cirrhotic HE and up to ten-fold in patients with acute liver failure. Hepatic and inter-organ trafficking of ammonia and its metabolite, glutamine (GLN), lead to hyperammonemic conditions. Removal of hepatic ammonia is a differentiated work that includes the hepatocyte, through the urea cycle, converting ammonia into GLN via glutamine synthetase. Under pathological conditions, such as liver damage or liver blood by-pass, the ammonia plasma level starts to rise and the risk of HE developing is high. Knowledge of the pathophysiology of HE is rapidly expanding and identification of focally localized triggers has led the development of new possibilities for HE to be considered. This editorial will focus on issues where, to the best of our knowledge, more research is needed in

  4. Hepatic encephalopathy: An approach to its multiple pathophysiological features

    PubMed Central

    Perazzo, Juan Carlos; Tallis, Silvina; Delfante, Amalia; Souto, Pablo Andrés; Lemberg, Abraham; Eizayaga, Francisco Xavier; Romay, Salvador

    2012-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric complex syndrome, ranging from subtle behavioral abnormalities to deep coma and death. Hepatic encephalopathy emerges as the major complication of acute or chronic liver failure. Multiplicity of factors are involved in its pathophysiology, such as central and neuromuscular neurotransmission disorder, alterations in sleep patterns and cognition, changes in energy metabolism leading to cell injury, an oxidative/nitrosative state and a neuroinflammatory condition. Moreover, in acute HE, a condition of imminent threat of death is present due to a deleterious astrocyte swelling. In chronic HE, changes in calcium signaling, mitochondrial membrane potential and long term potential expression, N-methyl-D-aspartate-cGMP and peripheral benzodiazepine receptors alterations, and changes in the mRNA and protein expression and redistribution in the cerebral blood flow can be observed. The main molecule indicated as responsible for all these changes in HE is ammonia. There is no doubt that ammonia, a neurotoxic molecule, triggers or at least facilitates most of these changes. Ammonia plasma levels are increased two- to three-fold in patients with mild to moderate cirrhotic HE and up to ten-fold in patients with acute liver failure. Hepatic and inter-organ trafficking of ammonia and its metabolite, glutamine (GLN), lead to hyperammonemic conditions. Removal of hepatic ammonia is a differentiated work that includes the hepatocyte, through the urea cycle, converting ammonia into GLN via glutamine synthetase. Under pathological conditions, such as liver damage or liver blood by-pass, the ammonia plasma level starts to rise and the risk of HE developing is high. Knowledge of the pathophysiology of HE is rapidly expanding and identification of focally localized triggers has led the development of new possibilities for HE to be considered. This editorial will focus on issues where, to the best of our knowledge, more research is needed in

  5. The why and wherefore of hepatic encephalopathy.

    PubMed

    Grover, Vijay Pb; Tognarelli, Joshua M; Massie, Nicolas; Crossey, Mary Me; Cook, Nicola A; Taylor-Robinson, Simon D

    2015-01-01

    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. PMID:26719720

  6. Sodium Benzoate for Treatment of Hepatic Encephalopathy

    PubMed Central

    Misel, Michael L.; Patton, Heather; Mendler, Michel

    2013-01-01

    Hepatic encephalopathy (HE) is a serious but usually reversible neuropsychiatric complication of cirrhosis, inborn errors of metabolism involving disorders of the urea cycle, and noncirrhotic portosystemic shunting that most commonly arises from a transjugular intrahepatic portosystemic shunting procedure. Symptoms can include alterations in cognitive function, neuromuscular activity, and consciousness, as well as sleep disorders and mood changes. HE is associated with significant morbidity and mortality and, if not properly treated, will lead to increased hospital admissions and healthcare costs. Although the standard therapies of lactulose and rifaximin (Xifaxan, Salix) are effective for most patients, these drugs may be associated with significant adverse effects and expense and, in some patients, inadequate therapeutic response. A need for adjunctive therapies exists. Drugs that target serum and tissue ammonia metabolism and elimination may be important adjuncts to drugs that reduce ammonia production and absorption from the gastrointestinal tract for patients with severe or persistent overt symptoms of HE. Sodium benzoate is an inexpensive adjunctive agent that can be used in addition to lactulose and rifaximin and may provide an option for some select patients with refractory HE who have failed to respond to standard therapies or who cannot afford them. Although sodium benzoate does not share the same adverse effect profiles of standard therapies for HE, its efficacy has not been well established. Given the significant dose-dependent sodium content of this therapy, it may not be appropriate for patients with significant fluid retention or kidney dysfunction. PMID:24711766

  7. The why and wherefore of hepatic encephalopathy

    PubMed Central

    Grover, Vijay PB; Tognarelli, Joshua M; Massie, Nicolas; Crossey, Mary ME; Cook, Nicola A; Taylor-Robinson, Simon D

    2015-01-01

    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. PMID:26719720

  8. Transport of AMPA receptors during long-term potentiation is impaired in rats with hepatic encephalopathy.

    PubMed

    Monfort, Pilar; Piedrafita, Blanca; Felipo, Vicente

    2009-12-01

    Cognitive function is impaired in patients with hepatic encephalopathy. Learning ability is also impaired in rats with hepatic encephalopathy due to portacaval shunts. Long-term potentiation (LTP) in hippocampus, considered the basis of some forms of learning and memory, is impaired in rats with portacaval shunt. We analyzed the mechanisms by which LTP is impaired in these rats. In control rats, application of the tetanus to induce LTP increases phosphorylation of Thr286 of calcium-calmodulin dependent protein kinase II. This activates the kinase which phosphorylates the GluR1 subunit of AMPA receptors in Ser831 and induces its translocation to the post-synaptic densities. All these steps are completely prevented in rats with hepatic encephalopathy in which the tetanus does not induce phosphorylation of CaMKII or GluR1 nor translocation of this subunit to the post-synaptic membrane. This would explain the impairment in LTP in these rats. PMID:19450629

  9. Useful tests for hepatic encephalopathy in clinical practice.

    PubMed

    Nabi, Eiman; Bajaj, Jasmohan S

    2014-01-01

    Hepatic encephalopathy (HE) is a serious complication of liver disease and portosystemic shunting that represents a continuum of neuropsychiatric changes and altered consciousness. It is classified as overt HE (OHE) when clinically apparent or as covert HE (CHE) in its mildest form. Progression of CHE to OHE and its impact of quality of life make its early diagnosis imperative. Several diagnostic techniques ranging from simple clinical scales to sophisticated computerized tests exist, yet diagnosis remains a challenge, due to the time, cost, and personnel involved. Psychometric tests appear promising due to their high sensitivity and low cost, but results are variable depending on age and education. The pros and cons of current diagnostic methods for OHE and CHE are reviewed, along with strategy for CHE testing. PMID:24357348

  10. New Methods of Testing and Brain Imaging in Hepatic Encephalopathy: A Review.

    PubMed

    Edula, Raja G R; Pyrsopoulos, Nikolaos T

    2015-08-01

    The diagnosis of hepatic encephalopathy is predominantly clinical, and the tests available assist in the diagnosis only by excluding other causes. Covert hepatic encephalopathy, which is defined as abnormal performance on psychometric tests when standard neurologic examination is completely normal, has gained widespread attention in recent years due to its effect on quality of life. This review focuses on the tests available to aid in the diagnosis of this significant complication of liver disease, and discusses the complex pathophysiologic mechanisms identified through new imaging techniques and their significance toward development of new therapeutic targets for this condition. PMID:26195200

  11. Covert and Overt Hepatic Encephalopathy: Diagnosis and Management.

    PubMed

    Patidar, Kavish R; Bajaj, Jasmohan S

    2015-11-01

    Hepatic encephalopathy (HE) is part of a spectrum of neurocognitive changes in cirrhosis. HE is divided into 2 broad categories based on severity: covert hepatic encephalopathy (CHE) and overt hepatic encephalopathy (OHE). CHE has a significant impact on a patient's quality of life, driving performance, and recently has been associated with increased hospitalizations and death. Likewise, OHE is associated with increased rates of hospitalizations and mortality, and poor quality of life. Given its significant burden on patients, care takers, and the health care system, early diagnosis and management are imperative. In addition, focus also should be directed on patient and family member education on the disease progression and adherence to medications. Treatment strategies include the use of nonabsorbable disaccharides, antibiotics (ie, rifaximin), and, potentially, probiotics. Other therapies currently under further investigation include L-ornithine-L-aspartate, ornithine phenylacetate, glycerol phenylbutyrate, molecular adsorbent recirculating system, and albumin infusion. PMID:26164219

  12. Gut microbiota: its role in hepatic encephalopathy.

    PubMed

    Rai, Rahul; Saraswat, Vivek A; Dhiman, Radha K

    2015-03-01

    Ammonia, a key factor in the pathogenesis of hepatic encephalopathy (HE), is predominantly derived from urea breakdown by urease producing large intestinal bacteria and from small intestine and kidneys, where the enzyme glutaminases releases ammonia from circulating glutamine. Non-culture techniques like pyrosequencing of bacterial 16S ribosomal ribonucleic acid are used to characterize fecal microbiota. Fecal microbiota in patients with cirrhosis have been shown to alter with increasing Child-Turcotte-Pugh (CTP) and Model for End stage Liver Disease (MELD) scores, and with development of covert or overt HE. Cirrhosis dysbiosis ratio (CDR), the ratio of autochthonous/good bacteria (e.g. Lachnospiraceae, Ruminococcaceae and Clostridiales) to non-autochthonous/pathogenic bacteria (e.g. Enterobacteriaceae and Streptococcaceae), is significantly higher in controls and patients with compensated cirrhosis than patients with decompensated cirrhosis. Although their stool microbiota do not differ, sigmoid colonic mucosal microbiota in liver cirrhosis patients with and without HE, are different. Linkage of pathogenic colonic mucosal bacteria with poor cognition and inflammation suggests that important processes at the mucosal interface, such as bacterial translocation and immune dysfunction, are involved in the pathogenesis of HE. Fecal microbiome composition does not change significantly when HE is treated with lactulose or when HE recurs after lactulose withdrawal. Despite improving cognition and endotoxemia as well as shifting positive correlation of pathogenic bacteria with metabolites, linked to ammonia, aromatic amino acids and oxidative stress, to a negative correlation, rifaximin changes gut microbiome composition only modestly. These observations suggest that the beneficial effects of lactulose and rifaximin could be associated with a change in microbial metabolic function as well as an improvement in dysbiosis. PMID:26041954

  13. Paroxysmal Amnesia Attacks due to Hashimoto's Encephalopathy

    PubMed Central

    Nar Senol, Pelin; Bican Demir, Aylin; Bora, Ibrahim; Bakar, Mustafa

    2016-01-01

    Hashimoto's encephalopathy is a rare disease which is thought to be autoimmune and steroid responsive. The syndrome is characterized by cognitive impairment, encephalopathy, psychiatric symptoms, and seizures associated with increased level of anti-thyroid antibodies. The exact pathophysiology underlying cerebral involvement is still lesser known. Although symptoms suggest a nonlesional encephalopathy in most of the cases, sometimes the clinical appearance can be subtle and may not respond to immunosuppressants or immunomodulatory agents. Here we report a case who presented with drowsiness and amnestic complaints associated with paroxysmal electroencephalography (EEG) abnormalities which could be treated only with an antiepileptic drug. PMID:27034679

  14. Treatment of chronic hepatic encephalopathy with levodopa 1

    PubMed Central

    Lunzer, Michael; James, I. M.; Weinman, J.; Sherlock, Sheila

    1974-01-01

    Three of six patients with chronic hepatic encephalopathy treated with levodopa showed a significant improvement. One patient was probably improved whilst the remaining two patients failed to show any benefit. Serial electroencephalography did not demonstrate significant changes. Treatment with levodopa was associated with an improvement in `speed-based' tasks as assessed by computerized psychometry. A significant rise in cerebral oxygen consumption was found during levodopa therapy. Gastrointestinal side effects were dose limiting. It is concluded that a therapeutic trial of levodopa in patients with chronic hepatic encephalopathy is indicated when the response to conventional therapy has been poor. PMID:4430473

  15. Nutritional assessment in cirrhotic patients with hepatic encephalopathy

    PubMed Central

    Romeiro, Fernando Gomes; Augusti, Laís

    2015-01-01

    Hepatic encephalopathy (HE) is one of the worst complications of liver disease and can be greatly influenced by nutritional status. Ammonia metabolism, inflammation and muscle wasting are relevant processes in HE pathophysiology. Malnutrition worsens the prognosis in HE, requiring early assessment of nutritional status of these patients. Body composition changes induced by liver disease and limitations superimposed by HE hamper the proper accomplishment of exams in this population, but evidence is growing that assessment of muscle mass and muscle function is mandatory due to the role of skeletal muscles in ammonia metabolism. In this review, we present the pathophysiological aspects involved in HE to support further discussion about advantages and drawbacks of some methods for evaluating the nutritional status of cirrhotic patients with HE, focusing on body composition. PMID:26730273

  16. Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions.

    PubMed

    Suraweera, Duminda; Sundaram, Vinay; Saab, Sammy

    2016-07-15

    Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal burden on caregivers. The diagnosis remains largely clinical, with the exclusion of possible other causes for the altered mental status. Current treatment strategies include nonabsorbable disaccharides and antibiotics. This review will focus on the diagnosis, management and clinical impact of hepatic encephalopathy. PMID:27377741

  17. Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions

    PubMed Central

    Suraweera, Duminda; Sundaram, Vinay; Saab, Sammy

    2016-01-01

    Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal burden on caregivers. The diagnosis remains largely clinical, with the exclusion of possible other causes for the altered mental status. Current treatment strategies include nonabsorbable disaccharides and antibiotics. This review will focus on the diagnosis, management and clinical impact of hepatic encephalopathy. PMID:27377741

  18. Detecting Minimal Hepatic Encephalopathy in an Endemic Country for Hepatitis B: The Role of Psychometrics and Serum IL-6

    PubMed Central

    Tsai, Chia-Fen; Chu, Chi-Jen; Huang, Yi-Hsiang; Wang, Yen-Po; Liu, Pei-Yi; Lin, Han-Chieh; Lee, Fa-Yauh; Lu, Ching-Liang

    2015-01-01

    Background & Aims It remains unknown what the prevalence of minimal hepatic encephalopathy is in Taiwan, a highly endemic country for chronic viral hepatitis infection. It is also unclear whether abnormal serum cytokine levels can be indicative of the presence of minimal hepatic encephalopathy. We aimed to standardize the tests of psychometric hepatic encephalopathy score and predictive value of proinflammatory cytokines in minimal hepatic encephalopathy in Taiwan. Methods 180 healthy subjects and 94 cirrhotic patients without a history of overt hepatic encephalopathy from a tertiary center were invited to participate in this cross-sectional study. Blood sampling for determination of serum levels of interleukin 6 and 18 and tumor necrosis factor-α was performed. Based on the normogram of psychometric hepatic encephalopathy score from healthy volunteers, patients with minimal hepatic encephalopathy were identified from the cirrhotic patients using the criterion of a psychometric hepatic encephalopathy score less than −4. Results In the healthy subjects, age and education were predictors of subtests of psychometric hepatic encephalopathy score. Minimal hepatic encephalopathy was identified in 27 (29%) cirrhotic patients. Serum interleukin 6 level (OR = 6.50, 95% CI = 1.64–25.76, P = 0.008) was predictive of the presence of minimal hepatic encephalopathy after multivariate analysis. Conclusions The psychometric hepatic encephalopathy score can be a useful tool for detecting patients with minimal hepatic encephalopathy in Taiwan and around one third of cirrhotic outpatients fulfill this diagnosis. A high serum interleukin 6 level is predictive of the presence of minimal hepatic encephalopathy. PMID:26039496

  19. Hepatic Encephalopathy Associated With Cancer or Anticancer Therapy

    PubMed Central

    Nott, Louise M.; Broadbridge, Vy T.; Price, Timothy

    2013-01-01

    ABSTRACT Hepatic encephalopathy is an uncommon cause of neurologic deterioration associated with hyperammonemia, which results from hepatic dysfunction or altered ammonia metabolism. Often overlooked, hyperammonemia may occur via any of several pathophysiological processes, and in the setting of malignancy, it is a potentially reversible cause of confusion and coma. Hepatic dysfunction as a result of malignant infiltration, chemotherapeutic toxicities, targeted anticancer therapies, reactivation hepatitis, portosystemic shunting, and transarterial chemoembolization (TACE) is discussed, and an approach to etiological diagnosis and management is outlined. PMID:23505573

  20. Post-TIPS Hepatic Encephalopathy Treated by Occlusion Balloon-Assisted Retrograde Embolization of a Coexisting Spontaneous Splenorenal Shunt

    SciTech Connect

    Shioyama, Yasukazu; Matsueda, Kiyoshi; Horihata, Koushi; Kimura, Masashi; Nishida, Norifumi; Kishi, Kazushi; Terada, Masaki; Sato, Morio; Yamada, Ryusaku

    1996-11-15

    A 51-year-old man with posthepatitis cirrhosis underwent a transjugular intrahepatic portosystemic shunt (TIPS) for bleeding of recurrent esophageal varices. The patient had a coexisting, spontaneous, splenorenal shunt. He subsequently developed hepatic encephalopathy, presumably due to excessive portosystemic shunting. Since medical management resulted in no significant improvement, the splenorenal shunt was embolized from the jugular vein approach via renal vein access during temporary balloon occlusion. Within a few days, the patient's hepatic encephalopathy resolved. Twelve months later the patient showed no recurrence of encephalopathy and had maintained a patent TIPS.

  1. Review article: the design of clinical trials in hepatic encephalopathy - an International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus statement

    PubMed Central

    Bajaj, J. S.; Cordoba, J.; Mullen, K. D.; Amodio, P.; Shawcross, D. L.; Butterworth, R. F.; Morgan, M. Y.

    2014-01-01

    Summary Background The clinical classification of hepatic encephalopathy is largely subjective, which has led to difficulties in designing trials in this field. Aims To review the current classification of hepatic encephalopathy and to develop consensus guidelines on the design and conduct of future clinical trials. Methods A round table was convened at the 14th International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) meeting. Key discussion points were the nomenclature of hepatic encephalopathy and the selection of patients, standards of care and end-points for assessing the treatment and secondary prevention of hepatic encephalopathy. Results It was generally agreed that severity assessment of hepatic encephalopathy in patients with cirrhosis, whether made clinically or more objectively, should be continuous rather than categorical, and a system for assessing the SONIC (Spectrum of Neuro-cognitive Impairment in Cirrhosis) was proposed. Within this system, patients currently classified as having minimal hepatic encephalopathy and Grade I hepatic encephalopathy would be classified as having Covert hepatic encephalopathy, whereas those with apparent clinical abnormalities would continue to be classified as overt hepatic encephalopathy. Some aspects of the terminology require further debate. Consensus was also reached on the patient populations, standards of care and endpoints to assess clinical trial outcomes. However, some compromises had to be made as there is considerable inter- and intravariability in the availability of some of the more objective surrogate performance markers. Conclusions The objectives of the round table were met. Robust, defendable guidelines for the conduct of future studies into hepatic encephalopathy have been provided. Outstanding issues are few and will continue to be discussed. PMID:21306407

  2. Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy

    SciTech Connect

    Bassett, M.L.; Mullen, K.D.; Scholz, B.; Fenstermacher, J.D.; Jones, E.A. )

    1990-03-01

    Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamma-aminobutyric acid in plasma contributing to the neural inhibition of hepatic encephalopathy would be that increased transfer of gamma-aminobutyric acid across the blood-brain barrier occurs in liver failure. The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. A modification of the Oldendorf intracarotid artery-injection technique was applied. (3H) gamma-aminobutyric acid, (14C) butanol, and 113mIn-labeled serum protein (transferrin) were injected simultaneously 4 s before decapitation. The ipsilateral brain uptake index of gamma-aminobutyric acid was determined from measurements of the 3 isotopes in 5 brain regions. Uncorrected or simple brain uptake indices of (3H) gamma-aminobutyric acid and (113mIn) transferrin were calculated using (14C) butanol as the highly extracted reference compound. The (113mIn) transferrin data were also used to correct the brain uptake index of (3H) gamma-aminobutyric acid for intravascular retention of (3H) gamma-aminobutyric acid. The methodology adopted minimized problems attributable to rapid (3H) gamma-aminobutyric acid metabolism, and slow brain washout and recirculation of the radiolabeled tracers. Both the uncorrected and corrected brain uptake indices of gamma-aminobutyric acid as well as the simple brain uptake index of transferrin were significantly increased in both stage II and III hepatic encephalopathy in all brain regions studied. Moreover, these brain uptake indices were significantly greater in stage III hepatic encephalopathy than in stage II hepatic encephalopathy.

  3. Hepatic Encephalopathy: Early Diagnosis in Pediatric Patients With Cirrhosis

    PubMed Central

    DARA, Naghi; SAYYARI, Ali-Akbar; IMANZADEH, Farid

    2014-01-01

    Objective As acute liver failure (ALF) and chronic liver disease (cirrhosis) continue to increase in prevalence, we will see more cases of hepatic encephalopathy. Primary care physician are often the first to suspect it, since they are familiar with the patient’s usual physical and mental status. This serious complication typically occurs in patients with severe comorbidities and needs multidisciplinary evaluation and care. Hepatic encephalopathy should be considered in any patient with acute liver failure and cirrhosis who presents with neuropsychiatric manifestations, decrease level of consciousness (coma), change of personality, intellectual and behavioral deterioration, speech and motor dysfunction. Every cirrhotic patient may be at risk; potential precipitating factors should be addressed in regular clinic visits. The encephalopathy of liver disease may be prominent, or can be present in subtle forms, such as decline of school performance, emotional outbursts, or depression. “Subtle form” of hepatic encephalopathy may not be obvious on clinical examination, but can be detected by neurophysiologic and neuropsychiatric testing. PMID:24665321

  4. Rats with minimal hepatic encephalopathy due to portacaval shunt show differential increase of translocator protein (18 kDa) binding in different brain areas, which is not affected by chronic MAP-kinase p38 inhibition.

    PubMed

    Agusti, Ana; Dziedzic, Jennifer L; Hernandez-Rabaza, Vicente; Guilarte, Tomas R; Felipo, Vicente

    2014-12-01

    Neuroinflammation plays a main role in neurological deficits in rats with minimal hepatic encephalopathy (MHE) due to portacaval shunt (PCS). Treating PCS rats with SB239063, an inhibitor of MAP-kinase-p38, reduces microglial activation and brain inflammatory markers and restores cognitive and motor function. The translocator protein-(18-kDa) (TSPO) is considered a biomarker of neuroinflammation. TSPO is increased in brain of PCS rats and of cirrhotic patients that died in hepatic coma. Rats with MHE show strong microglial activation in cerebellum and milder in other areas when assessed by MHC-II immunohistochemistry. This work aims were assessing: 1) whether binding of TSPO ligands is selectively increased in cerebellum in PCS rats; 2) whether treatment with SB239063 reduces binding of TSPO ligands in PCS rats; 3) which cell type (microglia, astrocytes) increases TSPO expression. Quantitative autoradiography was used to assess TSPO-selective (3)H-(R)-PK11195 binding to different brain areas. TSPO expression increased differentially in PCS rats, reaching mild expression in striatum or thalamus and very high levels in cerebellum. TSPO was expressed in astrocytes and microglia. Treatment with SB239063 did not reduces (3)[H]-PK11195 binding in PCS rats. SB239063 reduces microglial activation and levels of inflammatory markers, but not binding of TSPO ligands. This indicates that SB239063-induced neuroinflammation reduction in PCS rats is not mediated by effects on TSPO. Also, enhanced TSPO expression is not always associated with cognitive or motor deficits. If enhanced TSPO expression plays a role in mechanisms leading to neurological alterations in MHE, SB239063 would interfere these mechanisms at a later step. PMID:24307181

  5. Rats with minimal hepatic encephalopathy due to portacaval shunt show differential increase of translocator protein (18 kDa) binding in different brain areas, which is not affected by chronic MAP-kinase p38 inhibition

    PubMed Central

    Agusti, Ana; Dziedzic, Jennifer L.; Hernandez-Rabaza, Vicente; Guilarte, Tomas R.; Felipo, Vicente

    2014-01-01

    Neuroinflammation plays a main role in neurological deficits in rats with minimal hepatic encephalopathy (MHE) due to portacaval shunt (PCS). Treating PCS rats with SB239063, an inhibitor of MAP-kinase-p38, reduces microglial activation and brain inflammatory markers and restores cognitive and motor function. The translocator protein-(18-kDa) (TSPO) is considered a biomarker of neuro-inflammation. TSPO is increased in brain of PCS rats and of cirrhotic patients that died in hepatic coma. Rats with MHE show strong microglial activation in cerebellum and milder in other areas when assessed by MHC-II immunohistochemistry. This work aims were assessing: 1) whether binding of TSPO ligands is selectively increased in cerebellum in PCS rats; 2) whether treatment with SB239063 reduces binding of TSPO ligands in PCS rats; 3) which cell type (microglia, astrocytes) increases TSPO expression. Quantitative autoradiography was used to assess TSPO-selective 3H-(R)-PK11195 binding to different brain areas. TSPO expression increased differentially in PCS rats, reaching mild expression in striatum or thalamus and very high levels in cerebellum. TSPO was expressed in astrocytes and microglia. Treatment with SB239063 did not reduces 3[H]-PK11195 binding in PCS rats. SB239063 reduces microglial activation and levels of inflammatory markers, but not binding of TSPO ligands. This indicates that SB239063-induced neuroinflammation reduction in PCS rats is not mediated by effects on TSPO. Also, enhanced TSPO expression is not always associated with cognitive or motor deficits. If enhanced TSPO expression plays a role in mechanisms leading to neurological alterations in MHE, SB239063 would interfere these mechanisms at a later step. PMID:24307181

  6. Nutritional support in the treatment of chronic hepatic encephalopathy.

    PubMed

    Milke García, María del Pilar

    2011-06-01

    The prevalence of under nutrition in cirrhotic patients is 61% and it usually progresses as the disease becomes more advanced. The deterioration in the nutritional status and its associated metabolic derangements has raised doubts about the benefits of severe and prolonged protein restriction as a treatment for hepatic encephalopathy. However, the practice of dietary protein restriction for patients with liver cirrhosis is deeply embedded among medical practitioners and dietitians. To date, no solid conclusions may be drawn about the benefit of protein restriction. However, the negative effects of protein restriction are clear, that is, increased protein catabolism, the release of amino acids from the muscle, and possible worsening of hepatic encephalopathy. In conclusion, chronic protein restriction causes progressive and harmful protein depletion and must be avoided. PMID:22228881

  7. Contributions of Microdialysis to New Alternative Therapeutics for Hepatic Encephalopathy

    PubMed Central

    Rivera-Espinosa, Liliana; Floriano-Sánchez, Esaú; Pedraza-Chaverrí, José; Coballase-Urrutia, Elvia; Sampieri, Aristides; Ortega-Cuellar, Daniel; Cárdenas-Rodríguez, Noemí; Carmona-Aparicio, Liliana

    2013-01-01

    Hepatic encephalopathy (HE) is a common complication of cirrhosis, of largely reversible impairment of brain function occurring in patients with acute or chronic liver failure or when the liver is bypassed by portosystemic shunts. The mechanisms causing this brain dysfunction are still largely unclear. The need to avoid complications caused by late diagnosis has attracted interest to understand the mechanisms underlying neuronal damage in order to find markers that will allow timely diagnosis and to propose new therapeutic alternatives to improve the care of patients. One of the experimental approaches to study HE is microdialysis; this technique allows evaluation of different chemical substances in several organs through the recollection of samples in specific places by semi-permeable membranes. In this review we will discuss the contributions of microdialysis in the understanding of the physiological alterations in human hepatic encephalopathy and experimental models and the studies to find novel alternative therapies for this disease. PMID:23921686

  8. Hepatic encephalopathy coexists with acquired chronic hepatocerebral degeneration.

    PubMed

    Huang, Feng-Zhen; Hou, Xuan; Zhou, Tie-Qiao; Chen, Si

    2015-07-01

    Hyperkinetic extrapyramidal syndrome is the typical clinical characteristic of acquired hepatocerebral degeneration (AHD), but is usually not observed with hepatic encephalopathy (HE). We present a case of AHD coexisting with HE. Both conditions were secondary to liver cirrhosis and hepatitis C virus infection. The brain MRI showed bilateral and symmetric high T1 signal-intensity in the globus pallidus, and diffuse high signal-intensity of the hemispheric white matter on T2-FLAIR images. As we usually neglect the existence of AHD, the diagnosis is often ignored, especially when it coexists with HE. This case highlights the need to distinguish irreversible AHD from HE. PMID:26166598

  9. Glutamatergic and gabaergic neurotransmission and neuronal circuits in hepatic encephalopathy.

    PubMed

    Cauli, Omar; Rodrigo, Regina; Llansola, Marta; Montoliu, Carmina; Monfort, Pilar; Piedrafita, Blanca; El Mlili, Nisrin; Boix, Jordi; Agustí, Ana; Felipo, Vicente

    2009-03-01

    Patients with hepatic encephalopathy (HE) may present different neurological alterations including impaired cognitive function and altered motor activity and coordination. HE may lead to coma and death. Many of these neurological alterations are the consequence of altered neurotransmission. Hyperammonemia is a main contributor to the alterations in neurotransmission and in neurological functions in HE. Both glutamatergic and GABAergic neurotransmission are altered in animal models of HE. We review some of these alterations, especially those alterations in glutamatergic neurotransmission responsible for some specific neurological alterations in hyperammonemia and HE: the role 1) of excessive NMDA receptors activation in death induced by acute hyperammonemia; 2) of impaired function of the glutamate-nitric oxide-cGMP pathway, associated to NMDA receptors, in cognitive impairment in chronic HE; 3) of increased extracellular glutamate and activation of metabotropic glutamate receptors in substantia nigra in hypokinesia in chronic HE. The therapeutic implications are discussed. We also review the alterations in the function of the neuronal circuits between basal ganglia-thalamus-cortex modulating motor activity and the role of sequential alterations in glutamatergic and GABAergic neurotransmission in these alterations. HE would be a consequence of altered neuronal communication due to alterations in general neurotransmission involving different neurotransmitter systems in different neurons. PMID:19085094

  10. Advances in cirrhosis: Optimizing the management of hepatic encephalopathy.

    PubMed

    Liu, Andy; Perumpail, Ryan B; Kumari, Radhika; Younossi, Zobair M; Wong, Robert J; Ahmed, Aijaz

    2015-12-18

    Hepatic encephalopathy (HE) is a major complication of cirrhosis resulting in significant socioeconomic burden, morbidity, and mortality. HE can be further subdivided into covert HE (CHE) and overt HE (OHE). CHE is a subclinical, less severe manifestation of HE and requires psychometric testing for diagnosis. Due to the time consuming screening process and lack of standardized diagnostic criteria, CHE is frequently underdiagnosed despite its recognized role as a precursor to OHE. Screening for CHE with the availability of the Stroop test has provided a pragmatic method to promptly diagnose CHE. Management of acute OHE involves institution of lactulose, the preferred first-line therapy. In addition, prompt recognition and treatment of precipitating factors is critical as it may result in complete resolution of acute episodes of OHE. Treatment goals include improvement of daily functioning, evaluation for liver transplantation, and prevention of OHE recurrence. For secondary prophylaxis, intolerance to indefinite lactulose therapy may lead to non-adherence and has been identified as a precipitating factor for recurrent OHE. Rifaximin is an effective add-on therapy to lactulose for treatment and prevention of recurrent OHE. Recent studies have demonstrated comparable efficacy of probiotic therapy to lactulose use in both primary prophylaxis and secondary prophylaxis. PMID:26692331

  11. Advances in cirrhosis: Optimizing the management of hepatic encephalopathy

    PubMed Central

    Liu, Andy; Perumpail, Ryan B; Kumari, Radhika; Younossi, Zobair M; Wong, Robert J; Ahmed, Aijaz

    2015-01-01

    Hepatic encephalopathy (HE) is a major complication of cirrhosis resulting in significant socioeconomic burden, morbidity, and mortality. HE can be further subdivided into covert HE (CHE) and overt HE (OHE). CHE is a subclinical, less severe manifestation of HE and requires psychometric testing for diagnosis. Due to the time consuming screening process and lack of standardized diagnostic criteria, CHE is frequently underdiagnosed despite its recognized role as a precursor to OHE. Screening for CHE with the availability of the Stroop test has provided a pragmatic method to promptly diagnose CHE. Management of acute OHE involves institution of lactulose, the preferred first-line therapy. In addition, prompt recognition and treatment of precipitating factors is critical as it may result in complete resolution of acute episodes of OHE. Treatment goals include improvement of daily functioning, evaluation for liver transplantation, and prevention of OHE recurrence. For secondary prophylaxis, intolerance to indefinite lactulose therapy may lead to non-adherence and has been identified as a precipitating factor for recurrent OHE. Rifaximin is an effective add-on therapy to lactulose for treatment and prevention of recurrent OHE. Recent studies have demonstrated comparable efficacy of probiotic therapy to lactulose use in both primary prophylaxis and secondary prophylaxis. PMID:26692331

  12. Hepatic Encephalopathy Secondary to Intrahepatic Portosystemic Venous Shunt: Balloon-Occluded Retrograde Transvenous Embolization with n-Butyl Cyanoacrylate and Microcoils

    SciTech Connect

    Yamagami, Takuji; Nakamura, Toshiyuki; Iida, Shigeharu; Kato, Takeharu; Tanaka, Osamu; Matsushima, Shigenori; Ito, Hirotoshi; Okuyama, Chio; Ushijima, Yo; Shiga, Kensuke; Nishimura, Tsunehiko

    2002-06-15

    We report a 70-year-old woman with hepatic encephalopathy due to an intrahepatic portosystemic venous shunt that was successfully occluded by percutaneous transcatheter embolization with n-butyl cyanoacrylate and microcoils.

  13. GLUTAMINE IN THE PATHOGENESIS OF HEPATIC ENCEPHALOPATHY: THE TROJAN HORSE HYPOTHESIS REVISITED

    PubMed Central

    Rama Rao, Kakulavarapu V.; Norenberg, Michael D.

    2016-01-01

    Hepatic encephalopathy (HE) is major neuropsychiatric disorder occurring in patients with severe liver disease and ammonia is generally considered to represent the major toxin responsible for this condition. Ammonia in brain is chiefly metabolized (“detoxified”) to glutamine in astrocytes due to predominant localization of glutamine synthetase in these cells. While glutamine has long been considered innocuous, a deleterious role more recently has been attributed to this amino acid. This article reviews the mechanisms by which glutamine contributes to the pathogenesis of HE, how glutamine is transported into mitochondria and subsequently hydrolyzed leading to high levels of ammonia, the latter triggering oxidative and nitrative stress, the mitochondrial permeability transition and mitochondrial injury, a sequence of events we have collectively termed as the Trojan horse hypothesis of hepatic encephalopathy. PMID:23277414

  14. [Role of rifaximin in the treatment of hepatic encephalopathy].

    PubMed

    Sanchez-Delgado, Jordi; Miquel, Mireia

    2016-04-01

    Hepatic encephalopathy (HE) is a frequent and serious complication of liver cirrhosis. In addition to correction of the precipitating factors, the most commonly used treatments are non-absorbable disaccharides and rifaximin. Many of the recommendations are based on current clinical practice and there are few randomized controlled trials. Currently, rifaximin should be initiated during an episode of EH if, after 24-48 hours of non-absorbable disaccharide therapy, there is no clinical improvement. In recurrent EH, it is advisable to add rifaximin in patients under non-absorbable disaccharide therapy who develop a new episode. Currently, standard treatment with rifaximin for minimal EH is not recommended. Rifaximin is effective in the acute treatment of overt encephalopathy and in preventing recurrence. PMID:26545947

  15. Hepatitis E-associated encephalopathy in a renal transplant recipient

    PubMed Central

    de Vries, Marijke A; Samijn, Johnny P A; de Man, Rob; Boots, Johannes M M

    2014-01-01

    Hepatitis E virus genotype 3 is not rare in developed countries, and may cause chronic hepatitis in immunocompromised patients. This may not only lead to abnormalities in liver test and malaise, but to severe neurological symptoms as well. In this case, chronic hepatitis E infection caused encephalopathy, an atactic gait, Lhermitte's sign, incomplete bladder emptying and peripheral sensory neuropathy in a renal transplant recipient. The diagnosis was not performed until years after the onset of first symptoms and several months after the onset of neurological symptoms. If treated adequately, viral load can be reduced in over two-thirds of patients and neurological symptoms are often resolved. More widespread knowledge about this virus and its extrahepatic manifestations may lead to a quicker diagnosis, and may limit pathology. Serological screening should be added to standard pretransplant virological screening, so that, in the future, patients without antibodies could be vaccinated. PMID:24789162

  16. [Treatment of refractory hepatic encephalopathy associated with insertion of a transjugular intrahepatic portosystemic shunt through new endovascular techniques: a case report].

    PubMed

    Martínez Moreno, Belén; Bellot, Pablo; de España, Francisco; Palazón, José María; Such, José; Pérez-Mateo, Miguel

    2011-01-01

    Insertion of a transjugular intrahepatic portosystemic shunt (TIPS) is an increasingly used treatment in the management of the complications of portal hypertension. However, one of the complications of this technique is refractory or recurrent hepatic encephalopathy, which poses a difficult clinical problem. We report the case of a patient who underwent TIPS insertion to control bleeding due to esophageal varices. The patient subsequently developed refractory hepatic encephalopathy, requiring reduction of the caliber of the shunt. PMID:21652116

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

    PubMed Central

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

    2014-01-01

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

  18. Ammonia and hepatic encephalopathy: the more things change, the more they remain the same.

    PubMed

    Shawcross, D L; Olde Damink, S W M; Butterworth, R F; Jalan, R

    2005-09-01

    Ammonia is thought to be central in the pathogenesis of hepatic encephalopathy and has been of importance to generations dating back to the early Egyptians. Hippocrates 2500 years ago described 'encephalopathy' simply translated as 'inside head suffering.' Over 1500 papers have been written on hepatic encephalopathy since 1966, but only a minority of these actually refer to the original observation of hepatic encephalopathy and the link with ammonia made by Marcel Nencki and Ivan Pavlov in 1893 with very little acknowledgement being made to the early landmark studies which described the importance of the muscle and kidneys in maintaining ammonia homeostasis as well as the liver and gut. Furthermore, infection was recognized as being an important modulator of brain function by the ancient Greek physicians and philosophers. This review focuses upon the original experiments of Nencki and Pavlov and describes how they fit into what we understand about the pathophysiology and treatment of hepatic encephalopathy today. PMID:16167195

  19. Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure

    PubMed Central

    Chu, Chi-Jen; Hsiao, Ching-Chin; Wang, Teh-Fang; Chan, Cho-Yu; Lee, Fa-Yauh; Chang, Full-Young; Chen, Yi-Chou; Huang, Hui-Chun; Wang, Sun-Sang; Lee, Shou-Dong

    2005-01-01

    AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy. Prostacyclin (PGI2) and nitric oxide (NO) are important contributors to hyperdynamic circulation in portal hypertensive states. Our previous study showed that chronic inhibition of NO had detrimental effects on the severity of encephalopathy in thioacetamide (TAA)-treated rats due to aggravation of liver damage. To date, there are no detailed data concerning the effects of PGI2 inhibition on the severity of hepatic encephalopathy during fulminant hepatic failure. METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection of TAA (350 mg/(kg.d) for 3 d. Rats were divided into two groups to receive intraperitoneal injection of indomethacin (5 mg/(kg.d), n = 20) or normal saline (N/S, n = 20) for 5 d, starting 2 d before TAA administration. Severity of encephalopathy was assessed by the counts of motor activity measured with Opto-Varimex animal activity meter. Plasma tumor necrosis factor-α (TNF-α, an index of liver injury) and 6-keto-PGF1α (a metabolite of PGI2) levels were measured by enzyme-linked immunosorbent assay. RESULTS: As compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving indomethacin (20% vs 5%, P<0.01). Inhibition of PGI2 created detrimental effects on total movement counts (indomethacin vs N/S: 438±102 vs 841±145 counts/30 min, P<0.05). Rats treated with indomethacin had significant higher plasma levels of TNF-α (indomethacin vs N/S: 22±5 vs 10±1 pg/mL, P<0.05) and lower plasma levels of 6-keto-PGF1α (P<0.001), but not total bilirubin or creatinine (P>0.05), as compared with rats treated with N/S. CONCLUSION: Chronic indomethacin administration has detrimental effects on the severity of encephalopathy in TAA-treated rats and this phenomenon may be attributed to the

  20. The "Plateau" Phenomenon of Stepwise Extracorporeal Albumin Dialysis Bispectral Index Hepatic Encephalopathy Recovery.

    PubMed

    Dahaba, Ashraf A

    2015-12-15

    The Bispectral Index™ monitor, an electroencephalographic-derived parameter, can quantify hepatic encephalopathy cerebral function recovery and differentiate between West Haven grades 1 to 4. I report a very peculiar "plateau" phenomenon of 3 clear distinct plateaus of stepwise albumin dialysis Bispectral Index hepatic encephalopathy recovery during an 8-hour Molecular Adsorbent Recirculating System™ (MARS™) liver-assist extracorporeal detoxification, manifesting in conjunction with 3 West Haven grade recoveries. In the patients, I observed recovery of cerebral function after hepatic encephalopathy as a series of plateaus with abrupt transitions between the plateaus, rather than the gradual recovery I anticipated. PMID:26657702

  1. Contemporary Understanding and Management of Overt and Covert Hepatic Encephalopathy

    PubMed Central

    NeSmith, Meghan; Ahn, Joseph

    2016-01-01

    Hepatic encephalopathy (HE) is a major complication of liver disease that leads to significant morbidity and mortality. Caring for hospitalized patients with HE is becoming more complex, and the economic burden of HE continues to rise. Defining and diagnosing HE, particularly covert HE (CHE), remain challenging. In this article, we review new tools and those currently under development for the diagnosis of CHE and the latest advances in the acute and long-term management of overt HE (OHE) and CHE. In particular, we review the latest data on the use of lactulose and rifaximin for treatment of OHE and summarize the data on adjunctive agents such as sodium benzoate and probiotics. PMID:27182210

  2. Prevention and treatment of hepatic encephalopathy: focusing on gut microbiota.

    PubMed

    Garcovich, Matteo; Zocco, Maria Assunta; Roccarina, Davide; Ponziani, Francesca Romana; Gasbarrini, Antonio

    2012-12-14

    The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or porto-systemic shunting of blood flow and it manifests with progressive deterioration of the superior neurological functions. The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora and downregulation of systemic and gut-derived inflammation. This review will provide an overview of gut barrier function and the influence of gut-derived factors on HE, focusing on the role of gut microbiota in the pathogenesis of HE and the recent literature findings on its therapeutic manipulation. PMID:23239905

  3. PET and MR imaging of neuroinflammation in hepatic encephalopathy.

    PubMed

    Su, Yun Yan; Yang, Gui Fen; Lu, Guang Ming; Wu, Shawn; Zhang, Long Jiang

    2015-02-01

    Neurological or psychiatric abnormalities associated with hepatic encephalopathy (HE) range from subclinical findings to coma. HE is commonly accompanied with the accumulation of toxic substances in bloodstream. The toxicity effect of hyperammonemia on astrocyte, such as the alteration in neurotransmission, oxidative stress, astrocyte swelling, is considered as an important factor in the pathogenesis of HE. Besides, neuroinflammation has captured more attention in the process of HE, but the mechanism of neuroinflammation leading to HE remains unclear. Molecular imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) targeting activated microglia and/ or other mediators appear to be promising noninvasive approaches to assess HE. This review focuses on novel imaging and therapy strategies of neuroinflammation in HE. PMID:25514861

  4. Contemporary Understanding and Management of Overt and Covert Hepatic Encephalopathy.

    PubMed

    NeSmith, Meghan; Ahn, Joseph; Flamm, Steven L

    2016-02-01

    Hepatic encephalopathy (HE) is a major complication of liver disease that leads to significant morbidity and mortality. Caring for hospitalized patients with HE is becoming more complex, and the economic burden of HE continues to rise. Defining and diagnosing HE, particularly covert HE (CHE), remain challenging. In this article, we review new tools and those currently under development for the diagnosis of CHE and the latest advances in the acute and long-term management of overt HE (OHE) and CHE. In particular, we review the latest data on the use of lactulose and rifaximin for treatment of OHE and summarize the data on adjunctive agents such as sodium benzoate and probiotics. PMID:27182210

  5. Mapping Metabolic Brain Activity in Three Models of Hepatic Encephalopathy

    PubMed Central

    Méndez, Marta; Fidalgo, Camino; Aller, María Ángeles; Arias, Jaime; Arias, Jorge L.

    2013-01-01

    Cirrhosis is a common disease in Western countries. Liver failure, hyperammonemia, and portal hypertension are the main factors that contribute to human cirrhosis that frequently leads to a neuropsychiatric disorder known as hepatic encephalopathy (HE). In this study, we examined the differential contribution of these leading factors to the oxidative metabolism of diverse brain limbic system regions frequently involved in memory process by histochemical labelling of cytochrome oxidase (COx). We have analyzed cortical structures such as the infralimbic and prelimbic cotices, subcortical structures such as hippocampus and ventral striatum, at thalamic level like the anterodorsal, anteroventral, and mediodorsal thalamus, and, finally, the hypothalamus, where the mammillary nuclei (medial and lateral) were measured. The severest alteration is found in the model that mimics intoxication by ammonia, followed by the thioacetamide-treated group and the portal hypertension group. No changes were found at the mammillary bodies for any of the experimental groups. PMID:23573412

  6. Hepatic encephalopathy: effects of liver failure on brain function.

    PubMed

    Felipo, Vicente

    2013-12-01

    Liver failure affects brain function, leading to neurological and psychiatric alterations; such alterations are referred to as hepatic encephalopathy (HE). Early diagnosis of minimal HE reveals an unexpectedly high incidence of mild cognitive impairment and psychomotor slowing in patients with liver cirrhosis - conditions that have serious health, social and economic consequences. The mechanisms responsible for the neurological alterations in HE are beginning to emerge. New therapeutic strategies acting on specific targets in the brain (phosphodiesterase 5, type A GABA receptors, cyclooxygenase and mitogen-activated protein kinase p38) have been shown to restore cognitive and motor function in animal models of chronic HE, and NMDA receptor antagonists have been shown to increase survival in acute liver failure. This article reviews the latest studies aimed at understanding how liver failure affects brain function and potential ways to ameliorate these effects. PMID:24149188

  7. Multimodality magnetic resonance imaging in hepatic encephalopathy: An update

    PubMed Central

    Zhang, Xiao-Dong; Zhang, Long-Jiang; Wu, Sheng-Yong; Lu, Guang-Ming

    2014-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric complication of cirrhosis or acute liver failure. Currently, HE is regarded as a continuous cognitive impairment ranging from the mildest stage, minimal HE to overt HE. Hyperammonaemia and neuroinflammation are two main underlying factors which contribute to the neurological alterations in HE. Both structural and functional impairments are found in the white mater and grey mater involved in HE. Although the investigations into HE pathophysiological mechanism are enormous, the exact pathophysiological causes underlying HE remain controversial. Multimodality magnetic resonance imaging (MRI) plays an important role in helping to understand the pathological process of HE. This paper reviews the up-to-date multimodality MRI methods and predominant findings in HE patients with a highlight of the increasingly important role of blood oxygen level dependent functional MRI. PMID:25170210

  8. Lactulose enhances neuroplasticity to improve cognitive function in early hepatic encephalopathy

    PubMed Central

    Yang, Nan; Liu, He; Jiang, Yao; Zheng, Ji; Li, Dong-mei; Ji, Chao; Liu, Yan-yong; Zuo, Ping-ping

    2015-01-01

    Lactulose is known to improve cognitive function in patients with early hepatic encephalopathy; however, the underlying mechanism remains poorly understood. In the present study, we investigated the behavioral and neurochemical effects of lactulose in a rat model of early hepatic encephalopathy induced by carbon tetrachloride. Immunohistochemistry showed that lactulose treatment promoted neurogenesis and increased the number of neurons and astrocytes in the hippocampus. Moreover, lactulose-treated rats showed shorter escape latencies than model rats in the Morris water maze, indicating that lactulose improved the cognitive impairments caused by hepatic encephalopathy. The present findings suggest that lactulose effectively improves cognitive function by enhancing neuroplasticity in a rat model of early hepatic encephalopathy. PMID:26604907

  9. Brain concentrations of benzodiazepines are elevated in an animal model of hepatic encephalopathy

    SciTech Connect

    Basile, A.S.; Pannell, L.; Jaouni, T.; Gammal, S.H.; Fales, H.M.; Jones, E.A.; Skolnick, P. )

    1990-07-01

    Brain extracts from rats with hepatic encephalopathy due to thioacetamide-induced fulminant hepatic failure contained 4- to 6-fold higher concentrations of substances that inhibit radioligand binding to benzodiazepine receptors than corresponding control rat extracts. Both isocratic and gradient-elution HPLC indicated that this inhibitory activity was localized in 3-8 peaks with retention times corresponding to deschlorodiazepam, deschlorolorazepam, lorazepam, oxazepam, diazepam, and N-desmethyldiazepam. The presence of diazepam and N-desmethyldiazepam was confirmed by mass spectroscopy. Both mass spectroscopic and radiometric techniques indicated that the concentrations of N-desmethyldiazepam and diazepam in brain extracts from encephalopathic rats were 2-9 and 5-7 times higher, respectively, than in control brain extracts. While benzodiazepines have been identified previously in mammalian and plant tissues, this report demonstrates that concentrations of these substances are increased in a pathophysiological condition. These findings provide a rational basis for the use of benzodiazepine receptor antagonists in the management of hepatic encephalopathy in humans.

  10. Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation.

    PubMed

    Aldridge, Dominic R; Tranah, Edward J; Shawcross, Debbie L

    2015-03-01

    The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review. PMID:26041962

  11. Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

    PubMed Central

    Aldridge, Dominic R.; Tranah, Edward J.; Shawcross, Debbie L.

    2015-01-01

    The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review. PMID:26041962

  12. Focal cortical damage parallels cognitive impairment in minimal hepatic encephalopathy.

    PubMed

    Montoliu, Carmina; Gonzalez-Escamilla, Gabriel; Atienza, Mercedes; Urios, Amparo; Gonzalez, Olga; Wassel, Abdallah; Aliaga, Roberto; Giner-Duran, Remedios; Serra, Miguel A; Rodrigo, Jose M; Belloch, Vicente; Felipo, Vicente; Cantero, Jose L

    2012-07-16

    Little attention has been paid to cortical integrity in patients with minimal hepatic encephalopathy (MHE), although cognitive functions affected in early stages of liver disease are mainly allocated in different neocortical structures. Here we used cortical surface-based analysis techniques to investigate if patterns of cortical thinning accompany the mildest form of HE. To aim this goal, cortical thickness obtained from high-resolution 3T magnetic resonance imaging (MRI) was measured in patients with no MHE (NMHE), MHE, and healthy controls. Further correlation analyses were performed to examine whether scores in the critical flicker frequency (CFF) test, and blood ammonia levels accounted for the loss of cortical integrity in different stages of liver disease. Finally, we assessed group differences in volume of different subcortical regions and their potential relationships with CFF scores/blood ammonia levels. Results showed a focal thinning of the superior temporal cortex and precuneus in MHE patients when compared with NMHE and controls. Relationships between blood ammonia levels and cortical thickness of the calcarine sulcus accounted for impaired visual judgment in patients with MHE when compared to NMHE. Regression analyses between cortical thickness and CFF predicted differences between controls and the two groups of HE patients, but failed to discriminate between patients with NMHE and MHE. Taking together, these findings provide the first report of cortical thinning in MHE patients, and they yield novel insights into the neurobiological basis of cognitive impairment associated with early stages of liver diseases. PMID:22465844

  13. Cyclic GMP pathways in hepatic encephalopathy. Neurological and therapeutic implications.

    PubMed

    Montoliu, Carmina; Rodrigo, Regina; Monfort, Pilar; Llansola, Marta; Cauli, Omar; Boix, Jordi; Elmlili, Nisrin; Agusti, Ana; Felipo, Vicente

    2010-03-01

    Cyclic GMP (cGMP) modulates important cerebral processes including some forms of learning and memory. cGMP pathways are strongly altered in hyperammonemia and hepatic encephalopathy (HE). Patients with liver cirrhosis show reduced intracellular cGMP in lymphocytes, increased cGMP in plasma and increased activation of soluble guanylate cyclase by nitric oxide (NO) in lymphocytes, which correlates with minimal HE assessed by psychometric tests. Activation of soluble guanylate cyclase by NO is also increased in cerebral cortex, but reduced in cerebellum, from patients who died with HE. This opposite alteration is reproduced in vivo in rats with chronic hyperammonemia or HE. A main pathway modulating cGMP levels in brain is the glutamate-NO-cGMP pathway. The function of this pathway is impaired both in cerebellum and cortex of rats with hyperammonemia or HE. Impairment of this pathway is responsible for reduced ability to learn some types of tasks. Restoring the pathway and cGMP levels in brain restores learning ability. This may be achieved by administering phosphodiesterase inhibitors (zaprinast, sildenafil), cGMP, anti-inflammatories (ibuprofen) or antagonists of GABAA receptors (bicuculline). These data support that increasing cGMP by safe pharmacological means may be a new therapeutic approach to improve cognitive function in patients with minimal or clinical HE. PMID:20195723

  14. Evaluation of rifaximin in management of hepatic encephalopathy.

    PubMed

    Wahib, Ali A; El-Deen Salem, M Negm; Ahmed, Mostafa A; El-Dessouky, Yasser M M; El-Tiby, Diaa M; El-Mola, Khaled; El-Sayed, Abeer M

    2014-12-01

    This study evaluated the efficacy of rifaximin versus lactulose in the treatment of hepatic encephalopathy (HE). The study population included 50 patients who were diagnosed to have signs of the first to third degree HE, according to the West Haven criteria and classified into two groups. GI: included 25 patients who had HE and were treated with lactulose syrup (laxolac) 90 ml daily divided into 3 doses for 7 days. GII: included 25 patients who had HE and were treated with rifaximin 1200 mg daily divided into 3 doses for 7 days. Patients in both groups also received other measures of treatment of HE as daily enema and protein restriction. Rifaximin significantly improved various subjective and measurable components of HE including mental status, behavior, asterixis, and serum ammonia concentration. In acute HE of grade 1 to grade 3, rifaximin may be a good alternative to non-absorbable disaccharides as it is broad spectrum, non-absorbable antibiotic with rapid action and little side effects. It is better tolerated, associated with less frequent and shorter hospitalization in comparison to lactulose. PMID:25643509

  15. Severe hypoglycemic encephalopathy due to hypoallergenic formula in an infant.

    PubMed

    Ogawa, Erika; Ishige, Mika; Takahashi, Yuno; Kodama, Hiroko; Fuchigami, Tatsuo; Takahashi, Shori

    2016-08-01

    A 7-month-old girl was brought to hospital due to vomiting. Upon admission, she was in a convulsive state and stupor with extremely low blood glucose. Head computed tomography showed brain edema, and comprehensive treatment for acute encephalopathy was initiated immediately. Severe hypoglycemia, metabolic acidosis, elevation of ammonia and serum transaminases and creatine kinase suggested metabolic decompensation. Infusion of a high-glucose solution containing vitamins, biotin, and l-carnitine resolved the metabolic crisis quickly, but brain damage was irreversible. She was found to have been fed exclusively on a hypoallergenic formula (HF) for 7 months, although she was found later to be non-allergic. Evidence of inborn metabolic diseases was absent, therefore biotin deficiency and carnitine deficiency were concluded to be a consequence of reliance on a HF for a prolonged period. Health-care professionals should warn parents of the consequences of using HF. PMID:27324861

  16. Neuroinflammation contributes to hypokinesia in rats with hepatic encephalopathy: ibuprofen restores its motor activity.

    PubMed

    Cauli, Omar; Rodrigo, Regina; Piedrafita, Blanca; Llansola, Marta; Mansouri, Mohammad T; Felipo, Vicente

    2009-05-01

    Patients with hepatic encephalopathy show altered motor function, psychomotor slowing, and hypokinesia, which are reproduced in rats with portacaval shunts (PCS). Increased extracellular glutamate in substantia nigra pars reticulata (SNr) is responsible for hypokinesia in PCS rats. The mechanisms by which liver failure leads to increased extracellular glutamate in SNr remain unclear. Inflammation seems to act synergistically with hyperammonemia to induce neurological alterations in hepatic encephalopathy. It is therefore possible that inflammation-associated alterations may contribute to motor alterations in hepatic encephalopathy. The aim of this work was to assess whether treatment with an antiinflammatory, ibuprofen, is able to normalize extracellular glutamate in SNr and/or to improve hypokinesia in PCS rats. The amounts of the glutamate transporters GLT-1 and EAAC-1 are reduced by 26% and 32%, respectively, in SNr of PCS rats. This reduction is associated with a tenfold increase in extracellular glutamate in SNr and a reduction in motor activity. Chronic treatment with 30 mg/kg ibuprofen completely normalizes the amount of GLT-1 and EAAC-1 and significantly reduces (by 53%) extracellular glutamate in SNr of PCS rats. Moreover, ibuprofen, at 15 or 30 (but not at 5) mg/kg/day, completely eliminates hypokinesia, restoring normal motor activity. This supports the idea that inflammation is a main contributor to the induction of hypokinesia in hepatic encephalopathy. Moreover, these data point to the possible therapeutic utility of decreasing inflammation, by safe procedures, in the treatment of the motor deficits in patients with hepatic encephalopathy. PMID:19025766

  17. Rifaximin therapy and hepatic encephalopathy: Pros and cons

    PubMed Central

    Zullo, Angelo; Hassan, Cesare; Ridola, Lorenzo; Lorenzetti, Roberto; Campo, Salvatore MA; Riggio, Oliviero

    2012-01-01

    Hepatic encephalopathy (HE) is the second most common major complication in cirrhotics and it significantly impacts quality of life. Therapeutic approaches for HE treatment and prevention mainly continue to rely on ammonia-lowering strategies and non-absorbable disaccharides are currently considered the cornerstone therapy. Non-absorbable antibiotics, such as neomycin and paramomycin, are effective in treatment of acute HE episodes but their prolonged use for recurrence prevention is hampered by possible side-effects. To overcome these limitations, rifaximin use has been proposed. Rifaximin has been shown to be not superior to non-absorbable disaccharides for either HE treatment or prevention, with a similar incidence of side-effects. Cirrhosis significantly increases rifaximin absorption and this could be a cause for concern. Following long-term rifaximin therapy, Clostridium difficile colitis has been observed and Candida albicans has been isolated from 20% of patients. In addition, selection of resistant mutants of both Gram-negative and -positive bacteria in the gastrointestinal tract cannot be definitely ruled out. Electrolyte alterations (sodium and potassium) have been reported during rifaximin therapy, a warning for its long-term use in cirrhotics. Moreover, a potential interference with vitamin K production should be considered which could further impair the already altered clotting status of these patients. The therapeutic cost of rifaximin is markedly higher than non-absorbable disaccharides. While waiting for further safety data, caution should be used to limit the use of rifaximin therapy for a very short-term period in selected HE cirrhotics not responding to non-absorbable disaccharides. PMID:22966484

  18. Rifaximin therapy and hepatic encephalopathy: Pros and cons.

    PubMed

    Zullo, Angelo; Hassan, Cesare; Ridola, Lorenzo; Lorenzetti, Roberto; Campo, Salvatore Ma; Riggio, Oliviero

    2012-08-01

    Hepatic encephalopathy (HE) is the second most common major complication in cirrhotics and it significantly impacts quality of life. Therapeutic approaches for HE treatment and prevention mainly continue to rely on ammonia-lowering strategies and non-absorbable disaccharides are currently considered the cornerstone therapy. Non-absorbable antibiotics, such as neomycin and paramomycin, are effective in treatment of acute HE episodes but their prolonged use for recurrence prevention is hampered by possible side-effects. To overcome these limitations, rifaximin use has been proposed. Rifaximin has been shown to be not superior to non-absorbable disaccharides for either HE treatment or prevention, with a similar incidence of side-effects. Cirrhosis significantly increases rifaximin absorption and this could be a cause for concern. Following long-term rifaximin therapy, Clostridium difficile colitis has been observed and Candida albicans has been isolated from 20% of patients. In addition, selection of resistant mutants of both Gram-negative and -positive bacteria in the gastrointestinal tract cannot be definitely ruled out. Electrolyte alterations (sodium and potassium) have been reported during rifaximin therapy, a warning for its long-term use in cirrhotics. Moreover, a potential interference with vitamin K production should be considered which could further impair the already altered clotting status of these patients. The therapeutic cost of rifaximin is markedly higher than non-absorbable disaccharides. While waiting for further safety data, caution should be used to limit the use of rifaximin therapy for a very short-term period in selected HE cirrhotics not responding to non-absorbable disaccharides. PMID:22966484

  19. Neurosteroids in hepatic encephalopathy: Novel insights and new therapeutic opportunities.

    PubMed

    Butterworth, Roger F

    2016-06-01

    Hepatic encephalopathy (HE) is a serious neuropsychiatric disorder resulting from liver failure. Symptoms of HE include mild cognitive impairment, stupor and coma. Morphological changes to neuroglia (both astrocytes and microglia) occur in HE consisting of cytotoxic brain edema (astrocyte swelling) in acute liver failure and Alzheimer type-2 astrocytosis in cirrhosis. Visual-evoked responses in animals with liver failure and HE manifest striking similarities to those in animals treated with agonists of the GABA-A receptor complex. Neurosteroids are synthesized in brain following activation of translocator protein (TSPO), a mitochondrial neuroglial cholesterol-transporter protein. TSPO sites are activated in both animal models of HE as well as in autopsied brain tissue from HE patients. Activation of TSPO sites results in increased cholesterol transport into the mitochondrion followed by stimulation of a metabolic pathway culminating in the synthesis of allopregnanolone (ALLO) and tetrahydrodeoxycorticosterone (THDOC), neurosteroids with potent positive allosteric modulatory action on the GABA-A receptor complex. Concentrations of ALLO and THDOC in brain tissue from mice with HE resulting from toxic liver injury are sufficient to induce sedation in animals of the same species and significant increases in concentrations of ALLO have been reported in autopsied brain tissue from cirrhotic patients with HE leading to the proposal that "increased GABAergic tone" in HE results from that increased brain concentrations of this neurosteroid. Agents with the potential to decrease neurosteroid synthesis and/or prevent their modulatory actions on the GABA-A receptor complex may provide novel approaches to the management and treatment of HE. Such agents include indomethacin, benzodiazepine receptor inverse agonists and a novel series of compounds known as GABA-A receptor-modulating steroid antagonists (GAMSA). PMID:26589093

  20. Persistence of Cognitive Impairment after Resolution of Overt Hepatic Encephalopathy

    PubMed Central

    Bajaj, Jasmohan S; Schubert, Christine M; Heuman, Douglas M; Wade, James B; Gibson, Douglas P; Topaz, Allyne; Saeian, Kia; Hafeezullah, Muhammad; Bell, Debulon E; Sterling, Richard K; Stravitz, R Todd; Luketic, Velimir; White, Melanie B; Sanyal, Arun J

    2010-01-01

    Background & Aims In patients with cirrhosis, hepatic encephalopathy (HE) has acute but reversible as well as chronic components. We investigated the extent of residual cognitive impairment following clinical resolution of overt HE (OHE). Methods Cognitive function of cirrhotic patients was evaluated using psychometric tests (digit symbol [DS], block design [BD], and number connection [NCT-A&B]) and the inhibitory control test (ICT). Improvement (reduction) in ICT lures and 1st minus 2nd halves (ΔL1–2) were used to determine learning of response inhibition. Two cross-sectional studies (A and B) compared data from stable cirrhotics, with or without prior OHE. We then prospectively assessed cognitive performance, before and after the first episode of OHE. Results In study A, (226 cirrhotic patients) 54 had experienced OHE, 120 had minimal HE and 52 with no minimal HE. Despite normal mental status on lactulose after OHE, cirrhotics were cognitively impaired, based on results from all tests. Learning of response inhibition (ΔL1–2 ≥1), was evident in patients with minimal HE and no minimal HE, but was lost after OHE. In study B (50 additional patients who developed ≥1 documented OHE episode during follow-up), the number of OHE hospitalizations correlated with severity of residual impairment, indicated by ICT lures (r=0.5, P=0.0001), DST (r=−0.39, P=0.002) and NCT-B (r=0.33, P=0.04). In the prospective study (59 cirrhotics without OHE), 15 developed OHE; ICT lure response worsened significantly after OHE (12 before vs.18 after, P=0.0003) and learning of response inhibition was lost. The 44 patients who did not experience OHE did not have deteriorations in cognitive function in serial testing. Conclusion In cirrhosis, episodes of OHE are associated with persistent and cumulative deficits in working memory, response inhibition, and learning. PMID:20178797

  1. Current diagnosis and management of post-transjugular intrahepatic portosystemic shunt refractory hepatic encephalopathy.

    PubMed

    Pereira, Keith; Carrion, Andres F; Martin, Paul; Vaheesan, Kirubahara; Salsamendi, Jason; Doshi, Mehul; Yrizarry, Jose M

    2015-12-01

    Transjugular intrahepatic portosystemic shunt has evolved into an important option for management of complications of portal hypertension. The use of polytetrafluoroethylene covered stents enhances shunt patency. Hepatic encephalopathy (HE) remains a significant problem after TIPS placement. The approach to management of patients with refractory hepatic encephalopathy typically requires collaboration between different specialties. Patient selection for TIPS requires careful evaluation of risk factors for HE. TIPS procedure-related technical factors like stent size, attention to portosystemic pressure gradient reduction and use of adjunctive variceal embolization maybe important. Conservative medical therapy in combination with endovascular therapies often results in resolution or substantial reduction of symptoms. Liver transplantation is, however, the ultimate treatment. PMID:26332169

  2. A New-Onset Rash in the Setting of Rifaximin Treatment for Hepatic Encephalopathy

    PubMed Central

    Adebajo, Corlan; Aronsohn, Andrew; Jensen, Donald M.

    2014-01-01

    We present one of the first cases in the literature to describe an association between Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and rifaximin treatment in a patient with a recent diagnosis of alcoholic hepatitis, stage 2 hepatic encephalopathy, and no known existing allergies. Although SJS/TEN may be a rare reaction with rifaximin, it should be an important clinical consideration. PMID:26157902

  3. A New-Onset Rash in the Setting of Rifaximin Treatment for Hepatic Encephalopathy.

    PubMed

    Fritz, Cassandra D L; Adebajo, Corlan; Aronsohn, Andrew; Jensen, Donald M

    2014-10-01

    We present one of the first cases in the literature to describe an association between Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and rifaximin treatment in a patient with a recent diagnosis of alcoholic hepatitis, stage 2 hepatic encephalopathy, and no known existing allergies. Although SJS/TEN may be a rare reaction with rifaximin, it should be an important clinical consideration. PMID:26157902

  4. How to diagnose and manage hepatic encephalopathy: a consensus statement on roles and responsibilities beyond the liver specialist

    PubMed Central

    Dunk, Arthur A.; Jalan, Rajiv; Kircheis, Gerald; de Knegt, Robert J.; Laleman, Wim; Ramage, John K.; Wedemeyer, Heiner; Morgan, Ian E.J.

    2016-01-01

    Introduction Hepatic encephalopathy is defined as brain dysfunction caused by liver insufficiency and/or portosystemic shunting. Symptoms include nonspecific cognitive impairment, personality changes and changes in consciousness. Overt (symptomatic) hepatic encephalopathy is a common complication of cirrhosis that is associated with a poor prognosis. Patients with hepatic encephalopathy may present to healthcare providers who do not have primary responsibility for management of patients with cirrhosis. Therefore, we developed a series of ‘consensus points’ to provide some guidance on management. Methods Using a modified ‘Delphi’ process, consensus statements were developed that summarize our recommendations for the diagnosis and management of patients with hepatic encephalopathy. Points on which full consensus could not be reached are also discussed. Results Our recommendations emphasize the role of all healthcare providers in the identification of cognitive impairment in patients with cirrhosis and provide guidance on steps that might be considered to make a diagnosis of overt hepatic encephalopathy. In addition, treatment recommendations are summarized. Minimal hepatic encephalopathy can have a significant impact on patients; however, in most circumstances identification and management of minimal hepatic encephalopathy remains the responsibility of specialists in liver diseases. Conclusion Our opinion statements aim to define the roles and responsibilities of all healthcare providers who at times care for patients with cirrhosis and hepatic encephalopathy. We suggest that these recommendations be considered further by colleagues in other disciplines and hope that future guidelines consider the management of patients with cirrhosis and with a ‘suspicion’ of cognitive impairment through to a formal diagnosis of hepatic encephalopathy. PMID:26600154

  5. Toxic encephalopathy due to colchicine--Gloriosa superba poisoning.

    PubMed

    Gooneratne, Inuka Kishara; Weeratunga, Praveen; Caldera, Manjula; Gamage, Ranjanie

    2014-10-01

    Gloriosa superba, a flowering plant widespread in South and Southeast Asia, is implicated in many cases of self-poisoning. Colchicine is concentrated in the seeds and tubers and this mediates its toxicity. We describe a 28-year-old woman who developed delayed encephalopathy after eating G superba tubers. MR scan of brain showed bilateral symmetrical T2 basal ganglia hyperintensities in the caudate and lentiform nuclei. The delay in onset of encephalopathy is attributable to a direct-effect colchicine, probably mediated through its effect on microtubular transport. PMID:24591648

  6. Research progress in hepatic encephalopathy in recent 10 years: A Web of Science-based literature analysis

    PubMed Central

    Li, Nan

    2012-01-01

    OBJECTIVE: To analyze international research trends in hepatic encephalopathy and examine the role of neuroelectrophysiology and neuroimaging in diagnosis of hepatic encephalopathy. DATA RETRIEVAL: We performed a bibliometric analysis of studies on hepatic encephalopathy published during 2002–2011 retrieved from Web of Science. SELECTION CRITERIA: Inclusion criteria: (1) peer-reviewed published articles on hepatic encephalopathy; (2) original article, review, meeting abstract, proceedings paper, book chapter, editorial material, news items, and (3) published during 2002–2011. Exclusion criteria: (1) articles that required manual searching or telephone access; (2) documents that were not published in the public domain; and (3) corrected papers from the total number of articles. MAIN OUTCOME MEASURES: (1) Annual publication output; (2) type of publication; (3) publication by research field; (4) publication by journal; (5) publication by author; (6) publication by institution; (7) publication by country; (8) publication by institution in China; (9) most-cited papers. RESULTS: A total of 3 233 papers regarding hepatic encephalopathy were retrieved during 2002–2011. The number of papers gradually increased over the 10-year study period and was highest in 2010. Most papers appeared in journals with a focus on gastroenterology and hepatology. Among the included journals, Hepatology published the greatest number of papers regarding hepatic encephalopathy, and the published studies were highly cited. Thus, Hepatology appears to represent a key journal publishing papers on hepatic encephalopathy. Regarding distribution by country for publications on hepatic encephalopathy indexed in Web of Science during 2002–2011, the United States published highest number of papers, with China ranked ninth. As per distribution by institute for publications, the University of Montreal in Canada published the highest number of papers (n = 111). Among the Chinese institutes, Zhejiang

  7. The effects of propranolol on hepatic encephalopathy in patients with cirrhosis and portal hypertension.

    PubMed

    Dunk, A A; Moore, J; Symon, A; Dickie, A; Sinclair, T S; Mowat, N A; Brunt, P W

    1988-04-01

    Beta adrenoreceptor blocking drugs have been used for the prevention of haemorrhage from oesophageal varices. However, it is possible that these agents, by virtue of their effects on hepatic blood flow, may impair liver function and precipitate hepatic encephalopathy. We have therefore studied the effect of the beta blocking drug propranolol on hepatic encephalopathy in patients with cirrhosis and portal hypertension. Twenty patients were randomly assigned to receive 4 weeks treatment with propranolol or an identical-looking placebo, the former given in a dose sufficient to reduce resting pulse rate by greater than or equal to 25%. Before and after treatment patients were assessed for the severity of liver disease and the presence of encephalopathy. EEG mean cycle frequency and fasting arterial ammonia concentrations were also measured, and in order to detect latent hepatic encephalopathy, each patient underwent a battery of psychometric tests. Patients were blinded as to their treatment, as were those assessing their responses. Neither propranolol nor placebo had any significant effect on the parameters measured. On propranolol median EEG mean cycle frequency fell from 9.08 ct s-1 (range 8.63-11.0 ct s-1) to 8.73 ct s-1 (range 8.27-11.44 ct s-1), and median fasting arterial ammonia concentration fell from 66 mumol litre-1 (range 40-329 mumol litre-1) to 49 mumol litre-1 (range 37-188 mumol litre-1). Psychometric test values, while initially abnormal and suggestive of latent hepatic encephalopathy in the majority of patients, did not change significantly during the study. PMID:2979240

  8. Infusion of branched-chain enriched amino acid solution in patients with hepatic encephalopathy.

    PubMed

    Freund, H; Dienstag, J; Lehrich, J; Yoshimura, N; Bradford, R R; Rosen, H; Atamian, S; Slemmer, E; Holroyde, J; Fischer, J E

    1982-08-01

    Hospitalized patients with hepatic insufficiency often suffer from severe catabolic states and are in urgent need of nutritional support during their acute illness. Protein intolerence, however, remains a significant problem with respect to the provision of adequate nutrition, either enterally or parenterally. The following report is an anecdotal series of 63 consecutive patients in a large urban hospital treated prospectively with nutritional support using a prototype high branched-chain amino acid solution (FO80) given by technique of total parenteral nutrition by the subclavian or internal jugular route with hypertonic dextrose. Sixty-three patients, of which 42 had chronic liver disease (cirrhosis) with acute decompensation and 17 with acute hepatic injury as well as four with hepatorenal syndrome, are the subject of this report. All required intravenous nutritional support and were either intolerant to commercially available parenteral nutrition solutions or were in hepatic encephalopathy at the time they were initially seen. The cirrhotic patients had been hospitalized for a mean of 14.5 +/- 1.9 days before therapy, had a mean bilirubin of 13 mg/100 ml, and had been in coma for 4.8 +/- 0.7 days despite standard therapy. Patients with acute hepatitis had been in the hospital for 16.2 +/- 4.1 days before therapy, had a mean bilirubin of 25 mg/100 ml, and had been in coma 5.2 +/- 1.6 days before therapy. Routine tests of liver function, blood chemistries, amino acids, EEGs, and complex neurological testing including Reitan trailmaking tests were used in the evaluation of these patients. Up to 120 grams of synthetic amino acid solution with hypertonic dextrose was tolerated in these patients with improvement noted in encephalopathy of at least one grade in 87% of the patients with cirrhosis and 75% of the patients with hepatitis. Nitrogen balance was achieved when 75 to 80 grams of synthetic amino acids were administered. Survival was 45% in the cirrhotic group

  9. Early detection of hepatic encephalopathy by recording visual evoked potential (VEP).

    PubMed

    Zamir, Doron; Storch, Shimon; Kovach, Ivan; Storch, Rita; Zamir, Chen

    2002-01-01

    The visual evoked potential (VEP) record in response to a pattern stimulus is a non invasive and reliable method of detecting central and peripheral nerve system abnormalities. VEP recording have been used in animals with fulminant hepatic failure, and also in-patients with hepatic encephalopathy and acute severe hepatitis. Our aims were: a. to evaluate the potency of PVEP in assessing hepatic encephalopathy. b. to find the rate of pathologic PVEP in patients with advanced liver cirrhosis. VEP was recorded in 14 chronic liver cirrhotic patients (6 alcoholic, 6 HCV-related, 2 cryptogenic) and 14 controls. Patients with any neurologic abnormalities were excluded from the study. All patients were subjected to the Mental State Score (MSS) test, and venous blood ammonia was measured on the same day of VEP recording. In 10/14 (71%) patients some VEP recording abnormality was detected. In the cirrhotic patients, P100 latency was significantly longer (P < 0.05) than in controls. Low amplitude was observed in 8 patients compared to controls. Marked increase of N75 (3 patients) and marked increase of N145 (2 patients) were observed. Mean blood ammonia and MSS score were normal in all patients. No correlation was found between both MSS score and blood ammonia levels and the P100 delay. Five out of 10 patients with pathologic VEP developed hepatic encephalpathy during a follow-up of one year, compared to one out of 4 patients with no pathology on VEP recording. VEP recording may be a valuable tool in assessing patients with early hepatic encephalopathy and in predicting encephalopathy. PMID:12533959

  10. Non-hepatic hyperammonaemia: an important, potentially reversible cause of encephalopathy

    PubMed Central

    Hawkes, N; Thomas, G; Jurewicz, A; Williams, O; Hillier, C; McQueen, I; Shortland, G

    2001-01-01

    The clinical syndrome of encephalopathy is most often encountered in the context of decompensated liver disease and the diagnosis is usually clear cut. Non-hepatic causes of encephalopathy are rarer and tend to present to a wide range of medical specialties with variable and episodic symptoms. Delay can result in the development of potentially life threatening complications, such as seizures and coma.
Early recognition is vital. A history of similar episodes or clinical risk factors and early assessment of blood ammonia levels help establish the diagnosis. In addition to adequate supportive care, investigation of the underlying cause of the hyperammonaemia is essential and its reversal, where possible, will often result in complete recovery. Detection of an unborn error of metabolism should lead to the initiation of appropriate maintenance therapy and genetic counselling.


Keywords: hyperammonaemia; encephalopathy; portosystemic venous shunt; urea cycle defect PMID:11677282

  11. Branched-chain amino acids in the treatment of chronic hepatic encephalopathy.

    PubMed Central

    Eriksson, L S; Persson, A; Wahren, J

    1982-01-01

    The therapeutic efficacy of orally administered branched-chain amino acids in patients with liver cirrhosis and chronic encephalopathy was examined in a double blind, randomised crossover study. Seven patients with manifest hepatic cirrhosis and encephalopathy of six months' duration or longer ingested 30 g branched-chain amino acids or placebo during two 14-day periods. Psychometric tests and electroencephalograms were used to evaluate cerebral function. Neither clinical observations nor psychometric testing or electroencephalogram indicated a significant difference in the patients' response to branched-chain amino acids as compared with placebo. In four patients given branched-chain amino acids for longer periods (five to 22 weeks), psychometric tests also remained unchanged. The plasma concentrations of these acids after oral intake increased significantly, demonstrating adequate absorption. Basal plasma amino acid concentrations were unchanged, however, after branched-chain amino acid therapy. No side-effects were seen, which indicates that these amino acids are well tolerated as an extra protein supply in patients with chronic hepatic encephalopathy. As compared with placebo, however, no effect of branched-chain amino acids on the encephalopathy could be detected. PMID:6749604

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

    PubMed

    Kharb, Sandeep; Gundgurthi, Abhay; Pandit, Aditi; Brar, Karninder S; Garg, M K

    2012-11-01

    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. PMID:23226658

  13. Recent developments in the diagnosis and treatment of covert/minimal hepatic encephalopathy.

    PubMed

    De Rui, M; Montagnese, S; Amodio, P

    2016-04-01

    The terms minimal hepatic encephalopathy and covert hepatic encephalopathy are defined. Clinical assessment is unreliable and both require the use of diagnostic tools. Of these, psychometric tests are the most widely used. They require proper standardization and may be biased by patient cooperation or lack thereof. The measure of the critical flicker frequency and of the electroencephalogram, possibly quantified, are also useful. The alteration of any of them is not strictly parallel in size and may vary from patient to patient. When possible, the use of multiple measures might increase diagnostic reliability. These functional measures should be interpreted within the clinical/biochemical profile of the patient to exclude other disorders. A flow chart for treatment is proposed on the basis of current knowledge. PMID:26758861

  14. Clinical scenarios for the use of S100β as a marker of hepatic encephalopathy

    PubMed Central

    Duarte-Rojo, Andrés; Ruiz-Margáin, Astrid; Macias-Rodriguez, Ricardo U; Cubero, Francisco Javier; Estradas-Trujillo, José; Muñoz-Fuentes, Rosa Ma; Torre, Aldo

    2016-01-01

    AIM: To evaluate the association between serum concentrations of S100β in patients with cirrhosis and the presence of low grade hepatic encephalopathy (HE). METHODS: This was a cross-sectional study. The population was categorized into four groups healthy subjects, cirrhosis without HE, cirrhosis with covert hepatic encephalopathy (CHE) and cirrhosis with overt HE. Kruskal-Wallis, Mann Whitney’s U with Bonferroni adjustment Spearman correlations and area under the ROC were used as appropriate. RESULTS: A total of 61 subjects were included, 46 cirrhotic patients and 15 healthy volunteers. S100β values were different among all groups, and differences remained significant between groups 1 and 2 (P < 0.001), and also between groups 2 and 3 (P = 0.016), but not between groups 3 and 4. In cirrhotic patients with HE S100β was higher than in patients without HE [0.18 (0.14-0.28) ng/mL vs 0.11 (0.06-0.14) ng/mL, P < 0.001]. There was a close correlation between serum concentrations of S100β and psychometric hepatic encephalopathy score in patients with cirrhosis without HE compared to the patients with cirrhosis with CHE (r = -0.413, P = 0.019). ROC curve analysis yielded > 0.13 ng/mL as the best cutoff value of S100β for the diagnosis of HE (sensitivity 83.3%, specificity 63.6%). CONCLUSION: Serum concentrations of S100β are higher in patients with cirrhosis than in healthy volunteers, and are further increased in the presence of hepatic encephalopathy. The results suggest that serum biomarkers such as S100β could help in the correct characterization of incipient stages of HE. PMID:27158209

  15. Comparison of Rifaximin and Lactulose for the Treatment of Hepatic Encephalopathy: A Prospective Randomized Study

    PubMed Central

    Paik, Yong-Han; Han, Kwang-Hyub; Song, Kun Hoon; Kim, Myoung Hwan; Moon, Byung Soo; Ahn, Sang Hoon; Lee, Se Joon; Park, Hyo Jin; Lee, Dong Ki; Chon, Chae Yoon; Lee, Sang In; Moon, Young Myoung

    2005-01-01

    Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p=0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the posttreatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0→4.2, p=0.000); lactulose group (11.3→5.0, p=0.000)). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy. PMID:15988813

  16. Interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in minimal hepatic encephalopathy.

    PubMed

    Llansola, Marta; Montoliu, Carmina; Agusti, Ana; Hernandez-Rabaza, Vicente; Cabrera-Pastor, Andrea; Gomez-Gimenez, Belen; Malaguarnera, Michele; Dadsetan, Sherry; Belghiti, Majedeline; Garcia-Garcia, Raquel; Balzano, Tiziano; Taoro, Lucas; Felipo, Vicente

    2015-09-01

    The cognitive and motor alterations in hepatic encephalopathy (HE) are the final result of altered neurotransmission and communication between neurons in neuronal networks and circuits. Different neurotransmitter systems cooperate to modulate cognitive and motor function, with a main role for glutamatergic and GABAergic neurotransmission in different brain areas and neuronal circuits. There is an interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in HE. This interplay may occur: (a) in different brain areas involved in specific neuronal circuits; (b) in the same brain area through cross-modulation of glutamatergic and GABAergic neurotransmission. We will summarize some examples of the (1) interplay between glutamatergic and GABAergic neurotransmission alterations in different areas in the basal ganglia-thalamus-cortex circuit in the motor alterations in minimal hepatic encephalopathy (MHE); (2) interplay between glutamatergic and GABAergic neurotransmission alterations in cerebellum in the impairment of cognitive function in MHE through altered function of the glutamate-nitric oxide-cGMP pathway. We will also comment the therapeutic implications of the above studies and the utility of modulators of glutamate and GABA receptors to restore cognitive and motor function in rats with hyperammonemia and hepatic encephalopathy. PMID:25447766

  17. Creutzfeldt-Jakob-Like Syndrome due to Hypercalcemic Encephalopathy.

    PubMed

    Rösche, Johannes; Sieveking, Catharina; Kampf, Christina; Benecke, Reiner

    2015-10-01

    Hypercalcemia can cause a subacute syndrome of progressive dementia and marked changes in the electroencephalogram (EEG). We report a case of iatrogenic hypercalcemia with a close correlation between the clinical course and the EEG changes. A 73-year-old woman presented with a subacute syndrome of progressive dementia and bursts of 1.5 to 2 Hz intermittent rhythmic delta activity superimposed on a low-voltage background activity in the EEG. Clinical and EEG abnormalities rapidly resolved after normalization of serum calcium levels. As part of the diagnostic workup of a subacute progressive dementia, a serum calcium level and an EEG should be obtained to detect a Creutzfeldt-Jakob like syndrome in hypercalcemia. Unlike in Creutzfeldt-Jakob disease, and Creutzfeldt-Jakob-like syndrome induced by lithium intoxication, there are rarely myoclonic jerks and periodic discharges in hypercalcemic encephalopathy. PMID:24973231

  18. Impact of depressive symptoms and hepatic encephalopathy on health-related quality of life in cirrhotic hepatitis C patients.

    PubMed

    Barboza, Katherine C; Salinas, Lilian M; Sahebjam, Farhad; Jesudian, Arun B; Weisberg, Ilan L; Sigal, Samuel H

    2016-08-01

    Depression, common in chronic medical conditions, and hepatic encephalopathy (HE), a reversible neuropsychiatric syndrome due to liver dysfunction, are associated with impaired health-related quality of life (HRQOL) in cirrhosis and hepatitis C (HCV). This study investigated the impact of depression and HE on HRQOL in cirrhotic patients with HCV. A convenience sample of 43 ambulatory patients, with varying degrees of cirrhosis secondary to HCV, was prospectively enrolled in this study. Participants were assessed for any current depressive, fatigue, and daytime sleepiness symptoms and underwent a psychometric evaluation to determine the presence of HE symptoms. Participants reported current HRQOL on general health and liver disease-specific questionnaires. Diagnosis and current health status were confirmed via medical records. The associations between disease severity, depressive symptoms, HE, fatigue, and daytime sleepiness were measured. Predictors of HRQOL in this sample were determined. Depressive symptoms (70 %) and HE (77 %) were highly prevalent in this sample, with 58 % actively experiencing both conditions at the time of study participation. A significant positive association was found between depressive symptoms and HE severity (P = .05). Depressive symptoms were significantly associated with fatigue (P < .001), daytime sleepiness (P < .001), general HRQOL (P < .001), and disease-specific HRQOL (P < .001). HE was significantly associated with fatigue (P = .02), general HRQOL (P < .001), and disease-specific HRQOL (P < .001). Depressive symptoms and HE were significant predictors of reduced HRQOL (P < .001), with depressive symptoms alone accounting for 58.8 % of the variance. Depressive symptoms and HE accounted for 68.0 % of the variance. Findings suggest a possible pathophysiological link between depression and HE in cirrhosis, and potentially a wider-reaching benefit of treating minimal and overt HE than previously appreciated

  19. HCV encephalopathy - an artefact due to medical care?

    PubMed

    Weissenborn, K; Tillmann, H L

    2016-08-01

    Anti-HCV positive individuals frequently complain about chronic disabling fatigue, mood alterations and deficits in concentration and memory. Several data provide evidence that such alterations are unrelated to hepatitis C virus (HCV) viremia. Thus, merely being exposed to HCV in the past may be sufficient to trigger, but the HCV exposure itself. This commentary reviews the available data upon this topic with special reference to the paper by Lowry and colleagues published in this issue of the Journal of Viral hepatitis. We will carefully discuss scientific reasons, why HCV may be directly involved in the development of neuropsychiatric symptoms independent from ongoing detectable viremia, as suggested by epidemiological data. PMID:27225063

  20. Mechanisms of cognitive alterations in hyperammonemia and hepatic encephalopathy: therapeutical implications.

    PubMed

    Monfort, Pilar; Cauli, Omar; Montoliu, Carmina; Rodrigo, Regina; Llansola, Marta; Piedrafita, Blanca; El Mlili, Nisrin; Boix, Jordi; Agustí, Ana; Felipo, Vicente

    2009-01-01

    Patients with liver diseases (e.g. cirrhosis) may present hepatic encephalopathy (HE), an alteration in cerebral function which is a consequence of previous failure of liver function. Patients with minimal or clinical HE present different levels of cognitive impairment. Hyperammonemia is considered a main contributor to the neurological alterations in HE. Animal models of chronic HE (e.g. rats with portacaval shunts) or of "pure" hyperammonemia also show impaired cognitive function. The studies summarized here show that the impairment of some types of cognitive function in chronic HE is due to the impaired function of the glutamate-nitric oxide-cGMP pathway in brain. Both hyperammonemia and neuroinflammation contribute to the impairment of the pathway and of cognitive function. Treatment of rats with chronic HE or hyperammonemia with inhibitors of phosphodiesterase 5 restores the function of the glutamate-nitric oxide-cGMP pathway and cGMP levels in brain as well as the ability to learn a Y maze conditional discrimination task. The same beneficial effects may be obtained by treating the rats chronically with an anti-inflammatory, ibuprofen. As the function of this pathway is also altered in brain of patients died in HE, this alteration would also contribute to cognitive impairment in patients with HE. Increasing cGMP by using inhibitors of phosphodiesterase 5 (PDE-5) or anti-inflammatories (under safe conditions) would be therefore a new therapeutic approach to improve learning and memory performance in individuals with minimal or clinical HE. PMID:19428813

  1. Functional brain network changes associated with clinical and biochemical measures of the severity of hepatic encephalopathy.

    PubMed

    Jao, Tun; Schröter, Manuel; Chen, Chao-Long; Cheng, Yu-Fan; Lo, Chun-Yi Zac; Chou, Kun-Hsien; Patel, Ameera X; Lin, Wei-Che; Lin, Ching-Po; Bullmore, Edward T

    2015-11-15

    Functional properties of the brain may be associated with changes in complex brain networks. However, little is known about how properties of large-scale functional brain networks may be altered stepwise in patients with disturbance of consciousness, e.g., an encephalopathy. We used resting-state fMRI data on patients suffering from various degrees of hepatic encephalopathy (HE) to explore how topological and spatial network properties of functional brain networks changed at different cognitive and consciousness states. Severity of HE was measured clinically and by neuropsychological tests. Fifty-eight non-alcoholic liver cirrhosis patients and 62 normal controls were studied. Patients were subdivided into liver cirrhosis with no outstanding HE (NoHE, n=23), minimal HE with cognitive impairment only detectable by neuropsychological tests (MHE, n=28), and clinically overt HE (OHE, n=7). From the earliest stage, the NoHE, functional brain networks were progressively more random, less clustered, and less modular. Since the intermediate stage (MHE), increased ammonia level was accompanied by concomitant exponential decay of mean connectivity strength, especially in the primary cortical areas and midline brain structures. Finally, at the OHE stage, there were radical reorganization of the topological centrality-i.e., the relative importance-of the hubs and reorientation of functional connections between nodes. In summary, this study illustrated progressively greater abnormalities in functional brain network organization in patients with clinical and biochemical evidence of more severe hepatic encephalopathy. The early-than-expected brain network dysfunction in cirrhotic patients suggests that brain functional connectivity and network analysis may provide useful and complementary biomarkers for more aggressive and earlier intervention of hepatic encephalopathy. Moreover, the stepwise deterioration of functional brain networks in HE patients may suggest that hierarchical

  2. [Hepatitis due to herpes group viruses].

    PubMed

    Cisneros-Herreros, José M; Herrero-Romero, Marta

    2006-01-01

    In immunocompetent patients, primary infection by herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6, and Epstein-Barr virus (EBV) generally produces mild, self-limited hepatitis. Primary infection by HSV in neonates and pregnant women, and infection by VZV in hematological and bone marrow recipients can cause fulminant hepatitis without characteristic skin lesions. In liver transplant recipients, hepatitis is the most common expression of CMV infection and the related symptoms are indistinguishable from those of acute rejection. Persistent hepatitis is a manifestation of the syndrome of active chronic infection by the EBV. Fulminating hepatitis due to herpes virus can be treated effectively if therapy is started early; hence, a high degree of clinical suspicion and inclusion of herpes virus in the differential diagnosis of this syndrome is necessary. PMID:16792943

  3. Brainstem evoked response audiometry: an investigatory tool in detecting hepatic encephalopathy in decompensated chronic liver disease.

    PubMed

    Kabali, Balasubramanian; Velayutham, Gowri; Kapali, Suresh Chander

    2014-01-01

    It is estimated that globally there is a marked increase in liver disease with reports of rising morbidity and mortality, particularly in younger age groups. Brainstem auditory evoked potential (BAEP) was recorded in 60 decompensated chronic liver disease (DCLD) subjects who fulfilled the selection criteria and compared to 60 age and gender matched healthy subjects with normal liver functions. DCLD subjects were divided into two inter groups based on presence or absence of hepatic encephalopathy (HE). Group 1 comprises of 30 subjects of grade- I HE and Group 2 included 30 subjects without hepatic encephalopathy (NHE). Absolute and interpeak wave latencies were measured. Results were analysed by student independent t- test using SPSS software 11 version. Statistical significance was tested using P value. From the present study it can be concluded that the central nervous system is involved in liver cirrhosis evidenced by an abnormal BAEP latencies parameters. This shows that there may be progressive demyelination occurring along with axonal loss or dysfunction in liver cirrhosis HE. This study suggests that periodic evaluation of cirrhotic individuals to such test will help in monitoring the progress of encephalopathy. The prime goal of this study is early diagnosis and initiation of treatment before the onset of coma can reduce the fatality rate. PMID:25508308

  4. Brainstem evoked response audiometry: an investigatory tool in detecting hepatic encephalopathy in decompensated chronic liver disease.

    PubMed

    Kabali, Balasubramanian; Velayutham, Gowri; Kapali, Suresh Chander

    2014-01-01

    It is estimated that globally there is a marked increase in liver disease with reports of rising morbidity and mortality, particularly in younger age groups. Brainstem auditory evoked potential (BAEP) was recorded in 60 decompensated chronic liver disease (DCLD) subjects who fulfilled the selection criteria and compared to 60 age and gender matched healthy subjects with normal liver functions. DCLD subjects were divided into two inter groups based on presence or absence of hepatic encephalopathy (HE). Group 1 comprises of 30 subjects of grade- I HE and Group 2 included 30 subjects without hepatic encephalopathy (NHE). Absolute and interpeak wave latencies were measured. Results were analysed by student independent t- test using SPSS software 11 version. Statistical significance was tested using P value. From the present study it can be concluded that the central nervous system is involved in liver cirrhosis evidenced by an abnormal BAEP latencies parameters. This shows that there may be progressive demyelination occurring along with axonal loss or dysfunction in liver cirrhosis HE. This study suggests that periodic evaluation of cirrhotic individuals to such test will help in monitoring the progress of encephalopathy. The prime goal of this study is early diagnosis and initiation of treatment before the onset of coma can reduce the fatality rate. PMID:25464677

  5. Screening for minimal hepatic encephalopathy in patients with cirrhosis by cirrhosis-related symptoms and a history of overt hepatic encephalopathy

    PubMed Central

    Yoshimura, Emi; Ichikawa, Tatsuki; Miyaaki, Hisamitsu; Taura, Naota; Miuma, Satoshi; Shibata, Hidataka; Honda, Takuya; Takeshima, Fuminao; Nakao, Kazuhiko

    2016-01-01

    The diagnosis of minimal hepatic encephalopathy (MHE) is more difficult in comparison to the diagnosis of overt hepatic encephalopathy (OHE), as patients with MHE do not exhibit overt neurological deficits and must be diagnosed using specialized equipment. However, identifying MHE is critical for patients with cirrhosis, and a simple screening test is required. The present study aimed to evaluate the associations between MHE, clinical characteristics and questionnaire items regarding sleep disturbances and cirrhosis-related symptom score (CSS). A total of 91 patients who had cirrhosis without OHE were evaluated using various questionnaires [i.e., CSS, Epworth Sleepiness Scale, the Japanese version of the Pittsburgh Sleep Quality Index (PSQI) and the Japanese 36-item short-form health survey (SF-36)]. MHE was diagnosed using the neuropsychological test. MHE was associated with severe liver damage, which was indicated by liver damage markers and a history of OHE. In addition, MHE was associated with the CSS, PSQI and SF-36 results. The multivariate analyses revealed that a history of OHE was the factor that was the most strongly associated with MHE. Among patients without a history of OHE, MHE was most strongly associated with CSS, although it was also associated with severe liver damage and platelet counts. A prediction score (calculated using a history of OHE and CSS) provided an area under the receiver operating characteristic curve of 0.738 and a sensitivity of 0.671 for identifying MHE. In conclusion, a history of OHE and CSS may be useful for identifying MHE in patients with cirrhosis. PMID:27446540

  6. Cortical signature of patients with HBV-related cirrhosis without overt hepatic encephalopathy: a morphometric analysis.

    PubMed

    Wu, Xiu; Lv, Xiao-Fei; Zhang, Yu-Ling; Wu, Hua-Wang; Cai, Pei-Qiang; Qiu, Ying-Wei; Zhang, Xue-Lin; Jiang, Gui-Hua

    2015-01-01

    Previous studies have shown that patients with hepatitis B virus-related cirrhosis (HBV-RC) without overt hepatic encephalopathy (OHE) are associated with a varying degree of cognitive dysfunction. Several resting-state functional magnetic resonance imaging (fMRI) studies have been conducted to explore the neural correlates of such cognitive deficits, whereas little effort has been made to investigate the cortical integrity in cirrhotic patients without OHE. Here, using cortical thickness, surface area and local gyrification index (lGI), this study performed a comprehensive analysis on the cortical morphometry of patients with HBV-RC without OHE (HBV-RC-NOHE) vs. matched healthy controls. Compared with healthy controls, we found significantly increased cortical thickness in the bilateral lingual and parahippocampal gyrus, right posterior cingulate cortex, precuneus, peri-calcarine sulcus and fusiform gyrus in patient with HBV-RC-NOHE, which may closely relate to be the low-grade brain edema. Cortical gyrification analysis showed significantly increased lGI in the left superior and inferior parietal cortex as well as lateral occipital cortex, which was speculated to be associated with disruptions in white matter connectivity and sub-optimal intra-cortical organization. In addition, the mean cortical thickness/lGI of the regions with structural abnormalities was shown to be negatively correlated with psychometric hepatic encephalopathy score (PHES) of the patients with HBV-RC-NOHE. These morphological changes may serve as potential markers for the preclinical diagnosis and progression of HBV-RC-NOHE. PMID:26106307

  7. Cortical signature of patients with HBV-related cirrhosis without overt hepatic encephalopathy: a morphometric analysis

    PubMed Central

    Wu, Xiu; Lv, Xiao-Fei; Zhang, Yu-Ling; Wu, Hua-Wang; Cai, Pei-Qiang; Qiu, Ying-Wei; Zhang, Xue-Lin; Jiang, Gui-Hua

    2015-01-01

    Previous studies have shown that patients with hepatitis B virus-related cirrhosis (HBV-RC) without overt hepatic encephalopathy (OHE) are associated with a varying degree of cognitive dysfunction. Several resting-state functional magnetic resonance imaging (fMRI) studies have been conducted to explore the neural correlates of such cognitive deficits, whereas little effort has been made to investigate the cortical integrity in cirrhotic patients without OHE. Here, using cortical thickness, surface area and local gyrification index (lGI), this study performed a comprehensive analysis on the cortical morphometry of patients with HBV-RC without OHE (HBV-RC-NOHE) vs. matched healthy controls. Compared with healthy controls, we found significantly increased cortical thickness in the bilateral lingual and parahippocampal gyrus, right posterior cingulate cortex, precuneus, peri-calcarine sulcus and fusiform gyrus in patient with HBV-RC-NOHE, which may closely relate to be the low-grade brain edema. Cortical gyrification analysis showed significantly increased lGI in the left superior and inferior parietal cortex as well as lateral occipital cortex, which was speculated to be associated with disruptions in white matter connectivity and sub-optimal intra-cortical organization. In addition, the mean cortical thickness/lGI of the regions with structural abnormalities was shown to be negatively correlated with psychometric hepatic encephalopathy score (PHES) of the patients with HBV-RC-NOHE. These morphological changes may serve as potential markers for the preclinical diagnosis and progression of HBV-RC-NOHE. PMID:26106307

  8. Longitudinal brain white matter alterations in minimal hepatic encephalopathy before and after liver transplantation.

    PubMed

    Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chao-Long; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Huang, Chu-Chung; Lin, Ching-Po; Cheng, Yu-Fan

    2014-01-01

    Cerebral edema is the common pathogenic mechanism for cognitive impairment in minimal hepatic encephalopathy. Whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved after liver transplantation remains an open question. To characterize white matter integrity before and after liver transplantation in patients with minimal hepatic encephalopathy, multiple diffusivity indices acquired via diffusion tensor imaging was applied. Twenty-eight patients and thirty age- and sex-matched healthy volunteers were included. Multiple diffusivity indices were obtained from diffusion tensor images, including mean diffusivity, fractional anisotropy, axial diffusivity and radial diffusivity. The assessment was repeated 6-12 month after transplantation. Differences in white matter integrity between groups, as well as longitudinal changes, were evaluated using tract-based spatial statistical analysis. Correlation analyses were performed to identify first scan before transplantation and interval changes among the neuropsychiatric tests, clinical laboratory tests, and diffusion tensor imaging indices. After transplantation, decreased water diffusivity without fractional anisotropy change indicating reversible cerebral edema was found in the left anterior cingulate, claustrum, postcentral gyrus, and right corpus callosum. However, a progressive decrease in fractional anisotropy and an increase in radial diffusivity suggesting demyelination were noted in temporal lobe. Improved pre-transplantation albumin levels and interval changes were associated with better recoveries of diffusion tensor imaging indices. Improvements in interval diffusion tensor imaging indices in the right postcentral gyrus were correlated with visuospatial function score correction. In conclusion, longitudinal voxel-wise analysis of multiple diffusion tensor imaging indices demonstrated different white matter changes in minimal hepatic encephalopathy patients

  9. Refining the ammonia hypothesis: a physiology-driven approach to the treatment of hepatic encephalopathy.

    PubMed

    Tapper, Elliot B; Jiang, Z Gordon; Patwardhan, Vilas R

    2015-05-01

    Hepatic encephalopathy (HE) is one of the most important complications of cirrhosis and portal hypertension. Although the etiology is incompletely understood, it has been linked to ammonia directly and indirectly. Our goal is to review for the clinician the mechanisms behind hyperammonemia and the pathogenesis of HE to explain the rationale for its therapy. We reviewed articles collected through a search of MEDLINE/PubMed, Cochrane Database of Systematic Reviews, and Google Scholar between October 1, 1948, and December 8, 2014, and by a manual search of citations within retrieved articles. Search terms included hepatic encephalopathy, ammonia hypothesis, brain and ammonia, liver failure and ammonia, acute-on-chronic liver failure and ammonia, cirrhosis and ammonia, portosytemic shunt, ammonia and lactulose, rifaximin, zinc, and nutrition. Ammonia homeostatsis is a multiorgan process involving the liver, brain, kidneys, and muscle as well as the gastrointestinal tract. Indeed, hyperammonemia may be the first clue to poor functional reserves, malnutrition, and impending multiorgan dysfunction. Furthermore, the neuropathology of ammonia is critically linked to states of systemic inflammation and endotoxemia. Given the complex interplay among ammonia, inflammation, and other factors, ammonia levels have questionable utility in the staging of HE. The use of nonabsorbable disaccharides, antibiotics, and probiotics reduces gut ammoniagenesis and, in the case of antibiotics and probiotics, systemic inflammation. Nutritional support preserves urea cycle function and prevents wasting of skeletal muscle, a significant site of ammonia metabolism. Correction of hypokalemia, hypovolemia, and acidosis further assists in the reduction of ammonia production in the kidney. Finally, early and aggressive treatment of infection, avoidance of sedatives, and modification of portosystemic shunts are also helpful in reducing the neurocognitive effects of hyperammonemia. Refining the

  10. Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt in Patients with Recurrent Variceal Hemorrhage

    PubMed Central

    Peter, Popovič; Andrej, Zore; Katarina, Šurlan Popovič; Manca, Garbajs; Pavel, Skok

    2013-01-01

    Purpose. The purpose of this study was to determine the incidence and predictors of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) and endoscopic therapy (ET) in the elective treatment of recurrent variceal hemorrhage. Methods. Seventy patients were treated with elective TIPS and fifty-six patients with ET. Median observation time was 46.28 months in the TIPS group and 42.31 months in the ET group. Results. 30 patients (42.8%) developed clinically evident portosystemic encephalopathy in TIPS group and 20 patients (35.6%) in ET group. The difference between the groups was not statistically significant (P = 0.542; χ2 test). The incidence of new or worsening portosystemic encephalopathy was 24.3% in TIPS group and 10.7% in ET group. Multivariate analysis showed that ET treatment (P = 0.031), age of >65 years (P = 0.022), pre-existing HE (P = 0.045), and Child's class C (P = 0.051) values were independent predictors for the occurrence of HE. Conclusions. Procedure-related HE is a complication in a minority of patients treated with TIPS or ET. Patients with increased age, preexisting HE, and higher Child-Pugh score should be carefully observed after TIPS procedure because the risk of post-TIPS HE in these patients is higher. PMID:23606833

  11. Ammonia-induced senescence in cultured rat astrocytes and in human cerebral cortex in hepatic encephalopathy.

    PubMed

    Görg, Boris; Karababa, Ayse; Shafigullina, Aygul; Bidmon, Hans J; Häussinger, Dieter

    2015-01-01

    Hepatic encephalopathy (HE) is a frequent complication of liver cirrhosis and is due to a low-grade cerebral edema associated with oxidative/nitrosative stress. Recent reports suggest that cognitive impairment in cirrhotic patients may not resolve completely after an attack of manifest HE. As astrocyte dysfunction is central to the pathogenesis of HE and astrocytes are critically involved in synaptic plasticity, we tested for sustained impairment of astrocyte function by analyzing expression levels of senescence biomarkers in ammonia-treated cultured rat astrocytes and in postmortem brain samples from cirrhotic patients with or without HE. NH4 Cl time- and dose-dependently inhibited proliferation of cultured astrocytes by up to 45% (5 mmol/L, 72 h) and strongly increased senescence-associated β-galactosidase activity. Inhibition of astrocyte proliferation by ammonia was mediated by a l-methionine sulfoximine-, oxidative stress-, and p38(MAPK) -dependent activation of p53 associated with enhanced transcription of cell cycle inhibitory genes GADD45α and p21. Mitochondria and the nucleus were identified as sources of oxygen radical formation after prolonged NH4 Cl exposure. Concurrently, NH4 Cl (5 mmol/L) treatment inhibited both epidermal growth factor- and brain-derived neurotrophic factor (BDNF)-induced proliferation as well as BDNF-mediated astrocyte morphology changes through downregulation of the respective growth factor receptors epidermal growth factor receptor and truncated tyrosine receptor kinase B. Increased mRNA expression levels of senescence-associated genes were also found in post mortem brain samples from patients with liver cirrhosis with HE, but not in those without HE. The data suggest that ammonia toxicity and HE are associated with premature astrocyte senescence, which may impair neurotransmission and contribute to persistence of cognitive disturbances after resolution of episodes of overt HE. PMID:25092802

  12. Embolization of Portosystemic Shunts for Treatment of Medically Refractory Hepatic Encephalopathy

    PubMed Central

    Lynn, Amanda M.; Singh, Siddharth; Congly, Stephen E.; Khemani, Disha; Johnson, David H.; Wiesner, Russell H.; Kamath, Patrick S.; Andrews, James C.; Leise, Michael D.

    2016-01-01

    Treatment options for refractory hepatic encephalopathy (HE) are limited. Patients who fail medical management may harbor large portosystemic shunts (PSSs) which are possible therapeutic targets. This study aims to describe patient selection, effectiveness, and safety of percutaneous PSS embolization in those with medically refractory HE. A retrospective evaluation of consecutive adult patients with medically refractory HE referred for PSS embolization at a tertiary center was performed (2003–2015). Patient data collected included the type of HE, medications, Model for End-Stage Liver Disease (MELD) score, shunt type, embolization approach, and materials used. Outcomes of interest were immediate (7 days), intermediate (1–4 months), and longer-term (6–12 months) effectiveness and periprocedural safety. Effectiveness was determined based on changes in hospitalization frequency, HE medications, and symptoms. Twenty-five patients with large PSS were evaluated for shunt embolization. Five were excluded due to high MELD scores (n = 1), comorbid conditions (n = 1), or technical considerations (n = 3). Of 20 patients who underwent embolization, 13 had persistent and 7 had recurrent HE; 100% (20/20) achieved immediate improvement. Durable benefit was achieved in 100% (18/18) and 92% (11/12) at 1–4 and 6–12 months, respectively. The majority (67%; 8/12) were free from HE-related hospitalizations over 1 year; 10% developed procedural complications, and all resolved. Six developed new or worsening ascites. In conclusion, PSS embolization is a safe and effective treatment strategy that should be considered for select patients with medically refractory HE. PMID:26970243

  13. Efficacy of liver assisting in patients with hepatic encephalopathy with special focus on plasma exchange.

    PubMed

    Stenbøg, Poul; Busk, Troels; Larsen, Fin Stolze

    2013-06-01

    Severe liver injury result in development of hepatic encephalopathy (HE) and often also in brain edema that is a potentially fatal complication. HE and brain edema are correlated to the level and persistence of hyperammonemia and the presence of systemic inflammation. Treatment of HE and brain edema is based on restoring and keeping normal physiological variables including tonicity, blood gasses, lactate, temperature and vascular resistance by a wide variety of interventions. In addition liver support devices improve the stage of HE, cerebral metabolic rate for oxygen and glucose, and are used either as a bridge to liver transplantation or liver recovery in patients with fulminant hepatic failure and in patients with acute-on-chronic liver failure. This short review will mainly focus on the management and efficacy of doing plasma exchange on HE in patients with acute HE. PMID:23572273

  14. Generalized chorea due to delayed encephalopathy after acute carbon monoxide intoxication

    PubMed Central

    Sung, Yueh-Feng; Chen, Ming-Hua; Peng, Giia-Sheun; Lee, Jiunn-Tay

    2015-01-01

    Movement disorder due to delayed encephalopathy after carbon monoxide (CO) intoxication is uncommon. Generalized chorea, presenting as an initial symptom of delayed encephalopathy, is extremely rare. We describe a 60-year-old woman, who had completely recovered from acute CO poisoning, developed mental and behavioral changes, urinary incontinence and generalized chorea 2 weeks thereafter. T2-weighted brain magnetic resonance imaging showed extensive hyperintensity of the bilateral periventricular and subcortical white matter and the globus pallidus. Brain single-photon emission computed tomography (SPECT) with technetium-99 ethylene cysteine dimer showed inhomogeneous perfusion in the cerebral cortex, with decreased uptake in bilateral frontal regions. Delayed encephalopathy after acute CO intoxication was diagnosed, and the symptoms gradually improved after hyperbaric oxygen therapy (HBOT). This case report demonstrates that generalized chorea may be one of the initial presenting symptoms of delayed encephalopathy after acute CO intoxication. We hypothesize that the generalized chorea in our patient may have been caused by the subcortical white matter lesions, which most likely interrupted the basal ganglia-thalamocortical circuits and that HBOT may be the treatment of choice for such patients. PMID:25745326

  15. Generalized chorea due to delayed encephalopathy after acute carbon monoxide intoxication.

    PubMed

    Sung, Yueh-Feng; Chen, Ming-Hua; Peng, Giia-Sheun; Lee, Jiunn-Tay

    2015-01-01

    Movement disorder due to delayed encephalopathy after carbon monoxide (CO) intoxication is uncommon. Generalized chorea, presenting as an initial symptom of delayed encephalopathy, is extremely rare. We describe a 60-year-old woman, who had completely recovered from acute CO poisoning, developed mental and behavioral changes, urinary incontinence and generalized chorea 2 weeks thereafter. T2-weighted brain magnetic resonance imaging showed extensive hyperintensity of the bilateral periventricular and subcortical white matter and the globus pallidus. Brain single-photon emission computed tomography (SPECT) with technetium-99 ethylene cysteine dimer showed inhomogeneous perfusion in the cerebral cortex, with decreased uptake in bilateral frontal regions. Delayed encephalopathy after acute CO intoxication was diagnosed, and the symptoms gradually improved after hyperbaric oxygen therapy (HBOT). This case report demonstrates that generalized chorea may be one of the initial presenting symptoms of delayed encephalopathy after acute CO intoxication. We hypothesize that the generalized chorea in our patient may have been caused by the subcortical white matter lesions, which most likely interrupted the basal ganglia-thalamocortical circuits and that HBOT may be the treatment of choice for such patients. PMID:25745326

  16. Rifaximin versus Nonabsorbable Disaccharides for the Treatment of Hepatic Encephalopathy: A Meta-Analysis

    PubMed Central

    Wu, Dong; Wu, Shu-Mei; Lu, Jie; Zhou, Ying-Qun; Xu, Ling; Guo, Chuan-Yong

    2013-01-01

    Background. Many studies have found that the antibiotic rifaximin is effective for the treatment of hepatic encephalopathy. However, there is no uniform view on the efficacy and safety of rifaximin. Methods. We performed a meta-analysis through electronic searches to evaluate the efficacy and safety of rifaximin in comparison with nonabsorbable disaccharides. Results. A total of 8 randomized controlled trials including 407 patients were included. The efficacy of rifaximin was equivalent to nonabsorbable disaccharides according to the statistical data (risk ratio (RR): 1.06, 95% CI: 0.94–1.19; P = 0.34). Analysis showed that patients treated with rifaximin had better results in serum ammonia levels (weighted mean difference (WMD): −10.63, 95% CI: −30.63–9.38; P = 0.30), mental status (WMD: −0.32, 95% CI: −0.67–0.03; P = 0.07), asterixis (WMD: −0.12, 95% CI: −0.31–0.08; P = 0.23), electroencephalogram response (WMD: −0.21, 95% CI: −0.34–−0.09; P = 0.0007), and grades of portosystemic encephalopathy (WMD: −2.30, 95% CI: −2.78–−1.82; P < 0.00001), but only the last ones had statistical significance. The safety of rifaximin was better than nonabsorbable disaccharides (RR: 0.19, 95% CI: 0.10–0.34; P < 0.00001). Conclusion. Rifaximin is at least as effective as nonabsorbable disaccharides, maybe better for the treatment of hepatic encephalopathy. And the safety of rifaximin is better. PMID:23653636

  17. Rifaximin versus Nonabsorbable Disaccharides for the Treatment of Hepatic Encephalopathy: A Meta-Analysis.

    PubMed

    Wu, Dong; Wu, Shu-Mei; Lu, Jie; Zhou, Ying-Qun; Xu, Ling; Guo, Chuan-Yong

    2013-01-01

    Background. Many studies have found that the antibiotic rifaximin is effective for the treatment of hepatic encephalopathy. However, there is no uniform view on the efficacy and safety of rifaximin. Methods. We performed a meta-analysis through electronic searches to evaluate the efficacy and safety of rifaximin in comparison with nonabsorbable disaccharides. Results. A total of 8 randomized controlled trials including 407 patients were included. The efficacy of rifaximin was equivalent to nonabsorbable disaccharides according to the statistical data (risk ratio (RR): 1.06, 95% CI: 0.94-1.19; P = 0.34). Analysis showed that patients treated with rifaximin had better results in serum ammonia levels (weighted mean difference (WMD): -10.63, 95% CI: -30.63-9.38; P = 0.30), mental status (WMD: -0.32, 95% CI: -0.67-0.03; P = 0.07), asterixis (WMD: -0.12, 95% CI: -0.31-0.08; P = 0.23), electroencephalogram response (WMD: -0.21, 95% CI: -0.34--0.09; P = 0.0007), and grades of portosystemic encephalopathy (WMD: -2.30, 95% CI: -2.78--1.82; P < 0.00001), but only the last ones had statistical significance. The safety of rifaximin was better than nonabsorbable disaccharides (RR: 0.19, 95% CI: 0.10-0.34; P < 0.00001). Conclusion. Rifaximin is at least as effective as nonabsorbable disaccharides, maybe better for the treatment of hepatic encephalopathy. And the safety of rifaximin is better. PMID:23653636

  18. Ibuprofen hepatic encephalopathy, hepatomegaly, gastric lesion and gastric pentadecapeptide BPC 157 in rats.

    PubMed

    Ilic, Spomenko; Drmic, Domagoj; Zarkovic, Kamelija; Kolenc, Danijela; Brcic, Luka; Radic, Bozo; Djuzel, Viktor; Blagaic, Alenka Boban; Romic, Zeljko; Dzidic, Senka; Kalogjera, Livije; Seiwerth, Sven; Sikiric, Predrag

    2011-09-30

    Chronic ibuprofen (0.4 g/kg intraperitoneally, once daily for 4 weeks) evidenced a series of pathologies, not previously reported in ibuprofen-dosed rats, namely hepatic encephalopathy, gastric lesions, hepatomegaly, increased AST and ALT serum values with prolonged sedation/unconsciousness, and weight loss. In particular, ibuprofen toxicity was brain edema, particularly in the cerebellum, with the white matter being more affected than in gray matter. In addition, damaged and red neurons, in the absence of anti-inflammatory reaction was observed, particularly in the cerebral cortex and cerebellar nuclei, but was also present although to a lesser extent in the hippocampus, dentate nucleus and Purkinje cells. An anti-ulcer peptide shown to have no toxicity, the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, 10 μg, 10 ng/kg) inhibited the pathology seen with ibuprofen (i) when given intraperitoneally, immediately after ibuprofen daily or (ii) when given in drinking water (0.16 μg, 0.16 ng/ml). Counteracted were all adverse effects, such as hepatic encephalopathy, the gastric lesions, hepatomegaly, increased liver serum values. In addition, BPC 157 treated rats showed no behavioral disturbances and maintained normal weight gain. Thus, apart from efficacy in inflammatory bowel disease and various wound treatments, BPC 157 was also effective when given after ibuprofen. PMID:21645505

  19. Hepatic Encephalopathy With Corticospinal Tract Involvement Demonstrated by Diffusion Tensor Tractography

    PubMed Central

    Bang, Hyun; Lee, Hye Yeon; Kim, Bo-Ram; Lee, In-Sik; Jung, Heeyoune; Koh, Seong-Eun

    2015-01-01

    A 50-year-old man with liver cirrhosis and esophageal varix for 3 years was diagnosed with hematemesis and treated for a bleeding varix. However, bleeding recurred 11 days later, and he developed drowsiness with left hemiparesis. His left upper and lower extremity muscle strengths based on the manual muscle test at the onset were grade 2/5 and 1/5, respectively. The Babinski sign was positive. His serum ammonia level was elevated to 129.9 µg/dL (normal, 20-80 µg/dL). Magnetic resonance imaging revealed restriction on diffusion and T2-hyperintensities with decreased apparent diffusion coefficient values in the bilateral frontoparietooccipital cortex. The effect was more severe in the right hemisphere and right parietooccipital cortices, which were compatible with hepatic encephalopathy. Although the patient's mental status recovered, significant left-sided weakness and sensory deficit persisted even after 6 months. Diffusion tensor tractography (DTT) performed 3 months post-onset showed decreased volume of the right corticospinal tract. We reported a patient with hepatic encephalopathy involving the corticospinal tract by DTT. PMID:25750884

  20. Embolization of portal-systemic shunts in cirrhotic patients with chronic recurrent hepatic encephalopathy

    SciTech Connect

    Sakurabayashi, Shin; Sezai, Shuichi; Yamamoto, Yoshihiro; Hirano, Masanori; Oka, Hiroshi

    1997-03-15

    Purpose. To evaluate the efficacy of embolization of portal-systemic shunts in cirrhotic patients with chronic recurrent hepatic encephalopathy (CRHE). Methods. Seven cirrhotic patients with CRHE refractory to medical treatment (3 men and 4 women, mean age 66 years) were studied. Five patients had splenorenal shunts, 1 had a gastrorenal shunt, and 1 had an intrahepatic portal vein-hepatic vein shunt. Shunt embolization was performed using stainless steel coils, with a percutaneous transhepatic portal vein approach in 4 patients and a transrenal vein approach in 3 patients. Results. After embolization, the shunt disappeared in 4 patients on either ultrasound pulsed Doppler monitoring or portography. Complications observed in the 7 patients were fever, transient pleural effusion, ascites, and mild esophageal varices. For 3-6 months after embolization, the 4 patients whose shunts disappeared showed minimal or no reappearance of a shunt, and had no recurrence of encephalopathy. The serum ammonia levels decreased and electroencephalograms also improved. One of the 4 patients, who developed mild esophageal varices, required no treatment. Treatment was effective in 3 of the 4 patients (75%) who underwent embolization via a transhepatic portal vein. Conclusion. Transvascular embolization of shunts improved the outcome in 4 of 7 patients. The most effective embolization was achieved via the percutaneous transhepatic portal vein approach.

  1. Lactitol in the treatment of chronic hepatic encephalopathy: an open comparison with lactulose.

    PubMed Central

    Lanthier, P L; Morgan, M Y

    1985-01-01

    Lactulose is currently the drug of choice for the treatment of hepatic encephalopathy. It is, however, only available as a syrup which is contaminated with other sugars. Consequently patients may express aversion to its excessively sweet taste and many experience nausea because of its hyperosmolarity. Lactitol is a disaccharide analogue of lactulose which can be produced as a pure crystalline powder with a low relative sweetness. Theoretically it should have the same therapeutic effects as lactulose but fewer side effects. Five patients with chronic hepatic encephalopathy on maintenance lactulose were monitored clinically, psychometrically, and by measurement of venous blood ammonia, electroencephalogram mean cycle frequency, and cerebral blood flow during three months treatment with lactulose and a similar period on lactitol. Lactitol was at least as efficacious as lactulose but was more acceptable because its cathartic effect was more predictable, its formulation was more convenient and its less sweet taste preferred. Lactitol is the ideal successor to lactulose for treatment of this condition. PMID:3979914

  2. Serum metabolic signature of minimal hepatic encephalopathy by (1)H-nuclear magnetic resonance.

    PubMed

    Jiménez, Beatriz; Montoliu, Carmina; MacIntyre, David A; Serra, Miguel A; Wassel, Abdallah; Jover, María; Romero-Gomez, Manuel; Rodrigo, Jose M; Pineda-Lucena, Antonio; Felipo, Vicente

    2010-10-01

    Minimal hepatic encephalopathy (MHE) reduces quality of life of cirrhotic patients, predicts overt hepatic encephalopathy, and is associated with poor prognosis. We hypothesized that MHE arises once metabolic alterations derived from the liver reach a particular threshold. Our aim was to assess whether metabolic profiling of serum samples by high-field (1)H-nuclear magnetic resonance spectroscopy ((1)H NMR) and subsequent multivariate analyses would be useful to characterize metabolic perturbations associated with MHE and to identify potential metabolic biomarkers. Metabolic serum profiles from controls (n = 69) and cirrhotic patients without MHE (n = 62) and with MHE (n = 39) were acquired using high field NMR. Supervised modeling of the data provided perfect discrimination between healthy controls and cirrhotic patients and allowed the generation of a predictive model displaying strong discrimination between patients with and without MHE (R(2)Y = 0.68, Q(2)Y = 0.63). MHE patients displayed increased serum concentrations of glucose, lactate, methionine, TMAO, and glycerol, as well as decreased levels of choline, branch amino acids, alanine, glycine, acetoacetate, NAC, and lipid moieties. Serum metabonomics by (1)H NMR offers a useful approach for characterizing underlying metabolic differences between patients with and without MHE. This procedure shows great potential as a diagnostic tool of MHE as it objectively reflects measurable biochemical differences between the patient groups and may facilitate monitoring of both disease progression and effects of therapeutic treatments. PMID:20690770

  3. Pathophysiology and management of hepatic encephalopathy 2014 update: Ammonia toxicity and hyponatremia.

    PubMed

    Iwasa, Motoh; Takei, Yoshiyuki

    2015-12-01

    Hyperammonemia is a major factor involved in the pathogenesis of hepatic encephalopathy (HE). Ammonia elicits astrocyte swelling and causes brain edema. In addition, hyponatremia, a condition frequently observed in hepatic cirrhosis, also exacerbates brain edema, potentially becoming a factor that exacerbates HE. Therefore, as a treatment strategy for HE, alleviating ammonia toxicity is essential. In addition to restricting protein intake, synthetic disaccharides such as lactulose and lactitol, probiotics that improve gut flora, and rifaximin, an antibiotic with poor bioavailability, are also administrated. Additionally, branched-chain amino acids and carnitine have also been administrated. Moreover, we investigated the current trend in the concomitant use of drugs with different mechanisms of action. In Japan, the V2 receptor antagonist tolvaptan can be administrated to hepatic cirrhosis patients with fluid retention. This drug is also useful as a countermeasure for hyponatremia in hepatic cirrhosis, and elucidating its effects in HE patients may therefore become an agenda in the future. These observations indicate that ammonia toxicity, gut flora control and low sodium control are major focuses in HE improvement and long-term prognosis. PMID:25604571

  4. Cholestatic hepatitis due to Ecballium elaterium ingestion.

    PubMed

    Bizid, Sondès; Sabbah, Mériam; Msakni, Issam; Ben Slimene, Baha; Mohamed, Ghanem; Bouali, Riadh; Ben Abdallah, Hatem; Abdelli, Nabil

    2015-10-01

    Ecballium elaterium is an herbaceous plant belonging to the Cucurbitaceae family. This plant is fairly common in the Mediterranean regions. It is frequently consumed in infusion, mixture of fruit or even in aerosol in cases of fever or flu. This plant is known for its respiratory and ocular toxicity. Hepatotoxicity has never been described in the literature. We report a case of acute cholestatic hepatitis due to Ecballium elaterium in a 39 years old patient, with no past medical history. PMID:25573494

  5. Non invasive blood flow measurement in cerebellum detects minimal hepatic encephalopathy earlier than psychometric tests

    PubMed Central

    Felipo, Vicente; Urios, Amparo; Giménez-Garzó, Carla; Cauli, Omar; Andrés-Costa, Maria-Jesús; González, Olga; Serra, Miguel A; Sánchez-González, Javier; Aliaga, Roberto; Giner-Durán, Remedios; Belloch, Vicente; Montoliu, Carmina

    2014-01-01

    AIM: To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy. METHODS: Blood flow (BF) was analyzed by arterial spin labeling (ASL) in different brain areas of 14 controls, 24 cirrhotic patients without and 16 cirrhotic patients with minimal hepatic encephalopathy (MHE). Images were collected using a 3 Tesla MR scanner (Achieva 3T-TX, Philips, Netherlands). Pulsed ASL was performed. Patients showing MHE were detected using the battery Psychometric Hepatic Encephalopathy Score (PHES) consisting of five tests. Different cognitive and motor functions were also assessed: alterations in selective attention were evaluated using the Stroop test. Patients and controls also performed visuo-motor and bimanual coordination tests. Several biochemical parameters were measured: serum pro-inflammatory interleukins (IL-6 and IL-18), 3-nitrotyrosine, cGMP and nitrates+nitrites in plasma, and blood ammonia. Bivariate correlations were evaluated. RESULTS: In patients with MHE, BF was increased in cerebellar hemisphere (P = 0.03) and vermis (P = 0.012) and reduced in occipital lobe (P = 0.017). BF in cerebellar hemisphere was also increased in patients without MHE (P = 0.02). Bimanual coordination was impaired in patients without MHE (P = 0.05) and much more in patients with MHE (P < 0.0001). Visuo-motor coordination was impaired only in patients with MHE (P < 0.0001). Attention was slightly affected in patients without MHE and more strongly in patients with MHE (P < 0.0001). BF in cerebellar hemisphere and vermis correlated with performance in most tests of PHES [(number connection tests A (NCT-A), B (NCT-B)and line tracing test] and in the congruent task of Stroop test. BF in frontal lobe correlated with NCT-A. Performance in bimanual and visuomotor coordination tests correlated only with BF in cerebellar hemisphere. BF in occipital lobe correlates with performance in the PHES battery and with

  6. Endovascular Management of Refractory Hepatic Encephalopathy Complication of Transjugular Intrahepatic Portosystemic Shunt (TIPS): Comprehensive Review and Clinical Practice Algorithm.

    PubMed

    Pereira, Keith; Carrion, Andres F; Salsamendi, Jason; Doshi, Mehul; Baker, Reginald; Kably, Issam

    2016-02-01

    Transjugular intrahepatic portosystemic shunt (TIPS) has evolved as an effective intervention for treatment of complications of portal hypertension. The use of polytetrafluoroethylene-covered stents have improved the patency of the shunts and diminished the incidence of TIPS dysfunction. However, TIPS-related refractory hepatic encephalopathy (rHE) poses a significant challenge. Approximately 3-7 % of patients with TIPS develop rHE. Refractory hepatic encephalopathy is defined as a recurrent or persistent encephalopathy despite appropriate medical treatment. Hepatic encephalopathy can be an extremely debilitating complication that profoundly affects quality of life. The approach to management of patients with rHE is complex and typically requires collaboration between different specialties. Liver transplantation is the ultimate treatment for rHE; however, the ongoing shortage of organ donation markedly limits this treatment option. Alternative therapies such as shunt occlusion or reduction can control symptoms and serve as a 'bridge' therapy to liver transplantation. Therefore, interventional radiologists play a key role in the management of these patients by offering a variety of endovascular techniques. The purpose of this review is to highlight some of these endovascular techniques and to develop a therapeutic algorithm that can be applied in clinical practice for the management of rHE. PMID:26285910

  7. Changing face of hepatic encephalopathy: Role of inflammation and oxidative stress

    PubMed Central

    Seyan, Amit S; Hughes, Robin D; Shawcross, Debbie L

    2010-01-01

    The face of hepatic encephalopathy (HE) is changing. This review explores how this neurocognitive disorder, which is associated with both acute and chronic liver injury, has grown to become a dynamic syndrome that spans a spectrum of neuropsychological impairment, from normal performance to coma. The central role of ammonia in the pathogenesis of HE remains incontrovertible. However, over the past 10 years, the HE community has begun to characterise the key roles of inflammation, infection, and oxidative/nitrosative stress in modulating the pathophysiological effects of ammonia on the astrocyte. This review explores the current thoughts and evidence base in this area and discusses the potential role of existing and novel therapies that might abrogate the oxidative and nitrosative stresses inflicted on the brain in patients with, or at risk of developing, HE. PMID:20632436

  8. A systematic review and meta-analysis of the use of oral zinc in the treatment of hepatic encephalopathy

    PubMed Central

    2013-01-01

    Background and aim Because low serum zinc levels precipitate hepatic encephalopathy, zinc supplementation is considered a potential therapeutic option. The aim of this study was to assess the effects of oral zinc supplementation in the treatment of hepatic encephalopathy. Methods For this systematic review and meta-analysis, data sources included electronic databases (CENTRAL, MEDLINE, EMBASE) and manual searching. Randomized clinical trials of adult patients diagnosed with liver cirrhosis and hepatic encephalopathy were included. The types of interventions considered were any oral zinc supplementation versus no intervention, placebo, or other interventions for the management of hepatic encephalopathy. The data were analyzed by calculating the RR for each trial and expressing the uncertainty as 95% CI. Continuous data were analyzed by calculating the standard mean differences (SMD) between groups within each trial and their 95% CI. Statistical heterogeneity was defined as a P-value > 0.10 (χ2) or I2 > 25%. Results Four trials with a total of 233 patients were included. Oral zinc supplementation was associated with a significant improvement in performance on the number connection test (SMD –0.62; 95% CI –1.12 to –0.11) reported in three trials (n = 189), but not with encephalopathy recurrence reduction (RR 0.64; 95% CI 0.26 to 1.59) reported in two trials (n = 169). Other clinically significant outcomes (mortality, liver related morbidity, quality of life) were not reported. Conclusion Oral zinc supplementation improved performance on the number connection test, but no evidence about other clinical or biochemical outcomes was available. PMID:23742732

  9. Prolonged remission from hepatic encephalopathy with rifaximin: results of a placebo crossover analysis

    PubMed Central

    Bajaj, J S; Barrett, A C; Bortey, E; Paterson, C; Forbes, W P

    2015-01-01

    Background Rifaximin therapy reduced risk of hepatic encephalopathy (HE) recurrence and HE-related hospitalisations during a 6-month, randomised, placebo-controlled trial (RCT) and a 24-month open-label maintenance (OLM) study. However, the impact of crossover from placebo to rifaximin therapy is unclear. Aim To study the impact of crossing over from placebo to rifaximin treatment on breakthrough HE and hospitalisation rates using a within-subjects design. Methods Adults with cirrhosis and history of overt HE episodes, currently in HE remission, received placebo during the RCT and crossed over to rifaximin 550 mg twice daily during the OLM study. Rate of breakthrough overt HE episodes, hospitalisations and incidence and rate of adverse events (AEs) were analysed during RCT and first 6 months of OLM. Results Of 82 patients randomised to placebo in the RCT who crossed over to the OLM study, 39 experienced an HE episode during the RCT compared with 14 during the OLM study (P < 0.0001). Significantly lower rates of HE events were observed with rifaximin treatment compared with placebo treatment (P < 0.0001). Rates of HE-related hospitalisation were numerically lower during rifaximin treatment compared with placebo treatment, although not significant. Rates of most common AEs, serious AEs and infection-related AEs were similar between the two treatments. Conclusions This analysis confirms the repeatability of results from the RCT on safety and efficacy of rifaximin 550 mg twice daily in reducing the risk of hepatic encephalopathy recurrence, and suggests these findings are translatable outside of a rigorous, controlled trial setting. PMID:25339518

  10. Identifying minimal hepatic encephalopathy in cirrhotic patients by measuring spontaneous brain activity.

    PubMed

    Chen, Hua-Jun; Zhang, Ling; Jiang, Long-Feng; Chen, Qiu-Feng; Li, Jun; Shi, Hai-Bin

    2016-08-01

    It has been demonstrated that minimal hepatic encephalopathy (MHE) is associated with aberrant regional intrinsic brain activity in cirrhotic patients. However, few studies have investigated whether altered intrinsic brain activity can be used as a biomarker of MHE among cirrhotic patients. In this study, 36 cirrhotic patients (with MHE, n = 16; without MHE [NHE], n = 20) underwent resting-state functional magnetic resonance imaging (fMRI). Spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) in the fMRI signal. MHE was diagnosed based on the Psychometric Hepatic Encephalopathy Score (PHES). A two-sample t-test was used to determine the regions of interest (ROIs) in which ALFF differed significantly between the two groups; then, ALFF values within ROIs were selected as classification features. A linear discriminative analysis was used to differentiate MHE patients from NHE patients. The leave-one-out cross-validation method was used to estimate the performance of the classifier. The classification analysis was 80.6 % accurate (81.3 % sensitivity and 80.0 % specificity) in terms of distinguishing between the two groups. Six ROIs were identified as the most discriminative features, including the bilateral medial frontal cortex/anterior cingulate cortex, posterior cingulate cortex/precuneus, left precentral and postcentral gyrus, right lingual gyrus, middle frontal gyrus, and inferior/superior parietal lobule. The ALFF values within ROIs were correlated with PHES in cirrhotic patients. Our findings suggest that altered regional brain spontaneous activity is a useful biomarker for MHE detection among cirrhotic patients. PMID:26886109

  11. The contribution of endogenous benzodiazepine receptor ligands to the pathogenesis of hepatic encephalopathy

    SciTech Connect

    Basile, A.S. )

    1991-02-01

    The involvement of the gamma-aminobutyric acid A(GABAA) receptor complex in the pathogenesis of hepatic encephalopathy (HE) was examined in galactosamine-treated rabbits with HE caused by fulminant hepatic failure. Radioligand binding to the constituent components of the GABAA receptor complex was unchanged in rabbits with HE. However, partially purified extracts from encephalopathic rabbit brain were approximately three times more potent in inhibiting ({sup 3}H)Ro 15-1788 binding to benzodiazepine (BZ) receptors than extracts from control rabbits. The inhibition of radioligand binding to the BZ receptor produced by these extracts was competitive and reversible and was significantly enhanced by GABA. Further purification of these extracts by high-performance liquid chromatography (HPLC) indicated that the inhibitory activity was localized in several peaks, some of which had retention times corresponding to 1,4-benzodiazepine standards. The presence of diazepam in these extracts was confirmed using mass spectroscopy. Both mass spectroscopic and radiometric techniques demonstrated that the concentration of diazepam in brain extracts from encephalopathic rabbits was approximately 4 times greater than control extracts. These findings link the presence of BZ receptor agonists to the development of a neuropathological condition, thereby providing a rational basis for the use of BZ receptor antagonists in the management of HE in man.

  12. Rifaximin vs conventional oral therapy for hepatic encephalopathy: A meta-analysis

    PubMed Central

    Eltawil, Karim M; Laryea, Marie; Peltekian, Kevork; Molinari, Michele

    2012-01-01

    AIM: To characterize the efficacy of rifaximin in the management of hepatic encephalopathy (HE) as several randomized controlled studies have shown contradictory results on its effectiveness in comparison to other oral agents. METHODS: We performed a systematic review and random effects meta-analysis of all eligible trials identified through electronic and manual searches. Twelve randomized controlled trials met the inclusion criteria with a total of 565 patients. RESULTS: The clinical effectiveness of rifaximin was equivalent to disaccharides or other oral antibiotics [odds ratio (OR) 0.96; 95% CI: 0.94-4.08] but with a better safety profile (OR 0.27; 95% CI: 0.12-0.59). At the completion of treatment protocols, patients receiving rifaximin showed lower serum ammonia levels [weighted mean difference (WMD) = -10.65; 95% CI: -23.4-2.1; P = 0.10], better mental status (WMD = -0.24; 95% CI: -0.57-0.08; P = 0.15) and less asterixis (WMD -0.1; 95% CI -0.26-0.07; P = 0.25) without reaching statistical significance. On the other hand, other psychometric outcomes such as electroencephalographic response and grades of portosystemic encephalopathy were superior in patients treated with rifaximin in comparison to the control group (WMD = 0.21, 95% CI: -0.33-0.09, P = 0.0004; and WMD = -2.33, 95% CI: -2.68-1.98, P = 0.00001, respectively). Subgroup and sensitivity analysis did not show any significant difference in the above findings. CONCLUSION: Rifaximin appears to be at least as effective as other conventional oral agents for the treatment of HE with a better safety profile. PMID:22371636

  13. Invasive intracranial pressure monitoring is a useful adjunct in the management of severe hepatic encephalopathy associated with pediatric acute liver failure

    PubMed Central

    Kamat, Pradip; Kunde, Sachin; Vos, Miriam; Vats, Atul; Heffron, Thomas; Romero, Rene; Fortenberry, James D.

    2011-01-01

    Introduction Pediatric acute liver failure (ALF) is often accompanied by hepatic encephalopathy, cerebral edema and raised intracranial pressure (ICP). Elevated ICP can be managed more effectively with intracranial monitoring, but ALF-associated coagulopathy is often considered a contraindication for invasive monitoring due to risk for intracranial bleeding. We reviewed our experience with use of early ICP monitoring in ALF in children listed for liver transplantation. Methods Retrospective review of all intubated pediatric ALF patients with Grade 3 and Grade 4 encephalopathy requiring intracranial pressure monitoring and evaluated for potential liver transplant were identified from an institutional liver transplant patient database from 1999 to 2009. Result 14 patients were identified that met inclusion criteria. Age ranged from 7 months to 20 yrs. Diagnoses of ALF were infectious (3), drug induced (7), autoimmune hepatitis (2) and indeterminate (2). Grade 3 and 4 encephalopathy was seen in 10 (71%) and 4 (29%) patients respectively. CT scans prior to ICP monitor placement showed cerebral edema in 5 (35.7%) patients. Prior to ICP monitor placement, fresh frozen plasma, Vitamin K and activated recombinant factor VIIa were given to all 14 patients with significant improvement in coagulopathy (p<.04). Initial ICP ranged from 5 – 50 cmH2O; ICP was significantly higher in patients with cerebral edema by CT (p<.05). 11/14 (78%) patients received hypertonic saline and 3 (22%) received mannitol for elevated ICP. 8 of 14 (56%) monitored patients were managed to liver transplant with 100% surviving neurologically intact. 4/14 (28%) patients had spontaneous recovery without liver transplant. 2 of 14 (14%) patients died due to multiple organ failure prior to transplant. One patient had a small 9mm intracranial hemorrhage but survived after receiving a liver transplant. No patient developed intracranial infection. Conclusion In our series of patients, ICP monitoring had a

  14. Pharmacological manipulation of cyclic GMP levels in brain restores learning ability in animal models of hepatic encephalopathy: therapeutic implications

    PubMed Central

    Rodrigo, Regina; Monfort, Pilar; Cauli, Omar; Erceg, Slaven; Felipo, Vicente

    2006-01-01

    Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome present in patients with liver disease that includes impaired intellectual function. To develop therapeutic treatments to restore cognitive function, it is important to understand the molecular mechanisms that impair cognitive function in HE. This review summarizes data showing that: (a) cognitive function and learning are impaired in patients with liver disease and in animal models of chronic liver failure or hyperammonemia; (b) the glutamate–NO–cGMP pathway modulates some forms of learning; and (c) the function of this pathway is impaired in brain in vivo in rats with chronic hyperammonemia or liver failure and from patients who died from HE. Learning ability of hyperammonemic rats was restored by increasing cGMP by: (1) continuous intracerebral administration of zaprinast, an inhibitor of the cGMP-degrading phosphodiesterase; (2) chronic oral administration of sildenafil, an inhibitor of the phosphodiesterase that crosses the blood–brain barrier; and (3) continuous intracerebral administration of cGMP. The data summarized indicate that impairment of learning ability in rats with chronic liver failure or hyperammonemia is due to impairment of the glutamate–NO–cGMP pathway. Moreover, increasing extracellular cGMP by pharmacological means may be a new therapeutic approach to improve cognitive function in patients with HE. PMID:19412446

  15. Anomalous Gray Matter Structural Networks in Patients with Hepatitis B Virus-Related Cirrhosis without Overt Hepatic Encephalopathy

    PubMed Central

    Qiu, Ying-Wei; Cai, Pei-Qiang; Li, Jing; Jiang, Gui-Hua; Deng, Yan-Jia; Zhang, Xue-Lin; Wu, Pei-Hong; Xie, Chuan-Miao; Wen, Ge

    2015-01-01

    Background and Purpose Increasing evidence suggests that cirrhosis may affect the connectivity among different brain regions in patients before overt hepatic encephalopathy (OHE) occurs. However, there has been no study investigating the structural reorganization of these altered connections at the network level. The primary focus of this study was to investigate the abnormal topological organization of the structural network in patients with hepatitis B virus-related cirrhosis (HBV-RC) without OHE using structural MRI. Methods Using graph theoretical analysis, we compared the global and regional topological properties of gray matter structural networks between 28 patients with HBV-RC without OHE and 30 age-, sex- and education-matched healthy controls. The structural correlation networks were constructed for the two groups based on measures of gray matter volume. Results The brain network of the HBV-RC group exhibited a significant decrease in the clustering coefficient and reduced small-worldness at the global level across a range of network densities. Regionally, brain areas with altered nodal degree/betweenness centrality were observed predominantly in association cortices (frontal and temporal regions) (p < 0.05, uncorrected), including a significantly decreased nodal degree in the inferior temporal gyrus (p < 0.001, uncorrected). Furthermore, the HBV-RC group exhibited a loss of association hubs and the emergence of an increased number of non-association hubs compared with the healthy controls. Conclusion The results of this large-scale gray matter structural network study suggest reduced topological organization efficiency in patients with HBV-RC without OHE. Our findings provide new insight concerning the mechanisms of neurobiological reorganization in the HBV-RC brain from a network perspective. PMID:25786256

  16. Exploratory investigation on nitro- and phospho-proteome cerebellum changes in hyperammonemia and hepatic encephalopathy rat models.

    PubMed

    Brunelli, Laura; Campagna, Roberta; Airoldi, Luisa; Cauli, Omar; Llansola, Marta; Boix, Jordi; Felipo, Vicente; Pastorelli, Roberta

    2012-03-01

    Hepatic encephalopathy (HE) is a neurological disease associated with hepatic dysfunction. Current knowledge suggests that hyperammonemia, related to liver failure, is a main factor contributing to the cerebral alterations in HE and that hyperammonemia might impair signal transduction associated with post-translational modification of proteins such as tyrosine-nitration and phosphorylation. However, the molecular bases of the HE remain unclear and very little is known about the occurrence of post-translational modification on in vivo proteins. In this exploratory study we look for evidence of post-translation modifications of proteins in the cerebellum of experimental HE rat models using a proteomic approach. For the first time we showed that hyperammonemia without liver failure (HA rats) and experimental HE with liver failure due to portacaval shunt (PCS rats) lead to a reduced protein nitration in rat cerebellum, where the undernitrated proteins were involved in energy metabolism and cytoskeleton remodelling. Moreover we showed that tyrosine nitration loss of these proteins was not necessarily associated to a change in their phosphorylation state as result of the disease. Interestingly the rat cerebellum phosphoproteome was mainly perturbed in PCS rats, whereas HA rats did not shown appreciable changes in their phosphoprotein profile. Since the protein nitration level decreased similarly in the cerebellum of both HA and PCS rats, this implies that the two disease models share common effects but also present some differential signalling effects in the cerebellum of the same animals. This study highlights the interest for studying the concerted action of multiple signalling pathways in HE development. PMID:22083566

  17. Symptomatic hepatic hydrothorax successfully treated with transjugular intrahepatic portosystemic shunt (TIPS)–role of titration of portosystemic gradient reduction to avoid post-TIPS encephalopathy

    PubMed Central

    Krishnamoorthy, T L; Taneja, M; Chang, P E

    2014-01-01

    Key Clinical Message We describe a challenging case of hepatic hydrothorax secondary to nonalcoholic steatohepatitis cirrhosis. Our management involved successfully treating the hydrothorax with a transjugular intrahepatic porto-systemic shunt but having to manage the subsequent complication of hepatic encephalopathy. We conclude with a review of the available literature. PMID:25356258

  18. Covert Hepatic Encephalopathy Is Independently Associated With Poor Survival and Increased Risk of Hospitalization

    PubMed Central

    Patidar, Kavish R.; Thacker, Leroy R.; Wade, James B.; Sterling, Richard K.; Sanyal, Arun J.; Siddiqui, Mohammad S.; Matherly, Scott C.; Stravitz, R. Todd; Puri, Puneet; Luketic, Velimir A.; Fuchs, Michael; White, Melanie B.; Noble, Nicole A.; Unser, Ariel B.; Gilles, HoChong; Heuman, Douglas M.; Bajaj, Jasmohan S.

    2015-01-01

    OBJECTIVES Despite the high prevalence of covert hepatic encephalopathy (CHE) in cirrhotics without previous overt HE (OHE), its independent impact on predicting clinically relevant outcomes is unclear. The aim of this study was to define the impact of CHE on time to OHE, hospitalization, and death/transplant in prospectively followed up patients without previous OHE. METHODS Outpatient cirrhotics without OHE were enrolled and were administered a standard paper–pencil cognitive battery for CHE diagnosis. They were systematically followed up and time to first OHE development, hospitalization (liver-related/unrelated), and transplant/death were compared between CHE and no-CHE patients at baseline using Cox regression. RESULTS A total of 170 cirrhotic patients (55 years, 58% men, 14 years of education, Model for End-Stage Liver Disease (MELD 9), 53% hepatitis C virus (HCV), 20% nonalcoholic etiology) were included, of whom 56% had CHE. The entire population was followed up for 13.0±14.6 months, during which time 30% developed their first OHE episode, 42% were hospitalized, and 19% had a composite death/transplant outcome. Age, gender, etiology, the MELD score, and CHE status were included in Cox regression models for time to first OHE episode, hospitalization, death, and composite death/transplant outcomes. On Cox regression, despite controlling for MELD, those with CHE had a higher risk of developing OHE (hazard ratio: 2.1, 95% confidence interval 1.01–4.5), hospitalization (hazard ratio: 2.5, 95% confidence interval 1.4–4.5), and death/transplant (hazard ratio: 3.4, 95% confidence interval 1.2–9.7) in the follow-up period. CONCLUSIONS Covert HE is associated with worsened survival and increased risk of hospitalization and OHE development, despite controlling for the MELD score. Strategies to detect and treat CHE may improve these risks. PMID:25178701

  19. Rifaximin: a review of its use in reducing recurrence of overt hepatic encephalopathy episodes.

    PubMed

    Scott, Lesley J

    2014-12-01

    Oral rifaximin 550 mg (Refero(®); Targaxan(®); Tixteller(®); Xifaxan(®)) twice daily, either alone or more commonly with medicines containing lactulose, is approved in several countries, including the UK, EU and USA, for use in adults with liver disease to reduce the recurrence of episodes of overt hepatic encephalopathy (HE). Rifaximin is a broad-spectrum antibacterial that acts locally in the gut to reduce intestinal flora, including ammonia-producing species, with hyperammonaemia considered to play a central role in the pathogenesis of HE. In a 6-month, multinational trial in patients with liver disease, rifaximin 550 mg twice daily (± lactulose) was an effective and well tolerated treatment for reducing the recurrence of HE episodes. At study end, rifaximin therapy significantly prolonged the time to the first breakthrough HE episode compared with placebo (± lactulose), irrespective of geographical region or baseline patient and disease characteristics. Rifaximin treatment also significantly reduced HE-related hospitalizations and improved health-related quality of life compared with placebo. Furthermore, the efficacy of rifaximin with or without lactulose in reducing the recurrence of overt HE episodes was maintained after up to 2.5 years of treatment, with no new safety signals arising during this period. This article reviews the pharmacology and therapeutic efficacy of rifaximin 550 mg twice daily in reducing the recurrence of overt HE episodes in adults with liver disease. PMID:25352391

  20. Lactulose, rifaximin or branched chain amino acids for hepatic encephalopathy: what is the evidence?

    PubMed

    Gluud, Lise Lotte; Dam, Gitte; Borre, Mette; Les, Iñigo; Cordoba, Juan; Marchesini, Giulio; Aagaard, Niels Kristian; Vilstrup, Hendrik

    2013-06-01

    Hepatic encephalopathy (HE) is a serious complication of acute and chronic liver disease associated with severe morbidity and mortality. We performed updated random effects meta-analyses to evaluate the evidence for non-absorbable disaccharides (lactulose and lactitol), rifaximin and branched chain amino acids (BCAA). A meta-analysis of randomized trials showed that, compared with placebo or no intervention, non-absorbable disaccharides have beneficial effects on HE manifestations and prevention of HE episodes. The addition of rifaximin to non-absorbable disaccharides versus rifaximin alone was more beneficial than non-absorbable disaccharides used alone on both outcome measures. Likewise, a meta-analysis of randomised controlled trials found that oral BCAA supplements have beneficial effects on manifestations of HE compared with control supplements. The effect was found in a variety of clinical settings. No convincing effects of intravenous BCAA for episodic HE were identified. In conclusion, evidence-based treatment recommendations for patients with HE should include non-absorbable disaccharides combined with rifaximin or BCAA. Additional evidence is needed to evaluate the effect of combining all three interventions. PMID:23275147

  1. Role of dopaminergic and serotonergic neurotransmitters in behavioral alterations observed in rodent model of hepatic encephalopathy.

    PubMed

    Dhanda, Saurabh; Sandhir, Rajat

    2015-06-01

    The present study was designed to evaluate the role of biogenic amines in behavioral alterations observed in rat model of hepatic encephalopathy (HE) following bile duct ligation (BDL). Male Wistar rats subjected to BDL developed biliary fibrosis after four weeks which was supported by altered liver function tests, increased ammonia levels and histological staining (Sirius red). Animals were assessed for their behavioral performance in terms of cognitive, anxiety and motor functions. The levels of dopamine (DA), serotonin (5-HT), epinephrine and norepinephrine (NE) were estimated in different regions of brain viz. cortex, hippocampus, striatum and cerebellum using HPLC along with activity of monoamine oxidase (MAO). Cognitive assessment of BDL rats revealed a progressive decline in learning, memory formation, retrieval, exploration of novel environment and spontaneous locomotor activity along with decrease in 5-HT and NE levels. This was accompanied by an increase in MAO activity. Motor functions of BDL rats were also altered which were evident from decrease in the time spent on the rotating rod and higher foot faults assessed using narrow beam walk task. A global decrease was observed in the DA content along with an increase in MAO activity. Histopathological studies using hematoxylin-eosin (H&E) and cresyl violet exhibited marked neuronal degeneration, wherein neurons appeared more pyknotic, condensed and damaged. The results reveal that dopaminergic and serotonergic pathways are disturbed in chronic liver failure post-BDL which may be responsible for behavioral impairments observed in HE. PMID:25639545

  2. The effect of small intestinal bacterial overgrowth on minimal hepatic encephalopathy in patients with cirrhosis

    PubMed Central

    Feng, Yikuan; Cao, Bin; Tian, Qiang

    2015-01-01

    Introduction The aim of the study was to investigate the significance of factors associated with minimal hepatic encephalopathy (MHE) in cirrhotic patients. Material and methods Between September 2012 and August 2013, 60 cirrhotic patients, including MHE and non-MHE (NMHE) patients, were included in the study. Associated factors and clinical factors were analyzed to see if they were significantly different between MHE and non-MHE patients. Upon identifying the factors showing differences, we applied multivariate regression analysis to further decide which were the most significant ones to differentiate MHE from NMHE patients. Results There were 26 patients diagnosed with MHE and 34 with NMHE. Our results demonstrated that the prevalence rate of small intestinal bacterial overgrowth (SIBO) was highly associated with patients with MHE (65.4%, 17 out of 26), in contrast to the rate in NMHE patients (8.8%, 3 out of 34). We also found that factors including age, education level, intelligent test results, plasma albumin level and plasma ammonia levels were significantly different between MHE and NMHE patients. Ultimately, with logistic regression analysis, we found that SIBO was the most significant factor differentiating MHE patients from NMHE patients (p < 0.05). Conclusions In cirrhotic patients, SIBO was highly associated with MHE. This may further our understanding of the mechanisms of MHE and help to develop potential therapeutic interventions to treat cirrhotic patients with MHE. PMID:27279853

  3. Abnormal spontaneous brain activity in minimal hepatic encephalopathy: resting-state fMRI study

    PubMed Central

    Zhong, Wei-Jia; Zhou, Zhi-Ming; Zhao, Jian-Nong; Wu, Wei; Guo, Da-Jing

    2016-01-01

    PURPOSE We aimed to assess the abnormality of baseline spontaneous brain activity in minimal hepatic encephalopathy (MHE) by amplitude of low frequency fluctuation (ALFF) and fraction ALFF (fALFF). METHODS A total of 14 MHE patients and 14 healthy controls were included in our study. Both ALFF and fALFF of functional magnetic resonance imaging were calculated for statistical analysis. RESULTS Compared with healthy controls, patients with MHE had significantly decreased ALFF in the bilateral medial prefrontal cortex (MPFC), left superior frontal gyrus, right precentral gyrus, left opercular part of inferior frontal gyrus, left gyrus rectus, bilateral precuneus, and the posterior lobe of right cerebellum; and they had significantly decreased fALFF in the bilateral MPFC, right middle frontal gyrus, right superior temporal gyrus, and the posterior lobe of left cerebellum. CONCLUSION ALFF and fALFF changes in many brain regions demonstrate abnormality of the spontaneous neuronal activity in MHE. Especially the impairment of right precuneus and left MPFC may play a critical role in manifestation of MHE. Changes of ALFF and fALFF in the precuneus and the MPFC can be used as a potential marker for MHE. PMID:26742646

  4. Role of Magnetic Resonance in Understanding the Pathogenesis of Hepatic Encephalopathy

    PubMed Central

    Huda, A.; Gupta, R.K.; Rajakumar, N.; Thomas, M.A.

    2009-01-01

    A spectrum of neuropsychiatric abnormalities caused by portosystemic venous shunting occurs in hepatic encephalopathy (HE) patients with or without liver dysfunction. It is not completely clear how the astrocyte swelling leads to glial-neuronal dysfunction, and how the symptoms are manifested in HE. A major goal of this work is to review the current status of information available from the existing magnetic resonance (MR) modalities including MR imaging (MRI) and MR Spectroscopy (MRS) as well as other modalities in the understanding the pathogenesis of HE. First, we discuss briefly neuron-histopathology, neurotoxins, neuropsychological and neurophysiological tests. A short review on the progress with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) is then presented. In the remaining part of the manuscript, the following topics pertinent to understanding the pathogenesis of HE are discussed: MRI, diffusion tensor imaging (DTI), one-dimensional MRS based single- and multi-voxel based spectroscopic imaging techniques and two-dimensional MRS. PMID:20890387

  5. Progressive reduction of sleep time and quality in rats with hepatic encephalopathy caused by portacaval shunts.

    PubMed

    Llansola, M; Cantero, J L; Hita-Yañez, E; Mirones-Maldonado, M J; Piedrafita, B; Ahabrach, H; Errami, M; Agusti, A; Felipo, V

    2012-01-10

    Patients with liver cirrhosis show sleep disturbances. Insight into their relationship with hepatic encephalopathy (HE) can be obtained using animal models of HE. The aims of this work were to assess (1) whether rats with portacaval shunts (PCS), a model of HE, show alterations in sleep and if they are similar to those in patients with HE; (2) Whether hyperammonemia plays a role in these sleep alterations; and (3) the time course of sleep alterations in these animal models. Rats were subjected to PCS to induce HE. Another group of rats was fed an ammonium-containing diet to induce hyperammonemia. Polysomnographic recordings were acquired for 24 h and sleep architecture was analyzed in control, PCS, and hyperammonemic rats at 4, 7, and 11 weeks after surgery or diet, respectively. PCS rats show a significant reduction in rapid eye movement (REM) and non-rapid eye movement (NREM) sleep time and increased sleep fragmentation, whereas reduced sleep occurs at 4 weeks and worsens at 7 and 11 weeks, sleep fragmentation appears at 7 weeks and worsens at 11 weeks. Hyperammonemic rats show decreased REM sleep, starting at 7 weeks and worsening at 11 weeks, with no changes in NREM sleep or sleep fragmentation. Therefore, PCS rats are a good model to study sleep alterations in HE, their mechanisms, and potential treatment. Mild hyperammonemia mainly impacts mechanisms involved in REM generation and/or maintenance but does not seem to be involved in sleep fragmentation. PMID:22108612

  6. Inflammation: A novel target of current therapies for hepatic encephalopathy in liver cirrhosis

    PubMed Central

    Luo, Ming; Guo, Jian-Yang; Cao, Wu-Kui

    2015-01-01

    Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome that most commonly occurs in decompensated liver cirrhosis and incorporates a spectrum of manifestations that ranges from mild cognitive impairment to coma. Although the etiology of HE is not completely understood, it is believed that multiple underlying mechanisms are involved in the pathogenesis of HE, and one of the main factors is thought to be ammonia; however, the ammonia hypothesis in the pathogenesis of HE is incomplete. Recently, it has been increasingly demonstrated that inflammation, including systemic inflammation, neuroinflammation and endotoxemia, acts in concert with ammonia in the pathogenesis of HE in cirrhotic patients. Meanwhile, a good number of studies have found that current therapies for HE, such as lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, could inhibit different types of inflammation, thereby improving the neuropsychiatric manifestations and preventing the progression of HE in cirrhotic patients. The anti-inflammatory effects of these current therapies provide a novel therapeutic approach for cirrhotic patients with HE. The purpose of this review is to describe the inflammatory mechanisms behind the etiology of HE in cirrhosis and discuss the current therapies that target the inflammatory pathogenesis of HE. PMID:26557005

  7. Breathomics--exhaled volatile organic compound analysis to detect hepatic encephalopathy: a pilot study.

    PubMed

    Arasaradnam, R P; McFarlane, M; Ling, K; Wurie, S; O'Connell, N; Nwokolo, C U; Bardhan, K D; Skinner, J; Savage, R S; Covington, J A

    2016-03-01

    The current diagnostic challenge with diagnosing hepatic encephalopathy (HE) is identifying those with minimal HE as opposed to the more clinically apparent covert/overt HE. Rifaximin, is an effective therapy but earlier identification and treatment of HE could prevent liver disease progression and hospitalization. Our pilot study aimed to analyse breath samples of patients with different HE grades, and controls, using a portable electronic (e) nose. 42 patients were enrolled; 22 with HE and 20 controls. Bedside breath samples were captured and analysed using an uvFAIMS machine (portable e-nose). West Haven criteria applied and MELD scores calculated. We classify HE patients from controls with a sensitivity and specificity of 0.88 (0.73-0.95) and 0.68 (0.51-0.81) respectively, AUROC 0.84 (0.75-0.93). Minimal HE was distinguishable from covert/overt HE with sensitivity of 0.79 and specificity of 0.5, AUROC 0.71 (0.57-0.84). This pilot study has highlighted the potential of breathomics to identify VOCs signatures in HE patients for diagnostic purposes. Importantly this was performed utilizing a non-invasive, portable bedside device and holds potential for future early HE diagnosis. PMID:26866470

  8. Inflammation: A novel target of current therapies for hepatic encephalopathy in liver cirrhosis.

    PubMed

    Luo, Ming; Guo, Jian-Yang; Cao, Wu-Kui

    2015-11-01

    Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome that most commonly occurs in decompensated liver cirrhosis and incorporates a spectrum of manifestations that ranges from mild cognitive impairment to coma. Although the etiology of HE is not completely understood, it is believed that multiple underlying mechanisms are involved in the pathogenesis of HE, and one of the main factors is thought to be ammonia; however, the ammonia hypothesis in the pathogenesis of HE is incomplete. Recently, it has been increasingly demonstrated that inflammation, including systemic inflammation, neuroinflammation and endotoxemia, acts in concert with ammonia in the pathogenesis of HE in cirrhotic patients. Meanwhile, a good number of studies have found that current therapies for HE, such as lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, could inhibit different types of inflammation, thereby improving the neuropsychiatric manifestations and preventing the progression of HE in cirrhotic patients. The anti-inflammatory effects of these current therapies provide a novel therapeutic approach for cirrhotic patients with HE. The purpose of this review is to describe the inflammatory mechanisms behind the etiology of HE in cirrhosis and discuss the current therapies that target the inflammatory pathogenesis of HE. PMID:26557005

  9. Role of local and distant functional connectivity density in the development of minimal hepatic encephalopathy

    PubMed Central

    Qi, Rongfeng; Zhang, Long Jiang; Chen, Hui Juan; Zhong, Jianhui; Luo, Song; Ke, Jun; Xu, Qiang; Kong, Xiang; Liu, Chang; Lu, Guang Ming

    2015-01-01

    The progression of functional connectivity (FC) patterns from non-hepatic encephalopathy (non-HE) to minimal HE (MHE) is not well known. This resting-state functional magnetic resonance imaging (rs-fMRI) study investigated the evolution of intrinsic FC patterns from non-HE to MHE. A total of 103 cirrhotic patients (MHE, n = 34 and non-HE, n = 69) and 103 healthy controls underwent rs-fMRI scanning. Maps of distant and local FC density (dFCD and lFCD, respectively) were compared among MHE, non-HE, and healthy control groups. Decreased lFCD in anterior cingulate cortex, pre- and postcentral gyri, cuneus, lingual gyrus, and putamen was observed in both MHE and non-HE patients relative to controls. There was no difference in lFCD between MHE and non-HE groups. The latter showed decreased dFCD in inferior parietal lobule, cuneus, and medial frontal cortex relative to controls; however, MHE patients showed decreased dFCD in frontal and parietal cortices as well as increased dFCD in thalamus and caudate head relative to control and non-HE groups. Abnormal FCD values in some regions correlated with MHE patients’ neuropsychological performance. In conclusion, lFCD and dFCD were perturbed in MHE. Impaired dFCD in regions within the cortico-striato-thalamic circuit may be more closely associated with the development of MHE. PMID:26329994

  10. The Multi-Dimensional Burden of Cirrhosis and Hepatic Encephalopathy on Patients and Caregivers

    PubMed Central

    Bajaj, Jasmohan S.; Wade, James B.; Gibson, Douglas P.; Heuman, Douglas M.; Thacker, Leroy R.; Sterling, Richard K.; Stravitz, R. Todd; Luketic, Velimir; Fuchs, Michael; White, Melanie B.; Bell, Debulon E.; Gilles, HoChong; Morton, Katherine; Noble, Nicole; Puri, Puneet; Sanyal, Arun J.

    2014-01-01

    Objectives Cirrhosis and hepatic encephalopathy (HE) can adversely affect survival, but their effect on socioeconomic and emotional burden on the family is not clear. The aim was to study the emotional and socioeconomic burden of cirrhosis and HE on patients and informal caregivers. Methods A cross-sectional study in two transplant centers (Veterans and University) of cirrhotic patients and their informal caregivers was performed. Demographics for patient/caregivers, model-for-end-stage liver disease (MELD) score, and cirrhosis complications were recorded. Patients underwent a cognitive battery, sociodemographic, and financial questionnaires. Caregivers were given the perceived caregiver burden (PCB; maximum = 155) and Zarit Burden Interview (ZBI)-Short Form (maximum = 48) and questionnaires for depression, anxiety, and social support. Results A total of 104 cirrhotics (70% men, 44% previous HE, median MELD 12, 49% veterans) and their caregivers (66% women, 77% married, relationship duration 32 ± 14 years) were included. Cirrhosis severely impacted the family unit with respect to work (only 56% employed), finances, and adherence. Those with previous HE had worse unemployment (87.5 vs. 19%, P = 0.0001) and financial status (85 vs. 61%, P = 0.019) and posed a higher caregiver burden; PCB (75 vs. 65, P = 0.019) and ZBI (16 vs. 11, P = 0.015) compared with others. Cognitive performance and MELD score were significantly correlated with employment and caregiver burden. Veterans and non-veterans were equally affected. On regression, depression score, MELD, and cognitive tests predicted both PCB and ZBI score. Conclusions Previous HE and cognitive dysfunction are associated with worse employment, financial status, and caregiver burden. Cirrhosis-related expenses impact the family unit's daily functioning and medical adherence. A multidisciplinary approach to address this burden is required. PMID:21556040

  11. Depletion of the AMPAR reserve pool impairs synaptic plasticity in a model of hepatic encephalopathy.

    PubMed

    Schroeter, Annett; Wen, Shuping; Mölders, Andrea; Erlenhardt, Nadine; Stein, Valentin; Klöcker, Nikolaj

    2015-09-01

    Hepatic encephalopathy (HE) is the most common neuropsychiatric complication of acute or chronic liver failure. Clinical symptoms include cognitive and intellectual dysfunction as well as impaired motor activity and coordination. There is general consensus that increased levels of ammonia play a central role in the pathogenesis of HE. However, it is still elusive how cognitive performance including the ability to learn and memorize information is affected by ammonia at molecular levels. In the present study, we have employed a neuroglial co-culture model, which preserves neuroglial interplay but allows for cell-type specific molecular and functional analyses, to investigate glutamatergic neurotransmission under conditions of high ammonia. Chronic exposure to ammonia significantly reduced neuronal mRNA and protein expression of AMPA-subtype glutamate receptors (AMPARs), which mediate most fast excitatory neurotransmission in the brain. Surprisingly, neurons were able to fully maintain basal glutamatergic neurotransmission as recorded by AMPAR-mediated miniature excitatory postsynaptic currents (mEPSCs) even when >50% of total AMPARs were lost. However, long-lasting, activity-dependent changes in the efficacy of synaptic communication, which model the capability of the brain to learn and store information, were severely constrained. Whereas synaptic efficacy could still be depressed, an increase in synaptic strength was abolished. We conclude that neurons retain basal glutamatergic transmission at the expense of the extrasynaptic population of AMPARs, which is revealed when the extrasynaptic reserve pool is recruited in vain for synaptic potentiation. Our findings thus offer a molecular model, which might not only explain impaired synaptic plasticity in HE but also in other neurological diseases accompanied by a decrease in extrasynaptic AMPAR expression. PMID:26363416

  12. Covert hepatic encephalopathy: elevated total glutathione and absence of brain water content changes.

    PubMed

    Oeltzschner, Georg; Butz, Markus; Wickrath, Frithjof; Wittsack, Hans-Jörg; Schnitzler, Alfons

    2016-06-01

    Recent pathophysiological models suggest that oxidative stress and hyperammonemia lead to a mild brain oedema in hepatic encephalopathy (HE). Glutathione (GSx) is a major cellular antioxidant and known to be involved in the interception of both. The aim of this work was to study total glutathione levels in covert HE (minimal HE and HE grade 1) and to investigate their relationship with local brain water content, levels of glutamine (Gln), myo-inositol (mI), neurotransmitter levels, critical flicker frequency (CFF), and blood ammonia. Proton magnetic resonance spectroscopy ((1)H MRS) data were analysed from visual and sensorimotor cortices of thirty patients with covert HE and 16 age-matched healthy controls. Total glutathione levels (GSx/Cr) were quantified with respect to creatine. Furthermore, quantitative MRI brain water content measures were evaluated. Data were tested for links with the CFF and blood ammonia. GSx/Cr was elevated in the visual (mHE) and sensorimotor (mHE, HE 1) MRS volumes and correlated with blood ammonia levels (both P < 0.001). It was further linked to Gln/Cr and mI/Cr (P < 0.01 in visual, P < 0.001 in sensorimotor) and to GABA/Cr (P < 0.01 in visual). Visual GSx/Cr correlated with brain water content in the thalamus, nucleus caudatus, and visual cortex (P < 0.01). Brain water measures did neither show group effects nor correlations with CFF or blood ammonia. Elevated total glutathione levels in covert HE (< HE 2) correlate with blood ammonia and may be a regional-specific reaction to hyperammonemia and oxidative stress. Brain water content is locally linked to visual glutathione levels, but appears not to be associated with changes of clinical parameters. This might suggest that cerebral oedema is only marginally responsible for the symptoms of covert HE. PMID:26563124

  13. Mitochondrial dysfunction as a mediator of hippocampal apoptosis in a model of hepatic encephalopathy.

    PubMed

    Bustamante, J; Lores-Arnaiz, S; Tallis, S; Roselló, D M; Lago, N; Lemberg, A; Boveris, A; Perazzo, J C

    2011-08-01

    In this study, we describe the presence of apoptosis, associated with a mitochondrial dysfunction in the hippocampus of animals in an experimental model defined as minimal hepatic encephalopathy (MHE). This experimental model was studied after 10 days of induced portal vein calibrated stricture, leading to portal hypertension and to a moderate hyperammonemia, without the presence of other evident central nervous system changes. The molecular mechanisms here proposed indicate the presence of apoptotic intrinsic pathways that point to hippocampal mitochondria as an important mediator of apoptosis in this experimental model. In this model of MHE, the presence of DNA fragmentation is documented by 2.3-times increased number of TUNEL-positive cells. These findings together with a higher ratio of the Bcl-2 family members Bax/Bcl-xL in the outer mitochondrial membrane of the MHE animals together with 11% of cytochrome c release indicate the presence of apoptosis in this experimental model. A detailed analysis of the hippocampal mitochondrial physiology was performed after mitochondrial isolation. The determination of the respiratory rate in the presence of malate plus glutamate and ADP showed a 45% decrease in respiratory control in MHE animals as compared with the sham group. A marked decrease of cytochrome oxidase (complex IV of the electron transport chain) was also observed, showing 46% less activity in hippocampal mitochondria from MHE animals. In addition, mitochondria from these animals showed less ability to maintain membrane potential (ΔΨ (m)) which was 13% lower than the sham group. Light scattering experiments showed that mitochondria from MHE animals were more sensitive to swell in the presence of increased calcium concentrations as compared with the sham group. In addition, in vitro studies performed in mitochondria from sham animals showed that mitochondrial permeability transition (MPT) could be a mitochondrial mediator of the apoptotic signaling in the

  14. Clinical and Pathophysiological Characteristics of Cirrhotic Patients with Grade 1 and Minimal Hepatic Encephalopathy

    PubMed Central

    Thomsen, Karen Louise; Macnaughtan, Jane; Tritto, Giovanni; Mookerjee, Rajeshwar P.; Jalan, Rajiv

    2016-01-01

    Background and Aims EASL/AASLD hepatic encephalopathy (HE) guidelines proposed the alternative use of the term ‘Covert HE’ combining minimal HE (mHE) and Grade 1 HE into a single entity. However, longitudinal data to indicate that these are indeed a single entity are lacking. The aims of this study were to determine whether the occurrence of complications of cirrhosis requiring hospital admission and mortality were similar in these sub-groups of patients. Methods Clinically-stable cirrhotic patients (n = 106) with no previous history of ‘Overt HE’ were included over a 2-year period and classified as having no HE (n = 23), mHE (n = 39) or Grade 1 HE (n = 44). Standard biochemistry, venous ammonia, bacterial DNA and neutrophil function were measured at inclusion and the patients were followed for a mean of 230±95 days. Results Patients with Grade 1 HE had significantly more complications requiring hospitalisation (infection 9/18/34%; HE 4/8/18%; other 13/10/11%; P = 0.02) and significantly greater mortality (4/5/20%; P = 0.04) compared to patients with no HE or mHE respectively. Patients with mHE and grade 1 HE had similar ammonia levels, but higher than the no HE group (P<0.001). MELD score was similar between groups but Grade 1 HE patients had increased frequency of bacterial translocation (P = 0.06) and neutrophil spontaneous respiratory burst (P = 0.02) compared to patients with mHE. Conclusions The results of this study show for the first time that ‘Covert HE’ is a heterogeneous entity with significantly greater hospitalisations and mortality in the Grade 1 HE patients compared with mHE. Further prospective longer-term studies are required before EASL/AASLD guidance is fully implemented. PMID:26745876

  15. Rifaximin Improves Driving Simulator Performance in a Randomized Trial of Patients with Minimal Hepatic Encephalopathy

    PubMed Central

    Bajaj, Jasmohan S; Heuman, Douglas M; Wade, James B; Gibson, Douglas P; Saeian, Kia; Wegelin, Jacob A; Hafeezullah, Muhammad; Bell, Debulon E; Sterling, Richard K; Stravitz, R. Todd; Fuchs, Michael; Luketic, Velimir; Sanyal, Arun J

    2010-01-01

    Background & Aims Patients with cirrhosis and minimal hepatic encephalopathy (MHE) have driving difficulties but the effects of therapy on driving performance have not been assessed. We evaluated whether performance on a driving simulator improves in patients with MHE following treatment with rifaximin. Methods Patients with MHE who were current drivers were randomly assigned to placebo or rifaximin groups and followed for 8 weeks (n=42). Patients underwent driving simulation (driving and navigation tasks) at the start (baseline) and end of the study. We evaluated patients’ cognitive abilities, quality-of-life (using the Sickness Impact Profile [SIP]), serum levels of ammonia, levels of inflammatory cytokines, and MELD scores. The primary outcome was percent who improved in driving performance, calculated by: total driving errors=speeding + illegal turns + collisions. Results Over the 8-week study period, patients given rifaximin made significantly greater improvements than those given placebo in avoiding total driving errors (76% vs. 31%, P=0.013), speeding (81% vs. 33%, P=0.005), and illegal turns (62% vs. 19%, P=0.01). Of patients given rifaximin, 91% improved their cognitive performance, compared with 61% of patients given placebo (P=0.01); they also made improvements in the psycho-social dimension of the SIP, compared with the placebo group (P=0.04). Adherence to the assigned drug averaged 92%. Neither group had changes in ammonia levels or MELD scores, but patients in the rifaximin group had increased levels of the anti-inflammatory cytokine interleukin-10. Conclusions Patients with MHE significantly improve driving simulator performance following treatment with rifaximin, compared with placebo. PMID:20849805

  16. Microglial proliferation in the brain of chronic alcoholics with hepatic encephalopathy

    PubMed Central

    Dennis, Claude V.; Sheahan, Pamela J.; Graeber, Manuel B.; Sheedy, Donna L.; Kril, Jillian J.; Sutherland, Greg T.

    2014-01-01

    Hepatic encephalopathy (HE) is a common complication of chronic alcoholism and patients show neurological symptoms ranging from mild cognitive dysfunction to coma and death. The HE brain is characterized by glial changes, including microglial activation, but the exact pathogenesis of HE is poorly understood. During a study investigating cell proliferation in the subventricular zone of chronic alcoholics, a single case with widespread proliferation throughout their adjacent grey and white matter was noted. This case also had concomitant HE raising the possibility that glial proliferation might be a pathological feature of the disease. In order to explore this possibility fixed postmortem human brain tissue from chronic alcoholics with cirrhosis and HE (n = 9), alcoholics without HE (n = 4) and controls (n = 4) were examined using immunohistochemistry and cytokine assays. In total, 4/9 HE cases had PCNA- and a second proliferative marker, Ki-67-positive cells throughout their brain and these cells co-stained with the microglial marker, Iba1. These cases were termed ‘proliferative HE’ (pHE). The microglia in pHEs displayed an activated morphology with hypertrophied cell bodies and short, thickened processes. In contrast, the microglia in white matter regions of the non-proliferative HE cases were less activated and appeared dystrophic. pHEs were also characterized by higher interleukin-6 levels and a slightly higher neuronal density . These findings suggest that microglial proliferation may form part of an early neuroprotective response in HE that ultimately fails to halt the course of the disease because underlying etiological factors such as high cerebral ammonia and systemic inflammation remain. PMID:24346482

  17. Changes in sleep architecture and quality in minimal hepatic encephalopathy patients and relationship to psychological dysfunction

    PubMed Central

    Liu, Changyun; Zhou, Jianguang; Yang, Xuedong; Lv, Jiao; Shi, Yunxing; Zeng, Xiaohong

    2015-01-01

    Objectives: We examined changes in sleep quality and architecture in patients with minimal hepatic encephalopathy (MHE) and the impacts of sleep disruption on patient physical and psychological health. Methods: Ninety-eight MHE patients were examined by polysomnography (PSG) and the Pittsburg sleep quality inventory (PSQI). In addition, patients completed the SAS, SDS, and SCL-90 to examine the relationship between sleep quality and psychological health. Results: Mean relative durations of Stage 1 and Stage 2, sleep latency, microarousal frequency, and total sleep time (TST) were all lower in MHE patients compared to healthy controls (P<0.05 for all). Similarly, SWS and REM stage durations, REM latency, sleep maintenance rate, and sleep efficiency were lower than controls (P<0.01 for all). Mean PSQI scores were lower in MHE patients. Total SAS, SDS, and SCL-90 scores, as well as all SCL-90 subscores, were significantly higher in the MHE group (P<0.05), indicating significant psychological dysfunction. Longer SWS, longer REM, and lower microarousal frequency were associated with improved sleep quality (P<0.05), while shorter SWS and REM led to dyssomnia and daytime functional disturbance (P<0.05, P<0.01). Longer REM latency and higher microarousal frequency were associated with higher PSQI scores (P<0.05, P<0.01), while longer SWS, longer REM, and higher sleep maintenance rate were associated with lower PSQI scores (P<0.05, P<0.01). Finally, total PSQI score and sleep efficiency subscore were positively correlated with total SCL-90 and most SCL-90 subscores (P<0.05). Conclusions: MHE patients suffer from multiple subjective dyssomnias and changes in sleep architecture that are strongly correlated with psychological dysfunction. PMID:26885103

  18. Roles of changes in active glutamine transport in brain edema development during hepatic encephalopathy: an emerging concept.

    PubMed

    Zielińska, Magdalena; Popek, Mariusz; Albrecht, Jan

    2014-01-01

    Excessive glutamine (Gln) synthesis in ammonia-overloaded astrocytes contributes to astrocytic swelling and brain edema, the major complication of hepatic encephalopathy (HE). Much of the newly formed Gln is believed to enter mitochondria, where it is recycled to ammonia, which causes mitochondrial dysfunction (a "Trojan horse" mode of action). A portion of Gln may increase osmotic pressure in astrocytes and the interstitial space, directly and independently contributing to brain tissue swelling. Here we discuss the possibility that altered functioning of Gln transport proteins located in the cellular or mitochondrial membranes, modulates the effects of increased Gln synthesis. Accumulation of excess Gln in mitochondria involves a carrier-mediated transport which is activated by ammonia. Studies on the expression of the cell membrane N-system transporters SN1 (SNAT3) and SN2 (SNAT5), which mediate Gln efflux from astrocytes rendered HE model-dependent effects. HE lowered the expression of SN1 at the RNA and protein level in the cerebral cortex (cc) in the thioacetamide (TAA) model of HE and the effect paralleled induction of cerebral cortical edema. Neither SN1 nor SN2 expression was affected by simple hyperammonemia, which produces no cc edema. TAA-induced HE is also associated with decreased expression of mRNA coding for the system A carriers SAT1 and SAT2, which stimulate Gln influx to neurons. Taken together, changes in the expression of Gln transporters during HE appear to favor retention of Gln in astrocytes and/or the interstitial space of the brain. HE may also affect arginine (Arg)/Gln exchange across the astrocytic cell membrane due to changes in the expression of the hybrid Arg/Gln transporter y(+)LAT2. Gln export from brain across the blood-brain barrier may be stimulated by HE via its increased exchange with peripheral tryptophan. PMID:24072671

  19. Machine Learning Classification of Cirrhotic Patients with and without Minimal Hepatic Encephalopathy Based on Regional Homogeneity of Intrinsic Brain Activity

    PubMed Central

    Liu, Jun; Sun, Tao; Shen, Qun-Tai

    2016-01-01

    Machine learning-based approaches play an important role in examining functional magnetic resonance imaging (fMRI) data in a multivariate manner and extracting features predictive of group membership. This study was performed to assess the potential for measuring brain intrinsic activity to identify minimal hepatic encephalopathy (MHE) in cirrhotic patients, using the support vector machine (SVM) method. Resting-state fMRI data were acquired in 16 cirrhotic patients with MHE and 19 cirrhotic patients without MHE. The regional homogeneity (ReHo) method was used to investigate the local synchrony of intrinsic brain activity. Psychometric Hepatic Encephalopathy Score (PHES) was used to define MHE condition. SVM-classifier was then applied using leave-one-out cross-validation, to determine the discriminative ReHo-map for MHE. The discrimination map highlights a set of regions, including the prefrontal cortex, anterior cingulate cortex, anterior insular cortex, inferior parietal lobule, precentral and postcentral gyri, superior and medial temporal cortices, and middle and inferior occipital gyri. The optimized discriminative model showed total accuracy of 82.9% and sensitivity of 81.3%. Our results suggested that a combination of the SVM approach and brain intrinsic activity measurement could be helpful for detection of MHE in cirrhotic patients. PMID:26978777

  20. Differential regional responsiveness of astroglia in mild hepatic encephalopathy: An Immunohistochemical approach in bile duct ligated rat.

    PubMed

    Hiba, Omar El; Elgot, Abdeljalil; Ahboucha, Samir; Gamrani, Halima

    2016-05-01

    Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs in both acute and chronic liver failure. However, the pathomechanisms of the disease remains obscure. Neuropathological studies have demonstrated a primary gliopathy in humans as well as in animal models of chronic and acute liver failure. Here, we have investigated in an animal model of mild HE: the bile duct ligated rat (BDL) at the cirrhotic stage (4 weeks after surgery), the expression of the key marker of mature astrocytes; the glial fibrillary acidic protein (GFAP) in different brain areas such as: Substantia nigra pars compacta (SNc), Ventral tegmental area (VTA), hippocampus, dorsal striatum and brain cortex by means of immunohistochemistry. The immunohistochemical study showed, in BDL compared to the operated controls (shams), a diminished astrocyte reactivity corresponding to a loss of GFAP expression within SNc, VTA, hippocampus and dorsal striatum (p<0.05),whereas in the brain cortex astrocytes appeared strongly immunoreactive with increased GFAP expression (p<0.05) as compared to shams. Our finding demonstrated differential astroglial responses which depend to the specificity of the area investigated and its particular neuronal neighboring environment, and could have possible outcomes on the diverse neuronal functions especially those observed during the different episodes of hepatic encephalopathy. PMID:26995310

  1. Rifaximin treatment for reduction of risk of overt hepatic encephalopathy recurrence.

    PubMed

    Flamm, Steven L

    2011-05-01

    Hepatic encephalopathy (HE) is a common problem in patients with chronic liver disease and is characterized by diminished mentation and neuromuscular abnormalities. Symptoms range from subtle cognitive changes to coma and death. Gut-derived toxins such as ammonia are thought to play a central role in the pathogenesis of HE. Treatment strategies are directed at increased elimination or reduction of gut-derived ammonia in addition to correction of dynamic conditions that provoke bouts of HE. The standard of care for treatment of acute HE is lactulose, a nonabsorbable disaccharide that is thought to increase elimination and reduce absorption of ammonia. Although lactulose seems to work in the acute setting, the rate of recurrent HE on maintenance lactulose is high. Medications have been sought that reduce the rate of recurrent HE in patients at high risk for HE but none have been identified. Rifaximin is a poorly absorbed antibiotic that is thought to reduce ammonia production by eliminating ammonia-producing colonic bacteria. Many small studies have suggested that rifaximin is effective in treating acute HE and is extremely well tolerated. This led to a randomized, placebo-controlled, multicenter, multinational trial investigating the efficacy of rifaximin over a 6-month period in reducing the risk of recurrent HE in patients at baseline, but with a history of at least two bouts of acute HE in the previous 6 months prior to enrollment. Lactulose could be administered at the discretion of the investigator. A total of 299 patients were randomized to receive rifaximin or placebo; 91% of patients in each group received lactulose. Compared with placebo, patients at high risk for recurrent HE in the rifaximin group had highly statistically significant reductions in bouts of acute HE (58%) and reductions in hospitalizations related to HE (50%) over a 6-month period. The medication was well tolerated with a side-effect profile comparable to placebo. This led to the approval

  2. Rifaximin treatment for reduction of risk of overt hepatic encephalopathy recurrence

    PubMed Central

    Flamm, Steven L.

    2011-01-01

    Hepatic encephalopathy (HE) is a common problem in patients with chronic liver disease and is characterized by diminished mentation and neuromuscular abnormalities. Symptoms range from subtle cognitive changes to coma and death. Gut-derived toxins such as ammonia are thought to play a central role in the pathogenesis of HE. Treatment strategies are directed at increased elimination or reduction of gut-derived ammonia in addition to correction of dynamic conditions that provoke bouts of HE. The standard of care for treatment of acute HE is lactulose, a nonabsorbable disaccharide that is thought to increase elimination and reduce absorption of ammonia. Although lactulose seems to work in the acute setting, the rate of recurrent HE on maintenance lactulose is high. Medications have been sought that reduce the rate of recurrent HE in patients at high risk for HE but none have been identified. Rifaximin is a poorly absorbed antibiotic that is thought to reduce ammonia production by eliminating ammonia-producing colonic bacteria. Many small studies have suggested that rifaximin is effective in treating acute HE and is extremely well tolerated. This led to a randomized, placebo-controlled, multicenter, multinational trial investigating the efficacy of rifaximin over a 6-month period in reducing the risk of recurrent HE in patients at baseline, but with a history of at least two bouts of acute HE in the previous 6 months prior to enrollment. Lactulose could be administered at the discretion of the investigator. A total of 299 patients were randomized to receive rifaximin or placebo; 91% of patients in each group received lactulose. Compared with placebo, patients at high risk for recurrent HE in the rifaximin group had highly statistically significant reductions in bouts of acute HE (58%) and reductions in hospitalizations related to HE (50%) over a 6-month period. The medication was well tolerated with a side-effect profile comparable to placebo. This led to the approval

  3. Modulation of the Metabiome by Rifaximin in Patients with Cirrhosis and Minimal Hepatic Encephalopathy

    PubMed Central

    Bajaj, Jasmohan S.; Heuman, Douglas M.; Sanyal, Arun J.; Hylemon, Phillip B.; Sterling, Richard K.; Stravitz, R. Todd; Fuchs, Michael; Ridlon, Jason M.; Daita, Kalyani; Monteith, Pamela; Noble, Nicole A.; White, Melanie B.; Fisher, Andmorgan; Sikaroodi, Masoumeh; Rangwala, Huzefa; Gillevet, Patrick M.

    2013-01-01

    Hepatic encephalopathy (HE) represents a dysfunctional gut-liver-brain axis in cirrhosis which can negatively impact outcomes. This altered gut-brain relationship has been treated using gut-selective antibiotics such as rifaximin, that improve cognitive function in HE, especially its subclinical form, minimal HE (MHE). However, the precise mechanism of the action of rifaximin in MHE is unclear. We hypothesized that modulation of gut microbiota and their end-products by rifaximin would affect the gut-brain axis and improve cognitive performance in cirrhosis. Aim To perform a systems biology analysis of the microbiome, metabolome and cognitive change after rifaximin in MHE. Methods Twenty cirrhotics with MHE underwent cognitive testing, endotoxin analysis, urine/serum metabolomics (GC and LC-MS) and fecal microbiome assessment (multi-tagged pyrosequencing) at baseline and 8 weeks post-rifaximin 550 mg BID. Changes in cognition, endotoxin, serum/urine metabolites (and microbiome were analyzed using recommended systems biology techniques. Specifically, correlation networks between microbiota and metabolome were analyzed before and after rifaximin. Results There was a significant improvement in cognition(six of seven tests improved,p<0.01) and endotoxemia (0.55 to 0.48 Eu/ml, p = 0.02) after rifaximin. There was a significant increase in serum saturated (myristic, caprylic, palmitic, palmitoleic, oleic and eicosanoic) and unsaturated (linoleic, linolenic, gamma-linolenic and arachnidonic) fatty acids post-rifaximin. No significant microbial change apart from a modest decrease in Veillonellaceae and increase in Eubacteriaceae was observed. Rifaximin resulted in a significant reduction in network connectivity and clustering on the correlation networks. The networks centered on Enterobacteriaceae, Porphyromonadaceae and Bacteroidaceae indicated a shift from pathogenic to beneficial metabolite linkages and better cognition while those centered on autochthonous taxa

  4. 18F-DPA-714 PET Imaging for Detecting Neuroinflammation in Rats with Chronic Hepatic Encephalopathy

    PubMed Central

    Kong, Xiang; Luo, Song; Wu, Jin Rong; Wu, Shawn; De Cecco, Carlo N.; Schoepf, U. Joseph; Spandorfer, Adam J.; Wang, Chun Yan; Tian, Ying; Chen, Hui Juan; Lu, Guang Ming; Yang, Gui Fen; Zhang, Long Jiang

    2016-01-01

    Neuroinflammation is considered to be the pathogenesis of hepatic encephalopathy (HE), and imaging neuroinflammation is implicated in HE management. 11C-PK11195, a typical translocator protein (TSPO) radiotracer, is used for imaging neuroinflammation. However, it has inherent limitations, such as short half-life and limited availability. The purpose of this study was to demonstrate the efficiency of new generation TSPO radiotracer, 18F-DPA-714, in detecting and monitoring neuroinflammation of chronic HE. This study was divided into two parts. The first part compared 18F-DPA-714 and 11C-PK11195 radiotracers in ten HE induced rats [bile duct ligation (BDL) and fed hyperammonemic diet (HD)] and 6 control rats. The animal subjects underwent dynamic positron emission tomography (PET) during 2-day intervals. The 11C-PK11195 PET study showed no differences in whole brain average percent injected dose per gram (%ID/g) values at all time points (all P>0.05), while the 18F-DPA-714 PET study showed higher whole brain average %ID/g values in HE rats compared to control group rats at 900 s to 3300 s after injecting radiotracer (all P<0.05). The second part of the study evaluated the effectiveness of ibuprofen (IBU) treatment to chronic HE. Forty rats were classified into six groups, including Sham+normal saline (NS), Sham+IBU, BDL+NS, BDL+HD+NS, BDL+IBU, and BDL+HD+IBU groups. 18F-DPA-714 PET was used to image neuroinflammation. Whole and regional brain average %ID/g values, neurological features, inflammatory factors and activated microglia showed better in the IBU groups than in the NS groups (all P<0.05) and no difference was seen in the Sham groups compared to IBU groups (all P>0.05). In conclusion, this study demonstrated that 18F-DPA-714 is an ideal TPSO radiotracer for imaging neuroinflammation and monitoring anti-neuroinflammation treatment efficacy of chronic HE. PMID:27279913

  5. Erythromycin versus neomycin in the treatment of hepatic encephalopathy in cirrhosis: a randomized double-blind study

    PubMed Central

    2013-01-01

    Background Hepatic encephalopathy (HE) is a severe complication in patients with hepatic cirrhosis, which causes numerous hospital admissions and deaths. Antibiotics are the best options in HE treatment, but head-to-head comparisons between these drugs are scarce. Erythromycin combines the antimicrobial effect and prokinetic properties in the same drug, but it has never been used in HE treatment. Our aim was to evaluate the efficacy of erythromycin as an HE treatment. Methods We achieved a randomized controlled trial of adult patients with HE and hepatic cirrhosis admitted in our hospital. After randomization, the subjects received either erythromycin 250 mg or neomycin 1 g orally QID until hospital discharge or prescription of another antibiotic. All subjects were blindly evaluated every day towards quantifying clinical, neuropsychometric, hepatic and renal exams. Statistical analysis was employed to compare the groups and correlate the variables with hospitalization duration. Results 30 patients were evaluated (15 treated with each drug). At hospital admission, the groups were homogeneous, but the erythromycin group subjects achieved a shorter hospitalization stay (p = 0.032) and a more expressive reduction in alanine aminotranspherase levels (p = 0.026). Hospitalization duration was positively correlated with C reactive protein levels measured previous to (p = 0.015) and after treatment (p = 0.01). Conclusions In the sample evaluated erythromycin was associated with significant reductions in hospital stay and in alanine aminotranspherase values. Hospitalization time was positive correlated with C reactive protein levels measured before and after the treatments. PMID:23324408

  6. Contribution of altered signal transduction associated to glutamate receptors in brain to the neurological alterations of hepatic encephalopathy

    PubMed Central

    Felipo, Vicente

    2006-01-01

    Patients with liver disease may present hepatic enceph-alopathy (HE), a complex neuropsychiatric syndrome covering a wide range of neurological alterations, including cognitive and motor disturbances. HE reduces the quality of life of the patients and is associated with poor prognosis. In the worse cases HE may lead to coma or death. The mechanisms leading to HE which are not well known are being studied using animal models. The neurological alterations in HE are a consequence of impaired cerebral function mainly due to alterations in neurotransmission. We review here some studies indicating that alterations in neurotransmission associated to different types of glutamate receptors are responsible for some of the cognitive and motor alterations present in HE. These studies show that the function of the signal transduction pathway glutamate-nitric oxide-cGMP associated to the NMDA type of glutamate receptors is impaired in brain in vivo in HE animal models as well as in brain of patients died of HE. Activation of NMDA receptors in brain activates this pathway and increases cGMP. In animal models of HE this increase in cGMP induced by activation of NMDA receptors is reduced, which is responsible for the impairment in learning ability in these animal models. Increasing cGMP by pharmacological means restores learning ability in rats with HE and may be a new therapeutic approach to improve cognitive function in patients with HE. However, it is necessary to previously assess the possible secondary effects. Patients with HE may present psychomotor slowing, hypokinesia and bradykinesia. Animal models of HE also show hypolocomotion. It has been shown in rats with HE that hypolocomotion is due to excessive activation of metabotropic glutamate receptors (mGluRs) in substantia nigra pars reticulata. Blocking mGluR1 in this brain area normalizes motor activity in the rats, suggesting that a similar treatment for patients with HE could be useful to treat psychomotor slowing and

  7. Modulation of GABAA receptors by neurosteroids. A new concept to improve cognitive and motor alterations in hepatic encephalopathy.

    PubMed

    Agusti, Ana; Llansola, Marta; Hernández-Rabaza, Vicente; Cabrera-Pastor, Andrea; Montoliu, Carmina; Felipo, Vicente

    2016-06-01

    Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome affecting patients with liver diseases, mainly those with liver cirrhosis. The mildest form of HE is minimal HE (MHE), with mild cognitive impairment, attention deficit, psychomotor slowing and impaired visuo-motor and bimanual coordination. MHE may progress to clinical HE with worsening of the neurological alterations which may lead to reduced consciousness and, in the worse cases, may progress to coma and death. HE affects several million people in the world and is a serious health, social and economic problem. There are no specific treatments for the neurological alterations in HE. The mechanisms underlying the cognitive and motor alterations in HE are beginning to be clarified in animal models. These studies have allowed to design and test in animal models of HE new therapeutic approaches which have successfully restored cognitive and motor function in rats with HE. In this article we review the evidences showing that. PMID:26307490

  8. Reversal of Low-Grade Cerebral Edema After Lactulose/Rifaximin Therapy in Patients with Cirrhosis and Minimal Hepatic Encephalopathy

    PubMed Central

    Rai, Rahul; Ahuja, Chirag K; Agrawal, Swastik; Kalra, Naveen; Duseja, Ajay; Khandelwal, Niranjan; Chawla, Yogesh; Dhiman, Radha K

    2015-01-01

    OBJECTIVES: Decreased magnetization transfer ratio (MTR) in the brain characterizes cerebral edema (CE) in patients with liver cirrhosis, but the role of treatment on its reversibility has not been studied in patients who have minimal hepatic encephalopathy (MHE). This study was carried to evaluate the reversibility of CE with lactulose and rifaximin treatment in patients with MHE and role of ammonia, pro-inflammatory interleukins (IL-1, IL-6) and tumor necrosis factor (TNF)-α in its pathogenesis. METHODS: Twenty-three patients with cirrhosis (14 with MHE, 9 without MHE (NMHE)) and 6 healthy controls underwent ammonia, IL-1, IL-6, TNF-α estimation, and MTR in frontal white matter (FWM), parietal white matter (PWM), internal capsule (IC), and basal ganglia (BG). RESULTS: Ammonia was significantly higher in the cirrhosis group compared with controls and in MHE compared with the NMHE group. Ammonia correlated positively with IL-1 and IL-6. MTRs in FWM, PWM, IC, and BG were significantly lower in the MHE group compared with controls and in PWM, IC, and BG compared with the NMHE group. MHE patients showed significant MTR increase in FWM, PWM, and IC with treatment. IL-6 and ammonia had significant negative and significant positive psychometric hepatic encephalopathy score (PHES) correlation with MTR in various regions. CONCLUSIONS: This study, for the first time, demonstrated the reversibility of low-grade CE with treatment in patients with MHE. Negative correlation between ammonia, IL-6 levels, and MTR and positive correlation between PHES and MTR in MHE patients suggests the role of inflammation and ammonia in the genesis of low-grade CE. PMID:26378384

  9. Obstructive jaundice due to radiation-induced hepatic duct stricture

    SciTech Connect

    Chandrasekhara, K.L.; Iyer, S.K.

    1984-10-01

    A case of obstructive jaundice due to radiation-induced hepatic duct stricture is reported. The patient received postoperative radiation for left adrenal carcinoma, seven years prior to this admission. The sequelae of hepatobiliary radiation and their management are discussed briefly.

  10. Effect of Rifaximin, Probiotics, and l-Ornithine l-Aspartate on Minimal Hepatic Encephalopathy: A Randomized Controlled Trial

    PubMed Central

    Sharma, Kapil; Pant, Sanjay; Misra, Sriprakash; Dwivedi, Manisha; Misra, Alok; Narang, Sushil; Tewari, Reshu; Bhadoria, Ajeet S.

    2014-01-01

    Background/Aims: Minimal hepatic encephalopathy (MHE) implies subtle impairment of cognitive functions in the absence of features of overt encephalopathy. We aimed to determine the prevalence of MHE in patients with liver cirrhosis and to find out the effect of rifaximin, probiotics, and l-ornithine l-aspartate (LOLA) individually in reversal of MHE by comparing it with placebo group. Patients and Methods: This study was carried out in two phases. Phase I included the recruitment of 250 apparently healthy controls and extraction of normative data utilizing three neuropsychometric tests (NPTs) and critical flicker frequency (CFF) test. Phase II consisted of screening and recruitment of patients of MHE followed by drugs trial. A total of 317 cirrhotics were screened; 111 were excluded and the remaining 206 cirrhotics were screened for MHE using NPTs and/or CFF test. Of these, 124 patients with MHE were randomized to receive LOLA (n = 31), rifaximin (n = 31), probiotics (n = 32), for 2 months and were compared with patients who were given placebo (n = 30). Results: Out of 206 cirrhotics, 124 (60.19%) had MHE. Among these 124 MHE patients, 87 (70.16%) patients had CFF <39Hz, 112 (90.32%) patients with MHE had two or more abnormal NPTs, and 75 (60.48%) patients had abnormality on both the CFF values and more than two abnormal NPTs. Intention-to-treat analysis showed the number of patients who improved after giving treatment were 67.7% (21/31), 70.9% (22/31), 50% (16/32), and 30% (9/30) for LOLA, rifaximin, probiotics, and placebo, respectively. CFF scores and improvement in psychometric tests after treatment were significantly higher (P < 0.05) for LOLA, rifaximin, and probiotics as compared with placebo group. Conclusions: Prevalence of MHE is high in patients with cirrhosis of liver. Rifaximin, LOLA, and probiotics are better than giving placebo in patients with MHE. PMID:25038208

  11. 1H nuclear magnetic resonance spectroscopy-based metabonomic study in patients with cirrhosis and hepatic encephalopathy

    PubMed Central

    Dabos, Konstantinos John; Parkinson, John Andrew; Sadler, Ian Howard; Plevris, John Nicholas; Hayes, Peter Clive

    2015-01-01

    AIM: To identify plasma metabolites used as biomarkers in order to distinguish cirrhotics from controls and encephalopathics. METHODS: A clinical study involving stable cirrhotic patients with and without overt hepatic encephalopathy was designed. A control group of healthy volunteers was used. Plasma from those patients was analysed using 1H - nuclear magnetic resonance spectroscopy. We used the Carr Purcell Meiboom Gill sequence to process the sample spectra at ambient probe temperature. We used a gated secondary irradiation field for water signal suppression. Samples were calibrated and referenced using the sodium trimethyl silyl propionate peak at 0.00 ppm. For each sample 128 transients (FID’s) were acquired into 32 K complex data points over a spectral width of 6 KHz. 30 degree pulses were applied with an acquisition time of 4.0 s in order to achieve better resolution, followed by a recovery delay of 12 s, to allow for complete relaxation and recovery of the magnetisation. A metabolic profile was created for stable cirrhotic patients without signs of overt hepatic encephalopathy and encephalopathic patients as well as healthy controls. Stepwise discriminant analysis was then used and discriminant factors were created to differentiate between the three groups. RESULTS: Eighteen stabled cirrhotic patients, eighteen patients with overt hepatic encephalopathy and seventeen healthy volunteers were recruited. Patients with cirrhosis had significantly impaired ketone body metabolism, urea synthesis and gluconeogenesis. This was demonstrated by higher concentrations of acetoacetate (0.23 ± 0.02 vs 0.05 ± 0.00, P < 0.01), and b-hydroxybutarate (0.58 ± 0.14 vs 0.08 ± 0.00, P < 0.01), lower concentrations of glutamine (0.44 ± 0.08 vs 0.63 ± 0.03, P < 0.05), histidine (0.16 ± 0.01 vs 0.36 ± 0.04, P < 0.01) and arginine (0.08 ± 0.01 vs 0.14 ± 0.02, P < 0.03) and higher concentrations of glutamate (1.36 ± 0.25 vs 0.58 ± 0.04, P < 0.01), lactate (1.53 ± 0

  12. Posterior reversible encephalopathy syndrome with PLEDs-plus due to mesalamine

    PubMed Central

    Cherian, Ajith; Soumya, C. V.; Iype, Thomas; Mathew, Mini; Sandeep, P.; Thadam, Jessline K.; Chithra, P.

    2014-01-01

    A 32-year-old lady developed status epilepticus and acute visual loss while on mesalamine for Crohn's disease. Her clinical course and magnetic resonance imaging (MRI) were suggestive of posterior reversible encephalopathy syndrome (PRES). She had periodic lateralized epileptiform discharges plus (PLEDs-plus) on electroencephalogram (EEG), which responded to sodium valproate. Her vision improved from counting fingers at one-meter distance to 6/12. Though different cytotoxic drugs have been implicated as causative agents, this is the first case report of mesalamine-induced PRES. This case highlights the need for aggressive treatment of PLEDs-plus with EEG monitoring using a broad-spectrum antiepileptic drug like valproate, which has contributed to the rapid reversibility of vision in PRES subjects, and the need for a thorough drug history for etiological clues. PMID:24741259

  13. Subarachnoid hemorrhage due to ruptured intracranial aneurysm following posterior reversible encephalopathy syndrome.

    PubMed

    Nanba, Takamasa; Kashimura, Hiroshi; Saura, Hiroaki; Takeda, Masaru

    2016-01-01

    Although posterior reversible encephalopathy syndrome (PRES) is rarely associated with subarachnoid hemorrhage, to our knowledge, rupture of a concomitant cerebral aneurysm following PRES has not been reported. We describe a patient with atypical PRES involving the brainstem, thalamus, and periventricular white matter without cortical or subcortical edema of the parietooccipital lobe on magnetic resonance imaging, with rupture of a concomitant cerebral aneurysm. Preexisting extremely high blood pressure may trigger atypical PRES, and failure to lower blood pressure may lead to a concomitant aneurysm rupture. In the future treatment of hypertensive urgency with a recurrence of symptoms and mean arterial blood pressure >150 mmHg, it is advisable to immediately hospitalize the patient for aggressive blood pressure management, especially if PRES is suspected based on clinical and radiological features. PMID:27365964

  14. Subarachnoid hemorrhage due to ruptured intracranial aneurysm following posterior reversible encephalopathy syndrome

    PubMed Central

    Nanba, Takamasa; Kashimura, Hiroshi; Saura, Hiroaki; Takeda, Masaru

    2016-01-01

    Although posterior reversible encephalopathy syndrome (PRES) is rarely associated with subarachnoid hemorrhage, to our knowledge, rupture of a concomitant cerebral aneurysm following PRES has not been reported. We describe a patient with atypical PRES involving the brainstem, thalamus, and periventricular white matter without cortical or subcortical edema of the parietooccipital lobe on magnetic resonance imaging, with rupture of a concomitant cerebral aneurysm. Preexisting extremely high blood pressure may trigger atypical PRES, and failure to lower blood pressure may lead to a concomitant aneurysm rupture. In the future treatment of hypertensive urgency with a recurrence of symptoms and mean arterial blood pressure >150 mmHg, it is advisable to immediately hospitalize the patient for aggressive blood pressure management, especially if PRES is suspected based on clinical and radiological features. PMID:27365964

  15. GR3027 antagonizes GABAA receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy.

    PubMed

    Johansson, Maja; Agusti, Ana; Llansola, Marta; Montoliu, Carmina; Strömberg, Jessica; Malinina, Evgenya; Ragagnin, Gianna; Doverskog, Magnus; Bäckström, Torbjörn; Felipo, Vicente

    2015-09-01

    Hepatic encephalopathy (HE) is one of the primary complications of liver cirrhosis. Current treatments for HE, mainly directed to reduction of ammonia levels, are not effective enough because they cannot completely eliminate hyperammonemia and inflammation, which induce the neurological alterations. Studies in animal models show that overactivation of GABAA receptors is involved in cognitive and motor impairment in HE and that reducing this activation restores these functions. We have developed a new compound, GR3027, that selectively antagonizes the enhanced activation of GABAA receptors by neurosteroids such as allopregnanolone and 3α,21-dihydroxy-5α-pregnan-20-one (THDOC). This work aimed to assess whether GR3027 improves motor incoordination, spatial learning, and circadian rhythms of activity in rats with HE. GR3027 was administered subcutaneously to two main models of HE: rats with chronic hyperammonemia due to ammonia feeding and rats with portacaval shunts (PCS). Motor coordination was assessed in beam walking and spatial learning and memory in the Morris water maze and the radial maze. Circadian rhythms of ambulatory and vertical activity were also assessed. In both hyperammonemic and PCS rats, GR3027 restores motor coordination, spatial memory in the Morris water maze, and spatial learning in the radial maze. GR3027 also partially restores circadian rhythms of ambulatory and vertical activity in PCS rats. GR3027 is a novel approach to treatment of HE that would normalize neurological functions altered because of enhanced GABAergic tone, affording more complete normalization of cognitive and motor function than current treatments for HE. PMID:26138462

  16. GR3027 antagonizes GABAA receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy

    PubMed Central

    Johansson, Maja; Agusti, Ana; Llansola, Marta; Montoliu, Carmina; Strömberg, Jessica; Malinina, Evgenya; Ragagnin, Gianna; Doverskog, Magnus; Bäckström, Torbjörn

    2015-01-01

    Hepatic encephalopathy (HE) is one of the primary complications of liver cirrhosis. Current treatments for HE, mainly directed to reduction of ammonia levels, are not effective enough because they cannot completely eliminate hyperammonemia and inflammation, which induce the neurological alterations. Studies in animal models show that overactivation of GABAA receptors is involved in cognitive and motor impairment in HE and that reducing this activation restores these functions. We have developed a new compound, GR3027, that selectively antagonizes the enhanced activation of GABAA receptors by neurosteroids such as allopregnanolone and 3α,21-dihydroxy-5α-pregnan-20-one (THDOC). This work aimed to assess whether GR3027 improves motor incoordination, spatial learning, and circadian rhythms of activity in rats with HE. GR3027 was administered subcutaneously to two main models of HE: rats with chronic hyperammonemia due to ammonia feeding and rats with portacaval shunts (PCS). Motor coordination was assessed in beam walking and spatial learning and memory in the Morris water maze and the radial maze. Circadian rhythms of ambulatory and vertical activity were also assessed. In both hyperammonemic and PCS rats, GR3027 restores motor coordination, spatial memory in the Morris water maze, and spatial learning in the radial maze. GR3027 also partially restores circadian rhythms of ambulatory and vertical activity in PCS rats. GR3027 is a novel approach to treatment of HE that would normalize neurological functions altered because of enhanced GABAergic tone, affording more complete normalization of cognitive and motor function than current treatments for HE. PMID:26138462

  17. Differential Impact of Hyponatremia and Hepatic Encephalopathy on Health-Related Quality of Life and Brain Metabolite Abnormalities in Cirrhosis

    PubMed Central

    Ahluwalia, Vishwadeep; Wade, James B; Thacker, Leroy; Kraft, Kenneth A; Sterling, Richard K; Stravitz, R Todd; Fuchs, Michael; Bouneva, Iliana; Puri, Puneet; Luketic, Velimir; Sanyal, Arun J; Gilles, HoChong; Heuman, Douglas M; Bajaj, Jasmohan S

    2013-01-01

    Background Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair health-related quality-of-life (HRQOL) and cognition in cirrhosis. Aim To study effect of hyponatremia on cognition, HRQOL and brain MR spectroscopy (MRS) independent of HE. Methods Four cirrhotic groups(no HE/HN, HE alone, HN alone (sodium<130mEq/L),HE+HN) underwent cognitive testing, HRQOL using Sickness Impact Profile (SIP: higher score is worse; has psycho-social and physical sub-scores) and brain MRS (myoinositol(mI) and glutamate+glutamine(Glx)), which were compared across groups. A subset underwent HRQOL testing before/after diuretic withdrawal. Results 82 cirrhotics (30 no HE/HN, 25 HE, 17 HE+HN and 10 HN, MELD 12, 63% Hepatitis C) were included. Cirrhotics with HN alone and without HE/HN had better cognition compared to HE groups (median abnormal tests no-HE/HN:3, HN:3.5, HE:6.5,HE+HN:7, p=0.008). Despite better cognition, HN only patients had worse HRQOL in total and psychosocial SIP while both HN groups (with/without HE) had a significantly worse physical SIP(p<0.0001, all comparisons). Brain MRS showed lowest Glx in HN and highest in HE groups (p<0.02). mI levels were comparably decreased in the three affected (HE,HE+HN and HN) groups compared to no HE/HN and were associated with poor HRQOL. Six HE+HN cirrhotics underwent diuretic withdrawal which improved serum sodium and total/psycho-social SIP scores. Conclusions Hyponatremic cirrhotics without HE have poor HRQOL despite better cognition than those with concomitant HE. Glx levels were lowest in HN without HE but mI was similar across affected groups. HRQOL improved after diuretic withdrawal. Hyponatremia has a complex, non-linear relationship with brain Glx and mI, cognition and HRQOL. PMID:23665182

  18. Hyperammonemia and Systemic Inflammatory Response Syndrome Predicts Presence of Hepatic Encephalopathy in Dogs with Congenital Portosystemic Shunts

    PubMed Central

    Tivers, Mickey S.; Handel, Ian; Gow, Adam G.; Lipscomb, Vicky J.; Jalan, Rajiv; Mellanby, Richard J.

    2014-01-01

    Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common congenital abnormalities in dogs is a congenital portosystemic shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS often have clinical signs which mimic clinical signs observed in humans with HE. Our hypothesis is that the pathogenesis of HE in dogs with a cPSS is similar to humans with HE. The aim of the study was to measure a range of clinical, haematological and biochemical parameters, which have been linked to the development of HE in humans, in dogs with a cPSS and a known HE grade. One hundred and twenty dogs with a cPSS were included in the study and multiple regression analysis of clinical, haematological and biochemical variables revealed that plasma ammonia concentrations and systemic inflammatory response syndrome scores predicted the presence of HE. Our findings further support the notion that the pathogenesis of canine and human HE share many similarities and indicate that dogs with cPSS may be an informative spontaneous model of human HE. Further investigations on dogs with cPSS may allow studies on HE to be undertaken without creating surgical models of HE thereby allowing the number of large animals used in animal experimentation to be reduced. PMID:24392080

  19. Lower values of handgrip strength and adductor pollicis muscle thickness are associated with hepatic encephalopathy manifestations in cirrhotic patients.

    PubMed

    Augusti, L; Franzoni, L C; Santos, L A A; Lima, T B; Ietsugu, M V; Koga, K H; Moriguchi, S M; Betting, L E; Caramori, C A; Silva, G F; Romeiro, F G

    2016-08-01

    Hepatic encephalopathy (HE) is a late complication of liver cirrhosis and is clearly associated with poor outcomes. Chronic liver insufficiency leads to progressive muscle wasting, impairing ammonia metabolism and thus increasing the risk for HE. Given the association between lean mass and adductor pollicis muscle thickness (APMT), it has been used to predict outcome and complications in many conditions, but not yet in cirrhotic patients. Therefore, this article aimed to study the association between HE manifestations and measures related to muscle mass and strength. This cross-sectional study included 54 cirrhotic outpatients with HE varying from subclinical to grade II according to the West-Haven criteria, who were submitted to neuropsychometric tests, electroencephalogram, brain Single Photon Emission Computed Tomography (SPECT), anthropometric measurements, handgrip strength (HGS) and dual energy X-ray absorptiometry exam (DXA). Multiple logistic regression analysis was performed to investigate the association between body composition measures and HE grade. Analysis of the area under the receiver operator characteristic (AUROC) curve revealed the values related to neurological manifestations (HE grades I and II). Reductions in APMT and HGS were associated with higher HE grades, suggesting a big impact caused by the loss of muscle mass and function on HE severity. The link between HE manifestations and anthropometric measures, namely APMT and HGS, point to a significant relation concerning skeletal muscles and the neurological impairment in this population. PMID:27131802

  20. The Mind and Liver Test: A New Approach to the Diagnosis of Minimal Hepatic Encephalopathy in Resource-Poor Settings

    PubMed Central

    Ali, Sajjadh M. J.; Seward, James; Venkataraman, Jayanthi

    2014-01-01

    Background and Aims. Minimal hepatic encephalopathy (MHE) is diagnosed using neuropsychometric tests or neurophysiological tests that are either inapplicable to illiterate patient population in resource-poor settings or require sophisticated and expensive equipment. The available tests assess discrete domains of mental impairment. Our aim was (a) to design a neuropsychometric test that measures all domains of mental impairment in MHE using one metric; (b) to evaluate its sensitivity, specificity, and reproducibility. Methods. The mind and liver test (MALT), a psychometric test assessing cognition, memory, and psychometric impairment, each on a scale of 20, was designed keeping in mind the requirements of a universal test. 40 cirrhotics and 36 controls were subjected to critical flicker frequency (CFF) and MALT in same sitting. ROC curve was plotted for MALT using CFF as gold standard. Bland-Altman plot was used to find test-retest agreement. Results. CFF values and MALT scores varied significantly between the cases and the controls (P < 0.05). MALT was 94% sensitive and 83% specific. Using ROC with CFF as gold standard, the AUC for diagnosis of MHE using MALT score was 0.89. Test-retest agreement was high (ICC = 0.89). Conclusion. In this pilot study, MALT proved to be highly sensitive, specific, inexpensive, and reproducible. PMID:25548682

  1. Automation of o-dianisidine assay for ceruloplasmin activity analyses: usefulness of investigation in Wilson's disease and in hepatic encephalopathy.

    PubMed

    Siotto, Mariacristina; Pasqualetti, Patrizio; Marano, Massimo; Squitti, Rosanna

    2014-10-01

    Ceruloplasmin (Cp) is a serum ferroxidase that plays an essential role in iron metabolism. It is routinely tested by immunoturbidimetric assays that quantify the concentration of the protein both in its active and inactive forms. Cp activity is generally analyzed manually; the process is time-consuming, has a limited repeatability, and is not suitable for a clinical setting. To overcome these inconveniences, we have set the automation of the o-dianisidine Cp activity assay on a Cobas Mira Plus apparatus. The automation was rapid and repeatable, and the data were provided in terms of IU/L. The assay was adapted for human sera and showed a good precision [coefficient of variation (CV) 3.7 %] and low limit of detection (LoD 11.58 IU/L). The simultaneous analysis of Cp concentration and activity in the same run allowed us to calculate the Cp-specific activity that provides a better index of the overall Cp status. To test the usefulness of this automation, we tested this assay on 104 healthy volunteers and 36 patients with Wilson's disease, hepatic encephalopathy, and chronic liver disease. Cp activity and specific activity distinguished better patients between groups with respect to Cp concentration alone, and providing support for the clinical investigation of neurological diseases in which liver failure is one of the clinical hallmarks. PMID:24663495

  2. The mind and liver test: a new approach to the diagnosis of minimal hepatic encephalopathy in resource-poor settings.

    PubMed

    Das, Saurav; Ali, Sajjadh M J; Seward, James; Venkataraman, Jayanthi

    2014-01-01

    Background and Aims. Minimal hepatic encephalopathy (MHE) is diagnosed using neuropsychometric tests or neurophysiological tests that are either inapplicable to illiterate patient population in resource-poor settings or require sophisticated and expensive equipment. The available tests assess discrete domains of mental impairment. Our aim was (a) to design a neuropsychometric test that measures all domains of mental impairment in MHE using one metric; (b) to evaluate its sensitivity, specificity, and reproducibility. Methods. The mind and liver test (MALT), a psychometric test assessing cognition, memory, and psychometric impairment, each on a scale of 20, was designed keeping in mind the requirements of a universal test. 40 cirrhotics and 36 controls were subjected to critical flicker frequency (CFF) and MALT in same sitting. ROC curve was plotted for MALT using CFF as gold standard. Bland-Altman plot was used to find test-retest agreement. Results. CFF values and MALT scores varied significantly between the cases and the controls (P < 0.05). MALT was 94% sensitive and 83% specific. Using ROC with CFF as gold standard, the AUC for diagnosis of MHE using MALT score was 0.89. Test-retest agreement was high (ICC = 0.89). Conclusion. In this pilot study, MALT proved to be highly sensitive, specific, inexpensive, and reproducible. PMID:25548682

  3. α-Ketoglutaramate: An overlooked metabolite of glutamine and a biomarker for hepatic encephalopathy and inborn errors of the urea cycle

    PubMed Central

    Cooper, Arthur J. L.; Kuhara, Tomiko

    2013-01-01

    Glutamine metabolism is generally regarded as proceeding via glutaminase-catalyzed hydrolysis to glutamate and ammonia, followed by conversion of glutamate to α-ketoglutarate catalyzed by glutamate dehydrogenase or by a glutamate-linked aminotransferase (transaminase). However, another pathway exists for the conversion of glutamine to α-ketoglutarate that is often overlooked, but is widely distributed in nature. This pathway, referred to as the glutaminase II pathway, consists of a glutamine transaminase coupled to ω-amidase. Transamination of glutamine results in formation of the corresponding α-keto acid, namely, α-ketoglutaramate (KGM). KGM is hydrolyzed by ω-amidase to α-ketoglutarate and ammonia. The net glutaminase II reaction is: L-Glutamine + α-keto acid + H2O → α-ketoglutarate + L-amino acid + ammonia. In this mini-review the biochemical importance of the glutaminase II pathway is summarized, with emphasis on the key component KGM. Forty years ago it was noted that the concentration of KGM is increased in the cerebrospinal fluid (CSF) of patients with hepatic encephalopathy (HE) and that the level of KGM in the CSF correlates well with the degree of encephalopathy. In more recent work, we have shown that KGM is markedly elevated in the urine of patients with inborn errors of the urea cycle. It is suggested that KGM may be a useful biomarker for many hyperammonemic diseases including hepatic encephalopathy, inborn errors of the urea cycle, citrin deficiency and lysinuric protein intolerance. PMID:24234505

  4. [Recurrent posterior reversible encephalopathy due to vasospasm and cerebral hypoperfusionin in acute leukemia: a case report].

    PubMed

    Hiraide, Takuya; Matsubayashi, Tomoko; Ishigaki, Hidetoshi; Asahina, Miki; Sakaguchi, Kimiyoshi; Fukuda, Tokiko

    2015-11-01

    We report the case of a 4-year-old girl who presented with recurrent posterior reversible encephalopathy syndrome (PRES). She was diagnosed with B-precursor acute lymphocytic leukemia (ALL), and was administered remission-induction chemotherapy. On day 28 of the induction therapy, she experienced seizure and prolonged unconsciousness. Blood pressure was slightly elevated. MRI revealed cortical cytotoxic edema in the right temporal and occipital lobes. In the right occipital white matter the lesion with vasogenic edema also existed. Three days later, MRI showed vasogenic edema in subcortical white matter of the right temporal right occipital and bilateral occipital lobes. The lesions had receded with time. Since the seizure occurred, the chemotherapy had been discontinued. The episodes of seizure and prolonged consciousness recurred 22 days later. MRI revealed vasogenic edema in the right occipital lobe, and MR angiography demonstrated vessel irregularity and reduced branch visualization in the middle and posterior cerebral arteries. Arterial spin-labeling (ASL) showed hypoperfusion in both occipital lobes. It suggests that vasoconstriction and hypoperfusion could lead to recurrent PRES in this case. It is possible that ASL might be more sensitive than MRI in detecting the lesions of PRES. It should be noted that PRES might recur in leukemia. PMID:26717647

  5. Posterior Reversible Encephalopathy Syndrome due to High Dose Corticosteroids for an MS Relapse.

    PubMed

    Morrow, Sarah A; Rana, Robina; Lee, Donald; Paul, Terri; Mahon, Jeffrey L

    2015-01-01

    Increased blood pressure is a known adverse effect associated with corticosteroids but little is published regarding the risk with the high doses used in multiple sclerosis (MS). A 53-year-old female with known relapsing remitting MS presented with a new brainstem relapse. Standard of care treatment for an acute MS relapse, 1250 mg of oral prednisone for 5 days, was initiated. She developed an occipital headache and dizziness and felt generally unwell. These symptoms persisted after treatment was complete. On presentation to medical attention, her blood pressure was 199/110 mmHg, although she had no history of hypertension. MRI changes were consistent with posterior reversible encephalopathy syndrome (PRES), demonstrating abnormal T2 signal in both thalami, the posterior occipital and posterior parietal white matter with mild sulcal effacement. As her pressure normalized with medication, her symptoms resolved and the MRI changes improved. No secondary cause of hypertension was found. This is the first reported case of PRES secondary to high dose corticosteroid use for an MS relapse without a history of hypertension and with no other secondary cause of hypertension identified. This rare complication should be considered in MS patients presenting with a headache or other neurological symptoms during treatment for a relapse. PMID:26101676

  6. Solvent encephalopathy.

    PubMed Central

    King, M D; Day, R E; Oliver, J S; Lush, M; Watson, J M

    1981-01-01

    Nineteen children aged 8-14 years were admitted over a six-year period with an acute encephalopathy due to toluene intoxication. Seven had a history of euphoria and hallucinations. The remainder presented with coma (4), ataxia (3), convulsions (3), and behaviour disturbance with diplopia (2), A history of glue sniffing was elicited in 14, but in the remainder toluene assay confirmed the diagnosis. Thirteen children recovered completely; five still had psychological impairment and personality change on discharge from hospital but were lost to follow-up, and one has a persistent cerebellar ataxia one year after the acute episode, despite absence of further exposure. Toluene inhalation is an important cause of encephalopathy in children and may lead to permanent neurological damage. Diagnosis is most important if further damage due to continued abuse is to be prevented, and toluene assay is a valuable aid to diagnosis. PMID:6790121

  7. Hyaluronic Acid Levels Predict Risk of Hepatic Encephalopathy and Liver-Related Death in HIV/Viral Hepatitis Coinfected Patients

    PubMed Central

    Peters, Lars; Mocroft, Amanda; Soriano, Vincent; Rockstroh, Jürgen; Rauch, Andri; Karlsson, Anders; Knysz, Brygida; Pradier, Christian; Zilmer, Kai; Lundgren, Jens D.

    2013-01-01

    Background Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid’s (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study. Methods Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0–75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls). Results During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2–62.6) and 221.6 ng/mL (74.9–611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75–250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86–9.26, p<0.0007) and 28.22 (95% CI 14.95–46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR –5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001). Conclusions An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications. PMID:23724041

  8. Diphtheria, pertussis (whooping cough), and tetanus vaccine induced recurrent seizures and acute encephalopathy in a pediatric patient: Possibly due to pertussis fraction.

    PubMed

    Patel, Mahendra K; Patel, Tejas K; Tripathi, C B

    2012-01-01

    A 5-month-old male patient developed recurrent seizures and acute encephalopathy possibly due to first dose of diphtheria, pertussis (whooping cough), and tetanus (DPT) vaccine used for routine immunization. Postreaction computed tomography (CT) scan of brain, magnetic resonance imaging (MRI) of brain, and electroencephalogram were normal. Pertussis fraction of DPT vaccine is responsible for this reaction. It is suggested that acellular pertussis vaccine should be used instead of whole cell vaccine because it is associated with lower frequency of neurological complications, such as seizures, encephalopathy, and hypotensive episodes. However, acellular pertussis-containing vaccines are currently not affordable in most developing countries. PMID:22368426

  9. Diphtheria, pertussis (whooping cough), and tetanus vaccine induced recurrent seizures and acute encephalopathy in a pediatric patient: Possibly due to pertussis fraction

    PubMed Central

    Patel, Mahendra K.; Patel, Tejas K.; Tripathi, C. B.

    2012-01-01

    A 5-month-old male patient developed recurrent seizures and acute encephalopathy possibly due to first dose of diphtheria, pertussis (whooping cough), and tetanus (DPT) vaccine used for routine immunization. Postreaction computed tomography (CT) scan of brain, magnetic resonance imaging (MRI) of brain, and electroencephalogram were normal. Pertussis fraction of DPT vaccine is responsible for this reaction. It is suggested that acellular pertussis vaccine should be used instead of whole cell vaccine because it is associated with lower frequency of neurological complications, such as seizures, encephalopathy, and hypotensive episodes. However, acellular pertussis-containing vaccines are currently not affordable in most developing countries. PMID:22368426

  10. Ephrin/Ephrin receptor expression in ammonia-treated rat astrocytes and in human cerebral cortex in hepatic encephalopathy.

    PubMed

    Sobczyk, Karmela; Jördens, Markus S; Karababa, Ayse; Görg, Boris; Häussinger, Dieter

    2015-02-01

    Hepatic encephalopathy (HE) represents a neuropsychiatric syndrome, which evolves as a consequence of a low grade cerebral edema and a concomitant oxidative/nitrosative stress response. Ephrin receptors (EphR) and their ligands (ephrins) regulate astrocytic glutamate uptake and gliotransmitter release thereby governing neurotransmission, but their role in HE and ammonia toxicity is unclear. We therefore tested effects of ammonia on expression levels of EphR/ephrin isoforms in cultured rat astrocytes and analysed underlying mechanisms. NH4Cl induced mRNA expression changes of several EphR/ephrin isoforms in a methionine sulfoximine-, NADPH oxidase- and NO synthase-dependent manner in cultured astrocytes. A prominent upregulation was noted for EphR A4 mRNA and protein in NH4Cl-treated astrocytes. NH4Cl-treatment decreased EphR A4 molecular mass to similar extent as found in astrocytes treated with the N-glycosylation inhibitor tunicamycin. Knockdown of EphR A4 by siRNA, or treating astrocytes with NH4Cl or tunicamycin abolished fibroblast growth factor-induced and EphR A4-dependent astrocyte proliferation. NH4Cl-treatment also decreased GLAST mRNA levels in cultured astrocytes. This effect was sensitive to inhibitors of NAPDH oxidase or glutamine synthetase, but was insensitive to siRNA-mediated EphR A4 knockdown. Eph/ephrin gene expression changes were also found in post mortem brain samples of cirrhotic patients without or with HE compared to controls suggesting a potential in vivo relevance of the present findings. The present study suggests that ammonia modulates EphR/ephrin signaling in astrocytes and in the brain of cirrhotic patients with HE with potential implications for deranged neurotransmission in HE. PMID:25064044

  11. The GABAA receptor complex in hepatic encephalopathy. Autoradiographic evidence for the presence of elevated levels of a benzodiazepine receptor ligand

    SciTech Connect

    Basile, A.S.; Ostrowski, N.L.; Gammal, S.H.; Jones, E.A.; Skolnick, P. )

    1990-02-01

    Autoradiographic analysis was used to examine radioligand binding to benzodiazepine (BZ) and GABAA receptors in the brains of rabbits with hepatic encephalopathy (HE). Thin sections of whole brain from normal rabbits and rabbits with HE were mounted on slides and subdivided into two groups. One group was washed before incubation with radioligand, while the second group was not prewashed. (3H)Flunitrazepam binding to BZ receptors was decreased by 22% to 42% (p less than 0.05) in the cerebral cortex, superior and inferior colliculi, and cerebellum of unwashed sections from rabbits with HE compared to all other groups. The binding of (3H)Ro 15-1788 to unwashed sections from rabbits with HE was reduced by a similar degree (18% to 37%, p less than 0.05) in the cerebral cortex, hippocampus, superior colliculus, and cerebellar cortex. Incubation of sections with the GABA-mimetic muscimol and NaCl produced an additional decrease in (3H)flunitrazepam binding to the cortex and hippocampus (25% to 31%, p less than 0.05) in unwashed HE rabbit brain, but increased radioligand binding (27% to 71%, p less than 0.05) to several regions in control rabbits. No changes in radioligand binding to either GABAA or peripheral benzodiazepine receptors was observed between HE and control rabbit sections. These findings are consistent with previous electrophysiologic and neurochemical observations indicating no significant changes in either the function or density of GABAA or BZ receptors in this model of HE. Further, they indicate that a reversible BZ receptor ligand with agonist properties is present in the brain in HE. This substance may contribute to the enhancement of GABAergic tone observed in this syndrome.

  12. Probiotic and lactulose: influence on gastrointestinal flora and pH value in minimal hepatic encephalopathy rats

    PubMed Central

    Jiang, Shu-Man; Jia, Lin; Zhang, Mei-Hua

    2015-01-01

    Aim: The present study was conducted to investigate the influence on gastrointestinal flora, counts of bifidobacteria and Enterobacterceae in colon and pH value of gastrointestinal after lactulose and probiotic treatment on rat experimental minimal hepatic encephalopathy (MHE) induced by thioactamide (TAA). Methods: MHE was induced by intraperitoneal injection of TAA. 48 male MHE models were then randomly divided into 4 groups: control group (n = 12); MHE group (n = 12) received tap water ad libitum only; lactulose group (n = 12) and probiotics group (n = 12) gavaged respectively with 8 ml/kg of lactulose and 1.5 g/kg of probiotic preparation Golden Bifid (highly concentrated combination probiotic) dissolved in 2 ml of normal saline, once a day for 8 days. The latency of Brainstem auditory evoked potentials (BAEP) I was used as objective index of MHE. Counts of gastrointestinal flora, counts of bifidobacteria and Enterobacterceae in colon and pH value of gastrointestinal were examined respectively. Results: Compared to MHE group, counts of gastrointestinal flora has greatly decreased, ratio of bifidobacteria and Enterobacterceae has greatly increased, pH value of colon has greatly descended (P < 0.05). However, there was no significant difference between lactulose group and probiotic group (P > 0.05). Both lactulose and probiotics can effectively prevent bacteria translocation and overgrowth, intensify CR, improved value of B/E, and acidify intestinal, decreased pH value of colon. Conclusion: Probiotic compound Golden Bifid is as useful as lactulose for the prevention and treatment of MHE. Probiotic therapy may be a safe, natural, well-tolerated therapy appropriate for the long-term treatment of MHE. PMID:26309689

  13. Diagnosis of infectious canine hepatitis virus (CAV-1) infection in puppies with encephalopathy.

    PubMed

    Caudell, D; Confer, A W; Fulton, R W; Berry, A; Saliki, J T; Fent, G M; Ritchey, J W

    2005-01-01

    Nine weaned Labrador Retriever puppies from a litter of 11 were presented with signs of acute central nervous system (CNS) disease that included ataxia and blindness. All puppies died. Gross examination of tissues from 2 puppies revealed regionally diffuse hemorrhages in the brain stem and swollen hemorrhagic lymph nodes. Light microscopic examination of hematoxylin and eosin-stained tissues showed numerous large, basophilic intranuclear inclusion bodies within CNS vascular endothelium and occasionally in individual hepatocytes. Immunohistochemical staining of the tissue was positive using an antibody against canine adenovirus-1. Virus isolation for infectious canine hepatitis virus was achieved using inoculated cell cultures. Polymerase chain reaction amplification of DNA from cell culture material revealed shared homology with other mammalian adenoviruses. PMID:15690952

  14. Effect of H pylori infection and its eradication on hyperammo-nemia and hepatic encephalopathy in cirrhotic patients

    PubMed Central

    Chen, Shu-Jie; Wang, Liang-Jing; Zhu, Qin; Cai, Jian-Ting; Chen, Tao; Si, Jian-Min

    2008-01-01

    AIM: To investigate the relationship between H pylori infection, blood ammonia concentration and hepatic encephalopathy (HE), and the effect of H pylori eradication in cirrhotic patients. METHODS: From July 2003 to January 2005, 457 cirrhotic patients in five regions of Zhejiang Province were enrolled. Patients were evaluated for demographics, number connection test, H pylori infection, liver impairment, blood ammonia concentration and HE. Patients with H pylori infection were given 1 wk therapy with omeprazole plus clarithromycin and tinidazole. 14C urea breath test was performed and mental symptoms and blood ammonia level were reassessed after bacterium eradication. RESULTS: Overall H pylori infection rate was 60.6%, and HE occurred in 47.5% of cirrhotic patients. Subclinical HE (SHE) was detected in 55 of 117 cirrhotic patients. Blood ammonia concentration in H pylori negative (n = 180) and positive (n = 277) cirrhotic patients was 53.8 ± 51.4 and 78.4 ± 63.6 μmol/L, respectively (P < 0.01), which was significantly reduced to 53.5 ± 37.7 μmol/L after bacterium eradication (n = 126) (P < 0.01). Blood ammonia was 97.5 ± 81.0 μmol/L in H pylori-positive cirrhotic patients, and this did not significantly change in those with persistent infection after H pylori eradication (n = 11). HE was more frequently observed in patients with H pylori infection than in those without (58.5% vs 30.6%, P < 0.01). HE rate significantly dropped to 34.1% after H pylori eradiation (P < 0.01). H pylori prevalence significantly differed among cirrhotic patients with HE (74.4%), SHE (69.1%), and those without HE (53.2%) (P < 0.05). Blood ammonia level was significantly different among cirrhotic patients with HE (94.5 ± 75.6 μmol/L), SHE (59.9 ± 49.2 μmol/L), and without HE (47.3 ± 33.5 μmol/L) (P < 0.05). Logistic regression analysis showed that blood ammonia concentration, Child-Pugh stage, upper gastrointestinal bleeding, electrolyte disturbance, and urea nitrogen were risk

  15. Vascular plug-assisted retrograde transvenous obliteration of portosystemic shunts for refractory hepatic encephalopathy: a case report.

    PubMed

    Park, Jonathan K; Cho, Sung-Ki; Kee, Stephen; Lee, Edward W

    2014-01-01

    While balloon-assisted retrograde transvenous obliteration (BRTO) has been used for two decades in Asia for the management of gastric variceal bleeding, it is still an emerging therapy elsewhere. Given the shunt closure brought about by the procedure, BRTO has also been used for the management of portosystemic encephalopathy with promising results. Modified versions of BRTO have been developed, including plug-assisted retrograde transvenous obliteration (PARTO), where a vascular plug is deployed within a portosystemic shunt. To our knowledge, we present the first North American case of PARTO in the setting of a large splenorenal shunt for the management of portosystemic encephalopathy. PMID:24744943

  16. [EEG manifestations in metabolic encephalopathy].

    PubMed

    Lin, Chou-Ching K

    2005-09-01

    Normal brain function depends on normal neuronal metabolism, which is closely related to systemic homeostasis of metabolites, such as glucose, electrolytes, amino acids and ammonia. "Metabolic encephalopathy" indicates diffuse brain dysfunction caused by various systemic derangements. Electroencephalogram (EEG) is widely used to evaluate metabolic encephalopathy since 1937, when Berger first observed slow brain activity induced by hypoglycemia. EEG is most useful in differentiating organic from psychiatric conditions, identifying epileptogenicity, and providing information about the degree of cortical or subcortical dysfunction. In metabolic encephalopathy, EEG evolution generally correlates well with the severity of encephalopathy. However, EEG has little specificity in differentiating etiologies in metabolic encephalopathy. For example, though triphasic waves are most frequently mentioned in hepatic encephalopathy, they can also be seen in uremic encephalopathy, or even in aged psychiatric patients treated with lithium. Spike-and-waves may appear in hyper- or hypo-glycemia, uremic encephalopathy, or vitamin deficiencies, etc. Common principles of EEG changes in metabolic encephalopathy are (1) varied degrees of slowing, (2) assorted mixtures of epileptic discharge, (3) high incidence of triphasic waves, and (4), as a rule, reversibility after treatment of underlying causes. There are some exceptions to the above descriptions in specific metabolic disorders and EEG manifestations are highly individualized. PMID:16252619

  17. Hypothyroidism Due to Hepatic Hemangioendothelioma: A Case Report

    PubMed Central

    Peltek Kendirici, Havva Nur; Yılmaz Ağladıoğlu, Sebahat; Baş, Veysel Nijat; Özdemir, Sonay; Bozkurt, Ceyhun; Aycan, Zehra

    2010-01-01

    Although hemangioendothelioma (HHE) is a commonly encountered hepatic tumor during infancy, HHE−related hypothyroidism is rare. We present a patient who developed HHE−related hypothyroidism during the neonatal period and showed marked improvement in hypothyroidism by regression of HHE. A 28−day−old boy with TSH level of 77 mIU/mL on neonatal screening and diagnosed as congenital hypothyroidism was started on L−thyroxine (L−T4) (11 μg/kg/day) therapy on the 21th day of life. On physical examination, the liver was palpable 5 cm below the right costal margin, and the thyroid gland was nonpalpable. Thyroid ultrasonography was normal. Although L−T4 dose was increased to 15 μg/kg/day, TSH was not suppressed and free T3 level remained low. HHE in both lobes of the liver was detected by abdominal ultrasonography and magnetic resonance imaging. Treatment was started with prednisolone 2 mg/kg/day and alpha−interferon 3 million U/m2/3 times per week. Thyroid dysfunction was thought to be due to type 3 iodothyronine deiodinase activity expressed by HHE. L−T4 therapy was changed to Bitiron® tablet, which includes both T4 and T3, and euthyroidism was attained within 1 month. Thyroid hormone requirement was reduced and treatment was discontinued after regression of the HHE. At the most recent visit, the patient was 21 months old and off treatment. His growth and neurological development were normal for age and he was euthyroid. HHE should be considered in cases with severe hypothyroidism resistant to high−dose thyroid hormone replacement. The treatment of HHE in combination with T4 and T3 therapy results in euthyroidism. Conflict of interest:None declared. PMID:21274327

  18. Inhibitory Control Test, Critical Flicker Frequency, and Psychometric Tests in the Diagnosis of Minimal Hepatic Encephalopathy in Cirrhosis

    PubMed Central

    Sharma, Praveen; Kumar, Ajay; Singh, Shweta; Tyagi, Pankaj; Kumar, Ashish

    2013-01-01

    Background/Aim: Minimal hepatic encephalopathy (MHE) impairs health-related quality of life and driving ability of the patient. Objective: We assessed the utility of the inhibitory control test (ICT), critical flicker frequency (CFF), and psychometry in the diagnosis of MHE. Patients and Methods: Consecutive patients with cirrhosis underwent number connection tests A and B (NCT-A, B), digit symbol test (DST), line tracing test (LTT), serial dot test (SDT), CFF, and ICT at baseline and after four hours. Fifty healthy subjects served as controls for the ICT test. Results: Fifty patients with cirrhosis (43.4 ± 10.2 yrs, M: F 42:8) underwent psychometric tests [NCT-A (48.3 ± 17.7 vs. 42.6 ± 17.3 sec, P = 0.001), NCT-B (85.7 ± 40.1 vs. 90.2 ± 37.0 sec, P = 0.18), DST (23.5 ± 9.3 vs. 23.0 ± 8.7, P = 0.45), LTT (96.6 ± 48.2 vs. 96.8 ± 46.8 sec, P = 0.92), SDT (88.0 ± 39.5 vs. 83.4 ± 37.2 sec, P = 0.02)] at baseline and after four hours. Target accuracy of ICT was lower in patients with cirrhosis compared with controls (88.4 ± 5.6 vs. 95.6 ± 2.1, P = 0.01), whereas ICT lures were higher (18.3 ± 4.2 vs 10.2 ± 2.8, P = 0.01). Patients with cirrhosis showed a reduction in lures in the second evaluation compared with the first (18.3 ± 4.2 vs. 17.1 ± 4.3, P = 0.003) but no change in target accuracy (88.4 ± 5.6 vs. 88.4 ± 5.3, P = 0.97). Control subjects did not show any change either in lures (10.2 ± 2.8 vs. 10.3 ± 2.1, P = 0.65) or target accuracy (95.6 ± 2.1 vs. 95.5 ± 2.2, P = 0.82). The sensitivity and specificity of ICT test for the diagnosis of MHE at lure rate >16.5 was 88.5 and 56%, respectively. CFF in patients with MHE (38.4 ± 1.8 vs. 38.6 ± 1.5, P = 0.3) and non MHE (40.6 ± 2.2 vs. 40.8 ± 2.2, P = 0.6) did not show any difference after four hours as in controls (41.9 ± 2.4 vs. 42.1 ± 2.0, P = 0.3). Thirty one (31%) patients preferred psychometric tests, 57 (57%) preferred CFF and only 12 (12%) preferred ICT (P = 0.001). Conclusions: ICT

  19. Elevated intracranial dopamine impairs the glutamate-nitric oxide-cyclic guanosine monophosphate pathway in cortical astrocytes in rats with minimal hepatic encephalopathy

    PubMed Central

    DING, SAIDAN; HUANG, WEILONG; YE, YIRU; YANG, JIANJING; HU, JIANGNAN; WANG, XIAOBIN; LIU, LEPING; LU, QIN; LIN, YUANSHAO

    2014-01-01

    In a previous study by our group memory impairment in rats with minimal hepatic encephalopathy (MHE) was associated with the inhibition of the glutamate-nitric oxide-cyclic guanosine monophosphate (Glu-NO-cGMP) pathway due to elevated dopamine (DA). However, the effects of DA on the Glu-NO-cGMP pathway localized in primary cortical astrocytes (PCAs) had not been elucidated in rats with MHE. In the present study, it was identified that when the levels of DA in the cerebral cortex of rats with MHE and high-dose DA (3 mg/kg)-treated rats were increased, the co-localization of N-methyl-d-aspartate receptors subunit 1 (NMDAR1), calmodulin (CaM), nitric oxide synthase (nNOS), soluble guanylyl cyclase (sGC) and cyclic guanine monophosphate (cGMP) with the glial fibrillary acidic protein (GFAP), a marker protein of astrocytes, all significantly decreased, in both the MHE and high-dose DA-treated rats (P<0.01). Furthermore, NMDA-induced augmentation of the expression of NMDAR1, CaM, nNOS, sGC and cGMP localized in PCAs was decreased in MHE and DA-treated rats, as compared with the controls. Chronic exposure of cultured cerebral cortex PCAs to DA treatment induced a dose-dependent decrease in the concentration of intracellular calcium, nitrites and nitrates, the formation of cGMP and the expression of NMDAR1, CaM, nNOS and sGC/cGMP. High doses of DA (50 μM) significantly reduced NMDA-induced augmentation of the formation of cGMP and the contents of NMDAR1, CaM, nNOS, sGC and cGMP (P<0.01). These results suggest that the suppression of DA on the Glu-NO-cGMP pathway localized in PCAs contributes to memory impairment in rats with MHE. PMID:25059564

  20. Elevated intracranial dopamine impairs the glutamate‑nitric oxide‑cyclic guanosine monophosphate pathway in cortical astrocytes in rats with minimal hepatic encephalopathy.

    PubMed

    Ding, Saidan; Huang, Weilong; Ye, Yiru; Yang, Jianjing; Hu, Jiangnan; Wang, Xiaobin; Liu, Leping; Lu, Qin; Lin, Yuanshao

    2014-09-01

    In a previous study by our group memory impairment in rats with minimal hepatic encephalopathy (MHE) was associated with the inhibition of the glutamate‑nitric oxide‑cyclic guanosine monophosphate (Glu‑NO‑cGMP) pathway due to elevated dopamine (DA). However, the effects of DA on the Glu‑NO‑cGMP pathway localized in primary cortical astrocytes (PCAs) had not been elucidated in rats with MHE. In the present study, it was identified that when the levels of DA in the cerebral cortex of rats with MHE and high‑dose DA (3 mg/kg)‑treated rats were increased, the co‑localization of N‑methyl‑d‑aspartate receptors subunit 1 (NMDAR1), calmodulin (CaM), nitric oxide synthase (nNOS), soluble guanylyl cyclase (sGC) and cyclic guanine monophosphate (cGMP) with the glial fibrillary acidic protein (GFAP), a marker protein of astrocytes, all significantly decreased, in both the MHE and high‑dose DA‑treated rats (P<0.01). Furthermore, NMDA‑induced augmentation of the expression of NMDAR1, CaM, nNOS, sGC and cGMP localized in PCAs was decreased in MHE and DA‑treated rats, as compared with the controls. Chronic exposure of cultured cerebral cortex PCAs to DA treatment induced a dose‑dependent decrease in the concentration of intracellular calcium, nitrites and nitrates, the formation of cGMP and the expression of NMDAR1, CaM, nNOS and sGC/cGMP. High doses of DA (50 µM) significantly reduced NMDA‑induced augmentation of the formation of cGMP and the contents of NMDAR1, CaM, nNOS, sGC and cGMP (P<0.01). These results suggest that the suppression of DA on the Glu‑NO‑cGMP pathway localized in PCAs contributes to memory impairment in rats with MHE. PMID:25059564

  1. Clinical effects of rifaximin in patientswith hepatic encephalopathy intolerant or nonresponsive to previous lactulose treatment: An open-label, pilot study

    PubMed Central

    Sama, Claudia; Morselli-Labate, Antonio Maria; Pianta, Paolo; Lambertini, Laura; Berardi, Sonia; Martini, Gabriella

    2004-01-01

    Background: Hepatic encephalopathy (HE) is a metabolic-neurophysiologicsyndrome that occurs in patients with advanced hepatic disease. One of the main pathogenic mechanisms is represented by circulating toxins produced by the intestinal metabolism of nitrogenous compounds. The therapeutic approach to HE is mainly based on drugs that eliminate ammonia-producing bacteria. Objectives: The aim of this study was to evaluate the effects of the nonabsorbable antibiotic rifaximin in patients with HE who were intolerant or nonresponsive to treatment with an oral, nonabsorbable disaccharide (lactulose). Methods: This uncontrolled, open-label, pilot study was conducted at the University of Bologna, Bologna, Italy. Patients aged ≥ 18 years with histologically proven liver cirrhosis and HE were studied. All patients were intolerant or nonresponsive to previous treatment with lactulose. Rifaximin tablets were administered to patients at a dosage of 400 mg TID for 10 days. The portal systemic encephalopathy (PSE) index was evaluated at enrollment and at the end of the treatment period. Tolerability was assessed using hematology, biochemistry, and urinalysis and by recording adverse effects (AEs). Results: Twenty-six patients (18 men, 8 women; mean [SD] age, 55.8 [8.0] years) were enrolled (intolerants, n = 17; nonresponders, n = 9). All patients completed the study. Significant improvement was shown in most of the 5 components of the PSE index after rifaximin administration in both intolerants and nonresponders. At the end of the 10-day treatment period, the PSE index was significantly reduced in both intolerants and nonresponders. Rifaximin was well tolerated; no clinically relevant AEs were observed during the treatment period. Conclusions: This pilot study of patients with liver cirrhosis and HE who were intolerant or nonresponsive to previous treatment with an oral, nonabsorbable disaccharide suggests that treatment with rifaximin may be considered as an adjuvant or an

  2. Rats with mild bile duct ligation show hepatic encephalopathy with cognitive and motor impairment in the absence of cirrhosis: effects of alcohol ingestion.

    PubMed

    Giménez-Garzó, Carla; Salhi, Dounia; Urios, Amparo; Ruíz-Sauri, Amparo; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

    2015-02-01

    Studies in animal models allow identifying mechanisms and treatments for cognitive and motor alterations in hepatic encephalopathy (HE). Liver diseases leading to HE in humans have different aetiologies (alcoholic, viral, etc.). The International Society for Hepatic Encephalopathy points out that satisfactory model for HE resulting from alcoholic cirrhosis are lacking. This work aimed to develop and characterize an animal model for HE in alcoholic liver cirrhosis. To potentiate the effects of alcohol on liver we administered it (5, 8 or 10% in drinking water) to rats showing mild liver damage induced by "mild" bile duct ligation (MBDL), obtained by sectioning 3 out of 5 bile ducts. MBDL rats show increased markers of cholestasis and liver damage, hyperammonemia and inflammation. MBDL rats also show motor in-coordination, hypokinesia, impaired learning ability in a Y maze and reduced spatial memory in the Morris water maze. Ingesting 10% ethanol does not induce relevant liver damage in control rats but potentiates liver damage in MBDL rats. In contrast, ethanol did not enhance the biochemical or neurological alterations in MBDL rats. This supports that the combination of certain levels of hyperammonemia and inflammation is enough to induce mild cognitive impairment, even in the absence of liver cirrhosis. Rats with MBDL and MBDL-OH survived more than 3 months, allowing performing long-term studies on cognitive and motor alterations and on underlying mechanisms. MBDL-OH rats are a good model to study the mechanisms of ethanol-induced liver cirrhosis and the factors making the liver susceptible to ethanol damage. PMID:24838616

  3. Aberrant salience network and its functional coupling with default and executive networks in minimal hepatic encephalopathy: a resting-state fMRI study.

    PubMed

    Chen, Hua-Jun; Chen, Qiu-Feng; Liu, Jun; Shi, Hai-Bin

    2016-01-01

    The purposes of this study are to explore functional alterations in salience network (SN) and its functional coupling with default mode (DMN) and central executive (CEN) networks in minimal hepatic encephalopathy (MHE). Twenty cirrhotic patients with MHE, 23 cirrhotic patients without MHE (NHE), and 18 controls underwent resting-state fMRI and psychometric hepatic encephalopathy score (PHES) test. Independent component analysis was performed to obtain DMN (including three subsystems: anterior, inferior-posterior, and superior-posterior DMN [a/ip/spDMN]), SN, and CEN (including three subsystems: left-ventral, right-ventral, and dorsal CEN [lv/rv/dCEN]). The intrinsic functional connectivity (iFC) within (intra-iFC) and between (inter-iFC and time-lagged inter-iFC) networks was measured. MHE patients showed decreased intra-iFC within aDMN, SN, lvCEN, and rvCEN; and decreased inter-iFC and time-lagged inter-iFC between SN and ipDMN/spDMN/lvCEN and increased inter-iFC and time-lagged inter-iFC between SN and aDMN, compared with controls. A progressive trend in connectivity alterations was found as the disease developed from NHE to MHE. The inter-iFC between ipDMN/spDMN and SN was significantly correlated with PHES score. In conclusion, an aberrant SN and its functional interaction with the DMN/CEN are core features of MHE that are associated with disease progression and may play an important role in neurocognitive dysfunction in MHE. PMID:27250065

  4. Aberrant salience network and its functional coupling with default and executive networks in minimal hepatic encephalopathy: a resting-state fMRI study

    PubMed Central

    Chen, Hua-Jun; Chen, Qiu-Feng; Liu, Jun; Shi, Hai-Bin

    2016-01-01

    The purposes of this study are to explore functional alterations in salience network (SN) and its functional coupling with default mode (DMN) and central executive (CEN) networks in minimal hepatic encephalopathy (MHE). Twenty cirrhotic patients with MHE, 23 cirrhotic patients without MHE (NHE), and 18 controls underwent resting-state fMRI and psychometric hepatic encephalopathy score (PHES) test. Independent component analysis was performed to obtain DMN (including three subsystems: anterior, inferior-posterior, and superior-posterior DMN [a/ip/spDMN]), SN, and CEN (including three subsystems: left-ventral, right-ventral, and dorsal CEN [lv/rv/dCEN]). The intrinsic functional connectivity (iFC) within (intra-iFC) and between (inter-iFC and time-lagged inter-iFC) networks was measured. MHE patients showed decreased intra-iFC within aDMN, SN, lvCEN, and rvCEN; and decreased inter-iFC and time-lagged inter-iFC between SN and ipDMN/spDMN/lvCEN and increased inter-iFC and time-lagged inter-iFC between SN and aDMN, compared with controls. A progressive trend in connectivity alterations was found as the disease developed from NHE to MHE. The inter-iFC between ipDMN/spDMN and SN was significantly correlated with PHES score. In conclusion, an aberrant SN and its functional interaction with the DMN/CEN are core features of MHE that are associated with disease progression and may play an important role in neurocognitive dysfunction in MHE. PMID:27250065

  5. Hepatic veno-occlusive disease due to pyrrolizidine (Senecio) poisoning in Arizona.

    PubMed

    Stillman, A S; Huxtable, R; Consroe, P; Kohnen, P; Smith, S

    1977-08-01

    An infant with documented hepatic veno-occlusive disease due to ingestion of pyrrolizidine alkaloids is presented. The alkaloids were ingested in the form of an herbal tea commonly used as a folk remedy among the Mexican-American population. Among these people, this herb is known as gordolobo yerba. The patient presented with acute hepatocellular disease and portal hypertension which progressed over 2 months to extensive hepatic fibrosis. Other potential causes of hepatic venous occlusion were absent. PMID:873137

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

    PubMed Central

    Anand, Anil C.; Garg, Hitendra K.

    2015-01-01

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

  7. Toxic Encephalopathy

    PubMed Central

    Kim, Jae Woo

    2012-01-01

    This article schematically reviews the clinical features, diagnostic approaches to, and toxicological implications of toxic encephalopathy. The review will focus on the most significant occupational causes of toxic encephalopathy. Chronic toxic encephalopathy, cerebellar syndrome, parkinsonism, and vascular encephalopathy are commonly encountered clinical syndromes of toxic encephalopathy. Few neurotoxins cause patients to present with pathognomonic neurological syndromes. The symptoms and signs of toxic encephalopathy may be mimicked by many psychiatric, metabolic, inflammatory, neoplastic, and degenerative diseases of the nervous system. Thus, the importance of good history-taking that considers exposure and a comprehensive neurological examination cannot be overemphasized in the diagnosis of toxic encephalopathy. Neuropsychological testing and neuroimaging typically play ancillary roles. The recognition of toxic encephalopathy is important because the correct diagnosis of occupational disease can prevent others (e.g., workers at the same worksite) from further harm by reducing their exposure to the toxin, and also often provides some indication of prognosis. Physicians must therefore be aware of the typical signs and symptoms of toxic encephalopathy, and close collaborations between neurologists and occupational physicians are needed to determine whether neurological disorders are related to occupational neurotoxin exposure. PMID:23251840

  8. [Posterior reversible encephalopathy syndrome due to hypocalcemia: a description of a case and an analysis of a pathogenic role of electrolyte disturbances].

    PubMed

    Dobrynina, L A; Kalashnikova, L A; Bakulin, I S; Kremneva, E I; Krotenkova, M V; Shamtieva, K V

    2016-01-01

    Afemale patient with recurrent posterior reversible encephalopathy syndrome, severe hypocalcemia due to extirpation of the parathyroid glands is described. The disease was characterized by the acute development of headache, seizures, cognitive and behavioral disorders, mental confusion, transitory blood pressure increasing. The vasogenic edema in the posterior parts of the brain, detected by CT at the first exacerbation,was completely regressed. The residual neurological deficit and MRI changes remained after the recurrent exacerbations. Main clinical features of PRESare explained by hypocalcemia and accompanying electrolyte disturbances.The reported case shows the necessity to study blood electrolytes in patients with PRES to clarify their pathogenic role and the necessity of drug correction. PMID:27500881

  9. Scintigraphic study of regenerative nodules due to fulminant hepatic failure.

    PubMed

    Watanabe, Tomohiro; Kondo, Masahiko; Hirasa, Masahiro; Shirane, Hirofumi; Okabe, Yoshihiro; Ibuki, Yasuyoshi; Tomita, Shusuke; Orino, Akio; Todo, Akio; Wakatsuki, Yoshio; Chiba, Tsutomu; Kudo, Masatoshi

    2003-01-01

    We report the case of a 25-year-old woman with fulminant hepatic failure (FHF). Liver scintigraphy using (99m)Tc-galactosyl human serum albumin (GSA) and (99m)Tc-phytate produced interesting findings; regenerative nodules appeared as nodules of increased accumulation of (99m)Tc-GSA, whereas these nodules were expressed as defects of accumulation of (99m)Tc-phytate. These scintigraphic findings suggested that the functions of hepatocytes in regenerative nodules were maintained, whereas those of Kupffer cells were impaired. Although (99m)Tc-GSA scintigraphy indicated hepatic functional reserve enough to survive, she died despite intensive therapy including plasma exchange. Based on this case, it is recommended that not only (99m)Tc-GSA scintigraphy but also (99m)Tc-phytate scintigraphy is required to evaluate the prognosis of patients with FHF. PMID:12898364

  10. Encephalopathy in an infant with infantile spasms: possible role of valproate toxicity.

    PubMed

    Sivathanu, Shobhana; Sampath, Sowmya; Veerasamy, Madhubala; Sunderkumar, Satheeshkumar

    2014-01-01

    An infant presented with global developmental delay and infantile spasms. EEG was suggestive of hypsarrhythmia. She was started on sodium valproate, clonazepam and adrenocorticotropic hormone injection. After an initial improvement the child developed vomiting, altered sensorium and increase in frequency of seizures suggestive of encephalopathy. Valproate-induced hyperammonaemia or hepatic encephalopathy was considered and the drug was withheld following which there was a dramatic improvement. Paradoxically, the liver function tests and serum ammonia were normal. However, a complete reversal of encephalopathy, on withdrawal of the drug, strongly suggested an adverse drug reaction (ADR) due to valproic acid. Marginal elevation of serum valproic acid prompted us to use the Naranjo ADR probability score to confirm the diagnosis. This case highlights the fact that valproate toxicity can manifest with normal liver function and serum ammonia levels. This is the youngest reported case with this rare form of valproate-induced encephalopathy. PMID:24810446

  11. Bacopa monnieri Extract (CDRI-08) Modulates the NMDA Receptor Subunits and nNOS-Apoptosis Axis in Cerebellum of Hepatic Encephalopathy Rats

    PubMed Central

    Mondal, Papia; Trigun, Surendra Kumar

    2015-01-01

    Hepatic encephalopathy (HE), characterized by impaired cerebellar functions during chronic liver failure (CLF), involves N-methyl-D-aspartate receptor (NMDAR) overactivation in the brain cells. Bacopa monnieri (BM) extract is a known neuroprotectant. The present paper evaluates whether BM extract is able to modulate the two NMDAR subunits (NR2A and NR2B) and its downstream mediators in cerebellum of rats with chronic liver failure (CLF), induced by administration of 50 mg/kg bw thioacetamide (TAA) i.p. for 14 days, and in the TAA group rats orally treated with 200 mg/kg bw BM extract from days 8 to 14. NR2A is known to impart neuroprotection and that of NR2B induces neuronal death during NMDAR activation. Neuronal nitric oxide synthase- (nNOS-) apoptosis pathway is known to mediate NMDAR led excitotoxicity. The level of NR2A was found to be significantly reduced with a concomitant increase of NR2B in cerebellum of the CLF rats. This was consistent with significantly enhanced nNOS expression, nitric oxide level, and reduced Bcl2/Bax ratio. Moreover, treatment with BM extract reversed the NR2A/NR2B ratio and also normalized the levels of nNOS-apoptotic factors in cerebellum of those rats. The findings suggest modulation of NR2A and NR2B expression by BM extract to prevent neurochemical alterations associated with HE. PMID:26413124

  12. Glycerol Phenylbutyrate in Patients With Cirrhosis and Episodic Hepatic Encephalopathy: A Pilot Study of Safety and Effect on Venous Ammonia Concentration.

    PubMed

    Ghabril, Marwan; Zupanets, Igor A; Vierling, John; Mantry, Parvez; Rockey, Don; Wolf, David; O'Shea, Robert; Dickinson, Klara; Gillaspy, Heather; Norris, Catherine; Coakley, Dion F; Mokhtarani, Masoud; Scharschmidt, Bruce F

    2013-07-01

    Glycerol tri-(4-phenylbutyrate) (glycerol phenylbutyrate, GPB, HPN-100) mediates waste nitrogen excretion through conjugation with glutamine to form phenylacetylglutamine which is excreted in urine. This pilot study was performed to assess tolerability and effect on venous ammonia concentration in patients with cirrhosis and hepatic encephalopathy (HE). Patients underwent one week of 6 mL (6.6 g) twice daily (BID). GPB dosing followed by 3 weeks of 9 mL (9.9 g) BID dosing and underwent repeated blood sampling for ammonia concentration and pharmacokinetics. Fifteen patients were enrolled. Ammonia concentrations were lowest after overnight fast and increased post-prandially. Fasting ammonia concentrations were lower on GPB compared to baseline, with a decrease on the eighth day of 6 mL BID dosing to 45.4 (27.9) µmol/L (ULN ∼48 µmol/L) (P < .05). Nine milliliters BID yielded similar lowering but was associated with more adverse events and higher phenylacetate (PAA) plasma concentrations (PAA Cmax of 144 [125] vs. 292 [224] µg/mL on 6 and 9 mL, respectively). GPB dosed at 6 mL BID lowered fasting ammonia levels in cirrhotic patients with HE as compared with baseline, was better tolerated than 9 mL BID, and is appropriate for further evaluation in patients with cirrhosis and episodic HE. PMID:27121790

  13. [Cholestasic toxic hepatitis due to clopidogrel in a patient with multiple conditions].

    PubMed

    Etxeberria Lekuona, D; Méndez López, I; Mercado, M R; Oteiza, J; Arteaga, M; Jarne, V

    2016-01-01

    Clopidogrel is a thienopyridine-class antiplatelet drug commonly used in ischemic heart disease,cerebrovascular disease and peripheral artery disease.Liver toxicity due to this drug is very infrequent.We found 16 cases in the literature, and in only two of them liver biopsy was carried out. We report the case of a 78 year old patient with multiple conditions affected by severe toxic cholestatic hepatitis due to clopidogrel and the results of the liver biopsy performed. Hepatitis was resolved after discontinuing the drug.Based on the characteristics of this case and other previously published cases, we review the characteristics of toxic hepatitis due to clopidogrel and its diagnosis and treatment. PMID:27125614

  14. Diets in Encephalopathy.

    PubMed

    Abdelsayed, George G

    2015-08-01

    As many as 80% of patients with end-stage liver disease and hepatic encephalopathy have significant protein-calorie malnutrition. Because of the severe hypercatabolic state of cirrhosis, the provision of liberal amounts of carbohydrate (at least 35 to 40 kcal/kg per day), and between 1.2 and 1.6 g/kg of protein is necessary. Protein restriction is not recommended. Branched-chain amino acid supplementation and vegetable protein are associated with improved outcomes. Dietary supplementation with vitamins, minerals (with the notable exception of zinc) and probiotics should be decided on a case-by-case basis. PMID:26195204

  15. Cost-effectiveness analysis of rifaximin-α administration for the reduction of episodes of overt hepatic encephalopathy in recurrence compared with standard treatment in France

    PubMed Central

    Kabeshova, Anastasiia; Ben Hariz, Soumaia; Tsakeu, Elyonore; Benamouzig, Robert; Launois, Robert

    2016-01-01

    Background: Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that occurs most often in a context of acute or chronic liver disease. Despite the seriousness of the pathology, only a few treatments have been developed for improving its management. Rifaximin-α is the first treatment that has been clinically developed for overt HE (OHE) episodes. Recent results of clinical studies demonstrated its significant improvement in the health-related quality of life. The objective of the current study was to estimate the long-term cost-effectiveness of rifaximin-α used in combination with lactulose compared with lactulose monotherapy in cirrhotic patients, who have experienced at least two prior OHE events. Methods: A Markov model was used to estimate rifaximin-α cost-effectiveness, evaluating it from the perspective of all contributors as recommended by French health technology assessment guidelines. Costs were based on current French treatment practices. The transition between health states was based on the reanalysis of the rifaximin-α pivotal clinical trials RFHE3001 and RFHE3002. The main outcome of the model was cost per quality adjusted life year (QALY). Results: The results indicate that rifaximin-α is a cost-effective treatment option with an incremental cost per QALY gained of €19,187 and €18,517 over two different time horizons (2 and 5 years). The robustness of the model was studied using probabilistic sensitivity analysis. Conclusion: For the societal willingness to pay threshold of €27,000 per QALY gained, rifaximin-α in combination with lactulose is a cost-effective and affordable treatment for patients who have experienced at least two prior overt HE episodes. PMID:27366216

  16. Hepatic encephalopathy induces site-specific changes in gene expression of GluN1 subunit of NMDA receptor in rat brain.

    PubMed

    Ahmadi, Shamseddin; Poureidi, Mahsa; Rostamzadeh, Jalal

    2015-08-01

    We investigate changes in gene expression of GluN1 subunit of N-Methyl-D-Aspartate (NMDA) receptor in the prefrontal cortex (PFC), hippocampus and striatum in a rat model of hepatic encephalopathy (HE). We used male Wistar rats in which HE was induced after a common bile duct ligation (BDL). The animals were divided into three sets, and each set included three groups of control, sham operated and BDL. In the first set of animals, blood samples collected for biochemical analysis on day 21 of BDL. In the second set, changes in nociception threshold was assessed on day 21 of BDL using a hotplate test. In the third set, whole brain extracted, and the PFC, the hippocampus and the striatum in each rat were immediately dissected. We used a semi-quantitative RT-PCR method for evaluating the GluN1 gene expression. The biochemical analyses showed that plasma levels of ammonia and bilirubin in BDL rats were significantly increased compared to the sham control group on day 21 of BDL (P < 0.01). Nociception threshold was also increased in rats with BDL compared to sham group (P < 0.001). The results revealed that the GluN1 gene expression at mRNA levels in BDL group was decreased by 19 % in the PFC (P < 0.05) but increased by 82 % in the hippocampus (P < 0.01) compared to the sham control group; however, no significant change was observed in the striatum. It can be concluded that HE affects the GluN1 gene expression in rat brain with a site-specific pattern, and the PFC and hippocampus are more sensitive areas than striatum. PMID:25896221

  17. Rats with minimal hepatic encephalopathy show reduced cGMP-dependent protein kinase activity in hypothalamus correlating with circadian rhythms alterations.

    PubMed

    Felipo, Vicente; Piedrafita, Blanca; Barios, Juan A; Agustí, Ana; Ahabrach, Hanan; Romero-Vives, María; Barrio, Luis C; Rey, Beatriz; Gaztelu, Jose M; Llansola, Marta

    2015-01-01

    Patients with liver cirrhosis show disturbances in sleep and in its circadian rhythms which are an early sign of minimal hepatic encephalopathy (MHE). The mechanisms of these disturbances are poorly understood. Rats with porta-caval shunt (PCS), a model of MHE, show sleep disturbances reproducing those of cirrhotic patients. The aims of this work were to characterize the alterations in circadian rhythms in PCS rats and analyze the underlying mechanisms. To reach these aims, we analyzed in control and PCS rats: (a) daily rhythms of spontaneous and rewarding activity and of temperature, (b) timing of the onset of activity following turning-off the light, (c) synchronization to light after a phase advance and (d) the molecular mechanisms contributing to these alterations in circadian rhythms. PCS rats show altered circadian rhythms of spontaneous and rewarding activities (wheel running). PCS rats show more rest bouts during the active phase, more errors in the onset of motor activity and need less time to re-synchronize after a phase advance than control rats. Circadian rhythm of body temperature is also slightly altered in PCS rats. The internal period length (tau) of circadian rhythm of motor activity is longer in PCS rats. We analyzed some mechanisms by which hypothalamus modulate circadian rhythms. PCS rats show increased content of cGMP in hypothalamus while the activity of cGMP-dependent protein kinase was reduced by 41% compared to control rats. Altered cGMP-PKG pathway in hypothalamus would contribute to altered circadian rhythms and synchronization to light. PMID:26203935

  18. pH-sensitive microemulsion-based gels for removal of colonic ammonia: a novel preventative oral preparation for hepatic encephalopathy in rats.

    PubMed

    Zhang, Chun-Le; Duan, Zhi-Jun; Tian, Ge; Tian, Yan; He, Gao-Hong; Bian, Teng-Fei; Jin, Xue; Sun, Xiao-Yu; Liu, Zhen; Chang, Qing-Yong

    2015-05-01

    Microemulsions with limited stability in mimetic gastrointestinal environments have previously demonstrated potential for the effective removal of ammonia from artificial colonic fluid. Specialized pH‑sensitive microemulsion‑based gels for the removal of colonic ammonia (MBG‑RCA), however, possess relative stability in the gastrointestinal (GI) tract of normal rats, indicating potential use in in vivo applications. An investigation of the effects of oral MBG‑RCA was conducted in order to evaluate the reduction of intestinal ammonia and the prevention of hepatic encephalopathy (HE) in rat models. Eighty rats were allocated into eight 4‑day treatment groups: The HE model (intraperitoneal injection of thioacetamide) group; the high‑, medium‑ and low‑dose MBG‑RCA therapeutic groups (15, 10 and 5 ml/kg MBG‑RCA, respectively); and the normal, blank, lactulose and acetic acid control groups, each of which received daily treatment administration. Oral MBG‑RCA effects were identified using behavioral monitoring observed by an infrared night vision supervisory control system, electroencephalograms, blood ammonia levels, intestinal ammonia levels, liver functionality and pathological observation. High‑ and medium‑dose oral administrations of MBG‑RCA significantly decreased the blood and intestinal ammonia levels (P<0.05), improved liver functionality and reduced the clinical manifestations of HE in rats. MBG‑RCA demonstrated high clearance of rat colonic ammonia while maintaining sufficient stability in the GI tract, indicating the potential for the development of new clinically relevant oral preparations for the prevention of HE. Additionally, such preparations are advantageous in that ammonia is eliminated without the production of potentially harmful metabolic byproducts. PMID:25591795

  19. Management of Transjugular Intrahepatic Portosystemic Shunt (TIPS)-associated Refractory Hepatic Encephalopathy by Shunt Reduction Using the Parallel Technique: Outcomes of a Retrospective Case Series

    SciTech Connect

    Cookson, Daniel T. Zaman, Zubayr; Gordon-Smith, James; Ireland, Hamish M.; Hayes, Peter C.

    2011-02-15

    Purpose: 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). Materials and Methods: 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. Results: 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. Conclusion: 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.

  20. The Influence of Finasteride on Mean and Relative Spectral Density of EEG Bands in Rat Model of Thioacetamide-Induced Hepatic Encephalopathy.

    PubMed

    Mladenović, D; Hrnčić, D; Rašić-Marković, A; Macut, Dj; Stanojlović, O

    2016-08-01

    Liver failure is associated with a neuropsychiatric syndrome, known as hepatic encephalopathy (HE). Finasteride, inhibitor of neurosteroid synthesis, may improve the course of HE. The aim of our study was to investigate the influence of finasteride on mean and relative power density of EEG bands, determined by spectral analysis, in rat model of thioacetamide-induced HE. Male Wistar rats were divided into groups: (1) control; (2) thioacetamide-treated group, TAA (900 mg/kg); (3) finasteride-treated group, FIN (150 mg/kg); and (4) group treated with finasteride (150 mg/kg) and thioacetamide (900 mg/kg), FIN + TAA. Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered during 3 subsequent days, and in FIN + TAA group FIN was administered 2 h before every dose of TAA. EEG was recorded 22-24 h after treatment and analyzed by fast Fourier transformation. While TAA did not induce significant changes in the beta band, mean and relative power in this band were significantly higher in FIN + TAA versus control group (p < 0.01). TAA caused a significant decline in mean power in alpha, theta, and delta band, and in FIN + TAA group the mean power in these bands was significantly higher compared with control. While in TAA group relative power was significantly decreased in theta (p < 0.01) and increased in delta band (p < 0.01) versus control, the opposite changes were found in FIN + TAA group: an increase in theta (p < 0.01) and a decrease in delta relative power (p < 0.01). In this study, finasteride pretreatment caused EEG changes that correspond to mild TAA-induced HE. PMID:26951455

  1. Function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced in rodent model of hepatic encephalopathy.

    PubMed

    Nasehi, Mohammad; Mafi, Fatemeh; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

    2016-10-15

    Liver disease has been known for a long time to affect brain function. We now report the function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced by hepatic encephalopathy (HE) following bile duct ligation (BDL), a model of chronic liver disease. Assessment of spatial and object novelty detection memories was carried out in the non-associative task. It consists of placing mice in an open field containing five objects and, after three sessions of habituation, examining their reactivity to object displacement (spatial novelty) and object substitution (object novelty). Both spatial and object novelty detection memories were impaired by BDL after 4 weeks. In the BDL mice, pre-test intraperitoneal administration of naloxone (μ-opioidergic receptor antagonist) at dose of 0.9mg/kg restored while sulpiride (D2-like dopamine receptor antagonist) at dose of 40mg/kg potentiated object novelty detection memory deficit. However, SCH23390 (D1-like dopamine receptor antagonist) at dose of 0.04mg/kg or sulpiride (20mg/kg) restored spatial novelty detection memory deficit. Moreover, SCH23390 or sulpiride impaired while naloxone did not alter both memories in sham-operated mice. Furthermore, subthreshold dose co-administration of dopaminergic antagonists together or each one plus naloxone did not alter both memory impairments in BDL mice, while all of three co-administration groups impaired object novelty detection and co-administration of naloxone plus sulpiride impaired spatial detection memory in sham-operated mice. In conclusion, we suggest that opioidergic and dopaminergic systems through separate pathways may contribute in memory impairments induced by BDL in the non-associative task. PMID:27401106

  2. Hepatitis

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Hepatitis KidsHealth > For Kids > Hepatitis Print A A A ... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ...

  3. KCNQ2 encephalopathy

    PubMed Central

    Millichap, John J.; Park, Kristen L.; Tsuchida, Tammy; Ben-Zeev, Bruria; Carmant, Lionel; Flamini, Robert; Joshi, Nishtha; Levisohn, Paul M.; Marsh, Eric; Nangia, Srishti; Narayanan, Vinodh; Ortiz-Gonzalez, Xilma R.; Patterson, Marc C.; Pearl, Phillip L.; Porter, Brenda; Ramsey, Keri; McGinnis, Emily L.; Taglialatela, Maurizio; Tracy, Molly; Tran, Baouyen; Venkatesan, Charu; Weckhuysen, Sarah

    2016-01-01

    Objective: To advance the understanding of KCNQ2 encephalopathy genotype–phenotype relationships and to begin to assess the potential of selective KCNQ channel openers as targeted treatments. Methods: We retrospectively studied 23 patients with KCNQ2 encephalopathy, including 11 treated with ezogabine (EZO). We analyzed the genotype–phenotype relationships in these and 70 previously described patients. Results: The mean seizure onset age was 1.8 ± 1.6 (SD) days. Of the 20 EEGs obtained within a week of birth, 11 showed burst suppression. When new seizure types appeared in infancy (15 patients), the most common were epileptic spasms (n = 8). At last follow-up, seizures persisted in 9 patients. Development was delayed in all, severely in 14. The KCNQ2 variants identified introduced amino acid missense changes or, in one instance, a single residue deletion. They were clustered in 4 protein subdomains predicted to poison tetrameric channel functions. EZO use (assessed by the treating physicians and parents) was associated with improvement in seizures and/or development in 3 of the 4 treated before 6 months of age, and 2 of the 7 treated later; no serious side effects were observed. Conclusions: KCNQ2 variants cause neonatal-onset epileptic encephalopathy of widely varying severity. Pathogenic variants in epileptic encephalopathy are clustered in “hot spots” known to be critical for channel activity. For variants causing KCNQ2 channel loss of function, EZO appeared well tolerated and potentially beneficial against refractory seizures when started early. Larger, prospective studies are needed to enable better definition of prognostic categories and more robust testing of novel interventions. Classification of evidence: This study provides Class IV evidence that EZO is effective for refractory seizures in patients with epilepsy due to KCNQ2 encephalopathy. PMID:27602407

  4. Pulmonary and hepatic granulomatous disorders due to the inhalation of cement and mica dusts.

    PubMed Central

    Cortex Pimentel, J; Peixoto Menezes, A

    1978-01-01

    Hepatic and pulmonary granulomas were recognised in two workers exposed respectively to Portland cement and to muscovite dusts. The pulmonary lesions in the patient exposed to cement consisted of histiocytic granulomas and irregular fibrohyaline scars, and in the patient exposed to mica of a diffuse thickening of all interalveolar septa due to new formation of reticulin and collagen fibres and proliferation of fibroblasts and histiocytes. In the liver the following pathological findings were observed: focal or diffuse swelling of sinusoidal lining cells, sarcoid-type granulomas, and, in the case of mica exposure, perisinusoidal and portal tract fibrosis. Abundant inclusions of the inhaled material were identified within the pulmonary and hepatic lesions by histochemical and x-ray diffraction techniques. Images PMID:663882

  5. Hashimoto's encephalopathy.

    PubMed

    Schiess, Nicoline; Pardo, Carlos A

    2008-10-01

    Hashimoto's encephalopathy (HE) is a controversial neurological disorder that comprises a heterogenous group of neurological symptoms that manifest in patients with high titers of antithyroid antibodies. Clinical manifestations of HE may include encephalopathic features such as seizures, behavioral and psychiatric manifestations, movement disorders, and coma. Although it has been linked to cases of Hashimoto's thyroiditis or thyroid dysfunction, the most common immunological feature of HE is the presence of high titers of antithyroglobulin or anti-TPO (antimicrosomal) antibodies. At present, it is unclear whether antithyroid antibodies represent an immune epiphenomenon in a subset of patients with encephalopathic processes or they are really associated with pathogenic mechanisms of the disorder. The significance of classifying encephalopathies under the term HE will be determined in the future once the relevance of the role of antithyroid antibodies is demonstrated or dismissed by more detailed experimental and immunopathological studies. The responsiveness of HE to steroids or other therapies such as plasmapheresis supports the hypothesis that this is a disorder that involves immune pathogenic mechanisms. Further controlled studies of the use of steroids, plasmapheresis, or immunosuppressant medications are needed in the future to prove the concept of the pathogenic role of antithyroid antibodies in HE. PMID:18990131

  6. Affinities and densities of high-affinity (/sup 3/H)muscimol (GABA-A) binding sites and of central benzodiazepine receptors are unchanged in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy

    SciTech Connect

    Butterworth, R.F.; Lavoie, J.; Giguere, J.F.; Pomier-Layrargues, G.

    1988-09-01

    The integrity of GABA-A receptors and of central benzodiazepine receptors was evaluated in membrane preparations from prefrontal cortex and caudate nuclei obtained at autopsy from nine cirrhotic patients who died in hepatic coma and an equal number of age-matched control subjects. Histopathological studies revealed Alzheimer Type II astrocytosis in all cases in the cirrhotic group; controls were free from neurological, psychiatric or hepatic diseases. Binding to GABA-A receptors was studied using (/sup 3/H)muscimol as radioligand. The integrity of central benzodiazepine receptors was evaluated using (/sup 3/H)flunitrazepam and (/sup 3/H)Ro15-1788. Data from saturation binding assays was analyzed by Scatchard plot. No modifications of either affinities (Kd) or densities (Bmax) of (/sup 3/H)muscimol of central benzodiazepine binding sites were observed. These findings do not support recent suggestions that alterations of either high-affinity GABA or benzodiazepine receptors play a significant role in the pathogenesis of hepatic encephalopathy.

  7. Retroperitoneal Biloma due to Spontaneous Perforation of the Left Hepatic Duct

    PubMed Central

    Ishii, Kenjiro; Matsuo, Kazuhiro; Seki, Hiroaki; Yasui, Nobutaka; Sakata, Michio; Shimada, Akihiko; Matsumoto, Hidetoshi

    2016-01-01

    Patient: Male, 82 Final Diagnosis: Retroperitoneal biloma due to spontaneous perforation of the left hepatic duct Symptoms: Abdominal pain • high fever Medication: — Clinical Procedure: Emergent operation Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Spontaneous perforation of the bile duct in adults is very rare, particularly in cases accompanied by retroperitoneal biloma. We report a patient with retroperitoneal biloma due to a spontaneous perforation of the left hepatic duct. Case Report: An 82-year-old man was admitted to our institution with abdominal pain and a high fever. He had tenderness at the epi-mesogastrium. Computed tomography showed several stones in the gall bladder and common bile duct (CBD) and a few ascites. A substantial amount of fluid had collected from the dorsal stratum of the duodenum and pancreas head to the right paracolic gutter and anterior side of the right iliopsoas. Laboratory examination revealed a high inflammation score. He underwent emergent laparotomy. Biliary fluid was revealed after the mobilization of the pancreas head, duodenum, and right side of the colon. Bile duct perforation was suspected. Therefore, we exfoliated the dorsal side of the CBD to the cranial side, and intraoperative cholangiography was performed. However, the perforation site could not be detected. Cholecystectomy and choledocholithotomy were performed. A retrograde transhepatic biliary drainage tube was inserted, and primary closure of the CBD incision site was achieved. Postoperative cholangiography revealed leakage from the left hepatic duct near the caudate branch. Conclusions: There are a few reports of spontaneous bile duct perforation cases in the literature, particularly on infants or children with congenital anomalies, but it is rare in adults. It usually causes bile peritonitis, although bile duct perforation should be considered in the differential diagnosis of spontaneous retroperitoneal fluid collection in

  8. Autoimmune encephalopathies

    PubMed Central

    Leypoldt, Frank; Armangue, Thaís; Dalmau, Josep

    2014-01-01

    Over the last 10 years the continual discovery of novel forms of encephalitis associated with antibodies to cell-surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders that were previously unknown or mischaracterized. We review here the process of discovery, the symptoms, and the target antigens of twelve autoimmune encephatilic disorders, grouped by syndromes and approached from a clinical perspective. Anti-NMDAR encephalitis, several subtypes of limbic encephalitis, stiff-person spectrum disorders, and other autoimmune encephalitides that result in psychosis, seizures, or abnormal movements are described in detail. We include a novel encephalopathy with prominent sleep dysfunction that provides an intriguing link between chronic neurodegeneration and cell-surface autoimmunity (IgLON5). Some of the caveats of limited serum testing are outlined. In addition, we review the underlying cellular and synaptic mechanisms that for some disorders confirm the antibody pathogenicity. The multidisciplinary impact of autoimmune encephalitis has been expanded recently by the discovery that herpes simplex encephalitis is a robust trigger of synaptic autoimmunity, and that some patients may develop overlapping syndromes, including anti-NMDAR encephalitis and neuromyelitis optica or other demyelinating diseases. PMID:25315420

  9. Hepatitis

    MedlinePlus

    ... has been associated with drinking contaminated water. Hepatitis Viruses Type Transmission Prognosis A Fecal-oral (stool to ... risk for severe disease. Others A variety of viruses can affect the liver Signs and Symptoms Hepatitis ...

  10. Pathologic Femoral Neck Fracture Due to Fanconi Syndrome Induced by Adefovir Dipivoxil Therapy for Hepatitis B

    PubMed Central

    Lee, Yoon-Suk; Kim, Byung-Kook; Lee, Ho-Jae

    2016-01-01

    In Fanconi syndrome, hypophosphatemic osteomalacia is caused by proximal renal tubule dysfunction which leads to impaired reabsorption of amino acids, glucose, urate, and phosphate. We present a rare case of a 43-year-old Korean male who was found to have insufficiency stress fracture of the femoral neck secondary to osteomalacia due to Fanconi syndrome. He had been receiving low-dose adefovir dipivoxil (ADV, 10 mg/day) for the treatment of chronic hepatitis B virus infection for 7 years and he subsequently developed severe hypophosphatemia and proximal renal tubule dysfunction. The incomplete femoral neck fracture was fixed with multiple cannulated screws to prevent further displacement of the initial fracture. After cessation of ADV and correction of hypophosphatemia with oral phosphorus supplementation, the patient's clinical symptoms, such as bone pain, muscle weakness, and laboratory findings improved. PMID:27247753

  11. Pathologic Femoral Neck Fracture Due to Fanconi Syndrome Induced by Adefovir Dipivoxil Therapy for Hepatitis B.

    PubMed

    Lee, Yoon-Suk; Kim, Byung-Kook; Lee, Ho-Jae; Dan, Jinmyoung

    2016-06-01

    In Fanconi syndrome, hypophosphatemic osteomalacia is caused by proximal renal tubule dysfunction which leads to impaired reabsorption of amino acids, glucose, urate, and phosphate. We present a rare case of a 43-year-old Korean male who was found to have insufficiency stress fracture of the femoral neck secondary to osteomalacia due to Fanconi syndrome. He had been receiving low-dose adefovir dipivoxil (ADV, 10 mg/day) for the treatment of chronic hepatitis B virus infection for 7 years and he subsequently developed severe hypophosphatemia and proximal renal tubule dysfunction. The incomplete femoral neck fracture was fixed with multiple cannulated screws to prevent further displacement of the initial fracture. After cessation of ADV and correction of hypophosphatemia with oral phosphorus supplementation, the patient's clinical symptoms, such as bone pain, muscle weakness, and laboratory findings improved. PMID:27247753

  12. [Polyclonal activation due to Epstein-Barr virus superinfection in a case with chronic hepatitis B].

    PubMed

    Bakir Ozbey, Saliha; Mistik, Reşit; Gürcüoğlu, Emel; Oral, Barbaros; Göral, Güher

    2007-10-01

    Primary infection with Epstein-Barr virus (EBV) often occurs subclinically during childhood, resulting in a latent infection of B lymphocytes. In this report, a chronic hepatitis B case who presented with a serologic profile mimicking acute hepatitis B virus (HBV) infection and exhibiting transient autoantibody positivities because of the polyclonal activation of B cells due to EBV reactivation has been presented. The test results of 56 years old male patient who suffered from fatigue and pain on the right upper quadrant, revealed high levels of liver enzymes (AST: 187 U/L, ALT: 569 U/L), positivity of HBsAg, anti-HBc IgG and anti-HBe, and negativity of anti-HBc IgM, HBeAg and anti-HBs. Since HBV-DNA level was found 405,974 copies/mL by quantitative real time polymerase chain reaction (PCR), the patient was taken into follow-up. At the 6th month AST and ALT levels further elevated (352 U/L and 609 U/L, respectively), and anti-HBc IgM and anti-HBs became positive in addition to the previous positive markers of HBV. With the suspicion of superinfection, further laboratory investigations yielded negative results in CMV-IgM and Paul Bunnel test, while positive results in EBV anti-VCA IgM and IgG, anti-EBNA IgM and IgG, anti-p22 IgM and IgG and anti-EA IgM. In the follow-up period high levels of autoantibody positivities [rheumatoid factor (42.200 U/ml), anti-nuclear antibody (1/100) and anti-Ro-52] together with increased levels of total IgG, IgM and IgA were detected. In the following months, the levels of transaminases, total immunoglobulins and HBV-DNA have distinctively decreased, and in the 20th month the previous HBV profile regained (HBsAg, anti-HBc IgG and anti-HBe positive, anti-HBc IgM and anti-HBs negative, HBV-DNA: 6984 copies/ml) and the other pathological test results returned to normal. As a result, ALT increases seen during the course of chronic hepatitis B should not always be considered as HBV manifestations and the unusual serologic patterns should

  13. The Role of the Neurointensive Care Nursery for Neonatal Encephalopathy.

    PubMed

    Glass, Hannah C; Rowitch, David H

    2016-09-01

    Neonatal encephalopathy due to intrapartum events is estimated at 1 to 2 per 1000 live births in high-income countries. Outcomes have improved over the past decade due to implementation of therapeutic hypothermia, the only clinically available neuroprotective strategy for hypoxic-ischemic encephalopathy. Neonatal encephalopathy is the most common condition treated within a neonatal neurocritical care unit. Neonates with encephalopathy benefit from a neurocritical care approach due to prevention of secondary brain injury through attention to basic physiology, earlier recognition and treatment of neurologic complications, consistent management using guidelines and protocols, and use of optimized teams at dedicated referral centers. PMID:27524453

  14. A global amnesia associated with the specific variant of posterior reversible encephalopathy syndrome (PRES) that developed due to severe preeclampsia and malignant hypertension.

    PubMed

    Borovac, Josip Anđelo; Božić, Joško; Žaja, Nikola; Kolić, Krešimir; Hrboka, Vedran

    2016-04-01

    A case is reported of a 26-year-old primiparous woman in the 32nd week of gestation who presented to the emergency department with the symptoms of a severe headache, nausea and vomiting. The patient was diagnosed with preeclampsia that later progressed to eclampsia. This state was characterized by a sudden onset of a headache and diplopia that advanced to cortical blindness and precipitated significant alterations in mental status, most notable being global amnesia that resolved within 48 h. A post-partum magnetic resonance imaging of the brain in FLAIR mode revealed multiple cortico-subcortical areas of hyperintense signals suggestive of edematous lesions that chiefly involved occipital and parietal lobes with additional atypical manifestations. Such radiologic findings suggested a posterior reversible encephalopathy syndrome variant with the global amnesia as an extraordinary constituent. This unique feature should be acknowledged when treating a preeclamptic or hypertensive patient that exhibits neurological symptomatology and vision disturbances. PMID:27099774

  15. A global amnesia associated with the specific variant of posterior reversible encephalopathy syndrome (PRES) that developed due to severe preeclampsia and malignant hypertension

    PubMed Central

    Borovac, Josip Anđelo; Božić, Joško; Žaja, Nikola; Kolić, Krešimir; Hrboka, Vedran

    2016-01-01

    A case is reported of a 26-year-old primiparous woman in the 32nd week of gestation who presented to the emergency department with the symptoms of a severe headache, nausea and vomiting. The patient was diagnosed with preeclampsia that later progressed to eclampsia. This state was characterized by a sudden onset of a headache and diplopia that advanced to cortical blindness and precipitated significant alterations in mental status, most notable being global amnesia that resolved within 48 h. A post-partum magnetic resonance imaging of the brain in FLAIR mode revealed multiple cortico-subcortical areas of hyperintense signals suggestive of edematous lesions that chiefly involved occipital and parietal lobes with additional atypical manifestations. Such radiologic findings suggested a posterior reversible encephalopathy syndrome variant with the global amnesia as an extraordinary constituent. This unique feature should be acknowledged when treating a preeclamptic or hypertensive patient that exhibits neurological symptomatology and vision disturbances. PMID:27099774

  16. Hepatic Expression of Detoxification Enzymes Is Decreased in Human Obstructive Cholestasis Due to Gallstone Biliary Obstruction

    PubMed Central

    Chai, Jin; Feng, Xinchan; Zhang, Liangjun; Chen, Sheng; Cheng, Ying; He, Xiaochong; Yang, Yingxue; He, Yu; Wang, Huaizhi; Wang, Rongquan; Chen, Wensheng

    2015-01-01

    Background & Aims Levels of bile acid metabolic enzymes and membrane transporters have been reported to change in cholestasis. These alterations (e.g. CYP7A1 repression and MRP4 induction) are thought to be adaptive responses that attenuate cholestatic liver injury. However, the molecular mechanisms of these adaptive responses in human obstructive cholestasis due to gallstone biliary obstruction remain unclear. Methods We collected liver samples from cholestatic patients with biliary obstruction due to gallstones and from control patients without liver disease (n = 22 per group). The expression levels of bile acid synthetic and detoxification enzymes, membrane transporters, and the related nuclear receptors and transcriptional factors were measured. Results The levels of bile acid synthetic enzymes, CYP7B1 and CYP8B1, and the detoxification enzyme CYP2B6 were increased in cholestatic livers by 2.4-fold, 2.8-fold, and 1.9-fold, respectively (p<0.05). Conversely, the expression levels of liver detoxification enzymes, UGT2B4/7, SULT2A1, GSTA1-4, and GSTM1-4, were reduced by approximately 50% (p<0.05) in human obstructive cholestasis. The levels of membrane transporters, OSTβ and OCT1, were increased 10.4-fold and 1.8-fold, respectively, (p<0.05), whereas those of OSTα, ABCG2 and ABCG8 were all decreased by approximately 40%, (p<0.05) in human cholestatic livers. Hepatic nuclear receptors, VDR, HNF4α, RXRα and RARα, were induced (approximately 2.0-fold, (p<0.05) whereas FXR levels were markedly reduced to 44% of control, (p<0.05) in human obstructive cholestasis. There was a significantly positive correlation between the reduction in FXR mRNA and UGT2B4/7, SULT2A1, GSTA1, ABCG2/8 mRNA levels in livers of obstructive cholestatic patients (p<0.05). Conclusions The levels of hepatic detoxification enzymes were significantly decreased in human obstructive cholestasis, and these decreases were positively associated with a marked reduction of FXR levels. These findings

  17. Hepatitis

    MedlinePlus

    ... be serious. Some can lead to scarring, called cirrhosis, or to liver cancer. Sometimes hepatitis goes away by itself. If it does not, it can be treated with drugs. Sometimes hepatitis lasts a lifetime. Vaccines can help prevent some viral forms.

  18. Analysis of hepatic gene expression during fatty liver change due to chronic ethanol administration in mice

    SciTech Connect

    Yin, H.-Q.; Je, Young-Tae; Kim, Mingoo; Kim, Ju-Han; Kong, Gu; Kang, Kyung-Sun; Kim, Hyung-Lae; Yoon, Byung-IL; Lee, Mi-Ock; Lee, Byung-Hoon

    2009-03-15

    Chronic consumption of ethanol can cause cumulative liver damage that can ultimately lead to cirrhosis. To explore the mechanisms of alcoholic steatosis, we investigated the global intrahepatic gene expression profiles of livers from mice administered alcohol. Ethanol was administered by feeding the standard Lieber-DeCarli diet, of which 36% (high dose) and 3.6% (low dose) of the total calories were supplied from ethanol for 1, 2, or 4 weeks. Histopathological evaluation of the liver samples revealed fatty changes and punctate necrosis in the high-dose group and ballooning degeneration in the low-dose group. In total, 292 genes were identified as ethanol responsive, and several of these differed significantly in expression compared to those of control mice (two-way ANOVA; p < 0.05). Specifically, the expression levels of genes involved in hepatic lipid transport and metabolism were examined. An overall net increase in gene expression was observed for genes involved in (i) glucose transport and glycolysis, (ii) fatty acid influx and de novo synthesis, (iii) fatty acid esterification to triglycerides, and (iv) cholesterol transport, de novo cholesterol synthesis, and bile acid synthesis. Collectively, these data provide useful information concerning the global gene expression changes that occur due to alcohol intake and provide important insights into the comprehensive mechanisms of chronic alcoholic steatosis.

  19. Food Safety: Bovine Spongiform Encephalopathy (Mad Cow Disease).

    PubMed

    Acheson, David W. K.

    2002-01-01

    Bovine spongiform encephalopathy is just one of a group of diseases known as transmissible spongiform encephalopathies. Only recently has it become recognized that transmissible spongiform encephalopathies are likely due to proteins known as prions. Although it has been recognized that transmissible spongiform encephalopathies may readily spread within species, the recent observations that bovine spongiform encephalopathy in cattle may have originated from another transmissible spongiform encephalopathy in sheep, known as scrapie, is cause for concern. Further, bovine spongiform encephalopathy has now been strongly linked with a universally fatal human neurologic disease known as new variant Creutzfeldt-Jakob disease. Currently the only approach to preventing bovine spongiform encephalopathy, and subsequent new variant Creutzfeldt-Jakob disease in humans, from ingestion of bovine spongiform encephalopathy-infected material is to avoid consumption of contaminated food. Little can be done to treat food that will destroy prions and leave a palatable product. At this stage we are continuing to learn about transmissible spongiform encephalopathies and their implications on human health. This is an ever-changing situation and has an unpredictable element in terms of the extent of the current outbreaks in England and other parts of Europe. PMID:11984426

  20. Segmental Difference of the Hepatic Fibrosis from Chronic Viral Hepatitis due to Hepatitis B versus C Virus Infection: Comparison Using Dual Contrast Material-Enhanced MRI

    PubMed Central

    Shim, Jae Ho; Chung, Jae-Joon; Kim, Joo Hee; Kim, Ki Whang

    2011-01-01

    Objective We wanted to identify the geographic differences in hepatic fibrosis and their associations with the atrophy-hypertrophy complex in patients with chronic viral hepatitis using the dual-contrast material-enhanced MRI (DC-MRI) with gadopentetate dimeglumine and ferucarbotran. Materials and Methods Patients with chronic C (n = 22) and B-viral hepatitis (n = 35) were enrolled for determining the subjective grade of fibrosis (the extent and thickness of fibrotic reticulations) in the right lobe (RL), the caudate lobe (CL), the medial segment (MS) and the lateral segment (LS) of the liver, with using a 5-grade scale, on the gradient echo T2*-weighted images of DC-MRI. The fibrosis grades of different segments were compared using the Kruskal-Wallis test followed by post-hoc analysis to establish the segment-by-segment differences. The incidences of two pre-established morphologic signs of cirrhosis were also compared with each other between the two groups of patients. Results There were significant intersegmental differences in fibrosis grades of the C-viral group (p = 0.005), and the CL showed lower fibrosis grades as compared with the grades of the RL and MS, whereas all lobes were similarly affected in the B-viral group (p = 0.221). The presence of a right posterior hepatic notch was significantly higher in the patients with intersegmental differences of fibrosis between the RL and the CL (19 out of 25, 76%) than those without such differences (6 out of 32, 19%) (p < 0.001). An expanded gallbladder fossa showed no significant relationship (p = 0.327) with the segmental difference of the fibrosis grades between the LS and the MS. Conclusion The relative lack of fibrosis in the CL with more advanced fibrosis in the RL can be a distinguishing feature to differentiate chronic C-viral hepatitis from chronic B-viral hepatitis and this is closely related to the presence of a right posterior hepatic notch. PMID:21852903

  1. Bovine Spongiform Encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE), also referred to as “mad cow disease” is a chronic, non-febrile, neuro-degenerative disease affecting the central nervous system. The transmissible spongiform encephalopathies (TSEs) of domestic animals, of which BSE is a member includes scrapie of sheep...

  2. [Interferon-alpha and liver fibrosis in patients with chronic damage due to hepatitis C virus].

    PubMed

    Gonzalez-Huezo, María Sarai; Gallegos-Orozco, Juan Fernando

    2003-01-01

    The present review focuses on the published information published regarding the effects of interferon alpha therapy on liver fibrosis in patients with chronic liver damage secondary to hepatitis C infection. Data reviewed included results of the in vitro effects of interferon on hepatic cell line cultures with regards to indirect markers of fibrosis, activation of hepatic stellate cells and oxidative stress response. In the clinical arena, there is current clear evidence of a favorable histological outcome in patients with sustained viral response to interferon therapy. For this reason, the current review focuses more on the histological outcomes regarding liver fibrosis in patients who have not attained viral response to therapy (non-responders) or who already have biopsy defined cirrhosis. Data in these patients were analyzed according to the results of objective testing of fibrosis through the assessment of liver biopsy and its change during time, specially because the morbidity and mortality of this disease is directly related to the complications of liver cirrhosis and not necessarily to the persistence of the hepatitis C virus. Lastly, it is concluded that the process of liver fibrosis/cirrhosis is a dynamic one and that there is some evidence to support the usefulness of interferon alpha therapy as a means to halt or retard the progression of hepatic fibrosis. The result of current clinical trials in which interferon therapy is being used to modify the progression of fibrosis in non-responders or cirrhotic patients is eagerly awaited. PMID:14702938

  3. Herpes Simplex Virus Hepatitis in an Immunocompetent Adult: A Fatal Outcome due to Liver Failure

    PubMed Central

    Poley, Rachel A.; Snowdon, Jaime F.; Howes, Daniel W.

    2011-01-01

    Objective. To present a case of a healthy 41-year-old female who developed fulminant hepatic failure leading to death. The cause of hepatic failure identified on postmortem exam was herpes simplex virus hepatitis. Design. Observation of a single patient. Setting. Intensive care unit of a tertiary care university teaching hospital in Canada. Patient. 41-year-old previously healthy female presenting with a nonspecific viral illness and systemic inflammatory response syndrome. Intervention. The patient was treated with intravenous fluids and broad-spectrum antibiotics. On the second day of admission, she was found to have elevated transaminases, and, over 48 hours, she progressed to fulminant liver failure with disseminated intravascular coagulopathy, refractory lactic acidosis, and shock. She progressed to respiratory failure requiring intubation and mechanical ventilation. She was started on N-acetylcysteine, a bicarbonate infusion, hemodialysis, and multiple vasopressors and inotropes. Measurements and Main Results. Despite treatment, the patient died roughly 70 hours after her initial presentation to hospital. Her postmortem liver biopsy revealed herpes simplex virus hepatitis as her cause of death. Conclusions. Herpes simplex virus must be considered in all patients presenting with liver failure of unknown cause. If suspected, prompt treatment with acyclovir should be initiated. PMID:24826316

  4. Metabolic Causes of Epileptic Encephalopathy

    PubMed Central

    Pearl, Phillip L.

    2013-01-01

    Epileptic encephalopathy can be induced by inborn metabolic defects that may be rare individually but in aggregate represent a substantial clinical portion of child neurology. These may present with various epilepsy phenotypes including refractory neonatal seizures, early myoclonic encephalopathy, early infantile epileptic encephalopathy, infantile spasms, and generalized epilepsies which in particular include myoclonic seizures. There are varying degrees of treatability, but the outcome if untreated can often be catastrophic. The importance of early recognition cannot be overemphasized. This paper provides an overview of inborn metabolic errors associated with persistent brain disturbances due to highly active clinical or electrographic ictal activity. Selected diseases are organized by the defective molecule or mechanism and categorized as small molecule disorders (involving amino and organic acids, fatty acids, neurotransmitters, urea cycle, vitamers and cofactors, and mitochondria) and large molecule disorders (including lysosomal storage disorders, peroxisomal disorders, glycosylation disorders, and leukodystrophies). Details including key clinical features, salient electrophysiological and neuroradiological findings, biochemical findings, and treatment options are summarized for prominent disorders in each category. PMID:23762547

  5. Colectomy for Porto-Systemic Encephalopathy: Is it Still Topical?

    PubMed

    Ennaifer, Rym; Hayfa, Romdhane; Hefaiedh, Rania; Marsaoui, Lobna; Hadj, Najet Bel; Khalfallah, Tahar

    2013-01-25

    Hepatic encephalopathy (HE) is a common long term complication of porto-systemic shunt. We report herein the case of a 59-year-old man with Child-Pugh A cirrhosis treated successfully 9 years earlier with distal splenorenal shunt for uncontrolled variceal bleeding. In the last year, he developed a severe and persistent hepatic encephalopathy secondary to the shunt, which was resistant to medical therapy. As liver transplantation was not available and obliteration of the shunt was hazardous, we performed subtotal colectomy in order to reduce ammonia production. This therapeutic option proved successful, as the grade of encephalopathy decreased and the patient improved. Our experience indicates that colonic exclusion should be considered as an option in the management of HE refractory to medical treatment in highly selected patients when liver transplantation is not available or even as a bridge given the long waiting time on lists. PMID:24765497

  6. Antineutrophil Cytoplasmic Antibody Induction due to Infection: A Patient with Infective Endocarditis and Chronic Hepatitis C.

    PubMed

    Kamar, Fareed B; Hawkins, T Lee-Ann

    2016-01-01

    While antineutrophil cytoplasmic antibody (ANCA) is often used as a diagnostic marker for certain vasculitides, ANCA induction in the setting of infection is much less common. In the case of infective endocarditis, patients may present with multisystem disturbances resembling an autoimmune process, cases that may be rendered even trickier to diagnose in the face of a positive ANCA. Though not always straightforward, distinguishing an infective from an inflammatory process is pivotal in order to guide appropriate therapy. We describe an encounter with a 43-year-old male with chronically untreated hepatitis C virus infection who featured ANCA positivity while hospitalized with acute bacterial endocarditis. His case serves as a reminder of two of the few infections known to uncommonly generate ANCA positivity. We also summarize previously reported cases of ANCA positivity in the context of endocarditis and hepatitis C infections. PMID:27366166

  7. Antineutrophil Cytoplasmic Antibody Induction due to Infection: A Patient with Infective Endocarditis and Chronic Hepatitis C

    PubMed Central

    Kamar, Fareed B.; Hawkins, T. Lee-Ann

    2016-01-01

    While antineutrophil cytoplasmic antibody (ANCA) is often used as a diagnostic marker for certain vasculitides, ANCA induction in the setting of infection is much less common. In the case of infective endocarditis, patients may present with multisystem disturbances resembling an autoimmune process, cases that may be rendered even trickier to diagnose in the face of a positive ANCA. Though not always straightforward, distinguishing an infective from an inflammatory process is pivotal in order to guide appropriate therapy. We describe an encounter with a 43-year-old male with chronically untreated hepatitis C virus infection who featured ANCA positivity while hospitalized with acute bacterial endocarditis. His case serves as a reminder of two of the few infections known to uncommonly generate ANCA positivity. We also summarize previously reported cases of ANCA positivity in the context of endocarditis and hepatitis C infections. PMID:27366166

  8. Hepatitis in farmed hatchling Nile crocodiles (Crocodylus niloticus) due to chlamydial infection.

    PubMed

    Huchzermeyer, F W; Gerdes, G H; Foggin, C M; Huchzermeyer, K D; Limper, L C

    1994-03-01

    An investigation into the cause of acute mortality in farmed hatchling crocodiles Crocodylus niloticus led to the isolation of chlamydia from the livers of affected animals. Prominent pathological finds were acute hepatitis with intracellular chlamydial colonies and generalized oedema. A chlamydia presumed to be C. psittaci was isolated from livers of affected hatchlings. Mortality subsided after treatment with oxytetracycline. This disease is now recognized as being a major problem on crocodile farms in Zimbabwe. PMID:7745587

  9. Antibiotic-associated encephalopathy.

    PubMed

    Bhattacharyya, Shamik; Darby, R Ryan; Raibagkar, Pooja; Gonzalez Castro, L Nicolas; Berkowitz, Aaron L

    2016-03-01

    Delirium is a common and costly complication of hospitalization. Although medications are a known cause of delirium, antibiotics are an underrecognized class of medications associated with delirium. In this article, we comprehensively review the clinical, radiologic, and electrophysiologic features of antibiotic-associated encephalopathy (AAE). AAE can be divided into 3 unique clinical phenotypes: encephalopathy commonly accompanied by seizures or myoclonus arising within days after antibiotic administration (caused by cephalosporins and penicillin); encephalopathy characterized by psychosis arising within days of antibiotic administration (caused by quinolones, macrolides, and procaine penicillin); and encephalopathy accompanied by cerebellar signs and MRI abnormalities emerging weeks after initiation of antibiotics (caused by metronidazole). We correlate these 3 clinical phenotypes with underlying pathophysiologic mechanisms of antibiotic neurotoxicity. Familiarity with these types of antibiotic toxicity can improve timely diagnosis of AAE and prompt antibiotic discontinuation, reducing the time patients spend in the delirious state. PMID:26888997

  10. A case of thyroid storm complicated by acute hepatitis due to propylthiouracil treatment

    PubMed Central

    Hashim, Nazhri; Sze, Candy; Waterhouse, Mona

    2015-01-01

    Summary A 57-year-old female presented 17 days after treatment with radioactive iodine (RAI) for difficult-to-control hyperthyroidism. She was febrile, had a sinus tachycardia, and was clinically thyrotoxic. Her thyroid function tests showed a suppressed TSH <0.02 mU/l, with free thyroxine (FT4) >75 pmol/l and total triiodothyronine (TT3) 6.0 nmol/l. She was diagnosed with thyroid storm and was managed with i.v. fluids, propylthiouracil (PTU) 200 mg four times a day, prednisolone 30 mg once daily and propanolol 10 mg three times a day. She gradually improved over 2 weeks and was discharged home on PTU with β blockade. On clinic review 10 days later, it was noted that, although she was starting to feel better, she had grossly abnormal liver function (alanine transaminase (ALT) 852 U/l, bilirubin 46 μmol/l, alkaline phosphatase (ALP) 303 U/l, international normalized ratio (INR) 0.9, platelets 195×109/l). She was still mildly thyrotoxic (TSH <0.02 mU/l, FT4 31 pmol/l, TT3 1.3 nmol/l). She was diagnosed with acute hepatitis secondary to treatment with PTU. Ultrasound showed mild hepatic steatosis. PTU was stopped and she was managed with fluids and prednisolone 60 mg once daily and continued β blockade. Her liver function gradually improved over 10 days (bilirubin 9 μmol/l, ALT 164 U/l, ALP 195 U/l, INR 0.9, platelets 323×109/l) with conservative management and had normalised by clinic review 3 weeks later. This case highlights the potentially fatal, but rare, complications associated with both RAI and PTU, namely, thyroid storm and acute hepatitis respectively. Learning points Thyroid storm is an important, albeit rare, endocrinological emergency.Thyroid storm following RAI treatment is extremely rare.Management is with i.v. fluids, β blockade, anti-thyroid drugs and steroids.High dose glucocorticoid steroids can block the peripheral conversion of T4 to active T3.Liver dysfunction, acute hepatitis and potential hepatic failure

  11. Decreased exposure of atorvastatin in diabetic rats partly due to induction of hepatic Cyp3a and Oatp2.

    PubMed

    Shu, Nan; Hu, Mengyue; Liu, Can; Zhang, Mian; Ling, Zhaoli; Zhang, Ji; Xu, Ping; Zhong, Zeyu; Chen, Yang; Liu, Li; Liu, Xiaodong

    2016-10-01

    1. Atorvastatin is frequently prescribed for lowering blood cholesterol and for prevention of events associated with cardiovascular disease. The aim of this study was to investigate the pharmacokinetics of atorvastatin in diabetic rats. 2. Diabetes was induced in rats by combination of high-fat diet and low-dose streptozotocin (35 mg/kg). Plasma concentrations of atorvastatin following oral (10 mg/kg) and intravenous (2 mg/kg) administrations to rats were measured by LC-MS. Metabolism and uptake of atorvastatin in primary hepatocytes of experimental rats were assessed. Protein expressions and activities of hepatic Cyp3a and Oatp2 were further investigated. 3. Clearances of atorvastatin in diabetic rats following oral and intravenous administrations were remarkably increased, leading to marked decreases in area-under-the-plasma concentration-time curve (AUC). The estimated oral and systematic clearances of atorvastatin in diabetic rats were 4.5-fold and 2.0-fold of control rats, respectively. Metabolism and uptake of atorvastatin in primary hepatocytes isolated from diabetic rats were significantly increased, which were consistent with the up-regulated protein expressions and activities of hepatic Cyp3a and Oatp2. 4. All these results demonstrated that the plasma exposure of atorvastatin was significantly decreased in diabetic rats, which was partly due to the up-regulated activities and expressions of both hepatic Cyp3a and Oatp2. PMID:26864241

  12. Valproate-induced hyperammonemic encephalopathy enhanced by topiramate and phenobarbitone: A case report and an update

    PubMed Central

    Vivekanandan, S.; Nayak, S. Dinesh

    2010-01-01

    Although sodium valproate (VPA)-induced hepatic encephalopathy is a well-recognized entity, VPA can occasionally produce encephalopathy secondary to hyperammonemia in the presence of normal hepatic function, namely valproate-induced non-hepatic hyperammonemic encephalopathy (VNHE). Known risk factors include therapy with multiple antiepileptic drugs, especially when topiramate is one of the drugs; presence of underlying inborn errors of metabolism; febrile states; and insufficient nutritional intake. We describe a 5-year-old male child who developed VNHE while on polypharmacy with topiramate and phenobarbitone; the child also had poor nutritional intake. The encephalopathy reversed with withdrawal of VPA and treatment with L-carnitine. We emphasize the need for early recognition, investigation, and treatment of this potentially life-threatening condition. We also recommend that VPA, topiramate, and phenobarbitone should not be given in combination. PMID:20814502

  13. [Posterior reversible encephalopathy syndrome].

    PubMed

    Fischer, M; Schmutzhard, E

    2016-06-01

    Posterior reversible encephalopathy syndrome refers to a neurological disorder characterized by headache, disorders of consciousness, visual disturbances, epileptic seizures, and subcortical vasogenic edema. About two thirds of patients develop neurological symptoms, which are associated with blood pressure fluctuations. One hypothesis is that hypertensive episodes cause autoregulatory failure, and values above the upper limit of cerebral autoregulation result in a breakthrough followed by hyperperfusion and blood-brain barrier dysfunction. In another hypothesis, endothelial dysfunction triggered by numerous factors including preeclampsia, immunosuppressive agents, chemotherapeutics, sepsis, or autoimmune disorders is thought to be the key pathomechanism. Endo- or exogenic toxic agents including pharmacological substances, cytokines, or bacterial toxins are supposed to trigger endothelial activation and dysfunction resulting in the release of vasoconstrictors, pro-inflammatory mediators, and vascular leakage. Diagnosis is usually based on clinical and neuroimaging findings that frequently show a bilateral, symmetric, and parietooccipital pattern. However, the diagnosis can often only be confirmed during the course of disease after excluding important differential diagnoses. Currently, there is no specific treatment available. Lowering of arterial blood pressure and eliminating the underlying cause usually leads to an improvement of clinical and neuroradiological findings. Admission to a critical care unit is required in about 40 % of patients due to complicating conditions including status epilepticus, cerebral vasoconstriction, ischemia, or intracerebral hemorrhage. Prognosis is favorable; in the majority of patients neurological deficits and imaging findings resolve completely. PMID:27272329

  14. Chronic traumatic encephalopathy.

    PubMed

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

    2013-01-01

    Sports-related concussion has gained increased prominence, in part due to media coverage of several well-known athletes who have died from consequences of chronic traumatic encephalopathy (CTE). CTE was first described by Martland in 1928 as a syndrome seen in boxers who had experienced significant head trauma from repeated blows. The classic symptoms of impaired cognition, mood, behavior, and motor skills also have been reported in professional football players, and in 2005, the histopathological findings of CTE were first reported in a former National Football League (NFL) player. These finding were similar to Alzheimer's disease in some ways but differed in critical areas such as a predominance of tau protein deposition over amyloid. The pathophysiology is still unknown but involves a history of repeated concussive and subconcussive blows and then a lag period before CTE symptoms become evident. The involvement of excitotoxic amino acids and abnormal microglial activation remain speculative. Early identification and prevention of this disease by reducing repeated blows to the head has become a critical focus of current research. PMID:23314081

  15. Hepatic glutathione contributes to attenuation of thioacetamide-induced hepatic necrosis due to suppression of oxidative stress in diet-induced obese mice.

    PubMed

    Shirai, Makoto; Matsuoka, Miho; Makino, Toshihiko; Kai, Kiyonori; Teranishi, Munehiro; Takasaki, Wataru

    2015-08-01

    We previously reported that hepatic necrosis induced by thioacetamide (TA), a hepatotoxicant, was attenuated in mice fed a high-fat diet (HFD mice) in comparison with mice fed a normal rodent diet (ND mice). In this study, we focused on investigation of the mechanism of the attenuation. Hepatic content of thiobarbituric acid reactive substances (TBARS), an oxidative stress marker, significantly increased in ND mice at 24 and 48 hr after TA administration in comparison to that in vehicle-treated ND mice. At these time points, severe hepatic necrosis was observed in ND mice. Treatment with an established antioxidant, butylated hydroxyanisole, attenuated the TA-induced hepatic necrosis in ND mice. In contrast, in HFD mice, hepatic TBARS content did not increase, and hepatic necrosis was attenuated in comparison with ND mice at 24 and 48 hr after TA dosing. Metabolomics analysis regarding hepatic glutathione, a biological antioxidant, revealed decreased glutathione and changes in the amount of glutathione metabolism-related metabolites, such as increased ophtalmate and decreased cysteine, and this indicated activation of glutathione synthesis and usage in HFD mice. Finally, after treatment with L-buthionine-S,R-sulfoxinine, an inhibitor of glutathione synthesis, TA-induced hepatic necrosis was enhanced and hepatic TBARS contents increased after TA dosing in HFD mice. These results suggested that activated synthesis and usage of hepatic GSH, which suppresses hepatic oxidative stress, is one of the factors that attenuate TA-induced hepatic necrosis in HFD mice. PMID:26165648

  16. Hepatitis and splenitis due to systemic tetratrichomoniasis in an American white pelican (Pelecanus erythrorhynchos).

    PubMed

    Burns, Rachel E; Braun, Josephine; Armién, Aníbal G; Rideout, Bruce A

    2013-07-01

    A free-ranging, young adult, female American white pelican (Pelecanus erythrorhynchos), found dead on the grounds of the San Diego Zoo Safari Park in Southern California, had severe multifocal to coalescing necrotizing hepatitis and splenitis on postmortem examination. Histologically, within the large areas of necrosis were myriad pleomorphic, 5-20 µm in diameter, protozoal organisms with 1 to multiple nuclei. Ultrastructurally, the organisms were consistent with a trichomonad flagellate. Polymerase chain reaction and sequencing of the small subunit ribosomal RNA gene identified nucleotide sequences with 99% identity to Tetratrichomonas gallinarum, which is a common inhabitant of the intestinal tract of galliform and anseriform birds that has occasionally been associated with disease, including typhlitis and hepatitis. Damage to the cecal mucosa in the pelican from trematodes and secondary bacterial infection could have allowed invasion and systemic dissemination of the organism. Exposure of the pelican to a variety of native and exotic anseriform and galliform birds at the zoological institution could have led to cross-species infection and severe manifestation of disease in a novel host. PMID:23674462

  17. Alterations in the intrinsic electrophysiological properties of Purkinje neurons in a rat model of hepatic encephalopathy: Relative preventing effect of PPARγ agonist.

    PubMed

    Aghaei, Iraj; Hajali, Vahid; Dehpour, Ahmadreza; Haghani, Masoud; Sheibani, Vahid; Shabani, Mohammad

    2016-03-01

    Patients suffering from hepatic cirrhosis (HC) have been shown to have motor and cognitive impairments. The cerebellum, which controls coordinated and rapid movements, is a potential target for the deleterious effects of hyperammonemia induced by bile duct ligation. Therefore, the aim of this study was to determine the mechanisms of motor impairments observed in a rat model of HC and second objective of the current study was to evaluate the possible protective effect of pioglitazone (PIO) on these impairments. Male Wistar rats were used in the current study. Bile duct ligation (BDL) surgery was performed and pioglitazone administration was started two weeks after the surgery for the next four weeks. The effects of pioglitazone on BDL-induced electrophysiological changes of the Purkinje cerebellum neurons were evaluated by Whole-cell patch clamp recordings. Purkinje neurons from the BDL group exhibited significant changes in a number of electrophysiological properties and some alterations partially were counteracted by activation of peroxisome proliferator-activated receptor-γ. Purkinje cells from BDL groups showed a significant increase in the spontaneous firing frequency followed by a decrease in the action potential duration of half-amplitude and spike interval. Chronic administration of pioglitazone could contract this effect of BDL on event frequency and interevent interval, though the difference with the sham group was still significant in the duration of action potential. Results of the current study raise the possibility that BDL may profoundly affect the intrinsic membrane properties of the cerebellar Purkinje neurons and PIO administration can counteract some of these effects. PMID:26704786

  18. Intravascular Hemolysis and Septicemia due to Clostridium perfringens Emphysematous Cholecystitis and Hepatic Abscesses

    PubMed Central

    Cochrane, Justin; Bland, Lacie; Noble, Mary

    2015-01-01

    Context. Clostridium perfringens septicemia is often associated with translocation from the gastrointestinal or gastrourinary tract and occurs in patients who have malignancy or are immunocompromised. Clostridium perfringens septicemia is usually fatal without early identification, source control, and antibiotics. Case. We present a case of a 65-year-old female with Clostridium perfringens septicemia secondary to emphysematous cholecystitis, with progression to hepatic abscesses. Conclusion. Septicemia secondary to Clostridium perfringens is generally fatal if not detected early. Source control with surgery or percutaneous drainage and early antibiotic therapy is imperative. Hyperbaric oxygen therapy may reduce mortality. Clinicians caring for patients with sepsis and intravascular hemolysis must have Clostridium perfringens septicemia on their differential diagnosis with a low threshold for starting antibiotics and pursuing source of infection. PMID:26229537

  19. Abdominal Skin Rash After TACE Due to Non-Target Embolization of Hepatic Falciform Artery

    PubMed Central

    Bhalala, Mitesh; Vidholia, Aditi; Sao, Rahul; Sharma, Nisha; Mehta, Dhruv; McCabe, Sam; Bodin, Roxana

    2016-01-01

    Transcatheter arterial chemoembolization (TACE) is a well-recognized procedure for management of hepatocellular carcinoma. We present a 54-year-old man who presented with a periumbilical maculopapular skin rash that developed after an otherwise uneventful TACE procedure. A retrospective review of imaging was consistent with non-target embolization of the hepatic falciform artery (HFA). He was treated with oral non-steroidal antiinflammatory medication for 3 weeks with improvement, but had slight skin induration and an excoriated papule at 6-month follow-up. Non-target embolization of HFA is very rare, but clinicians and interventionalists should be aware of this complication, especially in patients predisposed to enlargement of HFA. PMID:27144210

  20. [Hashimoto's encephalopathy and autoantibodies].

    PubMed

    Yoneda, Makoto

    2013-04-01

    Encephalopathy occasionally occurs in association with thyroid disorders, but most of these are treatable. These encephalopathies include a neuropsychiatric disorder associated with hypothyroidism, called myxedema encephalopathy. Moreover, Hashimoto's encephalopathy (HE) has been recognized as a new clinical disease based on an autoimmune mechanism associated with Hashimoto's thyroiditis. Steroid treatment was successfully administered to these patients. Recently, we discovered that the serum autoantibodies against the NH2-terminal of α-enolase (NAE) are highly specific diagnostic biomarkers for HE. Further, we analyzed serum anti-NAE autoantibodies and the clinical features in many cases of HE from institutions throughout Japan and other countries. Approximately half of assessed HE patients carry anti-NAE antibodies. The age was widely distributed with 2 peaks (20-30 years and 50-70 years). Most HE patients were in euthyroid states, and all patients had anti-thyroid (TG) antibodies and anti-thyroid peroxidase (TPO) antibodies. Anti-TSH receptor (TSH-R) antibodies were observed in some cases. The common neuropsychiatry features are consciousness disturbance and psychosis, followed by cognitive dysfunction, involuntary movements, seizures, and ataxia. Abnormalities on electroencephalography (EEG) and decreased cerebral blood flow on brain SPECT were common findings, whereas abnormal findings on brain magnetic resonance imaging (MRI) were rare. HE patients have various clinical phenotypes such as the acute encephalopathy form, the chronic psychiatric form, and other particular clinical forms, including limbic encephalitis, progressive cerebellar ataxia, and Creutzfeldt-Jakob disease (CJD)-like form. The cerebellar ataxic form of HE clinically mimics spinocerebellar degeneration (SCD) and is characterized by the absence of nystagmus, absent or mild cerebellar atrophy, and lazy background activities on EEG. Taken together, these data suggest that the possibility of

  1. Movement Disorders in Non-Wilsonian Hepatic Cirrhotic Patients: The Subgroup Analysis of Various Phenotypes and Associated Risk Factors

    PubMed Central

    Methawasin, Kulthida; Chonmaitree, Piyanant; Wongjitrat, Chatchawan; Rattanamongkolgul, Suthee; Asawavichienjinda, Thanin

    2016-01-01

    Objective The aim of this subgroup analysis was to identify the risk factors associated with the development of various movement disorder phenotypes. Methods Eighty-three non-Wilsonian cirrhotic patients with abnormal movements were allocated into the following groups: intention tremor, bradykinesia, Parkinsonism, and abnormal ocular movements. These movement types were considered the primary outcomes as there was a sufficient sample size. Researchers took into consideration the gender, etiologies of cirrhosis, cirrhosis-related complications, hepatic encephalopathy, medical illness, and some neurological deficits as potential factors associated with these movement disorders. Results The male gender (p = 0.002) and alcoholic cirrhosis (p = 0.005) were significant factors for the prevalence of intention tremors. In bradykinesia, hepatic encephalopathy was highly statistically significant (p < 0.001), and females more commonly developed bradykinesia (p = 0.04). The Parkinsonism features in this study were confounded by hyperlipidemia (p = 0.04) and motor or sensory deficits (p = 0.02). Jerky pursuits and a horizontal nystagmus were detected. Jerky pursuits were significantly related to hepatic encephalopathy (p = 0.003) and bradykinesia, but there were no factors associated with the prevalence of nystagmus other than an intention tremor. Conclusions The association of alcoholic cirrhosis with the development of intention tremor indicates that the persistent cerebellar malfunction in cirrhotic patients is due to alcohol toxicity. The slowness of finger tapping and jerky pursuit eye movements are significantly associated with hepatic encephalopathy. Thus, further studies are needed to evaluate the diagnostic value of these two signs for an early detection of mild hepatic encephalopathy. PMID:27020458

  2. Encephalopathy in megacystis-microcolon-intestinal hypoperistalsis syndrome patients on long-term total parenteral nutrition possibly due to selenium deficiency.

    PubMed

    Hirato, Junko; Nakazato, Yoichi; Koyama, Hiroshi; Yamada, Ami; Suzuki, Norio; Kuroiwa, Minoru; Takahashi, Atsushi; Matsuyama, Shiro; Asayama, Kohtaro

    2003-09-01

    resulted from oxidative damage of the brain related to the low levels of glutathione peroxidase and other selenoproteins due to selenium deficiency. PMID:12845451

  3. Nonalcoholic Wernicke's encephalopathy.

    PubMed

    Welsh, Amanda; Rogers, Peter; Clift, Fraser

    2016-07-01

    Wernicke's encephalopathy (WE) is a serious neurologic condition resulting from thiamine deficiency. The majority of cases involve alcoholism; however, nonalcohol-associated WE does occur and is under-recognized. We discuss a case of a 22-year-old man with a history of Crohn's disease who presented to our emergency department with multiple neurologic complaints related to WE. PMID:25985980

  4. [Bovine spongiform encephalopathy].

    PubMed

    Suárez Fernández, G

    2001-01-01

    An histórical and conceptual review is made about Bovine Spongiform Encephalopathy or mad cows disease and an epidemiological analysis as a present and future health problem. This analysis of BSE should not be negative, considering the truths that we know today. PMID:11783042

  5. The transmissible spongiform encephalopathies of livestock.

    PubMed

    Greenlee, Justin J; Greenlee, M Heather West

    2015-01-01

    Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal protein-misfolding neurodegenerative diseases. TSEs have been described in several species, including bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, transmissible mink encephalopathy (TME) in mink, and Kuru and Creutzfeldt-Jakob disease (CJD) in humans. These diseases are associated with the accumulation of a protease-resistant, disease-associated isoform of the prion protein (called PrP(Sc)) in the central nervous system and other tissues, depending on the host species. Typically, TSEs are acquired through exposure to infectious material, but inherited and spontaneous TSEs also occur. All TSEs share pathologic features and infectious mechanisms but have distinct differences in transmission and epidemiology due to host factors and strain differences encoded within the structure of the misfolded prion protein. The possibility that BSE can be transmitted to humans as the cause of variant Creutzfeldt-Jakob disease has brought attention to this family of diseases. This review is focused on the TSEs of livestock: bovine spongiform encephalopathy in cattle and scrapie in sheep and goats. PMID:25991695

  6. Wernicke encephalopathy in a patient with liver failure: Clinical case report.

    PubMed

    Zhao, Pan; Zhao, Yanling; Wei, Zhenman; Chen, Jing; Yan, Lilong

    2016-07-01

    Early recognition and diagnosis of Wernicke encephalopathy is pivotal for the prognosis of this medical emergency, especially in patients with liver failure which predisposes individuals to develop hepatic encephalopathy. For these patients, distinguishing between hepatic encephalopathy and Wernicke encephalopathy is a challenge in real-world clinical practice.A male patient with 21-year medical history of liver cirrhosis presented diarrhea and ascites. One month before this visit, he was noted to have poor appetite and progressive fatigue. After admission, although several major symptoms, including diarrhea, ascites, hyponatremia, and hypoproteinemia, were greatly improved through appropriate treatments, his laboratory indicators were not changed much. His appetite was not reversed at discharge. On the 5th day after discharge, the patient suddenly became reluctant to speak and did not remember the recent happenings. Simultaneously, unsteady gait and strabismus occurred. On the basis of clinical manifestations and brain magnetic resonance imaging scan results, the patient was diagnosed as Wernicke encephalopathy and these relative symptoms were resolved after intravenous vitamin B1.To our knowledge, this is the second case report of Wernicke encephalopathy developing in a critically ill cirrhotic patient without hepatocellular carcinoma or operative intervention. Wernicke encephalopathy may be underdiagnosed in these patients and this case raises physicians' awareness of its possible onset. PMID:27399058

  7. Association of increased rate of condemnation of broiler carcasses due to hepatic abnormalities with immunosuppressive diseases in the broiler chicken industry in Saskatchewan.

    PubMed

    Amini, Keyvan; Zachar, Tara; Popowich, Shelly; Knezacek, Tennille; Goodhope, Bob; Willson, Philip; Gomis, Susantha

    2015-10-01

    The objective of this study was to identify the causative agents of hepatitis observed in broiler chickens at processing. Livers of chickens from 16 broiler farms in Saskatchewan with gross lesions of hepatitis were collected at processing. In addition to routine bacterial isolation and histopathological examination, serologic studies for infectious bursal disease virus (IBDV) and Chicken anaemia virus (CAV), calculation of the ratio of the weight of the bursa of Fabricius (BF) to body weight (BBW), and histopathological examination of the BF were done. Of the 264 livers with gross lesions, 83% had multifocal to coalescing necrotizing hepatitis, 16% had perihepatitis, and 1% had hemorrhages. No definitive causative microorganisms were isolated from the hepatic lesions; however, no significant bacterial isolations were made. Bursal atrophy, low BBW ratio, and high titer of antibody against IBDV each correlated with the rate of total condemnations (P = 0.0188, P = 0.0001, and P = 0.0073, respectively). Nucleotide sequencing of IBDV isolated from the BF identified the variant strains Delaware-E and 586. Condemnation because of hepatic lesions was correlated with titer of antibody against IBDV and BBW (P = 0.016 and P = 0.027). The results of this study demonstrate that hepatic lesions in Saskatchewan chickens are not currently caused by a primary bacterial pathogen but are associated with indicators of immunosuppression that is likely due to variant IBDV. PMID:26424905

  8. Association of increased rate of condemnation of broiler carcasses due to hepatic abnormalities with immunosuppressive diseases in the broiler chicken industry in Saskatchewan

    PubMed Central

    Amini, Keyvan; Zachar, Tara; Popowich, Shelly; Knezacek, Tennille; Goodhope, Bob; Willson, Philip; Gomis, Susantha

    2015-01-01

    The objective of this study was to identify the causative agents of hepatitis observed in broiler chickens at processing. Livers of chickens from 16 broiler farms in Saskatchewan with gross lesions of hepatitis were collected at processing. In addition to routine bacterial isolation and histopathological examination, serologic studies for infectious bursal disease virus (IBDV) and Chicken anaemia virus (CAV), calculation of the ratio of the weight of the bursa of Fabricius (BF) to body weight (BBW), and histopathological examination of the BF were done. Of the 264 livers with gross lesions, 83% had multifocal to coalescing necrotizing hepatitis, 16% had perihepatitis, and 1% had hemorrhages. No definitive causative microorganisms were isolated from the hepatic lesions; however, no significant bacterial isolations were made. Bursal atrophy, low BBW ratio, and high titer of antibody against IBDV each correlated with the rate of total condemnations (P = 0.0188, P = 0.0001, and P = 0.0073, respectively). Nucleotide sequencing of IBDV isolated from the BF identified the variant strains Delaware-E and 586. Condemnation because of hepatic lesions was correlated with titer of antibody against IBDV and BBW (P = 0.016 and P = 0.027). The results of this study demonstrate that hepatic lesions in Saskatchewan chickens are not currently caused by a primary bacterial pathogen but are associated with indicators of immunosuppression that is likely due to variant IBDV. PMID:26424905

  9. Posterior encephalopathy subsequent to cyclosporin A presenting as irreversible abulia.

    PubMed

    Nishie, Makoto; Kurahashi, Kozo; Ogawa, Masaya; Yoshida, Yasuji; Midorikawa, Hiroshi

    2003-08-01

    A case of cyclosporin A (Cys A)-induced posterior encephalopathy developed into persistent abulia despite rapid and marked improvement of abnormal T2- and FLAIR MRI hyperintense regions. Diffusion-weighted MRI signal intensity was also high at the onset. This change is atypical in Cys A-induced encephalopathy and was thought to predict poor recovery from the encephalopathy. Persistent abulia was probably due to marked hypoperfusion in the whole cortex including bilateral frontal lobes and basal ganglia as detected by SPECT. Apart from the breakdown of the blood-brain barrier, direct toxicity of Cys A to the brain may play a role in the pathogenesis of chronic, irreversible encephalopathy. PMID:12924507

  10. Herpes simplex virus type 1 hepatitis due to primary infection in a pancreas-kidney transplant recipient.

    PubMed

    Feugeas, J; Mory, S; Jeulin, H; Velay, A; Pertek, J-P; Ladriere, M; Losser, M-R

    2016-07-01

    Herpes simplex Virus (HSV) hepatitis is a rare complication of HSV-1 primary infection, with a delayed diagnosis, affecting mainly immunocompromised patients. We describe a case of HSV-1 hepatitis after primary infection occurring in the postoperative days after a pancreas-kidney transplantation. The patient presented with an unusual evolution of a persistent severe hepatitis associated with a persistent viremia (Quantitative Polymerase Chain Reaction) despite an adequate intravenous (iv) antiviral treatment. Abdominal computed tomography scan showed a miliary hepatitis. The diagnosis of HSV-1 hepatitis was confirmed by immuno-chemistry on liver biopsy. The donor was negative for anti-HSV antibodies, excluding contamination by the graft. This case report emphasizes a rather seldom risk of care-associated viral infections, predominantly in immunocompromised patients. PMID:27155056

  11. Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

    SciTech Connect

    Ma, Noelle; Nicholson, Catherine J.; Wong, Michael; Holloway, Alison C.; Hardy, Daniel B.

    2014-02-15

    While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced

  12. Wernicke's encephalopathy in a patient with masticator and parapharyngeal space abscess: a case report.

    PubMed

    Chin, Young-Jai; Yoon, Kyu-Ho; Park, Kwan-Soo; Park, Jae-An; Woo, Min-Ho

    2016-04-01

    Wernicke's encephalopathy is a fatal neurological disease caused by thiamine deficiency. Many reports indicate that Wernicke's encephalopathy is caused by malnutrition. We report the case of a 79-year-old female patient who had a left masticator space and parapharyngeal space abscess who was diagnosed with Wernicke's encephalopathy. She reported problems while eating due to the presence of the abscess, but the true quantities of food she was ingesting were never assessed. Clinicians have a responsibility to provide adequate nutritional support by ensuring that patients receive adequate nutrition. Clinicians should also keep in mind that Wernicke's encephalopathy may occur in patients who experienced prolonged periods of malnutrition. PMID:27162754

  13. Wernicke's encephalopathy in a patient with masticator and parapharyngeal space abscess: a case report

    PubMed Central

    2016-01-01

    Wernicke's encephalopathy is a fatal neurological disease caused by thiamine deficiency. Many reports indicate that Wernicke's encephalopathy is caused by malnutrition. We report the case of a 79-year-old female patient who had a left masticator space and parapharyngeal space abscess who was diagnosed with Wernicke's encephalopathy. She reported problems while eating due to the presence of the abscess, but the true quantities of food she was ingesting were never assessed. Clinicians have a responsibility to provide adequate nutritional support by ensuring that patients receive adequate nutrition. Clinicians should also keep in mind that Wernicke's encephalopathy may occur in patients who experienced prolonged periods of malnutrition. PMID:27162754

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

    PubMed

    Latt, N; Dore, G

    2014-09-01

    Wernicke encephalopathy is an acute, reversible neuropsychiatric emergency due to thiamine deficiency. Urgent and adequate thiamine replacement is necessary to avoid death or progression to Korsakoff syndrome with largely irreversible brain damage. Wernicke Korsakoff syndrome refers to a condition where features of Wernicke encephalopathy are mixed with those of Korsakoff syndrome. Although thiamine is the cornerstone of treatment of Wernicke encephalopathy, there are no universally accepted guidelines with regard to its optimal dose, mode of administration, frequency of administration or duration of treatment. Currently, different dose recommendations are being made. We present recommendations for the assessment and treatment of Wernicke encephalopathy based on literature review and our clinical experience. PMID:25201422

  15. Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy

    SciTech Connect

    Lockwood, A.H.; Yap, E.W.; Rhoades, H.M.; Wong, W.H. )

    1991-03-01

    We measured CBF and the CMRglc in normal controls and in patients with severe liver disease and evidence for minimal hepatic encephalopathy using positron emission tomography. Regions were defined in frontal, temporal, parietal, and visual cortex; the thalamus; the caudate; the cerebellum; and the white matter along with a whole-slice value obtained at the level of the thalamus. There was no difference in whole-slice CBF and CMRglc values. Individual regional values were normalized to the whole-slice value and subjected to a two-way repeated measures analysis of variance. When normalized CBF and CMRglc values for regions were compared between groups, significant differences were demonstrated (F = 5.650, p = 0.00014 and F = 4.58, p = 0.0073, respectively). These pattern differences were due to higher CBF and CMRglc in the cerebellum, thalamus, and caudate in patients and lower values in the cortex. Standardized coefficients extracted from a discriminant function analysis permitted correct group assignment for 95.5% of the CBF studies and for 92.9% of the CMRglc studies. The similarity of the altered pattern of cerebral metabolism and flow in our patients to that seen in rats subjected to portacaval shunts or ammonia infusions suggests that this toxin may alter flow and metabolism and that this, in turn, causes the clinical expression of encephalopathy.

  16. Treatment of epileptic encephalopathies.

    PubMed

    McTague, Amy; Cross, J Helen

    2013-03-01

    Epileptic encephalopathy is defined as a condition where the epileptic activity itself may contribute to the severe neurological and cognitive impairment seen, over and above that which would be expected from the underlying pathology alone. The epilepsy syndromes at high risk of this are a disparate group of conditions characterized by epileptic seizures that are difficult to treat and developmental delay. In this review, we discuss the ongoing debate regarding the significance of inter-ictal discharges and the impact of the seizures themselves on the cognitive delay or regression that is a common feature of these syndromes. The syndromes also differ in many ways and we provide a summary of the key features of the early-onset epileptic encephalopathies including Ohtahara and West syndromes in addition to later childhood-onset syndromes such as Lennox Gastaut and Doose syndromes. An understanding of the various severe epilepsy syndromes is vital to understanding the rationale for treatment. For example, the resolution of hypsarrhythmia in West syndrome is associated with an improvement in cognitive outcome and drives treatment choice, but the same cannot be applied to frequent inter-ictal discharges in Lennox Gastaut syndrome. We discuss the evidence base for treatment where it is available and describe current practice where it is not. For example, in West syndrome there is some evidence for preference of hormonal treatments over vigabatrin, although the choice and duration of hormonal treatment remains unclear. We describe the use of conventional and newer anti-epileptic medications in the various syndromes and discuss which medications should be avoided. Older possibly forgotten treatments such as sulthiame and potassium bromide also have a role in the severe epilepsies of childhood. We discuss hormonal treatment with particular focus on the treatment of West syndrome, continuous spike wave in slow wave sleep (CSWS)/electrical status epilepticus in slow wave

  17. [Effect of alcohol on organ microcirculation: its relation to hepatic, pancreatic and gastrointestinal diseases due to alcohol].

    PubMed

    Horie, Y; Ishii, H

    2001-10-01

    Although alcohol is well recognized as a systemic toxin, the enteric manifestations of alcohol abuse have only recently begun to be elucidated at the cellular and microvascular levels. Since the microvascular mechanism of the toxicity of alcohol has progressively been revealed, clinical applications of this research field should increase the availability of therapeutic options for alcohol-induced injuries of liver, pancreas and gastrointestinal (GI) tract. A high concentration of ethanol reduces GI and pancreas blood flow. Ethanol-induced GI hemorrhage, GI ulcer, and pancreatitis are initiated by the microcirculatory disturbance of GI mucosa and pancreas. Ethanol administration induces an increase in vasoactive agents such as endothelin and nitric oxide and oxidative stress. They appear to be involved in ethanol-induced GI and pancreatic injury. Regarding the effects of ethanol on the liver, small amount of ethanol increases hepatic blood flow, and prevents gut ischemia/reperfusion (I/R)-induced hepatic microvascular dysfunction and subsequent liver injury. While large amount of ethanol itself causes hepatic microvascular dysfunction, and aggravates the gut I/R-induced hepatic microvascular dysfunction and subsequent liver injury. Vasoactive agents and oxidative stress also appear to be involved in the liver injury. In endotoxemic animals, even small amount of ethanol causes hepatic microvascular dysfunction. Chronic ethanol consumption aggravates endotoxin-induced hepatic microvascular dysfunction. Chronic ethanol consumption aggravates gut I/R-induced leukostasis in the liver and hepatocellular injury associated with an enhanced expression of adhesion molecules, while it prevents the gut I/R-induced sinusoidal perfusion injury. Thus, effects of chronic ethanol consumption on the I/R injury are still controversial. PMID:11725532

  18. c-Myc and Transforming Growth Factor α Enhance the Development of Hepatic Lesions Due to Mutant β-Catenin in Transgenic Mice

    PubMed Central

    Jochem, Adam S; Holmes, Katie E; Stein, Timothy J

    2014-01-01

    Alterations in the Wnt signaling pathway are associated with diverse cancers, including hepatocellular carcinoma (HCC). The development of HCC is thought to be a multistage process in which multiple genetic alterations are necessary. Few studies have assessed the effect of aberrant Wnt signaling activity in association with other molecular alterations in HCC. Here we sought to determine whether co-overexpression of c-Myc or TGFα, 2 signaling molecules known to contribute to HCC development, enhanced the development of hepatic lesions associated with a stabilized β-catenin. The coexpression of mutant β-catenin with either c-Myc or TGFα within hepatocytes increased the severity of hepatic lesions compared with that associated with any of the transgenes expressed individually. The coexpression of mutant β-catenin with c-Myc or TGFα resulted in severe hepatomegaly necessitating the euthanasia of mice by an average of 156 and 128 d, respectively, after the cessation of doxycycline. The expression of mutant β-catenin alone resulted in mild to moderate hepatomegaly that prompted the euthanasia of mice by an average of 75 d after the cessation of doxycycline. Collectively, these findings indicate that coexpression of c-Myc or TGFα delays the onset of endstage hepatic disease yet enhances the severity of hepatic lesions due to mutant β-catenin. PMID:25402175

  19. Acute liver graft failure due to emergence of lamivudine resistant hepatitis B virus: rapid resolution during treatment with adefovir

    PubMed Central

    Mutimer, D; Feraz-Neto, B; Harrison, R; O'Donnell, K; Shaw, J; Cane, P; Pillay, D

    2001-01-01

    BACKGROUND—Strategies for prevention of liver graft reinfection by hepatitis B virus (HBV) have been developed during recent years. Initially, passive immunoprophylaxis with high titre HBV immunoglobulin (HBIg), followed by lamivudine prophylaxis, and then the combination of lamivudine and HBIg have been employed. However, suboptimal use of the combination may be associated with failure of prophylaxis reflected by the emergence of HBV species with genetic changes that confer resistance to lamivudine and HBIg. Reinfection of the graft by HBV can be associated with rapid development of liver failure.
CASE REPORT—A 43 year old HBV infected man received lamivudine before transplantation, and lamivudine and HBIg after transplantation. Despite prophylaxis, graft reinfection and severe hepatitis were observed. The observed serological evolution and genetic sequencing of the emergent HBV species suggested selection of lamivudine resistant and surface antigen escape mutants consecutively. Adefovir treatment began after the devlopment of graft failure.
OUTCOME—A rapid exponential decline in serum HBV titre was observed. Liver function tests normalised and signs of liver failure resolved.
CONCLUSION—The use of HBIg and lamivudine permits prevention of graft reinfection by HBV for the majority of patients. Adefovir, a potent inhibitor of lamivudine resistant HBV, should be used when failure of prophylaxis is associated with graft hepatitis.


Keywords: hepatitis B virus; adefovir; liver graft; lamivudine PMID:11709523

  20. Antibody-mediated pure red cell aplasia due to epoetin alfa during antiviral therapy of chronic hepatitis C.

    PubMed

    Stravitz, R Todd; Chung, Harold; Sterling, Richard K; Luketic, Velimir A; Sanyal, Arun J; Price, Angie S; Purrington, Amy; Shiffman, Mitchell L

    2005-06-01

    Anemia frequently complicates the treatment of chronic hepatitis C with interferon and ribavirin (RVN), requiring dose reduction and jeopardizing sustained virologic response. Increasingly, epoetin alfa is used to prevent anemia in this setting. Below, we report the first case of pure red cell aplasia (PRCA) in a patient with chronic hepatitis C who received epoetin alfa (Procrit) to manage anti-viral treatment-induced anemia. Red blood cell transfusion-dependence developed 16 wk after the patient was started on peginterferon alfa-2b and RVN for chronic hepatitis C despite the simultaneous administration of epoetin alfa and subsequent discontinuation of the antiviral medications. Bone marrow biopsy was consistent with PRCA. High-titer erythropoietin antibodies, assayed by two methods, appeared shortly after epoetin alfa was administered, and were associated with a decline in serum erythropoietin to undetectable levels. Erythropoietin antibodies directed toward epoetin alfa were shown to cross react with darbepoetin alfa (Aranesp), and a neutralization assay confirmed that they inhibited cell growth in the presence of erythropoietin. Transfusion-dependence resolved approximately 16 wk after discontinuing epoetin alfa, and 6 wk after starting danazol. PRCA caused by the development of erythropoietin antibodies is a potentially life-threatening complication of administering epoetin alfa to prevent the anemia associated with antiviral therapy in patients with chronic hepatitis C. PMID:15929778

  1. [RENDU-OSLER DISEASE: A RARE CAUSE OF AMMONIA ENCEPHALOPATHY].

    PubMed

    Dumont, R; Loly, J-P; Delwaide, J; Louis, E

    2016-02-01

    Hereditary Hemorrhagic Telangiectasia (HHT) also known as Rendu-Osler disease is a group of related disorders inherited in an autosomal dominant fashion and characterized by the development of arteriovenous malformations (AVM) in the skin, mucous membranes, and/or internal organs such as the brain, lungs, and liver. The prevalence of liver involvement is clinically estimated between 8 and 31 percent. It can be revealed by the following clinical signs : ascites, edema of the lower extremities, abdominal pain, dyspnea, and, rarely, hepatic encephalopathy and gastrointestinal bleeding associated with portal hypertension. This case illustrates the highlight of liver damage revealed by an ammonia encephalopathy associated with iconographic anomalies on ultrasonography and magnetic resonance liver as part of Rendu-Osler disease. PMID:27141651

  2. Chronic Traumatic Encephalopathy: A Review

    PubMed Central

    Saulle, Michael; Greenwald, Brian D.

    2012-01-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that is a long-term consequence of single or repetitive closed head injuries for which there is no treatment and no definitive pre-mortem diagnosis. It has been closely tied to athletes who participate in contact sports like boxing, American football, soccer, professional wrestling and hockey. Risk factors include head trauma, presence of ApoE3 or ApoE4 allele, military service, and old age. It is histologically identified by the presence of tau-immunoreactive NFTs and NTs with some cases having a TDP-43 proteinopathy or beta-amyloid plaques. It has an insidious clinical presentation that begins with cognitive and emotional disturbances and can progress to Parkinsonian symptoms. The exact mechanism for CTE has not been precisely defined however, research suggest it is due to an ongoing metabolic and immunologic cascade called immunoexcitiotoxicity. Prevention and education are currently the most compelling way to combat CTE and will be an emphasis of both physicians and athletes. Further research is needed to aid in pre-mortem diagnosis, therapies, and support for individuals and their families living with CTE. PMID:22567320

  3. Anaphylactic shock in a female patient due to a spontaneous rupture of a hepatic hydatid cyst: a case report.

    PubMed

    Horzic, M; Bunoza, D; Maric, K

    1996-01-01

    A 27-year-old female patient, a refugee from Bosnia and Herzegovina, was admitted to our hospital in a state of shock. She developed an anaphylactic reaction. The US and CT of abdomen revealed a spontaneous rupture of a hepatic hydatid cyst. An emergency operative procedure was performed and in the postoperative period she was treated conservatively with albendazol during the next two months. There was no recurrence of the disease. PMID:8975972

  4. Hepatitis Vaccines

    PubMed Central

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  5. Hepatitis Vaccines.

    PubMed

    Ogholikhan, Sina; Schwarz, Kathleen B

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  6. Cefepime-induced encephalopathy with normal renal function

    PubMed Central

    Meillier, Andrew; Rahimian, David

    2016-01-01

    Cefepime is a fourth-generation cephalosporin that is frequently used in a wide array of infections. Since approval for use, concerns have been raised due to adverse effects including seizures, encephalopathy and myoclonus especially if renal dysfunction is present. Despite having appropriate renal dose adjustments, cases have been found with adverse neurological effects. On this occasion, we present a case of a patient with normal renal function that had demonstrated cefepime-induced encephalopathy with full resolution of symptoms following discontinuation of the medication. PMID:27274853

  7. Posterior reversible encephalopathy syndrome with neurological sequelae - a case report.

    PubMed

    Nesteruk, Marta; Kurdyła, Anna; Nesteruk, Tomasz; Dorobek, Małgorzata

    2016-04-01

    Posterior reversible encephalopathy syndrome (PRES) is a set of neurological symptoms including impaired consciousness, cognitive disorders, seizures, blurred vision, dizziness and headache. The symptoms are closely related to the location of pathological changes in the brain; bilateral occipitto-parietal region is most often affected. Both focal neurological symptoms and encephalopathy are usually transient. We present the case of 64-year-old woman with PRES. She suffered from many internal diseases and was admitted to the hospital due to impaired consciousness, speech disorders, balance disorders. Significant neurological deterioration was observed within several days from the onset. Differential diagnosis included stroke and viral neuroinfection (cytosis 23 cells /ul, protein level of 93 mg/dl); magnetic resonance examination revealed lesions typical for posterior reversible encephalopathy.After 6 weeks of hospitalization patient condition improved, but did not restore to the premorbid state. The patient was discharged with generalized cognitive impairment. PMID:27137827

  8. The transmissible spongiform encephalopathies of livestock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal protein misfolding neurodegenerative diseases. TSEs have been described in several species including bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, tr...

  9. Sepsis Associated Encephalopathy

    PubMed Central

    Chaudhry, Neera; Duggal, Ashish Kumar

    2014-01-01

    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. PMID:26556425

  10. Sepsis-Associated Encephalopathy

    PubMed Central

    Cotena, Simona; Piazza, Ornella

    2012-01-01

    Summary Sepsis-associated encephalopathy (SAE) is defined as a diffuse or multifocal cerebral dysfunction induced by the systemic response to the infection without clinical or laboratory evidence of direct brain infection. Its pathogenesis is multifactorial. SAE generally occurs early during severe sepsis and precedes multiple-organ failure. The most common clinical feature of SAE is the consciousness alteration which ranges from mildly reduced awareness to unresponsiveness and coma. Diagnosis of SAE is primarily clinical and depends on the exclusion of other possible causes of brain deterioration. Electroencephalography (EEG) is almost sensitive, but it is not specific for SAE. Computed Tomography (CT) head scan generally is negative in case of SAE, while Magnetic Resonance Imaging (MRI) can show brain abnormalities in case of SAE, but they are not specific for this condition. Somatosensitive Evoked Potentials (SEPs) are sensitive markers of developing cerebral dysfunction in sepsis. Cerebrospinal fluid (CBF) analysis is generally normal, a part an inconstant elevation of proteins concentration. S100B and NSE have been proposed like biomarkers for diagnosis of SAE, but the existing data are controversial. SAE is reversible even if survivors of severe sepsis have often long lasting or irreversible cognitive and behavioral sequel; however the presence of SAE can have a negative influence on survival. A specific therapy of SAE does not exist and the outcome depends on a prompt and appropriate treatment of sepsis as whole. PMID:23905041

  11. [Mitochondrial neurogastrointestinal encephalopathy disease].

    PubMed

    Benureau, A; Meyer, P; Maillet, O; Leboucq, N; Legras, S; Jeziorski, E; Fournier-Favre, S; Jeandel, C; Gaignard, P; Slama, A; Rivier, F; Roubertie, A; Carneiro, M

    2014-12-01

    Mitochondrial neurogastrointestinal encephalopathy disease (MNGIE) is a rare autosomal-recessive syndrome, resulting from mutations in the TYMP gene, located at 22q13. The mutation induces a thymidine phosphorylase (TP) deficit, which leads to a nucleotide pool imbalance and to instability of the mitochondrial DNA. The clinical picture regroups gastrointestinal dysmotility, cachexia, ptosis, ophthalmoplegia, peripheral neuropathy, and asymptomatic leukoencephalopathy. The prognosis is unfavorable. We present the case of a 14-year-old Caucasian female whose symptoms started in early childhood. The diagnosis was suspected after magnetic resonance imaging (MRI), performed given the atypical features of mental anorexia, which revealed white matter abnormalities. She presented chronic vomiting, postprandial abdominal pain, and problems gaining weight accompanied by cachexia. This diagnosis led to establishing proper care, in particular an enteral and parenteral nutrition program. There is no known specific effective treatment, but numerous studies are in progress. In this article, after reviewing the existing studies, we discuss the main diagnostic and therapeutic aspects of the disease. We argue for the necessity of performing a cerebral MRI given the atypical features of a patient with suspected mental anorexia (or when the clinical pattern of a patient with mental anorexia seems atypical), so that MNGIE can be ruled out. PMID:25282463

  12. Non-Hyperammonemic valproate encephalopathy.

    PubMed

    Farooq, Omar; Zunga, Pervaiz M; Dar, Mohd I; Rather, Abdul Q; Rashid, Samia; Basu, Javid; Dar, Ishrat H; Ashraf, Mohd

    2014-04-01

    A 21-year-old male known case of primary hypothyroidism, Seizure disorder sequelae of an old trauma receiving sodium valproate, clobazam and phenobarbitone for control of Generalized tonic clonic seizures reported to neurology OPD with history of altered sensorium and gait unsteadiness for 1 week with history of hike in valproate dose 2 weeks before. On examination he was drowsy. Neurological examination was unremarkable except for gait unsteadiness and ataxia. Patient was admitted and evaluated for acute worsening. All (the) biochemical parameters including complete blood count, liver function tests, kidney function tests, routine urine examination, arterial blood gas analysis, blood and urine culture tests were normal. CSF analysis was also normal. Repeat MRI brain was also done which depicted all old changes with no fresh changes which will account for worsening of his sensorium. EEG was suggestive of diffuse encephalopathy. Thyroid function tests were also normal. Valproate encephalopathy was suspected and Valproate was empirically stopped and he was put on levetiracetam and phenytoin. His sensorium improved rapidly after stoppage of valproate with normalization of EEG. Serum valproate Levels were high with serum ammonia levels were in the normal range. We made the inference of nonhyperammoneamic valproate encephalopathy. This case highlights the existence of non-hyperammonemic valproate induced encephalopathy, suggesting mechanisms other than hyperammonemia responsible for this encephalopathy. PMID:25206067

  13. A rare case of glycine encephalopathy unveiled by valproate therapy.

    PubMed

    Subramanian, Velusamy; Kadiyala, Pramila; Hariharan, Praveen; Neeraj, E

    2015-01-01

    Glycine encephalopathy (GE) or nonketotic hyperglycinemia is an autosomal recessive disorder due to a primary defect in glycine cleavage enzyme system. It is characterized by elevated levels of glycine in plasma and cerebrospinal fluid usually presenting with seizures, hypotonia, and developmental delay. In our case, paradoxical increase in seizure frequency on starting sodium valproate led us to diagnose GE. PMID:26167219

  14. Molecular principles behind Boceprevir resistance due to mutations in hepatitis C NS3/4A protease.

    PubMed

    Nagpal, Neha; Goyal, Sukriti; Wahi, Divya; Jain, Ritu; Jamal, Salma; Singh, Aditi; Rana, Preeti; Grover, Abhinav

    2015-10-01

    The hepatitis C virus (HCV) infection is a primary cause of chronic hepatitis which eventually progresses to cirrhosis and in some instances might advance to hepatocellular carcinoma. According to the WHO report, HCV infects 130-150 million people globally and every year 350,000 to 500,000 people die from hepatitis C virus infection. Great achievement has been made in viral treatment evolution, after the development of HCV NS3/4A protease inhibitor (Boceprevir). However, efficacy of Boceprevir is compromised by the emergence of drug resistant variants. The molecular principle behind drug resistance of the protease mutants such as (V36M, T54S and R155K) is still poorly understood. Therefore in this study, we employed a series of computational strategies to analyze the binding of antiviral drug, Boceprevir to HCV NS3/4A protease mutants. Our results clearly demonstrate that the point mutations (V36M, T54S and R155K) in protease are associated with lowering of its binding affinity with Boceprevir. Exhaustive analysis of the simulated Boceprevir-bound wild and mutant complexes revealed variations in hydrophobic interactions, hydrogen bond occupancy and salt bridge interactions. Also, substrate envelope analysis scrutinized that the studied mutations reside outside the substrate envelope which may affect the Boceprevir affinity towards HCV protease but not the protease enzymatic activity. Furthermore, structural analyses of the binding site volume and flexibility show impairment in flexibility and stability of the binding site residues in mutant structures. In order to combat Boceprevir resistance, renovation of binding interactions between the drug and protease may be valuable. The structural insight from this study reveals the mechanism of the Boceprevir resistance and the results can be valuable for the design of new PIs with improved efficiency. PMID:26055089

  15. Hashimoto's Encephalopathy Presenting with Chorea.

    PubMed

    Sharan, Abhijeet; Sengupta, Sarbani; Mukhopadhyay, Sarmishtha; Ghosh, Bhaskar

    2015-09-01

    Hashimoto's encephalopathy (HE) is a steroid-responsive relapsing neuropsychiatric disorder associated with high titers of antithyroid antibody with or without thyroid dysfunction. We report a case of HE in a 78 year old female who developed sudden onset behavioral abnormalities associated with choreiform movement of extremities. All causes of vascular, infective, metabolic, autoimmune, paraneoplastic and toxic encephalopathy were excluded. Anti-thyroid peroxidase (anti-TPO) antibody was found to be raised with very high titre. A diagnosis of HE was made. Prompt treatment with high dose steroid led to dramatic improvement of symptoms including choreiform movement. PMID:27608878

  16. Long-term, low-dose tigecycline to treat relapsing bloodstream infection due to KPC-producing Klebsiella pneumoniae after major hepatic surgery.

    PubMed

    Morelli, Luca; Tartaglia, Dario; Furbetta, Niccolò; Palmeri, Matteo; Ferranti, Simone; Tagliaferri, Enrico; Di Candio, Giulio; Mosca, Franco

    2015-07-01

    A 68-year-old male underwent a right hepatectomy, resection of the biliary convergence, and a left hepatic jejunostomy for a Klatskin tumour. The postoperative course was complicated by biliary abscesses with relapsing bloodstream infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp). A 2-week course of combination antibiotic therapy failed to provide source control and the bacteraemia relapsed. Success was obtained with a regimen of tigecycline 100mg daily for 2 months, followed by tigecycline 50mg daily for 6 months, then 50mg every 48h for 3 months. No side effects were reported. PMID:25975648

  17. Uncommon cause of acute encephalopathy in liver cirrhosis.

    PubMed

    Dieuvil, Monique; Malaty, John

    2016-01-01

    A 49-year-old woman with a medical history of alcoholic cirrhosis status post-transjugular intrahepatic portosystemic shunt (post-TIPS) in 2012, and ongoing alcohol abuse, presented to the hospital, with haematuria. CT intravenous pyelogram (IVP) was normal except for 'a large intrahepatic cystic mass adjacent to the TIPS, causing intrahepatic biliary duct dilation'. The patient also presented with acute encephalopathy, jaundice, right upper quadrant abdominal pain and hyperbilirubinaemia (total bilirubin of 8.1 mg/dL with direct bilirubin of 3.0 mg/dL). She remained encephalopathic despite adequate treatment for alcohol withdrawal, hepatic encephalopathy and enterococcus urinary tract infection. MRI of the abdomen later confirmed presence of an obstructing biloma. The biloma, drained by CT-guided percutaneous drains, demonstrated an Escherichia coli and ESBL Klebsiella infection. The patient's encephalopathy completely resolved after treatment of the infected biloma. With adequate drainage, her hyperbilirubinaemia resolved to her post-TIPS baseline (total bilirubin of 3.7 mg/dL with direct bilirubin of 3.3 mg/dL). PMID:27194673

  18. A Case of Fulminant Hepatitis due to Echovirus 9 in a Patient on Maintenance Rituximab Therapy for Follicular Lymphoma

    PubMed Central

    Thomson, S. J.; Legg, Joanne; Narat, Santosh

    2015-01-01

    Rituximab is a CD20 monoclonal antibody commonly used in the treatment of haematological malignancies. It causes lymphopenia with subsequent compromised humoral immunity resulting in an increased risk of infection. A number of infections and viral reactivations have been described as complicating Rituximab therapy. We report an apparently unique case of echovirus 9 (an enterovirus) infection causing an acute hepatitis and significant morbidity in an adult patient on maintenance treatment of Rituximab for follicular lymphoma. We also describe potential missed opportunities to employ more robust screening for viral infections which may have prevented delays in the appropriate treatment and thus may have altered the patient's clinical course. We also make suggestions for lowering the threshold of viral testing in similar patients in the future. PMID:26106492

  19. Hyperammonemic encephalopathy induced by a combination of valproate and pivmecillinam.

    PubMed

    Lokrantz, C-M; Eriksson, B; Rosén, I; Asztely, F

    2004-04-01

    We describe the clinical and neurophysiological findings in a case of hyperammonemic encephalopathy. A 72-year-old woman taking valproate (VPA), as monotherapy for her partial epilepsy developed urinary tract infection. She was treated with pivmecillinam 600 mg daily. The following days she deteriorated and became stuporous. At admission her serum ammonia level was increased (113 mmol/l) but the liver function appeared normal. EEG showed bilateral triphasic waves and continuous high-amplitude delta-theta wave. The patient recovered rapidly after discontinuation of VPA and i.v. treatment with cefuroxime for her urinary tract infection. VPA-induced hyperammonemic encephalopathy in adults is a rare phenomenon, especially when VPA is used as monotherapy. It has been suggested that the VPA-induced hyperammonemic encephalopathy is due to reduced serum carnitine concentration. Pivmecillinam, a widely used antibiotic for treatment of urinary tract infections, is also known to decrease the serum carnitine concentration. Our case shows that caution is required when treatment with VPA is combined with pivmecillinam due to the risk of developing hyperammonemic encephalopathy. PMID:15016014

  20. Treatment of Chronic Hepatitis due to Hepatitis C Virus (CH-C) in India: A Randomized Controlled Trial Comparing Daily Interferon-alfa-2b and Ribavirin with Daily Interferon-alfa-2b and Glycyrrhizin—A Multicenter Study

    PubMed Central

    Acharya, Subrat K; Sreenivas, V; Gupta, Siddharth Datta; Kumar, Shakti; Chawla, Yogesh K; Tandon, Anurag; Habeeb, Aejaz; Kar, Premashish; Chowdhury, Abhijit; Choudhuri, Gourdas; Sarin, Shiv K; Amarapurkar, DN; Arankalle, Vidya; Gupte, Mohan D; Gupta, Sushma; Mukherjee, Deepali; Seth, Divya; Goyal, Rohit; Tandon, Badri N

    2012-01-01

    Background and Aim Pegylated-interferon-alfa (PEG-IFN-α) with ribavirin is an established treatment in chronic hepatitis due to hepatitis C virus (HCV) (CH-C). Such treatment is expensive and in resource-poor countries such as India, alternative less expensive therapy is needed. Methods Multicenter randomized controlled trial comparing two treatment regimens (interferon-alfa-2b [IFN-α-2b] 3 million unit/day [MU/day] and ribavirin 1000 mg/day [I+R] vs IFN-α-2b 3 MU/day and glycyrrhizin 250 mg [I+G]) in CH-C. Viral, host characteristics and therapeutic responses were assessed (ICMR—6 months trial for chronic hepatitis—CTRI/2008/091/000105). Results One hundred and thirty-one patients meeting the inclusion criteria were randomized to I + G (n=64) or I+R (n=67) during the period February 2002 to May 2005. About 85% (I+G=53, I+R=58) completed 6 months of treatment and 89% of them (I+G=46, I+R=53) completed 6 months of follow-up after completion of treatment. Hepatitis C virus genotype 3 was the major type detected (71% patients). The mean log10 viral load (copies/mL), histological activity index, and fibrosis stage for all patients were 5.1 ± 0.98, 5 ± 2, and 2± 1.5, respectively. Sustained viral response (SVR) was significantly higher in I + R group than in I + G group (65.7% vs 46.9%, OR=2.2, P = 0.03). Treatment with I + G was associated with significantly lower frequencies of leukopenia (2% vs 17%, P <0.01) and anemia (8% vs 40%, P <0.001) as compared to treatment with I + R. Conclusion Genotype 3 HCV infection with low viral load is prevalent in India. Daily IFN with ribavirin showed significantly better responses. Leukopenia and anemia were significantly more in ribavirin group. Responses observed with IFN + ribavirin were similar to the reported response rates with PEG-IFN suggesting that this modality may be considered as a cheaper alternative of treatment for chronic hepatitis C. PMID:25755401

  1. Delayed hypersensitivity reaction resulting in maculopapular-type eruption due to entecavir in the treatment of chronic hepatitis B.

    PubMed

    Kim, Jeong Tae; Jeong, Hye Won; Choi, Ki Hwa; Yoon, Tae Young; Sung, Nohyun; Choi, Young Ki; Kim, Eun Ha; Chae, Hee Bok

    2014-11-14

    Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare

  2. Is montelukast as effective as N-acetylcysteine in hepatic injury due to acetaminophen intoxication in rats?

    PubMed

    İçer, Mustafa; Zengin, Yilmaz; Gunduz, Ercan; Dursun, Recep; Durgun, Hasan Mansur; Turkcu, Gul; Yuksel, Hatice; Üstündağ, Mehmet; Guloglu, Cahfer

    2016-01-01

    This study aims to investigate the acute protective effect of montelukast sodium in hepatic injury secondary to acetaminophen (APAP) intoxication. This study used 60 rats. The rats were grouped into 6 groups. The control group was administered oral distilled water 10 ml/kg, the APAP group oral APAP 1 g/kg, the montelukast sodium (MK) group oral MK 30 mg/kg, the acetaminophen+N-acetylcysteine (APAP+NAC) group oral APAP 1 g/kg, followed by a single dose of intraperitoneal NAC 1.5 g/kg three hours later, the acetaminophen+montelukast sodium (APAP+MK) group oral APAP 1 g/kg, followed by oral MK 30 mg/kg 3 h later, the acetaminophen+N-acetylcysteine+montelukast sodium (APAP+NAC+MK) group oral APAP 1 g/kg, followed by a single intraperitoneal NAC 1.5 g/kg plus oral MK 30 mg/kg 3 h later. Blood and liver tissue samples were taken 24h after drug administration. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin were studied from the blood samples. Liver tissue samples were used for histopathological examination. Compared with the control group, serum AST and ALT activities were higher in the APAP and APAP+NAC groups. APAP+NAC, APAP+MK, and APAP+NAC+MK groups had reduced serum ALT and AST activities than the group administered APAP alone. APAP+MK and APAP+NAC+MK groups had a lower serum ALP activity than the control group. Histopathologically, there was a difference between the group administered APAP alone and the APAP+MK and APAP+NAC+MK groups. MK is as protective as NAC in liver tissue in APAP intoxication in rats. PMID:26462568

  3. Clinical and Neuroradiological Spectrum of Metronidazole Induced Encephalopathy: Our Experience and the Review of Literature.

    PubMed

    Roy, Ujjawal; Panwar, Ajay; Pandit, Alak; Das, Susanta Kumar; Joshi, Bhushan

    2016-06-01

    Metronidazole is an antimicrobial agent mainly used in the treatment of several protozoal and anaerobic infections, additionally, is often used in hepatic encephalopathy and Crohn disease. Apart from peripheral neuropathy, metronidazole can also cause symptoms of central nervous system dysfunction like ataxic gait, dysarthria, seizures, and encephalopathy which may result from both short term and chronic use of this drug and is collectively termed as "metronidazole induced encephalopathy"(MIE). Neuroimaging forms the backbone in clinching the diagnosis of this uncommon entity, especially in cases where there is high index of suspicion of intoxication. Although typical sites of involvement include cerebellum, brain stem and corpus callosum, however, lesions of other sites have also been reported. Once diagnosed, resolution of findings on Magnetic Resonance Imaging (MRI) of the Brain along with clinical improvement remains the mainstay of monitoring. Here we review the key clinical features and MRI findings of MIE as reported in medical literature. We also analyze implication of use of this drug in special situations like hepatic encephalopathy and brain abscess and discuss our experience regarding this entity. PMID:27504340

  4. Wernicke’s Encephalopathy: Increasing Clinician Awareness of This Serious, Enigmatic, Yet Treatable Disease

    PubMed Central

    Flynn, Alexandra; D’Empaire, Inna; Troutman, Megan M.

    2015-01-01

    Objective: Undiagnosed and/or undertreated Wernicke’s encephalopathy can result in permanent brain damage, long-term institutionalization, and death. The purpose of this article is to heighten clinical awareness of Wernicke’s encephalopathy and shed light on its diagnosis and treatment, which are often inconsistent due to unclear diagnostic criteria and limited practice guidelines. An update on the management of Wernicke’s encephalopathy is presented and several case reports and a quality improvement project from our hospital are described. Data Sources: PubMed, the Cochrane Database of Systematic Reviews, and PsycINFO were searched for English-language articles published between January 1991 and January 2014 using combinations of the following keywords: Wernicke’s encephalopathy, diagnosis, treatment/guideline(s), and thiamine. Study Selection: The automated search identified over 500 articles. A manual review of the related citations and reference lists from articles of interest was also conducted. The articles reviewed were chosen on the basis of author consensus and because they represented expert opinion or the highest quality of evidence available. Results: Diagnostic criteria are reviewed in this article and should be used to diagnose Wernicke’s encephalopathy with high sensitivity and specificity. The European Federation of Neurologic Societies and the Royal College of Physicians issued national guidelines for the diagnosis, prevention, and treatment of Wernicke’s encephalopathy. No benchmark national guidelines for treating Wernicke’s encephalopathy exist in the United States. Conclusions: Whenever Wernicke’s encephalopathy is suspected, treatment should be initiated immediately with intravenous thiamine because oral thiamine is inadequate for preventing permanent brain damage. An adequate dose of intravenous thiamine administrated in a timely manner is a safe and life-saving treatment for Wernicke’s encephalopathy that could preserve

  5. Portal hypertension induced by congenital hepatic arterioportal fistula: Report of four clinical cases and review of the literature

    PubMed Central

    Zhang, Dan-Ying; Weng, Shu-Qiang; Dong, Ling; Shen, Xi-Zhong; Qu, Xu-Dong

    2015-01-01

    Intrahepatic arterioportal fistula (IAPF) can be caused by many secondary factors. We report four cases of portal hypertension that were eventually determined to be caused by congenital hepatic arterioportal fistula. The clinical manifestations included ascites, variceal hemorrhage and hepatic encephalopathy. Computed tomography scans from all of the patients revealed the early enhancement of the portal branches in the hepatic arterial phase. All patients were diagnosed using digital subtraction angiography (DSA). DSA before embolization revealed an arteriovenous fistula with immediate filling of the portal venous radicles. All four patients were treated with interventional embolization. The four patients remained in good condition throughout follow-up and at the time of publication. IAPF is frequently misdiagnosed due to its rarity; therefore, clinicians should consider IAPF as a potential cause of non-cirrhotic portal hypertension. PMID:25717263

  6. Monitoring and managing hepatic disease in anaesthesia.

    PubMed

    Kiamanesh, D; Rumley, J; Moitra, V K

    2013-12-01

    Patients with liver disease have multisystem organ dysfunction that leads to physiological perturbations ranging from hyperbilirubinaemia of no clinical consequence to severe coagulopathy and metabolic disarray. Patient-specific risk factors, clinical scoring systems, and surgical procedures stratify perioperative risk for these patients. The anaesthetic management of patients with hepatic dysfunction involves consideration of impaired drug metabolism, hyperdynamic circulation, perioperative hypoxaemia, bleeding, thrombosis, and hepatic encephalopathy. PMID:24335399

  7. [Wernicke encephalopathy accompanying linitis plastica].

    PubMed

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

    2014-01-01

    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. PMID:24379094

  8. [CLINICAL ASPECTS OF SEPTIC ENCEPHALOPATHY].

    PubMed

    Fesenko, O V; Sinopal'nikov, A I; Filatov, V V; Danishevsky, S V; Styrt, E A

    2016-01-01

    Septic encephalopathy is a form of general cerebral dysfunction caused by a systemic inflammatory reaction. Its investigation encounters enormous difficulties for the lack of reliable biological markers of neuronal lesions and methods for the evaluation of consciousness in severely ill patients. Hence, the importance of correct clinical interpretation of the character and magnitude of CNS activity. Examples are presented demonstrating the difficulty of interpreting disorders in CNS activity associated with evere community-acquired pneumonia. PMID:27172727

  9. [Imaging in acute toxic encephalopathy].

    PubMed

    Dietemann, J-L; Botelho, C; Nogueira, T; Vargas, M I; Audibert, C; Abu Eid, M; Bogorin, A; Bernardo, R; Jacques, C; Kremer, S; Zöllner, G

    2004-09-01

    Neuroimaging, particularly MR imaging, plays a major role for the diagnosis of many acute toxic encephalopathies. Toxic disorders are related to drugs (immunosuppressive agents, chemotherapeutic agents, anti-epileptic drugs, heroin...), to metals (lead, manganese, mercury...), and to industrial and environmental chemicals (solvent, carbon monoxide...). MR imaging with diffusion and perfusion imaging provides information regarding brain lesions induced by the toxic agents (vasogenic edema, cytotoxic edema, infarction, hemorrhage, demyelination...). PMID:15545943

  10. IMPACT OF THE PEGYLATED-INTERFERON AND RIBAVIRIN THERAPY ON THE TREATMENT-RELATED MORTALITY OF PATIENTS WITH CIRRHOSIS DUE TO HEPATITIS C VIRUS

    PubMed Central

    DRESCH, Kelly Fernanda Nomura; de MATTOS, Angelo Alves; TOVO, Cristiane Valle; de ONOFRIO, Fernanda Quadros; CASAGRANDE, Leandro; FELTRIN, Alberi Adolfo; de BARROS, Iago Christofoli; de ALMEIDA, Paulo Roberto Lerias

    2016-01-01

    Although the protease inhibitors have revolutionized the therapy of chronic hepatitis C (CHC), the concomitant use of pegylated-interferon (PEG-IFN) and ribavirin (RBV) is associated to a high rate of adverse effects. In this study, we evaluated the consequences of PEG-IFN and RBV and their relationship with mortality in patients with cirrhosis. METHODS: Medical records of CHC who underwent treatment with PEG-IFN and RBV in a public hospital in Brazil were evaluated. All the patients with cirrhosis were selected, and their clinical and laboratory characteristics, response to treatment, side effects and mortality were evaluated. RESULTS: From the 1,059 patients with CHC, 257 cirrhotic patients were evaluated. Of these, 45 (17.5%) achieved sustained viral response (SVR). Early discontinuation of therapy occurred in 105 (40.8%) patients, of which 39 (15.2%) were due to serious adverse effects. The mortality rate among the 257 cirrhotic patients was 4.3%, occurring in 06/242 (2.4%) of the Child-A, and in 05/15 (33.3%) of the Child-B patients. In conclusion, the treatment of patients with cirrhosis due to HCV with PEG-IFN and RBV shows a low SVR rate and a high mortality, especially in patients with liver dysfunction. PMID:27253739

  11. In silico prioritization based on coexpression can aid epileptic encephalopathy gene discovery

    PubMed Central

    Oliver, Karen L.; Lukic, Vesna; Freytag, Saskia; Scheffer, Ingrid E.; Berkovic, Samuel F.

    2016-01-01

    Objective: To evaluate the performance of an in silico prioritization approach that was applied to 179 epileptic encephalopathy candidate genes in 2013 and to expand the application of this approach to the whole genome based on expression data from the Allen Human Brain Atlas. Methods: PubMed searches determined which of the 179 epileptic encephalopathy candidate genes had been validated. For validated genes, it was noted whether they were 1 of the 19 of 179 candidates prioritized in 2013. The in silico prioritization approach was applied genome-wide; all genes were ranked according to their coexpression strength with a reference set (i.e., 51 established epileptic encephalopathy genes) in both adult and developing human brain expression data sets. Candidate genes ranked in the top 10% for both data sets were cross-referenced with genes previously implicated in the epileptic encephalopathies due to a de novo variant. Results: Five of 6 validated epileptic encephalopathy candidate genes were among the 19 prioritized in 2013 (odds ratio = 54, 95% confidence interval [7,∞], p = 4.5 × 10−5, Fisher exact test); one gene was false negative. A total of 297 genes ranked in the top 10% for both the adult and developing brain data sets based on coexpression with the reference set. Of these, 9 had been previously implicated in the epileptic encephalopathies (FBXO41, PLXNA1, ACOT4, PAK6, GABBR2, YWHAG, NBEA, KNDC1, and SELRC1). Conclusions: We conclude that brain gene coexpression data can be used to assist epileptic encephalopathy gene discovery and propose 9 genes as strong epileptic encephalopathy candidates worthy of further investigation. PMID:27066588

  12. 1,2-Dichloroethane-induced toxic encephalopathy: a case series with morphological investigations.

    PubMed

    Chen, Shiyan; Zhang, Zhijian; Lin, Hong; Chen, Zixuan; Wang, Zhiqiang; Wang, Wei

    2015-04-15

    1,2-Dichloroethane (DCE) is commonly used as an industrial organic solvent and causes occupational diseases. Toxic encephalopathy is the most common and serious disorder resulting from DCE intoxication. Five patients who worked in shoemaking, pipemaking or a paint factory were identified as suffering from severe encephalopathy due to DCE intoxication. DCE-induced toxic encephalopathy manifests as various neurological deficits, with changes observable by neuroimaging. The main clinical manifestation is headache accompanied by intracranial hypertension. The typical cranial CT/MR scan of DCE toxic encephalopathy shows extensive brain edema and diffuse, symmetric, abnormal signal intensities in the cerebellar dentate nucleus, basal ganglia, and white matter in the bilateral cerebral hemispheres. The diagnosis of DCE toxic encephalopathy can be confirmed by the typical clinical and neuroimaging characteristics together with a history of exposure to substances contaminated with DCE. Dehydrating agents and glucocorticoids are the primary treatments. With early diagnosis and prompt treatment, promising results and recovery can be achieved. Effective prevention is expected to reduce the incidence of DCE toxic encephalopathy. PMID:25743226

  13. Laboratory activities involving transmissible spongiform encephalopathy causing agents

    PubMed Central

    Leunda, Amaya; Van Vaerenbergh, Bernadette; Baldo, Aline; Roels, Stefan; Herman, Philippe

    2013-01-01

    Since the appearance in 1986 of epidemic of bovine spongiform encephalopathy (BSE), a new form of neurological disease in cattle which also affected human beings, many diagnostic and research activities have been performed to develop detection and therapeutic tools. A lot of progress was made in better identifying, understanding and controlling the spread of the disease by appropriate monitoring and control programs in European countries. This paper reviews the recent knowledge on pathogenesis, transmission and persistence outside the host of prion, the causative agent of transmissible spongiform encephalopathies (TSE) in mammals with a particular focus on risk (re)assessment and management of biosafety measures to be implemented in diagnostic and research laboratories in Belgium. Also, in response to the need of an increasing number of European diagnostic laboratories stopping TSE diagnosis due to a decreasing number of TSE cases reported in the last years, decontamination procedures and a protocol for decommissioning TSE diagnostic laboratories is proposed. PMID:24055928

  14. Endogenous benzodiazepine-like compounds and diazepam binding inhibitor in serum of patients with liver cirrhosis with and without overt encephalopathy

    PubMed Central

    Avallone, R; Zeneroli, M; Venturini, I; Corsi, L; Schreier, P; Kleinschnitz, M; Ferrarese, C; Farina, F; Baraldi, C; Pecora, N; Frigo, M; Baraldi, M

    1998-01-01

    Background/Aim—Despite some controversy, it has been suggested that endogenous benzodiazepine plays a role in the pathogenesis of hepatic encephalopathy. The aim of the present study was to evaluate the concentrations of endogenous benzodiazepines and the peptide, diazepam binding inhibitor, in the blood of patients with liver cirrhosis with and without overt encephalopathy, and to compare these levels with those of consumers of commercial benzodiazepines. 
Subjects—Normal subjects (90), benzodiazepine consumers (14), and cirrhotic patients (113) were studied. 
Methods—Endogenous benzodiazepines were measured by the radioligand binding technique after high performance liquid chromatography (HPLC) purification. The presence of diazepam and N-desmethyldiazepam was assayed by HPLC-electrospray tandem mass spectrometry. Diazepam binding inhibitor was studied in serum by radioimmunoassay. 
Results—Endogenous benzodiazepines were below the limit of detection in 7% of patients with encephalopathy. When detectable, their levels were at least comparable with those of benzodiazepine consumers and correlated with the liver dysfunction but not the stage of encephalopathy. Serum levels of diazepam binding inhibitor tended to decrease when endogenous benzodiazepines levels increased. 
Conclusions—Endogenous benzodiazepines may accumulate in patients with liver cirrhosis during the course of the disease, and the phenomenon appears to be independent of the presence or absence of encephalopathy. 

 Keywords: benzodiazepine consumers; diazepam binding inhibitor; endogenous benzodiazepines; liver cirrhosis; overt hepatic encephalopathy PMID:9691927

  15. Hepatitis C virus and neurological damage

    PubMed Central

    Mathew, Shilu; Faheem, Muhammed; Ibrahim, Sara M; Iqbal, Waqas; Rauff, Bisma; Fatima, Kaneez; Qadri, Ishtiaq

    2016-01-01

    Chronic hepatitis C virus (HCV) infection exhibits a wide range of extrahepatic complications, affecting various organs in the human body. Numerous HCV patients suffer neurological manifestations, ranging from cognitive impairment to peripheral neuropathy. Overexpression of the host immune response leads to the production of immune complexes, cryoglobulins, as well as autoantibodies, which is a major pathogenic mechanism responsible for nervous system dysfunction. Alternatively circulating inflammatory cytokines and chemokines and HCV replication in neurons is another factor that severely affects the nervous system. Furthermore, HCV infection causes both sensory and motor peripheral neuropathy in the mixed cryoglobulinemia as well as known as an important risk aspect for stroke. These extrahepatic manifestations are the reason behind underlying hepatic encephalopathy and chronic liver disease. The brain is an apt location for HCV replication, where the HCV virus may directly wield neurotoxicity. Other mechanisms that takes place by chronic HCV infection due the pathogenesis of neuropsychiatric disorders includes derangement of metabolic pathways of infected cells, autoimmune disorders, systemic or cerebral inflammation and alterations in neurotransmitter circuits. HCV and its pathogenic role is suggested by enhancement of psychiatric and neurological symptoms in patients attaining a sustained virologic response followed by treatment with interferon; however, further studies are required to fully assess the impact of HCV infection and its specific antiviral targets associated with neuropsychiatric disorders. PMID:27134702

  16. Hepatitis C virus and neurological damage.

    PubMed

    Mathew, Shilu; Faheem, Muhammed; Ibrahim, Sara M; Iqbal, Waqas; Rauff, Bisma; Fatima, Kaneez; Qadri, Ishtiaq

    2016-04-28

    Chronic hepatitis C virus (HCV) infection exhibits a wide range of extrahepatic complications, affecting various organs in the human body. Numerous HCV patients suffer neurological manifestations, ranging from cognitive impairment to peripheral neuropathy. Overexpression of the host immune response leads to the production of immune complexes, cryoglobulins, as well as autoantibodies, which is a major pathogenic mechanism responsible for nervous system dysfunction. Alternatively circulating inflammatory cytokines and chemokines and HCV replication in neurons is another factor that severely affects the nervous system. Furthermore, HCV infection causes both sensory and motor peripheral neuropathy in the mixed cryoglobulinemia as well as known as an important risk aspect for stroke. These extrahepatic manifestations are the reason behind underlying hepatic encephalopathy and chronic liver disease. The brain is an apt location for HCV replication, where the HCV virus may directly wield neurotoxicity. Other mechanisms that takes place by chronic HCV infection due the pathogenesis of neuropsychiatric disorders includes derangement of metabolic pathways of infected cells, autoimmune disorders, systemic or cerebral inflammation and alterations in neurotransmitter circuits. HCV and its pathogenic role is suggested by enhancement of psychiatric and neurological symptoms in patients attaining a sustained virologic response followed by treatment with interferon; however, further studies are required to fully assess the impact of HCV infection and its specific antiviral targets associated with neuropsychiatric disorders. PMID:27134702

  17. Current understanding and neurobiology of epileptic encephalopathies.

    PubMed

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

    2016-08-01

    Epileptic encephalopathies are a group of diseases in which epileptic activity itself contributes to severe cognitive and behavioral impairments above and beyond what might be expected from the underlying pathology alone. These impairments can worsen over time. This concept has been continually redefined since its introduction. A few syndromes are considered epileptic encephalopathies: early myoclonic encephalopathy and Ohtahara syndrome in the neonatal period, epilepsy of infancy with migrating focal seizures, West syndrome or infantile spasms, Dravet syndrome during infancy, Lennox-Gastaut syndrome, epileptic encephalopathy with continuous spikes-and-waves during sleep, and Landau-Kleffner syndrome during childhood. The inappropriate use of this term to refer to all severe epilepsy syndromes with intractable seizures and severe cognitive dysfunction has led to confusion regarding the concept of epileptic encephalopathy. Here, we review our current understanding of those epilepsy syndromes considered to be epileptic encephalopathies. Genetic studies have provided a better knowledge of neonatal and infantile epilepsy syndromes, while neuroimaging studies have shed light on the underlying causes of childhood-onset epileptic encephalopathies such as Lennox-Gastaut syndrome. Apart from infantile spasm models, we lack animal models to explain the neurobiological mechanisms at work in these conditions. Experimental studies suggest that neuroinflammation may be a common neurobiological pathway that contributes to seizure refractoriness and cognitive involvement in the developing brain. PMID:26992889

  18. Encephalopathy in Wilson Disease: Copper Toxicity or Liver Failure?

    PubMed Central

    Ferenci, Peter; Litwin, Tomasz; Seniow, Joanna; Czlonkowska, Anna

    2015-01-01

    Hepatic encephalopathy (HE) is a complex syndrome of neurological and psychiatric signs and symptoms that is caused by portosystemic venous shunting with or without liver disease irrespective of its etiology. The most common presentation of Wilson disease (WD) is liver disease and is frequently associated with a wide spectrum of neurological and psychiatric symptoms. The genetic defect in WD leads to copper accumulation in the liver and later in other organs including the brain. In a patient presenting with Wilsonian cirrhosis neuropsychiatric symptoms may be caused either by the metabolic consequences of liver failure or by copper toxicity. Thus, in clinical practice a precise diagnosis is a great challenge. Contrary to HE in neurological WD consciousness, is very rarely disturbed and pyramidal signs, myoclonus dominate. Asterixis and many other clinical symptoms may be present in both disease conditions and are quite similar. However details of neurological assessment as well as additional examinations could help in differential diagnosis. PMID:26041965

  19. Understanding the drug resistance mechanism of hepatitis C virus NS5B to PF-00868554 due to mutations of the 423 site: a computational study.

    PubMed

    Jiao, Pingzu; Xue, Weiwei; Shen, Yulin; Jin, Nengzhi; Liu, Huanxiang

    2014-04-01

    NS5B, a hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) that plays a key role in viral replication, is an important target in the discovery of antiviral agents. PF-00868554 is a potent non-nucleoside inhibitor (NNI) that binds to the Thumb II allosteric pocket of NS5B polymerase and has shown significant promise in phase II clinical trials. Unfortunately, several PF-00868554 resistant mutants have been identified. M423 variants were the most common NS5B mutations that occurred after PF-00868554 monotherapy. In this study, we used molecular dynamics (MD) simulations, binding free energy calculations and free energy decomposition to explore the drug resistance mechanism of HCV to PF-00868554 resulting from three representative mutations (M423T/V/I) in NS5B polymerase. Free energy decomposition analysis reveals that the loss of binding affinity mainly comes from the reduction of both van der Waals (ΔE(vdw)) and electrostatic interaction contributions in the gas phase (ΔE(ele)). Further structural analysis indicates that the location of PF-00868554 and the binding mode changed due to mutation of the residue at the 423 site of NS5B polymerase from methionine to threonine, isoleucine or valine, which further resulted in the loss of binding ability of PF-00868554 to NS5B polymerase. The obtained computational results will have important value for the rational design of novel non-nucleoside inhibitors targeting HCV NS5B polymerase. PMID:24452008

  20. Baseline MELD Score Predicts Hepatic Decompensation during Antiviral Therapy in Patients with Chronic Hepatitis C and Advanced Cirrhosis

    PubMed Central

    Dultz, Georg; Seelhof, Martin; Herrmann, Eva; Welker, Martin-Walter; Friedrich-Rust, Mireen; Teuber, Gerlinde; Kronenberger, Bernd; von Wagner, Michael; Vermehren, Johannes; Sarrazin, Christoph; Zeuzem, Stefan; Hofmann, Wolf Peter

    2013-01-01

    Background and Aims In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV) infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined. Methods In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.18±2.72) were treated with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (onset of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization) as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks after initiation of antiviral therapy. To monitor long term sequelae of end stage liver disease an extended follow up for HCC development, transplantation and death was applied (240weeks, ±SD 136weeks). Results Eighteen patients (26.5%) achieved a sustained virologic response. During the observational period a hepatic decompensation was observed in 36.8%. Patients with hepatic decompensation had higher MELD scores (10.84 vs. 8.23, p<0.001) and higher mean bilirubin levels (26.74 vs. 14.63 µmol/l, p<0.001), as well as lower serum albumin levels (38.2 vs. 41.1 g/l, p = 0.015), mean platelets (102.64 vs. 138.95/nl, p = 0.014) and mean leukocytes (4.02 vs. 5.68/nl, p = 0.002) at baseline as compared to those without decompensation. In the multivariate analysis the MELD score remained independently associated with hepatic decompensation (OR 1.56, 1.18–2.07; p = 0.002). When the patients were grouped according to their baseline MELD scores, hepatic decompensation occurred in 22%, 59%, and 83% of patients with MELD scores of 6–9, 10–13, and >14, respectively. Baseline MELD score was significantly associated with the risk for transplantation/death (p<0.001). Conclusions Our data suggest that the

  1. Increased hepatic receptor interacting protein kinase 3 expression due to impaired proteasomal functions contributes to alcohol-induced steatosis and liver injury

    PubMed Central

    Wang, Shaogui; Ni, Hong-Min; Dorko, Kenneth; Kumer, Sean C.; Schmitt, Timothy M.; Nawabi, Atta; Komatsu, Masaaki; Huang, Heqing; Ding, Wen-Xing

    2016-01-01

    Chronic alcohol exposure increased hepatic receptor-interacting protein kinase (RIP) 3 expression and necroptosis in the liver but its mechanisms are unclear. In the present study, we demonstrated that chronic alcohol feeding plus binge (Gao-binge) increased RIP3 but not RIP1 protein levels in mouse livers. RIP3 knockout mice had decreased serum alanine amino transferase activity and hepatic steatosis but had no effect on hepatic neutrophil infiltration compared with wild type mice after Gao-binge alcohol treatment. The hepatic mRNA levels of RIP3 did not change between Gao-binge and control mice, suggesting that alcohol-induced hepatic RIP3 proteins are regulated at the posttranslational level. We found that Gao-binge treatment decreased the levels of proteasome subunit alpha type-2 (PSMA2) and proteasome 26S subunit, ATPase 1 (PSMC1) and impaired hepatic proteasome function. Pharmacological or genetic inhibition of proteasome resulted in the accumulation of RIP3 in mouse livers. More importantly, human alcoholics had decreased expression of PSMA2 and PSMC1 but increased protein levels of RIP3 compared with healthy human livers. Moreover, pharmacological inhibition of RIP1 decreased Gao-binge-induced hepatic inflammation, neutrophil infiltration and NF-κB subunit (p65) nuclear translocation but failed to protect against steatosis and liver injury induced by Gao-binge alcohol. In conclusion, results from this study suggest that impaired hepatic proteasome function by alcohol exposure may contribute to hepatic accumulation of RIP3 resulting in necroptosis and steatosis while RIP1 kinase activity is important for alcohol-induced inflammation. PMID:26769846

  2. Epilepsy Surgery in Pediatric Intractable Epilepsy with Destructive Encephalopathy

    PubMed Central

    Park, So Young; Kwon, Hye Eun; Kang, Hoon-Chul; Lee, Joon Soo; Kim, Dong Seok; Kim, Heung Dong

    2013-01-01

    Background and Purpose: The aim of the current study is to review the clinical features, surgery outcomes and parental satisfaction of children with destructive encephalopathy who underwent epilepsy surgery due to medically intractable seizures. Methods: 48 patients who underwent epilepsy surgery from October 2003 to August 2011 at Severance Children’s Hospital have been reviewed. The survey was conducted for functional outcomes and parental satisfaction at least 1 year after the surgery. Results: Epileptic encephalopathy including Lennox-Gastaut syndrome and infantile spasms was more prevalent than symptomatic focal epilepsy. Hypoxic ischemic injury accounted for most of the underlying etiology of the destructive encephalpathy, followed by central nervous system infection and head trauma. 27 patients (56.3%) underwent resective surgery and 21 patients (43.7%) underwent palliative surgery. 16 patients (33.3%) achieved seizure free and 27 parents (87.5%) reported satisfaction with the outcome of their children’s epilepsy surgery. In addition, 14 parents (77.8 %) whose children were not seizure free reported satisfaction with their children’s improvement in cognitive and behavior issues. Conclusions: Epilepsy surgery in destructive encephalopathy was effective for controlling seizures. Parents reported satisfaction not only with the surgical outcomes, but also with improvement of cognitive and behavior issues. PMID:24649473

  3. Encephalopathy after persistent vomiting: Three cases of non-alcohol-related Wernicke's encephalopathy.

    PubMed

    Antel, K; Singh, N; Chisholm, B; Heckmann, J M

    2015-06-01

    Wernicke's encephalopathy (WE) is a medical emergency. Although WE is commonly viewed in the context of alcoholism, it can be caused by thiamine deficiency secondary to persistent vomiting. Non-alcohol-related WE may be more catastrophic in onset and less likely to present with the classic features than WE with alcoholism as a cause. We describe three cases of WE due to persistent vomiting without alcoholism in patients with hyperemesis gravidarum, drug-induced hyperlactataemia, and an acute gastrointestinal illness in an already malnourished individual. Our cases highlight the importance of recognising WE when undernutrition, which may be caused by gastrointestinal disease or surgery, or malignancy, is compounded by vomiting. Expert guidelines suggest that WE must be considered in the emergency room in any individual with disturbed consciousness of unknown cause. Treatment is with parenteral thiamine before glucose administration. PMID:26716155

  4. Clinical and Neuroradiological Spectrum of Metronidazole Induced Encephalopathy: Our Experience and the Review of Literature

    PubMed Central

    Panwar, Ajay; Pandit, Alak; Das, Susanta Kumar; Joshi, Bhushan

    2016-01-01

    Metronidazole is an antimicrobial agent mainly used in the treatment of several protozoal and anaerobic infections, additionally, is often used in hepatic encephalopathy and Crohn disease. Apart from peripheral neuropathy, metronidazole can also cause symptoms of central nervous system dysfunction like ataxic gait, dysarthria, seizures, and encephalopathy which may result from both short term and chronic use of this drug and is collectively termed as “metronidazole induced encephalopathy”(MIE). Neuroimaging forms the backbone in clinching the diagnosis of this uncommon entity, especially in cases where there is high index of suspicion of intoxication. Although typical sites of involvement include cerebellum, brain stem and corpus callosum, however, lesions of other sites have also been reported. Once diagnosed, resolution of findings on Magnetic Resonance Imaging (MRI) of the Brain along with clinical improvement remains the mainstay of monitoring. Here we review the key clinical features and MRI findings of MIE as reported in medical literature. We also analyze implication of use of this drug in special situations like hepatic encephalopathy and brain abscess and discuss our experience regarding this entity. PMID:27504340

  5. Encephalopathy

    MedlinePlus

    ... pressure in the skull, prolonged exposure to toxic elements (including solvents, drugs, radiation, paints, industrial chemicals, and certain metals), chronic progressive trauma, poor nutrition, ...

  6. Pre-transplant portal vein thrombosis is an independent risk factor for graft loss due to hepatic artery thrombosis in liver transplant recipients

    PubMed Central

    Stine, Jonathan G.; Pelletier, Shawn J.; Schmitt, Timothy M.; Porte, Robert J.; Northup, Patrick G.

    2015-01-01

    Background Hepatic artery thrombosis is an uncommon but catastrophic complication following liver transplantation. We hypothesize that recipients with portal vein thrombosis are at increased risk. Methods Data on all liver transplants in the U.S. during the MELD era through September 2014 were obtained from UNOS. Status one, multivisceral, living donor, re-transplants, pediatric recipients and donation after cardiac death were excluded. Logistic regression models were constructed for hepatic artery thrombosis with resultant graft loss within 90 days of transplantation. Results 63,182 recipients underwent transplantation; 662 (1.1%) recipients had early hepatic artery thrombosis; of those, 91 (13.8%) had pre-transplant portal vein thrombosis, versus 7.5% with portal vein thrombosis but no hepatic artery thrombosis (p < 0.0001). Portal vein thrombosis was associated with an increased independent risk of hepatic artery thrombosis (OR 2.17, 95% CI 1.71–2.76, p < 0.001) as was donor risk index (OR 2.02, 95% CI 1.65–2.48, p < 0.001). Heparin use at cross clamp, INR, and male donors were all significantly associated with lower risk. Discussion Pre-transplant portal vein thrombosis is associated with post-transplant hepatic artery thrombosis independent of other factors. Recipients with portal vein thrombosis might benefit from aggressive coagulation management and careful donor selection. More research is needed to determine causal mechanism. PMID:27017168

  7. Suicide and Chronic Traumatic Encephalopathy.

    PubMed

    Iverson, Grant L

    2016-01-01

    For nearly 80 years, suicidality was not considered to be a core clinical feature of chronic traumatic encephalopathy (CTE). In recent years, suicide has been widely cited as being associated with CTE, and now depression has been proposed to be one of three core diagnostic features alongside cognitive impairment and anger control problems. This evolution of the clinical features has been reinforced by thousands of media stories reporting a connection between mental health problems in former athletes and military veterans, repetitive neurotrauma, and CTE. At present, the science underlying the causal assumption between repetitive neurotrauma, depression, suicide, and the neuropathology believed to be unique to CTE is inconclusive. Epidemiological evidence indicates that former National Football League players, for example, are at lower, not greater, risk for suicide than men in the general population. This article aims to discuss the critical issues and literature relating to these possible relationships. PMID:26449269

  8. Posterior Reversible Encephalopathy Syndrome in ALL.

    PubMed

    Millichap, J Gordon

    2015-07-01

    Investigators from Soochow University, Suzhou, China, studied the possible pathogenetic mechanisms and treatment of posterior reversible encephalopathy syndrome (PRES) observed in 11 cases of pediatric acute lymphoblastic leukemia (ALL) after induction chemotherapy. PMID:26933594

  9. Bovine Spongiform Encephalopathy: Atypical Pros and Cons

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transmissible spongiform encephalopathies (TSEs) are fatal neurologic diseases that affect several mammalian species including human beings. Four animal TSE agents have been reported: scrapie of sheep and goats; chronic wasting disease (CWD) of deer, elk, and moose; transmissible mink encephalopath...

  10. Neuroimaging in Neonatal Hypoxic Ischemic Encephalopathy.

    PubMed

    Krishnan, Pradeep; Shroff, Manohar

    2016-09-01

    Magnetic resonance (MR) imaging is emerging as one of the most important tools in identifying the etiology of neonatal encephalopathy as well as in predicting long-term outcomes. This makes it imperative to have a broader understanding of normal myelination of the neonatal brain on MR imaging and to be familiar with the spectrum of imaging features in ischemic and non-ischemic neonatal encephalopathy. Hypoxic ischemic injury (HIE) is one of the most common causes of neonatal encephalopathy and imaging appearances are influenced by factors such as the stage of maturation of the neonatal brain and severity as well as duration of ischemic insult. Other common causes of neonatal encephalopathy include infectious diseases, congenital disorders and inborn errors of metabolism. PMID:26909496

  11. Viral Hepatitis

    MedlinePlus

    ... Public Home » For Veterans and the Public Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... the Public Veterans and Public Home How is Hepatitis C Treated? Find the facts about the newest ...

  12. Viral Hepatitis

    MedlinePlus

    ... with hepatitis? How does a pregnant woman pass hepatitis B virus to her baby? If I have hepatitis B, what does my baby need so that she ... Can I breastfeed my baby if I have hepatitis B? More information on viral hepatitis What is hepatitis? ...

  13. Leucine metabolism in cirrhotic patients with hepatic encephalopathy

    SciTech Connect

    McGhee, A.S.

    1985-01-01

    The purpose of this study was to determine whether increased oxidation of or protein synthesis requiring leucine occurs in cirrhotic patients. Five control subjects and four subjects with cirrhosis were equilibrated on a baseline diet (0.6 g protein per kg ideal body weight (IBW)) with sufficient nonprotein calories to preclude negative nitrogen balance. An additional four patients were equilibrated on the same type of diet with a higher protein level (0.75 g per kg IBW). Control subjects and the patients were then studied during continuous infusion of L-(/sup 15/N, 1-/sup 13/C) leucine in the fasted state and, in the fed state, with a Propac diet which had the same distribution of energy nutrients as the baseline diets. Plasma levels of L-(/sup 15/N, 1-/sup 13/C), L-(1-/sup 13/C) and L-(/sup 15/N) leucine were measured during isotopic steady state by gas chromatography-mass spectrometry and fractional excretion of /sup 13/CO/sup 2/ in breath samples were analyzed by isotopic ratio mass spectrometry. During the fasted and fed states leucine metabolism was measured to quantitate rates of nitrogen flux (Q/sub N/), carbon flux (Q/sub c/) and oxidation to carbon dioxide and water (C). From these measured values, proteins breakdown (B), protein synthesis (S), deamination (X/sup 0/) and reamination (X/sub N/) were calculated. The results showed that protein synthesis and leucine metabolism were identical in controls and patients when both were fed a diet with 0.6 g protein/kg IBW and maintenance level of nonprotein calories. The data also showed that leucine metabolism can be quantitatively and reproducibly measured in subjects with cirrhosis.

  14. Steroid-responsive Encephalopathy Subsequently Associated with Alzheimer Disease Pathology: A Case Series

    PubMed Central

    Mateen, Farrah J.; Josephs, Keith A.; Parisi, Joseph E.; Drubach, Daniel A.; Caselli, Richard J.; Kantarci, Kejal; Lennon, Vanda; Jack, Clifford; Boeve, Bradley F.

    2011-01-01

    Background Steroid-responsive encephalopathies can considered vasculitic or nonvasculitic. Clinicopathological studies of nonvasculitic steroid-responsive encephalopathy are unusual, but can explain the range of diagnoses consistent with a steroid responsive presentation in life. Objective To extend the range of clinical features and pathological findings consistent with steroid-responsive encephalopathy. Design, Methods, and Patients A clinicopathological case series of four patients (ages 54–71 years, 2 women) with steroid-responsive encephalopathy followed at this institution until the time of death. Results Clinical features were suggestive of Creutzfeld-Jakob disease, dementia with Lewy Bodies, and parkinsonism, but pathological examination revealed only Alzheimer’s Disease-related findings without evidence of Lewy bodies or prion disease in all cases. All patients demonstrated marked, sustained improvement following steroid treatment, based on clinical, magnetic resonance imaging, and/or electroencephalogram studiesAlzheimer’s Disease was not diagnosed in life due to a lack of hippocampal atrophy on brain imaging and a dramatic symptomatic response to steroids. Conclusions Steroid-responsive encephalopathy is the clinical presentation of some patients with Alzheimer’s Disease related pathology at autopsy, and can be consistent with the clinical diagnoses of parkisonism, dementia with Lewy Bodies, or Creutzfeld-Jakob Disease in life. PMID:21714739

  15. Blood transfusion in sickle cell disease leading to posterior reversible encephalopathy syndrome (PRES).

    PubMed

    Raj, Shashi; Killinger, James; Overby, Philip

    2013-10-01

    Children with sickle cell disease have a very high risk of lifelong neurologic morbidity and mortality. Cerebrovascular accidents are a known complication in children with sickle cell disease. Posterior reversible encephalopathy syndrome is a constellation of acute neurologic findings increasingly recognized in pediatric critical care population with evidence of vasogenic edema on brain imaging possibly due to cerebral vascular endothelial cell dysfunction. This report, for the first time, describes a young adult with sickle cell disease who developed posterior reversible encephalopathy syndrome following blood transfusion. PMID:22899796

  16. Wernicke's encephalopathy and anabolic steroid drug abuse. Is there any possible relation?

    PubMed

    Christopoulos, P; Katsanoulas, C; Timplalexi, G; Lathyris, D; Vasiliagkou, S; Antoniadou, E

    2012-10-01

    Wernicke's encephalopathy is a reversible, neurologic disorder due to thiamine deficiency which is mainly related to chronic alcohol abuse. We report a case of a young male patient, who was bodybuilder and anabolic drug user, in whom encephalopathy was diagnosed after a short medical course in the ICU after a major upper gastrointestinal bleeding (Mallory-Weiss syndrome) and hypovolemic shock. His clinical condition was typical for Wernicke's encephalopathy and although neuroimaging tests were not indicative, the patient received thiamine supplement therapy, which resulted in rapid clinical improvement. The diagnosis was based only on clinical sings and anabolic drug abuse was considered as a possible predisposing factor for the manifestation of the syndrome. PMID:23935320

  17. Liver transplant in ethylmalonic encephalopathy: a new treatment for an otherwise fatal disease.

    PubMed

    Dionisi-Vici, Carlo; Diodato, Daria; Torre, Giuliano; Picca, Stefano; Pariante, Rosanna; Giuseppe Picardo, Sergio; Di Meo, Ivano; Rizzo, Cristiano; Tiranti, Valeria; Zeviani, Massimo; De Goyet, Jean De Ville

    2016-04-01

    Ethylmalonic encephalopathy is a fatal, rapidly progressive mitochondrial disorder caused byETHE1mutations, whose peculiar clinical and biochemical features are due to the toxic accumulation of hydrogen sulphide and of its metabolites, including thiosulphate. In mice with ethylmalonic encephalopathy, liver-targeted adeno-associated virus-mediatedETHE1gene transfer dramatically improved both clinical course and metabolic abnormalities. Reasoning that the same achievement could be accomplished by liver transplantation, we performed living donor-liver transplantation in an infant with ethylmalonic encephalopathy. Unlike the invariably progressive deterioration of the disease, 8 months after liver transplantation, we observed striking neurological improvement with remarkable achievements in psychomotor development, along with dramatic reversion of biochemical abnormalities. These results clearly indicate that liver transplantation is a viable therapeutic option for ETHE1 disease. PMID:26917598

  18. Wernicke's encephalopathy and anabolic steroid drug abuse. Is there any possible relation?

    PubMed Central

    Christopoulos, P; Katsanoulas, C; Timplalexi, G; Lathyris, D; Vasiliagkou, S; Antoniadou, E

    2012-01-01

    Wernicke's encephalopathy is a reversible, neurologic disorder due to thiamine deficiency which is mainly related to chronic alcohol abuse. We report a case of a young male patient, who was bodybuilder and anabolic drug user, in whom encephalopathy was diagnosed after a short medical course in the ICU after a major upper gastrointestinal bleeding (Mallory-Weiss syndrome) and hypovolemic shock. His clinical condition was typical for Wernicke's encephalopathy and although neuroimaging tests were not indicative, the patient received thiamine supplement therapy, which resulted in rapid clinical improvement. The diagnosis was based only on clinical sings and anabolic drug abuse was considered as a possible predisposing factor for the manifestation of the syndrome. PMID:23935320

  19. PPARα-Deficient ob/ob Obese Mice Become More Obese and Manifest Severe Hepatic Steatosis Due to Decreased Fatty Acid Oxidation

    PubMed Central

    Gao, Qian; Jia, Yuzhi; Yang, Gongshe; Zhang, Xiaohong; Boddu, Prajwal C.; Petersen, Bryon; Narsingam, Saiprasad; Zhu, Yi-Jun; Thimmapaya, Bayar; Kanwar, Yashpal S.; Reddy, Janardan K.

    2016-01-01

    Obesity poses an increased risk of developing metabolic syndrome and closely associated nonalcoholic fatty liver disease, including liver cancer. Satiety hormone leptin-deficient (ob/ob) mice, considered paradigmatic of nutritional obesity, develop hepatic steatosis but are less prone to developing liver tumors. Sustained activation of peroxisome proliferator–activated receptor α (PPARα) in ob/ob mouse liver increases fatty acid oxidation (FAO), which contributes to attenuation of obesity but enhances liver cancer risk. To further evaluate the role of PPARα-regulated hepatic FAO and energy burning in the progression of fatty liver disease, we generated PPARα-deficient ob/ob (PPARαΔob/ob) mice. These mice become strikingly more obese compared to ob/ob littermates, with increased white and brown adipose tissue content and severe hepatic steatosis. Hepatic steatosis becomes more severe in fasted PPARαΔob/ob mice as they fail to up-regulate FAO systems. PPARαΔob/ob mice also do not respond to peroxisome proliferative and mitogenic effects of PPARα agonist Wy-14,643. Although PPARαΔob/ob mice are severely obese, there was no significant increase in liver tumor incidence, even when maintained on a diet containing Wy-14,643. We conclude that sustained PPARα activation–related increase in FAO in fatty livers of obese ob/ob mice increases liver cancer risk, whereas deletion of PPARα in ob/ob mice aggravates obesity and hepatic steatosis. However, it does not lead to liver tumor development because of reduction in FAO and energy burning. PMID:25773177

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

    PubMed Central

    Advani, Rajiv; Kurz, Kathinka D.; Kurz, Martin W.

    2014-01-01

    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. PMID:24716022

  1. Wernicke's Encephalopathy Complicating Hyperemesis during Pregnancy

    PubMed Central

    Berdai, Mohamed Adnane; Labib, Smael; Harandou, Mustapha

    2016-01-01

    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. PMID:26989522

  2. Clinical review of genetic epileptic encephalopathies

    PubMed Central

    Noh, Grace J.; Asher, Y. Jane Tavyev; Graham, John M.

    2012-01-01

    Seizures are a frequently encountered finding in patients seen for clinical genetics evaluations. The differential diagnosis for the cause of seizures is quite diverse and complex, and more than half of all epilepsies have been attributed to a genetic cause. Given the complexity of such evaluations, we highlight the more common causes of genetic epileptic encephalopathies and emphasize the usefulness of recent technological advances. The purpose of this review is to serve as a practical guide for clinical geneticists in the evaluation and counseling of patients with genetic epileptic encephalopathies. Common syndromes will be discussed, in addition to specific seizure phenotypes, many of which are refractory to anti-epileptic agents. Divided by etiology, we overview the more common causes of infantile epileptic encephalopathies, channelopathies, syndromic, metabolic, and chromosomal entities. For each condition, we will outline the diagnostic evaluation and discuss effective treatment strategies that should be considered. PMID:22342633

  3. Wernicke's Encephalopathy Complicating Hyperemesis during Pregnancy.

    PubMed

    Berdai, Mohamed Adnane; Labib, Smael; Harandou, Mustapha

    2016-01-01

    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. PMID:26989522

  4. Pediatric Epileptic Encephalopathies: Pathophysiology and Animal Models.

    PubMed

    Shao, Li-Rong; Stafstrom, Carl E

    2016-05-01

    Epileptic encephalopathies are syndromes in which seizures or interictal epileptiform activity contribute to or exacerbate brain function, beyond that caused by the underlying pathology. These severe epilepsies begin early in life, are associated with poor lifelong outcome, and are resistant to most treatments. Therefore, they represent an immense challenge for families and the medical care system. Furthermore, the pathogenic mechanisms underlying the epileptic encephalopathies are poorly understood, hampering attempts to devise novel treatments. This article reviews animal models of the three classic epileptic encephalopathies-West syndrome (infantile spasms), Lennox-Gastaut syndrome, and continuous spike waves during sleep or Landau-Kleffner syndrome-with discussion of how animal models are revealing underlying pathophysiological mechanisms that might be amenable to targeted therapy. PMID:27544466

  5. Why the confusion in Hashimoto's encephalopathy?

    PubMed

    Jayasekera, Bodiabaduge A P; McShane, Michael Anthony; Roy, Prem; Anand, Geetha

    2011-01-01

    A 13-year-old girl presented with an afebrile seizure followed by prolonged confusion and visual hallucinations. Initial investigations in the form of blood tests, cerebrospinal fluid analysis and head imaging by CT, were normal. She represented with two further episodes within a period of 3 weeks. Further investigations considering infective, metabolic and some autoimmune causes of encephalopathy were negative. An MRI head scan was normal. Thyroid function testing disclosed primary hypothyroidism and elevated antithyroid antibodies. She responded well to glucocorticoid therapy for presumed Hashimoto's encephalopathy (HE). HE describes patients with various neurological manifestations with elevated titres of antithyroid antibodies. There are no clear criteria for diagnosis, with many cases labelled as HE. Responses to corticosteroid therapy are favourable. In patients with unexplained encephalopathy, HE should be considered given the favourable response to glucocorticoid therapy. PMID:22691944

  6. Hashimoto Encephalopathy or Neurosarcoidosis? A Case Report

    PubMed Central

    Sapkota, Biggya L.; Pitiyanuvath, Nataria

    2015-01-01

    Hashimoto encephalopathy (HE) is a rare autoimmune disease characterized by symptoms of acute or subacute encephalopathy associated with increased antithyroid antibody levels. Neurosarcoidosis is also a rare entity that occurs in less than 5% of patients with systemic sarcoidosis. Neurosarcoidosis usually presents with cranial neuropathies, myelopathy, or new-onset seizure. We report a case of a 49-year-old caucasian woman, previously healthy, who initially presented for a workup of a new-onset seizure. She had a gradually progressive course with neurocognitive decline and recurrent partial seizures refractory to conventional antiepileptic drugs. Her seizures responded well to a course of intravenous immunoglobulin. She was subsequently diagnosed with HE and pulmonary sarcoidosis based on serological and pathological studies. She improved neurologically once the seizures were controlled. Hashimoto encephalopathy is a rare condition that is potentially treatable and presents with various neuropsychiatric manifestations. It is a diagnosis of exclusion that requires a strong clinical suspicion and is often underrecognized. PMID:25829987

  7. Experimental Interspecies Transmission Studies of the Transmissible Spongiform Encephalopathies to Cattle: Comparison to Bovine Spongiform Encephalopathy in Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prion diseases or transmissible spongiform encephalopathies (TSEs) of animals include scrapie of sheep and goats; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of deer, elk and moose; and bovine spongiform encephalopathy (BSE) of cattle. Since the emergence of BSE and its pr...

  8. Concussion in Chronic Traumatic Encephalopathy

    PubMed Central

    Stein, Thor D.; Alvarez, Victor E.; McKee, Ann C.

    2015-01-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid β peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE. PMID:26260277

  9. Concussion in Chronic Traumatic Encephalopathy.

    PubMed

    Stein, Thor D; Alvarez, Victor E; McKee, Ann C

    2015-10-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid β peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE. PMID:26260277

  10. Endemicity and clinical picture of liver disease due to obstruction of the hepatic portion of the inferior vena cava in Nepal.

    PubMed

    Shrestha, S M; Okuda, K; Uchida, T; Maharjan, K G; Shrestha, S; Joshi, B L; Larsson, S; Vaidya, Y

    1996-02-01

    Obstructive lesion of the hepatic portion of the inferior vena cava is common in Nepal. The clinical data on 150 patients who were seen at the Liver Unit, Bir Hospital, Kathmandu, in three years from 1990 to 1992 were analysed. Although the majority of patients were over 20 years of age, 25 patients were below 10 years of age; there were more males than females in this study. This disease accounted for 17% of 866 patients with chronic liver disease and for nearly one quarter of 267 biopsies performed on this patient group during the same period. Obstructive lesions of the inferior vena cava seem to be more common among poor people with malnutrition. Clinically, our patient group could be divided into acute (n = 27), subacute (n = 43) and chronic (n = 80) cases. The important clinical features are hepatomegaly and/or ascites and, in chronic cases, prominent dilated superficial veins over the body trunk with cephalad flow. Ultrasound is the most helpful diagnostic procedure, especially in subacute and chronic cases, as it frequently demonstrates caval obstruction, thrombosis, dilated hepatic veins and intrahepatic collaterals. Diagnosis is confirmed by cavography, which shows a caval obstruction of varying lengths at the cavo-atrial junction or a marked narrowing of the hepatic portion of the vena cava. In subacute and chronic cases cavography also demonstrates collateral veins, such as the ascending lumbar, hemiazygos and azygos that drain into the superior vena cava. Chronic cases had periods of exacerbation often associated with bacterial infection. The aetiology of inferior vena cava obstruction at its hepatic portion is not known, but there seems to be a frequent association of bacterial infection with the disease. PMID:8672764

  11. Long-term survival in a child with severe encephalopathy, multiple respiratory chain deficiency and GFM1 mutations

    PubMed Central

    Brito, Sara; Thompson, Kyle; Campistol, Jaume; Colomer, Jaime; Hardy, Steven A.; He, Langping; Fernández-Marmiesse, Ana; Palacios, Lourdes; Jou, Cristina; Jiménez-Mallebrera, Cecilia; Armstrong, Judith; Montero, Raquel; Artuch, Rafael; Tischner, Christin; Wenz, Tina; McFarland, Robert; Taylor, Robert W.

    2015-01-01

    Background: Mitochondrial diseases due to deficiencies in the mitochondrial oxidative phosphorylation system (OXPHOS) can be associated with nuclear genes involved in mitochondrial translation, causing heterogeneous early onset and often fatal phenotypes. Case report: The authors describe the clinical features and diagnostic workup of an infant who presented with an early onset severe encephalopathy, spastic-dystonic tetraparesis, failure to thrive, seizures and persistent lactic acidemia. Brain imaging revealed thinning of the corpus callosum and diffuse alteration of white matter signal. Genetic investigation confirmed two novel mutations in the GFM1 gene, encoding the mitochondrial translation elongation factor G1 (mtEFG1), resulting in combined deficiencies of OXPHOS. Discussion: The patient shares multiple clinical, laboratory and radiological similarities with the 11 reported patients with mutations involving this gene, but presents with a stable clinical course without metabolic decompensations, rather than a rapidly progressive fatal course. Defects in GFM1 gene confer high susceptibility to neurologic or hepatic dysfunction and this is, to the best of our knowledge, the first described patient who has survived beyond early childhood. Reporting of such cases is essential so as to delineate the key clinical and neuroradiological features of this disease and provide a more comprehensive view of its prognosis. PMID:25852744

  12. Hyperammonemia-induced encephalopathy: A rare devastating complication of bariatric surgery

    PubMed Central

    Kromas, Michelle L; Mousa, Omar Y; John, Savio

    2015-01-01

    The clinical manifestations of hyperammonemia are usually easily identifiable to the clinician when associated with liver disease and lead to prompt diagnosis and treatment. However, hyperammonemia-induced encephalopathy is rare in adults in the absence of overt liver disease, thus diagnosis is often delayed or missed leading to potentially life threatening complications. Without proper treatment, such patients can decompensate rapidly with poor outcomes including seizures, coma, and death. Early assessment of plasma ammonia levels in patients with normal hepatic function and characteristic symptoms of encephalopathy can lead to early intervention while investigating the underlying etiology. We describe a patient who presented with a 2-year progression of waxing and waning acute mental status changes after a Roux-en-Y gastric bypass surgery. He was found to have elevated ammonia level as well as orotic aciduria; results consistent with a urea cycle disorder. After consulting neurology as well as toxicology, he ultimately improved after dietary protein restriction, sodium benzoate and lactulose therapy. While rare, clinicians should have a high index of suspicion for late onset urea cycle disorders in symptomatic patients presenting with encephalopathy secondary to hyperammonemia. PMID:25954483

  13. Chemical pleurodesis for the management of refractory hepatic hydrothorax in patients with decompensated liver cirrhosis

    PubMed Central

    Lee, Woo Jin; Park, Jung Ho; Park, Dong Il; Cho, Yong Kyun; Sohn, Chong Il; Jeon, Woo Kyu; Kim, Byung Ik

    2011-01-01

    Background/Aims Hepatic hydrothorax in patients with decompensated liver cirrhosis is a challenging problem. Treatment with diuretics and intermittent thoracentesis can be effective in selected patients. However, there are few effective therapeutic options in patients who are intolerant of these therapies. This study investigated the clinical usefulness of chemical pleurodesis with or without video-assisted thoracoscopic surgery (VATS) for patients with refractory hepatic hydrothorax. Methods Eleven consecutive patients with refractory hepatic hydrothorax who underwent chemical pleurodesis with or without VATS between July 2007 and February 2011 were enrolled in this study. The medical records and radiologic imagings of these patients were thoroughly reviewed. Results The median number of chemical pleurodesis sessions performed was 3 (range: 2-10). Successful pleurodesis was achieved in 8 of the 11 patients (72.7%), 5 (62.5%) of whom remained asymptomatic and hydrothorax free for a median follow-up of 16 weeks (range: 2-52 weeks). Complications were low-grade fever/leukocytosis (n=11, 100%), pneumonia (n=1, 9.1%), pneumothorax (n=4, 36.4%), azotemia/acute renal failure (n=6, 54.6%), and hepatic encephalopathy (n=4, 36.4%). Five patients were suspected as having procedure-related mortality (45.5%) due to the occurrence of acute renal failure with hepatic failure. The overall survival was significantly longer in the success group than in the non-success group. Conclusions Although chemical pleurodesis may improve the clinical symptoms and the radiologic findings in as many as 72.7% of patients with refractory hepatic hydrothorax, a significantly high prevalence of procedure-related morbidity and mortality hinders the routine application of this procedure for such patients. PMID:22310793

  14. Neuropsychological functioning in Wernicke's encephalopathy

    PubMed Central

    Behura, Sushree Sangita; Swain, Sarada Prasanna

    2015-01-01

    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 the severity

  15. PRIONS AND THE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

    EPA Science Inventory

    This book chapter is an invited, scholarly review of the mechanism(s) of TSEs for the 2nd edition of Metabolic Encephalopathies. Each chapter in the book assumes a professional knowledge of neuroscience and biochemistry, and the focus of the book is on the metabolic basis of dise...

  16. Epileptic encephalopathies: new genes and new pathways.

    PubMed

    Nieh, Sahar Esmaeeli; Sherr, Elliott H

    2014-10-01

    Epileptic encephalopathies represent a group of devastating epileptic disorders that occur early in life and are often characterized by pharmaco-resistant epilepsy, persistent severe electroencephalographic abnormalities, and cognitive dysfunction or decline. Next generation sequencing technologies have increased the speed of gene discovery tremendously. Whereas ion channel genes were long considered to be the only significant group of genes implicated in the genetic epilepsies, a growing number of non-ion-channel genes are now being identified. As a subgroup of the genetically mediated epilepsies, epileptic encephalopathies are complex and heterogeneous disorders, making diagnosis and treatment decisions difficult. Recent exome sequencing data suggest that mutations causing epileptic encephalopathies are often sporadic, typically resulting from de novo dominant mutations in a single autosomal gene, although inherited autosomal recessive and X-linked forms also exist. In this review we provide a summary of the key features of several early- and mid-childhood onset epileptic encephalopathies including Ohtahara syndrome, Dravet syndrome, Infantile spasms and Lennox Gastaut syndrome. We review the recent next generation sequencing findings that may impact treatment choices. We also describe the use of conventional and newer anti-epileptic and hormonal medications in the various syndromes based on their genetic profile. At a biological level, developments in cellular reprogramming and genome editing represent a new direction in modeling these pediatric epilepsies and could be used in the development of novel and repurposed therapies. PMID:25266964

  17. Intermediate dose 5-fluorouracil-induced encephalopathy.

    PubMed

    Kim, Yeon-A; Chung, Hyun Cheol; Choi, Hye Jin; Rha, Sun Young; Seong, Jin Sil; Jeung, Hei-Cheul

    2006-01-01

    As an acute neurotoxicity, high dose 5-fluorouracil (5-FU)-induced encephalopathy is well-known, but encephalopathy associated with lower dose is rarely reported. Here, we report a case of a male with anal cancer who was treated with 5-FU 1000 mg/m(2), continuous infusion for 5 days q4 weeks. At the second and the fourth cycles of chemotherapy, sudden confusion, cognitive dysfunction and disorientation occurred during 5-FU infusion. They were accompanied by hyperammonemia in the absence of focal neurological deficits or structural abnormalities. These symptoms completely disappeared and the serum ammonia level returned to normal after discontinuation of 5-FU and conservative care. In order to investigate a possible deficit of dihydropyrimidine dehydrogenase (DPD), we checked its mRNA level before and after treatment using real-time PCR. The patient's pre-treatment level was 80% compared with reference group, and it was elevated up to 187% of initial after 5-FU treatment, implying that that his encephalopathy may be 5-FU catabolite type rather than DPD deficiency. In conclusion, we report that encephalopathy can develop even with the dose of 5-FU lower than ever reported, and it should be considered as a differential diagnosis for proper management. PMID:16436463

  18. [Myoclonic encephalopathy associated with proton pump inhibitors].

    PubMed

    Boulliat, J; Polard, E; Colin, F; Bentué-Ferrer, D; Allain, H

    2004-03-01

    Two men (66 and 73 Years) with a cardiovascular history were hospitalized for rapid onset encephalopathy associated with myoclonia and an extrapyramidal syndrome. On the basis of the French Pharmacovigilance system, this symptomatology has been attributed to the coadministration of a proton pump inhibitor, lansoprazole (15mg/day) with levodopa. Lansoprazole withdrawal led to a normalisation of the situation. PMID:15037850

  19. Dysfunctional B-cell activation in cirrhosis due to hepatitis C infection associated with disappearance of CD27+ B-cell population

    PubMed Central

    Doi, Hiroyoshi; Iyer, Tara K.; Carpenter, Erica; Li, Hong; Chang, Kyong-Mi; Vonderheide, Robert H.; Kaplan, David E.

    2011-01-01

    Background Chronic hepatitis C virus infection is a leading cause of cirrhosis and hepatocellular carcinoma. Both advanced solid tumors and hepatitis C have previously been associated with memory B-cell dysfunction. In this study we sought to dissect the impact of viral infection, cirrhosis and liver cancer on memory B-cell frequency and function in the spectrum of HCV disease. Methods Peripheral blood from healthy donors, HCV-infected patients with F1–F2 liver fibrosis, HCV-infected patients with cirrhosis, patients with HCV-related hepatocellular carcinoma and non-HCV-infected cirrhotics were assessed for B-cell phenotype by flow cytometry. Isolated B-cells were stimulated with anti-CD40 antibodies and TLR9 agonist for assessment of costimulation marker expression, cytokine production, immunoglobulin production and CD4+ T-cell allostimulatory capacity. Results CD27+ memory B-cells, and more specifically CD27+IgM+ B-cells, were markedly less frequent in cirrhotic patients independent of HCV infection. Circulating B-cells in cirrhotics were hyporesponsive to CD40/TLR9 activation as characterized by CD70 upregulation, TNFβ secretion, IgG production and T-cell allostimulation. Lastly, blockade of TLR4 and TLR9 signaling abrogated the activation of normal donor B-cells by cirrhotic plasma suggesting a role for bacterial translocation in driving B-cell changes in cirrhosis. Conclusion Profound abnormalities in B-cell phenotype and function occur in cirrhosis independent of hepatitis C viral infection. These B-cell defects may explain in part the vaccine hyporesponsiveness and susceptibility to bacterial infection in this population. PMID:21932384

  20. Hepatitis Aand E Co-Infection with Worst Outcome.

    PubMed

    Saeed, Anjum; Cheema, Huma Arshad; Assiri, Asaad

    2016-06-01

    Infections are still a major problem in the developing countries like Pakistan because of poor sewage disposal and economic restraints. Acute viral hepatitis like Aand E are not uncommon in pediatric age group because of unhygienic food handling and poor sewage disposal, but majority recovers well without any complications. Co-infections are rare occurrences and physicians need to be well aware while managing such conditions to avoid worst outcome. Co-infection with hepatitis Aand E is reported occasionally in the literature, however, other concurrent infections such as hepatitis A with Salmonellaand hepatotropic viruses like viral hepatitis B and C are present in the literature. Co-infections should be kept in consideration when someone presents with atypical symptoms or unusual disease course like this presented case. We report here a girl child who had acute hepatitis A and E concurrent infections and presented with hepatic encephalopathy and had worst outcome, despite all the supportive measures being taken. PMID:27376213

  1. Adverse skin reactions due to pegylated interferon alpha 2b plus ribavirin combination therapy in a patient with chronic hepatitis C virus.

    PubMed

    Hashimoto, Yuki; Kanto, Hiromi; Itoh, Masatoshi

    2007-08-01

    Pegylated interferon (IFN)-alpha-2b with ribavirin has recently replaced "standard" IFN-alpha for the treatment of chronic hepatitis C. The most common side-effect of pegylated IFN-alpha-2b plus ribavirin combination therapy is localized inflammatory skin lesions at the site of injection. A 66-year-old female treated with once-weekly pegylated IFN-alpha-2b plus ribavirin for active chronic hepatitis C developed inflammatory skin lesions 2 months after starting antiviral treatment. The type of skin reactions observed were vesicle erythematous eruptions at the injection sites, and pruritic papular erythematous eruptions located on the face, neck, distal limbs, dorsa of the hands, trunk and buttocks away from the injection sites. Histological examination was performed on the pruritic papular erythematous eruption located on the left forearm, away from the injection sites. It showed epidermal spongiosis, a spongiotic microvesicle, and perivascular infiltration of the upper dermis with lymphocytes. The treatment was interrupted subsequently and the patient was rechallenged with pegylated IFN-alpha-2b plus ribavirin combination therapy, oral prednisolone with olopatadine hydrochloride and topical 0.1% diflucortolone valerate, which led to a significant improvement of skin lesions. Erythema with infiltration can occur at the injection sites of pegylated IFN-alpha-2b. However, the occurrence of vesicle erythematous eruptions away from the injection sites and autosensitization dermatitis apart from injection sites have not yet been frequently reported. PMID:17683392

  2. Causes of death in fulminant hepatic failure and relationship to quantitative histological assessment of parenchymal damage.

    PubMed

    Gazzard, B G; Portmann, B; Murray-Lyon, I M; Williams, R

    1975-10-01

    The clinical course and causes of death in 132 consecutive patients with fulminant hepatic failure and grade III or IV encephalopathy have been reviewed. 105 patients died and in 96 of these an autopsy examination was performed. In 36 patients there was cerebral oedema and the mean age of this group was significantly younger than the other fatal cases. In 28 patients death was attributed to major haemorrhage which originated in the gastrointestinal tract in 25. The prothrombin time ratio was not significantly greater in patients with major bleeding than in those without but they did have a significantly lower platelet count. Sepsis contributed to death in 12 patients. In 25 patients massive hepatic necrosis only was found at autopsy and death was considered to be due solely to hepatic failure. The degree of hepatocyte loss was assessed in 80 fatal cases by a histological morphometric technique on a needle specimen of liver taken immediately post-mortem. The proportion of the liver volume occupied by hepatocytes (hepatocyte volume fraction, HVF) was greatly reduced in all patients (normal 85+/-SD 5 percent) but the mean value was significantly higher in the patients dying with sepsis, cerebral oedema or haemorrhage than in the group in whom death was attributed solely to hepatic failure. There were ten patients in whom liver function was improving at the time of death which was due to cerebral (9) or haemorrhage (1). These observations suggest that many patients presently dying from fulminant hepatic failure may be expected to survive, once more effective therapy is available for the complications of the illness. PMID:172938

  3. Hepatitis virus panel

    MedlinePlus

    Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... or past infection, or immunity to hepatitis A Hepatitis B tests: Hepatitis B surface antigen (HBsAg), you have ...

  4. Hepatitis C and HIV

    MedlinePlus

    ... Problems : Hepatitis C Subscribe Translate Text Size Print Hepatitis C What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis B . Hepatitis C and HIV About 25% of people living ...

  5. Hepatitis B and HIV

    MedlinePlus

    ... Problems : Hepatitis B Subscribe Translate Text Size Print Hepatitis B What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis C . Hepatitis B and HIV About 10% of people living ...

  6. Development of an experimental rat model of hyperammonemic encephalopathy and evaluation of the effects of rifaximin.

    PubMed

    Tamaoki, Satoru; Suzuki, Hiroyuki; Okada, Mami; Fukui, Norio; Isobe, Mitsui; Saito, Tomoyuki

    2016-05-15

    Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with hepatic dysfunction. However, the precise mechanism of HE is unclear. To elucidate the mechanism, we developed a new rat model of HE with coma using a combination of subcutaneous splenic transposition, partial hepatectomy and portal vein stenosis. In this model, blood ammonia levels increase in the postcaval vein over time and markedly increase in the cerebrospinal fluid (CSF). The distribution of ammonia in the various blood vessels in the HE model suggests that the origin of peripheral blood and CSF ammonia is the mesenteric veins that drain blood from the gastrointestinal tract. Behavioral analysis revealed decreased pain response, increased passivity, and decreased pinna and corneal reflexes, followed by the development of coma. The development of coma in this model was frequent and reproducible. Increased S100 calcium-binding protein B (S100B: a biomarker for brain injury) in venous blood, as well as damaged brain tissue, increased intracranial pressure and cerebral edema were observed in rats with coma. A very high correlation was observed between the blood ammonia concentration in the postcaval vein and the onset of coma. Rifaximin, a poorly absorbed antibiotic that targets gut flora, significantly improved symptoms of HE. Based on these results, our rat model appears to reflect the pathological state of HE associated with acute liver failure and may be a useful model for analysis of hyperammonemic encephalopathy. PMID:26980242

  7. Hepatitis Testing

    MedlinePlus

    ... caused by viruses. They include hepatitis A, hepatitis B, and hepatitis C. To diagnose hepatitis, your health care provider will ask you about your medical history and symptoms, do a physical exam, and order blood tests. There are blood tests for each type of ...

  8. Serum levels of short-chain fatty acids in cirrhosis and hepatic coma.

    PubMed

    Clausen, M R; Mortensen, P B; Bendtsen, F

    1991-12-01

    Short-chain fatty acids cause reversible coma in animals and may contribute to the pathogenesis of the hepatic coma in humans. The concentrations of short-chain fatty acids in peripheral venous blood were significantly elevated in 15 patients with hepatic encephalopathy caused by cirrhosis (362 +/- 83 mumol/L; mean +/- S.E.M.) compared with 17 cirrhotic patients without encephalopathy (178 +/- 57 mumol/L) and 11 normal individuals (60 +/- 8 mumol/L). However, no correlation between the depth of coma and the level of short-chain fatty acids was found after repetitive measurements in the coma group. Compared with normal individuals, all short-chain fatty acids, except valerate, were elevated in patients with hepatic encephalopathy, whereas only the concentrations of isobutyrate and isovalerate were significantly elevated in cirrhotic patients without encephalopathy. The concentrations of short-chain fatty acids in 21 nonencephalopathic cirrhotic patients who underwent catheterization were equally distributed in the aorta (187 +/- 56 mumol/L), the hepatic vein (212 +/- 75 mumol/L), the azygos vein (140 +/- 37 mumol/L) and the renal vein (135 +/- 43 mumol/L) compared with peripheral venous blood (178 +/- 57 mumol/L). This study does not support the idea that short-chain fatty acids are of major importance in the pathogenesis of hepatic coma in patients with cirrhosis. PMID:1959851

  9. Erythropoietic and hepatic porphyrias.

    PubMed

    Gross, U; Hoffmann, G F; Doss, M O

    2000-11-01

    Porphyrias are divided into erythropoietic and hepatic manifestations. Erythropoietic porphyrias are characterized by cutaneous symptoms and appear in early childhood. Erythropoietic protoporphyria is complicated by cholestatic liver cirrhosis and progressive hepatic failure in 10%, of patients. Acute hepatic porphyrias (delta-aminolaevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) are characterized by variable extrahepatic gastrointestinal, neurological-psychiatric and cardiovascular manifestations requiring early diagnosis to avoid life-threatening complications. Acute hepatic porphyrias are pharmacogenetic and molecular regulatory diseases (without porphyrin accumulation) mainly induced by drugs, sex hormones, fasting or alcohol. The disease process depends on the derepression of hepatic delta-aminolaevulinic acid synthase following haem depletion. In contrast to the acute porphyrias, nonacute, chronic hepatic porphyrias such as porphyria cutanea tarda are porphyrin accumulation disorders leading to cutaneous symptoms associated with liver disease, especially caused by alcohol or viral hepatitis. Alcohol, oestrogens, haemodialysis, hepatitis C and AIDS are triggering factors. Porphyria cutanea tarda is the most common porphyria, followed by acute intermittent porphyria and erythropoietic protoporphyria. The molecular genetics of the porphyrias is very heterogenous. Nearly every family has its own mutation. The mutations identified account for the corresponding enzymatic deficiencies, which may remain clinically silent throughout life. Thus, the recognition of the overt disorder with extrahepatic manifestations depends on the demonstration of biochemical abnormalities due to these primary defects and compensatory hepatic overexpression of hepatic delta-aminolaevulinic acid synthase in the acute porphyrias. Consequently, haem precursors are synthesized in excess. The increased

  10. Head stereotypies in STXBP1 encephalopathy.

    PubMed

    Kim, Young Ok; Korff, Christian M; Villaluz, Mel Michel G; Suls, Arvid; Weckhuysen, Sarah; De Jonghe, Peter; Scheffer, Ingrid E

    2013-08-01

    STXBP1 encephalopathy is associated with a range of movement disorders. We observed head stereotypies in three patients. These comprised a slow (<1Hz), high-amplitude, horizontal, 'figure-of-eight' pattern, beginning at age 4-6 years and resulting in neck muscle hypertrophy, in two males; a faster (2-3Hz), side-to-side, 'no' movement, starting at the age of 9 years 6 months was observed in one female. Upper limb and truncal stereotypies and vocalization occurred intermittently with the head movements. The stereotypies increased with excitement but settled with concentration and sleep. Head and upper limb stereotypies are valuable clinical clues to the diagnosis of STXBP1 encephalopathy in patients with profound impairments. PMID:23763664

  11. Encephalopathy of infection and systemic inflammation.

    PubMed

    Young, G Bryan

    2013-10-01

    This review will discuss several intracranial infections and sepsis-associated encephalopathy. Intracranial infections and inflammation of interest to the neurologist and EEG technicians include viral and autoimmune encephalitides; bacterial, fungal, and other meningitides; cerebritis; and brain abscess and subdural empyema. Sepsis-associated encephalopathy refers to a diffuse brain dysfunction secondary to infection that is principally located outside of the central nervous system. It is much more common than all of the intracranial infections put together, at least for adults in Western society. It probably involves a number of mechanisms that are not mutually exclusive and likely vary from patient to patient. Morbidity and mortality are directly related to the severity of SAE. The earliest features of SAE are delirium and mild EEG slowing; it is crucial to recognize these early features and to search for and treat the underlying infection promptly to reduce mortality and morbidity. PMID:24084178

  12. Hashimoto's encephalopathy: A rare proteiform disorder.

    PubMed

    Montagna, Giacomo; Imperiali, Mauro; Agazzi, Pamela; D'Aurizio, Federica; Tozzoli, Renato; Feldt-Rasmussen, Ulla; Giovanella, Luca

    2016-05-01

    Hashimoto's encephalopathy (HE) is a rare not well understood, progressive and relapsing multiform disease, characterized by seizures, movement disorders, subacute cognitive dysfunction, psychiatric symptoms and responsiveness to steroid therapy. The disorder is generally associated with thyroid diseases and the most common feature is the presence of anti-thyroperoxidase antibodies (TPOAb). Patients are usually euthyroid or mildly hypothyroid at presentation. All age groups can be affected. The pathophysiology is still unclear, especially the link between elevated serum TPOAb and the encephalopathy. Most reported cases occurred in women and girls. Unspecific symptoms, non-pathognomonic laboratory neurophysiology and neuroimaging features make its diagnosis a real challenge for clinicians. The case of a 16 year old boy, with a clinical picture of HE associated with hypothyroidism, demonstrating an excellent response to high dose steroids is presented together with a systematic review of the literature. PMID:26849953

  13. Wernicke's encephalopathy induced by hyperemesis gravidarum

    PubMed Central

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

    2012-01-01

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

  14. Ciprofloxacin-associated posterior reversible encephalopathy

    PubMed Central

    Al Bu Ali, Waleed Hammad

    2013-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological syndrome characterised by numerous symptoms and of no specific aetiology. Headache, confusion, seizures, cortical visual disturbances or blindness are the key symptoms. As this syndrome is reversible and readily treated by interrupting or discontinuing the aetiology, it should sharply be acknowledged. Ciprofloxacin was associated with PRES in an adolescent male treated from chest infection. It was managed in a hospital intensive care unit and was observed until disappearance. PMID:23585504

  15. Transmissible Spongiform Encephalopathy and Meat Safety

    NASA Astrophysics Data System (ADS)

    Ward, Hester J. T.; Knight, Richard S. G.

    Prion diseases or transmissible spongiform encephalopathies (TSEs) comprise a wide-ranging group of neurodegenerative diseases found in animals and humans. They have diverse causes and geographical distributions, but have similar pathological features, transmissibility and, are ultimately, fatal. Central to all TSEs is the presence of an abnormal form of a normal host protein, namely the prion protein. Because of their potential transmissibility, these diseases have wide public health ramifications.

  16. Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion

    PubMed Central

    Hughes, Adrienne; Brown, Alisha; Valento, Matthew

    2016-01-01

    Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects. PMID:27625729

  17. [Drug therapy of patients with dyscirculatory encephalopathy].

    PubMed

    Macheret, Ie L; Khanenko, N V

    2002-01-01

    Results are submitted of treatment of discirculatory encephalopathy having developed against the background of arterial hypertension, with a combination of drugs aktovegin and captopril in 56 patients. The positive effect of the instituted monotherapy has been documented clinically, with correlation established with indices of additional methods of investigation. The secured results of treatment permit recommending actovegin and captopril for a wide use in practical medicine to treat patients in the above category. PMID:12145902

  18. Valproate-induced encephalopathy with predominant pancerebellar syndrome

    PubMed Central

    Verma, Rajesh; Kori, Prakash

    2012-01-01

    Valproate-induced hyperammonemic encephalopathy is a rare event clinically characterized by impaired sensorium, vomiting, headache, seizures and focal neurological deficits. The pathogenesis of this dreadful complication is not well understood, although hyperammonemia has been implicated in causation of encephalopathy. In this submission, we have highlighted a case of valproate-induced encephalopathy who presented mainly with bilateral cerebellar features and generalized slowing on electroencephalogram. High index of suspicion of valproate-induced hyperammonemic encephalopathy is required if diffuse ataxia is present as it is a potentially reversible clinical disorder. PMID:22345888

  19. Blood Biomarkers for Evaluation of Perinatal Encephalopathy

    PubMed Central

    Graham, Ernest M.; Burd, Irina; Everett, Allen D.; Northington, Frances J.

    2016-01-01

    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. PMID:27468268

  20. De novo mutations in epileptic encephalopathies.

    PubMed

    Allen, Andrew S; Berkovic, Samuel F; Cossette, Patrick; Delanty, Norman; Dlugos, Dennis; Eichler, Evan E; Epstein, Michael P; Glauser, Tracy; Goldstein, David B; Han, Yujun; Heinzen, Erin L; Hitomi, Yuki; Howell, Katherine B; Johnson, Michael R; Kuzniecky, Ruben; Lowenstein, Daniel H; Lu, Yi-Fan; Madou, Maura R Z; Marson, Anthony G; Mefford, Heather C; Esmaeeli Nieh, Sahar; O'Brien, Terence J; Ottman, Ruth; Petrovski, Slavé; Poduri, Annapurna; Ruzzo, Elizabeth K; Scheffer, Ingrid E; Sherr, Elliott H; Yuskaitis, Christopher J; Abou-Khalil, Bassel; Alldredge, Brian K; Bautista, Jocelyn F; Berkovic, Samuel F; Boro, Alex; Cascino, Gregory D; Consalvo, Damian; Crumrine, Patricia; Devinsky, Orrin; Dlugos, Dennis; Epstein, Michael P; Fiol, Miguel; Fountain, Nathan B; French, Jacqueline; Friedman, Daniel; Geller, Eric B; Glauser, Tracy; Glynn, Simon; Haut, Sheryl R; Hayward, Jean; Helmers, Sandra L; Joshi, Sucheta; Kanner, Andres; Kirsch, Heidi E; Knowlton, Robert C; Kossoff, Eric H; Kuperman, Rachel; Kuzniecky, Ruben; Lowenstein, Daniel H; McGuire, Shannon M; Motika, Paul V; Novotny, Edward J; Ottman, Ruth; Paolicchi, Juliann M; Parent, Jack M; Park, Kristen; Poduri, Annapurna; Scheffer, Ingrid E; Shellhaas, Renée A; Sherr, Elliott H; Shih, Jerry J; Singh, Rani; Sirven, Joseph; Smith, Michael C; Sullivan, Joseph; Lin Thio, Liu; Venkat, Anu; Vining, Eileen P G; Von Allmen, Gretchen K; Weisenberg, Judith L; Widdess-Walsh, Peter; Winawer, Melodie R

    2013-09-12

    Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10(-10) and P = 7.8 × 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum disorders. PMID:23934111

  1. Pathogenesis and management of alcoholic hepatitis.

    PubMed

    Haber, Paul S; Warner, Ross; Seth, Devanshi; Gorrell, Mark D; McCaughan, Geoffrey W

    2003-12-01

    Alcoholic hepatitis is a potentially life-threatening complication of alcoholic abuse, typically presenting with symptoms and signs of hepatitis in the presence of an alcohol use disorder. The definitive diagnosis requires liver biopsy, but this is not generally required. The pathogenesis is uncertain, but relevant factors include metabolism of alcohol to toxic products, oxidant stress, acetaldehyde adducts, the action of endotoxin on Kupffer cells, and impaired hepatic regeneration. Mild alcoholic hepatitis recovers with abstinence and the long-term prognosis is determined by the underlying disorder of alcohol use. Severe alcoholic hepatitis is recognized by a Maddrey discriminant function >32 and is associated with a short-term mortality rate of almost 50%. Primary therapy is abstinence from alcohol and supportive care. Corticosteroids have been shown to be beneficial in a subset of severely ill patients with concomitant hepatic encephalopathy, but their use remains controversial. Pentoxifylline has been shown in one study to improve short-term survival rates. Other pharmacological interventions, including colchicine, propylthiouracil, calcium channel antagonists, and insulin with glucagon infusions, have not been proven to be beneficial. Nutritional supplementation with available high-calorie, high-protein diets is beneficial, but does not improve mortality. Orthotopic liver transplantation is not indicated for patients presenting with alcoholic hepatitis who have been drinking until the time of admission, but may be considered in those who achieve stable abstinence if liver function fails to recover. PMID:14675260

  2. Retinal function and morphology are altered in cattle infected with the prion disease transmissible mink encephalopathy.

    PubMed

    Smith, J D; Greenlee, J J; Hamir, A N; Richt, J A; Greenlee, M H West

    2009-09-01

    Transmissible spongiform encephalopathies (TSEs) are a group of diseases that result in progressive and invariably fatal neurologic disease in both animals and humans. TSEs are characterized by the accumulation of an abnormal protease-resistant form of the prion protein in the central nervous system. Transmission of infectious TSEs is believed to occur via ingestion of prion protein-contaminated material. This material is also involved in the transmission of bovine spongiform encephalopathy ("mad cow disease") to humans, which resulted in the variant form of Creutzfeldt-Jakob disease. Abnormal prion protein has been reported in the retina of TSE-affected cattle, but despite these observations, the specific effect of abnormal prion protein on retinal morphology and function has not been assessed. The objective of this study was to identify and characterize potential functional and morphologic abnormalities in the retinas of cattle infected with a bovine-adapted isolate of transmissible mink encephalopathy. We used electroretinography and immunohistochemistry to examine retinas from 10 noninoculated and 5 transmissible mink encephalopathy-inoculated adult Holstein steers. Here we show altered retinal function, as evidenced by prolonged implicit time of the electroretinogram b-wave, in transmissible mink encephalopathy-infected cattle before the onset of clinical illness. We also demonstrate disruption of rod bipolar cell synaptic terminals, indicated by decreased immunoreactivity for the alpha isoform of protein kinase C and vesicular glutamate transporter 1, and activation of Müller glia, as evidenced by increased glial fibrillary acidic protein and glutamine synthetase expression, in the retinas of these cattle at the time of euthanasia due to clinical deterioration. This is the first study to identify both functional and morphologic alterations in the retinas of TSE-infected cattle. Our results support future efforts to focus on the retina for the development of

  3. Pharmacokinetics of hepatitis C virus NS5A inhibitor JNJ-56914845 (GSK2336805) in subjects with hepatic impairment.

    PubMed

    Adkison, Kimberly K; Gan, Jianjun; Elko-Simms, Lucinda; Gardner, Stephen; Dumont, Etienne; Jones, Lori S; Saunders, Joanne; Marbury, Thomas; Smith, William; Berg, Jolene; Galloway, Christopher; Stump, Patrick J

    2015-09-01

    JNJ-56914845 (GSK2336805) is a hepatitis C virus nonstructural protein 5A inhibitor under development for the treatment of chronic hepatitis C (CHC) infection. This open-label, parallel-group, 2-part study evaluated the pharmacokinetics and safety of a single oral 60 mg dose of JNJ-56914845 in 4 cohorts: healthy, mild, moderate, and severe hepatic impairment (n = 8/cohort). Severity of hepatic impairment was categorized using Child-Pugh score, and the healthy subjects were matched for age, sex, body mass index, and smoking status to the moderate hepatic impairment cohort. JNJ-56914845 plasma AUC0-∞ was 26%, 52%, and 45% lower in subjects with mild, moderate, and severe hepatic impairment, respectively, relative to healthy subjects with no difference in half-life among the groups. The apparent oral clearance and volume of distribution were higher in subjects with hepatic impairment. The lower plasma concentrations were largely explained by decreased plasma protein binding in hepatically impaired subjects. One subject with severe hepatic impairment had 2 non-drug-related serious adverse events: an esophageal bleed requiring hospitalization, encephalopathy. Although hepatically impaired subjects have lower exposures than healthy matched controls, they had similar or slightly higher exposures than those observed in past studies of noncirrhotic, CHC patients, suggesting that no dose adjustments for hepatic impairment will be needed. PMID:25857714

  4. Genetic investigations of the epileptic encephalopathies: Recent advances.

    PubMed

    Myers, C T; Mefford, H C

    2016-01-01

    The epileptic encephalopathies (EEs) are a group of epilepsy syndromes characterized by multiple seizure types, abundant epileptiform activity, and developmental delay or regression. Advances in genomic technologies over the past decade have accelerated our understanding of the genetic etiology of EE, which is largely due to de novo mutations. Chromosome microarrays to detect copy number variants identify a genomic cause in at least 5-10% of cases. Next-generation sequencing in the form of gene panels or whole exome sequencing have highlighted the role of de novo sequence changes and revealed extensive genetic heterogeneity. The novel gene discoveries in EE implicate diverse cellular pathways including chromatin remodeling, transcriptional regulation, and mTOR regulation in the etiology of epilepsy, highlighting new targets for potential therapeutic intervention. In this chapter, we discuss the rapid pace of gene discovery in EE facilitated by genomic technologies and highlight several novel genes and potential therapies. PMID:27323938

  5. In vivo assessment of diet-induced rat hepatic steatosis development by percutaneous single-fiber spectroscopy detects scattering spectral changes due to fatty infiltration

    NASA Astrophysics Data System (ADS)

    Piao, Daqing; Sultana, Nigar; Holyoak, G. Reed; Ritchey, Jerry W.; Wall, Corey R.; Murray, Jill K.; Bartels, Kenneth E.

    2015-11-01

    This study explores percutaneous single-fiber spectroscopy (SfS) of rat livers undergoing fatty infiltration. Eight test rats were fed a methionine-choline-deficient (MCD) diet, and four control rats were fed a normal diet. Two test rats and one control rat were euthanized on days 12, 28, 49, and 77 following initiation of the diet, after percutaneous SfS of the liver under transabdominal ultrasound guidance. Histology of each set of the two euthanized test rats showed mild and mild hepatic lipid accumulations on day 12, moderate and severe on day 28, severe and mild on day 49, and moderate and mild on day 77. Livers with moderate or higher lipid accumulation generally presented higher spectral reflectance intensity when compared to lean livers. Livers of the eight test rats on day 12, two of which had mild lipid accumulation, revealed an average scattering power of 0.37±0.14 in comparison to 0.07±0.14 for the four control rats (p<0.01). When livers of the test rats with various levels of fatty infiltration were combined, the average scattering power was 0.36±0.15 in comparison to 0.14±0.24 of the control rats (0.05

  6. Current Management of Alcoholic Hepatitis and Future Therapies

    PubMed Central

    Saberi, Behnam; Dadabhai, Alia S.; Jang, Yoon-Young; Gurakar, Ahmet; Mezey, Esteban

    2016-01-01

    Abstract Alcohol is one of the most common etiologies of liver disease, and alcoholic liver disease overall is the second most common indication for liver transplantation in the United States. It encompasses a spectrum of disease, including fatty liver disease, alcoholic hepatitis (AH), and alcoholic cirrhosis. AH can range from mild to severe disease, with severe disease being defined as: Discriminant Function (DF) ≥ 32, or Model for End-stage Liver Disease (MELD) ≥ 21, or presence of hepatic encephalopathy. Management of the mild disease consists mainly of abstinence and supportive care. Severe AH is associated with significant mortality. Currently, there is no ideal medical treatment for this condition. Besides alcohol cessation, corticosteroids have been used with conflicting results and are associated with an inherent risk of infection. Overall steroids have shown short term benefit when compared to placebo, but they have no obvious long term benefits. Pentoxifylline does not improve survival in patients with severe AH and is no longer recommended based on the results of the STOPAH (Steroid Or Pentoxifylline for Alcoholic Hepatitis) trial. Anti-tumor necrosis factor (TNF) agents are associated with increased risk of life threatening infections and death. Currently, early stage trials are underway, mainly targeting novel pathways based on disease pathogenesis, including modulation of innate immune system, inhibition of gut-liver axis and cell death pathways, and activation of transcription factor farnesyl X receptor (FXR). Future treatment may lie in human induced pluripotent stem cell (iPSC) technology, which is currently under investigation for the study of pathogenesis, drug discovery, and stem cell transplantation. Liver transplantation has been reported with good results in highly selected patients but is controversial due to limited organ supply. PMID:27350941

  7. Transient widespread cortical and splenial lesions in acute encephalitis/encephalopathy associated with primary Epstein-Barr virus infection.

    PubMed

    Zhang, Shuo; Feng, Juan; Shi, Yifang

    2016-01-01

    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. PMID:26600186

  8. Hepatitis B and Hepatitis C in Pregnancy

    MedlinePlus

    ... infected with the hepatitis B virus, can I breastfeed? • If I am infected with the hepatitis B ... infected with the hepatitis C virus, can I breastfeed? • Glossary What are hepatitis B and hepatitis C ...

  9. A rare MeCP2_e1 mutation first described in a male patient with severe neonatal encephalopathy.

    PubMed

    Soffer, Omri David; Sidlow, Richard

    2016-07-01

    Specific mutations in MECP2 cause Rett syndrome (RTT) in females whereas other mutations in the same gene cause several other syndromes in males, including X-linked intellectual disability (with and without spasticity) (OMIM 300055) and X-linked intellectual disability due to increased dosage of MECP2 (OMIM 300260). Males can also manifest an entity known as MECP2-related severe neonatal encephalopathy whose mutations are identical to those in females with RTT. We describe here the first case of MECP2-related severe neonatal encephalopathy caused by a mutation in exon one of MECP2, a mutation rarely identified in females with RTT. © 2016 Wiley Periodicals, Inc. PMID:27090848

  10. [A 6-year-old girl who exhibited residual reading disorder during the course of acute encephalopathy].

    PubMed

    Nagaharu, Sachiko; Inaba, Yuji; Motobayashi, Mitsuo; Misawa, Yuka; Fukuyama, Tetsuhiro; Higuchi, Tsukasa; Harada, Machiko

    2012-11-01

    We assessed a 6-year-old girl who developed status epilepticus and exhibited transient aphasia during the course of acute encephalopathy with late reduced diffusion, and who had a residual reading disorder in the recovery period. The aphasia appeared to be fluent aphasia and anomia, suggesting that the reading disorder during the recovery process was due to impairment of the phonological process. There were no biphasic seizures during the course of the patient's illness, but this case was acute encephalopathy with febrile convulsive status epilepticus (AEFCSE) from the standpoint of the characteristic imaging findings. Lesions in the left parietal and temporal lobes were detected on MRI diffusion-weighted images and by SPECT and MRS, and they appeared to be the lesions responsible for the aphasia and residual reading disorder. This case appears to be important from the standpoint of assessing the pathophysiology and the treatment of coexisting illness observed in acute encephalopathy. PMID:23240531

  11. Neem oil poisoning: Case report of an adult with toxic encephalopathy.

    PubMed

    Mishra, Ajay; Dave, Nikhil

    2013-09-01

    Neem oil has widespread use in Indian subcontinent due to its many bioactive properties. Azadirachtin, an active ingredient, is implicated in causing the effects seen in neem oil poisoning. Neem oil poisoning is rare in adults. This report highlights the toxicity associated with neem oil poisoning in an elderly male. The patient presented with vomiting, seizures, metabolic acidosis, and toxic encephalopathy. The patient recovered completely with symptomatic treatment. PMID:24339648

  12. Hepatitis virus panel

    MedlinePlus

    Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... There are different tests for hepatitis A and B. A positive test is ... may mean: You currently have a hepatitis infection. This may ...

  13. Hepatitis C and Incarceration

    MedlinePlus

    HEPATITIS C & INCARCERATION What is hepatitis? “Hepatitis” means inflammation or swelling of the liver. The liver is an important ... viral hepatitis: Hepatitis A, Hepatitis B, and Hepatitis C. They are all different from each other and ...

  14. Hepatitis C: Treatment

    MedlinePlus

    ... Public Home » Hepatitis C » Hepatitis C Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis C Treatment for Veterans and the Public Treatment ...

  15. Hepatic ischemia

    MedlinePlus

    Hepatic ischemia is a condition in which the liver does not get enough blood or oxygen, causing injury to ... pressure from any condition can lead to hepatic ischemia. Such conditions may include: Abnormal heart rhythms Dehydration ...

  16. Hepatitis D

    MedlinePlus

    ... if the hepatitis B virus is also present. Transmission Hepatitis D can be found in the blood, ... other body fluids of people who are infected. Transmission happens when infected body fluid enters another person’s ...

  17. Autoimmune hepatitis

    MedlinePlus

    Lupoid hepatitis; Chronic acute liver disease ... This form of hepatitis is an autoimmune disease . The body's immune system cannot tell the difference between healthy body tissue and harmful, outside ...

  18. Hepatitis C

    MedlinePlus

    ... 2014 Select a Language: Fact Sheet 507 Hepatitis C WHAT IS HEPATITIS C? HOW IS IT DIAGNOSED? ... treatment may be less likely to work. Hep C treatment is less effective for coinfected people. Cure ...

  19. Hepatitis A

    MedlinePlus

    ... an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... washed in untreated water Putting into your mouth a finger or object that came into contact with ...

  20. Hepatitis B

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000279.htm Hepatitis B To use the sharing features on this page, please enable JavaScript. Hepatitis B is irritation and swelling (inflammation) of the ...

  1. Hepatic osteodystrophy.

    PubMed

    Gatta, Angelo; Verardo, Alberto; Di Pascoli, Marco; Giannini, Sandro; Bolognesi, Massimo

    2014-09-01

    Metabolic disturbances of bone are frequent in patients with chronic liver disease. The prevalence of osteoporosis among patients with advanced chronic liver disease is reported between 12% and 55%; it is higher in primary biliary cirrhosis. All patients with advanced liver disease should be screened for osteoporosis with a densitometry, especially if the etiology is cholestatic and in the presence of other risk factors. Clinical relevance of hepatic osteodystrophy increases after liver transplantation. After liver transplant, a rapid loss of bone mineral density can be detected in the first 6 months, followed by stabilization and slight improvement of the values. At the time of transplantation, bone density values are very important prognostic factors. Therapy of hepatic osteodystrophy is based primarily on the control of risk factors: cessation of tobacco and alcohol assumption, reduction of caffeine ingestion, exercise, supplementation of calcium and vitamin D, limitation of drugs such as loop diuretics, corticosteroids, cholestyramine. Bisphosphonates have been proposed for the therapy of osteoporosis in patients with liver disease, particularly after liver transplantation. The possible side effects of oral administration of bisphosphonates, such as the occurrence of esophageal ulcerations, are of particular concern in patients with liver cirrhosis and portal hypertension, due to the risk of gastrointestinal hemorrhage from ruptured esophageal varices, although this risk is probably overestimated. PMID:25568651

  2. Hepatitis A

    MedlinePlus

    ... is an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... suggest medicines to help relieve your symptoms. The hepatitis A vaccine can prevent HAV. Good hygiene can also ...

  3. Hepatitis C

    MedlinePlus

    ... an inflammation of the liver. One type, hepatitis C, is caused by the hepatitis C virus (HCV). It usually spreads through contact with ... childbirth. Most people who are infected with hepatitis C don't have any symptoms for years. If ...

  4. Hepatitis A

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​​ Alternate Language URL Español Hepatitis A Page Content On this page: What is ... Nutrition Points to Remember Clinical Trials What is hepatitis A? Hepatitis * A is a virus , or infection, ...

  5. Autoimmune Hepatitis

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​​ Alternate Language URL Autoimmune Hepatitis Page Content On this page: What is autoimmune ... Points to Remember Clinical Trials What is autoimmune hepatitis? Autoimmune hepatitis is a chronic—or long lasting— ...

  6. Typical and atypical cases of bovine spongiform encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy of cattle, first detected in 1986 in the United Kingdom and subsequently in other countries. It is the most likely cause of variant Creutzfeldt-Jakob disease (vCJD) in humans, but the origin of BSE has not been eluci...

  7. The Spectrum of Disease in Chronic Traumatic Encephalopathy

    ERIC Educational Resources Information Center

    McKee, Ann C.; Stein, Thor D.; Nowinski, Christopher J.; Stern, Robert A.; Daneshvar, Daniel H.; Alvarez, Victor E.; Lee, Hyo-Soon; Hall, Garth; Wojtowicz, Sydney M.; Baugh, Christine M.; Riley, David O.; Kubilus, Caroline A.; Cormier, Kerry A.; Jacobs, Matthew A.; Martin, Brett R.; Abraham, Carmela R.; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.; Cantu, Robert C.

    2013-01-01

    Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging…

  8. Evaluation of the zoonotic potential of transmissible mink encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Successful transmission of Transmissible Mink Encephalopathy (TME) to cattle supports the bovine hypothesis to 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 as...

  9. Comparison of Transmissible Mink Encephalopathy Isolates in Raccoons

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Owing to its susceptibility to various transmissible spongiform encephalopathies (TSE) and relatively short incubation times, the raccoon (Procyon lotor) has been suggested as a model for TSE strain differentiation. Transmissible mink encephalopathy (TME) is a prion disease of undetermined origin in...

  10. Acute Pancreatitis, Hepatitis and Bone Erosion in Acute Yellow Phosphorous Compound Poisoning - A Rare Complication.

    PubMed

    Kamarthi, Prabhakar; Subramani, Parimala; Gopu, Arun Vardharaju; Prasad, Reddy; Srinivasa, Chandrakala

    2016-06-01

    We report a case of acute pancreatitis and hepatitis following ingestion of yellow phosphorous. The condition of the patient progressed to encephalopathy and bony erosion of the nasal septum. Fungal mass was observed in both the nasal cavities by endoscopy. Microbiological investigation revealed the identity of the fungus as Aspergillus flavus and Candida tropicalis. Patient improved with fluconazole treatment. PMID:27504287

  11. Acute Pancreatitis, Hepatitis and Bone Erosion in Acute Yellow Phosphorous Compound Poisoning – A Rare Complication

    PubMed Central

    Kamarthi, Prabhakar; Gopu, Arun Vardharaju; Prasad, Reddy; Srinivasa, Chandrakala

    2016-01-01

    We report a case of acute pancreatitis and hepatitis following ingestion of yellow phosphorous. The condition of the patient progressed to encephalopathy and bony erosion of the nasal septum. Fungal mass was observed in both the nasal cavities by endoscopy. Microbiological investigation revealed the identity of the fungus as Aspergillus flavus and Candida tropicalis. Patient improved with fluconazole treatment. PMID:27504287

  12. Primary brain tumors and posterior reversible encephalopathy syndrome

    PubMed Central

    Kamiya-Matsuoka, Carlos; Cachia, David; Olar, Adriana; Armstrong, Terri S.; Gilbert, Mark R.

    2014-01-01

    Background Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic encephalopathic state associated with reversible cerebral vasogenic edema. It is an increasingly recognized occurrence in the oncology population. However, it is very uncommon in patients with primary brain tumors (PBTs). The aim of this study was to analyze the clinicoradiological features and report the clinical outcomes of PRES in PBT patients. Methods We identified 4 cases with PBT who developed PRES at MD Anderson Cancer Center (MDACC) between 2012 and 2014. Clinical and radiological data were abstracted from their records. In addition, we also solicited 8 cases from the literature. Results The median age at PRES onset was 19 years, male-to-female ratio was 1:1, and the syndrome occurred in patients with ependymoma (n = 4), glioblastoma (n = 3), diffuse intrinsic pontine glioma (DIPG; n = 3), juvenile pilocytic astrocytoma (n = 1), and atypical meningioma (n = 1). Two glioblastomas and 2 DIPG cases received bevacizumab and vandetanib before the onset of symptoms, respectively. The most common clinical presentation was seizures (n = 7). Three MDACC patients recovered completely in 3–4 weeks after the onset of symptoms. One patient died due to active cancer and several comorbidities including PRES. Conclusions Hypertension seems to be the most important coexisting risk factor for development of PRES; however, the potential effects of chemotherapeutic agents in the pathogenesis of PRES should also be examined. The clinicoradiological course of PRES in PBT patients did not vary from the classical descriptions of PRES found in other causes. PRES must be considered as part of the differential diagnosis in patients with PBTs presenting with seizures or acute encephalopathy. PMID:26034631

  13. Direct acting antiviral therapy is curative for chronic hepatitis C/autoimmune hepatitis overlap syndrome

    PubMed Central

    Sahebjam, Farhad; Hajdu, Cristina H; Nortey, Esther; Sigal, Samuel H

    2016-01-01

    Autoimmune phenomena are common in patients with chronic hepatitis C. Management of chronic hepatitis C/autoimmune hepatitis syndrome has until recently been problematic due to the adverse effects of interferon on autoimmune processes and immunosuppression on viral replication. In this report we describe 3 patients with chronic hepatitis C/autoimmune hepatitis overlap syndrome who responded rapidly to direct acting anti-viral therapy. The resolution of the autoimmune process supports a direct viral role in its pathophysiology. PMID:27190580

  14. A Case of Severe Ganciclovir-Induced Encephalopathy

    PubMed Central

    Sakamoto, Hikaru; Hirano, Makito; Nose, Kazuhiro; Ueno, Shuichi; Oki, Takashi; Sugimoto, Koichi; Nishioka, Tsukasa; Kusunoki, Susumu; Nakamura, Yusaku

    2013-01-01

    Background Ganciclovir, a drug against cytomegalovirus (CMV) infection, is generally well tolerated, but can cause neurotoxicity such as encephalopathy. Although ganciclovir-induced encephalopathy has been described in several reports, a literature search revealed that ganciclovir concentrations in the blood or cerebrospinal fluid were previously measured in only 3 patients with encephalopathy. Symptoms usually include confusion and disturbed consciousness, which mimic CMV encephalitis. Prompt and accurate diagnosis is thus sometimes difficult, and is derived solely from accumulated clinical information of definite cases, since ganciclovir concentrations, not routinely measured, become available after several days or a few weeks. Case Presentation Here, we summarize clinical information of all patients with definite ganciclovir-induced encephalopathy including our own patient, who had severe symptoms, with the highest reported trough concentration of ganciclovir in the blood, and underwent therapeutic dialysis with complete recovery. Conclusion Our summary of patients with definite encephalopathy could lead to prompt and accurate diagnoses. PMID:24403897

  15. The Expanding Clinical Spectrum of Genetic Pediatric Epileptic Encephalopathies.

    PubMed

    Shbarou, Rolla; Mikati, Mohamad A

    2016-05-01

    Pediatric epileptic encephalopathies represent a clinically challenging and often devastating group of disorders that affect children at different stages of infancy and childhood. With the advances in genetic testing and neuroimaging, the etiologies of these epileptic syndromes are now better defined. The various encephalopathies that are reviewed in this article include the following: early infantile epileptic encephalopathy or Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, West syndrome, severe myoclonic epilepsy in infancy (Dravet syndrome), Landau-Kleffner syndrome, Lennox-Gastaut syndrome, and epileptic encephalopathy with continuous spike-and-wave during sleep. Their clinical features, prognosis as well as underlying genetic etiologies are presented and updated. PMID:27544470

  16. Histopathological and imaging modifications in chronic ethanolic encephalopathy.

    PubMed

    Folescu, Roxana; Zamfir, Carmen Lăcrămioara; Sişu, Alina Maria; Motoc, Andrei Gheorghe Marius; Ilie, Adrian Cosmin; Moise, Marius

    2014-01-01

    Chronic abuse of alcohol triggers different types of brain damage. The Wernicke-Korsakoff syndrome gets together Wernicke's encephalopathy and Korsakoff's syndrome. Another type of encephalopathy associated with chronic ethanol consumption is represented by the Marchiafava-Bignami malady or syndrome, an extremely rare neurological disorder, which is characterized by a demielinization of corpus callosum, extending as far as a necrosis. Because the frequency of ethanolic encephalopathy is increased and plays a major role in the sudden death of ethanolic patients, we have studied the chronic ethanolic encephalopathy both in deceased and in living patients, presenting different pathologies related to the chronic ethanol consumption. The present study investigated the effects of chronic ethanolic encephalopathy on the central nervous system based both on the histopathological exam of the tissular samples and the imaging investigation, such as MRI and CT. PMID:25329105

  17. Chronic Traumatic Encephalopathy and Movement Disorders: Update.

    PubMed

    Tarazi, Apameh; Tator, Charles H; Tartaglia, Maria Carmela

    2016-05-01

    Association of repetitive brain trauma with progressive neurological deterioration has been described since the 1920s. Punch drunk syndrome and dementia pugilistica (DP) were introduced first to explain symptoms in boxers, and more recently, chronic traumatic encephalopathy (CTE) has been used to describe a neurodegenerative disease in athletes and military personal with a history of multiple concussions. Although there are many similarities between DP and CTE, a number of key differences are apparent especially when comparing movement impairments. The aim of this review is to compare clinical and pathological aspects of DP and CTE with a focus on disorders of movement. PMID:27021775

  18. Post-dengue encephalopathy and Parkinsonism.

    PubMed

    Fong, Choong Yi; Hlaing, Chaw Su; Tay, Chee Geap; Ong, Lai Choo

    2014-10-01

    Parkinsonism as a neurologic manifestation of dengue infection is rare with only 1 reported case in an adult patient. We report a case of a 6-year-old child with self-limiting post-dengue encephalopathy and Parkinsonism. This is the first reported pediatric case of post-dengue Parkinsonism and expands the neurologic manifestations associated with dengue infection in children. Clinicians should consider the possibility of post-dengue Parkinsonism in children with a history of pyrexia from endemic areas of dengue. PMID:24776518

  19. Ammonia encephalopathy and awake craniotomy for brain language mapping: cause of failed awake craniotomy.

    PubMed

    Villalba Martínez, G; Fernández-Candil, J L; Vivanco-Hidalgo, R M; Pacreu Terradas, S; León Jorba, A; Arroyo Pérez, R

    2015-05-01

    We report the case of an aborted awake craniotomy for a left frontotemporoinsular glioma due to ammonia encephalopathy on a patient taking Levetiracetam, valproic acid and clobazam. This awake mapping surgery was scheduled as a second-stage procedure following partial resection eight days earlier under general anesthesia. We planned to perform the surgery with local anesthesia and sedation with remifentanil and propofol. After removal of the bone flap all sedation was stopped and we noticed slow mentation and excessive drowsiness prompting us to stop and control the airway and proceed with general anesthesia. There were no post-operative complications but the patient continued to exhibit bradypsychia and hand tremor. His ammonia level was found to be elevated and was treated with an infusion of l-carnitine after discontinuation of the valproic acid with vast improvement. Ammonia encephalopathy should be considered in patients treated with valproic acid and mental status changes who require an awake craniotomy with patient collaboration. PMID:25475698

  20. Magnetic Resonance Imaging of Bilirubin Encephalopathy: Current Limitations and Future Promise

    PubMed Central

    Wisnowski, Jessica L.; Panigrahy, Ashok; Painter, Michael J.; Watchko, Jon F.

    2014-01-01

    Infants with chronic bilirubin encephalopathy often demonstrate abnormal bilateral, symmetric, high-signal intensity on T2-weighted magnetic resonance imaging of the globus pallidus and subthalamic nucleus, consistent with the neuropathology of kernicterus. Early magnetic resonance imaging of at risk infants, while frequently showing increased T1-signal in these regions, may give false positive findings due to the presence of myelin in these structures. Advanced magnetic resonance imaging including diffusion-weighted imaging, magnetic resonance spectroscopy, and diffusion tensor imaging with tractography may shed new insights into the pathogenesis of bilirubin-induced brain injury and the neural basis of long-term disability in infants and children with chronic bilirubin encephalopathy. PMID:25267277

  1. Posterior Reversible Encephalopathy Syndrome with Bilateral Independent Epileptic Foci Precipitated By Guillain-Barrè Syndrome.

    PubMed

    Rossi, Rosario; Saddi, Maria Valeria; Mela, Alessandro; Ticca, Anna

    2016-01-01

    We report the case of a 56-year-old woman who developed status epilepticus (SE) related to independent occipital foci as clinical manifestation of posterior reversible encephalopathy syndrome (PRES) in the background of Guillain-Barrè syndrome (GBS). SE resulted from a series of focal seizures clinically characterized by left- and rightward deviations of the head and consequent oculoclonic movements. Electroencephalography recorded independent seizure activity in both occipital regions with alternate involvement of the two cerebral hemispheres. The epileptic foci corresponded topographically to parenchymal abnormalities of PRES in the occipital lobes. The manifestation of bilateral, independent occipital seizures with alternate deviations of the head and oculoclonic movements, previously not reported in patients with PRES, highlights the acute epileptogenicity of the cerebral lesions in this syndrome. Despite the variable clinical expression of seizures due to occipital damage in PRES, the development of independent seizure activity in both occipital lobes might represent a distinctive epileptic phenomenon of this encephalopathy. PMID:27403359

  2. Two patients with Hashimoto's encephalopathy and uncontrolled diabetes successfully treated with levetiracetam.

    PubMed

    Wong, Laura C; Freeburg, Joseph D; Montouris, Georgia D; Hohler, Anna D

    2015-01-15

    Hashimoto's encephalopathy (HE) is a rare syndrome of progressive or relapsing-remitting encephalopathy associated with elevated serum anti-thyroid antibody concentrations. It is thought to be an autoimmune process that generally responds well to high-dose corticosteroids and other immunomodulatory therapies. However, some patients are unresponsive to steroids or are unable to receive immune therapy. A viable alternative is needed for this group. Given that seizure and EEG abnormalities are commonly associated with this syndrome, we postulate that treatment with levetiracetam, which has duel anti-inflammatory and anti-seizure mechanisms, might show clinical benefit. We present the cases of two patients who met the criteria for HE but were unable to receive steroids due to labile diabetes. They were both successfully treated with levetiracetam. PMID:25467138

  3. Posterior Reversible Encephalopathy Syndrome with Bilateral Independent Epileptic Foci Precipitated By Guillain-Barrè Syndrome

    PubMed Central

    Rossi, Rosario; Saddi, Maria Valeria; Mela, Alessandro; Ticca, Anna

    2016-01-01

    We report the case of a 56-year-old woman who developed status epilepticus (SE) related to independent occipital foci as clinical manifestation of posterior reversible encephalopathy syndrome (PRES) in the background of Guillain-Barrè syndrome (GBS). SE resulted from a series of focal seizures clinically characterized by left- and rightward deviations of the head and consequent oculoclonic movements. Electroencephalography recorded independent seizure activity in both occipital regions with alternate involvement of the two cerebral hemispheres. The epileptic foci corresponded topographically to parenchymal abnormalities of PRES in the occipital lobes. The manifestation of bilateral, independent occipital seizures with alternate deviations of the head and oculoclonic movements, previously not reported in patients with PRES, highlights the acute epileptogenicity of the cerebral lesions in this syndrome. Despite the variable clinical expression of seizures due to occipital damage in PRES, the development of independent seizure activity in both occipital lobes might represent a distinctive epileptic phenomenon of this encephalopathy. PMID:27403359

  4. A Fatal Case of Wernicke's Encephalopathy after Sleeve Gastrectomy for Morbid Obesity

    PubMed Central

    Manatakis, Dimitrios K.; Georgopoulos, Nikolaos

    2014-01-01

    Wernicke's encephalopathy is an acute neuropsychiatric disorder, due to thiamine (vitamin B1) deficiency. It is traditionally described in chronic alcohol abusers; however obesity surgery is an emerging cause, as the number of bariatric procedures increases. A high index of clinical suspicion is required, since initial symptoms may be nonspecific and the classic triad of ophthalmoplegia, gait and stance disorders, and mental confusion is present only in one-third of patients. Laboratory tests can be within normal range and typical MRI brain lesions are found only in 50% of cases. Aggressive supplementation with intravenous thiamine should not be delayed until confirmation of diagnosis, as it may fully reverse symptoms, but almost half the patients will still display permanent neurological deficit. We present our experience with a fatal case of Wernicke's encephalopathy, following laparoscopic sleeve gastrectomy for morbid obesity. PMID:25276464

  5. Reducing the Cost of the Diagnostic Odyssey in Early Onset Epileptic Encephalopathies

    PubMed Central

    Mansilla, M. Adela; Campbell, Colleen A.

    2016-01-01

    Whole exome sequencing (WES) has revolutionized the way we think about and diagnose epileptic encephalopathies. Multiple recent review articles discuss the benefits of WES and suggest various algorithms to follow for determining the etiology of epileptic encephalopathies. Incorporation of WES in these algorithms is leading to the discovery of new genetic diagnoses of early onset epileptic encephalopathies (EOEEs) at a rapid rate; however, WES is not yet a universally utilized diagnostic tool. Clinical WES may be underutilized due to provider discomfort in ordering the test or perceived costliness. At our hospital WES is not routinely performed for patients with EOEE due to limited insurance reimbursement. In fact for any patient with noncommercial insurance (Medicaid) the institution does not allow sending out WES as this is not “established”/“proven to be highly useful and cost effective”/“approved test” in patients with epilepsy. Recently, we performed WES on four patients from three families and identified novel mutations in known epilepsy genes in all four cases. These patients had State Medicaid as their insurance carrier and were followed up for several years for EOEE while being worked up using the traditional/approved testing methods. Following a recently proposed diagnostic pathway, we analyzed the cost savings (US dollars) that could be accrued if WES was performed earlier in the diagnostic odyssey. This is the first publication that addresses the dollar cost of traditional testing in EOEE as performed in these four cases versus WES and the potential cost savings. PMID:27243033

  6. Human hereditary hepatic porphyrias.

    PubMed

    Nordmann, Yves; Puy, Hervé

    2002-11-01

    The human hereditary hepatic porphyrias are diseases due to marked deficiencies of enzymes in the heme biosynthetic pathway. Porphyrias can be classified as either hepatic or erythroid, depending on the major production site of porphyrins or their precursors. The pathogenesis of inherited hepatic porphyrias has now been defined at the molecular level. Some gene carriers are vulnerable to a range of exogenous and endogenous factors, which may trigger neuropsychiatric and/or cutaneous symptoms. Early diagnosis is of prime importance since it makes way for counselling. In this article we present an overview of recent advances on hepatic porphyrias: 5-aminolevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria (AIP), porphyria cutanea tarda (PCT), hereditary coproporphyria (HC), and variegate porphyria (VP). PMID:12367763

  7. Dengue causing fulminant hepatitis in a hepatitis B virus carrier.

    PubMed

    Agarwal, M P; Giri, S; Sharma, V; Roy, U; Gharsangi, K

    2011-01-01

    Dengue is an acute febrile illness resulting from infection by a flavivirus transmitted by the Aedes mosquito. It is characterized by bleeding manifestations and a plasma leak syndrome. Hepatic involvement in the form of elevation in transaminases is common. However, acute hepatic failure is uncommon. It is not known how the presence of an underlying chronic hepatitis or liver disease affects the likelihood of severity of hepatitis from dengue. The present report is of a 33-year-old man, a carrier of hepatitis B virus, who presented with fever, altered sensorium, thrombocytopenia, and coagulopathy. He was diagnosed to have developed acute hepatic failure due to dengue. The patient improved with supportive measures. PMID:21422600

  8. Clinical presentation of chronic traumatic encephalopathy

    PubMed Central

    Daneshvar, Daniel H.; Baugh, Christine M.; Seichepine, Daniel R.; Montenigro, Philip H.; Riley, David O.; Fritts, Nathan G.; Stamm, Julie M.; Robbins, Clifford A.; McHale, Lisa; Simkin, Irene; Stein, Thor D.; Alvarez, Victor E.; Goldstein, Lee E.; Budson, Andrew E.; Kowall, Neil W.; Nowinski, Christopher J.; Cantu, Robert C.; McKee, Ann C.

    2013-01-01

    Objective: The goal of this study was to examine the clinical presentation of chronic traumatic encephalopathy (CTE) in neuropathologically confirmed cases. Methods: Thirty-six adult male subjects were selected from all cases of neuropathologically confirmed CTE at the Boston University Center for the Study of Traumatic Encephalopathy brain bank. Subjects were all athletes, had no comorbid neurodegenerative or motor neuron disease, and had next-of-kin informants to provide retrospective reports of the subjects' histories and clinical presentations. These interviews were conducted blind to the subjects' neuropathologic findings. Results: A triad of cognitive, behavioral, and mood impairments was common overall, with cognitive deficits reported for almost all subjects. Three subjects were asymptomatic at the time of death. Consistent with earlier case reports of boxers, 2 relatively distinct clinical presentations emerged, with one group whose initial features developed at a younger age and involved behavioral and/or mood disturbance (n = 22), and another group whose initial presentation developed at an older age and involved cognitive impairment (n = 11). Conclusions: This suggests there are 2 major clinical presentations of CTE, one a behavior/mood variant and the other a cognitive variant. PMID:23966253

  9. Iatrogenic Coagulopathy and the Development of Posterior Reversible Encephalopathy Syndrome after L-asparaginase Chemotherapy.

    PubMed

    Rota, Eugenia; Vallisa, Daniele; Morelli, Nicola; Scagnelli, Paola

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological syndrome mostly related to hypertension, eclampsia, renal failure, or to chemotherapy and/or immunosuppressive drugs. Although the PRES pathophysiology is multifactorial, hypertension and endothelial dysfunction are hypothesized to be the pivotal factors. Here we report a case of PRES in an adult patient after chemotherapy (Escherichia coli L-asparaginase [L-ASP], daunorubicin, vincristine, and intrathecal methotrexate) for acute lymphoblastic leukemia. The development of the PRES was strictly associated with an iatrogenic coagulopathy induced by L-ASP, which inhibits the biosynthesis of hepatic coagulation factors. The nadir of platelet count, antithrombin III (ATIII) and fibrinogen curve was coincident with the onset of the PRES neurological picture; subsequently, the normalization of the ATIII and fibrinogen levels seemed to parallel the good clinical evolution. This case seems to provide new insights into the PRES pathophysiological mechanisms. PMID:27014503

  10. Iatrogenic Coagulopathy and the Development of Posterior Reversible Encephalopathy Syndrome after L-asparaginase Chemotherapy

    PubMed Central

    Rota, Eugenia; Vallisa, Daniele; Morelli, Nicola; Scagnelli, Paola

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological syndrome mostly related to hypertension, eclampsia, renal failure, or to chemotherapy and/or immunosuppressive drugs. Although the PRES pathophysiology is multifactorial, hypertension and endothelial dysfunction are hypothesized to be the pivotal factors. Here we report a case of PRES in an adult patient after chemotherapy (Escherichia coli L-asparaginase [L-ASP], daunorubicin, vincristine, and intrathecal methotrexate) for acute lymphoblastic leukemia. The development of the PRES was strictly associated with an iatrogenic coagulopathy induced by L-ASP, which inhibits the biosynthesis of hepatic coagulation factors. The nadir of platelet count, antithrombin III (ATIII) and fibrinogen curve was coincident with the onset of the PRES neurological picture; subsequently, the normalization of the ATIII and fibrinogen levels seemed to parallel the good clinical evolution. This case seems to provide new insights into the PRES pathophysiological mechanisms. PMID:27014503

  11. Factors influencing occurrence of postpartum haemorrhage in pregnant women with hepatitis E infection and deranged coagulation profile

    PubMed Central

    Puri, Manju; Patra, Sharda; Singh, Preeti; Malhotra, Nidhi; Trivedi, Shubha Sagar; Sharma, Sunita; Kumar, Ashish; Sarin, Shiv Kumar

    2011-01-01

    Coagulopathy is an important complication associated with hepatitis E virus (HEV) infection in pregnant women. Postpartum haemorrhage (PPH) remains a serious risk while managing the labour of these women. The aim of this paper is to study the factors influencing the occurrence of PPH in pregnant women with hepatitis E infection with coagulopathy. The labours of 38 pregnant women with hepatitis E and deranged coagulation profile were followed. Factors that may predict postpartum bleeding complications in women with HEV infection and deranged coagulation profile were statistically analysed. Of 38 pregnant women with acute viral hepatitis due to HEV, 13 (34%) suffered a PPH while 25 (66%) did not. On univariate analysis low alanine aminotransferase (P = 0.016), high international normalized ratio (P = 0.003), high levels of d-dimer (P = 0.008), presence of hepatic encephalopathy (P = 0.028), intrauterine fetal death (P = 0.001) and gastrointestinal bleeding (P = 0.004) were found to predict PPH. However, on multivariate analysis the only independent variable that predicted PPH was the presence gastrointestinal (GI) bleeding (odds ratio [OR] 11.363; 95% CI: 1.003, 125; P = 0.050). Women with GI bleeding have 11 times higher risk of PPH than those without a GI bleed; however, the confidence interval is very wide. Administration of fresh frozen plasma in the peripartum period reduces the risk of PPH. In conclusion, early recognition of factors which predict the risk of PPH and timely intervention with judicious use of blood and blood components in the peripartum period can improve the outcome of pregnant women with HEV infection with deranged coagulation.

  12. Proton Resonance Spectroscopy Study of the Effects of L-Ornithine-L-Aspartate on the Development of Encephalopathy, Using Localization Pulses with Reduced Specific Absorption Rate

    NASA Astrophysics Data System (ADS)

    Slotboom, J.; Vogels, B. A. P. M.; Dehaan, J. G.; Creyghton, J. H. N.; Quack, G.; Chamuleau, R. A. F. M.; Bovee, W. M. M. J.

    Using the SADLOVE ( single-shot adiabatic localized volume excitation) localization technique with reduced specific absorption rate phase-compensated 2π pulses for localization, in vivo rat brain spectra were obtained in order to study the possible beneficial effects of L-ornithine-L-aspartate (OA) on the development of encephalopathy induced by hyperammonemia in portacaval shunted rats, an experimental model for subacute hepatic encephalopathy. The in vivo1H spectra were quantified using a conjugate-gradient-based frequency-domain fitting procedure. OA treatment resulted in an about threefold lower increase in train lactate ( P < 0.0001) and a slower increase of brain glutamine ( P = 0.022) concentration. However, these changes in brain metabolism, including a significantly lower ammonia concentration during OA treatment, were not associated with a sig significant improvement in clinical symptoms of encephalopathy, suggesting either insufficient decrease in brain ammonia concentration or another effect of OA treatment counteracting the lowering effect on blood and brain ammonia and on brain glutamine and lactate. It is concluded that localized in vivo1H MRS of the brain in combination with other analytical techniques, such as in vivo microdialysis, is helpful in explaining pathophysiological changes during hyperammonemia-induced encephalopathy.

  13. Hepatitis B Vaccine

    MedlinePlus

    ... as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis B?Hepatitis B is a serious infection that affects the liver. It is caused by the hepatitis B virus. ...

  14. Hepatitis A Vaccine

    MedlinePlus

    Twinrix® (as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis A?Hepatitis A is a serious liver disease caused by the hepatitis A virus (HAV). HAV is found in ...

  15. Hepatitis C: Clinical Trials

    MedlinePlus

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  16. Autoimmune hepatitis

    MedlinePlus

    ... diseases. These include: Graves disease Inflammatory bowel disease Rheumatoid arthritis Scleroderma Sjogren syndrome Systemic lupus erythematosus Thyroiditis Type 1 diabetes Ulcerative colitis Autoimmune hepatitis may occur in family ...

  17. Hepatitis B

    MedlinePlus

    ... A Hepatitis B HPV (Human Papillomavirus) Influenza (Flu) Measles Meningococcal Disease Mumps Pertussis (Whooping Cough) Pneumococcal Disease Rubella (German Measles) Shingles (Herpes Zoster) Tetanus (Lockjaw) Professional Resources Adult ...

  18. [A new approach to the treatment of patients with circulatory encephalopathy].

    PubMed

    Kupnovyts'ka, M Iu; Lushchyk, U B; Herasymchuk, R D; Chmyr, H S; Iatsyshyn, R I; Dubanovych, L B

    1997-01-01

    Effects were studied of vincamin and tanakan in 68 patients with stage I, II and III discirculatory encephalopathy (as per WHO classification 1981). In 52% of the patients atherosclerosis of brain vessels was associated with arterial hypertension (group I), in 48 per cent venous discirculatory encephalopathy was diagnosable against the background of arterial hypertension (group IIA-20%) and arterial hypotension (group IIB-26%). Both tanakan and vincamin were found to be effective in group I patients; however, in stage III condition their effectiveness was no better than 42 and 15% respectively, which fact might be due to organic changes in the vascular wall. Tanakan appeared to be more beneficial in group II patients since venous dystonia is considered to be the main pathogenetic link in this context, and tanakan is known to improve the venous outflow from the cranial cavity. Almost in one-third of group IIB patients vincamin worsened general health status, especially so in stage III discirculatory encephalopathy, which fact may be related to peculiar effect of the drug on the arterial link of brain blood supply. PMID:9491724

  19. Pellagrous encephalopathy presenting as alcohol withdrawal delirium: A case series and literature review

    PubMed Central

    2012-01-01

    Background Alcohol withdrawal delirium (AWD) is associated with significant morbidity and mortality. Pellagra (niacin deficiency) can be a cause of delirium during alcohol withdrawal that may often be overlooked. Objectives We present a three-patient case series of pellagrous encephalopathy (delirium due to pellagra) presenting as AWD. Methods We provide a brief review of pellagra’s history, data on pellagra’s epidemiology, and discuss pellagra’s various manifestations, particularly as related to alcohol withdrawal. We conclude by providing a review of existing guidelines on the management of alcohol withdrawal, highlighting that they do not include pellagrous encephalopathy in the differential diagnosis for AWD. Results Though pellagra has been historically described as the triad of dementia, dermatitis, and diarrhea, it seldom presents with all three findings. The neurocognitive disturbance associated with pellagra is better characterized by delirium rather than dementia, and pellagra may present as an isolated delirium without any other aspects of the triad. Discussion Although endemic pellagra is virtually eradicated in Western countries, it continues to present as pellagrous encephalopathy in patients with risk factors for malnutrition such as chronic alcohol intake, homelessness, or AIDS. It may often be mistaken for AWD. Whenever pellagra is suspected, treatment with oral nicotinamide (100 mg three times daily for 3–4 weeks) prior to laboratory confirmation is recommended as an inexpensive, safe, and potentially life-saving intervention. PMID:23186222

  20. Immigration and viral hepatitis.

    PubMed

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J; Janssen, Harry L A

    2015-08-01

    WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants. PMID:25962882

  1. [Acute liver failure due to human herpesvirus 6 in an infant].

    PubMed

    Tronconi, G M; Mariani, B; Pajno, R; Fomasi, M; Cococcioni, L; Biffi, V; Bove, M; Corsin, P; Garbetta, G; Barera, G

    2012-01-01

    We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF) with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus), drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvirus 6 (HHV6) genome was positive with a significant number of copies for mL. A favorable evolution of the clinical symptoms and a progressive hematochemical resolution were obtained. Plasma and Vitamin K were administrated as a support therapy for treating coagulopathy. The present case report and the cases' review from the literature, evidence the importance of always including screening for HHV6 infection in the diagnostic approach to acute onset of liver failure. HHV6 is a common virus in the pediatric population with a greater number of cases of fulminant viral non-A, non-B, non-C hepatitis in immunocompetent patients due to this virus: these forms have often a high mortality rate and maybe necessitate liver transplantation; for this reason correct etiological agent identification is mandatory for the prognosis and it has to be based on the quantitative search of the virus's genome. Pathogenesis of liver-induced damage associated to HHV6 remains unclear; however in vitro studies demonstrate the potential hepatotoxicity effects of this virus. PMID:23342747

  2. Hyperammonemic Encephalopathy Caused by Carnitine Deficiency

    PubMed Central

    Zucker, Stephen D.

    2007-01-01

    Carnitine is an essential co-factor in fatty acid metabolism. Carnitine deficiency can impair fatty acid oxidation, rarely leading to hyperammonemia and encephalopathy. We present the case of a 35-year-old woman who developed acute mental status changes, asterixis, and diffuse muscle weakness. Her ammonia level was elevated at 276 μg/dL. Traditional ammonia-reducing therapies were initiated, but proved ineffective. Pharmacologic, microbial, and autoimmune causes for the hyperammonemia were excluded. The patient was severely malnourished and her carnitine level was found to be extremely low. After carnitine supplementation, ammonia levels normalized and the patient’s mental status returned to baseline. In the setting of refractory hyperammonemia, this case illustrates how careful investigation may reveal a treatable condition. PMID:18080167

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

    PubMed

    Lough, Mary E

    2012-06-01

    Wernicke's encephalopathy (WE) is a life threatening neurological disorder that results from thiamine (Vitamin B1) deficiency. Clinical signs include mental status changes, ataxia, occulomotor changes and nutritional deficiency. The conundrum is that the clinical presentation is highly variable. WE clinical signs, brain imaging, and thiamine blood levels, are reviewed in 53 published case reports from 2001 to 2011; 81 % (43/53) were non-alcohol related. Korsakoff Syndrome or long-term cognitive neurological changes occurred in 28 % (15/53). Seven WE cases (13 %) had a normal magnetic resonance image (MRI). Four WE cases (8 %) had normal or high thiamine blood levels. Neither diagnostic tool can be relied upon exclusively to confirm a diagnosis of WE. PMID:22577001

  4. Does this patient have hypertensive encephalopathy?

    PubMed

    Christopoulou, Foteini; Rizos, Evangelos C; Kosta, Paraskevi; Argyropoulou, Maria I; Elisaf, Moses

    2016-05-01

    A 63-year-old man was admitted to our hospital for further investigation and management of brain metastases. The patient was initially presented with a 4-day history of confusion. On the day of admission, the patient was confused, agitated, disorientated in place and time, and had visual disturbances. His blood pressure was repeatedly recorded high, with levels of systolic blood pressure between 170-210 mm Hg. A brain magnetic resonance imaging showed areas of high signal on T2 and fluid-attenuated inversion recovery images, located bilaterally in the white matter of the occipital regions and unilateral in the left frontal lobe, suggestive of posterior reversible encephalopathy syndrome. Aggressive treatment of hypertension resulted in complete resolution of the clinical and radiologic features of the syndrome. PMID:26896240

  5. Hypoxic Ischemic Encephalopathy: Pathophysiology and Experimental Treatments

    PubMed Central

    Allen, Kimberly A.; Brandon, Debra H.

    2011-01-01

    Hypoxic ischemic encephalopathy (HIE) is a serious birth complication affecting full term infants: 40–60% of affected infants die by 2 years of age or have severe disabilities. The majority of the underlying pathologic events of HIE are a result of impaired cerebral blood flow and oxygen delivery to the brain with resulting primary and secondary energy failure. In the past, treatment options were limited to supportive medical therapy. Currently, several experimental treatments are being explored in neonates and animal models to ameliorate the effects of secondary energy failure. This review discusses the underlying pathophysiologic effects of a hypoxic-ischemic event and experimental treatment modalities being explored to manage infants with HIE. Further research is needed to better understand if the long-term impact of the experimental treatments and whether the combinations of experimental treatments can improve outcomes in infants with HIE. PMID:21927583

  6. Chronic Traumatic Encephalopathy: The Impact on Athletes.

    PubMed

    Galgano, Michael A; Cantu, Robert; Chin, Lawrence S

    2016-01-01

    Chronic traumatic encephalopathy (CTE) is a devastating neuropsychological condition afflicting a small percentage of athletes partaking in high-impact sports. The onset of symptoms lags years behind the inciting events. Repetitive minor head injuries are felt to be the main etiology behind CTE. Routine radiographic imaging generally is unremarkable in cases of CTE. Functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) are advanced MRI-based sequences that have shown promise in detecting early radiographic findings that may be reflective of CTE. Progressive neuronal loss is the histopathological hallmark of this neurodegenerative disease. Strategizing earlier detection techniques is paramount in delivering optimal care to athletes afflicted with CTE. PMID:27088064

  7. Optic nerve hypoplasia, encephalopathy, and neurodevelopmental handicap.

    PubMed Central

    Burke, J P; O'Keefe, M; Bowell, R

    1991-01-01

    Abnormalities of the central nervous system are frequently described in optic nerve hypoplasia. In a longitudinal study of 46 consecutive children (32 term, 14 preterm) with bilateral optic nerve hypoplasia 32 (69.5%) had associated neurodevelopmental handicap. Of these, 90% had structural central nervous system abnormalities on computed tomographic brain scans. Neurodevelopmental handicap occurred in 62.5% of the term and 86% of the preterm infants respectively. Term infants had a greater incidence of ventral developmental midline defects and proportionately fewer maternal and/or neonatal complications throughout pregnancy, while encephaloclastic lesions were commoner among the premature infants. An association of optic nerve hypoplasia with the twin transfusion syndrome and prenatal vascular encephalopathies is described. PMID:2021594

  8. Brain MRI findings in Wernicke encephalopathy.

    PubMed

    Wicklund, Meredith R; Knopman, David S

    2013-08-01

    A 71-year-old woman with myelofibrosis on chemotherapy experienced an acute illness with nausea, vomiting, and diarrhea. Two weeks later, she developed an acute confusional state characterized by disorientation and fluctuating alertness with normal speech and language. Her neurologic examination demonstrated an upper motor neuron pattern of right hemiparesis. She reported double vision though ophthalmoparesis was not appreciated. Her gait was normal. While hospitalized, she developed generalized tonic-clonic seizures. Brain MRI revealed a small area of restricted diffusion of the left precentral gyrus (figure). She was diagnosed with a stroke with secondary seizures; however, as the confusional state resolved, she developed profound retrograde and anterograde amnesia. Review of the brain MRI showed high T2 signal in the medial thalamus and contrast enhancement of the mamillary bodies; a diagnosis of Wernicke-Korsakoff syndrome was entertained and she was started on thiamine replacement. The encephalopathy and hemiparesis resolved though she remains severely amnestic. PMID:24195023

  9. Neuroprotective Strategies after Neonatal Hypoxic Ischemic Encephalopathy

    PubMed Central

    Dixon, Brandon J.; Reis, Cesar; Ho, Wing Mann; Tang, Jiping; Zhang, John H.

    2015-01-01

    Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. We will identify understudied targets after HIE, as well as neuroprotective molecules that bring hope to future treatments such as melatonin, topiramate, xenon, interferon-beta, stem cell transplantation. This review will also discuss some of the most recent trials being conducted in the clinical setting and evaluate what directions are needed in the future. PMID:26389893

  10. Neuroprotective Strategies after Neonatal Hypoxic Ischemic Encephalopathy.

    PubMed

    Dixon, Brandon J; Reis, Cesar; Ho, Wing Mann; Tang, Jiping; Zhang, John H

    2015-01-01

    Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. We will identify understudied targets after HIE, as well as neuroprotective molecules that bring hope to future treatments such as melatonin, topiramate, xenon, interferon-beta, stem cell transplantation. This review will also discuss some of the most recent trials being conducted in the clinical setting and evaluate what directions are needed in the future. PMID:26389893

  11. Is chronic traumatic encephalopathy a real disease?

    PubMed

    Randolph, Christopher

    2014-01-01

    Chronic traumatic encephalopathy (CTE) has received widespread media attention and is treated in the lay press as an established disease, characterized by suicidality and progressive dementia. The extant literature on CTE is reviewed here. There currently are no controlled epidemiological data to suggest that retired athletes are at increased risk for dementia or that they exhibit any type of unique neuropathology. There remain no established clinical or pathological criteria for diagnosing CTE. Despite claims that CTE occurs frequently in retired National Football League (NFL) players, recent studies of NFL retirees report that they have an all-cause mortality rate that is approximately half of the expected rate, and even lower suicide rates. In addition, recent clinical studies of samples of cognitively impaired NFL retirees have failed to identify any unique clinical syndrome. Until further controlled studies are completed, it appears to be premature to consider CTE a verifiable disease. PMID:24412888

  12. Chronic Traumatic Encephalopathy: The Impact on Athletes

    PubMed Central

    Cantu, Robert; Chin, Lawrence S.

    2016-01-01

    Chronic traumatic encephalopathy (CTE) is a devastating neuropsychological condition afflicting a small percentage of athletes partaking in high-impact sports. The onset of symptoms lags years behind the inciting events. Repetitive minor head injuries are felt to be the main etiology behind CTE. Routine radiographic imaging generally is unremarkable in cases of CTE. Functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) are advanced MRI-based sequences that have shown promise in detecting early radiographic findings that may be reflective of CTE. Progressive neuronal loss is the histopathological hallmark of this neurodegenerative disease. Strategizing earlier detection techniques is paramount in delivering optimal care to athletes afflicted with CTE. PMID:27088064

  13. Genetics Home Reference: MECP2-related severe neonatal encephalopathy

    MedlinePlus

    ... onset encephalopathy with microcephaly Patient Support and Advocacy Resources (2 links) Rare Disease Clinical Research Network: Rett Syndrome, MECP2 Duplication and Rett-Related Disorders Natural History Study RettSyndrome.org GeneReviews (1 link) MECP2- ...

  14. [Follow-up of newborns with hypoxic-ischaemic encephalopathy].

    PubMed

    Martínez-Biarge, M; Blanco, D; García-Alix, A; Salas, S

    2014-07-01

    Hypothermia treatment for newborn infants with hypoxic-ischemic encephalopathy reduces the number of neonates who die or have permanent neurological deficits. Although this therapy is now standard of care, neonatal hypoxic-ischaemic encephalopathy still has a significant impact on the child's neurodevelopment and quality of life. Infants with hypoxic-ischaemic encephalopathy should be enrolled in multidisciplinary follow-up programs in order to detect impairments, to initiate early intervention, and to provide counselling and support for families. This article describes the main neurodevelopmental outcomes after term neonatal hypoxic-ischaemic encephalopathy. We offer recommendations for follow-up based on the infant's clinical condition and other prognostic indicators, mainly neonatal neuroimaging. Other aspects, such as palliative care and medico-legal issues, are also briefly discussed. PMID:24290154

  15. Acute hyperammonemic encephalopathy after 5-fluorouracil based chemotherapy

    PubMed Central

    Yi, Hee Jung; Hong, Kyung Sook; Moon, Nara; Chung, Soon Sup; Lee, Ryung-Ah

    2016-01-01

    5-Fluorouracil (5-FU) based chemotherapy has been commonly used to treat metastatic or advanced colon cancer as an adjuvant chemotherapy. Although the side effects of 5-FU such as gastrointestinal problems and neutropenia and thrombocytopenia are common, not many cases of 5-FU related encephalopathy are reported. Hyperammonemic encephalopathy is a rare central nervous system toxicity following 5-FU chemotherapy manifesting as altered mental status with elevated ammonia levels with no radiologic abnormality. We report one case of 5-FU induced hyperammonemic encephalopathy occurring after Folfox4 (oxaliplatin, folinic acid and 5-fluorouracil) chemotherapy in a colon cancer patient who presented with confused mental status soon after the chemotherapy and review the 5-FU related encephalopathy. PMID:26942162

  16. Acute hyperammonemic encephalopathy after 5-fluorouracil based chemotherapy.

    PubMed

    Yi, Hee Jung; Hong, Kyung Sook; Moon, Nara; Chung, Soon Sup; Lee, Ryung-Ah; Kim, Kwang Ho

    2016-03-01

    5-Fluorouracil (5-FU) based chemotherapy has been commonly used to treat metastatic or advanced colon cancer as an adjuvant chemotherapy. Although the side effects of 5-FU such as gastrointestinal problems and neutropenia and thrombocytopenia are common, not many cases of 5-FU related encephalopathy are reported. Hyperammonemic encephalopathy is a rare central nervous system toxicity following 5-FU chemotherapy manifesting as altered mental status with elevated ammonia levels with no radiologic abnormality. We report one case of 5-FU induced hyperammonemic encephalopathy occurring after Folfox4 (oxaliplatin, folinic acid and 5-fluorouracil) chemotherapy in a colon cancer patient who presented with confused mental status soon after the chemotherapy and review the 5-FU related encephalopathy. PMID:26942162

  17. Quantitative Risk Assessment of Bovine Spongiform Encephalopathy

    NASA Astrophysics Data System (ADS)

    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.

  18. Prion biology relevant to bovine spongiform encephalopathy.

    PubMed

    Novakofski, J; Brewer, M S; Mateus-Pinilla, N; Killefer, J; McCusker, R H

    2005-06-01

    Bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD) of deer and elk are a threat to agriculture and natural resources, as well as a human health concern. Both diseases are transmissible spongiform encephalopathies (TSE), or prion diseases, caused by autocatalytic conversion of endogenously encoded prion protein (PrP) to an abnormal, neurotoxic conformation designated PrPsc. Most mammalian species are susceptible to TSE, which, despite a range of species-linked names, is caused by a single highly conserved protein, with no apparent normal function. In the simplest sense, TSE transmission can occur because PrPsc is resistant to both endogenous and environmental proteinases, although many details remain unclear. Questions about the transmission of TSE are central to practical issues such as livestock testing, access to international livestock markets, and wildlife management strategies, as well as intangible issues such as consumer confidence in the safety of the meat supply. The majority of BSE cases seem to have been transmitted by feed containing meat and bone meal from infected animals. In the United Kingdom, there was a dramatic decrease in BSE cases after neural tissue and, later, all ruminant tissues were banned from ruminant feed. However, probably because of heightened awareness and widespread testing, there is growing evidence that new variants of BSE are arising "spontaneously," suggesting ongoing surveillance will continue to find infected animals. Interspecies transmission is inefficient and depends on exposure, sequence homology, TSE donor strain, genetic polymorphism of the host, and architecture of the visceral nerves if exposure is by an oral route. Considering the low probability of interspecies transmission, the low efficiency of oral transmission, and the low prion levels in nonnervous tissues, consumption of conventional animal products represents minimal risk. However, detection of rare events is challenging, and TSE

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

    PubMed Central

    Maramattom, Boby Varkey; Raja, Rajat; Balagopal, Anuroop

    2016-01-01

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

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

    PubMed

    Maramattom, Boby Varkey; Raja, Rajat; Balagopal, Anuroop

    2016-01-01

    Urea cycle disorders (UCD) are very rare metabolic disorders that present with encephalopathy and hyperammonemia. Of the UCDs, Arginase deficiency (ARD) is the rarest and presents in childhood with a progressive spastic diplegia or seizures. Acute presentation in adulthood is extremely unusual.[1] We present the first case of adult onset ARD presenting with encephalopathy and diffusion weighted MRI findings that resembled a moustache in the midbrain. PMID:27570396

  1. Developmental outcomes of newborn encephalopathy in the term infant.

    PubMed

    Badawi, N; Keogh, J M; Dixon, G; Kurinczuk, J J

    2001-06-01

    Newborn encephalopathy is a clinically defined condition of abnormal neurological behaviours in the newborn period. Though most cases have their origin in the preconceptional and antepartum period, newborn encephalopathy represents a crucial link between intrapartum events and permanent neurological problems in the child. The birth prevalence of newborn encephalopathy ranges from 1.8 to 7.7 per 1000 term live births according to the definition used and the population to which it is applied. Few studies have investigated the outcomes of newborn encephalopathy other than for cases solely attributed to intrapartum hypoxia. These adverse outcomes range from death to cerebral palsy, intellectual disability, and less severe neurological disabilities such as learning and behavioural problems. Outcomes following newborn encephalopathy may vary from country to country with 9.1% of affected babies dying in the newborn period in Western Australia and 10.1% manifesting cerebral palsy by the age of two. These compare to a case fatality of 30.5% in Kathmandu and a cerebral palsy rate of 14.5% by one year of age. The study by Robertson et al which followed children with hypoxic ischaemic encephalopathy found an incidence of impairment of 16% among survivors assessed at 8 years with 42% requiring school resource room help or special classes. This review emphasises the great need for comprehensive clinical and educational assessment as these infants approach school entry to enable appropriate educational provisions to be made. PMID:11450384

  2. Early experiences with a porcine hepatocyte-based bioartificial liver in acute hepatic failure patients.

    PubMed

    Morsiani, E; Pazzi, P; Puviani, A C; Brogli, M; Valieri, L; Gorini, P; Scoletta, P; Marangoni, E; Ragazzi, R; Azzena, G; Frazzoli, E; Di Luca, D; Cassai, E; Lombardi, G; Cavallari, A; Faenza, S; Pasetto, A; Girardis, M; Jovine, E; Pinna, A D

    2002-03-01

    Orthotopic liver transplantation (OLT) is the only effective therapeutic modality in severe acute hepatic failure (AHF). The scarcity of organs for transplantation leads to an urgent necessity for temporary liver support treatments in AHF patients. A hepatocyte-based bioartificial liver (BAL) is under investigation with the main purpose to serve as bridging treatment until a liver becomes available for OLT, or to promote spontaneous liver regeneration. We developed a novel radial-flow bioreactor (RFB) for three-dimensional, high-density hepatocyte culture and an integrated pumping apparatus in which, after plasmapheresis, the patient's plasma is recirculated through the hepatocyte-filled RFB. Two hundred thirty grams of freshly isolated porcine hepatocytes were loaded into the RFB for clinical liver support treatment. The BAL system was used 8 times in supporting 7 AHF patients in grade III-IV coma, all waiting for an urgent OLT Three patients with no history of previous liver diseases were affected by fulminant hepatic failure (FHF) due to hepatitis B virus, 3 by primary non-function (PNF) of the transplanted liver, and one by AHF due to previous abdominal trauma and liver surgery. Six out of 7 patients underwent OLT following BAL treatment(s), which lasted 6-24 hours. All patients tolerated the procedures well, as shown by an improvement in the level of encephalopathy, a decrease in serum ammonia, transaminases and an amelioration of the prothrombin time, with full neurological recovery after OLT Our initial clinical experience confirms the safety of this BAL configuration and suggests its clinical efficacy as a temporary liver support system in AHF patients. PMID:11999191

  3. Posterior reversible encephalopathy syndrome in leukemic children: a sensitive issue.

    PubMed

    Kridis, Wala Ben; Mdhaffer, Moez; Hentati, Yosr; Kammoun, Fatma; Milad, Abir; Haddar, Sondes; Mahfoudh, Khaireddine Ben; Triki, Chahinez; Elloumi, Moez

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is an acute central nervous system disorder characterized by reversible brain vasogenic edema. We report here a new case of a nine-year-old boy with B-cell acute lymphoblastic leukemia (B-ALL) who developed PRES secondary to induction chemotherapy including dexamethasone (dexamethasone®), vincristine (oncovin(®)), daunorubicin (adriblastine(®)) and intrathecal injection. Cerebral magnetic resonance imaging (MRI) showed high signal intensity on T2 at cortical and sub cortical region of parieto-frontal and parieto-occipital lobes. The patient was put under sodium valproate (depakine(®)) and we decided to continue dexamethasone (dexamethasone(®)) and daunorubicin (adriblastine(®)) injection. The MRI, after four weeks, was normal. So, we resumed vincristine (oncovin(®)) and we started L-asparaginase injections. Then, the outcome was favorable. The treatment of PRES is based on the withdrawal of the triggering factor to avoid the risk of irreversible lesions. But, due to the severity of leukemia the discontinuation of chemotherapy is difficult because of the risk of disease progression. PMID:24919742

  4. Hepatitis B

    MedlinePlus

    ... and Change Plan Wallet card for patients to record their alcohol use over a 4-week period as a way to monitor and reduce their drinking behavior. Glossary Definitions of terms commonly used with viral hepatitis and ...

  5. Hepatitis B

    MedlinePlus

    ... U.S. Preventive Services Task Force recommendation statement. Ann Intern Med . 2014;161(1):58-66. PMID 24863637 ... Development Conference Statement: Management of hepatitis B. Ann Intern Med . 2009;150:104-10. PMID: 19124811 www. ...

  6. Wernicke's encephalopathy complicating hyperemesis gravidarum: from the background to the present.

    PubMed

    Di Gangi, Stefania; Gizzo, Salvatore; Patrelli, Tito Silvio; Saccardi, Carlo; D'Antona, Donato; Nardelli, Giovanni Battista

    2012-08-01

    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. PMID:22003959

  7. Hepatic and extra-hepatic sequelae, and prevalence of viral hepatitis C infection estimated from routine data in at-risk groups

    PubMed Central

    2010-01-01

    Background Concerns about the hepatitis C virus (HCV) are due to the high risk of chronic liver disease and poor treatment efficacy. Synthesizing evidence from multiple data sources is becoming widely used to estimate HCV-infection prevalence. This paper aims to estimate the prevalence of HCV infection, and the hepatic and extrahepatic sequelae in at-risk groups, using routinely collected data in the Lazio region, Italy. Methods HCV laboratory surveillance and dialysis, hospital discharge, and drug-user registers were used as information sources to identify at-risk groups and to estimate HCV prevalence and sequelae. Full name and birth date were used as linkage keys for the various health registries. Prevalence was estimated as the percentage of cases within the general population and the at-risk groups, with 95% confidence intervals (95% CI) from 1997 to 2001. The risk of sequelae was estimated through a follow-up of hospital discharges up to December 31, 2004 and calculated as the prevalence ratio in HCV-positive and HCV-negative people, within each at-risk group, with 95% CI. Results There were 65,127 HCV-infected people in the study period; the prevalence was 1.24% (95%CI = 1.23%-1.25%) in the whole population, higher in males and older adults. Drug users (35.1%; 95%CI = 34.6-35.7) and dialysis patients (21.1%; 95%CI = 20.2%-22.0%) showed the highest values. Medical procedures with little exposure to blood resulted in higher estimates, ranging between 1.3% and 3.4%, which was not conclusively attributable to the surgical procedures. Cirrhosis, hepatocellular carcinoma and encephalopathy were the most frequent hepatic sequelae; cryoglobulinaemia and non-Hodgkin's lymphoma were the most frequent extrahepatic sequelae. Conclusions Synthesising data from multiple routine sources improved estimates of HCV prevalence and sequelae in dialysis patients and drug users, although prevalence validity should be assessed in survey and sequelae need a well

  8. The Neuropathology of Chronic Traumatic Encephalopathy

    PubMed Central

    McKee, Ann C.; Stein, Thor D.; Kiernan, Patrick T.; Alvarez, Victor E.

    2015-01-01

    Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE). Most instances of CTE occur in association with the play of sports, but CTE has also been reported in association with blast injuries and other neurotrauma. Symptoms of CTE include behavioral and mood changes, memory loss, cognitive impairment and dementia. Like many other neurodegenerative diseases, CTE is diagnosed with certainty only by neuropathological examination of brain tissue. CTE is a tauopathy characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles, astrocytic tangles and neurites in striking clusters around small blood vessels of the cortex, typically at the sulcal depths. Severely affected cases show p-tau pathology throughout the brain. Abnormalities in phosphorylated 43 kDa TAR DNA-binding protein are found in most cases of CTE; beta-amyloid is identified in 43%, associated with age. Given the importance of sports participation and physical exercise to physical and psychological health as well as disease resilience, it is critical to identify the genetic risk factors for CTE as well as to understand how other variables, such as stress, age at exposure, gender, substance abuse and other exposures, contribute to the development of CTE. PMID:25904048

  9. Posterior Reversible Encephalopathy Syndrome Complicating Traumatic Pancreatitis

    PubMed Central

    Sigurtà, Anna; Terzi, Valeria; Regna-Gladin, Caroline; Fumagalli, Roberto

    2016-01-01

    Abstract We are reporting a case of posterior reversible encephalopathy syndrome (PRES) developed in an unusual clinical scenario without the presence of the most described symptoms. PRES is a neurological and radiological syndrome described in many different clinical conditions. In children it has been mostly reported in association with hematological and renal disorders. Our patient was a 15 years old boy, admitted to our intensive care unit for pancreatitis after blunt abdominal trauma. During the stay in the intensive care unit, he underwent multiple abdominal surgical interventions for pancreatitis complications. He had a difficult management of analgesia and sedation, being often agitated with high arterial pressure, and he developed a bacterial peritonitis. After 29 days his neurological conditions abruptly worsened with neuroimaging findings consistent with PRES. His clinical conditions progressively improved after sedation and arterial pressure control. He was discharged at home with complete resolution of the neurological and imaging signs 2 months later. The pathophysiology of PRES is controversial and involves disordered autoregulation ascribable to hypertension and endothelial dysfunction. In this case both hypertension and endothelial activation, triggered by sepsis and pancreatitis, could represent the culprits of PRES onset. Even if there is no specific treatment for this condition, a diagnosis is mandatory to start antihypertensive and supportive treatment. We are therefore suggesting to consider PRES in the differential diagnosis of a neurological deterioration preceded by hypertension and/or septic state, even without other “typical” clinical features. PMID:27258506

  10. A critical review of chronic traumatic encephalopathy.

    PubMed

    Iverson, Grant L; Gardner, Andrew J; McCrory, Paul; Zafonte, Ross; Castellani, Rudy J

    2015-09-01

    Chronic traumatic encephalopathy (CTE) has been described in the literature as a neurodegenerative disease with: (i) localized neuronal and glial accumulations of phosphorylated tau (p-tau) involving perivascular areas of the cerebral cortex, sulcal depths, and with a preference for neurons within superficial cortical laminae; (ii) multifocal axonal varicosities and axonal loss involving deep cortex and subcortical white matter; (iii) relative absence of beta-amyloid deposits; (iv) TDP-43 immunoreactive inclusions and neurites; and (v) broad and diverse clinical features. Some of the pathological findings reported in the literature may be encountered with age and other neurodegenerative diseases. However, the focality of the p-tau cortical findings in particular, and the regional distribution, are believed to be unique to CTE. The described clinical features in recent cases are very similar to how depression manifests in middle-aged men and with frontotemporal dementia as the disease progresses. It has not been established that the described tau pathology, especially in small amounts, can cause complex changes in behavior such as depression, substance abuse, suicidality, personality changes, or cognitive impairment. Future studies will help determine the extent to which the neuropathology is causally related to the diverse clinical features. PMID:26183075

  11. Antibody-Mediated Autoimmune Encephalopathies and Immunotherapies.

    PubMed

    Gastaldi, Matteo; Thouin, Anaïs; Vincent, Angela

    2016-01-01

    Over the last 15 years it has become clear that rare but highly recognizable diseases of the central nervous system (CNS), including newly identified forms of limbic encephalitis and other encephalopathies, are likely to be mediated by antibodies (Abs) to CNS proteins. The Abs are directed against membrane receptors and ion channel-associated proteins that are expressed on the surface of neurons in the CNS, such as N-methyl D-aspartate receptors and leucine-rich, glioma inactivated 1 protein and contactin-associated protein like 2, that are associated with voltage-gated potassium channels. The diseases are not invariably cancer-related and are therefore different from the classical paraneoplastic neurological diseases that are associated with, but not caused by, Abs to intracellular proteins. Most importantly, the new antibody-associated diseases almost invariably respond to immunotherapies with considerable and sometimes complete recovery, and there is convincing evidence of their pathogenicity in the relatively limited studies performed so far. Treatments include first-line steroids, intravenous immunoglobulins, and plasma exchange, and second-line rituximab and cyclophosphamide, followed in many cases by steroid-sparing agents in the long-term. This review focuses mainly on N-methyl D-aspartate receptor- and voltage-gated potassium channel complex-related Abs in adults, the clinical phenotypes, and treatment responses. Pediatric cases are referred to but not reviewed in detail. As there have been very few prospective studies, the conclusions regarding immunotherapies are based on retrospective studies. PMID:26692392

  12. Chronic traumatic encephalopathy and other neurodegenerative proteinopathies.

    PubMed

    Tartaglia, Maria Carmela; Hazrati, Lili-Naz; Davis, Karen D; Green, Robin E A; Wennberg, Richard; Mikulis, David; Ezerins, Leo J; Keightley, Michelle; Tator, Charles

    2014-01-01

    "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 (AD) and frontotemporal lobar degeneration (FTLD). 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. PMID:24550810

  13. A Case of 5-Fluorouracil Induced Encephalopathy

    PubMed Central

    Kwon, Kyung A; Kwon, Hyuk-Chan; Kim, Min Chan; Kim, Sung-Hyun; Oh, Sung Yong; Lee, Suee

    2010-01-01

    Patients with reduced dihydropyrimidine dehydrogenase (DPD) activity are at risk for experiencing serious adverse effects following 5-fluorouracil (5-FU) based chemotherapy. Neurotoxicity is considered an extremely rare side effect of 5-FU. We report here on an unusual case of 5-FU induced encephalopathy. A 38-year-old woman with advanced gastric carcinoma was treated with adjuvant chemotherapy that consisted of infused 5-FU (1,000 mg/m2) for 5 days and cisplatin (60 mg/m2) on day 1 following total gastrectomy. Nineteen days after starting chemotherapy, the patient displayed a sudden onset of slurred speech, confusion, cognitive disturbances and paranoia. A magnetic resonance image (MRI) of the brain showed no structural abnormalities, and the other laboratory tests provided no explanations for her symptoms, other than a slightly elevated ammonia level. The patient was treated with a lactulose retention enema and thiamine infusion, the 5-FU was halted and her symptoms then recovered after 7 days. PMID:20622967

  14. Mycophenolate-Induced Posterior Reversible Encephalopathy Syndrome.

    PubMed

    Khajuria, Bhavik; Khajuria, Mansi; Agrawal, Yashwant

    2016-01-01

    A 29-year-old woman presented with diffuse anasarca and shortness of breath. Workup revealed a creatinine of 3.3 and a glomerular filtration rate of 17. The patient was also found to be pancytopenic with evidence of hemolytic anemia. A renal biopsy showed evidence of stage IV lupus nephritis with rapidly progressive glomerulonephritis. Her lupus was further classified as ANA negative and anti-dsDNA positive. Mycophenolate and triweekly hemodialysis were started along with a steroid burst of methylprednisolone 1 g for 3 days followed by prednisone 60 mg daily. Four days after discharge, the patient represented with a witnessed 3-minute seizure involving bowel incontinence, altered mental status, and tongue biting. She was given 2 mg intravenous lorazepam and loaded with 1000 mg levetiracetam for seizure prophylaxis. Magnetic resonance imaging of the head revealed bilateral posterior hemispheric subcortical edema, and the diagnosis of posterior reversible encephalopathy syndrome was made. Mycophenolate was immediately discontinued and replaced with cyclophosphamide. Strict blood pressure control below 140/90 mm Hg was maintained initially with intravenous nicardipine drip and then transitioned to oral nifedipine, clonidine, losartan, and minoxidil. A repeat head magnetic resonance imaging 8 days later showed resolved subcortical edema consistent with the patient's improved mental status. No permanent neurologic sequelae were recorded as a result of this hospital episode. PMID:25933141

  15. Hepatitis B Foundation

    MedlinePlus

    ... worldwide 2 Billion People have been infected with Hepatitis B Worldwide The Hepatitis B Foundation is working ... of people living with hepatitis B. Learn About Hepatitis B in 10 Other Languages . Resource Video See ...

  16. Hepatitis C - children

    MedlinePlus

    ... virus (HCV). Other common hepatitis virus infections include hepatitis A and hepatitis B . ... Elisofon SA, Jonas MMF. Viral hepatitis in children. In: Boyer TD, Manns MP, Sanyal AJ, eds. Zakim & Boyer's Hepatology: A Textbook of Liver Disease. 6th ed. ...

  17. Hepatitis A FAQs

    MedlinePlus

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis A FAQs for the Public Recommend on Facebook ...

  18. Delta agent (Hepatitis D)

    MedlinePlus

    Hepatitis D virus ... Hepatitis D virus (HDV) is found only in people who carry the hepatitis B virus. HDV may make liver ... B virus but who never had symptoms. Hepatitis D infects about 15 million people worldwide. It occurs ...

  19. Hepatitis C FAQs

    MedlinePlus

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis C FAQs for the Public Recommend on Facebook ...

  20. Hepatitis B FAQs

    MedlinePlus

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis B FAQs for the Public Recommend on Facebook ...