Ammonia Induced Encephalopathy from Valproic Acid in a Bipolar Patient: Case Report

Elgudin, Larissa; Hall, Yvonne; Schubert, Daniel

doi:10.2190/xw8e-q283-4429-ql71

Cited by 27 publications

(15 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Also, as previously noted, primates subjected to a nonlethal encephalopathic dose of ammonia will eventually fully recover 98. Full recovery in deeply encephalopathic patients who are hyperammonemic from any cause is not uncommon 54,103,135,136. Although there is evidence of morphological changes to astrocytes in autopsied brains of patients who died of hepatic encephalopathy, there is little evidence of net astrocytic cell death 21,102…”

Section: Astrocytes Glutamine Synthesis and Ammonia Neurotoxicitymentioning

confidence: 80%

Astrocyte Glutamine Synthetase: Importance in Hyperammonemic Syndromes and Potential Target for Therapy

et al. 2010

View full text Add to dashboard Cite

Summary:Many theories have been advanced to explain the encephalopathy associated with chronic liver disease and with the less common acute form. A major factor contributing to hepatic encephalopathy is hyperammonemia resulting from portacaval shunting and/or liver damage. However, an increasing number of causes of hyperammonemic encephalopathy have been discovered that present with the same clinical and laboratory features found in acute liver failure, but without liver failure. Here, we critically review the physiology, pathology, and biochemistry of ammonia (i.e., NH 3 plus NH 4 ϩ ) and show how these elements interact to constitute a syndrome that clinicians refer to as hyperammonemic encephalopathy (i.e., acute liver failure, fulminant hepatic failure, chronic liver disease). Included will be a brief history of the status of ammonia and the centrality of the astrocyte in brain nitrogen metabolism. Ammonia is normally detoxified in the liver and extrahepatic tissues by conversion to urea and glutamine, respectively. In the brain, glutamine synthesis is largely confined to astrocytes, and it is generally accepted that in hyperammonemia excess glutamine compromises astrocyte morphology and function. Mechanisms postulated to account for this toxicity will be examined with emphasis on the osmotic effects of excess glutamine (the osmotic gliopathy theory). Because hyperammonemia causes osmotic stress and encephalopathy in patients with normal or abnormal liver function alike, the term "hyperammonemic encephalopathy" can be broadly applied to encephalopathy resulting from liver disease and from various other diseases that produce hyperammonemia. Finally, the possibility that a brain glutamine synthetase inhibitor may be of therapeutic benefit, especially in the acute form of liver disease, is discussed. Key Words: Astrocyte swelling, cerebral edema, hepatic encephalopathy, hyperammonemia, glutamine synthetase. HISTORICAL PERSPECTIVESIn the early 1930s, van Caulaert and Deviller 1 and van Caulaert et al. 2 reported what may have been the first description of ammonia neurotoxicity in patients with liver disease. A few years later, Kirk 3 published a detailed study of nitrogen metabolism in control subjects and in patients with a variety of liver diseases. In the current review, hepatic encephalopathy is broadly categorized by the nature of the hepatic abnormality (i.e., acute liver failure, portal systemic shunts, and hepatocellular disease 4 ). Despite the limitations by today's standards of the analytical methods available in the mid1930s, Kirk was able to establish the basics of hepatic nitrogen metabolism in man as follows: 1) the portal vein is the major source of ammonia arising from the "putrefaction" of nitrogenous substances in the gut; 2) the liver is the major organ for removal of portal vein ammonia and for metabolism of amino acids; 3) most, if not all, urea is synthesized in the liver; and 4) the concentration of blood ammonia in normal subjects and in patients with liver disease is relatively low (a...

show abstract

Section: Astrocytes Glutamine Synthesis and Ammonia Neurotoxicitymentioning

confidence: 80%

Astrocyte Glutamine Synthetase: Importance in Hyperammonemic Syndromes and Potential Target for Therapy

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Other anticonvulsants such as phenytoin and carbamazepine may exacerbate VHE. Although there has been a case report describing VHE in a 35-year-old adult bipolar patient who presented to the ED with coma, it does not appear that this has been reported before in an adolescent patient (Elgudin et al 2003).…”

Section: Discussionmentioning

confidence: 86%

“…A second putative mechanism associated with hyperammonemia and VPA involves no hepatic injury. It is associated with inhibition of carbamoylphosphate synthetase-I, and ornithine transcarbamylase, enzymes in the urea cycle (Elgudin et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Bipolar Disorder and Valproate-Induced Hyperammonemic Encephalopathy in an Adolescent with Diabetes

Young

Coffey²

2010

Journal of Child and Adolescent Psychopharmacology

View full text Add to dashboard Cite

“…Serum levels between 50 and 100 µg/ml are generally accepted for a successful maintenance therapy but peaks up to 180 µg/ml were observed during therapy with 3 × 600 mg per os [6]. Laboratory results show an increased level of serum ammonia without signs of hepatic failure which helps to differentiate from hepatic encephalopathy [7]. EEG usually shows severe bilateral changes, e.g.…”

Section: Discussionmentioning

confidence: 99%

Valproate-Induced Hyperammonemic Encephalopathy

2006

View full text Add to dashboard Cite

Ammonia Induced Encephalopathy from Valproic Acid in a Bipolar Patient: Case Report

Cited by 27 publications

References 15 publications

Astrocyte Glutamine Synthetase: Importance in Hyperammonemic Syndromes and Potential Target for Therapy

Astrocyte Glutamine Synthetase: Importance in Hyperammonemic Syndromes and Potential Target for Therapy

Bipolar Disorder and Valproate-Induced Hyperammonemic Encephalopathy in an Adolescent with Diabetes

Valproate-Induced Hyperammonemic Encephalopathy

Contact Info

Product

Resources

About