Equine enteric hyperammonemia: time for a multicenter study?

The research article discusses the neurologic syndrome in horses known as Hepatic encephalopathy (HE) with hyperammonemia, its causes, symptoms and proposes the need for a multicenter study on the rare occurrence of enteric encephalopathy (EE) in horses without evidence of hepatic disease.

Hepatic Encephalopathy (HE) in Horses

• Hepatic encephalopathy (HE) with hyperammonemia is a common neurological disorder in horses, resulting from various liver diseases.
• HE signifies extensive liver cell degeneration or necrosis, or acquired or congenital shunting of the blood vascular system around the liver (portosystemic vascular shunting).
• The diagnosis happens by identifying hyperammonemia, concurrent with abnormal liver histopathology findings or increased levels of certain enzymes and acids indicating liver disease.

Enteric Encephalopathy (EE) in Horses

• EE has similar symptoms to HE but occurs in horses with enteric disease who have no signs of liver disease. It has been rarely reported, following just ten cases post an initial single case report in 1995.
• The paper discusses the possible biochemical processes contributing to hyperammonemia in horses with EE. It includes factors like increased extraneural glutamate that causes neuronal excitotoxicity, and the stimulatory impact of ammonia on receptors in the brain leading to increased neuron activity and dysfunction.
• The study highlights the role of mitochondrial permeability transition (MPT) in the dysfunction of astrocytes, a type of brain cell, in hyperammonemia.
• The authors mention that acute hyperammonemia often results in brain edema, which could significantly reduce survival chances. The process involves increased serotonin release, enhancing blood flow, and possibly increases in glutamate and a cellular detoxifying compound called glutathione.

Characteristics and Possible Causes of EE

• In the ten cases of EE described thus far, a consistent symptom was colic occurring up to four days before neurological signs developed.
• The study proposes that EE might result from an overgrowth of gut bacteria leading to increased ammonia synthesis or increased ammonia absorption possibly due to a compromised gut wall. This hypothesis is however tentative as in some cases no damage to the gut wall was observed.
• Contributing factors could include endotoxemia and the administration of nonsteroidal anti-inflammatory drugs (NSAIDs), both conditions that may increase gut wall permeability.
• The study also presents consistent biochemistry findings in these cases: metabolic acidosis, increased lactate concentration or anion gap, and high blood glucose. It suggests these changes could be common in equine enteric disease and thus show no definite linkage to the development of hyperammonemia.

Need for Multicenter Study

• The research ends calling for a multicenter study to determine the incidence, predisposing factors, and possible mechanisms underlying EE in horses. Such a study could increase our understanding of risk factors, allowing for timely therapeutic intervention to prevent a potentially fatal encephalopathy.