Hepatic encephalopathy in cats

© August, JR (2006) Consultations in Feline Internal Medicine, Vol 5.  Elsevier Saunders

Seizures associated with clinical signs of hepatic encephalopathy (HE) in cats occur relatively infrequently. Causes of HE include portosystemic shunting (usually congenital), severe hepatic lipidosis, cholangitis / cholangiohepatitis (either primary or secondary to infectious diseases such as FIP), neoplasia and end-stage liver disease. A myriad of metabolic imbalances and toxic substances act synergistically to produce neurological signs. The major contributor to the clinical signs observed is hyperammonemia. Mercaptans, indoles, and aromatic amino acids also play a role in abnormal neurotransmission and generation of false neurotransmitters available for use in the brain. Increases in excitatory neurotransmitters such as glutamate and alterations in endogenous benzodiazepines have been documented in animals with seizures. These endogenous benzodiazepines, or endozepines, which seem to be produced chiefly by the glial cells, have been partially purified in the human brain. The term endozepines designates both a diazepam-binding inhibitor and the peptides derived from it, including triakontatetraneuropeptide (TTN) and octadecaneuroepetide (ODN). High cerebral concentrations of these endozepines may explain the relative rarity of seizures in cats with HE. The exact role of these metabolic by-products in the generation of seizures has not been determined.

A rare cause of hepatic encephalopathy is a deficiency of hepatic urea cycle enzymes. 

Clinical signs

Depending on the underlying cause of the HE, most cats will be systemically ill. Jaundice is a common clinical sequela. Neurological signs are consistent with a diffuse forebrain localisation and commonly are episodic in onset. If seizures occur, they are accompanied by long periods of abnormal behaviour and mentation. Aberrant or bizarre behaviour, dementia, aggression, ataxia, head pressing, propulsive circling, blindness, ptyalism, and partial or generalised seizures, may be observed. In cases of portosystemic shunts, the aforementioned signs may occur within hours after eating and often are accompanied by severe ptyalism, Excess salivation is not a manifestation of seizure activity but is theorised to be due to cerebrocortical-mediated abnormal behaviour.

Diagnosis

Routine blood tests in addition to preprandial and postprandial bile acids, resting ammonia levels, abdominal ultrasound, rectal portal scintigraphy and intraoperative portography, and liver biopsy are useful diagnostic tools.

Treatment

Low-protein diets, oral and parenteral antibiotics, antifibrotic agents, and lactulose are indicated for medical treatment of HE depending on the underlying cause.

Surgical correction is the treatment of choice for an extrahepatic shunt in the feline patient. Placement of an ameroid ring constrictor on single extrahepatic portosystemic shunts in cats resulted in a low rate of surgical complication and post-operative mortality. Many cats did have postoperative complications. Neurological complications included central blindness, hyperthermia, frantic behaviour, and generalised motor seizures. The pathophysiological mechanism of post-ligational seizures is poorly understood. Alterations in benzodiazepine concentration have been associated with post-ligational seizures. Animals may decompensate as a consequence of down-regulation of receptors and rapid decrease in concentration of circulating neurotransmitters.

Medications with interfere with benzodiazepine receptors (endozepines), such as Flumazenil may be affective at alleviating clinical signs. Dose rates of 0.2 mg/cat given as required as an intravenous bolus have had some anecdotal benefits but more studies are needed to assess the viability of this drug in a clinical setting.