From the Guidelines
Encephalopathy is primarily caused by metabolic disturbances, such as liver failure leading to hepatic encephalopathy, which is often associated with hyperammonemia and other factors related to liver pathology 1. The main causes of encephalopathy can be categorized into several groups, including:
- Metabolic disturbances: liver failure leading to hepatic encephalopathy, kidney failure causing uremic encephalopathy, uncontrolled diabetes, and electrolyte imbalances
- Toxic exposures: alcohol, drugs, heavy metals, and industrial chemicals
- Infections: meningitis, encephalitis, and systemic infections leading to septic encephalopathy
- Oxygen deprivation: cardiac arrest, respiratory failure, carbon monoxide poisoning
- Traumatic brain injuries
- Autoimmune conditions: autoimmune encephalitis Other causes include hypertensive encephalopathy from severe high blood pressure, posterior reversible encephalopathy syndrome (PRES), nutritional deficiencies (particularly thiamine deficiency leading to Wernicke's encephalopathy), and neurodegenerative diseases. According to the 2021 ISHEN guidelines on animal models of hepatic encephalopathy 1, hyperammonemia remains a key focus in the pathogenesis of HE, but other factors associated with HE have also been identified. The symptoms of encephalopathy typically include altered mental status, confusion, personality changes, difficulty concentrating, memory problems, and in severe cases, seizures or coma. Treatment should focus on addressing the underlying cause while providing supportive care, as early identification and treatment of the specific cause is crucial for preventing permanent brain damage 1.
From the Research
Causes of Encephalopathy
- Hepatic encephalopathy (HE) is a complication of acute or chronic liver failure, involving multiple organ systems 2
- The condition is characterized by cognitive and motoric deficits of varying severity, and is thought to reflect the clinical manifestation of a low-grade cerebral edema 3
- The pathogenesis of HE is complex, and involves factors such as:
- Ammonia toxicity, which elicits astrocyte swelling and causes brain edema 4
- Hyponatremia, a condition frequently observed in hepatic cirrhosis, which exacerbates brain edema 4
- Oxidative/nitrosative stress and astrocyte swelling, which is associated with an oxidative/nitrosative stress response in the brain 3
- Precipitating factors such as electrolyte disturbances, bleeding, infections, high protein diet, diuretics, and sedatives 3
- Liver impairment is also a cause of HE, leading to a multitude of symptoms in affected patients, including change in level of consciousness, intellectual function, and neuromuscular function 5
Underlying Mechanisms
- The action of various factors integrates at the level of oxidative/nitrosative stress and astrocyte swelling, which is associated with an oxidative/nitrosative stress response in the brain 3
- Ammonia toxicity plays a major role in the pathogenesis of HE, and alleviating ammonia toxicity is essential for treatment 4
- The pathophysiological role of ammonia toxicity on astrocyte and neuronal injury/damage is also important, and may lead to permanent neuronal injury 6