What are the causes of metabolic encephalopathy?

Causes of Metabolic Encephalopathy

Metabolic encephalopathy is caused by multiple systemic disturbances that affect brain function, including hepatic failure, renal failure, electrolyte abnormalities, hypoxia, sepsis, and toxic exposures. 1, 2

Common Causes of Metabolic Encephalopathy

Hepatic Causes

• Hepatic encephalopathy in cirrhosis or acute liver failure 3, 1
• Portosystemic shunts 1
• Acute liver dysfunction 1

Electrolyte and Metabolic Disturbances

• Hyponatremia/hypernatremia 3, 1, 4
• Hypokalemia/hyperkalemia 3, 1
• Hypoglycemia/hyperglycemia 1, 4
• Hypercalcemia/hypocalcemia 3
• Uremia (renal failure) 3, 1
• Hypercapnia 3
• Acid-base disorders 1

Nutritional Deficiencies

• Thiamine deficiency (Wernicke's encephalopathy) 1
• Vitamin B12 deficiency 1
• Folate deficiency 1

Toxic Causes

• Medications:
  • Benzodiazepines 3, 1
  • Opioids 3, 1
  • Antiepileptic drugs 3
  • Levodopa 3
  • Anticholinergics 3
  • Lithium 3
  • Clozapine 3
  • Proton pump inhibitors (can worsen hepatic encephalopathy) 3
• Alcohol-related:
  • Acute intoxication 3, 1
  • Withdrawal 3, 1
  • Alcohol-related dementia 3
• Heavy metal poisoning 1
• Illicit drugs 1, 5

Infectious/Inflammatory

• Sepsis 1, 2
• Systemic inflammatory response syndrome 2
• Meningoencephalitis (infectious or autoimmune) 3, 1

Endocrine Disorders

• Thyroid dysfunction (hypo/hyperthyroidism) 3, 1
• Adrenal insufficiency 1
• Diabetic ketoacidosis 1

Vascular/Hypoxic

• Hypoxia/ischemia 2
• Hypertensive encephalopathy 1
• Cerebral microangiopathy 3

Inherited Metabolic Disorders

• Urea cycle defects 3, 1
• Mitochondrial disorders 1

Other Causes

• Sleep disorders (sleep apnea syndrome) 3
• Post-traumatic encephalopathy 3
• Neurodegenerative diseases (may coexist or be confused with metabolic encephalopathy) 3, 6

Diagnostic Approach

Essential Initial Laboratory Tests

• Complete blood count 1
• Comprehensive metabolic panel (including electrolytes, renal and liver function) 1
• Blood glucose 3, 1
• Ammonia levels (particularly for suspected hepatic encephalopathy) 1
• Arterial blood gas analysis 1
• Thyroid function tests 1
• Toxicology screen 1
• Vitamin levels (B12, folate, thiamine) 1

Imaging and Additional Testing

• Brain CT or MRI to rule out structural causes 1
• EEG to exclude subclinical seizures and provide evidence of focal/multifocal brain abnormality 3
• Lumbar puncture if infection is suspected 1

Management Principles

General Approach

1. Identify and treat the underlying cause 1, 7
2. Provide supportive care 7
3. Correct specific metabolic abnormalities 1
4. Protect the airway if consciousness is impaired 1
5. Monitor for complications 1

Specific Management for Common Causes

Hepatic Encephalopathy

• Identify and treat precipitating factors (infection, GI bleeding, constipation, etc.) 3, 1
• Lactulose administration (reduces blood ammonia) 1, 8
• Rifaximin as add-on therapy for recurrent episodes 1
• Avoid protein restriction; ensure adequate protein intake 1
• Consider liver transplantation for recurrent/persistent cases 1

Wernicke's Encephalopathy

• Immediate high-dose parenteral thiamine (200 mg three times daily) before any glucose administration 1
• Long-term thiamine supplementation 1

Electrolyte Disturbances

• Correct electrolyte abnormalities gradually, especially sodium (rapid correction can lead to osmotic demyelination syndrome) 1, 4
• Monitor serum electrolytes frequently during correction 1

Prognosis

Metabolic encephalopathy is associated with:

• Increased mortality (varies by cause; septic encephalopathy: 16-65%, hepatic encephalopathy with cirrhosis: <50% one-year survival) 1, 2
• Prolonged hospitalization 7
• Worse long-term cognitive outcomes 7

Early recognition and prompt treatment of the underlying cause are essential for improving outcomes in patients with metabolic encephalopathy 7, 2.