What is encephalopathy?

Encephalopathy: Definition, Types, and Clinical Approach

Encephalopathy is a clinical state of altered mental status, manifesting as confusion, disorientation, behavioral changes, or other cognitive impairments, with or without inflammation of brain tissue. 1 This condition represents brain dysfunction that can occur with or without structural brain damage.

Distinguishing Encephalopathy from Encephalitis

While often used interchangeably, these terms represent different pathophysiologic processes:

• Encephalopathy: Refers to altered mental status without necessarily having inflammation. It can be triggered by:

  • Metabolic or toxic conditions
  • Infectious agents (e.g., Bartonella henselae, influenza virus)
  • Systemic illness
  • Drug toxicity

• Encephalitis: Characterized specifically by brain inflammation due to:

  • Direct infection of brain parenchyma
  • Post-infectious processes (e.g., acute disseminated encephalomyelitis)
  • Autoimmune conditions (e.g., anti-NMDAR encephalitis) 1

Clinical Features of Encephalopathy

The major clinical manifestations include:

• Altered consciousness (required feature)
• Confusion and disorientation
• Behavioral changes
• Cognitive impairments
• Personality changes
• Decreased level of consciousness (from drowsiness to coma) 1

Additional features may include:

• Seizures
• Focal neurological deficits
• Speech disturbances
• Psychotic symptoms
• Changes in affect (apathy, anxiety, agitation) 1

Major Types of Encephalopathy

1. Infectious/Post-infectious Encephalopathy

• Associated with specific infectious agents without direct brain inflammation
• Examples: Influenza-associated encephalopathy, Bartonella henselae infection 1, 2

2. Metabolic Encephalopathy

• Caused by organ dysfunction or metabolic derangements
• Examples: Hepatic encephalopathy, uremic encephalopathy, hypoglycemic encephalopathy 3

3. Toxic Encephalopathy

• Due to exposure to toxins, medications, or drugs
• Examples: Systemic anticancer therapy-induced encephalopathy 1

4. Septic Encephalopathy

• Most frequent infection-associated encephalopathy in adults (50-70% of septic patients)
• Occurs in patients with extracranial focus of sepsis
• Characterized by progression from slowing of mentation to delirium and coma
• Neurological findings are usually symmetrical 1

5. Posterior Reversible Encephalopathy Syndrome (PRES)

• Presents with altered consciousness, visual disturbances, headaches, and seizures
• Associated with disruption of blood-brain barrier due to endothelial injury
• Risk factors include hypertension, renal impairment, immunosuppression 1

6. Autoimmune Encephalopathy

• Includes steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT)
• Can present with altered mental status, seizures, and cognitive dysfunction 4

Diagnostic Approach

A practical approach to diagnosing encephalopathy is to group etiologies by their pace of onset and evolution:

• Sudden (seconds to minutes)
• Acute (hours to days)
• Subacute (days to weeks)
• Chronic (weeks to months) 5

Key diagnostic steps include:

1. Thorough history focusing on:

   • Onset and progression of symptoms
   • Recent infections or fevers
   • Medication use and toxin exposure
   • Travel history
   • Contact with animals or insects 1

2. Physical examination focusing on:

   • Mental status assessment
   • Evidence of seizures
   • Focal neurological signs
   • Presence of rash or other systemic signs 1

3. Laboratory and imaging studies:

   • CSF analysis when appropriate
   • Brain imaging (CT/MRI)
   • EEG (especially to rule out non-convulsive status epilepticus)
   • Metabolic workup
   • Specific tests based on suspected etiology 1

Management Considerations

Management depends on the underlying cause:

• For toxic causes: Discontinuation of offending agent 1
• For PRES: Strict blood pressure control and supportive care 1
• For autoimmune encephalopathy: Corticosteroids may be beneficial 4
• For septic encephalopathy: Treatment of underlying infection 1
• For metabolic causes: Correction of underlying metabolic derangement

Important Caveats

• Non-convulsive status epilepticus can mimic encephalopathy and requires EEG for diagnosis 1
• The clinical features of encephalopathy are often non-specific and do not reliably identify a particular etiology 1
• Encephalopathy in cancer patients may be facilitated by concomitant septic disease, pre-existent leukoencephalopathy, and metabolic changes 1
• Subtle presentations of encephalopathy can be mistaken for psychiatric illness or substance abuse 1

Understanding the specific cause of encephalopathy is crucial for appropriate management and improving outcomes related to morbidity, mortality, and quality of life.