What are the causes and management of encephalopathy?

Causes of Encephalopathy

Encephalopathy has numerous etiologies including infectious, metabolic, toxic, autoimmune, and vascular causes, with the most common infection-associated encephalopathy being septic encephalopathy, found in 50-70% of septic patients. 1

Infectious Causes

• Viral encephalitis

  • Herpes simplex virus (HSV)
  • Varicella zoster virus (VZV) - can occur during primary infection or reactivation 1
  • Enteroviruses
  • Arboviruses (West Nile virus, Japanese encephalitis, tick-borne encephalitis)
  • Measles, mumps, influenza

• Bacterial causes

  • Septic encephalopathy - most common infection-associated encephalopathy 1
  • Listeria monocytogenes
  • Mycobacterium tuberculosis (TB meningitis)

• Parasitic/Other

  • Cerebral malaria
  • Toxoplasmosis (particularly in immunocompromised)
  • Cryptococcus neoformans

Metabolic Causes

• Hepatic encephalopathy - characterized by:

  • Hyperammonemia
  • Temporospatial disorientation
  • Fluctuating consciousness 1

• Other metabolic disorders

  • Uremic encephalopathy
  • Hypoglycemia/hyperglycemia
  • Hyponatremia/hypernatremia - hyponatremia below 130 mmol/L is an independent risk factor for hepatic encephalopathy 1
  • Hypoxic-ischemic encephalopathy
  • Thyroid disorders (hypo/hyperthyroidism)
  • Inherited metabolic disorders (especially urea cycle defects) 1

Toxic Causes

• Medications

  • Chemotherapeutic agents - can cause acute encephalopathy 1
  • Benzodiazepines - contraindicated in decompensated cirrhosis 1
  • Proton pump inhibitors (when used inappropriately) 1

• Substance-related

  • Alcohol (Wernicke's encephalopathy)
  • Illicit drugs
  • Industrial toxins

Autoimmune/Inflammatory Causes

• Antibody-mediated encephalitis

  • Characterized by sub-acute presentation (weeks-months)
  • May present with orofacial dyskinesia, choreoathetosis, faciobrachial dystonia
  • Intractable seizures or hyponatremia 1

• Acute Disseminated Encephalomyelitis (ADEM)

  • Post-infectious or post-vaccination
  • Predominantly affects subcortical white matter 1, 2

• Acute Necrotizing Encephalopathy (ANEC)

  • Rare but severe condition
  • Primarily caused by viral infections (particularly influenza)
  • Characterized by bilateral thalamic involvement on MRI 2

Vascular Causes

• Posterior Reversible Encephalopathy Syndrome (PRES)

  • Associated with abrupt blood pressure changes
  • Risk factors include pre-existing hypertension, renal impairment, autoimmune diseases
  • Presents with altered consciousness, visual disturbances, headaches, seizures 1

• Cerebral venous thrombosis

• Vasculitis

Other Causes

• Non-convulsive status epilepticus

  • Found in up to 8% of comatose patients with no clinical evidence of seizure activity 1
  • Requires EEG for diagnosis

• Cerebral edema and intracranial hypertension

  • Common complication in acute liver failure 1

• Sleep disorders

  • Sleep apnea syndrome 1

Clinical Features and Diagnostic Approach

Encephalopathy typically presents with:

• Altered mental status ranging from mild confusion to coma
• Disorientation and behavioral changes
• Decreased attention and concentration
• Seizures (in some cases)
• Focal neurological deficits (may be present)

Diagnostic workup should include:

1. Laboratory tests

   • Complete blood count
   • Metabolic panel (including glucose, electrolytes)
   • Liver and kidney function tests
   • Ammonia levels (for suspected hepatic encephalopathy)
   • Blood cultures (if infection suspected)
   • Toxicology screen

2. Cerebrospinal fluid analysis

   • Opening pressure
   • Cell count and differential
   • Protein and glucose
   • PCR for viral pathogens (HSV, VZV, enteroviruses)
   • Culture for bacteria
   • Specialized testing based on clinical suspicion

3. Neuroimaging

   • MRI is preferred over CT for most encephalopathies 1
   • CT may be needed before lumbar puncture if increased intracranial pressure is suspected

4. Electroencephalography (EEG)

   • Essential for diagnosing non-convulsive status epilepticus
   • Shows characteristic patterns in various encephalopathies

Management Principles

Management depends on the underlying cause but generally includes:

1. Treat the underlying cause

   • Antimicrobials for infectious causes
   • Correction of metabolic abnormalities
   • Removal of toxins/medications

2. For hepatic encephalopathy

   • Lactulose - reduces blood ammonia levels by 25-50% 3
   • Rifaximin (in combination with lactulose)
   • Avoid benzodiazepines 1
   • Monitor and correct hyponatremia 1

3. For cerebral edema/increased intracranial pressure

   • Elevate head of bed
   • Mannitol for severe ICP elevation
   • Consider ICP monitoring in severe cases 1

4. For autoimmune encephalitis

   • High-dose corticosteroids
   • Intravenous immunoglobulin (IVIG)
   • Plasma exchange in refractory cases 2

5. Supportive care

   • Airway management
   • Hemodynamic support
   • Seizure control
   • Prevention of complications

Pitfalls and Caveats

• Encephalopathy is often misdiagnosed or diagnosed late due to its non-specific presentation
• Multiple causes may coexist (e.g., sepsis and metabolic abnormalities)
• Focal neurological signs may be absent in many forms of encephalopathy
• Non-convulsive status epilepticus requires a high index of suspicion and EEG for diagnosis
• In travelers returning from endemic areas, consider tropical causes like malaria and dengue 1
• In immunocompromised patients, consider opportunistic infections and atypical presentations 1

Early recognition and prompt treatment of the underlying cause are essential for improving outcomes in all forms of encephalopathy.