Acute Encephalopathy

Change in level of consciousness associated with altered cognition and/or perception appearing over hours/days that is not secondary to prior/developing chronic dementia. Encephalopathy results in acute structural brain changes to non-structural, metabolic, toxic, infection related brain dysfunction

Manish KC
Manish KC
, Michael Madueke MBBS,
Shahram Khalid
Shahram Khalid


  • Change in level of consciousness associated with altered cognition and/or perception appearing over hours/days that is not secondary to prior/developing chronic dementia
  • Encephalopathy results in acute structural brain changes to non-structural, metabolic, toxic, infection related brain dysfunction
  • Change in mental status that affects a patient's perception
  • Abrupt deterioration in mental status not secondary to seizure or syncopal episode
  • Common neurological emergencies related to chronic neurological decline
  • Important cause of morbidity and mortality in ICU and post-operative patients


  • Commonly seen in elderly and critically ill patients
  • Over 250,000 patients affected in the US in the last decade
  • Death rate increases with increased severity of encephalopathy
  • Delirium/coma in septic encephalopathy doubles the risk of mortality


Causes of encephalopathy include

  • Metabolic Causes:
    • Hepatic encephalopathy
    • Hypoglycemia
    • Hypoxia
    • Hypercapnia
    • Uremia
    • Electrolyte abnormalities (hyponatraemia, hypo/hypercalcaemia, hypo/hypermagnesemia)
    • Hyperammonemia
    • Organic acid and amino acid disorders
    • Fatty acid oxidation disorders
    • Vitamin Deficiency: Thiamine, Folic acid, cobalamin, nicotinic acid
    • Toxins/poisons: (carbon monoxide, organic solvents, lead, manganese, mercury, carbon disulphide, heavy metals)
  • Infective causes:
    • Meningitis/Encephalitis
    • Parainfectious encephalomyelitis
    • Cerebral abscess
    • Neurosyphilis
    • HIV syndromes
    • Lyme disease
    • Systemic infections with septicemia
    • Progressive multifocal leukoencephalopathy
  • Neurological causes:
    • Stroke
    • Seizure
    • Subdural hematoma
    • Intracerebral hemorrhage
    • Subarachnoid hemorrhage with vasospasm
    • Hydrocephalus
    • Brain tumors
    • Migraine
  • Trauma:
    • Traumatic brain injury
    • Concussion
  • Acid-base disorders:
    • Acidosis
    • Alkalosis
  • Organ related causes:
    • Liver failure: Hyperammonemia
    • Renal failure: Uremia, electrolyte imbalance
    • Lung disease: CO2 narcosis
    • Thyroid dysfunction: Myxedema coma, hypothyroidism
    • Parathyroid dysfunction: Hypo/hyperparathyroidism
    • Pancreas dysfunction: Diabetes, hypoglycemia
    • Adrenal dysfunction: cushing syndrome, pheochromocytoma, Addison disease

Figure 1: Mechanism of Hypoglycemia induced encephalopathy

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Figure 2: Mechanism of Sepsis induced Acute encephalopathy

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Figure 3: Mechanism of Acute Metabolic Encephalopathy

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Clinical Features

  • Altered mental status
  • Altered sleep/wake pattern
  • Coma
  • Delirium
  • Disorientation
  • Hallucination
  • Impaired thinking
  • Impaired concentration
  • Agitation
  • Inappropriate behaviour
  • Inattention
  • Paratonic rigidity
  • Loss of deep tendon reflexes

Differential Diagnosis

  • Trauma
  • Meningitis/encephalitis
  • Intracranial Space-occupying lesion
  • Drug overdose or withdrawal
  • Hypoxia/ischemia
  • Hypertension
  • Cerebral vasculitis
  • Metabolic causes


  • Complete Blood count
  • Comprehensive metabolic profile
    • Effective for metabolic acute encephalopathy
  • CT scan of Head
    • Can detect hematoma, neoplasms, structural brain changes
  • MRI of brain
    • Can identify recent stroke, cerebral blood vessels and white matter changes
  • Lumbar puncture and CSF analysis
    • Useful for septic encephalopathy
    • Consider in Autoimmune encephalopathy
  • Electroencephalogram:
    • Most sensitive for sepsis induced acute encephalopathy
    • Findings: mild, diffuse, reversible slowing of background frequencies in sepsis
    • With deterioration of encephalopathy, changes in EEG are observed. Initial mild changes start with theta waves followed by delta waves then diffuse triphasic waves and eventually by Suppression
  • Urine and blood culture:
    • Detect septic changes
  • Drug chart screening


  • Correction of the underlying cause is the mainstay of treatment as this improves the systemic inflammation and allows speedy recovery of multiple organs including the brain
  • General management:
    • Supportive treatment: maintain oxygenation, circulation, normal body temperature, prevent agitation
    • Correction of electrolyte abnormalities, acidosis, seizures
    • Correction of underlying abnormalities
    • Avoidance of neurotoxic drugs
    • Reduce raised intracranial pressure:
      • Intubation and mechanical ventilation
      • Restrict fluids
      • Monitor Intracranial pressure
      • Use Mannitol 0.25-0.5 g/kg then furosemide l mg/kg for raised ICP
      • Pentobarbitone or thiopentone if necessary
  • Specific Management:
    • Hypoglycemia: IV bolus of glucose followed by infusion
    • Hyperammonemia:
      • Sodium Benzoate and Phenylacetic or phenylbutyric acid
      • Hemodialysis in case of very high ammonia (500-700ยตmol/l) or poor response to therapy
    • Organic acidemia: glycine, carnitine and hemodialysis
    • Liver disease: For acute Wilson disease, use albumin infusion, plasmapheresis, dialysis, and liver transplantation
    • Sepsis induced encephalopathy:
      • Correction of underlying source of infection
      • Intensive insulin therapy if hyperglycemia is observed
      • Activated protein C
      • Steroids
      • Appropriate use of antibiotics
      • Branched chain amino acids


  • Coma
  • Multiorgan failure
  • Permanent neurological damage
  • Death


  • Poor prognosis in patients with severe cerebral dysfunction
  • In sepsis induced encephalopathy, death rate depends upon the EEG changes
    • Mortality rate 0% in normal waves
    • Mortality rate 19% in theta waves
    • Mortality rate 36% in delta waves
    • Mortality rate 50% in triphasic waves
    • Mortality rate 67% in suppression waves
  • Death rate correlates with plasma level of biomarkers
  • Symptoms are reversible in the early stage of encephalopathy
  • Prognosis is poor as time passes
"If anyone saved a life, it would be as if he saved the life of all mankind"
"If anyone saved a life, it would be as if he saved the life of all mankind"

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