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

Primary Category
Neurocritical Care
Secondary Category
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 (500-700µmol/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
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  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV. Task Force on DSM-IV, editor. American Psychiatric Publication, 2000.
  • Venkatesan A, Geocadin RG. Diagnosis and management of acute encephalitis: A practical approach. Neurol Clin Pract. 2014;4(3):206–215. doi:10.1212/CPJ.0000000000000036
  • Lacobone E, Bailly-Salin J, Polito A, et al.: Sepsis-associated encephalopathy and its differential diagnosis Crit Care Med 2009 Vol. 37, No. 10 (Suppl.) DOI: 10.1097/CCM.0b013e3181b6ed58
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  • Wollff, J. A., Caroll, J. E,, Thuy, L. P., Haas, R. and Nyhan, W. L. Carnitine reduces fasting ketogenesis in patients with disorders of propionate metabolism. Lancet 1 (1986) 289-291.
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Manish KC

Written by

Manish KC

ECFMG Certified Physician, Clinical Research Coordinator at the Division of Gastroenterology, Hepatology, and Nutrition at the University of Louisville, Remote Researcher at the Larkin Health System, Miami, Florida

Shahram Khalid

Written by

Shahram Khalid

Physician Owner at Neurology Care

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