Acute Encephalopathy

Authors:

Manish KC, Michael Madueke MBBS,

Shahram Khalid

Introduction

• 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

Epidemiology

• 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

Etiology

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

Figure 2: Mechanism of Sepsis induced Acute encephalopathy

Figure 3: Mechanism of Acute Metabolic Encephalopathy

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

Diagnosis

• 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

Treatment

• 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

Complications

• Coma

• Multiorgan failure

• Permanent neurological damage

• Death

Prognosis

• 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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Bibliography

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