How is hepatic encephalopathy diagnosed and treated in children?

Diagnosis of Hepatic Encephalopathy in Children

The diagnosis of hepatic encephalopathy in children requires a combination of clinical assessment, neuropsychological testing, laboratory studies, and neurophysiological tests, with neuropsychological assessment being the gold standard for detecting minimal hepatic encephalopathy.

Clinical Assessment

Grading System

• Use the West Haven criteria for grading hepatic encephalopathy 1:
  • Grade I (Minimal/Covert): Mild confusion, impaired attention, personality changes
  • Grade II: Lethargy, disorientation, inappropriate behavior, asterixis
  • Grade III: Somnolence but responsive to stimuli
  • Grade IV: Coma

Clinical Manifestations

• Early signs 1:

  • Mild confusion
  • Impaired attention
  • Irritability
  • Personality changes
  • Sleep-wake cycle disturbances

• Progressive symptoms 1:

  • Disorientation to time and space
  • Inappropriate behavior
  • Lethargy
  • Asterixis
  • Myoclonic jerks
  • Hyperreflexia or hyporeflexia

• Advanced manifestations 1:

  • Somnolence
  • Stupor
  • Seizures
  • Coma

Diagnostic Methods

Neuropsychological Assessment

• Gold standard for diagnosis of minimal hepatic encephalopathy (MHE) 2
• Consists of tests that quantify brain dysfunction and interpretation of results 2
• Should assess multiple cognitive domains 2:
  • Attention and mental speed (most prominently affected)
  • Memory
  • Executive functions
  • Perception
  • Constructive abilities

Short Neuropsychological Batteries

• Psychometric Hepatic Encephalopathy Score (PHES) 2:
  • Specifically developed for MHE diagnosis
  • Combines five paper-pencil tests
  • Scores compared to normograms of healthy controls
  • Available for German, Italian, and Spanish populations

Computerized Tests

• Critical Flicker Frequency 2:

  • Assesses degree of vigilance
  • Shows covariation with severity of encephalopathy
  • Simple and reliable on repeated testing

• Other computerized tests 2:

  • Assess speed of mental processing (reaction time)
  • Assess accuracy of cognitive functions

Neurophysiological Tests

• Electroencephalography (EEG) 2, 1:

  • Objective assessment
  • Less affected by age or education
  • Useful for repeated studies (no learning effects)
  • Particularly valuable for unexplained altered mental status
  • Can detect non-convulsive status epilepticus

• Evoked potentials 2:

  • Objective assessment
  • Useful in difficult cases (patients with multiple comorbidities or low educational background)

Laboratory Tests

• Blood ammonia levels 1:

  • Essential for suspected hepatic encephalopathy
  • Proper sampling is crucial 2:
    • Fasting patient
    • Avoid venous stasis
    • EDTA-containing tube
    • Place immediately on ice
    • Transport to lab within 60-90 minutes
  • Note: The degree of hyperammonemia does not always correlate with clinical severity 3

• Additional laboratory tests 1:

  • Complete blood count
  • Comprehensive metabolic panel
  • Thyroid function tests
  • Toxicology screen if indicated

Neuroimaging

• Brain MRI 2, 1:

  • Preferred over CT to rule out structural causes
  • Assess for cerebral edema
  • Should be performed before lumbar puncture if contraindications exist

• Magnetic Resonance Spectroscopy (MRS) 2, 4, 5:

  • Shows good diagnostic performance in HE
  • Reveals changes in:
    • Increased glutamine/glutamate
    • Decreased choline
    • Decreased myo-inositol
  • Primarily in the parietal lobe
  • Limited accessibility (mainly academic hospitals)

• Diffusion Tensor Imaging (DTI) 4:

  • Mean diffusivity (MD) significantly higher in MHE
  • Frontal white matter MD has 73.5% sensitivity and 100% specificity for diagnosing MHE
  • Reliable objective tool for MHE diagnosis

Special Considerations in Children

Prevalence and Challenges

• Approximately 50% of children with chronic liver disease develop MHE 4
• Clinical manifestations can be challenging to identify in children 3
• Lack of standardized neuropsychological tests for all age ranges 5

Correlation with Biomarkers

• Brain metabolite changes correlate with 4, 5:
  • Plasma ammonia levels
  • Branched-chain to aromatic amino acids ratio (BCAA/AAA)
  • Inflammatory markers (IL-6, TNF-α)

Differential Diagnosis

Essential Workup for Differential Diagnosis 2

• Recent medical history (infections, trauma, withdrawal, psychotropic drugs)
• Complete medical history (diabetes, neurovascular diseases, epilepsy)
• Neurological examination
• Common blood tests
• Brain imaging (preferably MRI)
• Sometimes EEG

Common Differential Diagnoses 2

• Metabolic encephalopathy: uremia, hypercapnia, hypoglycemia
• Hydroelectrolytic disorders: hypokalemia, hypomagnesemia
• Drug-induced: antiepileptic drugs, levodopa, opiates, benzodiazepines
• Vitamin deficiencies: Wernicke-Korsakoff syndrome, vitamin B12/folate deficiency
• Cerebral microangiopathy
• Neurodegenerative diseases
• Psychiatric disorders

Management Approach

• Identify and treat the underlying cause of liver disease 3
• Reduce hyperammonemia 3:
  • Enteral medications (lactulose, rifaximin)
  • Consider extracorporeal liver support in severe cases
• For acute severe hepatic encephalopathy 2:
  • Glucocorticoid therapy (prednisone/prednisolone 0.5-1 mg/kg daily in adults, up to 2 mg/kg in children)
  • Abandon ineffective treatment quickly (within 1-2 weeks)
  • Consider liver transplantation if no improvement or clinical deterioration

Pitfalls and Caveats

• Ammonia levels do not always correlate with clinical severity 3
• MHE may be underdiagnosed due to subtle manifestations 2
• Neuropsychological test results may be affected by age, gender, and education level 2
• Careful assessment for hepatic encephalopathy is crucial as progression can indicate impending cerebral edema 3
• Neurophysiological tests provide limited behavioral information 2