Kernicterus - Pediatric - Lecture Slides, Slides of Pediatrics

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Kernicterus

History

• Earliest work on jaundice from Baumes-

1785, and Hervieux-

• Kernicterus was first described by Johannes

Orth, 1875

• He postulated that jaundice might have hematologic origins
• He noted that the brain in jaundiced adults wasn’t affected
• Christian Schmorl coined the term in 1904
• Translated, Kernicterus means jaundice of the ―kern‖ or nuclear region of the brain

Bilirubin Conjugation

Pathophysiology

Newborn Hyperbilirubinemia

• Relatively high hematocrit; more cells to

break down

• UDP-Glucuronyl Transferase is not fully

functional until 3-4 months of life

• Relative starvation state and slow transit

time, especially in breastfeeders

• Breastmilk contains beta-glucuronidase;

enterohepatic circulation is increased

Pathophysiology

• UCB is lipophilic and crosses the Blood-Brain Barrier
  • In vitro, free UCB will not precipitate out of solution unless in the presence of a polar lipid membrane
  • In theory, only free UCB crosses, albumin-bound does not.
  • BBB of infants is more permeable than adults, and acidosis causes it to be even more permeable.
• UCB has an affinity for the basal ganglia, hippocampus, cranial nerve nuclei - Mechanism is widely studied, but still unknown
• UCB interrupts metabolism in glial cells and causes apoptosis of neurons - Exact mechanisms are unknown, but definitely separate pathways. - Age of the cell is inversely proportional to susceptibility docsity.com

MRI of an infant who suffered from

severe Erythroblastosis Fetalis

Clinical Manifestations:

Bilirubin Encephalopathy

• Chronic Encephalopathy: (Perlstein’s Tetrad: Extrapyramidal Abnormalities, Hearing Loss, Gaze abnormality, and Dental Dysplasia)
• Extrapyramidal abnormalities: Facial grimacing, drooling, dysarthria, and athetosis--may develop by 18mo or delayed to 8or9 years.
• Hearing loss is usually due to injury of the cochlear nuclei in the brainstem. It may be the only manifestation
• Gaze abnormalities: Limitation of upward gaze, palsies
• Cerebral cortex is relatively spared, so intelligence is often close to normal.

Diagnosis

• Kernicterus is a pathologic diagnosis, not

clinical. Post-mortem exam of the brain is

the definitive diagnosis

• Clinically, kernicterus is suspected based on

the history of hyperbilirubinemia and the

clinical manifestations as mentioned above.

• The degree of hyperbilirubinemia does not correlate well with the development or severity of kernicterus.

Prevention: Treatment of

Hyperbilirubinemia

• Phototherapy
  • Initiate based on UCB level and baby’s age
  • Isomerizes UCB to Lumirubin, soluble in water and excreted via the kidney
• Exchange transfusion
  • Initiate if phototherapy fails, repeat as needed
  • Incidence of kernicterus has dropped since the advent
• Sn-Mesoporphyrin
  • Inhibits Heme-oxygenase, which is the rate-limiting enzyme in heme catabolism.
  • Only case reports thus far, where exchange transfusion was refused

Treatment

• Treatment of clinically suspected

kernicterus is centered around early

intervention from multiple disciplines

• Neurodevelopmental Pediatrics
• Neurology
• Physical and Occupational Therapy
• Audiology
• Ophthalmology
• Speech Therapy
• School, County, EFMP

Follow Up: Spasticity/Dystonia

• Botox, Baclofen for severe posturing
• Physical therapy for training of muscles and

teaching stretching techniques

• Occupational Therapy for independence and

activities of daily living

• Speech Therapy
• Equipment—Appropriate chairs, braces, etc

Follow Up: Gaze Abnormality

• Early involvement of ophthalmology
  • Strabismus surgery as needed
  • Correction/patching as needed

Follow Up: Cognitive Delays

• Cerebral cortex is usually relatively spared,

but cognitive delays may be present

• Neurodevelopmental Pediatrician to continually reassess for these delays
• Early diagnosis of learning disabilities
• Early intervention, special schools, IEPs as appropriate