Skip to main content
SpringerLink
Log in

Kernicterus (Bilirubin Encephalopathy)

  • Chapter
Developmental Neuropathology

Abstract

The first report of kernicterus is widely attributed to Orth (1875), but his description is not clear and emphasizes superficial staining of the brain and the ventricular walls. The first comprehensive description of the disease was given by Schmorl (1903), who distinguished two types of cerebral lesions in icteric infants. One was a diffuse staining of the tissue in infants with periventricular infarcts. The other lesion, called kernicterus by Schmorl, was observed in six infants who had selective icteric discoloration of the subthalamic nuclei, Ammon’s horn, lentiform nuclei, and dentate and olivary nuclei; the thalamus and cerebral cortex were spared. An intense yellow discoloration of many, though not all, of the nerve cells and a delicate staining of the intervening tissue were observed microscopically. Subsequent publications were reviewed by Zimmerman and Yannet (1933) and Péhu and Dollet (1939). The term “kernicterus” is now used to designate the pathologic lesions as well as the clinical disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ackerman BD, Dyer GY, Taylor PM (1971) Decline in serum bilirubin concentration coincident with clinical onset of kernicterus. Pediatrics 48:647–650

    PubMed  CAS  Google Scholar 

  • Ahdab-B armada M, Moossy J (1984) The neuropathology of kernicterus in the premature neonate: diagnostic problems. J Neuropathol Exp Neurol 43:45–56

    Article  PubMed  CAS  Google Scholar 

  • Bailey A, Robinson D, Dawson AM (1977) Does Gilbert’s disease exist? Lancet 1:931–933

    Article  PubMed  CAS  Google Scholar 

  • Balthasar K (1939) Über die Beteiligung des Globus pallidus bei Athetose und Paraballismus. Dtsch Z Nervenheilkd 148:243–261

    Article  Google Scholar 

  • Blanc WA, Johnson L (1959) Studies on kernicterus. Relationship with sulfonamide intoxication, Report on kernicterus in rats with glucuronyl transferase deficiency and review of pathogenesis. J Neuropathol Exp Neurol 18:165–187

    Article  PubMed  CAS  Google Scholar 

  • Brodersen R (1980) Bilirubin transport in the newborn infant, reviewed with relation to kernicterus. J Pediatr 96:349–356

    Article  PubMed  CAS  Google Scholar 

  • Brown AK, Burnett H (1957) Studies on the neonatal development of the glucuronide conjugating system. Am J Dis Child 94:510–511

    Google Scholar 

  • Chen H-C (1964) Kernicterus in the Chinese newborn. A morphological and spectrophotometric study. J Neuropathol Exp Neurol 23:527–549

    Article  PubMed  CAS  Google Scholar 

  • Chen H-C, Lien I-N, Lu T-C (1965) Kernicterus in newborn rabbits. Am J Pathol 46:331–343

    PubMed  CAS  Google Scholar 

  • Claireaux A (1950) Haemolytic disease of the newborn. Parts I and II. Arch Dis Child 25:61–80

    Article  PubMed  CAS  Google Scholar 

  • Claireaux AE, Cole PG, Lathe GH (1953) Icterus of the brain in the newborn. Lancet 2:1226–1230

    Article  Google Scholar 

  • Corner B (1955) Kernicterus and prematurity. Am J Dis Child 90:520–521

    Google Scholar 

  • Crigler JF, Najjar VA (1952) Congenital familial nonhemolytic jaundice with kernicterus. Pediatrics 10:169–180

    PubMed  Google Scholar 

  • Diamond I, Schmid R (1967) Oxidative phosphorylation in experimental bilirubin encephalopathy. Science 155:1288–1289

    Article  PubMed  CAS  Google Scholar 

  • Ebbesen F, Nyboe J (1983) Postnatal changes in the ability of plasma albumin to bind bilirubin. Acta Paediatr Scand 72:665–670

    Article  PubMed  CAS  Google Scholar 

  • Ernster L, Herlin L, Zetterström R (1957) Experimental studies on the pathogenesis of kernicterus. Pediatrics 20:647–652

    PubMed  CAS  Google Scholar 

  • Gardner WA Jr, Konigsmark BW (1969) Familial nonhemolytic jaundice: bilirubinosis and encephalopathy. Pediatrics 43:365–376

    PubMed  Google Scholar 

  • Gartner LM, Snyder RN, Chabon RS, Bernstein J (1970) Kernicterus: high incidence in premature infants with low serum bilirubin concentrations. Pediatrics 45:906–917

    PubMed  CAS  Google Scholar 

  • Hallervorden J, Meyer J-E (1956) Cerebrale Kinderlähmung. (Früherworbene körperliche und geistige Defektzustände.) In: Handbuch der Speziellen Pathologischen Anatomie und Histologie, vol XIII/4. Springer, Berlin Heidelberg Göttingen, pp 194–282

    Google Scholar 

  • Hansen TWR, Bratlid D (1986) Bilirubin and brain toxicity. Acta Paediatr Scand 75:513–522

    Article  PubMed  CAS  Google Scholar 

  • Haymaker W, Margoles C, Pentschew A, Jacob H, Lindenberg R, Saenz Arroyo L, Stochdorph O, Stowens D (1961) Pathology of kernicterus and posticteric encephalopathy. Presentation of 87 cases, with a consideration of pathogenesis and etiology. In: Kernicterus in Cerebral Palsy. CC Thomas, Springfield, Ill., pp 21–228

    Google Scholar 

  • Hsia DY-Y, Allen FH Jr, Gellis SS, Diamond LK (1952) Erythroblastosis fetalis. VIII. Studies of serum bilirubin in relation to kernicterus. N Engl J Med 247:668–671

    Article  PubMed  CAS  Google Scholar 

  • Jellinger K, Minauf M, Weissenbach G (1970) Hirnveränderungen bei kongenitalem nicht hämolytischem Ikterus (Crigler-Najjar-Syndrom). Acta Neuropathol (Berl) 16:141–147

    Article  CAS  Google Scholar 

  • Jervis GA (1959) Constitutional nonhemolytic hyperbilirubinemia with findings resembling kernicterus. Arch Neurol Psychiatry 81:55–64

    CAS  Google Scholar 

  • Jew JY, Williams TH (1977) Ultrastructural aspects of bilirubin encephalopathy in cochlear nuclei of the Gunn rat. J Anat 124:599–614

    PubMed  CAS  Google Scholar 

  • Johnson L, Sarmiento F, Blanc WA, Day R (1959) Kernicterus in rats with an inherited deficiency of glucuronyl transferase. Am J Dis Child 97:591–608

    CAS  Google Scholar 

  • Karp WB (1979) Biochemical alterations in neonatal hyperbilirubinemia and bilirubin encephalopathy: a review. Pediatrics 64:361–368

    PubMed  CAS  Google Scholar 

  • Landsteiner K, Wiener AS (1940) An agglutinable factor in human blood recognized by immune sera for rhesus blood. Proc Soc Exp Biol Med 43:223

    CAS  Google Scholar 

  • Lathe GH, Walker M (1958) The synthesis of bilirubin glucuronide in animal and human liver. Biochem J 70:705–712

    PubMed  CAS  Google Scholar 

  • Levine P, Burnham L, Katzin EM, Vogel P (1941) The role of iso-immunization in the pathogenesis of erythroblastosis fetalis. Am J Obstet Gynecol 42:925–937

    Google Scholar 

  • Levine RL, Fredericks WR, Rapoport SI (1982) Entry of bilirubin into the brain due to opening of the blood-brain barrier. Pediatrics 69:255–259

    PubMed  CAS  Google Scholar 

  • Lucey JF, Hibbard E, Behrman RE, Esquivel de Gallarde FO, Windle WF (1964) Kernicterus in asphyxiated newborn rhesus monkeys. Exp Neurol 9:43–58

    Article  Google Scholar 

  • Meriwether LS, Hager H, Scholz W (1955) Kernicterus. Hypoxemia, significant pathogenic factor. Arch Neurol Psychiatry 73:293–301

    CAS  Google Scholar 

  • Naiman JL, Kosoy MH (1964) Red cell glucose-6-phosphate dehydrogenase deficiency. A newly recognized cause of neonatal jaundice and kernicterus in Canada. Can Med Assoc J 91:1243–1249

    PubMed  CAS  Google Scholar 

  • Onari K (1925) Über zwei klinisch und anatomisch kompliziert liegende Fälle von Status marmoratus des Striatum (mit hochgradigen Veränderungen in anderen subcorticalen und corticalen Gebieten). Z Neurol Psychiatr 98:457–486

    Article  Google Scholar 

  • Orth J (1875) Ueber das Vorkommen von Bilirubinkrystallen bei neugeborenen Kindern. Arch Pathol Anat 63:447–462

    Article  Google Scholar 

  • Panizon F (1960) L’ictère grave du nouveau-né associé à une déficience en glucose-6-phosphate déhydrogénase. Biol Neonat 2:167–177

    Article  PubMed  CAS  Google Scholar 

  • Pearlman MA, Gartner LM, Lee K, Morecki R, Horoupian DS (1978) Absence of kernicterus in low-birth-weight infants from 1971 through 1976: comparison with findings in 1966 and 1967. Pediatrics 62:460–464

    PubMed  CAS  Google Scholar 

  • Péhu M, Dollet M (1939) L’ictère nucléaire du nouveau-né. Rev Fr Pediatr 15:349–390

    Google Scholar 

  • Rozdilsky B, Olszewski J (1960) Permeability of cerebral vessels to albumin in hyperbilirubinemia. Neurology 10:631–638

    PubMed  CAS  Google Scholar 

  • Sawasaki Y, Yamada N, Nakajima H (1976) Developmental features of cerebellar hypoplasia and brain bilirubin levels in a mutant (Gunn) rat with hereditary hyperbilirubinaemia. J Neurochem 27:577–583

    Article  PubMed  CAS  Google Scholar 

  • Schall L (1958) Vitamin K und Kernikterus der Frühgeborenen. Münch Med Wochenschr 100:932–933

    PubMed  CAS  Google Scholar 

  • Scharapow BI, Tschernomordik PM (1928) Zur Pathologie der Stammganglien (ein Fall des Status marmoratus und des Status dysmyelinisatus). J Psychol Neurol (Leipzig) 35:279–282

    Google Scholar 

  • Schmorl G (1903) Zur Kenntnis des Ikterus neonatorum, insbesondere der dabei auftretenden Gehirnveränderungen. Verh Dtsch Ges Pathol 6:109–115

    Google Scholar 

  • Scholz W (1941) Über den Einfluß chronischen Sauerstoffmangels auf das menschliche Gehirn. (Auf Grund des Hirnbefundes eines Achtzehnjährigen mit Morbus coeruleus bei angeborenem Herzfehler.) Z Neurol Psychiatr 171:426–450

    Article  Google Scholar 

  • Schutta HS, Johnson L (1971) Electron microscopic observations on acute bilirubin encephalopathy in Gunn rats induced by sulfadimethoxine. Lab Invest 24:82–89

    PubMed  CAS  Google Scholar 

  • Schutta HS, Johnson L, Neville HE (1970) Mitochondrial abnormalities in bilirubin encephalopathy. J Neuropathol Exp Neurol 29:296–305

    Article  PubMed  CAS  Google Scholar 

  • Sherwood AJ, Smith JF (1983) Bilirubin encephalopathy. Neuropathol Appl Neurobiol 9:171–285

    Article  Google Scholar 

  • Smith GD, Vella F (1960) Erythrocyte enzyme deficiency in unexplained kernicterus. Lancet 1:1133–1134

    Article  Google Scholar 

  • Spatz H (1934) Die Bedeutung der vitalen Färbung für die Lehre vom Stoffaustausch zwischen dem Zentralnervensystem und dem übrigen Körper. Das morphologische Substrat der Stoffwechselschranken im Zentralorgan. Arch Psychiatr Nervenkr 101:267–358

    Article  Google Scholar 

  • Turkei SB, Miller CA, Guttenberg ME, Moynes DR, Hodgman JE (1982) A clinical pathologic reappraisal of kernicterus. Pediatrics 69:267–272

    Google Scholar 

  • Vest M (1958) Insufficient glucuronide formation in the newborn and its relationship to the pathogenesis of icterus neonatorum. Arch Dis Child 33:473–476

    Article  PubMed  CAS  Google Scholar 

  • Vogt C, Vogt O (1920) Zur Lehre der Erkrankungen des striären Systems. J Psychol Neurol (Leipzig) 25, Ergänzungsheft 3:627–846

    Google Scholar 

  • Vogt MT, Basford RE (1968) The effect of bilirubin on the energy metabolism of brain mitochondria. J Neurochem 15:1313–1320

    Article  PubMed  CAS  Google Scholar 

  • Waser M, Kleihues P, Frick P (1986) Kernicterus in an adult. Ann Neurol 19:595–598

    Article  PubMed  CAS  Google Scholar 

  • Waters WJ, Richert DA, Rawson HH (1954) Bilirubin encephalopathy. Pediatrics 13:319–325

    PubMed  CAS  Google Scholar 

  • Wennberg RP, Ahlfors CE, Rasmussen LF (1979) The pathochemistry of kernicterus. Early Hum Dev 3/4: 353–372

    Google Scholar 

  • Winsnes A, Bratlid D (1972) Unconjugated and conjugated bilirubin in plasma from patients with erythroblastosis and neonatal hyperbilirubinemia. Acta Paediatr Scand 61:405–412

    Article  PubMed  CAS  Google Scholar 

  • Zimmerman HM, Yannet H (1933) Kernikterus: jaundice of the nuclear masses of the brain. Am J Dis Child 45:740–759

    Google Scholar 

  • Zimmerman HM, Yannet H (1935) Cerebral sequelae of icterus gravis neonatorum and their relation to kernikterus. Am J Dis Child 49:418–430

    Google Scholar 

  • Zuelzer WW, Cohen F (1957) ABO hemolytic disease and heterospecific pregnancy. Pediatr Clin North Am (May) 405–428

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Zentrum Neurologische Medizin, Abteilung Neuropathologie, Georg-August-Universität Göttingen, Robert-Koch-Straße 40, 3400, Göttingen, Germany

    Reinhard L. Friede

Authors
  1. Reinhard L. Friede
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Friede, R.L. (1989). Kernicterus (Bilirubin Encephalopathy). In: Developmental Neuropathology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73697-1_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-73697-1_9

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-73699-5

  • Online ISBN: 978-3-642-73697-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation