Skip to main content
Canadian Medical Association Journal logoLink to Canadian Medical Association Journal
. 1981 Feb 15;124(4):375-82, 425.

Reye's syndrome: a clinical review.

J F Crocker, P C Bagnell
PMCID: PMC1705231  PMID: 6783291

Abstract

Reye's syndrome is a virus-associated biphasic disease that causes acute encephalopathy in infants and children. Epidemiologic and experimental data support the hypothesis that it is a multifactorial disease of modern civilization. Just as young patients seem to be recovering uneventfully from the first phase of the illness, usually a nonspecific viral-like illness such as a respiratory tract infection or gastroenteritis, the second phase, encephalopathy, starts unexpectedly, with vomiting and sensorial changes. Identifying the syndrome early ;in the second phase and referring the child to a specialized centre with the experience, staff and facilities to manage this phase has improved the numbers and neurologic condition of survivors, though the overall mortality is still about 20%. Therapy is primarily directed at facilitating adequate cerebral perfusion pressure.

Full text

PDF
381

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aoki Y., Lombroso C. Prognostic value of electroencephalography in Reye's syndrome. Neurology. 1973 Apr;23(4):333–343. doi: 10.1212/wnl.23.4.333. [DOI] [PubMed] [Google Scholar]
  2. Aprille J. R. Reye's syndrome: patient serum alters mitochondrial function and morphology in vitro. Science. 1977 Aug 26;197(4306):908–910. doi: 10.1126/science.887930. [DOI] [PubMed] [Google Scholar]
  3. Baliga R., Fleischmann L. E., Chang C. H., Sarnaik A. P., Bidani A. K., Arcinue E. L. Acute renal failure in Reye's syndrome. Am J Dis Child. 1979 Oct;133(10):1009–1013. doi: 10.1001/archpedi.1979.02130100033006. [DOI] [PubMed] [Google Scholar]
  4. Berman W., Pizzi F., Schut L., Raphaely R., Holtzapple P. The effects of exchange transfusion on intracranial pressure in patients with Reye syndrome. J Pediatr. 1975 Dec;87(6 Pt 1):887–891. doi: 10.1016/s0022-3476(75)80899-7. [DOI] [PubMed] [Google Scholar]
  5. Bourgeois C. H., Shank R. C., Grossman R. A., Johnsen D. O., Wooding W. L., Chandavimol P. Acute aflatoxin B1 toxicity in the macaque and its similarities to Reye's syndrome. Lab Invest. 1971 Mar;24(3):206–216. [PubMed] [Google Scholar]
  6. Boutros A., Hoyt J., Menezes A., Bell W. Management of Reye's syndrome. A rational approach to a complex problem. Crit Care Med. 1977 Sep-Oct;5(5):234–238. [PubMed] [Google Scholar]
  7. Bove K. E., McAdams A. J., Partin J. C., Partin J. S., Hug G., Schubert W. K. The hepatic lesion in Reye's syndrome. Gastroenterology. 1975 Sep;69(3):685–697. [PubMed] [Google Scholar]
  8. Bradford W. D., Latham W. C. Acute encephalopathy and fatty hepatomegaly. Am J Dis Child. 1967 Aug;114(2):152–156. doi: 10.1001/archpedi.1967.02090230082008. [DOI] [PubMed] [Google Scholar]
  9. Brown T., Hug G., Lansky L., Bove K., Scheve A., Ryan M., Brown H., Schubert W. K., Partin J. C., Lloyd-Still J. Transiently reduced activity of carbamyl phosphate synthetase and ornithine transcarbamylase in liver of children with Reye's syndrome. N Engl J Med. 1976 Apr 15;294(16):861–867. doi: 10.1056/NEJM197604152941602. [DOI] [PubMed] [Google Scholar]
  10. Brunner R. L., O'Grady D. J., Partin J. C., Partin J. S., Schubert W. K. Neuropsychologic consequences of Reye syndrome. J Pediatr. 1979 Nov;95(5 Pt 1):706–711. doi: 10.1016/s0022-3476(79)80715-5. [DOI] [PubMed] [Google Scholar]
  11. Corey L., Rubin R. J., Bregman D., Gregg M. B. Diagnostic criteria for influenza B-associated Reye's syndrome: clinical vs. pathologic criteria. Pediatrics. 1977 Nov;60(5):702–708. [PubMed] [Google Scholar]
  12. Corey L., Rubin R. J., Hattwick M. A., Noble G. R., Cassidy E. A nationwide outbreak of Reye's Syndrome. Its epidemiologic relationship of influenza B. Am J Med. 1976 Nov;61(5):615–625. doi: 10.1016/0002-9343(76)90139-x. [DOI] [PubMed] [Google Scholar]
  13. Corey L., Rubin R. J., Hattwick M. A. Reye's syndrome: clinical progression and evaluation of therapy. Pediatrics. 1977 Nov;60(5):708–714. [PubMed] [Google Scholar]
  14. Corey L., Rubin R. J., Thompson T. R., Noble G. R., Cassidy E., Hattwick M. A., Gregg M. B., Eddins D. Influenza B-associated Reye's syndrome: incidence in Michigan and potential for prevention. J Infect Dis. 1977 Mar;135(3):398–407. doi: 10.1093/infdis/135.3.398. [DOI] [PubMed] [Google Scholar]
  15. Crocker J. F., Ozere R. L., Safe S. H., Digout S. C., Rozee K. R., Hutzinger O. Lethal interaction of ubiquitous insecticide carriers with virus. Science. 1976 Jun 25;192(4246):1351–1353. doi: 10.1126/science.179146. [DOI] [PubMed] [Google Scholar]
  16. Crocker J. F., Rozee K. R., Ozere R. L., Digout S. C., Hutzinger O. Insecticide and viral interaction as a cause of fatty visceral changes and encephalopathy in the mouse. Lancet. 1974 Jul 6;2(7871):22–24. doi: 10.1016/s0140-6736(74)91351-8. [DOI] [PubMed] [Google Scholar]
  17. De Vivo D. C. Reye syndrome: a metabolic response to an acute mitochondrial insult? Neurology. 1978 Feb;28(2):105–108. doi: 10.1212/wnl.28.2.105. [DOI] [PubMed] [Google Scholar]
  18. DeVivo D. C., Keating J. P., Haymond M. W. Reye syndrome: results of intensive supportive care. J Pediatr. 1975 Dec;87(6 Pt 1):875–880. doi: 10.1016/s0022-3476(75)80897-3. [DOI] [PubMed] [Google Scholar]
  19. Devivo D. C., Keating J. P. Reye's syndrome. Adv Pediatr. 1976;22:175–229. [PubMed] [Google Scholar]
  20. Fox D. W., Hart M. C., Bergeson P. S., Jarrett P. B., Stillman A. E., Huxtable R. J. Pyrrolizidine (Senecio) intoxication mimicking Reye syndrome. J Pediatr. 1978 Dec;93(6):980–982. doi: 10.1016/s0022-3476(78)81227-x. [DOI] [PubMed] [Google Scholar]
  21. Friend M., Trainer D. O. Polychlorinated biphenyl: interaction with duck hepatitis virus. Science. 1970 Dec 18;170(3964):1314–1316. doi: 10.1126/science.170.3964.1314. [DOI] [PubMed] [Google Scholar]
  22. Gall D. G., Cutz E., McClung H. J., Greenberg M. L. Acute liver disease and encephalopathy mimicking Reye syndrome. A report of three cases. J Pediatr. 1975 Dec;87(6 Pt 1):869–874. doi: 10.1016/s0022-3476(75)80896-1. [DOI] [PubMed] [Google Scholar]
  23. Gerber N., Dickinson R. G., Harland R. C., Lynn R. K., Houghton L. D., Antonias J. I., Schimschock J. C. Reye-like syndrome associated with valproic acid therapy. J Pediatr. 1979 Jul;95(1):142–144. doi: 10.1016/s0022-3476(79)80110-9. [DOI] [PubMed] [Google Scholar]
  24. Glasgow A. M., Cotton R. B., Dhiensiri K. Reye's syndrome. I. Blood ammonia and consideration of the nonhistologic diagnosis. Am J Dis Child. 1972 Dec;124(6):827–833. doi: 10.1001/archpedi.1972.02110180029003. [DOI] [PubMed] [Google Scholar]
  25. Gosseye S., De Meyer R., Maldague P. Reye's syndrome without fatty liver. Helv Paediatr Acta. 1976 Apr;30(6):509–513. [PubMed] [Google Scholar]
  26. Hanid M. A., Mackenzie R. L., Jenner R. E., Chase R. A., Mellon P. J., Trewby P. N., Janota I., Davis M., Silk D. B., Williams R. Intracranial pressure in pigs with surgically induced acute liver failure. Gastroenterology. 1979 Jan;76(1):123–131. [PubMed] [Google Scholar]
  27. Hilty M. D., McClung H. J., Haynes R. E., Romshe C. A., Sherard E. S., Jr Reye syndrome in siblings. J Pediatr. 1979 Apr;94(4):576–579. doi: 10.1016/s0022-3476(79)80013-x. [DOI] [PubMed] [Google Scholar]
  28. Hilty M. D., Romshe C. A., Delamater P. V. Reye's syndrome and hyperaminoacidemia. J Pediatr. 1974 Mar;84(3):362–365. doi: 10.1016/s0022-3476(74)80717-1. [DOI] [PubMed] [Google Scholar]
  29. Huttenlocher P. R. Reye's syndrome: relation of outcome to therapy. J Pediatr. 1972 May;80(5):845–850. doi: 10.1016/s0022-3476(72)80145-8. [DOI] [PubMed] [Google Scholar]
  30. Huttenlocher P. R., Schwartz A. D., Klatskin G. Reye's syndrome: ammonia intoxication as a possible factor in the encephalopathy. Pediatrics. 1969 Mar;43(3):443–454. [PubMed] [Google Scholar]
  31. Huttenlocher P. R., Trauner D. A. Reye's syndrome in infancy. Pediatrics. 1978 Jul;62(1):84–90. [PubMed] [Google Scholar]
  32. Kang E. S., Solomon S. S., Duckworth W. C., Burghen G. A., Schwenzer K. S. Abnormal pancreatic endocrine function in Reye's syndrome survivors and their relatives: a preliminary report. Pediatr Res. 1979 Jul;13(7):870–873. doi: 10.1203/00006450-197907000-00016. [DOI] [PubMed] [Google Scholar]
  33. LaBrecque D. R., Latham P. S., Riely C. A., Hsia Y. E., Klatskin G. Heritable urea cycle enzyme deficiency-liver disease in 16 patients. J Pediatr. 1979 Apr;94(4):580–587. doi: 10.1016/s0022-3476(79)80014-1. [DOI] [PubMed] [Google Scholar]
  34. Ladisch S., Lovejoy F. H., Hierholzer J. C., Oxman M. N., Strieder D., Vawter G. F., Finer N., Moore M. Extrapulmonary manifestations of adenovirus type 7 pneumonia simulating Reye syndrome and the possible role of an adenovirus toxin. J Pediatr. 1979 Sep;95(3):348–355. doi: 10.1016/s0022-3476(79)80505-3. [DOI] [PubMed] [Google Scholar]
  35. Lansky L. Letter: Clinical staging of Reye syndrome. J Pediatr. 1976 Jun;88(6):1070–1072. doi: 10.1016/s0022-3476(76)81098-0. [DOI] [PubMed] [Google Scholar]
  36. Linnemann C. C., Jr, Shea L., Kauffman C. A., Schiff G. M., Partin J. C., Schubert W. K. Association of Reye's syndrome with viral infection. Lancet. 1974 Jul 27;2(7874):179–182. doi: 10.1016/s0140-6736(74)91481-0. [DOI] [PubMed] [Google Scholar]
  37. Lloyd K. G., Davidson L., Price K., McClung H. J., Gall D. G. Catecholamine and octopamine concentrations in brains of patients with Reye syndrome. Neurology. 1977 Oct;27(10):985–988. doi: 10.1212/wnl.27.10.985. [DOI] [PubMed] [Google Scholar]
  38. Lovejoy F. H., Jr, Smith A. L., Bresnan M. J., Wood J. N., Victor D. I., Adams P. C. Clinical staging in Reye syndrome. Am J Dis Child. 1974 Jul;128(1):36–41. doi: 10.1001/archpedi.1974.02110260038007. [DOI] [PubMed] [Google Scholar]
  39. Miller J. D. Barbiturates and raised intracranial pressure. Ann Neurol. 1979 Sep;6(3):189–193. doi: 10.1002/ana.410060302. [DOI] [PubMed] [Google Scholar]
  40. Morens D. M., Halsey N. A., Schonberger L. B., Baublis J. V. Reye syndrome associated with vaccination with live virus vaccines. An exploration of possible etiologic relationships. Clin Pediatr (Phila) 1979 Jan;18(1):42–44. doi: 10.1177/000992287901800105. [DOI] [PubMed] [Google Scholar]
  41. Nelson D. B., Hurwitz E. S., Sullivan-Bolyai J. Z., Morens D. M., Schonberger L. B. Reye's syndrome in the United States in 1977-1978, a non-influenza B virus year. J Infect Dis. 1979 Sep;140(3):436–439. doi: 10.1093/infdis/140.3.436. [DOI] [PubMed] [Google Scholar]
  42. Norman M. G. Encephalopathy and fatty degeneration of the viscera in childhood: I. Review of cases at the Hospital for Sick Children, Toronto (1954-1966). Can Med Assoc J. 1968 Sep 28;99(11):522–526. [PMC free article] [PubMed] [Google Scholar]
  43. Orlowski J. P., Johannsson J. H., Ellis N. G. Encephalopathy and fatty metamorphosis of the liver associated with cold-agglutinin autoimmune hemolytic anemia. J Pediatr. 1979 Apr;94(4):569–575. doi: 10.1016/s0022-3476(79)80012-8. [DOI] [PubMed] [Google Scholar]
  44. Partin J. C. Reye's syndrome (encephalopathy and fatty liver). Diagnosis and treatment. Gastroenterology. 1975 Aug;69(2):511–518. [PubMed] [Google Scholar]
  45. Partin J. C., Schubert W. K., Partin J. S. Mitochondrial ultrastructure in Reye's syndrome (encephalopathy and fatty degeneration of the viscera). N Engl J Med. 1971 Dec 9;285(24):1339–1343. doi: 10.1056/NEJM197112092852402. [DOI] [PubMed] [Google Scholar]
  46. Pegelow C., Goldberg R., Turkel S., Powars D. Severe coagulation abnormalities in Reye syndrome. J Pediatr. 1977 Sep;91(3):413–416. doi: 10.1016/s0022-3476(77)81310-3. [DOI] [PubMed] [Google Scholar]
  47. RANDOLPH M., KRANWINKEL R., JOHNSON R., GELFMAN N. A. ENCEPHALOPATHY, HEPATITIS AND FAT ACCUMULATION IN VISCERA. Am J Dis Child. 1965 Jul;110:95–99. doi: 10.1001/archpedi.1965.02090030101017. [DOI] [PubMed] [Google Scholar]
  48. REYE R. D., MORGAN G., BARAL J. ENCEPHALOPATHY AND FATTY DEGENERATION OF THE VISCERA. A DISEASE ENTITY IN CHILDHOOD. Lancet. 1963 Oct 12;2(7311):749–752. doi: 10.1016/s0140-6736(63)90554-3. [DOI] [PubMed] [Google Scholar]
  49. Rockoff M. A., Marshall L. F., Shapiro H. M. High-dose barbiturate therapy in humans: a clinical review of 60 patients. Ann Neurol. 1979 Sep;6(3):194–199. doi: 10.1002/ana.410060303. [DOI] [PubMed] [Google Scholar]
  50. Roe C. R., Schonberger L. B., Gelbach S. H., Wies L. A., Sidbury J. B., Jr Enzymatic alterations in Reye's syndrome: prognostic implications. Pediatrics. 1975 Jan;55(1):119–126. [PubMed] [Google Scholar]
  51. Rosenfeld R. G., Liebhaber M. I. Acute encephalopathy in siblings. Reye syndrome vs salicylate intoxication. Am J Dis Child. 1976 Mar;130(3):295–297. doi: 10.1001/archpedi.1976.02120040073014. [DOI] [PubMed] [Google Scholar]
  52. Ryan N. J., Hogan G. R., Hayes A. W., Unger P. D., Siraj M. Y. Aflatoxin B1; its role in the etiology of Reye's syndrome. Pediatrics. 1979 Jul;64(1):71–75. [PubMed] [Google Scholar]
  53. Schiff G. M. Reye's syndrome. Annu Rev Med. 1976;27:447–452. doi: 10.1146/annurev.me.27.020176.002311. [DOI] [PubMed] [Google Scholar]
  54. Shaywitz B. A., Leventhal J. M., Kramer M. S., Venes J. L. Prolonged continuous monitoring of intracranial pressure in severe Reye's syndrome. Pediatrics. 1977 Apr;59(4):595–605. [PubMed] [Google Scholar]
  55. Shaywitz B. A., Venes J., Cohen D. J., Bowers M. B. Reye syndrome: monoamine metabolites in ventricular fluid. Neurology. 1979 Apr;29(4):467–472. doi: 10.1212/wnl.29.4.467. [DOI] [PubMed] [Google Scholar]
  56. Shield L. K., Coleman T. L., Markesbery W. R. Methyl bromide intoxication: neurologic features, including simulation of Reye syndrome. Neurology. 1977 Oct;27(10):959–962. doi: 10.1212/wnl.27.10.959. [DOI] [PubMed] [Google Scholar]
  57. Snodgrass P. J., DeLong G. R. Urea-cycle enzyme deficiencies and an increased nitrogen load producing hyperammonemia in Reye's syndrome. N Engl J Med. 1976 Apr 15;294(16):855–860. doi: 10.1056/NEJM197604152941601. [DOI] [PubMed] [Google Scholar]
  58. Sudo M., Tanioka K. I., Momoi T., Akaishi K., Suzuki Y. Identification of fatty acid methyl esters in kidneys and livers of two patients with Reye's syndrome. Clin Chim Acta. 1978 Mar 1;84(1-2):179–184. doi: 10.1016/0009-8981(78)90492-8. [DOI] [PubMed] [Google Scholar]
  59. Tanaka K., Kean E. A., Johnson B. Jamaican vomiting sickness. Biochemical investigation of two cases. N Engl J Med. 1976 Aug 26;295(9):461–467. doi: 10.1056/NEJM197608262950901. [DOI] [PubMed] [Google Scholar]
  60. Thaler M. M., Bruhn F. W., Applebaum M. N., Goodman J. Reye's syndrome in twins. J Pediatr. 1970 Oct;77(4):638–646. doi: 10.1016/s0022-3476(70)80206-2. [DOI] [PubMed] [Google Scholar]
  61. Thaler M. M., Hoogenraad N. J., Boswell M. Reye's syndrome due to a novel protein-tolerant variant of ornithine-transcarbamylase deficiency. Lancet. 1974 Aug 24;2(7878):438–440. doi: 10.1016/s0140-6736(74)91819-4. [DOI] [PubMed] [Google Scholar]
  62. Trauner D. A., Brown F., Ganz E., Huttenlocher P. R. Treatment of elevated intracranial pressure in Reye syndrome. Ann Neurol. 1978 Sep;4(3):275–278. doi: 10.1002/ana.410040315. [DOI] [PubMed] [Google Scholar]
  63. Truscott R., Pullin C., Halpern B., Wilcken B., Silink M., Griffiths H., Kilham H., Grunseit F. Suspected defect in fatty acid oxidation. N Engl J Med. 1978 Jul 20;299(3):152–152. doi: 10.1056/nejm197807202990314. [DOI] [PubMed] [Google Scholar]
  64. Washington R. L., Barkin R. M., Hillman J. R. Septicemic plague that mimics Reye's syndrome. Am J Dis Child. 1979 Apr;133(4):434–435. doi: 10.1001/archpedi.1979.02130040088018. [DOI] [PubMed] [Google Scholar]
  65. Zieve F. J., Zieve L., Doizaki W. M., Gilsdorf R. B. Synergism between ammonia and fatty acids in the production of coma: implications for hepatic coma. J Pharmacol Exp Ther. 1974 Oct;191(1):10–16. [PubMed] [Google Scholar]
  66. van Caillie M., Morin C. L., Roy C. C., Geoffroy G., McLaughlin B. Reye's syndrome: relapses and neurological sequelae. Pediatrics. 1977 Feb;59(2):245–249. [PubMed] [Google Scholar]

Articles from Canadian Medical Association Journal are provided here courtesy of Canadian Medical Association

RESOURCES