Journal of Inherited Metabolic Disease

, Volume 14, Issue 4, pp 436–458 | Cite as

Interrelationships of liver and brain with special reference to reye syndrome

  • J. K. Brown
  • H. Imam
Article

Summary

Reye syndrome is an acute non-inflammatory encephalopathy that can be precipitated by toxic, infective, metabolic or hypoxic upsets. The biochemical changes point to mitochondrial dysfunction and this is substantiated by structural changes in mitochondria on electron microscopy. The toxic metabolites that accumulate are similar to those incriminated in hepatic encephalopathy and other metabolic diseases. These metabolites exert their deleterious effects by direct neuronal damage, neurotransmitter blockade, vascular damage, cerebral oedema, hypoxic ischaemic damage, demyelination, retardation of brain growth and neuronal storage. Brain capillary endothelial cells are very rich in mitochondria and mitochondrial disorders can effect the central nervous system primarily, and not just as a consequence of systemic metabolic upset.

Keywords

Metabolic Disease Special Reference Mitochondrial Dysfunction Metabolic Upset Hepatic Encephalopathy 

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References

  1. Adams, R. D. and Foley, J. M. The neurological disorders associated with brain disease. In: Meritt, H. H. and Hare, C. C. (eds.)Metabolic and Toxic Diseases of the Nervous System, Vol. 32. Williams and Williams, Baltimore, 1953, pp. 198–237Google Scholar
  2. Alberts, B., Bray, D., Lewis, J., Raff, M., Roberts, K. and Watson, J. D. The mitochondria. In:The Cell. Garland Press, New York, 1989, pp. 342–366Google Scholar
  3. Ansevin, C. F. Reye syndrome: Serum induced alteration in brain mitochondrial function are blocked by fatty acids free albumin.Neurology 30 (1980) 160–166Google Scholar
  4. Bakay, L., Crawford, J. D. and White, J. C. The effects of intravenous fluids on cerebrospinal fluid pressure.Surg. Gynaecol. Obstet. 99 (1954) 48–52Google Scholar
  5. Baker, A. L. Amino acids in liver disease, a cause of hepatic encephalopathy.J. Am. Med. Assoc. 242 (1979) 355–356Google Scholar
  6. Beks, J. W. F. and Kerckhoffs, H. P. M. Studies on the water content of cerebral tissues and intracranial pressure in vasogenic brain oedema. In: Brock, M. and Dietz, H. (eds.)Intracranial Pressure 1. Springer Verlag, Berlin, 1972, pp. 119–126Google Scholar
  7. Benjamin, A. M. Control of glutaminase activity in rat brain cortex in vitro. Influence of glutamate, phosphate, ammonia, calcium and hydrogen ions.Brain Res. 208 (1981) 363–377Google Scholar
  8. Bessman, S. P. and Bradley, J. E. Uptake of ammonia by muscle: its implications in ammoniogenic coma.N. Engl. J. Med. 253 (1955) 1143–1147Google Scholar
  9. Bickford, R. G. and Butt, H. R. Hepatic coma and the electroencephalographic pattern.J. Clin. Invest. 34 (1955) 790–799Google Scholar
  10. Blasberg, R. G. Clearance of serum albumin from brain extracellular fluid, a possible role in cerebral oedema. In: Pappius, H. M. and Feindel, W. (eds.)Dynamics of Brain Oedema. Springer Verlag, Berlin, 1972, pp. 98–102Google Scholar
  11. Blaschke, T. F., Berk, P. D. and Scharschmidt, B. F. Crigler-Najjar syndrome an unusual course with development of neurologic damage at age 18.Paediatr. Res. 8 (1974) 573–590Google Scholar
  12. Bonell, H. J. and Beckwith, J. B. Fatty liver in sudden childhood death, implications for Reye's syndrome?Assoc. J. Dis. Child. 140 (1986) 30–33Google Scholar
  13. Borbola, J., Papp, J. G. and Szekeres, L. Effects of octanoate on the electrical activity of Purkinje cell.Experientia 30 (1974) 262–264Google Scholar
  14. Bove, K. E., McAdams, A. J. and Partin, J. C. The hepatic lesion in Reye's syndrome.Gastroenterology 69 (1975) 685–697Google Scholar
  15. Bougeneres, P. F., Rocchicciola, F. and Kolvra, S. Medium chain acy1 CoA dehydrogenase deficiency in two siblings with a Reye like syndrome.J. Paediatr. 106 (1985) 918–921Google Scholar
  16. Brain, W. R., Hunter, D. and Turnbull, H. M. Acute meningoencephalitis of childhood. Report of 6 cases.Lancet 1 (1929) 221–227Google Scholar
  17. Brown, J. K. Lumbar puncture and its hazards.Dev. Med. Child Neurol. 18 (1976) 803–816Google Scholar
  18. Brown, J. K. Valproate toxicity.Dev. Med. Child. Neurol. 30 (1988) 115–125Google Scholar
  19. Brown, J. K. Mechanisms of production of raised intracranial pressure. In Minns, R. A. (ed.)Problems of Intracranial Pressure in Childhood. MacKeith Press, Oxford, 1991a, pp. 13–37Google Scholar
  20. Brown, J. K. The pathological effects of raised intracranial pressure. In Minns, R. A. (ed.)Problems of Intracranial Pressure in Childhood. MacKeith Press, Oxford, 1991b, pp. 38–76Google Scholar
  21. Brown, J. K. and Habel, A. H. Toxic encephalopathy and acute brain swelling in children.Dev. Med. Child Neurol. 17 (1976) 659–679Google Scholar
  22. Brown, J. K., Ingram, T. T. S. and Seisha, S. S. Patterns of decerebration in infants and children.J. Neurol. Neurosurg. 36 (1973) 431–434Google Scholar
  23. Brown, J. K. and Steer, C. R. S. Strategies in the management of acute encephalopathies. In: Gordon, N. and McKinlay, I. (eds.)Neurologically Sick Children. Blackwell Scientific, Oxford, 1986, pp. 219–294Google Scholar
  24. Brown, R. E. and Madge, G. E. Fatty acid and mitochondrial injury in Reye's syndrome.N. Engl. J. Med. 286 (1972) 287–288Google Scholar
  25. Bruton, C. J., Corsellis, J. A. N. and Russel, A. Hereditary hyperammoninaemia.Brain 93 (1970) 423–434Google Scholar
  26. Burchell, A., Waddell, I. D., Stewart, L. and Hume, R. Perinatal diagnosis of type IC glycogen storage disease.J. Inher. Metab. Dis. 12 (1989), Suppl. 2, 315–317Google Scholar
  27. Cavanagh, J. B. and Kyu, M. H. Type II Alzheimer changes experimentally produced in astrocytes in the rat.J. Neurol. Sci. 12 (1971) 63–75Google Scholar
  28. Center for Disease Control. Follow up on Reye's syndrome.United States Morbidity and Mortality weekly report. 29 (1980) 321–322Google Scholar
  29. Chen, S., Sieve, L. and Mahadevan, V. Mercaptans and dimethyl sulfide in the breath of patients with cirrhosis of the liver.J. Lab. Clin. Med. 75 (1970) 628–635Google Scholar
  30. Claireaux, A. E. Hemolytic disease of the newborn. A clinical pathological study of 157 cases.Arch. Dis. Child. 25 (1950) 61–80Google Scholar
  31. Coates, P. M., Hale, D. E. and Stanley, C. A. Systemic carnitine deficiency stimulating Reye's syndrome.J. Paediatr. 105 (1984) 679–682Google Scholar
  32. Cuilleret, G., Pomier-Layarargues, G., Pons, F., Cadilhac, J. and Michel, H. Changes in brain catecholamine levels in human cirrhotic hepatic encephalopathy.Gut 21 (1980) 656–569Google Scholar
  33. Dahl, D. R. Short chain fatty acid inhibition of rat brain Na/K. Adenosine triphosphatase.J. Neurol. Chem. 15 (1968) 815–820Google Scholar
  34. Diamond, I., Bilirubin encephalopathy. In Goldensohn, E. S., Appel, S. H., (eds.)Scientific Approaches to Clinical Neurology. Lea and Febiger, Philadelphia, 1977, pp. 1212–1233Google Scholar
  35. Editorial. Reye's syndrome and aspirin epidemiological association and inborn errors of metabolism.Lancet 2 (1987) 421–431Google Scholar
  36. Edwards, J. C., Howell, S. C. and Taylor, K. W. Fatty acids as regulators of glucagon secretion.Nature 224 (1969) 808–809Google Scholar
  37. Faraj, B. A., Bowers, P. A., Isaacs, J. W. and Rudman, D. Hypertyraminaemia in cirrhotic patients.N. Engl. J. Med. 294 (1976) 1360–1363Google Scholar
  38. Filipe, J. I. and Lake, B. D.Histochemistry in Pathology. Churchill Livingstone, Edinburgh, 1983, pp. 53–69Google Scholar
  39. Finberg, L., Luttrell, C. and Redd, H. Pathogenesis of lesions in the nervous system in hypernatraemic states. 2 experimental studies of gross anatomical changes and alterations of chemical composition of the tissues.Paediatrics 23 (1959) 46–53Google Scholar
  40. Fischer, J. E.False Neurotransmitters and Hepatic Coma. Research Publications. Association Nervous and Mental Disorders, 53. Raven Press, New York, 1974, 53–73Google Scholar
  41. Fishman, R. A. Effects of isotonic intravenous solutions on normal and increased intracranial pressure.Arch. Neurol. Psychiatry 70 (1953) 350–360Google Scholar
  42. Gerschenfeld, H. M., Wald, F., Zadunaisky, J. A. and De Roberts, E. D. P. Functions of astroglia in the water ion metabolism of the central nervous system. An electron microscopic study.Neurology 9 (1959) 412–425Google Scholar
  43. Glasgow, A. M., Eng, G. and Engel, A. G. Systemic carnitine deficiency simulating Reye's syndrome.J. Paediatr. 96 (1980) 889–891Google Scholar
  44. Glasgow, J. F. T., Hicks, E. M., Jenkins, J. G., Keilty, S. R., Black, G. W. and Kannin, T. F. Reye's syndrome.Br. J. Hosp. Med. 34 (1985) 42–45Google Scholar
  45. Glion, E., Szemberg, A. and Taubman, L. G. Glutamine estimation in cerebrospinal fluid in cases of liver cirrhosis and hepatic coma.J. Lab. Clin. Med. 53 (1959) 714–719Google Scholar
  46. Grimm, G., Ferenci, P., Katzenschlager, R. and Madl, C. Improvement of hepatic encephalopathy treated with flumazenil.Lancet 2 (1988) 1392–1394Google Scholar
  47. Habel, A. H. and Simpson, H. Osmolar relation between cerebrospinal fluid and serum in hyperosmolar hypernatraemic dehydration.Arch. Dis. Child. 51 (1976) 660–666Google Scholar
  48. Hall, S. M. Reye's syndrome and aspirin. A review.J. R. Soc. Med. 79 (1986) 596–598Google Scholar
  49. Hall, S. and Bellman, M. Reye's syndrome in the British Isles. First annual report of the joint British Paediatric Association and Communicable Disease Surveillance Center Surveillance Scheme.Br. Med. J. 288 (1984) 548–550Google Scholar
  50. Hockwald, G. M., Marlin, A. E., Wald, A. and Malhan, C. Movement of water between blood brain and CSF as cerebral oedema. In: Pappius, J. H. M. and Feindel, W. (eds.)Dynamics of Brain Edema. Springer Verlag, Berlin, 1976, pp 129–137Google Scholar
  51. Hourani, B. T., Harrlin, E. M. and Reynolds, T. B. Cerebrospinal fluid glutamine as a measure of hepatic encephalopathy.Arch. Intern. Med. 127 (1971) 1033–1036Google Scholar
  52. Hurwitz, E. S. and Goodman, R. A. A cluster of cases of Reye's syndrome associated with chickenpox.Paediatrics 70 (1982) 901–906Google Scholar
  53. Hurwitz, E. S., Nelson, D. B., Davis, C., Morens, D. and Schonberger, L. B. National surveillance for Reye's syndrome: a 5 year review.Paediatrics 70 (1982) 895–900Google Scholar
  54. Huttenlocher, P. R., Schwartz, A. D. and Klatskin, G. Reye's syndrome: ammonia intoxication as a possible factor in encephalopathy.Paediatrics 43 (1969) 443–454Google Scholar
  55. Johnson, R. T. and Yates, P. O. Brain stem haemorrhages in expanding supratentorial conditions.Acta Radiol. 46 (1956) 250–256Google Scholar
  56. Kay, J. D. S., Hilton-Jones, D. and Hyman, N. Valproate toxicity and ornithine carbamyl transferase deficiency.Lancet 2 (1986) 1283–1284Google Scholar
  57. Kinsell, L. W., Harper, H. A., Giese, G. K. and Margen, S. Studies in methionine metabolism.J. Clin. Invest. 28 (1949) 1439–1450Google Scholar
  58. Laidlaw, J. and Read, A. E. The E.E.G. on hepatic encephalopathy.Clin. Sci. 24 (1963) 109–120Google Scholar
  59. Lam, K. C., Tall, A. R., Goldstein, G. B. and Mistills, S. P. Role of a false neurochemical transmitter, octopamine in the pathogenesis of hepatic and renal encephalopathy.Scand. J. Gastroenterol. 8 (1973) 465–472Google Scholar
  60. Levin, M., Kay, J. D. S. and Gould, J. D. Haemorrhagic shock and encephalopathy: a new syndrome with a high mortality in young children.Lancet 2 (1983) 64–67Google Scholar
  61. Linscheer, W. G., Blum, A. L. and Platt, R. R. Transfer of medium chain fatty acids from blood to spinal fluid in patients with cirrhosis.Gastroenterology 58 (1970) 509–515Google Scholar
  62. Lockwood, A. H. Ammonia induced encephalopathy. In: McCandless, S. W. (ed.)Cerebral Energy Metabolism and Metabolic Encephalopathy. Plenum Press, New York, 1985, pp. 203–207Google Scholar
  63. Lockwood, A. H., Ginsberg, M. D., Butler, C. M. and Cuttierez, M. T. Selective effects of ammonia on regional brain glucose metabolism.Ann. Neurol. 12 (1982) 114–120Google Scholar
  64. Lou, H. C., Lassen, N. A., Tweed, W. A., Johnson, G., Jones, M. and Palahniuk, R. K. Pressure passive cerebral blood flow and breakdown of the blood-brain barrier in experimental fetal asphyxia.Acta Paediatr. Scand. 68 (1979) 57–63Google Scholar
  65. Lovejoy, F. H., Smith, A. L., Bressman, M. J., Wood, J. N., Victor, D. I. and Adams, P. E. Clinical staging in Reye's syndrome.Am. J. Dis. Child. 128 (1974) 36–41Google Scholar
  66. Martinez-Hernandes, A., Bell, K. P. and Norenberg, M. D. Glutamine synthetase: glial localisation in brain.Science 195 (1977) 1356–1358Google Scholar
  67. Mamunes, P., DeVries, G. H., Miller, C. D. and David, R. B. Fatty acid quantitation in Reye's syndrome. In: Pollack, J. D. (ed.)Reye's Syndrome. Grune and Stratton, New York, 1975, pp. 245–254Google Scholar
  68. McClain, C. J., Zieve, L., Doizaki, W. M., Gilbertstadt, S. and Onstat, G. R. Blood methianethiol in alcoholic liver disease with and without hepatic encephalopathy.Gut 21 (1980) 318–323Google Scholar
  69. Milhorat, T. H.Cerebrospinal Fluid and the Brain Edemas. Neuroscience Society, New York, 1987Google Scholar
  70. Minns, R. A. Clinical application of ventricular pressure monitoring in children.Zeitschrift fur Kinderchirurgie und Grenzgebiete 224 (1977) 430–443Google Scholar
  71. Montague, W. and Taylor, K. W. Regulation of insulin secretion by short chain fatty acids.Nature 217 (1968) 853Google Scholar
  72. Natowicz, M. and Kelley, R. Mendelian etiologies of stroke.Ann. Neurol. 21 (1987) 175–189Google Scholar
  73. Norenberg, M. D. A light and electron microscopic study of experimental portal-systemic (ammonia) encephalopathy.Lab. Invest. 36 (1977) 618–627Google Scholar
  74. Norenberg, M. D. and Lapham, L. W. The astrocyte response in experimental portal-systemic encephalopathy: An electron microscopic study.J. Neuropathol. Exp. Neurol. 33 (1974) 422–435Google Scholar
  75. Odell, G. B. and Schutta, M. S. Bilirubin encephalopathy. In: McCandless, D. (ed.)Cerebral Energy Metabolism and Metabolic Encephalopathy. Plenum Press, New York, 1985, pp. 229–261Google Scholar
  76. Oldendorf, W. H. and Brown, J. W. Greater number of capiliary endothelial cell mitochondria in brain than muscle.Proc. Soc. Exp. Biol. Med. 149 (1975) 736–738Google Scholar
  77. Pappius, H. M. and Feindel, W. (eds.)Dynamics of Brain Edema. Springer Verlag, Berlin, 1976Google Scholar
  78. Partin, J. C., Partin, J. S., Schubert, W. K. and McLaurin, R. L. Brain ultrastructure in Reye's syndrome.J. Neuropathol. Exp. Neurol. 34 (1975) 425–444Google Scholar
  79. Perry, L. T., Hansen, S. and MacLean, J. CSF and plasma glutamine elevation by anticonvulsant therapy, a potential diagnostic and therapeutic trap.Clin. Res. 33 (1975) 610AGoogle Scholar
  80. Phelps, M. W., Hoffman, E. J. and Raybard, C. Factors which affect the uptake and retention of 13 NH3.Stroke 8 (1977) 694–702Google Scholar
  81. Pollitt, R. J. Inherited disorders of straight chain fatty acid oxidation.Arch. Dis. Child. 62 (1987) 6–7Google Scholar
  82. Raichle, M. E. and Grubb, R. L. Regulation of brain water permeability by centrally released vasopressin.Brain Res. 143 (1978) 191–194Google Scholar
  83. Rennebohm, R. M., Heubi, J. E., Daugherty, C. C. and Daniels, S. R. Reye's syndrome in children receiving salicylate therapy for connective tissue disease.J. Paediatr. 107 (1985) 877–880Google Scholar
  84. Reye, R. D. K., Morgan, G. and Baral, J. Encephalopathy and fatty degeneration of the viscera: A disease entity in childhood.Lancet 2 (1963) 749–752Google Scholar
  85. Roe, C. R., Millington, D. S., Maltby, D. A. and Kinnebrew, P. Recognition of medium chain assay CoA dehydrogenase deficiency in asymptomatic siblings of children dying of sudden infant death or Reye like syndrome.J. Paediatr. 108 (1986) 13–18Google Scholar
  86. Rothman, S. M. and Ulney, J. W. Glutamate and the pathophysiology of hypoxic-ischaemic brain damage.Ann. Neurol. 19 (1986) 105–111Google Scholar
  87. Rothstein, J. D. and Herlong, H. F. Neurologic manifestation of hepatic disease.Neurol. Clin. 7 (1989) 563–578Google Scholar
  88. Rudman, D., Glambos, J. T., Smith, R. B., Salam, A. and Warren, W. D. (1973). Comparison of the effects of various amino acids upon the blood ammonia concentration of patients with liver disease.Am. J. Clin. Nutr. 26 (1973) 916–925Google Scholar
  89. Shults, W. T., Fountain, E. N. and Lynch, C. E. Methanethiol poisoning — irreversible coma and haemolytic anaemia following inhalation.J. Am. Med. Assoc. 211 (1970) 2153–2154Google Scholar
  90. Sinniah, D. and Baskaran, G. Margosa oil poisoning in a case of Reye's syndrome.Lancet 1 (1981) 487–489Google Scholar
  91. Stahl, J. Studies of the blood ammonia in liver disease. The diagnostic, prognostic and therapeutic significance.Ann. Intern. Med. 58 (1963) 1–24Google Scholar
  92. Starko, K. M. and Mullick, F. G. Hepatic and cerebral pathology findings in children with fatal salicylate intoxication: further evidence of a causal relationship between salicylate and Reye's syndrome.Lancet 1 (1983) 326–329Google Scholar
  93. Tanaka, K., Kean, E. A. and Johnson, B. Jamaican vomiting sickness: biochemical investigation of 2 cases.N. Engl. J. Med. 295 (1976) 461–467Google Scholar
  94. Tanner, S.Paediatric Hepatology. Current Reviews in Paediatrics. Churchill Livingstone, Edinburgh, 1989, pp. 223–255Google Scholar
  95. Trauner, D. A. and Adams, H. Intracranial pressure elevations during octanoate infusion in rabbits: an experimental model of Reye's syndrome.Paediatr. Res. 15 (1981) 1097–1099Google Scholar
  96. Vaklamp, T., Meijer, A. J., Wilms, J. and Chamuleau, R. A. F. Inhibition of mitochondrial electron transfer in rats by ethanethiol and methane-thiol.Clin. Sci. 56 (1979) 147–156Google Scholar
  97. Vergara, F., Plum, F. and Duffy, T. E. Alpha ketoglutaramate: increased concentration in CSF of patients in hepatic coma.Science 1983 (1974) 81–83Google Scholar
  98. Waller, R. L. Methanethiol inhibition of mitochondrial respiration.Toxicol. Appl. Pharmacol. 42 (1977) 111–117Google Scholar
  99. Warren, K. S. and Schenker, S. Effect of an inhibitor of glutamine synthesis (methionine sulfoximine) on ammonia toxicity and metabolism.J. Lab. Clin. Med. 64 (1964) 442–449Google Scholar
  100. Wasterlain, C. E. and Posner, J. B. Cerebral edema in water intoxication. Clinical and chemical observations.Arch. Neurol. 19 (1968) 71–78Google Scholar
  101. Weber, F. L. Hepatic encephalopathy. In: Williams, R. and Maddrey, W. C. (eds.)Liver. Butterworths, London, 1984, pp. 242–282Google Scholar
  102. Weizman, Z., Mussafi, H. and Ishay, J. S. Multiple hornet stings with features of Reye's syndrome.Gastroenterology 89 (1985) 1407–1410Google Scholar
  103. Wojtczac, L. Effects of long chain fatty acids and acetyl CoA on mitochondrial permeability and energy coupling processes.J. Bioeng. Biomembranes 8 (1976) 293–311Google Scholar
  104. Zieve, L. Coma production with NH4+ synergistic factors.Gastroenterology 78 (1980) 1327Google Scholar
  105. Zieve, L. Encephalopathy due to short and medium chain fatty acid. In: McCandless, D. W. (ed.)Cerebral Energy Metabolism and Metabolic Encephalopathy. Plenum Press, New York, 1985, pp. 163–177Google Scholar
  106. Zieve, L. and Brunner, G. Encephalopathy due to mercaptans and phenols. In: McCandless, D. W. (ed.)Cerebral Energy Metabolism and Metabolic Encephalopathy. Plenum Press, New York, 1985, pp. 179–210Google Scholar
  107. Zieve, L. and Olson, R. L. Can hepatic coma be caused by a reduction of brain noradrenaline or dopamine?Gut 18 (1977) 688–691Google Scholar
  108. Zieve, L., Doizaki, W. M. and Zieve, F. J. Synergism between mercaptans and ammonia or fatty acids in the production of coma.J. Lab. Clin. Med. 83 (1974) 16–28Google Scholar

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© SSIEM and Kluwer Academic Publishers 1991

Authors and Affiliations

  • J. K. Brown
    • 1
  • H. Imam
    • 1
  1. 1.Department of Paediatric NeurologyRoyal Hospital for Sick ChildrenEdinburghScotland

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