Central Nervous System Complications of Severe Hyponatremia

  • Richard H. Sterns


The brain has an astonishing ability to adapt to osmotic disturbances: survival has been recorded at serum sodium concentrations ranging from 85 to 272 mmol/1 (1). However, because this adaptation takes time, the brain does not take well to abrupt changes (1–3). A sudden onset of severe hypernatremia dehydrates the brain, shrinking it away from its vascular attachments and causing fatal cerebral hemorrhage (4). An acute onset of severe hyponatremia causes cerebral edema, swelling the brain beyond the capacity of the cranial vault and causing fatal herniation (5). Once the brain has adapted to an abnormal osmotic environment, rapid correction of the disturbance may also be injurious. We have long known that overenthusiastic rehydration of patients with chronic hypernatremia may result in cerebral edema and seizures (4). More recently it has been shown that excessively aggressive correction of chronic hyponatremia may cause delayed neurologic deterioration and brain demyelination — a phenomenon that has been dubbed the “osmotic demyelination syndrome”(1–3,6–9).


Cerebral Edema Serum Sodium Concentration Central PONTINE MYELINOLYSIS Water Intoxication Rapid Correction 
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  1. 1.
    Stems RH, Spital A: Disorders of water balance. In: “Fluids and Electrolytes” (Eds JP Kokko, RL Tannen), Saunders, Philadelphia, 1990, pp 139–194.Google Scholar
  2. 2.
    Sterns RH, Thomas DJ, Herndon RM: Brain dehydration and neurologic deterioration after rapid correction of hyponatremia. Kidney Int, 35:69–75, 1989.PubMedCrossRefGoogle Scholar
  3. 3.
    Sterns RH: The Management of symptomatic hyponatremia. Seminars in Nephrology, 10(6): 503–514, 1990.PubMedGoogle Scholar
  4. 4.
    Ross EJ, Christie SBM: Hypernatremia. Medicine, 48: 441–473, 1969.PubMedCrossRefGoogle Scholar
  5. 5.
    Arieff AI, Llach F, Massry SG: Neurologic manifestations and morbidity of hyponatremia: Correlation with brain water and electrolytes. Medicine, 55:121–129, 1976.PubMedCrossRefGoogle Scholar
  6. 6.
    Kleinschmidt-DeMasters BK, Norenberg MD: Rapid correction of hyponatremia causes demyelination: Relation to central pontine myelinolysis. Science, 211: 1068–1070, 1981.PubMedCrossRefGoogle Scholar
  7. 7.
    Laureno R: Central pontine myelinolysis following rapid correction of hyponatremia. Ann Neurol, 13: 232–242, 1983.PubMedCrossRefGoogle Scholar
  8. 8.
    Norenberg MD, Leslie KO, Robertson AS: Association between rise in serum sodium and central pontine myelinolysis. Ann Neurol, 40: 66–69, 1983.Google Scholar
  9. 9.
    Sterns RH, Riggs JE, Schochet SS Jr: Osmotic demyelination syndrome following correction of hyponatremia. N Engl J Med, 314: 1535–1542, 1986.PubMedCrossRefGoogle Scholar
  10. 10.
    Lien YH, Shapiro JI, Chan L: Effects of hypernatremia on organic brain osmoles. J Clin Invest, 85: 1427, 1990.PubMedCrossRefGoogle Scholar
  11. 11.
    Thurston JH, Hauhart RE, Nelson JS: Adaptive decreases in amino acids (taurine in particular) creatine, and electrolytes prevent cerebral edema in hyponatremic mice. Rapid correction (experimental model of central pontine myelinolysis) causes dehydration and shrinkage of brain. Metab Brain Dis, 2: 233–241, 1987.CrossRefGoogle Scholar
  12. 12.
    Rowntree, LG: The effects on marnais of the administration of excessive quantities of water. J Pharmacol Exp Ther, 29: 135–159, 1926.Google Scholar
  13. 13.
    Cluitsman FHM, Meinders AE: Management of severe hyponatremia: rapid or slow correction? Am J Med, 88: 161–166, 1990.CrossRefGoogle Scholar
  14. 14.
    Helwig FC, Schutz CB, Curry DE: Water intoxication. Report of a fatal human case, with pathologic and experimental studies. JAMA, 104: 1569–1575, 1935.Google Scholar
  15. 15.
    Fraser CL, Arieff AI: Fatal central diabetes mellitus and insipidus resulting from untreated hyponatremia: A new syndrome. Ann Intern Med, 112: 113–119, 1990.PubMedGoogle Scholar
  16. 16.
    Arieff AI: Hyponatremia, convulsions, respiratory arrest, and permanent brain damage after elective surgery in healthy women. N Engl J Med, 314: 1529–1535, 1986.PubMedCrossRefGoogle Scholar
  17. 17.
    Anastassiades E., Wilson R, Stewart JSW, Perkin GD: Fatal brain oedema due to accidental water intoxication. Br Med J, 287: 1181–1182, 1983.CrossRefGoogle Scholar
  18. 18.
    Raskind M: Psychosis, polydipsia, and water intoxication. Report of a fatal case. Arch Gen Psych, 30: 112–114, 1974.Google Scholar
  19. 19.
    Peh LH, Devan GS, Low BL: A fatal case of water intoxication in a schizophrenic patient. Br J Psych, 156: 891–894, 1990.CrossRefGoogle Scholar
  20. 20.
    Arieff AI: Osmotic failure: Physiology and strategies for treatment. Hosp Pract, 23: 173–194, 1988.Google Scholar
  21. 21.
    Berl T: Treating hyponatremia: damned if we do and damned if we don’t. Kidney Int, 37:1006–1018, 1990.PubMedCrossRefGoogle Scholar
  22. 22.
    Helwig FC, Schutz CB, Kuhn HP: Water intoxication. Moribund patient cured by administration of hypertonic salt solution. JAMA, 110: 644–645, 1938Google Scholar
  23. 23.
    Berginer VM, Osimani A, Berjiner J, Barmeir E: CT brain scan in acute water intoxication. J Neurol Neurosurg Psychiatr, 48: 841–842, 1985.PubMedCrossRefGoogle Scholar
  24. 24.
    Kott E, Marcus Y: Acute brain edema due to water loading in a young woman. Eur Neurol, 24: 221–224, 1985.PubMedCrossRefGoogle Scholar
  25. 25.
    Bartholomew LG, Scholz DA: Reversible post-operative neurological symptoms. Report of five cases secondary to water intoxication and sodium depletion. JAMA, 162: 22–26, 1956.Google Scholar
  26. 26.
    Scott JC Jr, Welch JS, Herman IB: Water intoxication and sodium depletion in surgical patients. Obstet Gynecol, 26: 168–175, 1965.PubMedGoogle Scholar
  27. 27.
    Wynn V, Rob CG: Water intoxication. Differential diagnosis of the hypotonic syndromes. Lancet I: 587–594, 1954.CrossRefGoogle Scholar
  28. 28.
    Zimmerman B, Wagensteen OH: Observations on water intoxication in surgical patients. Surgery, 34: 654–669, 1952.Google Scholar
  29. 29.
    Ahmad AJ, Clark EH, Jacobs HS: Water intoxication associated with oxytocin infusion. Postgrad Med J, 51: 249–252, 1975.PubMedCrossRefGoogle Scholar
  30. 30.
    Feeney JG: Water intoxication and oxytocin. Br Med J, 285: 243, 1982.CrossRefGoogle Scholar
  31. 31.
    Lauersen NH, Birnbaum SJ: Water intoxication associated with oxytocin administration during saline-induced abortion. Am J Obstet Gynecol, 121: 2–6, 1975.PubMedGoogle Scholar
  32. 32.
    Morgan DB, Kirwan NA, Hancock KW, Robinson D, Howe JG, Ahmad S: Water intoxication and oxytocin infusion. Br J Obstet, 84: 6–12, 1977.CrossRefGoogle Scholar
  33. 33.
    Gupta R, Coen NH: Oxytocin, “salting out”, and water intoxication. JAMA, 220: 681–683, 1972.PubMedCrossRefGoogle Scholar
  34. 34.
    Lillien A: Oxytocin-induced water intoxication. A report of a maternal death. Obstet Gynecol, 32: 171–173, 1968.Google Scholar
  35. 35.
    Cheng JC, Zikos D, Skopicki HA, Peterson DR, Fisher KA: Long-term neurologic outcome in psychogenic water drinkers with severe symptomatic hyponatremia: the effect of rapid correction. Am J Med, 88: 561–566, 1990.PubMedCrossRefGoogle Scholar
  36. 36.
    Hariprasad MK, Eisinger RP, Nadler IM, Padmanabhan CS, Nidus BD: Arch Intern Med, 140: 1639–1642, 1980.PubMedCrossRefGoogle Scholar
  37. 37.
    Jose CJ, Perez-Cruet J: Incidence and morbidity of self-induced water intoxication in state mental hospital patients. Am J Psychiatr, 136: 221–222, 1989.Google Scholar
  38. 38.
    Rosenbaum JF, Rothman JS, Murray GB: Psychosis and water intoxication. J Clin Psychiatr, 146: 127–131, 1985.Google Scholar
  39. 39.
    Singh S, Padi MH, Bullard H: Water intoxication in psychiatric patients. Am J Psychiatr, 137: 127–131, 1985.Google Scholar
  40. 40.
    Smith WO, Clark ML: Self-induced water intoxication in schizophrenic patients. Am J Psychiatr, 137: 1055–1060, 1980.PubMedGoogle Scholar
  41. 41.
    Rendell M, McGrane D, Cuesta M: Fatal compulsive water drinking. JAMA 240: 2557–2559, 1978.PubMedCrossRefGoogle Scholar
  42. 42.
    Vieweg WVR, David JJ, Rowe WT, Wampler GJ, Burns WJ, Spradlin WW: Death from self-induced water intoxication among patients with schizophrenic disorders. J Nerv Mental Dis, 173: 161–165, 1985.CrossRefGoogle Scholar
  43. 43.
    Sterns RH: Severe symptomatic hyponatremia: treatment and outcome. A study of 64 cases. Ann Intern Med, 107: 656–664, 1987.PubMedGoogle Scholar
  44. 44.
    Ayus JC, Krothapalli RK, Arieff AI: Sexual difference in survival with severe symptomatic hyponatremia. Kidney Int, 33: 180, 1988 (Abstract).Google Scholar
  45. 45.
    Rothenberg DM, Berns AS, Ivankovich AD: Isotonic hyponatremia following transurethral prostate resection. J Clin Anesth, 2: 48–49, 1990.PubMedCrossRefGoogle Scholar
  46. 46.
    Fraser CL, Kuchareczyk J, Arieff AI, Rollin C, Sarnacki P, Norman D: Sex differences result in increased morbidity from hyponatremia in female rats. Am J Physiol, 256: R880–R885, 1989.PubMedGoogle Scholar
  47. 47.
    Fraser CL, Sarnacki P: Na+-K+ ATPase pump function in rat brain synaptosomes is different in males and females. Am J Physiol, 157: E284–E289, 1989.Google Scholar
  48. 48.
    Sterns RH, Silver S, Thomas D: Sexual equality in hyponatremia. Kidney Int, 37: 268, 1990 (Abstract).Google Scholar
  49. 49.
    Verbalis JG, Drutarosky MD: Sexual dimorphism of brain adaptation to chronic hyponatremia in rats. Kidney Int, 37: 269, 1990 (Abstract).Google Scholar
  50. 50.
    Verbalis JG, Drutarosky MD: Adaptation to chronic hypoosmolality in rats. Kidney Int, 34: 351–360, 1988.PubMedCrossRefGoogle Scholar
  51. 51.
    Boon AP, Potter AE: Extensive extrapontine and central pontine myelinolysis associated with correction of profound hyponatremia. Neuropath Appl Neurobiol, 13: 1–9, 1987.CrossRefGoogle Scholar
  52. 52.
    DaCunha C, Bertorini TE, Lawrence J, Witherington: Central pontine myelinolysis — a preventable condition. J Tenn Med Assoc, 79: 469–472, 1986.Google Scholar
  53. 53.
    Gerard E, Healy ME, Hesselink JR: MR demonstration of mesencephalic lesions in osmotic demyelination syndrome (central pontine myelinolysis). Neuroradiology, 29: 582–584, 1987.PubMedCrossRefGoogle Scholar
  54. 54.
    Hazratji SMA, Kim RC, Lee SH, Marasigan AV: Evolution of pontine and extrapontine myelinolysis. J Comput Assist Tomoagr, 7(2): 356–361, 1983.CrossRefGoogle Scholar
  55. 55.
    Walker JV, Englander RN: Central pontine myelinolysis following rapid correction of hyponatremia in an alcoholic. Am J Kidney Dis, 12: 531–533, 1988.PubMedGoogle Scholar
  56. 56.
    Covey CM, Arieff AI: Disorders of sodium and water metabolism and their effects on the central nervous system. Advances in Nephrology, 13: 1–128, 1978.Google Scholar
  57. 57.
    Brunner JE, Redmond JM, Haggar AM, Kruger MSN, Elias S: Central pontine myelinolysis and pontine lesions after rapid correction of hyponatremia: a prospective magnetic imaging study. Ann Neurol, 27: 61–66, 1990.PubMedCrossRefGoogle Scholar
  58. 58.
    Miller GM, Baker HL Jr, Okazaki H, Whisnant JP: Central pontine myelinolysis and its imitators: MR findings. Radiology, 168: 795–802, 1988.PubMedGoogle Scholar
  59. 59.
    Tomlinson BE, Pierides AM, Braddley WG: Central pontine myelinolysis. Q J Med, 45: 373–386, 1976.PubMedGoogle Scholar
  60. 60.
    Wright DG, Laureno R, Victor M: Pontine and extrapontine myelinolysis. Brain, 102: 361–385, 1989.CrossRefGoogle Scholar
  61. 61.
    Clifford DB, Gado MH, Levy BK: Osmotic demyelination syndrome. Lack of pathologic and radiologic imaging correlation. Arch Neurol, 46: 343–347, 1989.PubMedGoogle Scholar
  62. 62.
    Laureno R, Karp BI: Pontine and extrapontine myelinolysis following rapid correction of hyponatremia. Lancet, I: 1439–1441, 1988.CrossRefGoogle Scholar
  63. 63.
    Sterns RH: Neurologic deterioration following treatment for hyponatremia. Am J Kidney Dis, 13: 434–437, 1989.PubMedGoogle Scholar
  64. 64.
    Verbalis JG, Martinez J: Neurological and neuropathological sequelae of controlled correction of hypoosmolality in chronically hyponatremic rats. Kidney Int, 1991 (in press).Google Scholar
  65. 65.
    Illowsky BP, Laureno R: Encephalopathy and myelinolysis after rapid correction of hyponatremia. Brain, 110: 855–867, 1987.PubMedCrossRefGoogle Scholar
  66. 66.
    Norenberg MD, Papendick RE: Chronicity of hyponatremia as a factor in experimental myelinolysis. Ann Neurol, 15: 544–547, 1984.PubMedCrossRefGoogle Scholar
  67. 67.
    Riggs JE, Schochet SS: Osmotic stress, osmotic myelinolysis, and oligodendrocyte topography. Arch Pathol Lab Med, 113: 1386–1388, 1989.PubMedGoogle Scholar
  68. 68.
    Plum F, Posner JB, Hain RF: Delayed neurological deterioration after anoxia. Arch Intern Med, 110: 56–63, 1962.Google Scholar
  69. 69.
    Ayus JC, Krothapalli RK, Arieff AI: Treatment of symptomatic hyponatremia and its relation to brain damage. N Engl J Med, 317: 1190–1195, 1987.PubMedCrossRefGoogle Scholar
  70. 70.
    Mickel HS, Oliver CN, Starke-Reed PE: Protein oxidation and myelinolysis occur in brain following rapid correction of hyponatremia. Biochemical & Biophysical Research Communications, 172(1): 92–97, 1990.CrossRefGoogle Scholar
  71. 71.
    Abramow M, Cogan E: Clinical aspects and pathophysiology of diuretic-induced hyponatremia. Advances in Nephrology, 13: 1–28, 1984.PubMedCrossRefGoogle Scholar
  72. 72.
    Ayus JC, Krothapalli RK, Arieff: Changing concepts in the treatment of severe symptomatic hyponatremia. Rapid correction and possible relation to central pontine myelinolysis. Am J Med, 78: 897–902, 1985.PubMedCrossRefGoogle Scholar
  73. 73.
    Sterns RH: The treatment of hyponatremia: First, do no harm. Am J Med, 88: 557–560, 1990.PubMedCrossRefGoogle Scholar
  74. 74.
    Sterns RH: The management of hyponatremic emergencies. Critical Care Clinics, 7(1): 127–142, 1991.PubMedGoogle Scholar

Copyright information

© Springer-Verlag London Limited 1991

Authors and Affiliations

  • Richard H. Sterns
    • 1
  1. 1.Division of Nephrology, Department of MedicineUniversity of Rochester School of Medicine, Rochester General HospitalRochesterUSA

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