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High Altitude Cerebral Edema and Acute Mountain Sickness

A Pathophysiology Update

  • Chapter
Hypoxia

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 474))

Abstract

The diagnosis, treatment and prevention of high altitude cerebral edema (HACE) are fairly well established. The major unresolved issues are 1) the pathophysiology, 2) the individual susceptibility, and 3) the relationship of HACE to acute mountain sickness (AMS) and to high altitude pulmonary edema (HAPE).

In the context of the two types of cerebral edema, cytotoxic (intracellular) and vasogenic, a leaking of proteins and water through the blood-brain barrier (BBB), a recent MRI study in persons ill with HACE (16) suggested a predominantly vasogenic mechanism. Causes of increased BBB permeability might include mechanical factors (loss of autoregulation and increased capillary pressure), ischemia, neurogenic influences (adrenergic and cholinergic activation), and a host of permeability mediators. Once vasogenic edema develops, cytotoxic edema generally follows, and although likely in HACE, this is still unproven. Symptoms of HACE are related to increased intracranial pressure (ICP), and death is from brain herniation. Treatment is directed both to lowering ICP by reducing the volume of intracranial contents, and to stopping the vasogenic leak.

Evidence is accumulating that established moderate to severe AMS is due to cerebral edema, but whether this is true for early AMS (headache) is unclear. New work suggests that the brain swells on ascent to altitude, but that this is unrelated to AMS. Preliminary data showing that those with less cerebrospinal fluid volume (a tighter fit of the brain in the cranium) were more likely to develop AMS supports the hypothesis of Ross that those with less ability to accommodate the increased brain volume are the ones that suffer AMS. The blood-brain barrier and intracranial hemodynamics are the two key elements in the pathophysiology of HACE and AMS.

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References

  1. Abbott, N., and P. Revest. Control of brain endothelial permeability. Cerebrovasc Brain Metb Rev 3: 39–72, 1991.

    CAS  Google Scholar 

  2. Akiyama, Y., K. Koshimura, T. Ohue, K. Lee, S. Miwa, S. Yamagata, and H. Kikuchi. Effects of hypoxia on the activity of the dopaminergic neuron system in the rat striatum as studied by in vivo brain microdialysis. J Neurochem 57: 997–1002, 1991.

    Article  PubMed  CAS  Google Scholar 

  3. Banderet, L. E., and H. R. Lieberman. Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Res Bull 22: 759–762, 1989.

    Article  PubMed  CAS  Google Scholar 

  4. Clark, I. Can excessive iNOS induction explain much of the illness of acute mountain sickness? (Abstract). In: Hypoxia: Into the Next Millennium, edited by R.C. Roach, P.D. Wagner and P.H. Hackett. New York: Kluwer Academic/Plenum Publishers, 1999.

    Google Scholar 

  5. Claybaugh, J. R., D. P. Brooks, and A. Cymerman. Hormonal control of fluid and electrolyte balance at high altitude in normal subjects. In: Hypoxia and Mountain Medicine, edited by J. R. Sutton, G. Coates and C. S. Houston. Burlington, VT: Queen City Press, 1992.

    Google Scholar 

  6. Consolazio, C. F., H. L. Johnson, and H. J. Krzywicki. Body fluids, body composition, and metabolic aspects of high-altitude adaptation. In: Physiological Adaptations: Desert and Mountain, edited by M. K. Yousef, S. M. Horvath and R. W. Bullard. New York, NY: Academic Press, 1972, p. 227–241.

    Google Scholar 

  7. Dill, D. B., O. O. Benson, W. H. Forbes, and F. G. Hall. Benzedrine sulphate (amphetamine) and acute anoxia. I. respiratory effects. J Aviat Med 11: 1–6, 1940.

    Google Scholar 

  8. Gibson, G. E., W. Pulsinelli, J. P. Blass, and T. E. Duffy. Brain dysfunction in mild to moderate hypoxia. Am J Med 70: 1247–1254, 1981.

    Article  PubMed  CAS  Google Scholar 

  9. Green, H., B. Roy, S. Grant, M. Burnett, C. Otto, A. Pipe, and D. McKenzie. Down-regulation in muscle Na-K ATPase concentration following a 21 day expedition to 6200 m (Abstract). In: Hypoxia: Into the Next Millennium, edited by R.C. Roach, P.D. Wagner and P.H. Hackett. New York: Kluwer Academic/Plenum Publishers, 1999

    Google Scholar 

  10. Grubb, R. L., M. E. Raichle, J. O. Eichling, and M. M. Ter-Pogossian. The effects of changes in PaCO2 on cerebral blood volume, blood flow, and vascular mean transit time. Stroke 5: 630–639, 1974.

    Article  PubMed  Google Scholar 

  11. Gwan, K., J. Gazendam, and A. K. Van Zanten. Influence of hypoxia on the composition of isolated edema fluid in cold-induced brain edema. J Neurosurg 51: 78–84, 1979.

    Article  Google Scholar 

  12. Hackett, P., and G. Hartig. Cerebral blood velocity and cerebral spinal fluid pressure in acute mountain sickness. In: Hypoxia and Mountain Medicine, edited by J. Sutton, G. Coates and C. Houston. Burlington, Vermont: Quenn City Printers, 1991, p. 302.

    Google Scholar 

  13. Hackett, P. H., I. D. Rennie, R. F. Grover, and J. T. Reeves. Acute mountain sickness and the edemas of high altitude: A common pathogenesis? Respir Physiol 46: 383–390, 1981.

    Article  PubMed  CAS  Google Scholar 

  14. Hackett, P. H., I. D. Rennie, and H. D. Levine. The incidence, importance, and prophylaxis of acute mountain sickness. Lancet 2: 1149–1154, 1976.

    Article  PubMed  CAS  Google Scholar 

  15. Hackett, P. H., and R. C. Roach. High-altitude medicine. In: Wilderness Medicine, edited by P. A. Auerbach. St. Louis: Mosby, 1995, p. 1–37.

    Google Scholar 

  16. Hackett, P. H., P. R. Yarnell, R. Hill, K. Reynard, J. Heit, and J. McCormick. High-altitude cerebral edema evaluated with magnetic resonance imaging: clinical correlation and pathophysiology. JAMA 280: 1920–1925, 1998.

    Article  PubMed  CAS  Google Scholar 

  17. Hannon, J. P., K. S. Chinn, and J. L. Shields. Effects of acute high altitude exposure on body fluids. Fed Proc 28: 1178–1184, 1969.

    PubMed  CAS  Google Scholar 

  18. Hansen, J. E., and W. O. Evans. A hypothesis regarding the pathophysiology of acute mountain sickness. Arch Environ Health 21: 666–669, 1970.

    PubMed  CAS  Google Scholar 

  19. Hartig, G. S., and P. H. Hackett. Cerebral spinal fluid pressure and cerebral blood velocity in acute mountain sickness. In: Hypoxia and Mountain Medicine, edited by J. R. Sutton, G. Coates and C. S. Houston. Burlington, VT: Queen City Press, 1992.

    Google Scholar 

  20. Honig, A. Electrolytes, body fluid volumes and renal function in acute hypoxic hypoxia. Acta Physiol Pol 30: 93–125, 1979.

    PubMed  CAS  Google Scholar 

  21. Houston, C. S., and J. G. Dickinson. Cerebral form of high altitude illness. Lancet 2: 758–761, 1975.

    Article  PubMed  CAS  Google Scholar 

  22. Icenogle, M., D. Kilgore, J. Sanders, A. Caprihan, and R. Roach. Cranial CSF volume (cCSF) is reduced by altitude exposure but is not related to early acute mountain sickness (AMS) (Abstract). In: Hypoxia: Into the Next Millennium, edited by R.C. Roach, P.D. Wagner and P.H. Hackett. New York: Kluwer Academic/Plenum Publishers, 1999

    Google Scholar 

  23. Kilgore, D., J. Loeppky, J. Sanders, A. Caprihan, M. Icenogle, and R. Roach. Corpus callosum (CC) MRI: Early altitude exposure (Abstract). In: Hypoxia: Into the Next Millennium, edited by R.C. Roach, P.D. Wagner and P.H. Hackett. New York: Kluwer Academic/Plenum Publishers, 1999

    Google Scholar 

  24. Klatzo, I. Pathophysiologic aspects of brain edema. Acta Neuropath (Berl) 72: 236–239, 1987.

    Article  CAS  Google Scholar 

  25. Klatzo, I. Presidential address: Neuropathologie aspects of brain edema. J Neuropath Exp Neurol 26: 1–14, 1967.

    Article  PubMed  CAS  Google Scholar 

  26. Kobayashi, T., S. Koyama, K. Kubo, M. Fukushima, and S. Kusama. Clinical features of patients with high altitude pulmonary edema in Japan. Chest 92: 814–821, 1987.

    Article  PubMed  CAS  Google Scholar 

  27. Krasney, J. A. Cerebral hemodynamics and high altitude cerebral edema. In: Hypoxia: Women at Altitude, edited by C. S. Houston and G. Coates. Burlington: Queen City Publishers, 1997, p. 254–267.

    Google Scholar 

  28. Krasney, J. A. A neurogenic basis for acute altitude illness. Med Sci Sports Exerc 26: 195208, 1994.

    Google Scholar 

  29. Krasney, J. A., D. C. Curran-Everett, and J. Iwamoto. High altitude cerebral edema: An animal model. In: Hypoxia: The Adaptations, edited by J. R. Sutton, G. Coates and J. E. Remmers. Philadelphia, PA: BC Dekker, 1990, p. 200–205.

    Google Scholar 

  30. Lassen, N. A. The brain: cerebral blood flow. In: Hypoxia: Man at Altitude, edited by J. R. Sutton, N. L. Jones and C. S. Houston. New York, NY: Thieme-Stratton, 1982, p. 9–13.

    Google Scholar 

  31. Lassen, N. A., and A. M. Harper. High-altitude cerebral oedema. Lancet: 1154, 1975.

    Google Scholar 

  32. Levine, B. Dynamic cerebral autoregulation at high altitude (Abstract). In: Hypoxia: Into the Next Millennium, edited by R.C. Roach, P.D. Wagner and P.H. Hackett. New York: Kluwer Academic/Plenum Publishers, 1999.

    Google Scholar 

  33. Levine, B. D., K. Yoshimura, T. Kobayashi, M. Fukushima, T. Shibamoto, and G. Ueda. Dexamethasone in the treatment of acute mountain sickness. N Engl J Med 321: 1707–1713, 1989.

    Article  PubMed  CAS  Google Scholar 

  34. Matsuzawa, Y., T. Kobayashi, K. Fujimoto, S. Shinozaki, and S. Yoshikawa. Cerebral edema in acute mountain sickness. In: High Altitude Medicine, edited by G. Ueda, J. T. Reeves and M. Sekiguchi. Matsumoto, Japan: Shinshu Univ Press, 1992, p. 300–304.

    Google Scholar 

  35. Mayhan, W., and D. Heistad. Role of veins and cerebral venous pressure in disruption of the blood-brain barrier. Circ Res 59: 216–220, 1986.

    Article  PubMed  CAS  Google Scholar 

  36. Miller, J. Volume and pressure in the craniospinal axis. Clin Neurosurg 22: 76–105, 1975.

    PubMed  CAS  Google Scholar 

  37. Muza, S., T. Lyons, P. Rock, C. Fulco, B. Beidleman, S. Smith, I. Morocz, G. Zientaral, and A. Cymerman. Effect of altitude exposure on brain volume and development of acute mountain sickness (AMS) (Abstract). In: Hypoxia: Into the Next Millennium, edited by R.C. Roach, P.D. Wagner and P.H. Hackett. New York: Kluwer Academic/Plenum Publishers, 1999.

    Google Scholar 

  38. Nordqvist, L. The sagittal diameter of the spinal cord and subarachnoid space in different age groups: a roentgenographic post-mortem study. Act Radiol Diagn (Stockh) suppl 227: 1–96, 1964.

    Google Scholar 

  39. Ogawa, S., S. Koga, and R. Kuwabara. Hypoxia-induced increased permeability of endothelial monolayers occurs through lowering of cellular cAMP levels. Am J Physiol 262: C546–0554, 1992.

    PubMed  CAS  Google Scholar 

  40. Raichle, M., B. Hartman, J. Eichung, and L. Sharpe. Central noradrenergic regulation of cerebral blood flow and vascular permeability. Proc Nat Acad Sci, 1975.

    Google Scholar 

  41. Richalet, J. P., A. Hornych, C. Rathat, J. Aumont, P. Larmignant, and P. Remy. Plasma prostaglandins, leukotrienes and thromboxane in acute high altitude hypoxia. Respir Physiol 85: 205–215, 1991.

    Article  PubMed  CAS  Google Scholar 

  42. Ropper, A. Raised intracranial pressure in neurologic disease. Sem Neurology 4: 397–407, 1984.

    Article  Google Scholar 

  43. Ross, R. T. The random nature of cerebral mountain sickness. Lancet 1: 990–991, 1985.

    Article  PubMed  CAS  Google Scholar 

  44. Schilling, L. Mediators of vasogenic edema. In: Hypoxia: Into the Next Millennium, edited by R.C. Roach, P.D. Wagner and P.H. Hackett. New York: Kluwer Academic/Plenum Publishers, 1999.

    Google Scholar 

  45. Schilling, L., and M. Wahl. Brain edema: Pathogenesis and therapy. Kidney Int 51: S69–S75, 1997.

    Article  Google Scholar 

  46. Severinghaus, J. Cerebral Circulation at Altitude. In: High Altitude, edited by T. Hornbein and R. Schoene. New York: Marcel Decker, 1999.

    Google Scholar 

  47. Severinghaus, J. W. Hypothetical roles of angiogenesis, osmotic swelling, and ischemia in high-altitude cerebral edema. J Appl Physiol 79: 375–9, 1995.

    PubMed  CAS  Google Scholar 

  48. Shapiro, K., A. Marmarou, and K. Shulman. Characterization of clinical CSF dynamics and neural axis compliance using the pressure-volume index. I: The normal pressure-volume index. Ann Neurol 7: 508–514, 1980.

    Article  PubMed  CAS  Google Scholar 

  49. Singh, I., P. K. Khanna, M. C. Srivastava, M. Lal, S. B. Roy, and C. S. V. Subramanyam. Acute mountain sickness. N Engl J Med 280: 175–184, 1969.

    Article  PubMed  CAS  Google Scholar 

  50. Sutton, J. R., and N. Lassen. Pathophysiology of acute mountain sickness and high altitude pulmonary oedema: an hypothesis. Bull Europ Physiopath Respir 15: 1045–1052, 1979.

    CAS  Google Scholar 

  51. West, J. B., and O. Mathieu-Costello. High altitude pulmonary edema is caused by stress failure of pulmonary capillaries. Intl J Sport Med 13: S54–S58, 1992.

    Article  Google Scholar 

  52. Wright, A. D., C. H. Imray, M. S. Morrissey, R. J. Marchbanks, and A. R. Bradwell. Intracranial pressure at high altitude and acute mountain sickness. Clin Sci Colch 89: 2014, 1995.

    Google Scholar 

  53. Yang, S. P., and J. A. Krasney. Cerebral blood flow and metabolic responses to sustained hypercapnia in awake sheep. J Cereb Blood Flow Metab 15: 115–123, 1995.

    Article  PubMed  CAS  Google Scholar 

  54. Zavasky, D., and P. Hackett. Cerebral etiology of acute mountain sickness MRI findings. Wilderness Environ Med 6: 229–230, 1995.

    Google Scholar 

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Author information

Authors and Affiliations

  1. St. Mary’s Hospital and Medical Center, University of Washington School of Medicine and Emergency Department, Grand Junction, Colorado, USA

    Peter H. Hackett

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Editors and Affiliations

  1. Department of Life Sciences, New Mexico Highlands University, Las Vegas, New Mexico, USA

    Robert C. Roach

  2. Department of Medicine, University of California San Diego, La Jolla, California, USA

    Peter D. Wagner

  3. St. Mary’s Hospital and Medical Center, University of Washington School of Medicine and Emergency Department, Grand Junction, Colorado, USA

    Peter H. Hackett

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Hackett, P.H. (1999). High Altitude Cerebral Edema and Acute Mountain Sickness. In: Roach, R.C., Wagner, P.D., Hackett, P.H. (eds) Hypoxia. Advances in Experimental Medicine and Biology, vol 474. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4711-2_2

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  • DOI: https://doi.org/10.1007/978-1-4615-4711-2_2

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