Cerebral spinal fluid dynamics: Effect of hypoxia and implications for high-altitude illness

Justin S. Lawley, Benjamin D. Levine, Michael A. Williams, Jon Malm, Anders Eklund, David M. Polaner, Andrew W. Subudhi, Peter H. Hackett, Robert C. Roach

Research output: Contribution to journalReview articlepeer-review

44 Scopus citations


The pathophysiology of acute mountain sickness and high-altitude cerebral edema, the cerebral forms of high-altitude illness, remain uncertain and controversial. Persistently elevated or pathological fluctuations in intracranial pressure are thought to cause symptoms similar to those reported by individuals suffering cerebral forms of high-altitude illness. This review first focuses on the basic physiology of the craniospinal system, including a detailed discussion of the long-term and dynamic regulation of intracranial pressure. Thereafter, we critically examine the available literature, based primarily on invasive pressure monitoring, that suggests intracranial pressure is acutely elevated at altitude due to brain swelling and/or elevated sagittal sinus pressure, but normalizes over time. We hypothesize that fluctuations in intracranial pressure occur around a slightly elevated or normal mean intracranial pressure, in conjunction with oscillations in arterial PO2 and arterial blood pressure. Then these modest fluctuations in intracranial pressure, in concert with direct vascular stretch due to dilatation and/or increased blood pressure transmission, activate the trigeminal vascular system and cause symptoms of acute mountain sickness. Elevated brain water (vasogenic edema) may be due to breakdown of the blood-brain barrier. However, new information suggests cerebral spinal fluid flux into the brain may be an important factor. Regardless of the source (or mechanisms responsible) for the excess brain water, brain swelling occurs, and a "tight fit" brain would be a major risk factor to produce symptoms; activities that produce large changes in brain volume and cause fluctuations in blood pressure are likely contributing factors.

Original languageEnglish (US)
Pages (from-to)251-262
Number of pages12
JournalJournal of applied physiology
Issue number2
StatePublished - Jan 15 2016


  • Acute mountain sickness
  • Headache and intracranial pressure
  • High-altitude cerebral edema

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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