title: The cerebral etiology of high-altitude cerebral edema and acute mountain sickness.
abstract: Despite normal cerebral oxygenation and normal global cerebral metabolism, vasogenic edema develops in humans (and sheep) who become moderately ill with AMS/ HACE during 24 hr or more of hypoxic exposure. Hypoxic cerebral vasodilatation appears to be a necessary ingredient but does not per se explain the development of brain edema. In addition to mechanical factors, a number of biochemical mediators might play a role in altering the blood-brain barrier. Brain cell swelling (cytotoxic edema) likely has a role only in the later stages of HACE and not in AMS. The hypothesis that AMS is due to cerebral edema appears to be true for moderate-to-severe illness, but whether early AMS, especially the headache, is caused by edema is not known. Other mechanisms for the headache, perhaps similar to those of migraine, need to be explored. New data suggest that the brain swells on ascent to high altitudes regardless of AMS. Whether this is due to edema or engorgement with blood is not yet clear. The "tight fit" hypothesis proposes that individual anatomy of the craniospinal axis determines tolerance to mild brain edema and might help explain individual susceptibility; preliminary studies support this notion. Therapy for AMS and HACE is directed to reducing brain volume and stopping the BBB leak (i.e., oxygenation, diuretics, and steroids) before secondary ischemia develops. New therapies directed specifically toward the defect in BBB permeability are likely to be successful.
authors.affiliation: University of Washington School of Medicine, Seattle, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Hackett
mesh_terms: D000531:Altitude; D000532:Altitude Sickness / Q000209:etiology* / Q000503:physiopathology; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000503:physiopathology; D001929:Brain Edema / Q000209:etiology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006801:Humans; D002534:Hypoxia, Brain / Q000209:etiology / Q000503:physiopathology; D007427:Intracranial Pressure