High altitude cerebral edema and acute mountain sickness: A pathophysiology update

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.