Evidence against cytotoxic edema includes the high levels of hypoxemia (low bloodstream oxygen) needed to cause it.It is not known why some are more vulnerable to HACE than others. One theory is that variations in brain size play a role, but the increase in brain volume from edema does not likely cause cranial vault impingement. The presence of large sulci indicate the condition may be influenced by the brain tightly fitting. Elevated intracranial pressure is generally accepted to be a late effect of HACE. High central venous pressure may also occur late in the conditions progression.One study demonstrated that normal autorelation of cerebral blood flow does not cause HACE. What role the sympathetic nervous system plays in determining who gets HACE is unclear, but it may have an effect.Another theory about the cause of HACE is that hypoxia may induce nitrous oxide synthase. Vasodilation is caused by the release of nitric oxide and adenosine. This in turn can increase vascular permeability and causes edema. This may combine with low levels of cytokines to cause HACE. Diagnosis
Generally, high-altitude pulmonary edema (HAPE) or AMS precede HACE. In patients with AMS, the onset of HACE is usually indicated by vomiting, headache that does not respond to non-steroidal anti-inflammatory drugs, hallucinations, and stupor. In some situations, however, AMS progresses to HACE without these symptoms. HACE must be distinguished from conditions with similar symptoms, including stroke, intoxication, psychosis, diabetic symptoms, meningitis, or ingestion of toxic substances.
It should be the first diagnosis ruled out when sickness occurs while ascending to a high altitude. Prevention
HACE is generally preventable by ascending gradually with frequent rest days while climbing or trekking. Not ascending more than 1,000 metres (3,300 ft) daily and not sleeping at a greater height than 300 metres (980 ft) more than the previous night is recommended. The risk of developing HACE is diminished if acetazolamide or dexamethasone are administered. Generally, the use of acetazolamide is preferred, but dexamethasone can be used for prevention if there are side effects or contraindications. Some individuals are more susceptible to HACE than others, and physical fitness is not preventive. Age and sex do not by themselves affect vulnerability to HACE. Treatment
Patients with HACE should be brought to lower altitudes and provided supplemental oxygen, and rapid descent is sometimes needed to prevent mortality. Early recognition is important because as the condition progresses patients are unable to descend without assistance. Dexamethasone should also be administered, although it fails to ameliorate some symptoms that can be cured by descending to a lower altitude. It can also mask symptoms, and they sometimes resume upon discontinuation. Dexamethasones prevention of angiogenesis may explain why it treats HACE well. Three studies that examined how mice and rat brains react to hypoxia gave some credence to this idea.If available, supplemental oxygen can be used as an adjunctive therapy, or when descent is not possible.