High-altitude cerebral edema

High-altitude cerebral edema (HACE) is a medical condition in which the brain swells with fluid because of the physiological effects of traveling to a high altitude. It generally appears in patients who have acute mountain sickness and involves disorientation, lethargy, and nausea among other symptoms. It occurs when the body fails to acclimatize while ascending to a high altitude. High-altitude cerebral edema (HACE) is a medical condition in which the brain swells with fluid because of the physiological effects of traveling to a high altitude. It generally appears in patients who have acute mountain sickness and involves disorientation, lethargy, and nausea among other symptoms. It occurs when the body fails to acclimatize while ascending to a high altitude. It appears to be a vasogenic edema (fluid penetration of the blood–brain barrier), although cytotoxic edema (cellular retention of fluids) may play a role as well. Individuals with the condition must immediately descend to a lower altitude or coma and death can occur. Patients are usually given supplemental oxygen and dexamethasone as well. HACE can be prevented by ascending to heights slowly to allow the body more time to acclimatize. Acetazolamide also helps prevent the condition. Untreated patients usually die within 48 hours. Those who receive treatment may take weeks to fully recover. It is a rare condition, occurring in less than one percent of people who ascend to 4,000 metres (13,000 ft). First described in 1913, little was known about the cause of the condition until MRI studies were performed in the 1990s. Early symptoms of high-altitude cerebral edema (HACE) generally correspond with those of moderate to severe acute mountain sickness (AMS). Initial symptoms of HACE commonly include confusion, loss of consciousness, fever, ataxia, photophobia, rapid heart beat, lassitude, and an altered mental state. Sufferers generally attempt to cease physical activities, regardless of their necessity for survival. Severe headaches develop and sufferers lose the ability to sit up. Retinal venous dilation occurs in 59% of people with HACE. Rarer symptoms include brisk deep tendon reflexes, retinal hemorrhages, blurred vision, extension plantar reflexes, and ocular paralysis. Cranial nerve palsies occur in some unusual cases. In the bestselling 1996 non-fiction book Into Thin Air: A Personal Account of the Mt. Everest Disaster, Jon Krakauer describes the effects of HACE upon Dale Kruse, a forty-four-year-old dentist and one of the members of Scott Fischer's team: ‘Kruse was having an incredibly difficult time simply trying to dress himself. He put his climbing harness on inside out, threaded it through the fly of his wind suit, and failed to fasten the buckle; fortunately, Fisher and Neal Beidleman noticed the screwup before Kruse started to descend. 'If he'd tried to rappel down the ropes like that,' says Beidleman, 'he would have immediately popped out of his harness and fallen to the bottom of the Lhotse Face.'‘'It was like I was very drunk,' Kruse recollects. 'I couldn't walk without stumbling, and completely lost the ability to think or speak. It was a really strange feeling. I'd have some word in my mind, but I couldn't figure out how to bring it to my lips. So Scott and Neal had to get me dressed and make sure my harness was on correctly, then Scott lowered me down the fixed ropes.' By the time Kruse arrived in Base Camp, he says, 'it was still another three or four days before I could walk from my tent to the mess tent without stumbling all over the place.'’ Patients with HACE have an elevated white blood cell count, but otherwise their blood count and biochemistry are normal. If a lumbar puncture is performed, it will show normal cerebral spinal fluid and cell counts but an increase in pressure. In one study, CT scans of patients with HACE exhibited ventricle compression and low density in the cerebellum. Only a few autopsies have been performed on fatal cases of HACE; they showed swollen gyri, spongiosis of white matter, and compressed sulci. There was some variation between individuals, and the results may not be typical of HACE deaths. Most people who travel to high altitudes acclimatize. Acclimatization precludes the development of HACE by maintaining adequate levels of cerebral oxygen. The primary cause of HACE is hypoxia (oxygen deprivation). This occurs after the body is exposed to a low-oxygen environment and before it acclimatizes. The rate of change from a normal oxygen environment and how little oxygen is in the new environment can be used to predict the chance of developing HACE. Prolonged exertion in low oxygen also causes serious hypocapnia, lower carbon dioxide in the bloodstream, which may play a role in HACE. These factors cause the brain to swell with fluid, resulting in severe impairment. If the swelling is untreated, it causes death by brain herniation. The brain swelling is likely a result of vasogenic edema, the penetration of the blood–brain barrier by fluids. This process has been observed in MRI studies. Hypoxia increases extracellular fluid, which passes through the vasogenic endothelium in the brain. The leaking may be caused by increased pressure, or it may be caused by inflammation that makes the endothelium vulnerable to leaking. An MRI study found microhemorrhages in the corpus callosum of HACE patients, and hypoxia may also cause microvascular permeability. It has been hypothesized that vascular endothelial growth factor may cause the vascular permeability at the root of HACE. MRI scans of patients with HACE showed increased T2 in the corpus callosum, although grey matter was unchanged. This demonstrated that the blood-brain barrier was broken by cerebral blood vessels, thus interfering with white matter metabolism. Another study looked at the brains of HACE sufferers several months after their recovery; it showed hemosiderin deposits in the corpus callosum, evidence of vascular permeability. While there is strong evidence that vasogenic edema plays a major role in HACE, cytotoxic edema, cellular retention of fluids, may contribute as well. Cytotoxic edema may be caused by the failure of cellular ion pumps, which results from hypoxia. Then intracellular sodium and osmolarity increase, and there is an influx of water that causes cellular swelling. After the failure of the ATPase pumps, free radicals form and cause damage that complicates the edema. Evidence against cytotoxic edema includes the high levels of hypoxemia (low bloodstream oxygen) needed to cause it.