High-altitude cerebral edema
High-altitude cerebral edema | |
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Other names | High-altitude cerebral oedema[1] (HACO) |
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
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). Although it was first described in 1913, little was known about the cause of the condition until MRI studies were performed in the 1990s.
Signs and symptoms
Early symptoms of HACE generally correspond with those of moderate to severe
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, Fischer 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
Mechanism
Most people who travel to high altitudes
The brain swelling is likely a result of vasogenic edema, the penetration of the blood–brain barrier by fluids.[16] 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.[9] An MRI study found microhemorrhages in the corpus callosum of HACE patients,[16] and hypoxia may also cause microvascular permeability.[9] It has been hypothesized that vascular endothelial growth factor may cause the vascular permeability at the root of HACE.[17] 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.[18] Another study looked at the brains of people with HACE several months after their recovery; it showed hemosiderin deposits in the corpus callosum, evidence of vascular permeability.[8]
While there is strong evidence that vasogenic edema plays a major role in HACE, cytotoxic edema, cellular retention of fluids, may contribute as well.
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.[17] The presence of large sulci indicate the condition may be influenced by the brain tightly fitting.[21] Elevated intracranial pressure is generally accepted to be a late effect of HACE.[22][23] High central venous pressure may also occur late in the condition's progression.[17]
One study demonstrated that normal autorelation of
Another theory about the cause of HACE is that hypoxia may induce nitrous oxide synthase.[25] Vasodilation is caused by the release of nitric oxide and adenosine.[13] This in turn can increase vascular permeability and causes edema. This may combine with low levels of cytokines to cause HACE.[25]
Diagnosis
Generally,
Prevention
HACE is generally preventable by ascending gradually with frequent rest days while climbing or trekking.[26][20] 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.[27] The risk of developing HACE is diminished if acetazolamide or dexamethasone are administered.[16] Generally, the use of acetazolamide is preferred, but dexamethasone can be used for prevention if there are side effects or contraindications.[28] Some individuals are more susceptible to HACE than others,[20] and physical fitness is not preventive.[29] Age and sex do not by themselves affect vulnerability to HACE.[5]
Treatment
Patients with HACE should be brought to lower altitudes and provided supplemental oxygen,[18] and rapid descent is sometimes needed to prevent mortality.[30] Early recognition is important because as the condition progresses patients are unable to descend without assistance.[9] Dexamethasone should also be administered,[16] although it fails to ameliorate some symptoms that can be cured by descending to a lower altitude.[9] It can also mask symptoms, and they sometimes resume upon discontinuation.[20] Dexamethasone's prevention of angiogenesis may explain why it treats HACE well.[17] Three studies that examined how mice and rat brains react to hypoxia gave some credence to this idea.[17][25]
If available, supplemental oxygen can be used as an adjunctive therapy, or when descent is not possible. FiO2 should be titrated to maintain arterial oxygen saturation of greater than 90%, bearing in mind that oxygen supply is often limited in high altitude clinics/environments.[31]
In addition to oxygen therapy, a portable hyperbaric chamber (
Although AMS is not life-threatening,[20] HACE is usually fatal within 24 hours if untreated.[4] Without treatment, the patient will enter a coma[4] and then die.[4] In some cases, patients have died within a few hours, and a few have survived for two days.[5] Descriptions of fatal cases often involve climbers who continue ascending while experiencing the condition's symptoms.[5]
Prognosis
Recovery varies between days and weeks,[9] but most recover in a few days.[26] After the condition is successfully treated, it is possible for climbers to reascend. Dexamethesone should be discontinued, but continual acetazolamide is recommended.[30] In one study, it took patients between one week and one month to display a normal CT scan following HACE.[8]
Epidemiology
HACE occurs in 0.5% to 1% of people who climb or trek between 4,000 metres (13,000 ft) and 5,000 metres (16,000 ft).[16] In some unusual cases, up to 30% of members of expeditions have had the condition.[5] The condition is seldom seen below 3,000 metres (9,800 ft),[5] but in some rare cases it has developed as low as 2,500 metres (8,200 ft).[35] The condition generally does not occur until an individual has spent 48 hours at an altitude of 4,000 metres (13,000 ft).[16]
History
HACE was first described by a medical officer stationed in Chile in 1913, but few took note of it.[5][27] Later, access to air travel made the condition more common because it allowed more people access to high mountains, such as those in the Himalayas.[3] One early description of HACE may have been published in 1969 after a group of Indian soldiers made a rapid ascent to almost 6,000 metres (20,000 ft).[36] It is not definitely established whether they had HACE or acute decompression sickness.[22] MRI has been used to study the effects of high altitude on the brain,[18] providing the best evidence about the condition.[20] A 1998 MRI study of nine climbers with HACE clearly demonstrated vasogenic edema.[37]
Data about HACE are lacking because it generally occurs in remote areas, far from hospitals[38] and is generally rare.[29] It is uncommon for doctors to be able to study victims within six days of the condition's development.[19] Animal models of HACE have not been developed.[39] Several genes are being examined for the role they may play in the development of the condition.[40]
Increased education and helicopter capabilities have combined to cut the number of deaths from the condition.
References
- ^ 'Oedema' is the standard form defined in the Concise Oxford English Dictionary (2011), with the precision that the spelling in the United States is 'edema'.
- ^ a b c Bärtsch & Swenson 2013, p. 2296.
- ^ a b c Rosenberg 2012, p. 146.
- ^ a b c d e Bärtsch & Swenson 2013, p. 2294.
- ^ a b c d e f g h i j Schoene et al. 2012, p. 301.
- ^ Wilson, Newman & Imray 2009, p. 185.
- ^ a b c Wilson, Newman & Imray 2009, p. 177.
- ^ a b c d e Schoene et al. 2012, p. 303.
- ^ a b c d e f g h i Schoene et al. 2012, p. 304.
- ^ Imray et al. 2010, p. 470.
- ^ Imray et al. 2010, p. 468.
- ^ Imray et al. 2010, p. 469.
- ^ a b c d Rosenberg 2012, p. 147.
- ^ Wilson, Newman & Imray 2009, p. 182.
- ^ Rosenberg 2012, pp. 146–50.
- ^ a b c d e f g h Bärtsch & Swenson 2013, p. 2295.
- ^ a b c d e Schoene et al. 2012, p. 306.
- ^ a b c d Rosenberg 2012, p. 148.
- ^ a b c Schoene et al. 2012, p. 305.
- ^ a b c d e f g h Schoene 2008.
- ^ Wilson, Newman & Imray 2009, p. 183.
- ^ a b Wilson, Newman & Imray 2009, p. 181.
- ^ Imray et al. 2010, p. 474.
- ^ Imray et al. 2010, p. 472.
- ^ a b c Schoene et al. 2012, p. 307.
- ^ a b Imray et al. 2010, p. 467.
- ^ a b c Wilson, Newman & Imray 2009, p. 175.
- ^ Bärtsch & Swenson 2013, p. 2298.
- ^ a b Imray et al. 2010, p. 471.
- ^ a b Bärtsch & Swenson 2013, p. 2299.
- PMID 20591379. Retrieved 13 December 2013.
- PMID 20591379. Retrieved 13 December 2013.
- ^ Wilson, Newman & Imray 2009, p. 179.
- ^ a b Imray et al. 2010, p. 478.
- ^ Wilson, Newman & Imray 2009, p. 176.
- ^ Rosenberg 2012, pp. 146 & 150.
- ^ Wilson, Newman & Imray 2009, p. 184.
- ^ Bärtsch & Swenson 2013, p. 2300.
- ^ Imray et al. 2010, p. 475.
- ^ Wilson, Newman & Imray 2009, p. 180.
Bibliography
- Bärtsch, Peter; Swenson, Erik (2013). "Acute High-Altitude Illnesses". PMID 23758234.
- Imray, Chris; Wright, Alex; Subudhi, Andrew; Roach, Robert (2010). "Acute Mountain Sickness: Pathophysiology, Prevention, and Treatment". Progress in Cardiovascular Diseases. 52 (6): 467–484. PMID 20417340.
- Rosenberg, Gary (2012). Molecular Physiology and Metabolism of the Nervous System (5 ed.). ISBN 978-0-19-539427-6.
- Schoene, Robert (2008). "Illnesses at High Altitude". PMID 18682459.
- Schoene, Robert; Milledge, James; Luks, Andrew; West, John (2012). High Altitude Medicine and Physiology. ISBN 978-1-4441-5432-0.
- Wilson, Mark; Newman, Stanton; Imray, Chris (2009). "The Cerebral Effects of Ascent to High Altitudes". S2CID 268646.