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发表于 2007-12-11 23:24
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这是一个最近的，比较权威的全面的研究。
http://science-community.sciam.com/thread.jspa?threadID=300004508
Brain Cells into Thin Air
by
R. Douglas Fields
National Institutes of Mental Health
Washington, D.C.
"Mount Everest is very easy to climb, only just a little too high." - The Observer, Jan 25, 1953.
Three attributes of a good mountaineer are high pain threshold, bad memory, and ... I forget the third. - R. Douglas Fields
Climbing Mount Everest is not so difficult; the hard part is getting down intact. According to a recent brain imaging study, almost no one does. Of thirteen climbers in the study who attempted Mount Everest, none returned without brain damage. The study also scanned the brains of climbers who attempted less extreme summits. For those of us who love to climb, the results are less than elevating. It seems that almost no one, whether the weekend warrior chaperoned to the summit or the seasoned mountaineer, will return from the high peaks with a brain in the same condition it was in beforehand.
What Goes On in a Climber's Brain?
The first scientific study of the effects of high altitude on the human brain were made by nineteenth century Italian physiologist Angelo Mosso, who made direct observations on a man whose brain was partly exposed as a result of an accident. Mosso, peeking into the man's skull, observed vague changes in swelling of the brain, but the crude methods available at the time limited his analysis.
Now a similar experiment has been done with modern noninvasive brain imaging. In the study reviewed here, "Evidence of Brain Damage After High-Altitude Climbing by Means of Magnetic Resonance Imaging," neurologists Nicholas Fayed and colleagues at the Clinica Queron and Miguel Servet University Hospital in Zarogoza, Spain, gave MRI brain scans to 35 climbers (12 professionals and 23 amateurs) who had returned from high-altitude expeditions, including 13 who had attempted Everest.
The results on the Everest climbers are the most stark. Of the thirteen climbers, three had made the summit, at 8480 meters, three had reached 8100 meters, and seven topped out between 6500 and 7500 meters. Though the expedition suffered no major mishaps and none of the 12 professional climbers suffered any obvious signs of high-altitude illness, only one of the 13 climbers returned with a normal brain scan. The brain scans showed that all but one climber suffered cortical atrophy and enlargement of the Virchow-Robin spaces. These are spaces surrounding brain blood vessels that drain brain fluid and communicate with the lymph system. Widening of these VR spaces is seen in the elderly, but rarely in young people. The amateur climber's brain had also suffered subcortical lesions in the frontal lobes.
Signs Acute and Subtle
A person's tolerance to hypoxia (lack of oxygen) varies according to differences in innate physiology and physical conditioning, which can help the body and brain better tolerate the exertion and physiological stresses of high-altitude mountaineering. But no one is immune to hypoxia's effects.
The first stage of high altitude sickness is called acute mountain sickness, which can cause headache, insomnia, dizziness, fatigue, nausea, and vomiting. The next stage up in seriousness is high-altitude cerebral edema (that is, brain swelling), also known as HACE, which is potentially fatal.
Both are rooted in the body's reaction to low levels of oxygen. Lack of oxygen to the brain directly impairs or damages brain cells. In addition, the walls of blood capillaries in the brain and elsewhere begin to leak at altitude, and this leaked fluid causes dangerous swelling, pressing the brain outward against the rigid skull. Sometimes the optic nerves swell so badly they bulge into the back of the eye, degrading vision and causing retinal hemorrhages. Meanwhile, blood, concentrated from dehydration and thickened by increased numbers of red blood cells, more easily clots, and this clotting, along with the hemorrhage from the thinned capillaries, increases the chance of stroke. A climber suffering HACE may experience amnesia, confusion, delusions, emotional disturbance, personality changes, and loss of consciousness.
This acute high-altitude disease has long been known to cause brain damage. But one of the sobering things about the Fayed study is that none of the Everest climbers experienced high altitude cerebral edema, and the only acute case of mountain sickness was a mild one suffered by the expedition's amateur climber. Yet even all the professional mountaineers showed lasting brain damage -- presumably suffered on previous ascents to the high mountains, because their MRI scans were abnormal before the Mt. Everest ascent and unchanged after.
How High is too High -- and Will It Get Better?
Of course, Everest is extreme. What about ventures to lesser high altitudes? Fayed and colleagues also studied an eight-person team that attempted Aconcagua, a 6,926-meter summit in the Andes. Two climbers reached the summit, five ascended to 6000-6400 meters, and one reached 5500 meters. Yet three members experienced acute mountain sickness and two displayed symptoms of brain edema -- probably because they ascended more rapidly from lower altitudes than did the Everest climbers. All eight Aconcagua climbers showed cortical atrophy on MRI. Seven showed the enlarged Virchow-Robin spaces, and four showed numerous subcortical lesions. Some needed no brain scan to tell them their brains had been injured. One of the climbers suffered aphasia (problems with speech), from which he recovered 6 months later. Two complained of transient memory loss after returning, and three others struggled with bradypsychia (slowed mental function).
The body is remarkably resilient--does the brain recover from these mountaineering wounds? To answer this important question, the researchers re-examined the same climbers three years after the expedition, with no other high-altitude climbing intervening. In all cases, the brain damage was still evident on the second brain scan.
Still, Aconcagua is one of the world's highest mountains -- in the top 100. Mont Blanc, in the Alps, is less extreme. With a summit at 4810 meters, it is climbed each year by thousands of mountaineers who probably do not expect injury to their "second favorite organ," to use Woody Allen's nomenclature for the brain. Yet the researchers found that of seven climbers reaching the summit of Mount Blanc, two returned with enlarged VR spaces.
Because Why?
The study suggests that chronic exposure to high altitudes is not required to experience irreversible brain damage. In fact, amateurs seem to be at greater risk, since they are more likely to suffer acute mountain sickness or high-altitude cerebral edema. At the same time, the experience needed to become a well-acclimated professional seems to take its own toll; compared to the amateurs, however, the professional climbers in this study suffered greater cortical atrophy overall, which suggests an ever-increasing cumulative toll.
Mountain climbing is growing in popularity, and with good reason. It can provide experiences of a lifetime; a communion with Nature and with friends that feeds the soul; intense and enduring rewards surpassing those found within the bounds of routine; and adventure and challenge that builds courage, stamina, and fortitude. It also gets you into incomparable mountain wilderness -- though that is vanishing under the transforming pressure of a warming, polluted atmosphere that is melting the alpine snows and under the repellent litter and human waste strewn along paths to even remote peaks. Sadly, many urgently sense that the singular "it" residing in George Mallory's pithy raison d'ascent, "Because it's there!", may soon be gone.
Approximately 5000 climbers ascend Himalayan peaks every year, and many thousands more climb high in the Alps and Andes. Many spend huge sums to mount expeditions or pay enormous fees to be guided to the summit. This fascinating but sobering research by Fayed and colleagues makes it clear that these climbers are paying for the privilege with something more than hard-earned cash. They're paying with brain tissue.
R. Douglas Fields (shown here climbing the Nose of El Capitan in Yosemite) is a frequent contributor to Scientific American and Scientific American Mind and chief of the Nervous System Development and Plasticity Section at the National Institute of Child Health and Development, where he investigates neural development and the interactions between neurons and glia.
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Edited by David Dobbs at 11/30/2007 11:43 AM
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Edited by David Dobbs at 11/30/2007 11:43 AM
Posted by David Dobbs Sep 25, 2007 3:00 AM EDT
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Any ideas about an altitude cut-off for such effects? Or if there are any differences between climbers from low regions and people who live at higher altitudes? I wonder about effects in the high cities and villages of the world, those above 3,000 meters.
by Guest Sep 25, 2007 3:00 AM
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I do not know of any studies at lower altitudes, but as mentioned in my article, effects were observed in climbers reaching the summit of Mont Blanc (4810). My guess it depends on how rapidly you ascend. Personally, I've felt altitude sickness at 9500 feet when I flew in from sea level and charged off toward the summit without adequate time to adjust. I think most people have experienced this. Brain damage is more likely to occur in climbers who are not properly acclimatized to the altitudes. Certainly people living at higher altitudes are better able to resist these problems. Your genes, environment, and physical fitness are all important variables. The study referenced another scientific study of Sherpas (native mountaineers of Nepal) verifying their legendary ability to resist the damaging effects of high altitude. Only 1 in 7 Sherpas had symptoms at extreme altitude and showed periventricular brain lesions, compared with 13 of 21 lowland climbers (Garrido, et al., Clin. Sci (Lond) 1996;90:81-85).
by Guest Sep 25, 2007 3:00 AM
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A minor correction to an otherwise fine article: The mountain listed in the photo caption is Broad Peak, not "Mt. Broad." (Of course, after numerous trips above 5,000 meters, I may be the one who is confused!)
by Guest Sep 26, 2007 3:00 AM
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Interesting article. If time of ascent and elevation to which the climber is acclimated are more significant than the summit's absolute elevation, I wonder how widespread this effect might be. Imagine, for example, a person who lives in a coastal area flying into Colorado Springs to visit friends, who immediately take them on a tourist drive to the summit of Pikes Peak (4300 m). And I suspect a large number of climbers who summit Mt. Rainer (~4200 m) are from the Seattle area (basically sea-level), and only need drive about two hours before starting the climb.
by Guest Sep 26, 2007 3:00 AM
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Excellent questions! One of the most interesting findings in this study was that these changes in brain structure occurred in many cases without the climber experiencing any severe high altitude sickness. It seems possible to me that lowlanders ascending to moderately high altitude without proper time to adjust might be subject to similar brain injury problems without being aware of it. Possibly this study will spark interest in such studies and perhaps in studying non-climbers who find themselves in situations similar to what you describe.
The body has many mechanisms to adapt to hypoxia. Some of these require turning on genes that enable your body to adjust its cardiovascular system and cellular biochemistry to function normally in an environment with reduced oxygen, but this can take a couple days to become fully implemented. There is no question that ascending before your body has had time to adapt to high altitude will put you in physiological stress and lead to cellular injury. Because of the nature of this study, the sample size is quite small. A larger study might find behavioral, physiological, or genetic explanations for why some elite climbers (like Chris Warner in the photo) escape this health risk. Perhaps they are the ones who take it easy and ascend more slowly at first. Climbers are acutely aware of this need to adjust to altitude, but they have no real scientific data to direct their ascent rate and profile. Maybe this will change with a bit more research.
by Guest Sep 26, 2007 3:00 AM
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As am armchair, part-time climber I enjoyed the article very much, although I noted some personal cognition issues when I was reading it. (Sorry for the marginal joke.)
The article makes it apparent that there is MRI-documented, physical brain damage in many high-altitude climbers. Have there been any tests of cognition done in climbers, before and after climbs, or longitudinally over time, which demonstrate that the physical brain changes actually have negative functional correlates, long-term or otherwise?
While one could, and possibly should argue, that any brain damage (shrinkage) is unacceptable, with the remarkable resiliency of the human brain, and its powers of reserve, perhaps minor degrees of physical damage don't equate to significant long-term neurological sequelae.
I also wonder if there have ever been any studies correlating MRI or other radiodiagnostic testing with pathologic studies in these individuals? These studies would both be very interesting and may have clinical implications for ICU patients who are severely hypoxemic.
If one were to correct for causes of mortality directly related to climbing (e.g. falls, disease, cold-related injury, etc.) I wonder if frequent, or infrequent climbers for that matter, have a higher off-mountain mortality rate (controlling for other normobaric, risk-taking behavior), a higher rate of dementia, or earlier entry into the nursing home pool? Aside from at a party has anyone run into an experienced climber drooling in a corner somewhere?
by Guest Sep 26, 2007 3:00 AM
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Doug Fields was having trouble logging in, so I pass these on from him:
Hi Dennis, Thanks for these interesting questions. Below are some starts at answers.
Studies on impairment
There are a large number of studies on cognitive impairment caused by hypoxia in animal and clinical research, but I don't know of ones focused specifically on climbers that provide data correlating structural changes in the brain with performance on functional tests. As mentioned in the article, climbers can suffer temporary and permanent cognitive impairment from altitude sickness. There are only a few neuroimaging studies of climbers available, so we don't have much data to go on. The reports tend to be anecdotal, because brain scans are not generally given to climbers who don't get ill. Certainly climbers who suffer HACE are at high risk for brain damage.
Three previous cases of climbers who suffered HACE are discussed in the Fayed study. Lesions in part of the brain (globus pallidus) were associated with significant personality changes after recovery (Jeong et al., J. Korean Med. Soc. 2002, 17:861-863), and two cases showed irreversible subcortical dementia and severe neuropsychiatric symptoms (Usui, et al., High Alt. Med. Biol. 2004;5, 77-81). In another MRI study of 9 patients with HACE, 7 had abnormalities in the corpus callosum (fibers connecting the two hemispheres), and all patients recovered (Hackett et al., JAMA 1998;280,1920-1925).
But what you are more interested in knowing is effects of altitude on climbers who do not suffer HACE. An MRI study of 26 Spanish climbers ascending over 7000m without oxygen, abnormalities were seen in 46% of them (Garrido et al., J. Sports Med. 1993;14, 232-234), and in another study of 9 climbers with MRI before and after ascent, 5 climbers had abnormal brain scans, but two of these climbers had suffered high-altitude illness (Garrido et al., Eur. J. Appl. Physiol. Occup. Physiol. 1995;70:477-481). However, there is another study showing no MRI changes in 8 climbers who participated in 3 expeditions ascending to 7100m (Anooshiravani et al.,, Med. Sci. Sports Exerc. 1999;31, 969-972).
Clearly, more research is needed. Some of the structural changes, such as cortical atrophy, provide a firm basis for cognitive decline, and some of these alterations in the brain appear to be surprisingly persistent. The brain is indeed remarkably resilient, however. Indeed, a well-established phenomenon in the field of hypoxia research is "preconditioning", in which an initial exposure to hypoxia greatly increases resistance to cellular (and neuronal) damage caused by a subsequent hypoxic event experienced much later.
I do not know if there are good long-term statistics available on climber's mental and physical health as a group, which might uncover possible chronic health dangers that could be prevented by improved practices. Perhaps someone in the climbing community will know of a database somewhere. This could be extremely helpful, because medical exploration is far behind mountaineer's exploration of high summits. Today's mountaineers are pioneers in a venture that that more people every day are having an opportunity to enjoy.
When I started SCUBA diving in 1968, we used the decompression tables that the Navy developed by setting dive limits that would not kill a Navy SEAL. Later people figured out that not everyone has the physiology of a Navy SEAL, and death is maybe not the best bench mark to use for sport diving. They revised the tables and diving is safer. With experience and scientific research, the medical implications of pushing the diving tables became apparent in chronic diving-related illnesses. I'll bet alpine climbing is much the same. Live and learn. Practices will improve and climbing will become safer. I think the lesson is to respect the need to acclimatize to the altitude. In the past climbers probably felt that if they were not suffering severely, they were fine. Maybe...maybe not.
Non-mountaineering hypoxia
I have received a number of questions like yours related to other non-mountaineering situations where hypoxia may lead to brain damage. General anesthesia does present a potential risk of brain damage due to depressed respiratory function resulting in hypoxia, but this is well recognized. This is why one doctor, your anesthesiologist, is always assigned to sit there and do nothing else but watch your blood gasses and other vital signs. This makes the procedure safe, and I would not worry about it if you are about to undergo surgery. Brain damage due to hypoxia accompanies many other medical conditions, such as heart attack, and in difficult deliveries of newborns, cerebral palsy can result from damaged neurons or damaged cells that form myelin insulation on axons (oligodendrocytes) from hypoxia. (Physiologically, infants are much better equipped to handle hypoxia however.) There is concern and some controversy about cognitive decline following coronary artery bypass surgery when a heart-lung machine takes over the job of supplying the brain with oxygen. The data are mixed and the issue is controversial, but there is no question about the negative cognitive effects of not having a coronary artery bypass if you need one.
by David Dobbs Sep 27, 2007 3:00 AM
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Some of the latest research into cell death and resuscitation following a heart attack suggests that it is not the lack of oxygen which causes the cell death, but rather reperfusion injury when the patient is revived. Here is a link to a recent article: http://www.msnbc.msn.com/id/18368186/site/newsweek/. In the Advanced Cardiac Life Support class I most recently attended, the chief instructor said they were getting a higher post-resuscitation success rate when the patient was NOT ventilated. In Arizona, I understand that for out-of-hospital arrest, they are not breathing for the patient for up to 30 minutes.
All this proposes a question: Do we know that it is the hypoxia that causes the brain damage, or might it happen after the climbers have returned to lower altituds and are "reperfusing" their brains?
by Guest Sep 30, 2007 3:00 AM
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发表于 2007-10-30 06:02
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