Chronic Mountain Sickness
Chronic mountain sickness (CMS) is the least studied cerebrovascular impairment of the high-altitude illnesses. Unlike acute mountain sickness (AMS) which may affect people within hours of exposure to high-altitude, CMS only affects certain populations who are native or long-time residents of high-altitude. AMS is characterized by nausea, fatigue and insomnia as well as other symptoms in individuals who have recently ascended to high altitude. More serious progression of AMS can lead to life-threatening problems such as high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE). CMS, in contrast, although sharing many symptoms with AMS, only affects permanent high-altitude dwellers.
Three distinct high-altitude populations have been studied to determine the incidence of CMS and to determine whether certain populations are better able to live in hypoxic conditions. Studies on Andeans, Ethiopians and Tibetans have shown that the incidence of CMS is not equal between all populations (1). Perhaps owing to time since migration, the incidence of CMS seems to be highest in Andeans (~50% incidence recorded in Peruvian high-altitude dwellers) followed by Tibetans (~35%) and finally Ethiopians (0%) where no report of CMS has been recorded. Given that it is thought Homo sapiens originated around the area that would today be Ethiopia-Kenya, Ethiopian high-altitude dwellers would have been living at these altitudes longer than the other groups (2). The longer time of residence may have increased their adaptation to the environment more so than the Andeans who would have migrated later.
CMS is characterized by extreme polycythemia (haematocrits upwards of 65% have been reported (3)) and shares many symptoms with AMS, such as headache, dizziness, sleep disturbances, fatigue, cyanosis and palpitations (4). Due to the polycythemia CMS can be fatal. Over time the haematocrits of these individuals at altitude increases to cope with the ambient hypoxia and to maintain adequate oxygen delivery to the tissues. However, this increase in haematocrit increases the viscosity of the blood and places a larger afterload on the heart. Ultimately this increased stress on the heart places the individual at higher risk of cardiac failure and possible death (5). Unfortunately, the etiology of CMS remains unclear and has yet to be fully determined. There have been some suggestions that decreased respiratory sensitivity to hypoxia and carbon dioxide with resulting hypoventilation, hypoxia and marked polycythemia may be a potential cause, however, research is currently ongoing (6).
There is currently no well-established medication for the treatment of CMS which poses a considerable problem to the populations affected by it. Presently, treatment for CMS involves descent to sea-level whereupon the symptoms begin to disappear. As soon as these individuals return to altitude, however, the symptoms reappear (3). For most populations affected by CMS, leaving their homes and livelihoods on the mountains to work elsewhere at sea-level is not an option which presents a widespread problem that needs to be addressed. In Andeans, for example, where studies have shown these populations to have the highest incidence of CMS, many people moved to altitude to work in the mines. Generations of people have now lived at altitude and are either unwilling or unable to move back to sea-level where they face the prospect of being unemployed and away from their close social networks at home. As such, people become more desperate for working procedures and many controversial treatments have been reported in the past to help “cure” their CMS. Treatments such as leeches, marrow radiotherapy and phlebotomies (blood-letting) are not uncommon and many people may opt to undergo them to escape the suffering from CMS and to prevent the need to move to sea-level. More serious reports of the use of phenylhydrazine, a toxic haemolytic agent, have also been made. Phenylhydrazine destroys red blood cells which help decrease the haematocrit; however, phenylhydrazine can also cause liver and kidney damage and severely limits the work capacity of an individual due to its disruption of oxygen transport. An overdose of phenylhydrazine can be fatal (7).
Given the desperation of many of these people it is understandable why they may opt for such drastic treatments, however, efforts should be made to find safer treatments for CMS and to stop the practise of these potentially dangerous procedures. Unfortunately, because CMS does not receive much publicity research into potential treatments is slow. Also, as CMS only affects native populations of East Africa, the Andes Mountains and the Himalayas, many researchers opt to work with AMS, which more often affects North Americans and Europeans and does not require them to conduct research at these different locations across the world. Our research team is one of only a handful of teams that travels to these locations to study the native populations and help elucidate the pathology of this disease as well as, importantly, determine safe ways to allow these populations to live at their high-altitude homes. It was due in part to our research that we now know the differences in CMS distributions across the world. By studying the cardiovascular and cerebrovascular physiology of these different groups, especially the well-adapted Ethiopians, we hope to be able to find ways to confer the adaptation measures seen in well-adapted groups to help treat those populations with higher incidences of CMS. Already a research team in Bolivia has managed to test the efficacy of a new drug, acetazolamide, for the treatment of CMS due to past studies by our group, as well as others, in Andean highlanders. Acetazolamide is a carbonic anhydrase inhibitor and is known to promote diuresis, cerebral blood flow and stimulate ventilation via metabolic acidosis. Their study on Andeans showed a ~7% decrease in mean haematocrit and a 5% increase in nocturnal arterial oxygen saturation in the experimental group with no serious side-effects. (8). Although this is a step in the right direction further studies are required to decrease the haematocrits further in a similarly safe manner.
CMS is a debilitating disease that can be fatal if untreated. Just as importantly, however, are the social implications of the illness. The only established way to treat CMS has been to relocate people from their native homes at altitude to sea-level; a transition that can be very difficult to make. Few groups conduct research on CMS and its potential treatments due to the difficulty inherent in conducting field-research at altitude and the fact that it does not affect populations in North America or Europe where most altitude research occurs. Intensifying the publicity of CMS and its associated problems for the populations affected by it could help counter this trend and allow for the creation of better and faster treatments.
Inderjeet Sahota is studying for an MSc in cardiovascular physiology at Simon Fraser University in Canada
isahota(at)sfu.ca
References
1. Claydon, Victoria E., et al. Cerebrovascular Responses to Hypoxia and Hypocapnia in Ethiopian High Altitude Dwellers. Stroke. 2008; 39: 336-342.
2. Brugniaux, Julien V., et al. Cerebrovascular responses to altitude. Respiratory Physiology & Neurobiology. 2007; 158: 212-223.
3. Norcliffe, L. J., et al. Cerebrovascular responses to hypoxia and hypocapnia in high-altitude dwellers. Journal of Physiology. 2005; 566: 287-294.
4. Monge, Carlos C., Leon-Velarde, Fabiola and Arregui, Alberto. Chronic Mountain Sickness in Andeans. In: Thomas F. Hornbein and Robert B. Schoene. High Altitude: An Exploration of Human Adaptation. New York: Marcel Dekker; 2001. p. 815-838.
5. Nadel, Ethan. Environmental Physiology. In: Walter F. Boron and Emile L. Boulpaep. Medical Physiology. Philadelphia : Elsevier; 2005, p. 1256-1267.
6. Hultgren, Herb. High Altitude Medicine. Stanford, USA: Hultgren Publications, 1997.
7. Zubieta-Calleja, G R, Zubieta-Castillo, G and Zubieta-Calleja, L. Inadequate Treatment of Excessive Erythrocytosis. Acta Andina. 1995; 4: 123-126.
8. Richalet, Jean-Paul, et al. Acetazolamide: A Treatment for Chronic Mountain Sickness. American Journal of Respiratory and Critical Care Medicine. 2005; 172: 1427-1433.