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  • Updated 06.06.2023
  • Released 07.13.1999
  • Expires For CME 06.06.2026

Mountain sickness: neurologic aspects



Acute mountain sickness (or altitude sickness) affects climbers who rapidly ascend to heights of at least 2500 meters (8200 feet). The symptoms of acute mountain sickness include headache, fever, fatigue, nausea, dizziness, anorexia, and sleep disturbances. This article describes the management of acute mountain sickness. Acetazolamide, which reduces the formation of CSF, is the main drug therapy, and additional drugs include nonsteroidal antiinflammatory drugs for headache and dexamethasone for cerebral edema. Oxygen inhalation at 1 L/minute and descent to lower altitudes are recommended.

Key points

• Acute mountain sickness occurs after ascent to an altitude of at least 2500 meters (8200 feet).

• Symptoms include headache, fever, fatigue, nausea, dizziness, anorexia, and sleep disturbances.

• If symptoms are not relieved, or with further ascent, cerebral and pulmonary edema may occur.

• Treatment is medical, with supplementary oxygen therapy.

• If symptoms persist, the affected person should descend to a lower altitude.

Historical note and terminology

There are two well-known high-altitude syndromes: (1) acute mountain sickness, which occurs within a few hours to a few days at high altitude; and (2) chronic mountain sickness, also called Monge disease, which develops after several years of residence at high altitude (85). Acute mountain sickness (or altitude sickness) affects climbers or other individuals who rapidly ascend to heights of at least 2500 m (8200 ft). Some of the highest mountain passes that can be reached by motorized vehicles contain warnings to individuals regarding the risk of acute mountain sickness.

Acute mountain sickness may develop into high-altitude pulmonary edema or high-altitude cerebral edema, but it is still unclear whether these share a common pathophysiology. A subacute form of mountain sickness was described in Indian soldiers in Kashmir who developed pulmonary hypertension and congestive heart failure within a few months of living at altitudes of 5800 to 6700 m (19,000-22,000 ft) (02).

Early reports of high-altitude illness. The first documented report of mountain sickness was reportedly by a Chinese official, Too-Kin, between 37 and 32 BC when he encountered difficulties crossing the Kilik Pass (4827 m; 15840 ft) into what is present-day Afghanistan (43). He described headache and vomiting and gave names such as "the Great Headache Mountain" and "the Little Headache Mountain" to the mountains on his route. In the year 403, a Chinese man crossing into Kashmir, a companion of the Chinese Buddhist monk Fa Hsien (337–c 422 CE; also referred to as Faxian, Fa-Hien, Fa-hsien, and Sehi), died with difficulty in breathing and foam at his mouth, a condition now recognized as high-altitude pulmonary edema (43). Similar cases were described by the Spanish Jesuit missionary Father José de Acosta (1539 or 1540–1600) in 1590 in the high Andes of Peru (01).

José de Acosta (1539-1600)

(Courtesy of Wikimedia Commons. Public domain. Figure restored and edited by Dr. Douglas J Lanska.)

Beginnings of high-altitude medicine. High-altitude physiology and the study of acute and chronic mountain sickness was pioneered by a series of European physiologists from France, Italy, and Great Britain, particularly beginning in the last quarter of the 19th century.

In 1877, French physiologist Paul Bert (1833–1886), acknowledged as a pioneer in the investigation of the effects of atmospheric pressure on body function, recognized hypoxia as the cause of altitude sickness (10). French physician and physiologist Denis Jourdanet (1815–1892) spent many years in Mexico studying the effects of high altitude (116).

Italian physiologist Angelo Mosso. In 1894, Italian physiologist Angelo Mosso (1846–1910) was among the first to conduct serious and systematic investigations at high altitude. Mosso led a series of scientific expeditions in which he and his colleagues studied many aspects of high-altitude physiology using remarkably simple, though effective, tools. Among these included an experiment performed by his brother, Ugolino Mosso (1854–1909), to measure the quantity of carbonic acid eliminated in half an hour by a medical student. Mosso documented a case of mountain illness at an altitude of 4559 m (14,960 ft) in the Italian Alps bordering Switzerland and was probably the first to record periodic breathing at high altitude (86).

Mosso's experiments with "rarefied air." Mosso performed experiments on the cerebral circulation, including experiments on two boys who had sustained head injuries. Mosso concluded that "[a]rtificial air, owing to its rarefaction, produces the same effects as those due to a diminution of barometric pressure. We may therefore conclude that mountain-sickness is not caused by the mechanical action or the diminished weight of the atmosphere, but by its rarefaction, which acts chemically on the metabolism of the nervous system" (86).

Mosso's high-altitude physiology laboratory at Capanna Regina Margherita. To facilitate his studies, Mosso established a simple high-altitude laboratory at Capanna Regina Margherita (Queen Margherita Hut). The construction of this high-altitude hut on Monte Rosa, in Italian territory near the international border between Italy and Switzerland, had been directed by the Italian Alpine Club in 1889. The hut was prebuilt in the valley, then brought part of the way by mule and the remainder by mountaineers, before being assembled at an onsite mountain hut for alpinists. It was opened in 1893 in the presence of Margherita of Savoy (1851–1926), Queen of Italy, a dedicated mountaineer to whom the hut is dedicated. The hut soon became an important research center for Mosso's studies of high-altitude medicine. A new hut, built around 1898, was also used by Mosso and various colleagues. Then, because the hut was quite small, a newer, lower-altitude research center ("Istituto Mosso") was built near the Salati Pass, in Valsesia Valley (Alagna Valsesia), in 1907 at an elevation of about 2900 meters (9500 ft). The prior Margherita Hut was dismantled in the late 1970s and was replaced in 1980 by the current hut on the summit of Punta Gnifetti, a subpeak of Monte Rosa. At 4554 m (14,940 ft), it is the highest building in Europe. The hut continues to serve as a research station for high-altitude medicine, but it also serves as a simply equipped.

The 1911 Anglo-American Expedition to Pikes Peak. The most important high-altitude expedition of the early 20th century was the 1911 Anglo-American Expedition to Pikes Peak, which included British physiologists John S Haldane FRS (1860–1936) and Claude Gordon Douglas (1882–1963) from Oxford; Yandell Henderson (1873–1944), Professor of Physiology at Yale University Medical School; and Edward Christian Schneider (1874–1954), Professor of Biology at Colorado College (in Colorado Springs, Colorado). At the time, Haldane was already famous for his intrepid self-experimentation, which led to many important discoveries about the nature of gases and their effects on the human body. Pikes Peak, just outside Colorado Springs, was an excellent site because of its substantial altitude of 4300 m (14,100 ft), convenient access via a cog railway, and comfortable living accommodation (115). Measurements were first made at sea level, then on the summit for 5 weeks, and then again at sea level.

British physician and physiologist John S Haldane FRS (1860-1936) in 1920

Haldane was famous for his intrepid self-experimentation, which led to many important discoveries about the nature of gases and their effect on the human body. Half-length photograph, seated at desk, full face. Interior view of...

The wide range of studies conducted during the expedition included descriptions of acute mountain sickness, studies of the hemoglobin dissociation curve at high altitude, assessments of the volume and gas content of exhaled air at rest and with varying intensity of exercise at high altitude, studies of periodic breathing, and studies of the cardiac response to high altitude (and hypoxia) (33). They also showed (in an appendix) the observations made by J Richards, Mining Engineer, concerning the increase of hemoglobin percentage at a high altitude in Bolivia. One error was the conclusion that the arterial P(O(2)) could considerably exceed the alveolar value, implying oxygen secretion by the lung (115).

British physiologist and clinical pathologist Mabel FitzGerald (1872–1973) was invited to be a member of the expedition but did not join the men on the summit. Instead, she visited various mining camps in Colorado at lower altitudes where she conducted classic studies of alveolar gas partial pressures and hemoglobin values (38; 37; 114; 115; 45; 113; 112).

Nathan Zuntz. German physiologist Nathan Zuntz (1847–1920) was a pioneer of modern altitude physiology and aviation medicine. For his high-altitude respiratory physiology experiments, and particularly for studies of hypoxia, Zuntz utilized a pneumatic chamber of the Jewish Hospital in Berlin (127). In 1885, Zuntz and German physician and pharmacologist August Julius Geppert (1856–1937) invented a respiratory gas analyzer, the Zuntz-Geppert'schen Respirationsapparat (Zuntz-Geppert respiratory apparatus).

From 1893, many of his field studies were conducted at the Capanna Regina Margherita international research station at the apex of Monte Rosa, Italy, where he worked with German physiologist Adolf Loewy (1862–1936), Italian physiologist Angelo Mosso (1846–1910), and Austrian Arnold Durig (1872–1961) (47). For his field studies, Zuntz devised a portable gas exchange measuring device (Gasuhr) that he sometimes combined with a portable kymograph for simultaneous registration of pulse and respiratory movements (127)

With his assistant, Austrian physiologist Hermann von Schrötter (1870–1928) and German meteorologists Arthur Berson (1859-1942) and Reinhard Süring (1866–1950), he made two high-altitude balloon ascents that reached an altitude of 5000 meters in 1902.

In 1906, Zuntz published a classic monograph that summarized his high-altitude research: Höhenklima und Bergwanderungen in ihrer Wirkung auf den Menschen (High-Altitude Climate and Mountaineering and their Effect on Humans) (127).

In 1910, Zuntz participated in a scientific expedition to the Pico de Teide volcano (summit at 3715 m or 12,188 ft) in the Canary Islands with Schrötter and Austrian physiologist Arnold Durig (1872–1961) and British physiologist Joseph Barcroft (1872–1947).

Participants of an expedition to Teneriffa, including Austrian physiologist Arnold Durig (1872-1961), British physiologist Sir Joseph Barcroft FRS (18...

Back row from left to right: British respiratory physiologist Claude Gordon Douglas FRS (1882-1963), German biochemist Carl Neuberg (1877-1956), French astronomer and mathematician Jean Mascart (1872-1935; at Tenerife to observ...

High-altitude studies of Sir Joseph Barcroft FRS in Peru 1921–1922. British physiologist Sir Joseph Barcroft FRS (1872–1947) is best known for his studies at high altitude and the oxygenation of blood (116; 72).

In the winter of 1921 to 1922, Barcroft and colleagues made observations on the effect of high altitude on the physiological processes of the human body, which were carried out in the Peruvian Andes, chiefly at Cerro de Pasco (06). They studied the relation of oxygen pressure in alveolar air to that in arterial blood at different altitudes for different members of the expedition, documenting fairly marked oxygen desaturation in the blood at 14,200 feet compared to results at sea level, as well as considerable interindividual variation at high altitude. Barcroft documented a rapid rise in the concentration of red blood cells while expedition members were at high altitude but then a return to baseline levels after return to sea level. At high altitudes, a "trifling amount" of exercise dramatically increased blood flow. At high altitudes, exercise caused a precipitous drop in oxygen saturation of the blood, or what Barcroft termed a "descent of position of utilisation in [the] oxygen dissociation curve when muscular work was undertaken." One factor that complicated assessments was that blood volume changed in a complicated fashion that seemed to be related to ambient temperature: when expedition members passed through tropical climes to and from Peru, their blood volumes increased by about 1.5 liters when their vascular beds expanded (ie, from cutaneous vasodilation).