Neurological manifestations in chronic mountain sickness: the burning feet-burning hands syndrome

Thomas, P. K.; King, R. H. M.; Feng, Shui; Muddle, J. R.; Workman, J. M.; Gamboa, Jorge L.; Tapia, R; Vargas, Manuel; Appenzeller, Otto

doi:10.1136/jnnp.69.4.447

Cited by 24 publications

(26 citation statements)

References 23 publications

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“…Surprisingly, this syndrome is rare in Tibet. CMS is characterized by profound hypoxia, polycythemia, neurologic symptoms and signs, blood vessel proliferation and, prominently, migraine [2]. Neurally mediated vasodilatation in the cerebral vessels is an important feature of migraine at sea level [3].…”

Section: Introductionmentioning

confidence: 99%

Cerebral vasoreactivity in Andeans and headache at sea level

Appenzeller¹,

Passino

Roach

et al. 2004

Journal of the Neurological Sciences

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Section: Introductionmentioning

confidence: 99%

Cerebral vasoreactivity in Andeans and headache at sea level

Appenzeller¹,

Passino

Roach

et al. 2004

Journal of the Neurological Sciences

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“…5 We hypothesized that cerebrovascular responsiveness to NO donors would predict the ability for adaptation to life at high altitude. To test this proposal, we compared cerebral blood flow velocity (CBV) responses to NO donors in 2 populations: Peruvian native highlanders, who frequently have CMS, 6 and Ethiopian altitude natives, in whom maladaptation to altitude has not been reported. Furthermore, we asked whether using baseline CBV at low and high altitudes in the 2 populations as an expression of the "trait of interest" and the response of the cerebral vessels to an exogenous NO donor as an indicator of "fitness" for survival(s) in the mountains could predict the better adaptation to altitude life of Ethiopian highlanders.…”

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confidence: 99%

Cerebral Vasodilatation to Exogenous NO Is a Measure of Fitness for Life at Altitude

Appenzeller

Claydon

Gulli

et al. 2006

Stroke

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Background and Purpose-Andean highlanders, unlike Ethiopians, develop chronic mountain sickness (CMS), a maladaptation to their native land. Ambient hypoxia induces NO-mediated vasodilatation. Fitness for life at altitude might be revealed by cerebrovascular responses to NO. Methods-Nine altitude-native men were examined at 3622 and 794 m in Ethiopia and compared with 9 altitude-native Andean men tested at 4338 and 150 m in Peru. We assessed CMS scores, hematocrits, end-tidal pressure of carbon dioxide (P ET CO 2 ), oxygen saturations, and cerebral blood flow velocity (CBV). We evaluated fitness for life at altitude from the cerebrovascular response to an exogenous NO donor. Results-At high altitude, CMS scores and hematocrits were higher in Andeans, and they had lower oxygen saturations.Ethiopians had higher P ET CO 2 at all study sites. At low altitude, saturations were similar in both groups. Responsiveness of the cerebral circulation to NO was minimal in Ethiopians at low altitude, whereas Andeans had a large response. In contrast, at high altitude, Ethiopians showed large responses, and Peruvians had minimal responses. Conclusions-By our measure, high altitude-native Peruvians were well-adapted lowlanders, whereas Ethiopian highlanders were well adapted to altitude life. Environmental pressures were sufficient for human adaptation to chronic hypoxia in Africa but not South America. The mechanisms underlying these differences are unknown, although studies of neurovascular diseases suggest that this may be related to a NO receptor polymorphism. Key Words: altitude Ⅲ nitric oxide Ⅲ cerebral hypoxia Ⅲ cerebrovascular circulation Ⅲ evolution A ltitude is an inhospitable environment for humans, and yet permanent settlements are found at 5100 m. 1 The fall in barometric pressure with increasing altitude in these habitats reduces the availability of oxygen compared with sea level. Therefore, hypoxia in the mountains is inescapable. Ethiopian highlanders are, by some measures, the best adapted for life at altitude, 2 showing no evidence of chronic mountain sickness (CMS), a failure to adapt to altitude that is commonly seen in the high Andes. 3,4 The severity of CMS is inversely related to fitness for survival in the Andes.A key measure of survival in the mountains is the maintenance of optimal oxygen concentrations in all tissues. An adequate blood flow to the brain is essential for maintenance of a proper oxygen supply, and blood flow, in turn, is profoundly affected by changes in oxygen availability. In response to hypoxia, blood vessels, including those in the cerebral circulation, undergo NO-mediated vasodilatation. Inappropriate release of NO with hypoxia has been implicated in some maladaptation syndromes in sojourners to altitude. 5 We hypothesized that cerebrovascular responsiveness to NO donors would predict the ability for adaptation to life at high altitude. To test this proposal, we compared cerebral blood flow velocity (CBV) responses to NO donors in 2 populations: Peruvian native highlanders, who freq...

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“…This may have been the result of severe hypoxia during sleep [21]. However, saturation in controls and CMS was comparable, and appropriate for altitude, during wakefulness, when assessed by us ( Table 2).…”

Section: Discussionmentioning

confidence: 99%

“…1) and in those who inexplicably lost the adaptation to their native land and developed chronic mountain sickness (CMS). CMS is characterized by neurologic symptoms, blood vessel proliferation, autonomic dysfunction and polycythemia [21]. We also examined the effects of sea level normoxia on gene expression in the same subjects within 1 h of arrival in Lima.…”

mentioning

confidence: 99%

Gene expression, autonomic function and chronic hypoxia:lessons from the Andes

et al. 2006

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Autonomic function is altered by altitude in sojourners and natives. We hypothesized that these physiologic responses are modulated by changes in gene expression. We compared gene product levels in 20 natives of Cerro de Pasco (CP), (4338 m), 10 of which had chronic mountain sickness (CMS) established by a CMS-scoring system, with gene products in the same men after 1 h at sea level. We further compared the results with those obtained from 10 US men residing at 1500 m. We measured gene products in white cells by reverse transcription polymerase chain reaction (RT-PCR). We focused on genes important in vascular autonomic physiology, and/or activated by hypoxia; hypoxia inducible factor 1-alpha (HIF 1-alpha), 2 splicing variants of vascular endothelial growth factor (VEGF); VEGF-121, VEGF-165, and phosphoglycerate kinase 1 (PGK 1). Normal CP natives showed high expression of all genes in CP, compared to US controls. Within 1 h of arrival at sea level, they had comparable levels to US residents. In CMS, the gene products were higher in CP. Although gene products decreased in Lima in this group, they never reached US values. VEGF 121 and 165 were correlated (P<0.001). VEGF 165 was higher in CMS in CP (P=0.006), and was positively correlated with CMS-score (R=0.86, P<0.001), and negatively correlated with arterial saturation (R=-0.79, P<0.001). Our findings underscore the changes in gene expression levels in intact humans in response to environmental stress. These changes may support the physiologic alterations induced by the ambient hypoxia at altitude and impact organism survival. They also suggest therapeutic strategies for autonomic and neurodegenerative diseases at sea level.

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Neurological manifestations in chronic mountain sickness: the burning feet-burning hands syndrome

Cited by 24 publications

References 23 publications

Cerebral vasoreactivity in Andeans and headache at sea level

Cerebral vasoreactivity in Andeans and headache at sea level

Cerebral Vasodilatation to Exogenous NO Is a Measure of Fitness for Life at Altitude

Gene expression, autonomic function and chronic hypoxia:lessons from the Andes

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