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• W2029418311 abstract "We read with interest the excellent review by Wilson and co-authors1Wilson MH Newman S Imray CH The cerebral effects of ascent to high altitudes.Lancet Neurol. 2009; 8: 175-191Summary Full Text Full Text PDF PubMed Scopus (327) Google Scholar about the neurological syndromes and their associated pathophysiological changes of cerebral perfusion that occur on ascent to high altitudes and lead to cerebral oedema.According to the authors, identifying those who will develop acute mountain sickness (AMS) is unpredictable. However, obesity has been associated with increased risk of AMS in a hypobaric environment.2Ri-Li G Chase PJ Witkowski S et al.Obesity: associations with acute mountain sickness.Ann Intern Med. 2003; 139: 253-257Crossref PubMed Scopus (89) Google Scholar AMS is characterised by elevated cerebral capillary pressure, impaired cerebral autoregulation, disruption of the blood–brain barrier by various hypoxia-regulated mediators, and free radicals, all of which are typical features of endothelial dysfunction. At moderate altitude, patients with metabolic syndrome develop transient impairment of flow-mediated dilatation, a measure of endothelial dysfunction.3Frick M Rinner A Mair J et al.Transient impairment of flow-mediated vasodilatation in patients with metabolic syndrome at moderate altitude (1,700 m).Int J Cardiol. 2006; 109: 82-87Summary Full Text Full Text PDF PubMed Scopus (16) Google ScholarWe have recently reported the development of AMS in a 44-year-old man with metabolic syndrome during high altitude ascent (5050 m).4Strapazzon G Cogo A Semplicini A Acute mountain sickness in a subject with metabolic syndrome at high altitude.High Alt Med Biol. 2008; 9: 245-248Crossref PubMed Scopus (7) Google Scholar We proposed that the endothelial dysfunction, a consistent feature of the metabolic syndrome exacerbated by hypoxia at altitude, made this individual prone to AMS. However, we could not find any correlation between the elevation of blood pressure, heart rate, and the Lake Louise score, and we could rule out hypertension and sympathetic stimulation as determinants of AMS.On the basis of our case report and of previous studies,4Strapazzon G Cogo A Semplicini A Acute mountain sickness in a subject with metabolic syndrome at high altitude.High Alt Med Biol. 2008; 9: 245-248Crossref PubMed Scopus (7) Google Scholar we suggest that metabolic syndrome and endothelial dysfunction are major risk factors for AMS and predispose individuals to the cerebral effects of ascent to high altitude. We favour the hypothesis that endothelial dysfunction of any cause has a pivotal role in the pathogenesis of AMS through impaired regulation of cerebral circulation.5Van Osta A Moraine JJ Mélot C et al.Effects of high altitude exposure on cerebral hemodynamics in normal subjects.Stroke. 2005; 36: 557-560Crossref PubMed Scopus (79) Google Scholar The metabolic syndrome should be thought of as a contraindication to high-altitude ascent, and patients with metabolic syndrome should be carefully monitored for early signs of AMS.We have no conflicts of interest. We read with interest the excellent review by Wilson and co-authors1Wilson MH Newman S Imray CH The cerebral effects of ascent to high altitudes.Lancet Neurol. 2009; 8: 175-191Summary Full Text Full Text PDF PubMed Scopus (327) Google Scholar about the neurological syndromes and their associated pathophysiological changes of cerebral perfusion that occur on ascent to high altitudes and lead to cerebral oedema. According to the authors, identifying those who will develop acute mountain sickness (AMS) is unpredictable. However, obesity has been associated with increased risk of AMS in a hypobaric environment.2Ri-Li G Chase PJ Witkowski S et al.Obesity: associations with acute mountain sickness.Ann Intern Med. 2003; 139: 253-257Crossref PubMed Scopus (89) Google Scholar AMS is characterised by elevated cerebral capillary pressure, impaired cerebral autoregulation, disruption of the blood–brain barrier by various hypoxia-regulated mediators, and free radicals, all of which are typical features of endothelial dysfunction. At moderate altitude, patients with metabolic syndrome develop transient impairment of flow-mediated dilatation, a measure of endothelial dysfunction.3Frick M Rinner A Mair J et al.Transient impairment of flow-mediated vasodilatation in patients with metabolic syndrome at moderate altitude (1,700 m).Int J Cardiol. 2006; 109: 82-87Summary Full Text Full Text PDF PubMed Scopus (16) Google Scholar We have recently reported the development of AMS in a 44-year-old man with metabolic syndrome during high altitude ascent (5050 m).4Strapazzon G Cogo A Semplicini A Acute mountain sickness in a subject with metabolic syndrome at high altitude.High Alt Med Biol. 2008; 9: 245-248Crossref PubMed Scopus (7) Google Scholar We proposed that the endothelial dysfunction, a consistent feature of the metabolic syndrome exacerbated by hypoxia at altitude, made this individual prone to AMS. However, we could not find any correlation between the elevation of blood pressure, heart rate, and the Lake Louise score, and we could rule out hypertension and sympathetic stimulation as determinants of AMS. On the basis of our case report and of previous studies,4Strapazzon G Cogo A Semplicini A Acute mountain sickness in a subject with metabolic syndrome at high altitude.High Alt Med Biol. 2008; 9: 245-248Crossref PubMed Scopus (7) Google Scholar we suggest that metabolic syndrome and endothelial dysfunction are major risk factors for AMS and predispose individuals to the cerebral effects of ascent to high altitude. We favour the hypothesis that endothelial dysfunction of any cause has a pivotal role in the pathogenesis of AMS through impaired regulation of cerebral circulation.5Van Osta A Moraine JJ Mélot C et al.Effects of high altitude exposure on cerebral hemodynamics in normal subjects.Stroke. 2005; 36: 557-560Crossref PubMed Scopus (79) Google Scholar The metabolic syndrome should be thought of as a contraindication to high-altitude ascent, and patients with metabolic syndrome should be carefully monitored for early signs of AMS. We have no conflicts of interest. High-altitude cerebral effects: risks and mechanisms – Authors' replyWe thank Strapazzon and Semplicini for their comments on our Review1 and for their interesting hypothesis based on their case report.2 They suggest that the endothelial dysfunction associated with metabolic syndrome constitutes a major risk factor for AMS. Although we believe that endothelial dysfunction (eg, caused by hypoxia or intercurrent illness) and obesity (through mechanisms of increased energy of exertion, increased oxygen requirements, increased blood flow, and other associated conditions such as sleep apnoea) might well contribute to AMS, obesity can not be said to predict AMS, and obesity should certainly not be a contraindication to high-altitude ascent. Full-Text PDF" @default.
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• W2029418311 title "High-altitude cerebral effects: risks and mechanisms" @default.
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