Network analysis reveals distinct clinical syndromes underlying acute mountain sickness.
Acute mountain sickness (AMS) is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Different pathophysiological mechanisms are now thought to underlie headache and sleep disturbance during acute exposure to high altitude. Hence, these symptoms may not belong together as a single syndrome. Using a novel visual analogue scale (VAS), we sought to undertake a systematic exploration of the symptomatology of AMS using an unbiased, data-driven approach originally designed for analysis of gene expression. Symptom scores were collected from 292 subjects during 1110 subject-days at altitudes between 3650 m and 5200 m on Apex expeditions to Bolivia and Kilimanjaro. Three distinct patterns of symptoms were consistently identified. Although fatigue is a ubiquitous finding, sleep disturbance and headache are each commonly reported without the other. The commonest pattern of symptoms was sleep disturbance and fatigue, with little or no headache. In subjects reporting severe headache, 40% did not report sleep disturbance. Sleep disturbance correlates poorly with other symptoms of AMS (Mean Spearman correlation 0.25). These results challenge the accepted paradigm that AMS is a single disease process and describe at least two distinct syndromes following acute ascent to high altitude. This approach to analysing symptom patterns has potential utility in other clinical syndromes.
Royal Air Force Centre of Aviation Medicine, RAF Henlow, Beds, United Kingdom ; Apex (Altitude Physiology Expeditions), c/o Dr. J. K. Baillie, Critical Care Medicine, University of Edinburgh, Royal Infirmary of Edinburgh, United Kingdom.
David P
DP
Hall
Apex (Altitude Physiology Expeditions), c/o Dr. J. K. Baillie, Critical Care Medicine, University of Edinburgh, Royal Infirmary of Edinburgh, United Kingdom.
Ian J C
IJ
MacCormick
Apex (Altitude Physiology Expeditions), c/o Dr. J. K. Baillie, Critical Care Medicine, University of Edinburgh, Royal Infirmary of Edinburgh, United Kingdom.
Alex T
AT
Phythian-Adams
Apex (Altitude Physiology Expeditions), c/o Dr. J. K. Baillie, Critical Care Medicine, University of Edinburgh, Royal Infirmary of Edinburgh, United Kingdom ; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Nina M
NM
Rzechorzek
Apex (Altitude Physiology Expeditions), c/o Dr. J. K. Baillie, Critical Care Medicine, University of Edinburgh, Royal Infirmary of Edinburgh, United Kingdom.
David
D
Hope-Jones
Apex (Altitude Physiology Expeditions), c/o Dr. J. K. Baillie, Critical Care Medicine, University of Edinburgh, Royal Infirmary of Edinburgh, United Kingdom.
Sorrel
S
Cosens
Apex (Altitude Physiology Expeditions), c/o Dr. J. K. Baillie, Critical Care Medicine, University of Edinburgh, Royal Infirmary of Edinburgh, United Kingdom.
Stewart
S
Jackson
Apex (Altitude Physiology Expeditions), c/o Dr. J. K. Baillie, Critical Care Medicine, University of Edinburgh, Royal Infirmary of Edinburgh, United Kingdom ; Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom.
Matthew G D
MG
Bates
William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
David J
DJ
Collier
Division of Genetics and Genomics, Roslin Institute, Edinburgh, United Kingdom.
David A
DA
Hume
Division of Genetics and Genomics, Roslin Institute, Edinburgh, United Kingdom.
Thomas
T
Freeman
Apex (Altitude Physiology Expeditions), c/o Dr. J. K. Baillie, Critical Care Medicine, University of Edinburgh, Royal Infirmary of Edinburgh, United Kingdom ; Academic Unit of Respiratory Medicine, Department of Infection and Immunity, University of Sheffield, Sheffield, United Kingdom.
A A Roger
AA
Thompson
Apex (Altitude Physiology Expeditions), c/o Dr. J. K. Baillie, Critical Care Medicine, University of Edinburgh, Royal Infirmary of Edinburgh, United Kingdom ; Division of Genetics and Genomics, Roslin Institute, Edinburgh, United Kingdom.
John Kenneth
JK
Baillie
D000208:Acute Disease; D000328:Adult; D000531:Altitude; D000532:Altitude Sickness / Q000175:diagnosis* / Q000209:etiology / Q000517:prevention & control; D000975:Antioxidants / Q000008:administration & dosage; D001838:Bolivia; D005101:Expeditions; D005221:Fatigue / Q000150:complications; D005260:Female; D006261:Headache / Q000150:complications; D006801:Humans; D008297:Male; D009051:Mountaineering; D010879:Piperazines / Q000008:administration & dosage; D011687:Purines / Q000008:administration & dosage; D012720:Severity of Illness Index; D000068677:Sildenafil Citrate; D012893:Sleep Wake Disorders / Q000150:complications; D013450:Sulfones / Q000008:administration & dosage; D011795:Surveys and Questionnaires; D013577:Syndrome; D013636:Tanzania; D014665:Vasodilator Agents / Q000008:administration & dosage; D064232:Visual Analog Scale; D055815:Young Adult
D000975:Antioxidants; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate