Network Analysis Reveals Distinct Clinical Syndromes Underlying Acute Mountain Sickness

Abstract

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.

The 2018 Lake Louise Acute Mountain Sickness Score

“…Two independent reports in 2013 provided empirical evidence that sleep disturbance is discordant from other symptoms of AMS (MacInnis et al, 2013;Hall et al, 2014). Hall et al (2014) used network analysis of data from 292 research volunteers exposed to altitudes from 3650 to 5200 m to demonstrate that sleep disturbance correlated poorly with other symptoms of AMS. Importantly, sleep disturbance was absent in 40% of cases with severe headache, long considered a hallmark of AMS.…”

“…With 25 years of use in hundreds of publications, the Lake Louise AMS score has provided a robust and practical tool for researchers to diagnose and to score the severity of AMS. Recent opinion (Milledge, 2014) and research (MacInnis et al, 2013;Hall et al, 2014) have suggested that updating the Lake Louise AMS score is in order. This article outlines the brief historical background, reviews diagnostic criteria, describes modifications to the score, and offers suggested experimental procedures that may improve the use of the score in future studies.…”

Incidence of acute mountain sickness in UK Military Personnel on Mount Kenya

“…This was observational data and collected by the participants and not by direct questioning by a medical officer or on the basis of clinical signs. The validity of the LLS itself has recently been questioned with Hall et al 25 proposing that AMS presents distinct clinical syndromes rather than one entity and that headache is not a feature of all. The LLS was employed as the most widely used score and the score recommended for research purposes 11…”

Treatable traits and therapeutic targets: Goals for systems biology in infectious disease

“…This is the fundamental attraction of high-throughput technologies e the probability of measuring important signals is greater if more signals are measured. That such groupings of patients, or disease endotypes, exist is already clear: therapeuticallyimportant sub-classifications have recently been discovered that redefine the clinical syndromes of asthma [30,31], ARDS [32], and acute mountain sickness [33]. In two related autoimmune conditions, ANCA-associated vasculitis (AAV) and systemic lupus erythematosus (SLE), a T-cell gene expression signature clearly delineates two distinct endotypes [34].…”