Dataset Information

Serum neurofilament level increases after ascent to 4559 m but is not related to acute mountain sickness.

ABSTRACT:

Background and purpose

At high altitude the brain is exposed to hypoxic stress, which may result in neurological conditions, with acute mountain sickness (AMS) being the most common. We aimed to test the hypothesis that rapid ascent to high altitude alters neuro-axonal integrity, which can be detected by increased concentration of serum neurofilament light (sNfL) in the blood and may even be exaggerated in people with AMS.

Methods

Serum neurofilament light was measured using a single-molecule array (Simoa, Quanterix, Lexington, MA, USA) assay at low altitude (423 m) in 47 healthy study participants and 44 h after rapid and active ascent to high altitude (4559 m). Peripheral oxygen saturation (SpO₂ ) and partial pressures of oxygen (pO₂ ) were obtained at low and high altitude. The Acute Mountain Sickness-Cerebral (AMS-C) scoring system was used to assess AMS incidence and AMS severity.

Results

There was an increase in sNfL from its baseline value compared with its value at high altitude (6.34 ± 1.96 vs. 7.19 ± 3.14 pg/ml; p = 0.014), but sNfL level did not correlate with SpO₂ (r = -0.19; p = 0.066) or pO₂ (r = -0.19; p = 0.068). The incidence of AMS at high altitude was 62%. Neither at low altitude (p = 0.706) nor at high altitude (p = 0.985) was there a difference in sNfL between participants with and without AMS as measured 3 days after rapid ascent and 44 h of high-altitude exposure. Altitude sNfL did not correlate with AMS-C, either overall or with single-item scores such as headache severity.

Conclusions

Rapid ascent of healthy people to high altitude provokes an increase in sNfL 44 h after arrival at 4559 m, which is not related to the magnitude of hypoxemia or AMS incidence and severity, suggesting that neuro-axonal injury does not directly contribute to AMS.

SUBMITTER: Sareban M

PROVIDER: S-EPMC7898504 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Serum neurofilament level increases after ascent to 4559 m but is not related to acute mountain sickness.

Sareban Mahdi M Berger Marc Moritz MM Pinter Daniela D Buchmann Arabella A Macholz Franziska F Schmidt Peter P Schiefer Lisa L Schimke Magdalena M Niebauer Josef J Steinacker Jürgen Michael JM Treff Gunnar G Khalil Michael M

European journal of neurology 20201126 3

<h4>Background and purpose</h4>At high altitude the brain is exposed to hypoxic stress, which may result in neurological conditions, with acute mountain sickness (AMS) being the most common. We aimed to test the hypothesis that rapid ascent to high altitude alters neuro-axonal integrity, which can be detected by increased concentration of serum neurofilament light (sNfL) in the blood and may even be exaggerated in people with AMS.<h4>Methods</h4>Serum neurofilament light was measured using a sin ...[more]

PMID: 33095952

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Project description:BackgroundAcute Mountain Sickness (AMS) is a pathophysiologic process that occurs in non-acclimated susceptible individuals rapidly ascending to high-altitude. Barometric pressure falls at high altitude and it translates to a decreased partial pressure of alveolar oxygen (PAO2) and arterial oxygen (PaO2). A gradual staged ascent with sufficient acclimatization can prevent AMS but emergent circumstances requiring exposure to rapid atmospheric pressure changes - such as for climbers, disaster or rescue team procedures, and military operations - establishes a need for effective prophylactic medications. This systematic review and meta-analysis aim to analyze the incidence of AMS during emergent ascent of non-acclimatized individuals receiving inhaled budesonide compared to placebo.MethodsThis current meta-analysis was conducted according to the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We searched PubMed, Google Scholar and Embase for relevant studies. The efficacy of budesonide in reducing incidence of AMS was evaluated by calculating the pooled ORs and 95% CIs. The efficacy of budesonide in maintaining hemoglobin-oxygen saturation was evaluated by calculating standard mean difference (SMD) and 95% confidence intervals.ResultsWe found that at high altitude, inhaled budesonide was effective in reducing the incidence of mild AMS [OR: 0.37; 95% CI, 0.14 to 0.9, p = 0.042] but was ineffective in reducing the incidence of severe AMS [OR: 0.46; 95% CI, 0.14 to 1.41, p = 0.17]. Inhaled budesonide was also effective in maintaining SpO2 (SMD: 0.47; 95% CI, 0.09 to 0.84, p = 0.014) at high altitude. However, it was not effective in maintaining or improving pulmonary function at high altitude. Systematic-review found no adverse effects of budesoide in the dose used for prophylaxis of AMS.ConclusionsOur systematic review showed that prophylactic inhaled budesonide is effective in preventing mild AMS during emergency ascent but not effective in preventing severe AMS. Though statistically significant, authors recommend caution in interpretation of data and questions for further well designed randomized studies to evaluate the role of budesonide in prophylaxis of AMS during an emergent ascent.

Project description:Individuals sojourning at high altitude (≥2,500m) often develop acute mountain sickness (AMS). However, substantial unexplained inter-individual variability in AMS severity exists. Untargeted metabolomics assays are increasingly used to identify novel biomarkers of susceptibility to illness, and to elucidate biological pathways linking environmental exposures to health outcomes. This study used untargeted nuclear magnetic resonance (NMR)-based metabolomics to identify urine metabolites associated with AMS severity during high altitude sojourn. Following a 21-day stay at sea level (SL; 55m), 17 healthy males were transported to high altitude (HA; 4,300m) for a 22-day sojourn. AMS symptoms measured twice daily during the first 5days at HA were used to dichotomize participants according to AMS severity: moderate/severe AMS (AMS; n=11) or no/mild AMS (NoAMS; n=6). Urine samples collected on SL day 12 and HA days 1 and 18 were analyzed using proton NMR tools and the data were subjected to multivariate analyses. The SL urinary metabolite profiles were significantly different (p≤0.05) between AMS vs. NoAMS individuals prior to high altitude exposure. Differentially expressed metabolites included elevated levels of creatine and acetylcarnitine, and decreased levels of hypoxanthine and taurine in the AMS vs. NoAMS group. In addition, the levels of two amino acid derivatives (4-hydroxyphenylpyruvate and N-methylhistidine) and two unidentified metabolites (doublet peaks at 3.33ppm and a singlet at 8.20ppm) were significantly different between groups at SL. By HA day 18, the differences in urinary metabolites between AMS and NoAMS participants had largely resolved. Pathway analysis of these differentially expressed metabolites indicated that they directly or indirectly play a role in energy metabolism. These observations suggest that alterations in energy metabolism before high altitude exposure may contribute to AMS susceptibility at altitude. If validated in larger cohorts, these markers could inform development of a non-invasive assay to screen individuals for AMS susceptibility prior to high altitude sojourn.

Dataset Information

Serum neurofilament level increases after ascent to 4559 m but is not related to acute mountain sickness.

Background and purpose

Methods

Results

Conclusions

Publications

Serum neurofilament level increases after ascent to 4559 m but is not related to acute mountain sickness.

Similar Datasets

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