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. 2024 Nov;14(11):e70165.
doi: 10.1002/brb3.70165.

Neurofilament Light Chain Is Associated With Acute Mountain Sickness

Klaus Berek  1 , Anna Lindner  1 , Franziska Di Pauli  1 , Gabriel Bsteh  2   3 , Benedikt Treml  4 , Markus Ponleitner  2   3 , Clemens Engler  5 , Axel Kleinsasser  4 , Thomas Berger  2   3 , Maria Wille  6 , Martin Burtscher  6 , Florian Deisenhammer  1 , Harald Hegen  1
Affiliations

Neurofilament Light Chain Is Associated With Acute Mountain Sickness

Klaus Berek et al. Brain Behav. 2024 Nov.

Abstract

Background: Neurological symptoms are common in acute mountain sickness (AMS); however, the extent of neuroaxonal damage remains unclear. Neurofilament light chain (NfL) is an established blood biomarker for neuroaxonal damage.

Objective: To investigate whether plasma (p) NfL levels increase after simulated altitude exposure, correlate with the occurrence of AMS, and might be mitigated by preacclimatization.

Methods: Healthy subjects were exposed to simulated high altitude (4500 m) by the use of a normobaric hypoxic chamber at the University of Innsbruck two times, that is, within Cycle 1 (C1) over 12 h, and within Cycle 2 (C2) for another 12 h but with a random assignment to prior acclimatization or sham acclimatization. Before each cycle (measurement [M] 1 and 3) and after each cycle (M2 and M4), clinical data (arterial oxygen saturation [SaO2], heart rate, and Lake Louise AMS score [LLS]) and plasma samples were collected. pNfL was measured using single-molecule array (Simoa) technique.

Results: pNfL levels did not significantly change within each study cycle, but increased over the total study period (M1: 4.57 [3.34-6.39], M2: 4.58 [3.74-6.0], M3: 5.64, and M4: 6.53 [4.65-7.92] pg/mL, p < 0.001). Subjects suffering from AMS during the study procedures showed higher pNfL levels at M4 (6.80 [6.19-8.13] vs. 5.75 [4.17-7.35], p = 0.048), a higher total pNfL increase (2.88 [1.21-3.48] vs. 0.91 [0.53-1.48], p = 0.022) compared to subjects without AMS. An effect of preacclimatization on pNfL levels could not be observed.

Conclusions: pNfL increases alongside exposure to simulated altitude and is associated with AMS.

Keywords: acute mountain sickness; biomarker; headache; high altitude; neurofilament light chain.

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Conflict of interest statement

Klaus Berek has participated in meetings sponsored by and received travel funding or speaker honoraria from Roche, Teva, Merck, Biogen, Sanofi and Novartis. He is associate editor of Frontiers in Immunology/Neurology, Section Multiple Sclerosis and Neuroimmunology. Franziska Di Pauli has participated in meetings sponsored by, received honoraria (lectures, advisory boards, and consultations) or travel funding from Bayer, Biogen, Merck, Novartis, Sanofi‐Genzyme, Teva, Celgene and Roche. Gabriel Bsteh has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene/BMS, Janssen, Lilly, Merck, Novartis, Roche, Sanofi‐Genzyme and Teva, and received honoraria for consulting Biogen, Celgene/BMS, Janssen, Novartis, Roche, Sanofi‐Genzyme and Teva. He has received unrestricted research grants from Celgene/BMS and Novartis. Benedikt Treml received speaker honoraria or travel funding from AOP Orphan, Pfizer and Fresenius. Markus Ponleitner has participated in meetings sponsored by, received speaker or consulting honoraria from Amicus and travel funding from Amicus, Merck, Novartis and Sanofi‐Genzyme. Thomas Berger has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for MS: Allergan, Bayer, Biogen, Bionorica, Biologix, BMS/Celgene, Eisai, Janssen‐Cilag, Jazz/GW, Horizon, MedDay, Merck, Novartis, Octapharma, Roche, Sandoz, Sanofi‐Genzyme, UCB, Teva. His institution has received financial support in the past 12 months by unrestricted research grants (Biogen, Bayer, BMS/Celgene, Merck, Novartis, Sanofi Aventis, Teva and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Merck, Novartis, Octapharma, Roche, Sanofi‐Genzyme, Teva. Florian Deisenhammer has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Alexion, Almirall, Biogen, Celgene, Merck, Novartis, Roche and Sanofi‐Genzyme. His institution received scientific grants from Biogen and Sanofi‐Genzyme. Harald Hegen has participated in meetings sponsored by, received speaker honoraria or travel funding from Bayer, Biogen, Bristol Myers Squibb, Horizon, Janssen, Merck, Novartis, Sanofi‐Genzyme, Siemens, Teva, and received honoraria for acting as consultant for Biogen, Bristol Myers Squibb, Novartis, Roche, Sanofi‐Genzyme and Teva. He is associate editor of Frontiers in Neurology. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Study‐related procedures. Pipettes indicate sampling time‐points.
FIGURE 2
FIGURE 2
Longitudinal plasma NfL levels and NfL Z scores in subjects before and after altitude exposure. The X‐axis depicts the different sampling time‐points; sampling time‐points 1 and 2 before and after study Cycle 1, sampling time‐points 3 and 4 before and after study Cycle 2. NfL = neurofilament light.
FIGURE 3
FIGURE 3
Factors associated with the occurrence of AMS. LLS was assessed according to (Roach et al. 2018). “SaO2 decrease” is the decrease of SaO2 3 h after exposure to simulated high altitude. “pNfL increase total” indicates the increase of pNfL from M1 to M4. AMS = acute mountain sickness; LLS = Lake Louise Acute Mountain Sickness Score; M1/M4 = measurement 1/4; pNfL = plasma neurofilament light; SaO2 = arterial oxygen saturation.
See this image and copyright information in PMC

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