MRI Evidence: Acute Mountain Sickness Is Not Associated with Cerebral Edema Formation during Simulated High Altitude

Department of Sports Science, Medical Section, University of Innsbruck, Innsbruck, Austria.
PLoS ONE (Impact Factor: 3.53). 11/2012; 7(11):e50334. DOI: 10.1371/journal.pone.0050334
Source: PubMed

ABSTRACT Acute mountain sickness (AMS) is a common condition among non-acclimatized individuals ascending to high altitude. However, the underlying mechanisms causing the symptoms of AMS are still unknown. It has been suggested that AMS is a mild form of high-altitude cerebral edema both sharing a common pathophysiological mechanism. We hypothesized that brain swelling and consequently AMS development is more pronounced when subjects exercise in hypoxia compared to resting conditions. Twenty males were studied before and after an eight hour passive (PHE) and active (plus exercise) hypoxic exposure (AHE) (F(i)O(2) = 11.0%, P(i)O(2)∼80 mmHg). Cerebral edema formation was investigated with a 1.5 Tesla magnetic resonance scanner and analyzed by voxel based morphometry (VBM), AMS was assessed using the Lake Louise Score. During PHE and AHE AMS was diagnosed in 50% and 70% of participants, respectively (p>0.05). While PHE slightly increased gray and white matter volume and the apparent diffusion coefficient, these changes were clearly more pronounced during AHE but were unrelated to AMS. In conclusion, our findings indicate that rest and especially exercise in normobaric hypoxia are associated with accumulation of water in the extracellular space, however independent of AMS development. Thus, it is suggested that AMS and HACE do not share a common pathophysiological mechanism.

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    ABSTRACT: Abstract Willmann, Gabriel, Florian Gekeler, Kai Schommer, and Peter Bärtsch. Update on high altitude cerebral edema including recent work on eye. High Alt Med Biol. 15:112-122, 2014.-This review summarizes recent research on high altitude cerebral edema (HACE) and on the eye with focus on the retina and optic nerve as visible brain tissue at high altitude. Hemosiderin deposits in the corpus callosum have been characterized as rather specific long-lasting footprints of HACE, indicating a leak of the blood-brain barrier (BBB) and resulting in microhemorrhages. These are compatible with the concept of increased capillary pressure due to venous outflow limitation as suggested by Wilson et al. There are no human data on the role of vascular permeability in HACE, while animal models of uncertain relevance for human HACE suggest that an impaired integrity of the BBB through VEGF and ROS is more important than hemodynamic changes. Examinations by ultrasound show an inconsistent increase of the optic nerve sheath diameter, whereas unequivocal optic disc swelling (ODS), increased retinal vessel diameter, as well as retinal vessel leakage occur at high altitude. However, whether these morphological changes correlate with symptoms of AMS as a possible precursor of HACE or high altitude headache supporting the concept of venous outflow limitation remains questionable and is discussed in detail in this article.
    High Altitude Medicine & Biology 06/2014; 15(2):112-22. DOI:10.1089/ham.2013.1142 · 1.82 Impact Factor
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    ABSTRACT: The present study assessed the isolated and synergetic effects of hypoxic exposure and prolonged exercise on cerebral volume and subedema and symptoms of acute mountain sickness (AMS). Twelve healthy males performed three semirandomized blinded 11-hour sessions with (1) an inspiratory oxygen fraction (FiO2) of 12% and 4-hour cycling, (2) FiO2=21% and 4-hour cycling, and (3) FiO2=8.5% to 12% at rest (matching arterial oxygen saturation measured during the first hypoxic session). Volumetric, apparent diffusion coefficient (ADC), and arterial spin labelling 3T magnetic resonance imaging sequences were performed after 30 minutes and 10 hours in each session. Thirty minutes of hypoxia at rest induced a significant increase in white-matter volume (+0.8±1.0% compared with normoxia) that was exacerbated after 10 hours of hypoxia at rest (+1.5±1.1%) or with cycling (+1.6±1.1%). Total brain parenchyma volume increased significantly after 10 hours of hypoxia with cycling only (+1.3±1.1%). Apparent diffusion coefficient was significantly reduced after 10 hours of hypoxia at rest or with cycling. No significant change in cerebral blood flow was observed. These results demonstrate changes in white-matter volume as early as after 30 minutes of hypoxia that worsen after 10 hours, probably due to cytotoxic edema. Exercise accentuates the effect of hypoxia by increasing total brain volume. These changes do not however correlate with AMS symptoms.Journal of Cerebral Blood Flow & Metabolism advance online publication, 27 August 2014; doi:10.1038/jcbfm.2014.148.
    Journal of Cerebral Blood Flow & Metabolism 08/2014; 34(11). DOI:10.1038/jcbfm.2014.148 · 5.34 Impact Factor
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    ABSTRACT: Despite decades of research, the exact pathogenic mechanisms underlying acute mountain sickness (AMS) are still poorly understood. This fact frustrates the search for novel pharmacological prophylaxis for AMS. The prevailing view is that AMS results from an insufficient physiological response to hypoxia and that prophylaxis should aim at stimulating the response. Starting off from the opposite hypothesis that AMS may be caused by an initial excessive response to hypoxia we suggest that directly or indirectly blunting specific parts of the response might provide promising research alternatives. This reasoning is based on the observations that 1) humans, once acclimatized, can climb Mt Everest experiencing arterial partial oxygen pressures (PaO2 ) as low as 25 mmHg without AMS symptoms, 2) paradoxically AMS usually develops at much higher PaO2 levels, and 3) several biomarkers, suggesting initial activation of specific pathways at such PaO2 , are correlated with AMS. Apart from looking for substances that stimulate certain hypoxia triggered effects, such as the ventilatory response to hypoxia, we suggest to also investigate pharmacological means aiming at blunting certain other specific hypoxia activated pathways, or stimulating their agonists, in the quest for better pharmacological prophylaxis for AMS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Acta Physiologica 03/2015; DOI:10.1111/apha.12486 · 4.25 Impact Factor

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