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      Quantification of Optic Disc Edema during Exposure to High Altitude Shows No Correlation to Acute Mountain Sickness

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          Abstract

          Background

          The study aimed to quantify changes of the optic nerve head (ONH) during exposure to high altitude and to assess a correlation with acute mountain sickness (AMS). This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study.

          Methodology/Principal Findings

          A confocal scanning laser ophthalmoscope (cSLO, Heidelberg Retina Tomograph, HRT3®) was used to quantify changes at the ONH in 18 healthy participants before, during and after rapid ascent to high altitude (4559 m). Slitlamp biomicroscopy was used for clinical optic disc evaluation; AMS was assessed with Lake Louise (LL) and AMS-cerebral (AMS-c) scores; oxygen saturation (SpO 2) and heart rate (HR) were monitored. These parameters were used to correlate with changes at the ONH. After the first night spent at high altitude, incidence of AMS was 55% and presence of clinical optic disc edema (ODE) 79%. Key stereometric parameters of the HRT3® used to describe ODE (mean retinal nerve fiber layer [RNFL] thickness, RNFL cross sectional area, optic disc rim volume and maximum contour elevation) changed significantly at high altitude compared to baseline ( p<0.05) and were consistent with clinically described ODE. All changes were reversible in all participants after descent. There was no significant correlation between parameters of ODE and AMS, SpO 2 or HR.

          Conclusions/Significance

          Exposure to high altitude leads to reversible ODE in the majority of healthy subjects. However, these changes did not correlate with AMS or basic physiologic parameters such as SpO 2 and HR. For the first time, a quantitative approach has been used to assess these changes during acute, non-acclimatized high altitude exposure. In conclusion, ODE presents a reaction of the body to high altitude exposure unrelated to AMS.

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          Most cited references49

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          High-altitude illness.

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            Magnetic resonance imaging evidence of cytotoxic cerebral edema in acute mountain sickness.

            The present study applied T2- and diffusion-weighted magnetic resonance imaging to examine if mild cerebral edema and subsequent brain swelling are implicated in the pathophysiology of acute mountain sickness (AMS). Twenty-two subjects were examined in normoxia (21% O2), after 16 hours passive exposure to normobaric hypoxia (12% O2) corresponding to a simulated altitude of 4,500 m and after 6 hours recovery in normoxia. Clinical AMS was diagnosed in 50% of subjects during hypoxia and corresponding headache scores were markedly elevated (P<0.05 versus non-AMS). Hypoxia was associated with a mild increase in brain volume (+7.0+/-4.8 ml, P<0.05 versus pre-exposure baseline) that resolved during normoxic recovery. Hypoxia was also associated with an increased T2 relaxation time (T2rt) and a general trend toward an increased apparent diffusion coefficient (ADC). During the normoxic recovery, brain volume and T2rt recovered to pre-exposure baseline values, whereas a more marked reduction in ADC in the splenium of the corpus callosum (SCC) was observed (P<0.05). While changes in brain volume and T2rt were not selectively different in AMS, ADC values were consistently lower (P<0.05 versus non-AMS) and associated with the severity of neurologic symptoms. Acute mountain sickness was also characterized by an increased brain to intracranial volume ratio (P<0.05 versus non-AMS). These findings indicate that mild extracellular vasogenic edema contributes to the generalized brain swelling observed at high altitude, independent of AMS. In contrast, intracellular cytotoxic edema combined with an anatomic predisposition to a 'tight-fit' brain may prove of pathophysiologic significance, although the increase in brain volume in hypoxia was only about 0.5% of total brain volume.
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              High-altitude cerebral edema evaluated with magnetic resonance imaging: clinical correlation and pathophysiology.

              Because of its onset in generally remote environments, high-altitude cerebral edema (HACE) has received little scientific attention. Understanding the pathophysiology might have implications for prevention and treatment of both this disorder and the much more common acute mountain sickness. To identify a clinical imaging correlate for HACE and determine whether the edema is primarily vasogenic or cytotoxic. Case-comparison study. Community hospitals accessed by helicopter from mountains in Colorado and Alaska. A consecutive sample of 9 men with HACE, between 18 and 35 years old, 8 of whom also had pulmonary edema, were studied after evacuation from high-altitude locations; 5 were mountain climbers and 4 were skiers. The control group, matched for age, sex, and altitude exposure, consisted of 3 subjects with high-altitude pulmonary edema only and 3 who had been entirely well at altitude. Four patients with HACE were available for follow-up imaging after complete recovery. Magnetic resonance imaging (MRI) of the brain during acute, convalescent, and recovered phases of HACE, and once in controls, immediately after altitude exposure. Seven of the 9 patients with HACE showed intense T2 signal in white matter areas, especially the splenium of the corpus callosum, and no gray matter abnormalities. Control subjects demonstrated no such abnormalities. All patients completely recovered; in the 4 available for follow-up MRI, the changes had resolved entirely. We conclude that HACE is characterized on MRI by reversible white matter edema, with a predilection for the splenium of the corpus callosum. This finding provides a clinical imaging correlate useful for diagnosis. It also suggests that the predominant mechanism is vasogenic (movement of fluid and protein out of the vascular compartment) and, thus, that the blood-brain barrier may be important in HACE.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                1 November 2011
                : 6
                : 11
                : e27022
                Affiliations
                [1 ]Centre for Ophthalmology, University of Tuebingen, Tübingen, Baden-Württemberg, Germany
                [2 ]Department of Sports Medicine, Medical Clinic, University Hospital Heidelberg, Heidelberg, Germany
                [3 ]Department of Ophthalmology, Otorhinolaryngology and Head & Neck Surgery, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil
                Institut de la Vision, France
                Author notes

                Conceived and designed the experiments: GW MDF FG AS. Performed the experiments: MDF GW AS KS FG. Analyzed the data: AS AM MDF KS FG GW. Contributed reagents/materials/analysis tools: FG KS KUBS EZ. Wrote the paper: GW MDF FG. Substantial contributions to analysis and interpretation of data: MDF AM AS GW KS FG. Drafted the article or revised it critically for important intellectual content: GW MDF FG KS.

                Article
                PONE-D-11-15132
                10.1371/journal.pone.0027022
                3206056
                22069483
                5a672f6e-5cbc-4634-bcd9-4c11bd7f0678
                Willmann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 4 August 2011
                : 7 October 2011
                Page count
                Pages: 9
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Ocular System
                Ocular Anatomy
                Comparative Anatomy
                Neurological System
                Neuroscience
                Cellular Neuroscience
                Medicine
                Anatomy and Physiology
                Comparative Anatomy
                Ocular System
                Ophthalmology
                Retinal Disorders
                Sports and Exercise Medicine

                Uncategorized
                Uncategorized

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