Exposure to 16 h of normobaric hypoxia induces ionic edema in the healthy brain.

Following prolonged exposure to hypoxic conditions, for example, due to ascent to high altitude, stroke, or traumatic brain injury, cerebral edema can develop. The exact nature and genesis of hypoxia-induced edema in healthy individuals remain unresolved. We examined the effects of prolonged, normobaric hypoxia, induced by 16 h of exposure to simulated high altitude, on healthy brains using proton, dynamic contrast enhanced, and sodium MRI. This dual approach allowed us to directly measure key factors in the development of hypoxia-induced brain edema: (1) Sodium signals as a surrogate of the distribution of electrolytes within the cerebral tissue and (2) Ktrans as a marker of blood-brain-barrier integrity. The measurements point toward an accumulation of sodium ions in extra- but not in intracellular space in combination with an intact endothelium. Both findings in combination are indicative of ionic extracellular edema, a subtype of cerebral edema that was only recently specified as an intermittent, yet distinct stage between cytotoxic and vasogenic edemas. In sum, here a combination of imaging techniques demonstrates the development of ionic edemas following prolonged normobaric hypoxia in agreement with cascadic models of edema formation.

Genetic Predisposition to High-Altitude Pulmonary Edema.

Background: Exaggerated pulmonary arterial hypertension (PAH) is a hallmark of high-altitude pulmonary edema (HAPE). The objective of this study was therefore to investigate genetic predisposition to HAPE by analyzing PAH candidate genes in a HAPE-susceptible (HAPE-S) family and in unrelated HAPE-S mountaineers. Materials and Methods: Eight family members and 64 mountaineers were clinically and genetically assessed using a PAH-specific gene panel for 42 genes by next-generation sequencing. Results: Two otherwise healthy family members, who developed re-entry HAPE at 3640 m during childhood, carried a likely pathogenic missense mutation (c.1198T>G p.Cys400Gly) in the Janus Kinase 2 (JAK2) gene. One of them progressed to a mild form of PAH at the age of 23 years. In two of the 64 HAPE-S mountaineers likely pathogenic variants have been detected, one missense mutation in the Cytochrome P1B1 gene, and a deletion in the Histidine-Rich Glycoprotein (HRG) gene. Conclusions: This is the first study identifying an inherited missense mutation of a gene related to PAH in a family with re-entry HAPE showing a progression to borderline PAH in the index patient. Likely pathogenic variants in 3.1% of HAPE-S mountaineers suggest a genetic predisposition in some individuals that might be linked to PAH signaling pathways.

Decreased contrast sensitivity at high altitude.

BACKGROUND/AIMS: The aim of this study was to investigate a change in visual acuity and contrast sensitivity (CS) during high altitude exposure in healthy subjects due to the effects of hypobaric hypoxia. This study is related to the Tübingen High Altitude Ophthalmology study. METHODS: Visual acuity and Weber CS were tested monocularly using the Freiburger Visual Acuity and Contrast Test under standardised conditions in 14 healthy subjects at high altitude at the Capanna Margherita (4559 m, Italy) and compared with baseline measurements in Tübingen (341 m, Germany). Intraindividual differences between baseline and follow-up examinations were calculated by multivariate analysis of variance for repeated measures. Clinical parameters of peripheral oxygen saturation (SpO2) and heart rate (HR) as well as scores for acute mountain sickness (AMS) were correlated to psychophysical tests by Pearson's correlation coefficient. RESULTS: A significant decrease in CS with a mean effect size of -0.13 logCS was found for Weber CS (day 1=-0.16±0.22, p=0.01; day 2=-0.10±0.2, p=0.049; day 3=-0.12±0.19, p=0.03) at high altitude compared with baseline. Visual acuity remained unchanged. Decreased CS correlated with SpO2 (r=0.53, p=0.046) but not with HR (r=- 0.16, p=0.59) and occurred irrespective of AMS at high altitude. CONCLUSION: High altitude exposure leads to decreased CS. Changes occur independent of AMS. This finding is of clinical importance to trekkers and mountaineers exposed to high altitude as visual processing in particular under mesopic conditions at dusk and dawn is altered. Furthermore, it provides novel insight into hypoxia related changes in CS function.

Optic nerve oedema at high altitude occurs independent of acute mountain sickness.

BACKGROUND/AIMS: The study aims to investigate changes in the optic nerve sheath diameter (ONSD) at high altitude and to assess correlation to optic disc oedema (ODE) and acute mountain sickness (AMS). This investigation is part of the Tübingen High Altitude Ophthalmology study. METHODS: Fourteen volunteers ascended to 4559 m for 4 days before returning to low altitude. Ultrasonography of ONSD, quantification of optic disc parameters using a scanning laser ophthalmoscope and fluorescein angiography were performed at 341 m and at high altitude. Pearson's coefficient was used to correlate changes in ONSD with the optic disc and AMS. Assessment of AMS was performed using the Lake Louise (LL) and AMS-cerebral (AMS-C) scores of the Environmental Symptom Questionnaire-III. All volunteers were clinically monitored for heart rate (HR) and oxygen saturation (SpO2). RESULTS: The mean ONSD at high altitude (4.6±0.3 mm, p<0.05) was significantly increased compared with baseline (3.8±0.4 mm) and remained enlarged throughout high-altitude exposure. This change in ONSD did not correlate with AMS (AMS-C, r=0.26, p=0.37; LL, r=0.21, p=0.48) and high-altitude headache (r=0.54, p=0.046), or clinical parameters of SpO2 (r=0.11, p=0.72) and HR (r=0.22, p=0.44). Increased ONSD did not correlate with altered key stereometric parameters of the optic disc describing ODE at high altitude (r<0.1, p>0.5). CONCLUSION: High-altitude exposure leads to marked oedema formation of the optic nerve independent of AMS. Increased ONSD and ODE reflect hypoxia-driven oedema formation of the optic nerve at high altitude, providing important pathophysiological insight into high-altitude illness development and for future research.

Effect of High Altitude Exposure on Intraocular Pressure Using Goldmann Applanation Tonometry.

Willmann, Gabriel, Kai Schommer, Maximilian Schultheiss, M. Dominik Fischer, Karl-Ulrich Bartz-Schmidt, Florian Gekeler, and Andreas Schatz. Effect of high altitude exposure on intraocular pressure using Goldmann applanation tonometry. High Alt Med Biol. 18:114-120, 2017. AIMS: The aim of the study was to quantify changes of intraocular pressure (IOP) during exposure to 4559 m using the state-of-the-art method of Goldmann applanation tonometry for IOP measurement and to detect correlations between IOP and acute mountain sickness (AMS) in a prospective manner. METHODS: IOP was measured using a Goldmann applanation tonometer AT 900® (Haag-Streit, Switzerland) and central corneal thickness (CCT) with the anterior segment module of a Spectralis™ HRA+OCT® device (Heidelberg Engineering, Germany) at baseline and high altitude. Assessment of AMS was performed using the Lake Louise and AMS-C questionnaires, and Pearson's correlation coefficient was calculated for association between IOP and AMS. RESULTS: Raw IOP values at high altitude were not significantly changed compared to baseline. IOP adjusted to the increase in CCT at high altitude, which is known to alter IOP levels, showed a significant reduction for corrected IOP values on day 3 of exposure (morning -2.1 ± 1.2 mmHg; evening -2.3 ± 1.1 mmHg; p < 0.05). No correlation of IOP with AMS or clinical parameters (heart rate and SpO2) at high altitude was noted. CONCLUSIONS: IOP showed a significant reduction of IOP levels when corrected for increased CCT values at high altitude. Furthermore, the prospective measurement of IOP is not useful in diagnosing AMS or for the prediction of more severe high altitude related illnesses as the decrease in IOP and symptoms of AMS do not correlate during altitude exposure.

Exercise and cancer: return to work as a firefighter with ostomy after rectal carcinoma - a case report.

BACKGROUND: Colorectal cancer survivors are deconditioned through anticancer therapy. Furthermore, about 10% of them have a permanent ostomy which is associated with weakened abdominal muscles and an increased risk of a hernia. This case study reports on how a firefighter with rectal carcinoma and ostomy was trained to regain operational fitness. METHODS: A 44-year-old firefighter (178 cm, 82 kg) with an adenocarcinoma of the rectum (diagnosed 24 months prior) had been treated with neoadjuvant radiochemotherapy and surgery. After 2 temporary ileostomies, a permanent colostomy was performed 14 weeks before the start of a 9-months training program. The program included sensorimotor, endurance, and strength training of increasing volume and intensity. Endurance, strength, and patient reported outcomes were assessed every 2 to 3 months. RESULTS: Training frequency varied from 1 to 3 sessions/week, although 3 to 5 sessions/week were prescribed. Peak power output was 150, 158, 167, 192, and 175 watts at baseline, 2, 4, 6, and 9 months. Maximal oxygen uptake increased from 1.56 L/min (19.0 mL/min/kg) to 2.39 L/min (28.8 mL/min/kg) after 6 months. Maximal isokinetic peak torque (MIPT) of the knee extensors were 138.0 and 196.5 Nm (Newton meter) at baseline and 6 months. MIPT of the elbow and hip flexors increased from 51.8 to 66.0 Nm and 213.8 to 239.7 Nm, respectively, after 6 months. Physical fatigue decreased by 65% and distress by about 50% after 9 months. The firefighter passed a test for occupational fitness after 6 months and was permitted to work with an exterior crew on a pump truck. CONCLUSION: It is possible for colorectal cancer survivors with ostomy to regain occupational fitness for physically demanding tasks like firefighting through an individually tailored and supervised training program.

Does High Alveolar Fluid Reabsorption Prevent HAPE in Individuals with Exaggerated Pulmonary Hypertension in Hypoxia?

An exaggerated increase in pulmonary arterial systolic pressure (PAsP) is a highlight of high altitude pulmonary edema (HAPE). However, the incidence of HAPE at 4559 m was much lower in altitude-naïve individuals with exaggerated pulmonary vasoconstriction (HPV) in normobaric hypoxia than in known HAPE-susceptibles, indicating that elevated PAsP alone is insufficient to induce HAPE. A decreased nasal potential difference (NPD) has been found in HAPE-susceptibles, where, based on animal models, NPD serves as surrogate of alveolar epithelial ion transport. We hypothesize that those HAPE-resistant individuals with high HPV may be protected by elevated alveolar Na and fluid reabsorption, which might be detected as increased NPD. To test this hypothesis, we measured NPD in normoxia of subjects who were phenotyped in previous studies as high altitude tolerant (controls), known HAPE-susceptibles with high HPV (HP+HAPE), as well as individuals with high HPV but without HAPE (HP-no-HAPE) at 4559 m. NPD and amiloride-sensitive NPD were lower in HP+HAPE than in controls, whereas HP-no-HAPE were not different from either group. There were no differences in Cl-transport between groups. Our results show low nasal ion transport in HAPE but higher transport in those individuals with the highest HPV but without HAPE. This indicates that in some individuals with high PAsP at high altitude high alveolar fluid reabsorption might protect them from HAPE.

Reversible Increase of Central Choroidal Thickness During High-Altitude Exposure.

PURPOSE: This study aimed to quantify the impact of high altitude on choroidal thickness and relate changes of altered choroidal blood flow to clinical parameters and acute mountain sickness (AMS). This work is related to the Tübingen High Altitude Ophthalmology (THAO) study. METHODS: Enhanced depth imaging spectral-domain optical coherence tomography was used to quantify macular choroidal layer thickness. Peripheral oxygen saturation, heart rate, and AMS scores were assessed in eight healthy subjects at baseline (altitude, 341 m) and at altitude (4559 m) for respective correlations. RESULTS: Longitudinal analysis revealed a significant (P = 0.011, ANOVA) increase in central choroidal thickness (CCT) during altitude exposure (CCT baseline = 271 ± 9 µm; CCT altitude = 288 ± 9 µm) due to an increased choroidal blood flow. Incidence of AMS at altitude was 50%, peripheral oxygen saturation decreased by 25%, and heart rate increased by 39%. All changes were completely reversible after descent to low altitudes. CONCLUSIONS: A small but significant increase in choroidal thickness was observed upon acute altitude exposure to 4559 m. This increase in choroidal blood flow was not related to AMS and was fully reversible after return to low altitude.

Remote ischemic preconditioning delays the onset of acute mountain sickness in normobaric hypoxia.

Acute mountain sickness (AMS) is a neurological disorder occurring when ascending too fast, too high. Remote ischemic preconditioning (RIPC) is a noninvasive intervention protecting remote organs from subsequent hypoxic damage. We hypothesized that RIPC protects against AMS and that this effect is related to reduced oxidative stress. Fourteen subjects were exposed to 18 hours of normoxia (21% oxygen) and 18 h of normobaric hypoxia (12% oxygen, equivalent to 4500 m) on different days in a blinded, randomized order. RIPC consisted of four cycles of lower limb ischemia (5 min) and 5 min of reperfusion, and was performed immediately before the study room was entered. A control group was exposed to hypoxia (12% oxygen, n = 14) without RIPC. AMS was evaluated by the Lake Louise score (LLS) and the AMS-C score of the Environmental Symptom Questionnaire. Plasma concentrations of ascorbate radicals, oxidized sulfhydryl (SH) groups, and electron paramagnetic resonance (EPR) signal intensity were measured as biomarkers of oxidative stress. RIPC reduced AMS scores (LLS: 1.9 ± 0.4 vs. 3.2 ± 0.5; AMS-C score: 0.4 ± 0.1 vs. 0.8 ± 0.2), ascorbate radicals (27 ± 7 vs. 65 ± 18 nmol/L), oxidized SH groups (3.9 ± 1.4 vs. 14.3 ± 4.6 µmol/L), and EPR signal intensity (0.6 ± 0.2 vs. 1.5 ± 0.4 × 10(6)) after 5 h in hypoxia (all P < 0.05). After 18 hours in hypoxia there was no difference in AMS and oxidative stress between RIPC and control. AMS and plasma markers of oxidative stress did not correlate. This study demonstrates that RIPC transiently reduces symptoms of AMS and that this effect is not associated with reduced plasma levels of reactive oxygen species.

Exercise training intensity prescription in breast cancer survivors: validity of current practice and specific recommendations.

PURPOSE: Cancer survivors are recommended to perform 150 min/week of moderate or 75 min/week of vigorous aerobic exercise, but it remains unclear how moderate and vigorous intensities can be prescribed. Therefore, it was investigated whether and how intensity prescriptions for healthy adults by the American College of Sports Medicine (ACSM) need to be adapted for breast cancer survivors. METHODS: Fifty-two breast cancer survivors (stage 0-III, age 52 ± 9 years, BMI 25.4 ± 3.5 kg/m2) performed cardiopulmonary exercise tests at the end of primary therapy. Intensity classes defined as percentages of maximal heart rate (HRmax), heart rate reserve (HRR), and maximal oxygen uptake (VO2max) were compared to the ACSM's intensity classes using oxygen uptake reserve as reference. RESULTS: The prescriptions for moderate and vigorous exercise intensities were significantly different between breast cancer survivors and healthy adults when using VO2max (moderate 50-66 vs. 46-63 and vigorous 67-91 vs. 64-90% VO2max) or HRR (moderate 26-50 vs. 40-59 and vigorous 51-88 vs. 60-89 % HRR), but not when using HRmax (moderate 65-76 vs. 64-76 and vigorous 77-94 vs. 77-95% HRmax). CONCLUSIONS: In breast cancer survivors, intensity prescriptions for healthy adults result in considerably too intense training if HRR is used as guiding factor. Prescriptions using VO2max result in a slightly too low exercise intensity, whereas recommendations in percentages of HRmax appear valid. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors should not uncritically adopt exercise intensity prescriptions for healthy adults. Specific prescriptions for the studied population are provided.

Exercise intensity classification in cancer patients undergoing allogeneic HCT.

OBJECTIVE: Exercise intervention studies during and after cancer treatment show beneficial effects for various physical and psychosocial outcomes. Current exercise intensity guidelines for cancer patients are rather general and have been adapted from American College of Sports Medicine (ACSM) recommendations for healthy individuals. Intensive cancer treatment regimens such as allogeneic hematopoietic stem cell transplantation (allo-HCT) may change the cardiovascular response to acute exercise. Therefore, we evaluated the relationships between %V˙O2 reserve (%V˙O2R, reference) and %HRR, %HRmax, and %V˙O2max and compared calculated intensities with given intensities by ACSM. METHODS: Measurements before and 180 d after allo-HCT from a randomized controlled trial were used. Only patients who reached maximal effort and at least two exercise stages in our maximal incremental cycling test were included. Before allo-HCT, 106 patients were included, and 180 d after treatment, 49 patients met our inclusion criteria. Individual regression lines were calculated with V˙O2R as the reference. Calculated exercise intensities for endurance training prescription were compared with ACSM values. RESULTS: Before allo-HCT, %HRR values of patients were significantly lower than ACSM values, and %HRmax and %V˙O2max values were significantly higher (except 90% HRmax, which was significantly lower, all P < 0.01). One hundred eighty days after allo-HCT, values for %HRR were not significantly different to ACSM values (except 90%, which was significantly lower, P = 0.01), whereas %HRmax and %V˙O2max were significantly higher (all P < 0.05). Furthermore, regression models revealed no influence of beta-blockers on calculated intensities. CONCLUSIONS: ACSM's exercise intensity recommendations for endurance training may not be applicable for cancer patients during and 180 d after allo-HCT because they may not meet the targeted intensity class, with the exception of %HRR 180 d after allo-HCT.

Missing correlation of retinal vessel diameter with high-altitude headache.

The most common altitude-related symptom, high-altitude headache (HAH), has recently been suggested to originate from restricted cerebral venous drainage in the presence of increased inflow caused by hypoxia. In support of this novel hypothesis, retinal venous distension was shown to correlate with the degree of HAH. We quantified for the first time retinal vessel diameter changes at 4559 m using infrared fundus images obtained from a state of the art Spectralis™ HRA+OCT with a semiautomatic VesselMap 1® software. High-altitude exposure resulted in altered arterial and venous diameter changes at high altitude, however, independent of headache burden.

Update on high altitude cerebral edema including recent work on the eye.

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.

Exposure to high altitude alters tear film osmolarity and breakup time.

AIMS: High altitude provides environmental conditions with dry air and cold temperatures that may facilitate the development of dry eye symptoms. This study investigated, for the first time, the quality of the tear film during high altitude exposure in healthy subjects. This study is related to the Tübingen High Altitude Ophthalmology (THAO) study. METHODS: Tear film osmolarity (TFO), tear film breakup time (TBUT), and Schirmer I and II were used to assess tear film properties under standardized conditions in 14 healthy subjects on day 1, 2, and 4 during exposure to high altitude at the Capanna Margherita (CM; 4559 m, Italy) compared to baseline measurements in Tübingen (341 m, Germany) before (BL1) and after (BL2) exposure. RESULTS: Upon arrival at CM, a significant increase in intra-individual TFO (309.1 ± 19.3, 332.2 ± 24.1, 335.5 ± 28.7, 329.7 ± 19.0, and 308.5 ± 15.3 mOsms/L at BL1, day 1, 2, 4, and BL2, respectively) and a significant decrease of TBUT (11.2 ± 5.2, 7.3 ± 5.2, 7.2 ± 11.6, 4.5 ± 2.3, and 8.7 ± 4.6 seconds at BL1, day 1, 2, 4, and BL2, respectively) were found. Schirmer test changes at high altitude remained statistically nonsignificant compared to baseline. Comparisons of parameters between BL1 and BL2 showed no statistically significant differences and recordings of right and left eyes for TBUT and Schirmer did not differ significantly on any day measured. CONCLUSION: High altitude exposure leads to an altered tear film resulting in an increased TFO and a reduced TBUT. These changes were fully reversible after descent. This is of clinical importance to populations living in high altitude areas and to trekkers and mountaineers exposed to high altitude due to their ever-increasing number.

Attenuation of S-cone function at high altitude assessed by electroretinography.

As impaired S-cone function has been reported psychophysically this study assessed S-cone function during high altitude exposure using electroretinography (ERG) and investigated a possible association with severity of acute mountain sickness (AMS). This work is related to the Tübingen High Altitude Ophthalmology (THAO) study. Standard ERG equipment was used (Diagnosys LLC, Cambridge, UK) with special protocol settings to extract S-cone function. Twelve subjects were analyzed in the current study and examinations were performed in Tübingen, Germany (341m) as baseline and thereafter at the Capanna Margherita, Italy (4559m) at high altitude. Results were compared using a paired t-test. Correlations between ERG measurements and oxygen saturation (SpO2), heart rate (HR) and scores of acute mountain sickness (AMS-C and LL) were calculated using Pearson's correlation coefficients. Amplitudes of S-cone b-waves decreased significantly at high altitude (p=0.02). No significant changes were observed for implicit times of b-waves (p=0.63), a-waves (p=0.75) or for a-wave amplitudes (p=0.78). The incidence of AMS was 50% at high altitude according to AMS-C and LL scores (AMS-C⩾0.7 and LL⩾5). Heart rate increased to 84±10min(-1) and SpO2 decreased to 71.9±5.7% at high altitude. No significant correlation was found between S-cone ERG parameters and SpO2, HR, AMS-C and LL. For the first time our study defines a significant impairment of S-cone function at high altitude time using objective state of the art examination methods. No correlation between the functional impairment of S-cones and levels of AMS was detected.

Pupillary light reaction during high altitude exposure.

PURPOSE: This study aimed to quantify the pupillary light reaction during high altitude exposure using the state of the art Compact Integrated Pupillograph (CIP) and to investigate a potential correlation of altered pupil reaction with severity of acute mountain sickness (AMS). This work is related to the Tübingen High Altitude Ophthalmology (THAO) study. METHODS: Parameters of pupil dynamics (initial diameter, amplitude, relative amplitude, latency, constriction velocity) were quantified in 14 healthy volunteers at baseline (341 m) and high altitude (4559 m) over several days using the CIP. Scores of AMS, peripheral oxygen saturation and heart rate were assessed for respective correlations with pupil dynamics. For statistical analysis JMP was used and data are shown in terms of intra-individual normalized values (value during exposure/value at baseline) and the 95% confidence interval for each time point. RESULTS: During high altitude exposure the initial diameter size was significantly reduced (p<0.05). In contrast, the amplitude, the relative amplitude and the contraction velocity of the light reaction were significantly increased (p<0.05) on all days measured at high altitude. The latency did not show any significant differences at high altitude compared to baseline recordings. Changes in pupil parameters did not correlate with scores of AMS. CONCLUSIONS: Key parameters of the pupillary light reaction are significantly altered at high altitude. We hypothesize that high altitude hypoxia itself as well as known side effects of high altitude exposure such as fatigue or exhaustion after ascent may account for an altered pupillogram. Interestingly, none of these changes are related to AMS.

Hemosiderin deposition in the brain as footprint of high-altitude cerebral edema.

OBJECTIVE: Based on recent findings of microhemorrhages (MHs) in the corpus callosum (CC) in 3 individuals after nonfatal high-altitude cerebral edema (HACE), we hypothesized that hemosiderin depositions in the brain after high-altitude exposure are specific for HACE and remain detectable over many years. METHODS: This was a cross-sectional study involving 37 mountaineers in 4 groups: 10 had experienced HACE, 8 high-altitude pulmonary edema, 11 severe acute mountain sickness, and 8 had climbed to altitudes ≥6,962 m without developing any high-altitude illness. HACE was defined as ataxia necessitating assistance with walking and/or decreased consciousness. Within <1 to 38 months after the qualifying incident, MRI of the brain was performed using a 3-tesla scanner and high-resolution susceptibility-weighted magnetic resonance sequences for detection of hemosiderin depositions, which were quantified by a score. RESULTS: Unequivocal MHs located in the splenium of the CC were found in 8 subjects and questionable MHs were found in 2 subjects 1 to 35 months after HACE. They were located outside the CC in 5 more severe cases. MHs remained unchanged in those reexamined after 12 to 50 months. A few unequivocal MHs in the splenium of the CC were found in one subject after severe acute mountain sickness, while one subject with high-altitude pulmonary edema and 2 of the extreme altitude climbers had questionable lesions. In all other subjects, MHs were unequivocally absent. CONCLUSIONS: MHs detectable by susceptibility-weighted MRI predominantly in the splenium of the CC are long-lasting footprints of HACE.

Impact of meteorological conditions on abdominal aortic aneurysm rupture: evaluation of an 18-year period and review of the literature.

OBJECTIVE: To examine the influence of local meteorological conditions on the onset of ruptured abdominal aortic aneurysms (AAA). METHODS: A review of 6551 consecutive days with a total of 191 ruptured AAA was performed between January, 1994 and December, 2011. Days with and without ruptured AAA were compared considering local meteorological data. A systematic review of the literature was performed. RESULTS: Atmospheric pressure, cloudiness, relative humidity, precipitation, and water vapor pressure were comparable at event and nonevent days. The 4-day variance of atmospheric pressure prior to event days was significantly higher compared to nonevent days. Maximal and average temperature and water vapor pressure were significant lower at event days. Binary regression analysis identified a higher 4-day variance in atmospheric pressure as an independent factor for ruptures. CONCLUSIONS: Further studies-collected at different geographic and climate areas-are necessary to prove that meteorological conditions may trigger the incidence of ruptured AAA.

Electroretinographic assessment of retinal function at high altitude.

Although hypoxia plays a key role in the pathophysiology of many common and well studied retinal diseases, little is known about the effects of high-altitude hypoxia on retinal function. The aim of the present study was to assess retinal function during exposure to high-altitude hypoxia using electroretinography (ERG). This work is related to the Tübingen High Altitude Ophthalmology (THAO) study. Electroretinography was performed in 14 subjects in Tübingen, Germany (341 m) and at high altitude at La Capanna Regina Margherita, Italy (4,559 m) using an extended protocol to assess functional integrity of various retinal layers. To place findings in the context of acute mountain sickness, correlations between ERG measurements and oxygen saturation, heart rate, and scores of acute mountain sickness (AMS) were calculated. At high altitude, the maximum response of the scotopic sensitivity function, the implicit times of the a- and b-wave of the combined rod-cone responses, and the implicit times of the photopic negative responses (PhNR) were significantly altered. A-wave slopes and i-waves were significantly decreased at high altitude. The strongest correlation was found for PhNR and O2 saturation (r = 0.68; P < 0.05). Of all tested correlations, only the photopic b-wave implicit time (10 cd·s/m(2)) was significantly correlated with severity of AMS (r = 0.57; P < 0.05). ERG data show that retinal function of inner, outer, and ganglion cell layer is altered at high-altitude hypoxia. Interestingly, the most affected ERG parameters are related to combined rod-cone responses, which indicate that phototransduction and visual processing, especially under conditions of rod-cone interaction, are primarily affected at high altitude.