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129 records · Page 8

SPACEFLIGHT ASSOCIATED NEURO-OCULAR SYNDROME (SANS): 2023 CLINICAL UPDATE

INTRODUCTION Spaceflight Associated Neuro-ocular Syndrome (SANS) is a condition unique to long-duration spaceflight, with an unclear pathogenesis and pathophysiology, and no perfect terrestrial analog. Approximately 66% of long duration spaceflight (LDSF) astronauts present with the earliest indication of SANS, which is defined as development of any of the following signs in at least one eye during or immediately following spaceflight: 1) optic disc edema (ODE; represented by an increase of ≥ 20 microns in peripapillary total retinal thickness [ΔTRT]); 2) chorioretinal folds; 3) globe flattening; and 4) excessive shift in refractive error (≥ +0.75D). Each of these signs presents potential risk to a crewmember’s vision and mission effectiveness, with ODE posing the highest risk overall. It is not yet known what severity and/or duration of these signs might lead to acute or permanent impacts to ocular anatomy or visual performance. Brain anatomical changes also occur during long-duration spaceflight and are being monitored in the astronaut population; however, these changes have not yet been associated with functional decrements or with SANS. An update will be provided on the latest SANS clinical analyses, diagnostics, and program initiatives. METHODS Data were obtained from clinical records and SANS subject matter experts (SMEs) to compile a SANS clinical update. Areas of interest include: 1) prevalence of SANS signs, 2) defining clinical thresholds for SANS, and 3) an overview of current and planned SANS clinical efforts. DISCUSSION SANS Sign Prevalence: Analysis at the time of this abstract submission indicates that the approximate prevalence of primary SANS findings in USOS LDSF crewmembers is: 64% for ODE (≥ 20-micron ΔTRT), 15% for chorioretinal folds, 26% for globe flattening, and 14% for hyperopic shifts in refractive error (≥ +0.75D). Clinical Thresholds:  The Earliest Indication of SANS was presented publicly for the first time at the 2020 NASA Human Research Program Investigators’ Workshop. See definition in Introduction section (above).  Clinically Concerning SANS – Development of any of the following signs during or immediately following spaceflight: 1) ODE (≥ 55-micron ΔTRT* and/or Frisèn grade ≥1*), 2) sharp chorioretinal folds in the vicinity of the macula, or 3) moderate globe flattening.  Pathological SANS with an Acute Functional Impact – Development of any of the following signs/symptoms during or immediately following spaceflight: 1) visual field loss (e.g., enlarged blindspot), 2) distorted centralvision, or 3) shift in refractive error beyond power of available correction (e.g., “space anticipation glasses”).  Pathological SANS affecting Long-Term Health – Development of any of the following signs/symptoms during or following spaceflight: 1) permanent visual field loss, 2) reduced retinal nerve fiber layer (RNFL) thickness, 3) permanently distorted central vision, 4) atrophy of retinal pigment epithelium (RPE) or photoreceptors, or 5) choroidal neovascularization. Current & Planned Clinical Efforts (accurate at time of abstract submission): All SANS diagnostic hardware are performing nominally onboard the International Space Station: vision screening, fundoscope, optical coherence tomography (OCT) device, ultrasound, and tonometer. The Goggle-Based Visual Field (GBVF) device is nearing completion of its clinical validation study at Ohio State University and is planned for parabolic flight testing in fiscal year 2023 (FY23); pending positive results, this sequence may pave the way towards an ISS technology demonstration in FY24.

T J Brunstetter↗

Defining Change Thresholds: What Change Is Outside Typical Sources of Variation?

Researchers often have a difficult time defining meaningful thresholds for change. We sometimes identify subtle changes but what amount of change is beyond typical sources of variation? This is especially complicated when trying to understand new disease pathogenesis like the constellation of eye changes leading to Spaceflight-associated Neuro-ocular Syndrome (SANS). To support decision makers in defining minimal meaningful change, we used a Bayesian hierarchical model to estimate innate sources of variability such as natural day to day variation. Healthy subjects were recruited and imaged with MRI, OCT, and US on separate days and measured by several technicians. Models were developed specifying random effects for the sources of variation – between left and right eyes, within-individuals over time, between raters, and finally between individuals. This allowed us to find the posterior distribution for the total typical variation, within an eye, which we use to define a threshold where change beyond typical sources of variation is likely. This threshold is now used as our earliest indicator of systematic increase in Total Retinal Thickness (a precursor to optic disc edema).

Millennia Young↗

Effect of Strict Head Down Tilt Bedrest on Pituitary Gland Height

BACKGROUND Pituitary gland deformity and loss of pituitary height have been identified in astronauts postflight, hypothesized to be related to increased intracranial pressure or intracranial pressure pulsatility exposure from prolonged weightlessness. Microgravity-induced chronic headward fluid shift has been suggested as a root cause of intracranial compliance changes leading to altered intracranial pressure dynamics. Elevated intracranial pressure or pressure pulsatility is theorized to promote the development of an arachnoid diverticulum, which herniates into the pituitary fossa via a defect in the diaphragma sellae compressing the pituitary gland. We aimed to determine if chronic headward fluid induced by strict head-down tilt bed rest (HDTBR) can cause similar quantitative changes in pituitary gland height. METHODS Control group data from two 6-degree HDTBR studies were analyzed (SANS CM and AGBRESA). The AGBRESA study collected MRI data at Baseline, 14 days into HDTBR (HDTBR-14), 52 days into HDTBR (HDTBR-52), and three days into Recovery (R+ 3) and included eight healthy adults (2 women), age = 33 ± 8 years. The SANS CM collected MRI data at Baseline, 15 days into HDTBR (HDTBR-15), 29 days into HDTBR (HDTBR-29), and 12 days into Recovery (R+12) and included twelve healthy adults (4 women), age = 34 ± 9 years. Pituitary gland height was evaluated using a sagittal, 3D T1-MPRAGE sequence obtained on a dedicated 3T Siemens Biograph MRI scanner using a 32-channel head coil. Following the reconstruction of a true orthogonal sagittal plane of the pituitary gland using a 3D multiplanar reconstruction tool (Horosproject.org), the anterior pituitary mid-gland height at the pituitary stalk level was quantified according to the methodology described by Kramer et al. . A paired t-test was used to evaluate changes from the baseline measurements. FINDINGS The mean height of the pituitary gland at baseline was 6.5 ± 1.7 mm (AGBRESA) and 5.7 ± 1.6 mm (SANS CM). From baseline measurements, the SANS CM STUDY data showed a decrease in mean pituitary height of 0.3 mm (p=.011) at HDTBR-15, 0.5 mm at HDTBR-29 (p<.001) and 0.2 mm at R+12 (p=.02). From baseline measurements, the AGBRESA data showed a decrease in mean pituitary height of 0.3 mm (p=.06) at HDTBR-14, 0.6 mm at HDTBR-52 (p<.002) and 0.2 mm at R+3 (p=.13). CONCLUSION HDTBR results in progressive loss of pituitary height, which is most severe with the longest HDTBR exposure. Early pituitary height loss was the same at HDTBR-14 (AGBRESA) and HDTBR-15 (SANS CM). Residual pituitary height loss was the same at R+12 and R+3 but only significant in the latter (SANS CM). The degree of pituitary height loss at HDTBR-52 replicates the 0.6 mm height loss found in long-duration astronauts after approximately six months of microgravity exposure (p<.01, preflight mean height=5.9 mm). The hormonal effects of pituitary height loss are unknown in astronauts and HDTBR subjects and should be investigated in future studies. Future work will examine the individual variability in the loss of pituitary gland height and whether those changes are associated with other SANS findings, such as optic disc edema.

L A Kramer↗