Spaceflight-Induced Intracranial Hypertension and Visual Impairment: Pathophysiology and Countermeasures.

Visual impairment intracranial pressure (VIIP) syndrome is considered an unexplained major risk for future long-duration spaceflight. NASA recently redefined this syndrome as Spaceflight-Associated Neuro-ocular Syndrome (SANS). Evidence thus reviewed supports that chronic, mildly elevated intracranial pressure (ICP) in space (as opposed to more variable ICP with posture and activity on Earth) is largely accounted for by loss of hydrostatic pressures and altered hemodynamics in the intracranial circulation and the cerebrospinal fluid system. In space, an elevated pressure gradient across the lamina cribrosa, caused by a chronic but mildly elevated ICP, likely elicits adaptations of multiple structures and fluid systems in the eye which manifest themselves as the VIIP syndrome. A chronic mismatch between ICP and intraocular pressure (IOP) in space may acclimate the optic nerve head, lamina cribrosa, and optic nerve subarachnoid space to a condition that is maladaptive to Earth, all contributing to the pathogenesis of space VIIP syndrome. Relevant findings help to evaluate whether artificial gravity is an appropriate countermeasure to prevent this seemingly adverse effect of long-duration spaceflight.

Cerebrovascular Effects of Lower Body Negative Pressure at 3T MRI: Implications for Long-Duration Space Travel.

BACKGROUND: Optic disc edema develops in most astronauts during long-duration spaceflight. It is hypothesized to result from weightlessness-induced venous congestion of the head and neck and is an unresolved health risk of space travel. PURPOSE: Determine if short-term application of lower body negative pressure (LBNP) could reduce internal jugular vein (IJV) expansion associated with the supine posture without negatively impacting cerebral perfusion or causing IJV flow stasis. STUDY TYPE: Prospective. SUBJECTS: Nine healthy volunteers (six women). FIELD STRENGTH/SEQUENCE: 3T/cine two-dimensional phase-contrast gradient echo; pseudo-continuous arterial spin labeling single-shot gradient echo echo-planar. ASSESSMENT: The study was performed with two sequential conditions in randomized order: supine posture and supine posture with 25 mmHg LBNP (LBNP25 ). LBNP was achieved by enclosing the lower extremities in a semi-airtight acrylic chamber connected to a vacuum. Heart rate, bulk cerebrovasculature flow, IJV cross-sectional area, fractional IJV outflow relative to arterial inflow, and cerebral perfusion were assessed in each condition. STATISTICAL TESTS: Paired t-tests were used to compare measurement means across conditions. Significance was defined as P < 0.05. RESULTS: LBNP25 significantly increased heart rate from 64 ± 9 to 71 ± 8 beats per minute and significantly decreased IJV cross-sectional area, IJV outflow fraction, cerebral arterial flow rate, and cerebral arterial stroke volume from 1.28 ± 0.64 to 0.56 ± 0.31 cm2 , 0.75 ± 0.20 to 0.66 ± 0.28, 780 ± 154 to 708 ± 137 mL/min and 12.2 ± 2.8 to 9.7 ± 1.7 mL/cycle, respectively. During LBNP25 , there was no significant change in gray or white matter cerebral perfusion (P = 0.26 and P = 0.24 respectively) and IJV absolute mean peak flow velocity remained ≥4 cm/sec in all subjects. DATA CONCLUSION: Short-term application of LBNP25 reduced IJV expansion without decreasing cerebral perfusion or inducing IJV flow stasis. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Using hierarchical unsupervised learning to integrate and reduce multi-level and multi-paraspinal muscle MRI data in relation to low back pain.

PURPOSE: The paraspinal muscles (PSM) are a key feature potentially related to low back pain (LBP), and their structure and composition can be quantified using MRI. Most commonly, quantifying PSM measures across individual muscles and individual spinal levels renders numerous separate metrics that are analyzed in isolation. However, comprehensive multivariate approaches would be more appropriate for analyzing the PSM within an individual. To establish and test these methods, we hypothesized that multivariate summaries of PSM MRI measures would associate with the presence of LBP symptoms (i.e., pain intensity). METHODS: We applied hierarchical multiple factor analysis (hMFA), an unsupervised integrative method, to clinical PSM MRI data from unique cohort datasets including a longitudinal cohort of astronauts with pre- and post-spaceflight data and a cohort of chronic LBP subjects and asymptomatic controls. Three specific use cases were investigated: (1) predicting longitudinal changes in pain using combinations of baseline PSM measures; (2) integrating baseline and post-spaceflight MRI to assess longitudinal change in PSM and how it relates to pain; and (3) integrating PSM quality and adjacent spinal pathology between LBP patients and controls. RESULTS: Overall, we found distinct complex relationships with pain intensity between particular muscles and spinal levels. Subjects with high asymmetry between left and right lean muscle composition and differences between spinal segments PSM quality and structure are more likely to increase in pain reported outcome after prolonged time in microgravity. Moreover, changes in PSM quality and structure between pre and post-spaceflight relate to increase in pain after prolonged microgravity. Finally, we show how unsupervised hMFA recapitulates previous research on the association of CEP damage and LBP diagnostic. CONCLUSION: Our analysis considers the spine as a multi-segmental unit as opposed to a series of discrete and isolated spine segments. Integrative and multivariate approaches can be used to distill large and complex imaging datasets thereby improving the clinical utility of MRI-based biomarkers, and providing metrics for further analytical goals, including phenotyping.

Visual disturbances during prolonged space missions.

PURPOSE OF REVIEW: During prolonged spaceflight, astronauts often experience ocular changes, due to constant head-ward fluid shifts in space as compared with Earth. This article reviews symptoms, likely causes, and potential solutions, such as lower body negative pressure, to counteract space-associated neuroocular syndrome (SANS). RECENT FINDINGS: Low gravity conditions and other aspects of spaceflight affect the eye detrimentally, causing SANS which is characterized by optic disc edema, choroidal thickening, cotton wool spots, and a hyperopic shift. SANS is probably caused by altered hemodynamic flows in the head and neck as well as mildly elevated intracranial and intraocular pressures. Carbon dioxide and other chemicals in space-craft may influence SANS as well. SANS may be counteracted by using lower body negative pressure, thigh cuffs, spacecraft engineering, and/or artificial gravity by a centrifuge. SUMMARY: Prolonged space missions are associated with optic disc edema, choroidal thickening, cotton wool spots, and a hyperopic shift. Possible causes and countermeasures are currently being researched to reduce the risk of SANS. Although many countermeasures to SANS are under investigation lower body negative pressure exhibits great promise in counteracting the headward fluid shifts in space. Understanding and prevention of SANS is critical to future space exploration, especially to long-duration missions to the moon and Mars.

The effect of simulated microgravity on lumbar spine biomechanics: an in vitro study.

PURPOSE: Disc herniation risk is quadrupled following spaceflight. This study tested the hypothesis that swelling-induced disc height increases (comparable to those reported in spaceflight) stiffen the spine and elevate annular strain and nuclear pressure during forward bending. METHODS: Eight human lumbar motion segments were secured to custom-designed testing jigs and subjected to baseline flexion and compression and pure moment flexibility tests. Discs were then free-swelled in saline to varying supraphysiologic heights consistent with prolonged weightlessness and re-tested to assess biomechanical changes. RESULTS: Swelling-induced disc height changes correlated positively with intradiscal pressure (p < 0.01) and stiffening in flexion (p < 0.01), and negatively with flexion range of motion (p < 0.05). Swelling-induced increases in disc height also led to increased annular surface strain under combined flexion with compression. Disc wedge angle decreased with swelling (p < 0.05); this loss of wedge angle correlated with decreased flexion range of motion (R (2) = 0.94, p < 0.0001) and decreased stiffness fold change in extension (p < 0.05). CONCLUSION: Swelling-induced increases in disc height decrease flexibility and increase annular strain and nuclear pressure during forward bending. These changes, in combination with the measured loss of lordotic curvature with disc swelling, may contribute toward increased herniation risk. This is consistent with clinical observations of increased disc herniation rates after microgravity exposure and may provide the basis for future countermeasure development.

Disc herniations in astronauts: What causes them, and what does it tell us about herniation on earth?

PURPOSE: Recent work showed an increased risk of cervical and lumbar intervertebral disc (IVD) herniations in astronauts. The European Space Agency asked the authors to advise on the underlying pathophysiology of this increased risk, to identify predisposing factors and possible interventions and to suggest research priorities. METHODS: The authors performed a narrative literature review of the possible mechanisms, and conducted a survey within the team to prioritize research and prevention approaches. RESULTS AND CONCLUSIONS: Based on literature review the most likely cause for lumbar IVD herniations was concluded to be swelling of the IVD in the unloaded condition during spaceflight. For the cervical IVDs, the knowledge base is too limited to postulate a likely mechanism or recommend approaches for prevention. Basic research on the impact of (un)loading on the cervical IVD and translational research is needed. The highest priority prevention approach for the lumbar spine was post-flight care avoiding activities involving spinal flexion, followed by passive spinal loading in spaceflight and exercises to reduce IVD hyper-hydration post-flight.

Body posture and backpack loading: an upright magnetic resonance imaging study of the adult lumbar spine.

PURPOSE: Axial loading of the spine while supine, simulating upright posture, decreases intervertebral disc (IVD) height and lumbar length and increases lumbar lordosis. The purpose of this study is to measure the adult lumbar spine's response to upright posture and a backpack load using upright magnetic resonance imaging (MRI). We hypothesize that higher spinal loads, while upright and with a backpack, will compress lumbar length and IVD height as well as decrease lumbar lordosis. METHODS: Six volunteers (45 ± 6 years) underwent 0.6 T MRI scans of the lumbar spine while supine, upright, and upright with a 10 % body weight (BW) backpack. Main outcomes were IVD height, lumbar spinal length (distance between anterior-superior corners of L1 and S1), and lumbar lordosis (Cobb angle between the superior endplates of L1 and S1). RESULTS: The 10 % BW load significantly compressed the L4-L5 and L5-S1 IVDs relative to supine (p < 0.05). The upright and upright plus 10 % BW backpack conditions significantly compressed the anterior height of L5-S1 relative to supine (p < 0.05), but did not significantly change the lumbar length or lumbar lordosis. CONCLUSIONS: The L4-L5 and L5-S1 IVDs compress, particularly anteriorly, when transitioning from supine to upright position with a 10 % BW backpack. This study is the first radiographic analysis to describe the adult lumbar spine wearing common backpack loads. The novel upright MRI protocol described allows for functional, in vivo, loaded measurements of the spine that enables the study of spinal biomechanics and therapeutic interventions.

Intraocular/Intracranial pressure mismatch hypothesis for visual impairment syndrome in space.

Visual impairment intracranial pressure syndrome (VIIP) is considered a major risk for future human spaceflight. Loss of hydrostatic pressure gradients in vascular and cerebrospinal fluid systems due to the removal of gravity associated with subsequent intracranial and intraocular fluid shifts and the resulting intraocular/intracranial pressure mismatch might be important etiology factors causingVIIP syndrome. Acclimation changes in the ocular and cerebral circulation and the two fluid systems during chronic microgravity exposure and their underlying mechanisms need further elucidation. Relevant findings may help to validate the pressure differential hypothesis for VlIP syndrome and to evaluate whether a gravity based countermeasure is needed.

Accuracy of water displacement hand volumetry using an ethanol and water mixture.

BACKGROUND: The traditional water displacement method for measuring limb volume is improved by adding ethanol to water. METHODS: Four solutions were tested (pure water, 0.5% ethanol, 3% ethanol, and 6% ethanol) to determine the most accurate method when measuring the volume of a known object. RESULTS: The 3% and 6% ethanol solutions significantly reduced (P < 0.001) the mean standard deviation of 10 measurements of a known sphere (390.1 +/- 0.25 mi) from 2.27 ml with pure water to 0.9 ml using the 3% alcohol solution and to 0.6 using 6% ethanol solution (the mean coefficients of variation were reduced from 0.59% for water to 0.22% for 3% ethanol and 0.16% for 6% ethanol). The spheres' volume measured with pure water, 0.5% ethanol solution, 3% ethanol solution, and 6% ethanol solution was 383.2 +/- 2.27 ml, 384.4 +/- 1.9 ml, 389.4 +/- 0.9 ml, and 390.2 +/- 0.6 ml, respectively. Using the 3% and 6% ethanol solutions to measure hand volume blindly in 10 volunteers significantly reduced the mean coefficient of variation for hand volumetry from 0.91% for water to 0.52% for the 3% ethanol solution (P < 0.05) and to 0.46% for the 6% ethanol solution (P < 0.05). The mean standard deviation from all 10 subjects decreased from 4.2 ml for water to 2.3 ml for 3% ethanol solution and 2.1 ml for the 6% solution. DISCUSSION: These findings document that the accuracy and reproducibility of hand volume measurements are improved by small additions of ethanol, most likely by reducing surface tension of water.

Self-Generated Lower Body Negative Pressure Exercise: A Low Power Countermeasure for Acute Space Missions.

Microgravity in spaceflight produces headward fluid shifts which probably contribute to Spaceflight-Associated Neuro-Ocular Syndrome (SANS). Developing new methods to mitigate these shifts is crucial for preventing SANS. One possible strategy is the use of self-generated lower body negative pressure (LBNP). This study evaluates biological or physiological effects induced by bed rest to simulate adaptations to microgravity. Participants were tested during powered LBNP and dynamic self-generated (SELF) LBNP at 25 mmHg for 15 min. The results were compared to the physiologic responses observed in seated upright and supine positions without LBNP, which served as controls for normal gravitational effects on fluid dynamics. Eleven participants' (five male, six female) heart rates, blood pressures, and cross-sectional areas (CSA) of left and right internal jugular veins (IJV) were monitored. Self-generated LBNP, which requires mild to moderate physical activity, significantly elevated heart rate and blood pressure (p < 0.01). Self-generated LBNP also significantly reduced right IJV CSA compared to supine position (p = 0.005), though changes on the left side were not significant (p = 0.365). While the effects of SELF and traditional LBNP on IJV CSA were largely similar, traditional LBNP significantly reduced IJV CSA on both sides. Given its low mass, volume, and power requirements, SELF LBNP is a promising countermeasure against SANS. Results from this study warrant longer-term studies of SELF LBNP under simulated spaceflight conditions.

Space physiology VI: exercise, artificial gravity, and countermeasure development for prolonged space flight.

When applied individually, exercise countermeasures employed to date do not fully protect the cardiovascular and musculoskeletal systems during prolonged spaceflight. Recent ground-based research suggests that it is necessary to perform exercise countermeasures within some form of artificial gravity to prevent microgravity deconditioning. In this regard, it is important to provide normal foot-ward loading and intravascular hydrostatic-pressure gradients to maintain musculoskeletal and cardiovascular function. Aerobic exercise within a centrifuge restores cardiovascular function, while aerobic exercise within lower body negative pressure restores cardiovascular function and helps protect the musculoskeletal system. Resistive exercise with vibration stimulation may increase the effectiveness of resistive exercise by preserving muscle function, allowing lower intensity exercises, and possibly reducing risk of loss of vision during prolonged spaceflight. Inexpensive methods to induce artificial gravity alone (to counteract head-ward fluid shifts) and exercise during artificial gravity (for example, by short-arm centrifuge or exercise within lower body negative pressure) should be developed further and evaluated as multi-system countermeasures.

Maximizing information from space data resources: a case for expanding integration across research disciplines.

Regulatory systems are affected in space by exposure to weightlessness, high-energy radiation or other spaceflight-induced changes. The impact of spaceflight occurs across multiple scales and systems. Exploring such interactions and interdependencies via an integrative approach provides new opportunities for elucidating these complex responses. This paper argues the case for increased emphasis on integration, systematically archiving, and the coordination of past, present and future space and ground-based analogue experiments. We also discuss possible mechanisms for such integration across disciplines and missions. This article then introduces several discipline-specific reviews that show how such integration can be implemented. Areas explored include: adaptation of the central nervous system to space; cerebral autoregulation and weightlessness; modelling of the cardiovascular system in space exploration; human metabolic response to spaceflight; and exercise, artificial gravity, and physiologic countermeasures for spaceflight. In summary, spaceflight physiology research needs a conceptual framework that extends problem solving beyond disciplinary barriers. Administrative commitment and a high degree of cooperation among investigators are needed to further such a process. Well-designed interdisciplinary research can expand opportunities for broad interpretation of results across multiple physiological systems, which may have applications on Earth.

Movement-induced knot migration after anterior stabilization in the shoulder.

PURPOSE: This study compared the status of suture knots immediately after repair and after shoulder motion to evaluate the possibility of movement-induced knot migration to a location nearer the glenoid. METHODS: We included 10 shoulders from 5 cadavers in the study. After posterior capsulotomy, a Bankart lesion was created. A capsulolabral repair was then performed with 3 knot-tying suture anchors. All knots were positioned on the capsular side, far from the articular surface. After the repair was complete, a photograph was taken with a metal rod placed to reference absolute distance. After passive pendulum motion was applied, another photograph was taken. The length of the suture strand from the knot base to the anchor insertion site was measured during both the initial repair and post-motion periods. RESULTS: Initial distances were 4.83 ± 1.09 mm for the inferior knot, 4.70 ± 0.97 mm for the middle knot, and 3.84 ± 1.25 mm for the superior knot. After motion, the distances were 3.52 ± 1.21 mm (P = .01), 3.07 ± 0.81 mm (P < .001), and 2.69 ± 1.18 mm (P = .016), respectively. Additional observations showed changes in direction and security of the knot. The change in knot direction from an initial orientation facing the capsular side to a new orientation facing the glenoid was observed in 5 of 10 inferior, 7 of 10 middle, and 6 of 10 superior knots. In addition, knot loosening was noted for the last half-hitches in 4 inferior knots and 1 middle knot. CONCLUSIONS: Intentional placement of suture knots away from the joint surface was not maintained after motion at the shoulder. CLINICAL RELEVANCE: Movement-induced knot migration may be detrimental to articular cartilage in the event that a knot becomes interposed between the glenoid and humeral head.

Loop securities of arthroscopic sliding-knot techniques when the suture loop is not evenly tensioned.

PURPOSE: The purpose of this study was to evaluate the loop security of arthroscopic sliding knots when tension is only applied to the post strand and not the loop strand. METHODS: Six different locking sliding knots (Weston, Nicky, Roeder, SMC, San Diego, and Dines) were included. Loop securities were evaluated in 2 ways: with a conventional method (equal tension applied to the suture loop) and with a worst-case scenario (WCS) method (only the post strand of the suture loop was tensioned). Differences between test methods were evaluated for significance. To help assess the applicability of each test method, loop-security testing in a cadaveric shoulder was performed with 1 type of knot (SMC). RESULTS: Loop securities with the conventional method versus the WCS method were as follows: 10.74 ± 4.20 N versus 6.90 ± 3.90 N for Weston, 21.25 ± 14.74 N versus 8.73 ± 3.35 N for Nicky, 26.14 ± 15.57 N versus 7.95 ± 4.23 N for Roeder, 42.67 ± 22.96 N versus 8.67 ± 4.33 N for SMC, 52.99 ± 21.36 N versus 18.25 ± 10.58 N for San Diego, and 89.27 ± 27.96 N versus 12.48 ± 3.40 N for Dines (P < .05 for each knot). All knots failed at significantly lower loads when the suture loop was not evenly tensioned. Cadaveric testing (SMC) resulted in a loop security of 5.53 ± 6.06 N, which was similar to the WCS setting. CONCLUSIONS: The locking mechanism of the sliding knots is maintained when the suture loop is evenly tensioned at both post and non-post strands. When tension is not applied to the non-post strand side, the knots slide more easily and fail at lower loads than previously reported. CLINICAL RELEVANCE: When surgeons tie locking sliding knots in single-row rotator cuff repair, they should be aware that the knots could fail at much lower loads than previously reported.

Anterior-posterior transcranial ultrasound to measure cranial oscillations.

BACKGROUND: We aimed to provide information on whether or not the correlation between body tilt and the pulse amplitude of transcranial ultrasonic time-of-flight waveform can be observed in the anterior-posterior skull direction. Also, we asked the question whether or not the skull pulsation can be detected since the cranial bones involved are thicker. METHODS: The experimental model of body tilt that alters intracranial pressure by shifting body fluid headward was employed. Transcranial ultrasound waveforms were examined in 15 healthy volunteers positioned at five tilt angles of +30 degrees, 0 degrees, -30 degrees, -60 degrees, and -90 degrees from the horizontal body position. A pulse-echo transducer was placed on the middle forehead and ultrasound waveforms were recorded. Synchronized variations in the ultrasonic time-of-flight with heartbeats were monitored using the pulsed phase locked loop technique for the output voltage of the ultrasound transducer. Simultaneous effects of body tilt on cardiovascular parameters were also evaluated. RESULTS: Pulse amplitudes of ultrasonic time-of-flight waveforms were found to vary with body tilt. Repeated-measures ANOVA and regression analysis showed a negative correlation between body tilt angle and pulse amplitude. The regression line has the equation: pulse amplitude = (1.158-0.01023 x tilt angle) x 10(-4) voltage. There was no such relationship between head-down body tilt and altered mean blood pressure or heart rate. CONCLUSION: An increase in the pulse amplitude of the anterior-posterior transcranial ultrasonic time-of-flight waveform can be detected when the head-down body tilt angle increases.

Cardiovascular, Lymphatic, and Ocular Health in Space.

Life on Earth has evolved continuously under Earth's 1 G force and the protection of the magnetosphere. Thus, astronauts exhibit maladaptive physiological responses during space travel. Exposure to harmful cosmic radiation and weightlessness are unique conditions to the deep-space environment responsible for several spaceflight-associated risks: visual impairment, immune dysfunction, and cancer due to cosmic radiation in astronauts. The evidence thus reviewed indicates that microgravity and cosmic radiation have deleterious effects on the cardiovascular, lymphatic, and vision systems of astronauts on long-duration space missions. The mechanisms responsible for the decline in these systems are potentially due to cytoskeletal filament rearrangement, endothelial dysfunction, and muscular atrophy. These factors may alter fluid hemodynamics within cardiovascular and lymphatic vasculatures such that greater fluid filtration causes facial and intracranial edema. Thus, microgravity induces cephalad fluid shifts contributing to spaceflight-associated neuro-ocular syndrome (SANS). Moreover, visual impairment via retinal ischemia and altered nitric oxide production may alter endothelial function. Based on rodent studies, cosmic radiation may exacerbate the effects of microgravity as observed in impaired endothelium and altered immunity. Relevant findings help understand the extent of these risks associated with spaceflight and suggest relevant countermeasures to protect astronaut health during deep-space missions.

Spaceflight-Associated Vascular Remodeling and Gene Expression in Mouse Calvaria.

Astronauts suffer from a loss of bone mass at a rate of 1.5% per month from lower regions of the body during the course of long-duration (>30 days) spaceflight, a phenomenon that poses important risks for returning crew. Conversely, a gain in bone mass may occur in non-load bearing regions of the body as related to microgravity-induced cephalad fluid shift. Representing non-load bearing regions with mouse calvaria and leveraging the STS-131 (15-day) and BION-M1 (30-day) flights, we examined spatial and temporal calvarial vascular remodeling and gene expression related to microgravity exposure compared between spaceflight (SF) and ground control (GC) cohorts. We examined parasagittal capillary numbers and structures in calvaria from 16 to 23 week-old C57BL/6 female mice (GC, n = 4; SF, n = 5) from STS-131 and 19-20 week-old C57BL/6 male mice (GC, n = 6; SF, n = 6) from BION-M1 using a robust isolectin-IB4 vessel marker. We found that the vessel diameter reduces significantly in mice exposed to 15 days of spaceflight relative to control. Capillarization increases by 30% (SF vs. GC, p = 0.054) in SF mice compared to GC mice. The vessel numbers and diameter remain unchanged in BION-M1 mice calvarial section. We next analyzed the parietal pro-angiogenic (VEGFA) and pro-osteogenic gene (BMP-2, DMP1, RUNX2 and OCN) expression in BION-M1 mice using quantitative RT-PCR. VEGFA gene expression increased 15-fold while BMP-2 gene expression increased 11-fold in flight mice compared to GC. The linkage between vascular morphology and gene expression in the SF conditions suggests that angiogenesis may be important in the regulation of pathological bone growth in non-weight bearing regions of the body. Short-duration microgravity-mediated bone restructuring has implications in planning effective countermeasures for long-duration flights and extraterrestrial human habitation.

Changes in Optic Nerve Head and Retinal Morphology During Spaceflight and Acute Fluid Shift Reversal.

Importance: Countermeasures that reverse the headward fluid shift experienced in weightlessness have the potential to mitigate spaceflight-associated neuro-ocular syndrome. This study investigated whether use of the countermeasure lower-body negative pressure during spaceflight was associated with changes in ocular structure. Objective: To determine whether changes to the optic nerve head and retina during spaceflight can be mitigated by brief in-flight application of 25-mm Hg lower-body negative pressure. Design, Setting, and Participants: In the National Aeronautics and Space Administration's "Fluid Shifts Study," a prospective cohort study, optical coherence tomography scans of the optic nerve head and macula were obtained from US and international crew members before flight, in-flight, and up to 180 days after return to Earth. In-flight scans were obtained both under normal weightless conditions and 10 to 20 minutes into lower-body negative pressure exposure. Preflight and postflight data were collected in the seated, supine, and head-down tilt postures. Crew members completed 6- to 12-month missions that took place on the International Space Station. Data were analyzed from 2016 to 2021. Interventions or Exposures: Spaceflight and lower-body negative pressure. Main Outcomes and Measures: Changes in minimum rim width, optic cup volume, Bruch membrane opening height, peripapillary total retinal thickness, and macular thickness. Results: Mean (SD) flight duration for the 14 crew members (mean [SD] age, 45 [6] years; 11 male crew members [79%]) was 214 (72) days. Ocular changes on flight day 150, as compared with preflight seated, included an increase in minimum rim width (33.8 µm; 95% CI, 27.9-39.7 µm; P < .001), decrease in cup volume (0.038 mm3; 95% CI, 0.030-0.046 mm3; P < .001), posterior displacement of Bruch membrane opening (-9.0 µm; 95% CI, -15.7 to -2.2 µm; P = .009), and decrease in macular thickness (fovea to 500 µm, 5.1 µm; 95% CI, 3.5-6.8 µm; P < .001). Brief exposure to lower-body negative pressure did not affect these parameters. Conclusions and Relevance: Results of this cohort study suggest that peripapillary tissue thickening, decreased cup volume, and mild central macular thinning were associated with long-duration spaceflight. Acute exposure to 25-mm Hg lower-body negative pressure did not alter optic nerve head or retinal morphology, suggesting that longer durations of a fluid shift reversal may be needed to mitigate spaceflight-induced changes and/or other factors are involved.

Biomechanical changes in the lumbar spine following spaceflight and factors associated with postspaceflight disc herniation.

BACKGROUND CONTEXT: For chronic low back pain, the causal mechanisms between pathological features from imaging and patient symptoms are unclear. For instance, disc herniations can often be present without symptoms. There remains a need for improved knowledge of the pathophysiological mechanisms that explore spinal tissue damage and clinical manifestations of pain and disability. Spaceflight and astronaut health provides a rare opportunity to study potential low back pain mechanisms longitudinally. Spaceflight disrupts diurnal loading on the spine and several lines of evidence indicate that astronauts are at a heightened risk for low back pain and disc herniation following spaceflight. PURPOSE: To examine the relationship between prolonged exposure to microgravity and the elevated incidence of postflight disc herniation, we conducted a longitudinal study to track the spinal health of twelve NASA astronauts before and after approximately 6 months in space. We hypothesize that the incidence of postflight disc herniation and low back complaints associates with spaceflight-included muscle atrophy and pre-existing spinal pathology. STUDY DESIGN: This is a prospective longitudinal study. PATIENT SAMPLE: Our sample included a cohort of twelve astronaut crewmembers. OUTCOME MEASURES: From 3T MRI, we quantified disc water content (ms), disc degeneration (Pfirrmann grade), vertebral endplate irregularities, facet arthropathy and/ fluid, high intensity zones, disc herniation, multifidus total cross-sectional area (cm2), multifidus lean muscle cross-sectional area (cm2), and muscle quality/composition (%). From quantitative fluoroscopy we quantified, maximum flexion-extension ROM (°), maximum lateral bending ROM (°), and maximum translation (%). Lastly, patient outcomes and clinical notes were used for identifying postflight symptoms associated with disc herniations from 3T MRI. METHODS: Advanced imaging data from 3T MRI were collected at three separate time points in relation to spending six months in space: (1) within a year before launch ("pre-flight"), (2) within a week after return to Earth ("post-flight"), and (3) between 1 and 2 months after return to Earth ("recovery"). Fluoroscopy of segmental kinematics was collected at preflight and postflight timepoints. We assessed the effect of spaceflight and postflight recovery on longitudinal changes in spinal structure and function, as well as differences between crew members who did and did not present a symptomatic disc herniation following spaceflight. RESULTS: Half of our astronauts (n=6) experienced new symptoms associated with a new or previously asymptomatic lumbar disc protrusion or extrusion following spaceflight. We observed decreased multifidus muscle quality following spaceflight in the lower lumbar spine, with a reduced percentage of lean muscle at L4L5 (-6.2%, p=.009) and L5S1 (-7.0%, p=.006) associated with the incidence of new disc herniation. Additionally, we observed reduced lumbar segment flexion-extension ROM for L2L3 (-17.2%, p=.006) and L3L4 (-20.5%, p=.02) following spaceflight, and furthermore that reduced ROM among the upper three lumbar segments (-24.1%, p=.01) associated with the incidence of disc herniation. Existing endplate pathology was most prevalent in the upper lumbar spine and associated with reduced segmental ROM (-20.5%, p=.02). CONCLUSIONS: In conclusion from a 10-year study investigating the effects of spaceflight on the lumbar spine and risk for disc herniation, we found the incidence of lumbar disc herniation following spaceflight associates with compromised multifidus muscle quality and spinal segment kinematics, as well as pre-existing spinal endplate irregularities. These findings suggest differential effects of spinal stiffness and muscle loss in the upper versus lower lumbar spine regions that may specifically provoke risk for symptomatic disc herniation in the lower lumbar spine following spaceflight. Results from this study provide a unique longitudinal assessment of mechanisms and possible risk factors for developing disc herniations and related low back pain. Furthermore, these findings will help inform physiologic countermeasures to maintain spinal health in astronauts during long-duration missions in space.