MRI-based quantification of posterior ocular globe flattening during 60 days of strict 6° head-down tilt bed rest with and without daily centrifugation.

Spaceflight associated neuro-ocular syndrome (SANS) is associated with acquired optic disc edema, hyperopia, and posterior globe flattening in some astronauts during long-duration spaceflight possibly due to the headward fluid redistribution in microgravity. The goal of this study was to assess whether strict head-down tilt (HDT) bed rest as a spaceflight analog would produce globe flattening and whether centrifugation could prevent these changes. Twenty-four healthy subjects separated into three groups underwent 60 days of strict 6° HDT bed rest: one control group with no countermeasure (n = 8) and two countermeasure groups exposed to 30 min daily of short-arm centrifugation as a means of artificial gravity (AG), either intermittent (iAG, n = 8) or continuous (cAG, n = 8). Magnetic resonance images (MRI) were collected at baseline, HDT-day 14, HDT-day 52, and 3 days after bed rest. An automated method was applied to quantify posterior globe volume displacement compared with baseline scans. On average, subjects showed an increasing degree of globe volume displacement with bed rest duration (means ± SE: 1.41 ± 1.01 mm3 on HDT14 and 4.04 ± 1.19 mm3 on HDT52) that persisted post-bed rest (5.51 ± 1.26 mm3). Application of 30 min daily AG did not have a significant impact on globe volume displacement (P = 0.42 for cAG and P = 0.93 for iAG compared with control). These results indicate that strict 6° HDT bed rest produced displacement of the posterior globe with a trend of increasing displacement with longer duration that was not prevented by daily 30 min exposure to AG.NEW & NOTEWORTHY Head-down tilt (HDT) bed rest is commonly used as a spaceflight analog for investigating spaceflight associated neuro-ocular syndrome (SANS). Posterior ocular globe flattening has been identified in astronauts with SANS but until now has not been investigated during HDT bed rest. In this study, posterior ocular globe volume displacement was quantified before, during, and after HDT bed rest and countermeasures were tested for their potential to reduce the degree of globe flattening.

Optic nerve sheath diameter and spaceflight: defining shortcomings and future directions.

Neuro-ocular changes during long-duration space flight are known as spaceflight-associated neuro-ocular syndrome (SANS). The ability to detect, monitor, and prevent SANS is a priority of current space medicine research efforts. Optic nerve sheath diameter (ONSD) measurement has been used both terrestrially and in microgravity as a proxy for measurements of elevated intracranial pressure. ONSD shows promise as a potential method of identifying and quantitating neuro-ocular changes during space flight. This review examines 13 studies measuring ONSD and its relationship to microgravity exposure or ground-based analogs, including head-down tilt, dry immersion, or animal models. The goal of this correspondence is to describe heterogeneity in the use of ONSD in the current SANS literature and make recommendations to reduce heterogeneity in future studies through standardization of imaging modalities, measurement techniques, and other aspects of study design.

Human Health during Space Travel: State-of-the-Art Review.

The field of human space travel is in the midst of a dramatic revolution. Upcoming missions are looking to push the boundaries of space travel, with plans to travel for longer distances and durations than ever before. Both the National Aeronautics and Space Administration (NASA) and several commercial space companies (e.g., Blue Origin, SpaceX, Virgin Galactic) have already started the process of preparing for long-distance, long-duration space exploration and currently plan to explore inner solar planets (e.g., Mars) by the 2030s. With the emergence of space tourism, space travel has materialized as a potential new, exciting frontier of business, hospitality, medicine, and technology in the coming years. However, current evidence regarding human health in space is very limited, particularly pertaining to short-term and long-term space travel. This review synthesizes developments across the continuum of space health including prior studies and unpublished data from NASA related to each individual organ system, and medical screening prior to space travel. We categorized the extraterrestrial environment into exogenous (e.g., space radiation and microgravity) and endogenous processes (e.g., alteration of humans' natural circadian rhythm and mental health due to confinement, isolation, immobilization, and lack of social interaction) and their various effects on human health. The aim of this review is to explore the potential health challenges associated with space travel and how they may be overcome in order to enable new paradigms for space health, as well as the use of emerging Artificial Intelligence based (AI) technology to propel future space health research.

Optic disc edema and chorioretinal folds develop during strict 6° head-down tilt bed rest with or without artificial gravity.

Spaceflight associated neuro-ocular syndrome (SANS) is hypothesized to develop as a consequence of the chronic headward fluid shift that occurs in sustained weightlessness. We exposed healthy subjects (n = 24) to strict 6° head-down tilt bed rest (HDTBR), an analog of weightlessness that generates a sustained headward fluid shift, and we monitored for ocular changes similar to findings that develop in SANS. Two-thirds of the subjects received a daily 30-min exposure to artificial gravity (AG, 1 g at center of mass, ~0.3 g at eye level) during HDTBR by either continuous (cAG, n = 8) or intermittent (iAG, n = 8) short-arm centrifugation to investigate whether this intervention would attenuate headward fluid shift-induced ocular changes. Optical coherence tomography images were acquired to quantify changes in peripapillary total retinal thickness (TRT), retinal nerve fiber layer thickness, and choroidal thickness, and to detect chorioretinal folds. Intraocular pressure (IOP), optical biometry, and standard automated perimetry data were collected. TRT increased by 35.9 µm (95% CI, 19.9-51.9 µm, p < 0.0001), 36.5 µm (95% CI, 4.7-68.2 µm, p = 0.01), and 27.6 µm (95% CI, 8.8-46.3 µm, p = 0.0005) at HDTBR day 58 in the control, cAG, and iAG groups, respectively. Chorioretinal folds developed in six subjects across the groups, despite small increases in IOP. Visual function outcomes did not change. These findings validate strict HDTBR without elevated ambient CO2 as a model for investigating SANS and suggest that a fluid shift reversal of longer duration and/or greater magnitude at the eye may be required to prevent or mitigate SANS.

Acute encephalitis, myoclonus and Sweet syndrome after mRNA-1273 vaccine.

A patient presented with fever, generalised rash, confusion, orofacial movements and myoclonus after receiving the first dose of mRNA-1273 vaccine from Moderna. MRI was unremarkable while cerebrospinal fluid showed leucocytosis with lymphocyte predominance and hyperproteinorrachia. The skin evidenced red, non-scaly, oedematous papules coalescing into plaques with scattered non-follicular pustules. Skin biopsy was consistent with a neutrophilic dermatosis. The patient fulfilled the criteria for Sweet syndrome. A thorough evaluation ruled out alternative infectious, autoimmune or malignant aetiologies, and all manifestations resolved with glucocorticoids. While we cannot prove causality, there was a temporal correlation between the vaccination and the clinical findings.

Exploration of Multiparameter Hematoma 3D Image Analysis for Predicting Outcome After Intracerebral Hemorrhage.

BACKGROUND: Rapid diagnosis and proper management of intracerebral hemorrhage (ICH) play a crucial role in the outcome. Prediction of the outcome with a high degree of accuracy based on admission data including imaging information can potentially influence clinical decision-making practice. METHODS: We conducted a retrospective multicenter study of consecutive ICH patients admitted between 2012-2017. Medical history, admission data, and initial head computed tomography (CT) scan were collected. CT scans were semiautomatically segmented for hematoma volume, hematoma density histograms, and sphericity index (SI). Discharge unfavorable outcomes were defined as death or severe disability (modified Rankin Scores 4-6). We compared (1) hematoma volume alone; (2) multiparameter imaging data including hematoma volume, location, density heterogeneity, SI, and midline shift; and (3) multiparameter imaging data with clinical information available on admission for ICH outcome prediction. Multivariate analysis and predictive modeling were used to determine the significance of hematoma characteristics on the outcome. RESULTS: We included 430 subjects in this analysis. Models using automated hematoma segmentation showed incremental predictive accuracies for in-hospital mortality using hematoma volume only: area under the curve (AUC): 0.85 [0.76-0.93], multiparameter imaging data (hematoma volume, location, CT density, SI, and midline shift): AUC: 0.91 [0.86-0.97], and multiparameter imaging data plus clinical information on admission (Glasgow Coma Scale (GCS) score and age): AUC: 0.94 [0.89-0.99]. Similarly, severe disability predictive accuracy varied from AUC: 0.84 [0.76-0.93] for volume-only model to AUC: 0.88 [0.80-0.95] for imaging data models and AUC: 0.92 [0.86-0.98] for imaging plus clinical predictors. CONCLUSIONS: Multiparameter models combining imaging and admission clinical data show high accuracy for predicting discharge unfavorable outcome after ICH.

Brain Physiological Response and Adaptation During Spaceflight.

More than half of astronauts returning from long-duration missions on the International Space Station present with neuro-ocular structural and/or functional changes, including optic disc edema, optic nerve sheath distension, globe flattening, choroidal folds, or hyperopic shifts. This spaceflight-associated neuro-ocular syndrome (SANS) represents a major risk to future exploration class human spaceflight missions, including Mars missions. Although the exact pathophysiology of SANS is unknown, evidence thus far suggests that an increase in intracranial pressure (ICP) relative to the upright position on Earth, which is due to the loss of hydrostatic pressure gradients in space, may play a leading role. This review focuses on brain physiology in the spaceflight environment, specifically on how spaceflight may affect ICP and related indicators of cranial compliance, potential factors related to the development of SANS, and findings from spaceflight as well as ground-based spaceflight analog research studies.

Serum magnesium level and hematoma expansion in patients with intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) is a devastating subtype of stroke that results in significant rates of mortality and morbidities. The initial hematoma volume, hematoma expansion (HE), blood pressure (BP), and coagulopathy are considered strong predictors of clinical outcomes and mortality. Low serum magnesium (Mg++) levels have been shown to be associated with larger initial hematoma and greater HE. Coagulopathy, platelet dysfunction, high BP, and increased inflammatory response might form the mechanistic link between low serum Mg++ levels, larger hematoma size and greater HE. However, randomized clinical trials administering intravenous Mg++ have shown no benefit over placebo in ICH patients. The confounding effect of hypocalcemia and a delay in Mg++ trafficking across the blood-brain barrier might explain the futile results for intravenous Mg++ therapy. In the current review, we will discuss the evidence regarding the possible role of low serum Mg++ level on HE in acute ICH.

The Role of Serum Calcium Level in Intracerebral Hemorrhage Hematoma Expansion: Is There Any?

Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke, with a high rate of mortality and morbidity. Even with the best current medical or surgical interventions, outcomes remain poor. The location and initial hematoma volume are strong predictors of mortality. Hematoma expansion (HE) is a further marker of poor prognosis that may be at least partly preventable. Several risk factors for HE have been identified, including baseline ICH volume, anticoagulation, and computed tomography angiography spot signs. Recent studies have shown the correlation of serum calcium (Ca++) levels on admission with HE. Low serum Ca++ level has been associated with larger hematoma volume at the time of presentation, HE, and worse outcome. Although the causal and mechanistic links between low serum Ca++ level and HE are not well understood, several mechanisms have been proposed including coagulopathy, platelet dysfunction, and higher blood pressure (BP) in the context of low serum Ca++ level. However, low serum Ca++ level might be only a biomarker of the adaptive response due to acute inflammatory response following acute ICH. The purpose of the current review is to discuss the evidence regarding the possible role of low serum Ca++ level on HE in acute ICH.

Quantitative Pupillometry for Detection of Intracranial Pressure Changes During Head-Down Tilt.

BACKGROUND: There is a need to develop noninvasive methods to monitor intracranial pressure (ICP). Pupillary reactivity decreases in patients with elevated ICP with demonstrated cerebral edema. We sought to determine whether pupillary reactivity is affected when ICP is elevated in the absence of brain edema. METHODS: Healthy subjects and individuals with idiopathic intracranial hypertension (IIH) underwent pupillometry in different positions (upright, supine, and head-down tilt) and during different physiological maneuvers. A separate group of healthy subjects were tested in the upright resting position only. The pupillary dynamics were measured with a pupillometer. RESULTS: Healthy and IIH subjects were enrolled. In the healthy subjects the change from upright to head-down tilt led to a Neurological Pupil Index (NPI) decrease from 4.30 to 4.12, while maximum pupil size and minimum pupil size increased from 4.74 to 5.19 and 3.04 to 3.44, respectively. In the IIH group the maximum pupil size, minimum pupil size, and latency increased in magnitude with a decline in head tilt. The mean NPI of IIH subjects, 4.37, was greater than the healthy mean, 4.25. Also, the mean IIH Max and Min, 5.02 and 3.25, were greater than the healthy mean, 4.62 and 2.92. DISCUSSION: We observed changes in the pupillary reactivity in all subjects based on changes in position and task. There were also differences between the healthy and IIH subjects. This is consistent with our hypothesis that elevated intracranial pressure may result in decreased pupillary reactivity even in the absence of brain edema.Soeken TA, Alonso A, Grant A, Calvillo E, Gutierrez-Flores B, Clark J, Donoviel D, Bershad EM. Quantitative pupillometry for detection of intracranial pressure changes during head-down tilt. Aerosp Med Hum Perform. 2018; 89(8):717-723.

Graphical and statistical analyses of the oculocardiac reflex during a non-invasive intracranial pressure measurement.

PURPOSE: This study aimed to examine the incidence of the oculocardiac reflex during a non-invasive intracranial pressure measurement when gradual external pressure was applied to the orbital tissues and eye. METHODS: Patients (n = 101) and healthy volunteers (n = 56) aged 20-75 years who underwent a non-invasive intracranial pressure measurement were included in this retrospective oculocardiac reflex analysis. Prespecified thresholds greater than a 10% or 20% decrease in the heart rate from baseline were used to determine the incidence of the oculocardiac reflex. RESULTS: None of the subjects had a greater than 20% decrease in heart rate from baseline. Four subjects had a greater than 10% decrease in heart rate from baseline, representing 0.9% of the total pressure steps. Three of these subjects were healthy volunteers, and one was a glaucoma patient. CONCLUSION: The incidence of the oculocardiac reflex during a non-invasive intracranial pressure measurement procedure was very low and not associated with any clinically relevant effects.

Internal Jugular Vein Volume During Head-Down Tilt and Carbon Dioxide Exposure in the SPACECOT Study.

BACKGROUND: Cerebral hemodynamics and venous outflow from the brain may be altered during exposure to microgravity or head-down tilt (HDT), an analog of microgravity, as well as by increased ambient CO2 exposure as experienced on the International Space Station. METHODS: Six healthy subjects underwent baseline tilt table testing at 0°, 6°, 12°, 18°, 24°, and 30° HDT. The right internal jugular (IJ) vein cross-sectional area (CSA) was measured at four intervals from the submandibular to the clavicular level and IJ volume was calculated. Further measurements of the IJ vein were made after ∼26 h of 12° HDT bed rest with either ambient air or 0.5% CO2 exposure, and plasma and blood volume were assessed after 4 h, 24 h, and 28.5 h HDT. RESULTS: IJ vein CSA and volume increased with progressively steeper HDT angles during baseline tilt table testing, with more prominent filling of the IJ vein at levels closer to the clavicle. Exposure to 26 h of 12° HDT bed rest with or without increased CO2, however, had little additional effect on the IJ vein. Further, bed rest resulted in a decrease in plasma volume and blood volume, although changes did not depend on atmospheric conditioning or correlate directly with changes in IJ vein CSA or volume. DISCUSSION: The hydrostatic effects of HDT can be clearly determined through measurement of the IJ vein CSA and volume; however, IJ vein dimensions may not be a reliable indicator of systemic fluid status during bed rest.Marshall-Goebel K, Stevens B, Rao CV, Suarez JI, Calvillo E, Arbeille P, Sangi-Haghpeykar H, Donoviel DB, Mulder E, Bershad EM, the SPACECOT Investigators Group. Internal jugular vein volume during head-down tilt and carbon dioxide exposure in the SPACECOT Study. Aerosp Med Hum Perform. 2018; 89(4):351-356.

Effects of -12° head-down tilt with and without elevated levels of CO2 on cognitive performance: the SPACECOT study.

Microgravity and elevated levels of CO2 are two common environmental stressors in spaceflight that may affect cognitive performance of astronauts. In this randomized, double-blind, crossover trial (SPACECOT), 6 healthy males (mean ± SD age: 41 ± 5 yr) were exposed to 0.04% (ambient air) and 0.5% CO2 concentrations during 26.5-h periods of -12° head-down tilt (HDT) bed rest with a 1-wk washout period between exposures. Subjects performed the 10 tests of the Cognition Test Battery before and on average 0.1, 5.2, and 21.0 h after the initiation of HDT bed rest. HDT in ambient air induced a change in response strategy, with increased response speed (+0.19 SD; P = 0.0254) at the expense of accuracy (-0.19 SD; P = 0.2867), resulting in comparable cognitive efficiency. The observed effects were small and statistically significant for cognitive speed only. However, even small declines in accuracy can potentially cause errors during mission-critical tasks in spaceflight. Unexpectedly, exposure to 0.5% CO2 reversed the response strategy changes observed under HDT in ambient air. This was possibly related to hypercapnia-induced cerebrovascular reactivity that favors cortical regions in general and the frontal cortex in particular, or to the CNS arousing properties of mildly to moderately increased CO2 levels. There were no statistically significant time-in-CO2 effects for any cognitive outcome. The small sample size and the small effect sizes are major limitations of this study and its findings. The results should not be generalized beyond the group of investigated subjects until they are confirmed by adequately powered follow-up studies. NEW & NOTEWORTHY Simulating microgravity with exposure to 21 h of -12° head-down tilt bed rest caused a change in response strategy on a range of cognitive tests, with a statistically significant increase in response speed at the expense of accuracy. Cognitive efficiency was not affected. The observed speed-accuracy tradeoff was small but may nevertheless be important for mission-critical tasks in spaceflight. Importantly, the change in response strategy was reversed by increasing CO2 concentrations to 0.5%.

Untreated hypertension as predictor of in-hospital mortality in intracerebral hemorrhage: A multi-center study.

PURPOSE: Hypertension is a significant risk factor for intracerebral hemorrhage (ICH). The importance of managing blood pressure to reduce the risk of ICH has been recognized. However, few studies have focused on ICH outcomes due to untreated hypertension. MATERIALS AND METHODS: We conducted a 5-year, retrospective, multicenter study of 490 consecutive ICH patients with histories of untreated-hypertension (n=56), treated-hypertension (n=314), and normotension (n=120). Demographics, symptom onset, vital signs, laboratory tests, and CT imaging were documented alongside in-hospital treatments, complications, and length of stay. RESULTS: Untreated-hypertension subjects were found to be significantly younger than treated-hypertension. They were found to have lower rates of anticoagulant use (p<0.01), antiplatelet use (p<0.01), and hyperlipidemia (p<0.01) than subjects with treated-hypertension. In a multivariate model, untreated-hypertension, age ≥65years, ≥3 outpatient antihypertensive medications, and hematoma volumes ≥30ml were all associated with significantly increased in-hospital mortality. In contrast, mortality was lower in patients receiving ≥3 antihypertensive medications while in-hospital. CONCLUSIONS: Subjects with untreated-hypertension were younger and had fewer comorbidities when compared with treated-hypertension and were similar when compared to normotensive individuals. Once demographic and in-hospital factors were accounted for, untreated-hypertension subjects demonstrated significantly increased in-hospital mortality following ICH when compared with normotensive individuals.

Real-time Noninvasive Monitoring of Intracranial Fluid Shifts During Dialysis Using Volumetric Integral Phase-Shift Spectroscopy (VIPS): A Proof-of-Concept Study.

BACKGROUND: Cerebral edema, which is associated with increased intracranial fluid, is often a complication of many acute neurological conditions. There is currently no accepted method for real-time monitoring of intracranial fluid volume at the bedside. We evaluated a novel noninvasive technique called "Volumetric Integral Phase-shift Spectroscopy (VIPS)" for detecting intracranial fluid shifts during hemodialysis. METHODS: Subjects receiving scheduled hemodialysis for end-stage renal disease and without a history of major neurological conditions were enrolled. VIPS monitoring was performed during hemodialysis. Serum osmolarity, electrolytes, and cognitive function with mini-mental state examination (MMSE) were assessed. RESULTS: Twenty-one monitoring sessions from 14 subjects (4 women), mean group age 50 (SD 12.6), were analyzed. The serum osmolarity decreased by a mean of 6.4 mOsm/L (SD 6.6) from pre- to post-dialysis and correlated with an increase in the VIPS edema index (E-Dex) of 9.7% (SD 12.9) (Pearson's correlation r = 0.46, p = 0.037). Of the individual determinants of serum osmolarity, changes in serum sodium level correlated best with the VIPS edema index (Pearson's correlation, r = 0.46, p = 0.034). MMSE scores did not change from pre- to post-dialysis. CONCLUSIONS: We detected an increase in the VIPS edema index during hemodialysis that correlated with decreased serum osmolarity, mainly reflected by changes in serum sodium suggesting shifts in intracranial fluids.

Increased cerebral blood volume pulsatility during head-down tilt with elevated carbon dioxide: the SPACECOT Study.

Astronauts aboard the International Space Station (ISS) have exhibited hyperopic shifts, posterior eye globe flattening, dilated optic nerve sheaths, and even optic disk swelling from spaceflight. Elevated intracranial pressure (ICP) consequent to cephalad fluid shifts is commonly hypothesized as contributing to these ocular changes. Head-down tilt (HDT) is frequently utilized as an Earth-based analog to study similar fluid shifts. Sealed environments like the ISS also exhibit elevated CO2, a potent arteriolar vasodilator that could further affect cerebral blood volume (CBV) and cerebral blood flow, intracranial compliance, and ICP. A collaborative pilot study between the National Space Biomedical Research Institute and the German Aerospace Center tested the hypotheses that 1) HDT and elevated CO2 physiologically interact and 2) cerebrovascular pulsatility is related to HDT and/or elevated CO2 In a double-blind crossover study (n = 6), we measured CBV pulsatility via near-infrared spectroscopy, alongside noninvasive ICP and intraocular pressure (IOP) during 28-h -12° HDT at both nominal (0.04%) and elevated (0.5%) ambient CO2 In our cohort, CBV pulsatility increased significantly over time at cardiac frequencies (0.031 ± 0.009 µM/h increase in total hemoglobin concentration pulsatility amplitude) and Mayer wave frequencies (0.019 ± 0.005 µM/h increase). The HDT-CO2 interaction on pulsatility was not robust but rather driven by one individual. Significant differences between atmospheres were not detected in ICP or IOP. Further work is needed to determine whether individual differences in pulsatility responses to CO2 relate to visual changes in space.NEW & NOTEWORTHY Cerebral blood volume (CBV) pulsatility-as measured by near-infrared spectroscopy-increases over time during -12° head-down tilt at both cardiac and Mayer wave frequencies. CBV pulsatility appeared to increase more under elevated (0.5%) CO2 at Mayer wave frequencies in some individuals. If similar dynamic pulsatility increases occur in astronauts, there is the potential to initiate vascular and possibly other remodeling processes that lead to symptoms associated with sustained increases in intracranial pressure.

Safety and Effectiveness of Factor VIII Inhibitor Bypassing Activity (FEIBA) and Fresh Frozen Plasma in Oral Anticoagulant-Associated Intracranial Hemorrhage: A Retrospective Analysis.

BACKGROUND: Oral anticoagulant (OAT)-associated intracranial hemorrhage (ICH) is a life-threatening emergency for which prothrombin complex concentrates (PCC) are considered first-line reversal agents. The only approved PCC in the USA for warfarin-associated ICH is non-activated PCC. Little data are available regarding the safety and effectiveness of factor VIII inhibitor bypassing activity (FEIBA) which is an activated prothrombin complex concentrate (aPCC). The aim of this analysis was to assess the safety and effectiveness of FEIBA compared to fresh frozen plasma (FFP) for reversal of OAT-associated ICH. METHODS: Data were retrospectively collected to compare coagulation markers and in-hospital clinical outcomes in patients who received aPCC with or without FFP versus FFP alone for the reversal of OAT-associated ICH. RESULTS: Eighty-four patients met inclusion criteria; 50 patients received FFP alone, and 34 patients received FEIBA (mean dose 20 U/kg) with or without FFP for OAT-associated ICH. The proportion of diagnosed thrombotic events during hospitalization was similar in both groups (8% in the FFP group vs. 12% in the FEIBA group; P = 0.56). Median time to INR < 1.5 was achieved faster in the FEIBA group versus the FFP group (0.5 h [IQR 0.5-1.] vs. 10 h [IQR 5-16.3], respectively; P < 0.001) reflecting a trend toward shorter median time to neurosurgical intervention. Hematoma expansion, length of stay, and all-cause mortality were similar between both groups. CONCLUSIONS: Administration of FEIBA does not appear to increase the risk of thrombotic events compared with FFP. FEIBA administration resulted in faster INR reversal with a trend toward shorter time to neurosurgical intervention. However, there was no difference in hematoma expansion, mortality or length of stay.

An international collaboration studying the physiological and anatomical cerebral effects of carbon dioxide during head-down tilt bed rest: the SPACECOT study.

Exposure to the microgravity environment results in various adaptive and maladaptive physiological changes in the human body, with notable ophthalmic abnormalities developing during 6-mo missions on the International Space Station (ISS). These findings have led to the hypothesis that the loss of gravity induces a cephalad fluid shift, decreased cerebral venous outflow, and increased intracranial pressure, which may be further exacerbated by increased ambient carbon dioxide (CO2) levels on the ISS. Here we describe the SPACECOT study (studying the physiological and anatomical cerebral effects of CO2 during head-down tilt), a randomized, double-blind crossover design study with two conditions: 29 h of 12° head-down tilt (HDT) with ambient air and 29 h of 12° HDT with 0.5% CO2 The internationally collaborative SPACECOT study utilized an innovative approach to study the effects of headward fluid shifting induced by 12° HDT and increased ambient CO2 as well as their interaction with a focus on cerebral and ocular anatomy and physiology. Here we provide an in-depth overview of this new approach including the subjects, study design, and implementation, as well as the standardization plan for nutritional intake, environmental parameters, and bed rest procedures.NEW & NOTEWORTHY A new approach for investigating the combined effects of cephalad fluid shifting and increased ambient carbon dioxide (CO2) is presented. This may be useful for studying the neuroophthalmic and cerebral effects of spaceflight where cephalad fluid shifts occur in an elevated CO2 environment.