Spaceflight associated neuro-ocular syndrome (SANS), previously called spaceflight-induced visual impairment, is hypothesized to be a result of increased intracranial pressure (ICP), although experiments directly measuring ICP in parabolic flight have shown ICP to be in normal physiological ranges during acute weightless exposure. The study of visual changes and ICP in astronauts on long-duration flights is a relatively recent topic of interest to space medicine professionals. Although reported signs and symptoms have not appeared to be severe enough to cause blindness in the near term, long term consequences of chronically elevated intracranial pressure are unknown.
NASA has reported that fifteen long-duration male astronauts (45–55 years of age) have experienced confirmed visual and anatomical changes during or after long-duration flights. Optic disc edema, globe flattening, choroidal folds, hyperopic shifts and an increased intracranial pressure have been documented in these astronauts. Some individuals experienced transient changes post-flight while others have reported persistent changes with varying degrees of severity.
Although the exact cause is not known, it is suspected that microgravity-induced fluid shift towards the head and comparable physiological changes play a significant role in these changes. Other contributing factors may include pockets of increased carbon dioxide (CO2) and an increase in sodium intake. It seems unlikely that resistive or aerobic exercise are contributing factors, but they may be potential countermeasures to reduce intraocular pressure (IOP) or ICP in-flight.
Causes and current studies Although a definitive cause (or set of causes) for the symptoms outlined in the Existing Long-Duration Flight Occurrences section is unknown, it is thought that venous congestion in the brain brought about by cephalad fluid shifts may be a unifying pathologic mechanism. Additionally, a recent study reports changes in cerebrospinal fluid (CSF) hydrodynamics and increased diffusivity around the optic nerve under simulated microgravity conditions which may contribute to ocular changes in spaceflight. As part of the effort to elucidate the cause(s), NASA has initiated an enhanced occupational monitoring program for all mission astronauts with special attention to signs and symptoms related to ICP.
Similar findings have been reported among Russian cosmonauts who flew long-duration missions on Mir. The findings were published by Mayasnikov and Stepanova in 2008.
Animal research from the Russian Bion-M1 mission indicates duress of the cerebral arteries may induce reduced blood flow, thereby contributing to impaired vision.
On 2 November 2017, scientists reported that significant changes in the position and structure of the brain have been found in astronauts who have taken trips in space, based on magnetic resonance imaging (MRI) studies. Astronauts who took longer space trips were associated with greater brain changes.
CO2 Carbon dioxide (CO2) is a natural product of metabolism. People typically exhale around 200mL of CO2 per minute at rest and over 4.0 L at peak exercise levels. In a closed environment, CO2 levels can quickly rise and can be expected to a certain degree in an environment such as the International Space Station (ISS). Nominal CO2 concentrations on Earth are approximately 0.23 mmHg while nominal CO2 levels aboard the ISS are up to 20 times that at 2.3 to 5.3 mmHg. Those astronauts who experienced VIIP symptoms were not exposed to CO2 levels in excess of 5 mmHg.
Ventilation and heart rate increase as CO2 rise. Hypercapnia also stimulates vasodilation of cerebral blood vessels, increased cerebral blood flow and elevated ICP presumably leading to headache, visual disturbance and other central nervous system (CNS) symptoms. CO2 is a known potent vasodilator and an increase in cerebral perfusion pressure will increase the CSF production by about 4%.
Since air movement is reduced in microgravity, local pockets of increased CO2 concentrations may form. Without proper ventilation, CO2 concentrations ppCO2 could rise above 9mmHg within 10 minutes around a sleeping astronaut's mouth and chin. More data is needed to fully understand the individual and environmental factors that contribute to CO2-related symptoms in microgravity.
Sodium intake A link between increased ICP and altered sodium and water retention was suggested by a report in which 77% of IIH patients had evidence of peripheral edema and 80% with orthostatic retention of sodium and water. Impaired saline and water load excretions were noted in the upright position in IIH patients with orthostatic edema compared to lean and obese controls without IIH. However, the precise mechanisms linking orthostatic changes to IIH were not defined, and many IH patients do not have these sodium and water abnormalities. Astronauts are well known to have orthostatic intolerance upon reentry to gravity after long-duration spaceflight, and the dietary sodium on orbit is also known to be in excess of 5 grams per day in some cases. The majority of the NASA cases did have high dietary sodium during their increment. The ISS program is working to decrease in-flight dietary sodium intake to less than 3 grams per day. Prepackaged foods for the International Space Station were originally high in sodium at 5300 mg/d. This amount has now been substantially reduced to 3000 mg/d as a result of NASA reformulation of over ninety foods as a conscious effort to reduce astronaut sodium intake.
Exercise While exercise is used to maintain muscle, bone and cardiac health during spaceflight, its effects on ICP and IOP have yet to be determined. The effects of resistive exercise on the development of ICP remains controversial. An early investigation showed that the brief intrathoracic pressure increase during a Valsalva maneuver resulted in an associated rise in ICP. Two other investigations using transcranial Doppler ultrasound techniques showed that resistive exercise without a Valsalva maneuver resulted in no change in peak systolic pressure or ICP. The effects of resistive exercise in IOP are less controversial. Several different studies have shown a significant increase in IOP during or immediately after resistive exercise.
There is much more information available regarding aerobic exercise and ICP. The only known study to examine ICP during aerobic exercise by invasive means showed that ICP decreased in patients with intracranial hypertension and those with normal ICP. They suggested that because aerobic exercise is generally done without Valsalva maneuvers, it is unlikely that ICP will increase during exercise. Other studies show global brain blood flow increases 20–30% during the transition from rest to moderate exercise.
More recent work has shown that an increase in exercise intensity up to 60% VO2max results in an increase in CBF, after which CBF decreases towards (and sometimes below) baseline values with increasing exercise intensity.
Biomarkers Several biomarkers may be used for early VIIP Syndrome detection. The following biomarkers were suggested as potential candidates by the 2010 Visual Impairment Summit:
albumin aquaporin atrial naturetic peptide CRP/inflammation markers immunoglobin G index insulin-like growth factors myelin basic protein oligoclonal bands platelet count S-100 somatostatin tet-transactivator (TTA) vasopressin
Also, gene expression profiling, epigenetic modifications, CO2 retaining variants, single-nucleotide polymorphisms and copy number variants should be expanded in order to better characterize the individual susceptibility to develop the VIIP syndrome. As the etiology of the symptoms is more clearly defined, the appropriate biomarkers will be evaluated.
One-carbon metabolism (homocysteine) While the common theories regarding vision issues during flight focus on cardiovascular factors (fluid shift, intracranial hypertension, CO2 exposure, etc.), the difficulty comes in trying to explain how on any given mission, breathing the same air and exposed to the same microgravity, why some crewmembers have vision issues while others do not. Data identified as part of an ongoing nutrition experiment found biochemical evidence that the folate-dependent one-carbon metabolic pathway may be altered in those individuals who have vision issues. These data have been published and summarized by the ISS Program, and described in a journal sponsored pubcast.
In brief: serum concentrations of metabolites of the folate, vitamin B-12 dependent one carbon metabolism pathway, specifically, homocysteine, cystathionine, 2-methylcitric acid, and methylmalonic acid were all significantly (P<0.001) higher (25–45%) in astronauts with ophthalmic changes than in those without such changes. These differences existed before, during, and after flight. Serum folate tended to be lower (P=0.06) in individuals with ophthalmic changes. Preflight serum concentrations of cystathionine and 2-methylcitric acid, and mean in-flight serum folate, were significantly (P<0.05) correlated with changes in refraction (postflight relative to preflight).
Thus, data from the Nutrition SMO 016E provide evidence for an alternative hypothesis: that individuals with alterations in this metabolic pathway may be predisposed to anatomic and/or physiologic changes that render them susceptible to ophthalmologic damage during space flight. A follow-up project has been initiated (the "One Carbon" study) to follow up and clarify these preliminary findings.
Space obstructive syndrome An anatomic cause of the microgravity related intracranial hypertension and visual disturbances has been proposed and is termed Space Obstructive Syndrome or SOS. This hypothesis has the possibility of linking the various symptoms and signs together through a common mechanism in a cascade phenomenon, and explaining the findings in one individual and not another due to specific anatomic variations in the structural placement of the internal jugular vein. This hypothesis was presented in May 2011 at the annual meeting of the Aerospace Medicine Association in Anchorage, Alaska, and was published in January, 2012.
In 1G on earth, the main outflow of blood from the head is due to gravity, rather than a pumping or vacuum mechanism. In a standing position, the main outflow from the head is through the vertebral venous system because the internal jugular veins, located primarily between the carotid artery and the sternocleidomastoid muscle are partially or completely occluded due to the pressure from these structures, and in a supine position, the main outflow is through the internal jugular veins as they have fallen laterally due to the weight of the contained blood, are no longer compressed and have greatly expanded in diameter, but the smaller vertebral system has lost the gravitational force for blood outflow. In microgravity, there is no gravity to pull the internal jugular veins out from the zone of compression (Wiener classification Zone I), and there is also no gravitational force to pull blood through the vertebral venous system. In microgravity, the cranial venous system has been put into minimal outflow and maximal obstruction. This then causes a cascade of cranial venous hypertension, which decreases CSF resorption from the arachnoid granulations, leading to intracranial hypertension and papilledema. The venous hypertension also contributes to the head swelling seen in photos of astronauts and the nasal and sinus congestion along with headache noted by many. There is also subsequent venous hypertension in the venous system of the eye which may contribute to the findings noted on ophthalmic exam and contributing to the visual disturbances noted.