Spaceflight-Associated Neuro-Ocular Syndrome (SANS)

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Disease Entity

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Disease

Spaceflight associated Neuro-Ocular Syndrome (SANS)—formerly called visual impairment and intracranial pressure (VIIP) syndrome[1]—is a constellation of findings and symptoms that have been found in astronauts who have undergone long duration space flight (LDSF) missions in microgravity environments (e.g., International Space Station (ISS)) 2.

Etiology

The precise etiology of SANS remains ill defined.

Risk Factors

The primary risk factor for SANS is extended exposure to the unique microgravity environment of LDSF (e.g. ISS)[2]. Subjective symptoms from SANS follow a dose dependent response with up to 23% experiencing changes in near distance visual acuity after short duration shuttle missions and up to 48% reporting near visual acuity changes after LDSF ISS missions[2]. In addition, up to 45% of astronauts flying missions greater than 30 days demonstrate ocular abnormalities through fundus examination and orbital and brain imaging[3] with or without the presence of subjective symptoms.

Pathophysiology

Although the exact etiology of SANS is still unkown it is believed that cephalad fluid shifts to the head, neck and orbits occur in microgravity environments due to impaired gravity assisted lymphatic, CSF and vascular drainage. These cephalad fluid shifts may cause increased hydrostatic pressure in the brain (intracranial pressure)[2] and orbit (optic nerve sheath). Two primary hypotheses have emerged. First, cephalad fluid shifts may lead to increased intracranial volume and/or pressure. This elevated CSF pressure around the brain may be transferred down the ON sheaths to the orbit and cause disc edema as well as globe flattening. Some studies have demonstrated that cerebral autoregulation is preserved during spaceflight[4] yet venous stasis in both the jugular and femoral veins has been observed during spaceflight and suggests venous congestion[6] which might impact CSF outflow and can create a terrestrial IIH like picture[6]. This congestion may also inhibit vortex vein drainage and cause choroidal thickening that could add to axial shortening and the observed hyperopic shift[2]. Interestingly, the signs of SANS may persist even after a return to normal earth gravity including the presence of mildly elevated CSF opening pressures[2] choroidal folds, and disc edema.[3,7].The absence of classical symptoms as seen in terrestrial IIH, including headache, tinnitus, transient visual obscurations, nausea, vomiting and the lack of data on inflight CSF opening pressure make this “IIH like” theory arguable. A second hypothesis is that SANS is due to microgravity induced changes in the physiology of CSF and subtle variations in interpersonal physiology of flow and drainage within the optic nerve sheath itself. CSF infusion studies show linear optic nerve sheath distention up to a saturation point which varies from person to person [1 8]and might explain the asymmetric findings in both IIH[9] and SANS. CSF flow within the obit is generally understood as related to inflow and outflow of CSF but postural/gravitational effects, ventricular pulsations and pulse pressure of the choroid plexus may also have a role[9]. The optic nerve sheath acts as a blind loop for CSF flow which raises questions about the nature of CSF outflow and circulation. In addition to drainage into venous vasculature, lymphatic drainage is believed to play a role as seen by the presence of India ink in lymphatics after injections into the optic nerve subarachnoid space[10]. Contrast infusion studies in IIH patients[9] by Killer et al demonstrate compartmentalization of the optic nerve sheath which is further supported by the presence of high to low chemical gradients between the optic nerve and intracranial subarachnoid spaces[11]. The combination of venous and lymphatic stasis may contribute to an optic nerve sheath compartment syndrome in the presence of only borderline increases to ICP. This may also explain the persistence of ocular abnormalities[2,3,7] by creating structural derangements in the local anatomy and physiologic processes.

Diagnosis

History

Duration of LDSF[2] and repeat exposure3[] may increase the risk of SANS. Subjective symptoms and objective clinical and imaging (e.g., OCT) signs appear as early as after 3 weeks of exposure on ISS[2].

Physical examination

During physical examination astronauts may exhibit deficits in visual acuity most noticeable at near distances which will also reflect in increased hyperopic sphere with manifest refraction on earth[2]. Funduscopic examination may demonstrate any combination of choroidal folds, disc edema, cotton wool spots[2,3].

Signs

Astronauts with SANS may have disc edema, choroidal folds, cotton wool spots, nerve fiber layer thickening on OCT, globe flattening and hyperopic shift[2].

Symptoms

The most frequent symptomatic complaint among astronauts experiencing SANS is decreased near vision caused by a hyperopic shift in vision of up to 1.5 diopters which can appear as early as after 3 weeks of microgravity exposure[2]. Less frequently observed symptoms also include visual scotomas[2] and headaches. Despite bearing superficial similarities to terrestrial idiopathic intracranial hypertension, astronauts do not experience diplopia, pulsatile tinnitus or transient visual obscurations,[2] the common symptoms of IIH[12]. Some astronauts do report nonspecific headaches. Additionally, no changes in best corrected visual acuity, color vision or other complaints have been noted to date

Diagnostic procedures

Diagnostic procedures in astronauts experiencing SANS to date have included pre and post post MRI, pre-, intra-, and post flight OCT, orbital ultrasound, and occasional postflight lumbar punctures [2]. Findings from these imaging procedures may show structural correlates to the clinical findings of optic disc edema, globe flattening, dilation of the optic nerve sheath as well as thickening and tortuosity of the optic nerve [2]. MRI imaging may show increases to optic nerves sheath diameter and optic nerve diameter with “kinks” to the optic nerve visible as T2 hyper intensities (96%)[13]. Posterior globe flattening and pituitary dome concavity with posterior stalk deviation were also seen within the microgravity exposure cohorts[13]. Cephalad brain shift has also been demonstrated on post flight MRI. In flight diagnostic procedures are limited by astronaut expertise and equipment portability. OCT and funduscopic examination have been performed with remote data transmission to terrestrial ophthalmologists during missions and demonstrated optic disc edema, chorioretinal folds, and cotton wool spots[2]. Lumbar puncture and MRI have also been used to assess SANS but are limited to terrestrial use. Evaluation of SANS with MRI may show flattening of posterior globes, distended optic nerve sheaths, tortuous optic nerves and papilledema[2]. Lumbar punctures performed in the context of SANS typically demonstrate normal to borderline increased opening CSF pressures which have been documented as high as 28.5 cmH20 at 2 months after landing[2]. Many of these findings bear a similarity to terrestrial IIH; however, the findings in SANS frequently present asymmetrically[2] which is uncommon for IIH[14].

Laboratory test

There is no labotratory testing for SANS

Management

General treatment

“Space Anticipation Glasses” to account for the frequent hyperopic shift seen in many astronauts are offered on ISS [2.] Considering the cephalad fluid shift seen in microgravity, some efforts have focused on simulating gravity by creating relative lower body negative pressure to mimic gravity[15]. Efforts have successfully decreased ICP but have yet to be applied during spaceflight[15].

Medical therapy

Acetazolamide (Diamox) is available on ISS but has not been deployed to date.

Medical follow up

Astronauts participate in continued long term longitudinal health evaluations after return to earth

Surgery

No astronaut has required surgery for SANS.

Complications

No permanent visual loss has occurred in SANS.

Prognosis

Outcomes in SANS have been variable to date. Hyperopic shift in astronauts gradually resolves upon return to earth gravity on the order of several weeks to months; however, some reports exist of a permanent hyperopic visual changes[2]. Some of the diagnostic findings may persist years after return to earth gravity. Persistence of choroidal folds have been documented more than 5 years after return[2] and optic disc swelling has persisted in some up to 2 years after mission[7].

References

1. Wostyn P, Deyn PP De. Optic Nerve Sheath Distention as a Protective Mechanism Against the Visual Impairment and Intracranial Pressure Syndrome in Astronauts. 2017;(September 2017):2017-2020. doi:10.1167/iovs.17-22600

2. Mader TH, Gibson CR, Pass AF, et al. Optic Disc Edema, Globe Flattening, Choroidal Folds, and Hyperopic Shifts Observed in Astronauts after Long-duration Space Flight. Ophthalmology. 2011;118(10):2058-2069. doi:10.1016/j.ophtha.2011.06.021

3. Mader TH, Gibson CR, Pass AF, et al. Optic disc edema in an astronaut after repeat long-duration space flight. J Neuro-Ophthalmology. 2013;33(3):249-255. doi:10.1097/WNO.0b013e31829b41a6

4. Iwasaki K, Levine BD, Zhang R, et al. Human cerebral autoregulation before , during and after spaceflight. J Physiol. 2007;579(Pt 3):799-810. doi:10.1113/jphysiol.2006.119636

5. Arbeille P, Roumy J. Adaptation of the left heart , cerebral and femoral arteries , and jugular and femoral veins during short- and long-term head-down tilt and space ¯ ights. 2001:157-168. doi:10.1007/s004210100473

6. Alperin N, Lee SH, Mazda M, et al. Evidence for the importance of extracranial venous flow in patients with idiopathic intracranial hypertension (IIH). In: Acta Neurochirurgica, Supplementum. ; 2005. doi:10.1007/3-211-32318-X_28

7. Mader TH, Gibson CR, Otto CA, et al. Persistent Asymmetric Optic Disc Swelling after Long-Duration Space Flight: Implications for Pathogenesis. J Neuro-Ophthalmology. 2017;37(2):133-139. doi:10.1097/WNO.0000000000000467

8. Hansen H-C, Helmke K. Validation of the optic nerve sheath response to changing cerebrospinal fluid pressure: ultrasound findings during intrathecal infusion tests. J Neurosurg. 2009. doi:10.3171/jns.1997.87.1.0034

9. Killer HE, Jaggi GP, Flammer J, Miller NR, Huber AR, Mironov A. Cerebrospinal fluid dynamics between the intracranial and the subarachnoid space of the optic nerve. Is it always bidirectional? Brain. 2007. doi:10.1093/brain/awl324

10. Killer HE, Laeng HR, Groscurth P. Lymphatic Capillaries in the Meninges of the Human Optic Nerve. J Neuro-Ophthalmology. 1999;19(4):222???228. doi:10.1097/00041327-199912000-00002

11. Killer HE, Jaggi GP, Flammer J, Miller NR, Huber AR. The optic nerve: A new window into cerebrospinal fluid composition? Brain. 2006;129(4):1027-1030. doi:10.1093/brain/awl045

12. Giuseffi V, Wall M, Siegel PZ, Rojas PB. Symptoms and disease associations in idiopathic intracranial hypertension (pseudotumor cerebri): a case-control study. Neurology. 1991.

13. Kramer LA, Sargsyan AE, Hasan KM, Polk JD, Hamilton DR. Orbital and Intracranial Effects of Microgravity: Findings at 3-T MR Imaging. Radiology. 2012;263(3):819-827. doi:10.1148/radiol.12111986

14. Bidot S, Bruce BB, Saindane AM, Newman NJ, Biousse V. Asymmetric papilledema in idiopathic intracranial hypertension. J Neuro-Ophthalmology. 2015;35(1):31-36. doi:10.1097/WNO.0000000000000205