NASA s Visual Impairment & Intracranial Pressure Risk: Utilizing the ISS for Risk Reduction

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Abraham McKenzie
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1 NASA s Visual Impairment & Intracranial Pressure Risk: Utilizing the ISS for Risk Reduction Christian Otto, M.D. Lead Scientist, NASA VIIP Project Page No. 1 1 St Annual ISS Research & Development Conference Denver Marriot City Center, CO Tuesday June 26, 2012.

2 VIIP Clinical Findings To date 15 U.S. ISS long-duration spaceflight astronauts have developed some or all of the following findings: Eye Findings Hyperopic shift Choroidal folds Cotton wool spots Optic Nerve Sheath Distention Globe flattening Edema of the Optic disc (papilledema) Signs of elevated intracranial pressure High postflight intracranial pressure in four crew members: mmHg (Normal: 7-15mmHg) or, cmh2o, Normal: cmH2O Page No. 2

Initial Identification of the VIIP: Subjective Changes in

a subjective degradation in vision, primarily increasing

distant vision intact Normal Eye (1 mm decrease in axial

3 Initial Identification of the VIIP: Subjective Changes in Vision 50% of long- duration (ISS) mission astronauts report a subjective degradation in vision, primarily increasing farsightedness Hyperopic shift Decreased near visual acuity, distant vision intact Normal Eye (1 mm decrease in axial length is equivalent to a 3 diaper hyperopic shift) Hyperopic Eye Page No. 3

Pre to Post Flight Papilledema: A Clinical Sign of

Grade 3 edemarightand Grade 1 edemaleft.

4 Pre to Post Flight Papilledema: A Clinical Sign of Raised Intracranial Pressure Pre Flight Fundoscopic images of the right and left optic disc. Pre Flight OD OS Post Flight Fundoscopic images of the right and left optic disc showing Grade 3 edemarightand Grade 1 edemaleft. Post Flight OD OS Page No. 4

5 In Flight B-scan Ultrasound Page No. 5

6 ISS Inflight Crew Ultrasound Imaging: Additional Signs of Raised Intracranial Pressure 1. Increased Optic Nerve Sheath Diameter Terrestrial Normal<5.9mm 3. Raised Optic Disc Postflight 2. Posterior Globe Flattening Preflight Postflight Flattening of Posterior Globe Postflight Page No. 6

7 Choroidal Folds Postflight Postflight OD OD OS Preflight Postflight Inferior Superior Inferior Superior Thickening of the choroid secondary to venous blood engorgement from ug fluid shift Page No. 7

8 VIIP Clinical Practice Guideline & Classification Case Classification (U.S. ISS Crew) (As of Jan 2012) 36 U.S. ISS crew flown to date: Confirmed non-cases N=5 Unclassified crew N=16 CPG Class One N=2 CPG Class Two N=8 CPG Class Three N=1 CPG Class Four N=4 30% Class 1&2 15% Class 3&4 Current VIIP Incidence in U.S. crew = 41.7% Page No. 8 Potential long-term changes: Decreased near visual acuity Peripheral vision loss Neurocognitive changes Higher risk likely on longer exploration missions (dose-response)

9 Piecing Together Visual Impairment and Elevated Intracranial Pressure in Spaceflight A Three-Part Story 1. The Vascular System 2. The Brain 3. The Eye + + Page No. 9

8m/s 2 CEPHALAD FLUID SHIFT 1G Supine Loss of Hydrostatic Drainage

10 Loss of Hydrostatic Drainage & Cerebral Venous Congestion 1G 0G Cerebral Venous Congestion X 9.8m/s 2 CEPHALAD FLUID SHIFT 1G Supine Loss of Hydrostatic Drainage Adapted from Rowell, 1988 Adapted from Hargens & Richardson, Respiratory Physiology & Neurobiology Page No. 10

11 Tilt Angle vs ICP & CVP: Positional Fluid Shifts Converted to mmhg ICP 24mmHg CVP=9mmHg ICP 9.6mmHg CVP=5mmHg ICP-1.8mmHg CVP=0mmHg 1. Chapman et al. The Relationship between Ventricular Fluid Pressure and Body Position in Normal Subjects with Shunts. Neurosurgery Hirvonen et al Hemodynamic changes due to Trendelenburg positioning and pneumoperitoneum during laproscopic hysterectomy, Acta Anaesthesiologica Scandiavica Page No. 11

12 Monroe Kelly Principle & ICP Accommodation of up to 120ml volume change while maintaining normal ICP Page No. 12

13 Fluid Shift & Inadequate Cerebral Venous & CSF Accommodation May Increase ICP in 0G Venous congestion Page No. 13 0G Cephalad fluid shift causes venous blood & CSF outflow resistance

14 Page No. 14 Occupational Data Mining in ISS Crew: Cardiovascular Variables Biochemistry: LDL Cardiovascular Variable Significant Correlation Across CPG Classification HDL - Triglycerides - Hemoglobin A1c Fasting serum glucose Homocysteine Body Composition: Body Mass Index Percentage Body Fat Cardiac: Resting blood pressure (pre-in-post flight) Pulse Pressure (pre-in-post flight) CT Coronary Calcium Score - Aerobic Capacity: Decreased Maximal Oxygen Uptake All correlated factors adversely affect vascular structure & function

15 Occupational Data Mining in ISS Crew : Ocular Variables Ocular Variable Significant Correlation across CPG Classification Eye Findings: Refractive vision change Retinal Nerve Fiber Layer Optic Nerve Sheath Diameter Intraocular Pressure Page No. 15

16 A Working Model: Potential Interaction of the CNS, Vascular, & Ocular System in the VIIP +OCSFP Cerebral Venous Blood +CSFP Cerebral Venous Congestion +OVP +VP X9.8m/s 2 Loss of Hydrostatic Drainage Adapted from Rekate Page No. 16

17 Impact of Inflight Exacerbating Factors? Resistive Exercise Does in-flight resistance training cause additional transient elevations in ICP? High Oral Sodium Intake Prepackaged Foods High in sodium Up to 5000mg+ per day Inflight Pharmaceuticals Effects on VIIP? Page No. 17

18 CO 2 Levels on ISS Adapted from Alperin et al. Radiology, 2000 CO 2 CO 2 is an extremely potent vasodilator Every 1mmHg increase PaCO 2 =4% increase in dilation CO 2 mission average=3.56mmhg (0.33%) 10x normal sea level atmospheric: % Average Peak CO 2 =8.32mmHg (0.7%) (20x) X X Cephalad Fluid Shift CO 2 also causes increased CSF production due to increased flux of HCO3 - across choroid plexus & accompanying H2O Page No. 18

19 ISS In-flight Ocular Study Preflight Exams In-flight Exams Post flight Exams L-21/18 mo L-21/18 mo MRI Of Brain and Orbits Without Contrast Fundoscopy - Tonometry Visual Acuity Including Questionnaire & Amsler Grid Testing Other Tests - biomicroscopy (slit lamp), high resolution retinal photography, OCT (high resolution), and A-Scan. A L-9/6 mo L-12/9 mo L-6/3 mo L-12/9 & L-6/3 mo Ultrasound Eye/Orbit L-9/6 mon Fundoscopy - Blood Pressure Tonometry Visual Acuity Including Questionnaire, Amsler Grid Testing, & Other visual tests Other Tests - biomicroscopy (slit lamp), high resolution retinal photography, OCT (high resolution), and A-Scan. A L+10 L+30 L+60 L+100 L+120 R-30 L+30, R-30 & as clinically indicated Ultrasound Eye/Orbit Fundoscopy - Tonometry Visual Acuity Including Questionnaire & Amsler Grid Testing L+100 Visual Acuity Including Questionnaire & Amsler Grid Testing L+10, 30, 60, 90, 120, & R-30 Ultrasound Eye/Orbit Fundoscopy - Tonometry With Blood Pressure Visual Acuity + Amsler Grid Testing Vascular Compliance With Blood Pressure R+1/3 Research Tests R+30 R+90 R+180 R+1/3, 30, 90, 180, 365 MRI Of Brain and Orbits Without Contrast Ultrasound Eye/Orbit Fundoscopy - Blood Pressure Tonometry Visual Acuity Including Questionnaire, Amsler Grid Testing, & other visual tests Other Tests - biomicroscopy (slit lamp), high resolution retinal photography, OCT (high resolution), and A-Scan. A R+365 Page No. 19 Vascular Compliance With Blood Pressure Vascular Compliance With Blood Pressure

20 ISS In-flight Studies: Braslet Occlusion Cuff Sequesters venous blood in the legs No Braslet Leg Leg Braslet IJ Vein IJ Vein Neck Neck Duncan et al. NASA SDTO Page No. 20

21 Russian Chibis LBNP Device (Negative Pressure) Page No. 21

22 Non-Invasive Intracranial Pressure Measurement Vittamed 205 Monitor Cochlear and Cerebral Fluid Pressure (CCFP) Analyzer Page No. 22

23 VIIP Knowledge & Technlogy Transfer to Terrestrial Medicine VIIP risk has brought together leading authorities in neurology, neurosurgery & ophthalmology The VIIP syndrome is challenging them to view their own area of expertise from a unique perspective The NASA VIIP team continues to disseminate advances in understanding the VIIP syndrome with the clinical community: E.g. CSF Symposium, John s Hopkins, UT Optometry Improved understanding of glaucoma Improved diagnosis & treatment of Idiopathic Intracranial Hypertension Technology transfer to terrestrial medicine: Assessment of Intracranial pressure using novel techniques & new protocols New remote guidance techniques Advancing telemedicine using standard clinical tools Page No. 23

24 NASA s Visual Impairment & Intracranial Pressure Risk: Utilizing the ISS for Risk Reduction Christian Otto, M.D. Lead Scientist, NASA VIIP Project Page No St Annual ISS Research & Development Conference Denver Marriot City Center, CO Tuesday June 26, 2012.

Common Characteristics of the Cases Approximately 6 month duration ISS mission All had normal preflight eye examinations Past medical history was negative for systemic

25 Common Characteristics of the Cases Approximately 6 month duration ISS mission All had normal preflight eye examinations Past medical history was negative for systemic disease; and none had used medications before or during their mission that could increase ICP (e.g., vitamin A, tetracycline, corticosteroids, or nalidixic acid) Page No. 25

26 Redistribution of Venous Pressures From 1G to 0G Standing 1G 0G Cranium is rigid Venous congestion Obligate arterial flow Transcapillary leak ++ICP~ m/s 2 X 1. Hirvonen et al. Hemodynamic changes due to Trendelenburg positioning and pneumoperitoneum during laproscopic hysterectomy, Acta Anaesthesiologica Scandiavica Hinghofer-Szalkay Gravity, the hydrorostatic indifference concept and the cardiovascular system. European Journal of Applied Physiology, 2010 Page No Chapman et al. The Relationship between Ventricular Fluid Pressure and Body Position in Normal Subjects with Shunts. Neurosurgery Gisolf et al. Human cerebral outflow pathway depends on posture and central venous pressure. Journal of Physiology, 2004.

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