Effect of gravity and microgravity on intracranial pressure

Abstract

Key points: Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure on Earth. Gravity has a profound effect on fluid distribution and pressure within the human circulation. In contrast to prevailing theory, we observed that microgravity reduces central venous and intracranial pressure. This being said, intracranial pressure is not reduced to the levels observed in the 90 deg seated upright posture on Earth. Thus, over 24 h in zero gravity, pressure in the brain is slightly above that observed on Earth, which may explain remodelling of the eye in astronauts.

Abstract: Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure (ICP). This syndrome is considered the most mission-critical medical problem identified in the past decade of manned spaceflight. We recruited five men and three women who had an Ommaya reservoir inserted for the delivery of prophylactic CNS chemotherapy, but were free of their malignant disease for at least 1 year. ICP was assessed by placing a fluid-filled 25 gauge butterfly needle into the Ommaya reservoir. Subjects were studied in the upright and supine position, during acute zero gravity (parabolic flight) and prolonged simulated microgravity (6 deg head-down tilt bedrest). ICP was lower when seated in the 90 deg upright posture compared to lying supine (seated, 4 ± 1 vs. supine, 15 ± 2 mmHg). Whilst lying in the supine posture, central venous pressure (supine, 7 ± 3 vs. microgravity, 4 ± 2 mmHg) and ICP (supine, 17 ± 2 vs. microgravity, 13 ± 2 mmHg) were reduced in acute zero gravity, although not to the levels observed in the 90 deg seated upright posture on Earth. Prolonged periods of simulated microgravity did not cause progressive elevations in ICP (supine, 15 ± 2 vs. 24 h head-down tilt, 15 ± 4 mmHg). Complete removal of gravity does not pathologically elevate ICP but does prevent the normal lowering of ICP when upright. These findings suggest the human brain is protected by the daily circadian cycles in regional ICPs, without which pathology may occur.

Keywords: bedrest; idiopathic intracranial hypertension; ocular remodeling; posture; space.

Figure 1. Diagrammatic presentation of the experimental set‐up

A and B, intracranial pressure (A) and central venous pressure (B) were measured directly via fluid coupled pressure transducers. C–E, beat‐by‐beat arterial blood pressure (C), arterial cuff pressure (D) and jugular venous cross‐sectional area (E) were measured non‐invasively. Note that intracranial, central venous and arterial pressure recordings were referenced to the external auditory meatus and right atrium, respectively (dashed lines). [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2. Changing from the sitting to supine posture on Earth increases ICP

A, experimental set‐up used to quantify pressure changes associated with change in posture on Earth. Gz, head‐to‐foot hydrostatic gradient irrespective of position, which is eliminated in the supine posture. Gx, front‐to‐back hydrostatic gradient, which is present in the supine posture. Gy, side‐to‐side hydrostatic gradient. Needle access to an Ommaya reservoir and placement of a peripherally inserted central catheter permitted intracranial pressure (ICP) and central venous pressure (CVP) measurement by fluid‐coupled pressure transducers, which were referenced to the external auditory meatus and right atrium, such that ICP and CVP were accurate throughout changes in posture. Arterial blood pressure (BP) was obtained by electrosphygmomanometry. B, original recording of changes in ICP in one participant by changing from the 90 deg sitting upright posture to the supine posture. C, mean ICP and CVP are higher, whereas BP is slightly lower in the 90 deg sitting upright posture compared to supine; n = 8, paired t tests. Black circles, males; white diamonds, females. D, original 2D images of jugular veins in the 90 deg sitting upright posture and supine posture from one participant. Jugular vein volume is smaller in the 90 deg sitting upright posture compared to supine; n = 8, paired t test. E, participants (n = 4) were passively placed in the 90, 60, 30 and 0 deg positions for 2 min (left). Hydrostatic indifference point (HIP)_CSF, where CSF pressure remains constant despite changes in posture, was calculated for each individual from the 90 deg seated upright and supine ICP. Prediction of ICP in the 30 and 60 deg positions (right) by subtraction of the height of the fluid column superior to the HIP_CSF with tilt angle (α). [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3. Microgravity reduces ICP in the supine posture

A, successive brief periods of microgravity (∼20 s) were generated during parabolic flight as participants lay in the supine posture, in which the Gz hydrostatic gradient is eliminated but the Gx gradient remains. In 0 g all hydrostatic gradients are absent. B, original recordings in one participant of changes in intracranial pressure (ICP), central venous pressure (CVP), left ventricular stroke volume (SV) and gravity throughout sox parabolas. Increased SV despite a fall in CVP during 0 g confirms cardiac ventricular distension due to a fall in intrathoracic pressure and thus an increase in the transmural cardiac filling pressure. The continuous line and the dashed line indicate the beginning and end of the first 0 g period. ICP increases at the beginning of the parabola as gravity almost doubles in the Gx direction. However, immediately upon entering 0 g, ICP falls rapidly to approximately the supine 1 g value. ICP then continues to fall, and by the end of the 0 g period, ICP is lower than the supine 1 g value. C, mean ICP and CVP decrease, and BP remains stable in 0 g compared to the supine 1 g posture; n = 8, paired t tests. D, original 2D images of jugular veins show further distension in 0 g compared to the supine 1 g posture. E and F, relationships between the fall in ICP in 0 g with (E) body weight and (F) HIP_CSF; n = 8, linear regression. Black circles, males; white diamonds, females. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 4. Dissociation between 24 h ICP on Earth versus microgravity as a characteristic for optic remodeling during long duration space flight

A, difference between 24 h intracranial pressure (ICP) on Earth (calculated as 2/3 × 90 deg sitting upright ICP + 1/3 × supine ICP, where supine ICP is assumed to reflect sleep) and during 0 g parabolic flight (assumed to reflect ICP throughout long duration space flight). B, the same data split into males versus females. Although subject numbers are too low for conclusive between‐group statistical analysis, removal of a single suspected outlier (>2SD from the mean) in the male cohort (dashed circle) suggests that females may have a smaller pressure differential between Earth and microgravity; n = 7 males, n = 3 females, unpaired t test. Black circles, males; white diamonds, females. This calculation reflects the 24 h difference in ICP between Earth and microgravity environments, assuming short‐term measurements during parabolic flight reflect long‐term measurements in space. Due to gravity, the brain and eye expect to ‘see’ a low pressure environment throughout two‐thirds of the day, and therefore in microgravity a greater relative posterior optic pressure would be ‘felt’ throughout spaceflight, especially in males, which may explain the increased severity of optic remodelling observed in male versus female astronauts. The single male ‘outlier’ may also explain the atypical male astronauts completely devoid of visual impairment in space.

Figure 5. Twenty‐four hours of simulated microgravity does not elevate ICP

A, diagram of the experimental set‐up used to simulate microgravity. Note that in −6 deg head‐down tilt (HDT), the Gx hydrostatic gradient and a slight foot‐to‐head Gz hydrostatic gradient exist. B, original recordings in one participant of changes in arterial blood pressure (BP), intracranial pressure (ICP) and central venous pressure (CVP) throughout 24 h of simulated microgravity. The beat‐to‐beat blood pressure device was turned off during sleep. Arrow indicates onset of passive tilt to the −6 deg HDT position. Note the compressed time scale in the second graph to demonstrate the transition from supine to HDT. C, in every subject, ICP was slightly higher in the −6 deg HDT position compared to the supine posture, which is entirely explained by the increase in Gz, foot‐to‐head hydrostatic column within the CSF and venous compartments (Fig. 6). During sleep, ICP falls below the supine value and, importantly, ICP returns to the supine baseline value after 24 h of −6 deg HDT; n = 4, one‐way ANOVA, ^* P < 0.05 vs. 0 deg. C, during sleep in −6 deg HDT, CVP is lower than the supine value, and remains slightly lower than the supine value in three of the four subjects after 24 h of −6 deg HDT; n = 4, one‐way ANOVA, ^* P < 0.05 vs. 0 deg. D, jugular vein distension persists throughout 24 h of −6 deg HDT, one‐way ANOVA with follow‐up test, 5 min (P = 0.0), 3 h (P = 0.09) and 24 h (P = 0.15) vs. 0 deg. Black circles, males. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 6. Simple hydrostatics explain the increase in intracranial pressure with acute −6 deg head down tilt (HDT)

A, in the −6 deg HDT model, the head is placed below the heart. Therefore, the slight foot‐to‐head (Gz) hydrostatic gradient causes pressure within both the venous and cerebral spinal fluid systems to increase proportional the length of the hydrostatic column superior to their respective hydrostatic indifference points. B, from the supine measurement of central venous pressure and the L‐HIP_vein, dural sinus pressure (P_d) was predicted to increase by 2.9 ± 0.2 mmHg. Thus, according to the Davson equation, intracranial pressure (ICP) must rise to exceed dural sinus pressure to maintain cerebral spinal fluid absorption into the sinus. Indeed, the predicted increase in ICP based on the L‐HIP_CSF model (1.2 ± 0.6 mmHg) and the measured increase in ICP (1.8 ± 0.5 mmHg) were similar. Nevertheless, the important take home message is that ICP did not increase substantially beyond that expected by simple hydrostatic gradients, and thus cephalad fluid shifts do not cause disproportionate and pathological increases in ICP. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 7. Sleeping in simulated microgravity does not reduce intracranial compliance

A, original recordings of pulsatile changes in intracranial pressure (ICP) in the awake supine position (top), in the −6 deg HDT position (HDT) just prior to sleep (middle) and during quiet rest/sleeping as document by a Registered Nurse in one human participant. B, pressure–volume intracranial compliance curve. In the steep part of the compliance curve, a 1 ml change in volume (during each heart beat) causes a much larger increase in ICP pulsatility than in the flat portion of the curve; thus, intracranial pulse amplitude (ICP_AMP) reflects the compliance state of the intracranial compartment. C, successive diastolic and systolic peaks were detected from continous ICP data by an automated ECG‐gated time‐windowing algorithm. ICP_AMP was averaged over 2 min of steady‐state in each condition. D, compared to the supine position, ICP_AMP fell slightly in three of the four participants just prior to falling asleep and remained below the supine value while resting quietly/asleep. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 8. 0.7% carbon dioxide inhalation does not increase ICP during real or simulated microgravity

Carbon dioxide (CO₂) was administered via a tight fitting facemask for 3–5 min prior to a set of parabolas or steady‐state data collection during bedrest. A, the intracranial pressure (ICP) response to 0.7% CO₂ is similar between the supine and acute (5 min) and prolonged (24 h) simulated microgravity conditions. Note that 0.7% CO₂ did not clinically increase ICP even after 5 min of HDT despite mean ICP being slightly elevated; n = 4, one‐way ANOVA. B, comparison of the decrease in ICP during microgravity whilst breathing normal air (normoapnia) versus 0.7% CO₂; n = 8, paired t test. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 9. Resistance exercise transiently increased ICP if combined with a Valsalva manoeuvre

Original recordings in one participant of changes in intracranial pressure (ICP), central venous pressure (CVP) and arterial blood pressure (BP) during repetitive leg press exercise while breathing 0.7% carbon dioxide. A, during 0 g, ICP rises during leg extension and falls with leg flexion (relaxation). The synchronized rise and fall in CVP and BP indicates that the participant performed a Valsalva manoeuvre during each leg extension. B, in the HDT position, ICP, CVP and BP rise during leg extension and fall with leg flexion (relaxation) during five leg press exercises with a controlled Valsalva manoeuvre. C, in the HDT position, ICP and BP remain mostly stable during five leg press exercises performed with a controlled Muller manoeuvre. D–G, individual and mean intracranial pressure responses to the combination of 0.7% carbon dioxide and leg press exercise in the (D) supine posture, (E) during acute microgravity, (F) during acute simulated microgravity and (G) during prolonged simulated microgravity. Microgravity, n = 8, paired t tests; supine and HDT conditions, n = 4, one‐way ANOVA, ^* P ≤ 0.05 vs. baseline. [Color figure can be viewed at wileyonlinelibrary.com]