Early brain swelling in acute hypoxia

Abstract

Acute mountain sickness (AMS) and high-altitude cerebral edema share common clinical characteristics, suggesting cerebral swelling may be an important factor in the pathophysiology of AMS. Hypoxia and hypocapnia associated with high altitude are known to exert strong effects on the control of the cerebral circulation, yet how these effects interact during acute hypoxia, and whether AMS-susceptible subjects may have a unique response, is still unclear. To test if self-identified AMS-susceptible individuals show altered brain swelling in response to acute hypoxia, we used quantitative arterial spin-labeling and volumetric MRI to measure cerebral blood flow and cerebrospinal fluid (CSF) volume changes during 40 min of acute hypoxia. We estimated changes in cerebral blood volume (CBV) (from changes in cerebral blood flow) and brain parenchyma swelling (from changes in CBV and CSF). Subjects with extensive high-altitude experience in two groups participated: self-identified AMS-susceptible (n = 6), who invariably experienced AMS at altitude, and self-identified AMS-resistant (n = 6), who almost never experienced symptoms. During 40-min hypoxia, intracranial CSF volume decreased significantly [-10.5 ml (SD 6.9), P < 0.001]. There were significant increases in CBV [+2.3 ml (SD 2.5), P < 0.005] and brain parenchyma volume [+8.2 ml (SD 6.4), P < 0.001]. However, there was no significant difference between self-identified AMS-susceptible and AMS-resistant groups for these acute-phase changes. In acute hypoxia, brain swelling occurs earlier than previously described, with significant shifts in intracranial CSF occurring as early as 40 min after exposure. These acute-phase changes are present in all individuals, irrespective of susceptibility to AMS.

Cerebral Volumetric Changes Induced by Prolonged Hypoxic Exposure and Whole-Body Exercise

“…Some previous studies suggested that MRI signs of cerebral subedema may be observed as early as during the first hour of hypoxic exposure. 5,6 In the present study, white-matter volume already increased significantly after 30 minutes of hypoxic exposure. This time point coincides with significant and near maximal reduction in cerebral oxygenation measured by near-infrared spectroscopy during a 4-hour hypoxic exposure (FiO 2 = 0.12) at rest.…”

“…The absence of significant change in ADC after 30 minutes of exposure suggests that edema is not responsible for this early increase in whitematter volume. From unchanged CBF, it may be extrapolated that cerebral blood volume was also unchanged, 6 but the relationship between CBF and cerebral blood volume may not be always straightforward especially with potential changes in venous blood volume. 7 We recently showed that prefrontal total haemoglobin concentration measured by near-infrared spectroscopy increased within 30 minutes of hypoxic exposure at rest, suggesting that an increase in cerebral blood volume may occur after short duration hypoxic exposure and might underlie an increase in cerebral volume as observed in the present study.…”

“…changes in CSF volume within the present experimental conditions. 6 Volumetric regional changes were not investigated in the present study because we previously observed (unpublished data) that spatial normalization to standard templates induces slight images distortions able to interfere with subtle brain volumetric changes. Although previous studies suggest a rather homogenous effect of hypoxia and exercise on the main cerebral regions, 14 further studies are needed to determine whether specific regions of the brain may show larger hypoxiainduced alterations.…”

Normobaric hypoxia and symptoms of acute mountain sickness: Elevated brain volume and intracranial hypertension

“…found elevated brain volume, particularly gray matter, during periods of hypoxemia, [9][10][11] which is unlikely to be due to the accumulation of brain edema. [12][13][14] Furthermore, lumbar pressure is elevated in individuals with suspected high-altitude cerebral edema, 15 but not in individuals with AMS after 18 hours in normobaric hypoxia.…”

Cerebral Diffusion and T2: MRI Predictors of Acute Mountain Sickness during Sustained High-Altitude Hypoxia

“…The first step down the path to brain swelling is hypothesized to be increased cerebral blood flow and associated increased cerebral blood volume, which directly produces brain swelling-leading to increased capillary pressure and cerebral edema. We previously found that increased cerebral blood flow is a common outcome of ascent to high altitude, 17 as is cerebral swelling and reduced CSF volume, 18 but neither was associated with a greater propensity to develop AMS. An alternate hypothesis for brain swelling and symptoms of AMS may relate to compromised cerebral energy status.…”