Investigation of Whole-Brain White Matter Identifies Altered Water Mobility in the Pathogenesis of High-Altitude Headache

Abstract

Elevated brain water is a common finding in individuals with severe forms of altitude illness. However, the location, nature, and a causative link between brain edema and symptoms of acute mountain sickness such as headache remains unknown. We examined indices of brain white matter water mobility in 13 participants after 2 and 10 hours in normoxia (21% O 2 ) and hypoxia (12% O 2 ) using magnetic resonance imaging. Using a whole-brain analysis (tract-based spatial statistics (TBSS)), mean diffusivity was reduced in the left posterior hemisphere after 2 hours and globally reduced throughout cerebral white matter by 10 hours in hypoxia. However, no changes in T 2 relaxation time (T 2 ) or fractional anisotropy were observed. The TBSS identified an association between changes in mean diffusivity, fractional anisotropy, and T 2 both supra and subtentorially after 2 and 10 hours, with headache score after 10 hours in hypoxia. Region of interest-based analyses generally confirmed these results. These data indicate that acute periods of hypoxemia cause a shift of water into the intracellular space within the cerebral white matter, whereas no evidence of brain edema (a volumetric enlargement) is identifiable. Furthermore, these changes in brain water mobility are related to the intensity of high-altitude headache.

Investigation of prolonged hypobaric hypoxia-induced change in rat brain using T2 relaxometry and diffusion tensor imaging at 7T

“…In the present study, iron deposits might have resulted in a significant T2 decrease of the Dg region in the 14-day HH group. It is clear from the current study that cytotoxic edema occurs in hippocampal subfields in response to prolonged HH, which is in accordance to earlier studies which showed a decrease in ADC values in the cerebral GM region (Hunt et al, 2013;Lawley et al, 2013).…”

“…A decrease in ADC may indicate redistribution of water from the extracellular to the intracellular compartment, which is being hypothesized as cytotoxic edema in the cerebral GM due to hypoxia (Pulsinelli, 1985). This decrease in ADC values was in agreement with earlier studies performed on mountaineers (Hunt et al, 2013;Lawley et al, 2013). Histopathology of 7-day HH rats revealed a change in CA1 architecture.…”

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

“…Furthermore, 24 hours before and during each visit, participants consumed a standardized diet. 12 Each visit consisted of a 10-hour exposure to normobaric normoxia (21% O 2 ) or normobaric hypoxia (12% O 2 ) in a temperature (23 C) and humidity (40%) controlled environmental chamber. Participants were assigned to each exposure in a randomized order (www.randomisation.com, by J.S.L.)…”

“…[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. 9 Thus, the precise role brain volume and ICP play in causing symptoms of AMS is still debated.…”

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

“…2,7 Although the 'tight-fit' hypothesis suggests that increased brain volume and subsequent enhanced intracranial pressure may underlie AMS symptoms, 7 the link between changes in brain volumes, signs of cerebral edema, and symptoms of AMS typically developing over the first 6 to 12 hours of hypoxic exposure remains controversial. 3,4,[8][9][10] Some reports suggest that performing physical activity during the first hours of hypoxic exposure may accentuate symptoms of AMS. [11][12][13] Only one recent study compared the effects of hypoxic exposure for 8 hours associated or not with physical exercise (3 times 30 minutes of moderate intensity exercise) on brain volume and cerebral edema.…”