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

<jats:sec><jats:title>Objective</jats:title><jats:p>The study was undertaken to determine whether normobaric hypoxia causes elevated brain volume and intracranial pressure in individuals with symptoms consistent with acute mountain sickness (AMS).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Thirteen males age = (26 (sd 6)) years were exposed to normobaric hypoxia (12% O<jats:sub>2</jats:sub>) and normoxia (21% O<jats:sub>2</jats:sub>). After 2 and 10 hours, AMS symptoms were assessed alongside ventricular and venous vessel volumes, cerebral blood flow, regional brain volumes, and intracranial pressure, using high‐resolution magnetic resonance imaging.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In normoxia, neither lateral ventricular volume (<jats:italic>R</jats:italic><jats:sup>2</jats:sup> = 0.07, <jats:italic>p</jats:italic> = 0.40) nor predominance of unilateral transverse venous sinus drainage (<jats:italic>R</jats:italic><jats:sup>2</jats:sup> = 0.07, <jats:italic>p</jats:italic> = 0.45) was related to AMS symptoms. Furthermore, despite an increase in cerebral blood flow after 2 hours of hypoxia (hypoxia vs normoxia: Δ148ml/min<jats:sup>−1</jats:sup>, 95% confidence interval [CI] = 58 to 238), by 10 hours, when AMS symptoms had developed, cerebral blood flow was normal (Δ−51ml/min<jats:sup>−1</jats:sup>, 95% CI = −141 to 39). Conversely, at 10 hours brain volume was increased (Δ59ml, 95% CI = 8 to 110), predominantly due to an increase in gray matter volume (Δ73ml, 95% CI = 25 to 120). Therefore, cerebral spinal fluid volume was decreased (Δ−40ml, 95% CI = −67 to −14). The intracranial pressure response to hypoxia varied between individuals, and as hypothesized, the most AMS‐symptomatic participants had the largest increases in intracranial pressure (AMS present, Δ7mmHg, 95% CI = −2.5 to 17.3; AMS not present, Δ−1mmHg, 95% CI = −3.3 to 0.5). Consequently, there was a significant relationship between the change in intracranial pressure and AMS symptom severity (<jats:italic>R</jats:italic><jats:sup>2</jats:sup> = 0.71, <jats:italic>p</jats:italic> = 0.002).</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>The data provide the strongest evidence to date to support the hypothesis that the “random” nature of AMS symptomology is explained by a variable intracranial pressure response to hypoxia. ANN NEUROL 2014;75:890–898</jats:p></jats:sec>