Lessons from altitude: cerebral perfusion insights and their potential translational clinical significance.

Abstract

The long-held assumption that transcranial Doppler middle cerebral artery velocity is a surrogate for cerebral blood flow has been questioned in certain circumstances, particularly where tissue oxygenation changes. What advances does it highlight? Cerebral venous outflow restriction appears to be implicated in the development of high-altitude cerebral oedema. Rapid ascent to high altitude commonly results in acute mountain sickness and, on occasion, potentially fatal high-altitude cerebral oedema. The exact pathophysiological mechanisms behind these syndromes remain to be determined. One of the main theories to explain the development of acute mountain sickness is an increase in intracranial pressure. Vasogenic (extracellular water accumulation attributable to increased permeability of the blood-brain barrier) and cytotoxic (intracellular) oedema have also been postulated as potential mechanisms that underlie high-altitude cerebral oedema. Recently published findings derived from a very challenging field study (obtained at altitudes of up to 7950 m), substantiated by sea-level hypoxic magnetic resonance angiography studies, have given new insights into the maintenance of cerebral blood flow at altitude. This report provides new perspectives and potential mechanisms to account for the maintenance of cerebral oxygen delivery at high and extreme altitude. In particular, the long-held assumption that transcranial Doppler middle cerebral artery velocity is a surrogate for cerebral blood flow has been shown to be incorrect in certain circumstances. The emerging evidence for a potential third mechanism, namely the restrictive venous outflow hypothesis, in the development of high-altitude cerebral oedema, over and above the accepted vasogenic and cytotoxic hypotheses, is also appraised.