White matter hyperintensities on MRI in high-altitude U-2 pilots

Objective: To demonstrate that U-2 pilot occupational exposure to hypobaria leads to increased incidence of white matter hyperintensities (WMH) with a more uniform distribution throughout the brain irrespective of clinical neurologic decompression sickness history. Methods: We evaluated imaging findings in 102 U-2 pilots and 91 controls matched for age, health, and education levels. Three-dimensional, T2-weighted, high-resolution (1-mm isotropic) imaging data were collected using fluid-attenuated inversion recovery sequence on a 3-tesla MRI scanner. Whole-brain and regionalWMHvolume and number were compared between groups using a 2-tailed Wilcoxon rank sum test. Results: U-2 pilots demonstrated an increase in volume (394%; p 5 0.004) and number (295%; p, 0.001) ofWMH. Analysis of regional distribution demonstratedWMH more uniformly distributed throughout the brain in U-2 pilots compared with mainly frontal distribution in controls. Conclusion: Pilots with occupational exposure to hypobaria showed a significant increase inWMH lesion volume and number. Unlike the healthy controls with predominantly WMH in the frontal white matter, WMH in pilots were more uniformly distributed throughout the brain. This is consistent with our hypothesized pattern of damage produced by interaction between microemboli and cerebral tissue, leading to thrombosis, coagulation, inflammation, and/or activation of innate immune response, although further studies will be necessary to clarify the pathologic mechanisms responsible.