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NEWS FROM THE AAN ANNUAL MEETING: High-Altitude Pilots Shown to Have More White Matter Damage Than Other Pilots

Moran, Mark

doi: 10.1097/01.NT.0000428467.67481.57
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Two new studies — among the first to examine neurological effects on pilots who fly at altitudes few other humans experience — suggest that U2 pilots have significantly more white matter lesions than pilots who fly at lower altitudes.

U2 pilots who fly at extraordinarily high altitudes appear to show significantly great numbers of high-density white matter lesions on MRI, and also demonstrate mild differences on cognitive tests compared with pilots who fly at lower altitudes.

Those were the findings from two studies that will be presented at the AAN annual meeting later this month.

The two studies are among the first to look at the neurological effects on pilots who fly at altitudes few other humans experience; U2 spy planes are known to fly as high as 70,000 feet, where the curvature of the earth can be seen.

Study author and neurologist Stephen McGuire, MD, of Lackland Air Force Base in San Antonio, TX, emphasized in an interview with Neurology Today that U2 pilots are a unique, exceptionally healthy breed, and that the subjects in the two studies do not demonstrate clinical symptoms. Nevertheless, the findings from the two reports have prompted the Air Force to make adjustments in flight routines and equipment as a way to protect pilots, Dr. McGuire told Neurology Today.

And while the studies speak narrowly to neurological effects in a very select subgroup, their findings raise questions about whether there is a lower-altitude threshold for neurological effects in less healthy or neurologically compromised individuals, he said.

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In one study, 94 U-2 pilots and 67 normative controls (Air Force pilots who do not fly at extreme altitudes) underwent 3T brain magnetic resonance imaging.

Dr. McGuire and colleagues found that the total number and volume of the subcortical high-density white matter lesions found within the pilots was significantly greater than those within the comparative normative data set.

“Before we did this study, the Air Force had identified a three-fold increase in episodes of neurological decompression sickness in U2 pilots in 2006 and again in 2010,” Dr. McGuire said. “The Air Force is very concerned about protecting its personnel and this had never occurred before in the life of the U2 program. We started evaluating the index cases [of neurological decompression sickness] and found an increased amount of white matter hyperintensities.

“Because we had found that in the index cases, the Air Force then asked us to look at active duty U2 pilots. Over 90 percent of our pilots came voluntarily to San Antonio for imaging and again we found an increase in subcortical hyperintensities. What was interesting is that these were not at the gray-white junction, but were in the subcortex.

“The next question was: how do we know these are not an artifact of technology? So, we imaged a comparative population of Air Force pilots — also very healthy active duty military personnel but who do not fly at such extreme altitudes. What we confirmed is that our U2 pilots are significantly different from normative controls with regard to the number and volume of white matter lesions.”

Dr. McGuire said the precise pathophysiology by which extreme altitude may influence the formation of lesions is unknown, but some research suggests effects on the thrombotic system or an inflammatory process.

He explained that when pilots reach extreme hypobaric altitudes nitrogen in the body will bubble possibly causing occluded vessels and ischemia. “We are not sure of the pathophysiology, but it appears we are seeing a shower of microemboli,” Dr. McGuire said.

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In a second study, Dr. McGuire and colleagues conducted cognitive testing on 48 high-altitude (U2) military pilots before pilot training and 85 after extreme hypobaric exposure. Sixty non-exposed military pilots (AFP) served as controls. Baseline and current cognitive tests — using the Multidimensional Aptitude Battery II and the MicroCog Assessment of Cognitive Functioning — were compared between U2 and non-exposed pilot groups, and the same tests were also compared within the same pilot.

The researchers found that U2 pilots demonstrated statistically significant differences in general cognitive proficiency, information processing accuracy, reasoning, and memory compared with Air Force pilots not exposed to extreme altitudes.

Dr. McGuire explained that as a result of the findings, pilots must now perform a mandatory “pre-breathing” exercise period before flying aimed at de-nitrogenating the body. (Previously the pre-breathing exercise period had been considered optional.) And, he said, the Air force is in the process of pressurizing U2 flight cabins, and implementing MRI screening before and after flight duty.

The studies are groundbreaking in an area that has only slim literature. A January 2010 report in the journal Aviation, Space, and Environmental Medicine reported a near-fatal case of neurological decompression sickness (DCS) in a U2 pilot.

“Despite the stellar safety record in aviation-related DCS since 1960, this case demonstrates that DCS remains a serious potential threat to flight operations,” the researchers stated. “The potential for DCS will persist as advances in aerospace technology continue to push the limits of high altitude flight.”

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John Hastings, MD, a neurologist and consultant to the Federal Aviation Administration, called the two Air Force studies “interesting.” He said the use of 3T MRI technology reveals many anomalies of unknown clinical import; but he said the use of a control group along with pre- and post-exposure comparisons does point to the potential clinical significance of the MRI and cognitive findings.

Peter Brugger, PhD, of the department of neurology at the University Hospital of Zurich, who has done research on neurological effects of high-altitude mountain climbing, likewise called the studies “intriguing” and said they raise interesting research questions about effects at lower altitudes.

“The pilots under study are so different from the general population, but it's possible to make inferences to more frequent conditions,” he told Neurology Today.

Dr. McGuire said there is anecdotal evidence that exposure to much lower altitudes may have neurological effects. “Where is the threshold?” he wondered. “What about flying at 15,000 or 8,000 feet in a commercial airline?

“Practicing neurologists need to know that altitude can cause white matter injury without hypoxia and some impairment of executive functioning,” Dr. McGuire said. “There is a question about how hypobaric you need to be, and where the threshold is if you have someone whose brain is already compromised.”

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• Jersey SL, Baril RT, Millhouse CM, et al. Severe neurological decompression sickness in a U-2 pilot. Aviat Space Environ Med 2010; 81:64–68.
    ©2013 American Academy of Neurology