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August 20, 2013; 81 (8) Article

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

Stephen McGuire, Paul Sherman, Leonardo Profenna, Patrick Grogan, John Sladky, Anthony Brown, Andrew Robinson, Laura Rowland, Elliot Hong, Beenish Patel, David Tate, Elaine S. Kawano, Peter Fox, Peter Kochunov
First published August 19, 2013, DOI: https://doi.org/10.1212/WNL.0b013e3182a1ab12
Stephen McGuire
From the U.S. Air Force School of Aerospace Medicine, Aerospace Medicine Consultation Division (S.M., L.P.) and Airmen Integration Research Division (E.S.K.), Wright-Patterson AFB, OH; Department of Neurology (S.M., A.B., P.F.) and Research Imaging Institute (P.F.), University of Texas Health Sciences Center, San Antonio; Departments of Neuroradiology (P.S.) and Neurology (S.M., P.G., J.S., A.R.), 59th Medical Wing, Lackland AFB, TX; Maryland Psychiatric Research Center (L.R., E.H., B.P., P.K.), University of Maryland School of Medicine, Baltimore; and Henry M. Jackson Foundation for the Advancement of Military Science (D.T.), San Antonio Military Medical Center, TX.
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Paul Sherman
From the U.S. Air Force School of Aerospace Medicine, Aerospace Medicine Consultation Division (S.M., L.P.) and Airmen Integration Research Division (E.S.K.), Wright-Patterson AFB, OH; Department of Neurology (S.M., A.B., P.F.) and Research Imaging Institute (P.F.), University of Texas Health Sciences Center, San Antonio; Departments of Neuroradiology (P.S.) and Neurology (S.M., P.G., J.S., A.R.), 59th Medical Wing, Lackland AFB, TX; Maryland Psychiatric Research Center (L.R., E.H., B.P., P.K.), University of Maryland School of Medicine, Baltimore; and Henry M. Jackson Foundation for the Advancement of Military Science (D.T.), San Antonio Military Medical Center, TX.
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Leonardo Profenna
From the U.S. Air Force School of Aerospace Medicine, Aerospace Medicine Consultation Division (S.M., L.P.) and Airmen Integration Research Division (E.S.K.), Wright-Patterson AFB, OH; Department of Neurology (S.M., A.B., P.F.) and Research Imaging Institute (P.F.), University of Texas Health Sciences Center, San Antonio; Departments of Neuroradiology (P.S.) and Neurology (S.M., P.G., J.S., A.R.), 59th Medical Wing, Lackland AFB, TX; Maryland Psychiatric Research Center (L.R., E.H., B.P., P.K.), University of Maryland School of Medicine, Baltimore; and Henry M. Jackson Foundation for the Advancement of Military Science (D.T.), San Antonio Military Medical Center, TX.
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Patrick Grogan
From the U.S. Air Force School of Aerospace Medicine, Aerospace Medicine Consultation Division (S.M., L.P.) and Airmen Integration Research Division (E.S.K.), Wright-Patterson AFB, OH; Department of Neurology (S.M., A.B., P.F.) and Research Imaging Institute (P.F.), University of Texas Health Sciences Center, San Antonio; Departments of Neuroradiology (P.S.) and Neurology (S.M., P.G., J.S., A.R.), 59th Medical Wing, Lackland AFB, TX; Maryland Psychiatric Research Center (L.R., E.H., B.P., P.K.), University of Maryland School of Medicine, Baltimore; and Henry M. Jackson Foundation for the Advancement of Military Science (D.T.), San Antonio Military Medical Center, TX.
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John Sladky
From the U.S. Air Force School of Aerospace Medicine, Aerospace Medicine Consultation Division (S.M., L.P.) and Airmen Integration Research Division (E.S.K.), Wright-Patterson AFB, OH; Department of Neurology (S.M., A.B., P.F.) and Research Imaging Institute (P.F.), University of Texas Health Sciences Center, San Antonio; Departments of Neuroradiology (P.S.) and Neurology (S.M., P.G., J.S., A.R.), 59th Medical Wing, Lackland AFB, TX; Maryland Psychiatric Research Center (L.R., E.H., B.P., P.K.), University of Maryland School of Medicine, Baltimore; and Henry M. Jackson Foundation for the Advancement of Military Science (D.T.), San Antonio Military Medical Center, TX.
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Anthony Brown
From the U.S. Air Force School of Aerospace Medicine, Aerospace Medicine Consultation Division (S.M., L.P.) and Airmen Integration Research Division (E.S.K.), Wright-Patterson AFB, OH; Department of Neurology (S.M., A.B., P.F.) and Research Imaging Institute (P.F.), University of Texas Health Sciences Center, San Antonio; Departments of Neuroradiology (P.S.) and Neurology (S.M., P.G., J.S., A.R.), 59th Medical Wing, Lackland AFB, TX; Maryland Psychiatric Research Center (L.R., E.H., B.P., P.K.), University of Maryland School of Medicine, Baltimore; and Henry M. Jackson Foundation for the Advancement of Military Science (D.T.), San Antonio Military Medical Center, TX.
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Andrew Robinson
From the U.S. Air Force School of Aerospace Medicine, Aerospace Medicine Consultation Division (S.M., L.P.) and Airmen Integration Research Division (E.S.K.), Wright-Patterson AFB, OH; Department of Neurology (S.M., A.B., P.F.) and Research Imaging Institute (P.F.), University of Texas Health Sciences Center, San Antonio; Departments of Neuroradiology (P.S.) and Neurology (S.M., P.G., J.S., A.R.), 59th Medical Wing, Lackland AFB, TX; Maryland Psychiatric Research Center (L.R., E.H., B.P., P.K.), University of Maryland School of Medicine, Baltimore; and Henry M. Jackson Foundation for the Advancement of Military Science (D.T.), San Antonio Military Medical Center, TX.
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Laura Rowland
From the U.S. Air Force School of Aerospace Medicine, Aerospace Medicine Consultation Division (S.M., L.P.) and Airmen Integration Research Division (E.S.K.), Wright-Patterson AFB, OH; Department of Neurology (S.M., A.B., P.F.) and Research Imaging Institute (P.F.), University of Texas Health Sciences Center, San Antonio; Departments of Neuroradiology (P.S.) and Neurology (S.M., P.G., J.S., A.R.), 59th Medical Wing, Lackland AFB, TX; Maryland Psychiatric Research Center (L.R., E.H., B.P., P.K.), University of Maryland School of Medicine, Baltimore; and Henry M. Jackson Foundation for the Advancement of Military Science (D.T.), San Antonio Military Medical Center, TX.
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Elliot Hong
From the U.S. Air Force School of Aerospace Medicine, Aerospace Medicine Consultation Division (S.M., L.P.) and Airmen Integration Research Division (E.S.K.), Wright-Patterson AFB, OH; Department of Neurology (S.M., A.B., P.F.) and Research Imaging Institute (P.F.), University of Texas Health Sciences Center, San Antonio; Departments of Neuroradiology (P.S.) and Neurology (S.M., P.G., J.S., A.R.), 59th Medical Wing, Lackland AFB, TX; Maryland Psychiatric Research Center (L.R., E.H., B.P., P.K.), University of Maryland School of Medicine, Baltimore; and Henry M. Jackson Foundation for the Advancement of Military Science (D.T.), San Antonio Military Medical Center, TX.
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Beenish Patel
From the U.S. Air Force School of Aerospace Medicine, Aerospace Medicine Consultation Division (S.M., L.P.) and Airmen Integration Research Division (E.S.K.), Wright-Patterson AFB, OH; Department of Neurology (S.M., A.B., P.F.) and Research Imaging Institute (P.F.), University of Texas Health Sciences Center, San Antonio; Departments of Neuroradiology (P.S.) and Neurology (S.M., P.G., J.S., A.R.), 59th Medical Wing, Lackland AFB, TX; Maryland Psychiatric Research Center (L.R., E.H., B.P., P.K.), University of Maryland School of Medicine, Baltimore; and Henry M. Jackson Foundation for the Advancement of Military Science (D.T.), San Antonio Military Medical Center, TX.
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David Tate
From the U.S. Air Force School of Aerospace Medicine, Aerospace Medicine Consultation Division (S.M., L.P.) and Airmen Integration Research Division (E.S.K.), Wright-Patterson AFB, OH; Department of Neurology (S.M., A.B., P.F.) and Research Imaging Institute (P.F.), University of Texas Health Sciences Center, San Antonio; Departments of Neuroradiology (P.S.) and Neurology (S.M., P.G., J.S., A.R.), 59th Medical Wing, Lackland AFB, TX; Maryland Psychiatric Research Center (L.R., E.H., B.P., P.K.), University of Maryland School of Medicine, Baltimore; and Henry M. Jackson Foundation for the Advancement of Military Science (D.T.), San Antonio Military Medical Center, TX.
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Elaine S. Kawano
From the U.S. Air Force School of Aerospace Medicine, Aerospace Medicine Consultation Division (S.M., L.P.) and Airmen Integration Research Division (E.S.K.), Wright-Patterson AFB, OH; Department of Neurology (S.M., A.B., P.F.) and Research Imaging Institute (P.F.), University of Texas Health Sciences Center, San Antonio; Departments of Neuroradiology (P.S.) and Neurology (S.M., P.G., J.S., A.R.), 59th Medical Wing, Lackland AFB, TX; Maryland Psychiatric Research Center (L.R., E.H., B.P., P.K.), University of Maryland School of Medicine, Baltimore; and Henry M. Jackson Foundation for the Advancement of Military Science (D.T.), San Antonio Military Medical Center, TX.
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Peter Fox
From the U.S. Air Force School of Aerospace Medicine, Aerospace Medicine Consultation Division (S.M., L.P.) and Airmen Integration Research Division (E.S.K.), Wright-Patterson AFB, OH; Department of Neurology (S.M., A.B., P.F.) and Research Imaging Institute (P.F.), University of Texas Health Sciences Center, San Antonio; Departments of Neuroradiology (P.S.) and Neurology (S.M., P.G., J.S., A.R.), 59th Medical Wing, Lackland AFB, TX; Maryland Psychiatric Research Center (L.R., E.H., B.P., P.K.), University of Maryland School of Medicine, Baltimore; and Henry M. Jackson Foundation for the Advancement of Military Science (D.T.), San Antonio Military Medical Center, TX.
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Peter Kochunov
From the U.S. Air Force School of Aerospace Medicine, Aerospace Medicine Consultation Division (S.M., L.P.) and Airmen Integration Research Division (E.S.K.), Wright-Patterson AFB, OH; Department of Neurology (S.M., A.B., P.F.) and Research Imaging Institute (P.F.), University of Texas Health Sciences Center, San Antonio; Departments of Neuroradiology (P.S.) and Neurology (S.M., P.G., J.S., A.R.), 59th Medical Wing, Lackland AFB, TX; Maryland Psychiatric Research Center (L.R., E.H., B.P., P.K.), University of Maryland School of Medicine, Baltimore; and Henry M. Jackson Foundation for the Advancement of Military Science (D.T.), San Antonio Military Medical Center, TX.
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Citation
White matter hyperintensities on MRI in high-altitude U-2 pilots
Stephen McGuire, Paul Sherman, Leonardo Profenna, Patrick Grogan, John Sladky, Anthony Brown, Andrew Robinson, Laura Rowland, Elliot Hong, Beenish Patel, David Tate, Elaine S. Kawano, Peter Fox, Peter Kochunov
Neurology Aug 2013, 81 (8) 729-735; DOI: 10.1212/WNL.0b013e3182a1ab12

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Abstract

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 regional WMH volume 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 = 0.004) and number (295%; p < 0.001) of WMH. Analysis of regional distribution demonstrated WMH 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 in WMH 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.

GLOSSARY

BET=
brain extraction tool;
DCS=
decompression sickness;
FLAIR=
fluid-attenuated inversion recovery;
FMRIB=
Functional MRI of the Brain;
NDCS=
neurologic decompression sickness;
RF=
radiofrequency;
3D=
3-dimensional;
USAF=
United States Air Force;
WMH=
white matter hyperintensities

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at www.neurology.org

  • Received March 20, 2013.
  • Accepted in final form May 9, 2013.
  • © 2013 American Academy of Neurology
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Letters: Rapid online correspondence

  • pilot control group
    • Julian Hellmann-Regen, Sect. Clinical Neurobiology, Dept. of Psychiatry, Charite Campus Benjamin Franklinjulian.hellmann@charite.de
    • Julian Hellmann-Regen, Kim Hinkelmann, Francesca Regen
    Submitted September 24, 2013
  • Pilot control group
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    Submitted September 24, 2013
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