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Original Investigation |

Prospectively Assessed Clinical Outcomes in Concussive Blast vs Nonblast Traumatic Brain Injury Among Evacuated US Military Personnel

Christine L. Mac Donald, PhD1,2; Ann M. Johnson1; Linda Wierzechowski, RN3; Elizabeth Kassner, RN3; Theresa Stewart, RN3; Elliot C. Nelson, MD4; Nicole J. Werner, PhD1; David Zonies, MD, MPH3; John Oh, MD3,5; Raymond Fang, MD3,6; David L. Brody, MD, PhD1
[+] Author Affiliations
1Department of Neurology, Washington University School of Medicine, St Louis, Missouri
2Department of Neurological Surgery, University of Washington, Seattle
3Landstuhl Regional Medical Center, Landstuhl, Germany
4Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri
5Department of Trauma, Critical Care, and Acute Care Surgery, Walter Reed National Military Medical Center, Baltimore, Maryland
6US Air Force Center for Sustainment of Trauma and Readiness Skills, R. Adams Cowley Shock Trauma Center, University of Maryland, Baltimore
JAMA Neurol. 2014;71(8):994-1002. doi:10.1001/jamaneurol.2014.1114.
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Importance  Blast injury has been identified as the signature injury in the conflicts in Iraq and Afghanistan. However it remains to be determined whether fundamental differences may exist between blast-related traumatic brain injury (TBI) and TBI due to other mechanisms.

Objectives  To determine similarities and differences between clinical outcomes in US military personnel with blast-related vs. non-blast-related concussive TBI and to identify the specific domains of impairment that best correlate with overall disability.

Design, Setting, and Participants  Prospective cohort study involving active duty US Military personnel evacuated from Iraq or Afghanistan to Landstuhl Regional Medical Center, in Landstuhl, Germany. Four groups of participants were enrolled from 2010 to 2013: (1) blast plus impact complex TBI (n=53), (2) non-blast related TBI with injury due to other mechanisms (n=29), (3) blast-exposed controls evacuated for other medical reasons (n=27) (4) non-blast-exposed controls evacuated for other medical reasons (n=69). All patients with TBI met Department of Defense criteria for concussive (mild) TBI. The study participants were evaluated 6-12 months after injury at Washington University in St Louis. In total, 255 subjects were enrolled in the study, and 183 participated in follow-up evaluations, 5 of whom were disqualified.

Main Outcomes and Measures  In-person clinical examinations included evaluation for overall disability, a standardized neurological exam, headache questionnaires, neuropsychological test battery, combat exposure and alcohol use surveys, and structured interview evaluations for post-traumatic stress disorder (PTSD) and depression.

Results  Global outcomes, headache severity, neuropsychological performance, and surprisingly even PTSD severity and depression were indistinguishable between the two TBI groups, independent of mechanism of injury. Both TBI groups had higher rates of moderate to severe overall disability than the respective control groups: 41/53 (77%) of blast plus impact TBI and 23/29 (79%) of nonblast TBI vs. 16/27 (59%) of blast-exposed controls and 28/69 (41%) of non-blast-exposed controls. In addition, blast-exposed controls had worse headaches and more severe PTSD than non-blast-exposed controls. Self-reported combat exposure intensity was higher in the blast plus impact TBI group than in nonblast TBI group and was higher in blast-exposed controls than in non-blast-exposed controls. However, combat exposure intensity did not correlate with PTSD severity in the TBI groups, but a modest positive correlation was observed in the controls. Overall outcomes were most strongly correlated with depression, headache severity, and number of abnormalities on neuropsychological testing. However a substantial fraction of the variance in overall outcome was not explained by any of the assessed measures.

Conclusions and Relevance  One potential interpretation of these results is that TBI itself, independent of injury mechanism and combat exposure intensity, is a primary driver of adverse outcomes. Many other important factors may be as yet unmeasured, and adverse outcomes following war-time injuries are difficult to fully explain.

Trial Registration  clinicaltrials.gov Identifier: NCT01313130.

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Figure 1.
Worse Global Outcomes After Traumatic Brain Injury (TBI) Than in Control Subjects Among Evacuated US Military Personnel

Results were assessed at 6 to 12 months after enrollment. P values were calculated using 1-tailed Mann-Whitney test and were reported if significant after correction for multiple comparisons at P < .0125. GOS-E indicates Glasgow Outcome Scale–Extended.

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Figure 2.
Clinical Measures Collected at 6 to 12 Months After Injury

A, Neuropsychological test performance abnormalities were detected in subsets of patients with traumatic brain injury (TBI). The number of patients with neuropsychological test abnormalities (defined as >2 SDs outside the mean for the nonblast control group) is displayed by group compared with what would be expected by chance (blue bars). The percentage of patients is shown to account for the differences in the numbers of patients across groups. The dotted box indicates the group of patients who had poor performance on 2 or more of 18 neuropsychological assessments. P values were calculated using χ2 test between each group vs expected numbers by chance. B, Headache impairment was assessed by the Migraine Disability Assessment (MIDAS) (maximum score, 180). C, Posttraumatic stress disorder (PTSD) severity was assessed by the Clinician-Administered PTSD Scale for DSM-IV (CAPS) (maximum score, 136). The CAPS total severity comparison of blast control subjects vs patients with blast plus impact TBI was not significant (P = .06). D, Depression severity was assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS) (maximum score, 60). Higher scores indicate worse impairment. P values were calculated using 1-tailed Mann-Whitney test and were reported if significant after correction for multiple comparisons at P < .0125. NS indicates not significant.

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Figure 3.
Correlations Between Combat Exposure Intensity and Posttraumatic Stress Disorder

A, Combat exposure intensity was assessed by the Combat Exposures Scale (CES). Higher scores indicate greater self-reported combat exposure (maximum score, 41). P values were calculated using 1-tailed Mann-Whitney test and were reported if significant after correction for multiple comparisons at P < .0125. B, A positive correlation was found between the Clinician-Administered PTSD Scale for DSM-IV (CAPS) total score and the combat exposure intensity measured by the CES in control subjects. C, In contrast, no correlation was observed between the CAPS total score and the CES score in the traumatic brain injury (TBI) groups. NS indicates not significant.

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