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Early Clinical Predictors of 5-Year Outcome After Concussive Blast Traumatic Brain Injury
Open accessAbstract
Importance: The long-term clinical effects of wartime traumatic brain injuries (TBIs), most of which are mild, remain incompletely described. Current medical disability cost estimates from world conflicts continually surpass projections. Additional information regarding long-term functional trajectory is needed to reduce this extensive public health burden. Objectives: To examine 5-year clinical outcomes leveraging existing clinical data collected at 1 year after injury in the same patients and to identify early risk factors for long-term disability. Design, Setting, and Participants: This prospective, longitudinal study enrolled active-duty US military after concussive blast injury (n = 50) in the acute to subacute stage and combat-deployed control individuals (n = 44) in Afghanistan or after medical evacuation to Germany from November 1, 2008, through July 1, 2013. One- and 5-year clinical evaluations were completed in the United States. All concussive blast injuries met the Department of Defense definition of mild, uncomplicated TBI. In-person clinical evaluations included standardized evaluations for neurobehavior, neuropsychological performance, and mental health burden that were essentially identical to the evaluations completed at 1-year follow-up. Data were analyzed from October 1 through November 30, 2016. Main Outcomes and Measures: Changes in the in-person standardized evaluations for neurobehavior, neuropsychological performance, and mental health burden from the 1- to 5-year follow-up. Predictive modeling was used to identify early risk factors for long-term disability. Results: Among the 94 participants (87 men [93%] and 7 women [7%]; mean [SD] age, 34 [8] years), global disability, satisfaction with life, neurobehavioral symptom severity, psychiatric symptom severity, and sleep impairment were significantly worse in patients with concussive blast TBI compared with combat-deployed controls, whereas performance on cognitive measures was no different between groups at the 5-year evaluation. Logistic regression on the dichotomized Extended Glasgow Outcome Scale (GOS-E) at 5 years as a measure of overall disability identified brain injury diagnosis, preinjury intelligence, motor strength, verbal fluency, and neurobehavioral symptom severity at 1 year as risk factors for a poor outcome at 5 years, with an area under the curve of 0.92 indicating excellent prediction strength. Thirty-six of 50 patients with concussive blast TBI (72%) had a decline in the GOS-E from the 1- to 5-year evaluations, in contrast with only 5 of 44 combat-deployed controls (11%). Worsening of symptoms in concussive blast TBI was also observed on measures of posttraumatic stress disorder and depression. Service members with concussive blast TBI experienced evolution, not resolution, of symptoms from the 1- to 5-year outcomes. Conclusions and Relevance: Considerable decline was observed in military service members with concussive blast TBI when comparing 1- and 5-year clinical outcomes. These results advocate for new treatment strategies to combat the long-term and extremely costly effect of these wartime injuries.
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“The severity of depressive symptoms following concussion is strongly correlated with global disability, rate of recovery, and quality of life (4, 10, 11).”
From Adaptive trial for the treatment of depressive symptoms associated with concussion using accelerated intermittent theta burst stimulation (ADEPT): rationale, design and methods (2025) · cites this paper as [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Military service members (SMs) and veterans who have sustained one or more concussions during their service have significantly higher rates of persistent depressive symptoms and suicidality compared to non-injured peers.”
From Adaptive trial for the treatment of depressive symptoms associated with concussion using accelerated intermittent theta burst stimulation (ADEPT): rationale, design and methods (2025) · cites this paper as [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Despite the common occurrence of chronic cognitive subjective symptomology after mTBI, extant research shows a lack of a consistent relationship with cognitive performance on formal neuropsychological examination, including samples of military personnel”
From Can mild traumatic brain injury alter cognition chronically? A LIMBIC-CENC multicenter study. (2023) · cites this paper as Mac Donald et al., 2017
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Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research
Maas, A. I. R., Menon, D. K., Adelson, P. D., Andelic, N., Bell, M. J., Belli, A., Bragge, P., Brazinova, A., Büki, A., Chesnut, R. M., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30371-x · Cited by 2,609
Self-citationEpidemiology of Chronic Effects of Traumatic Brain Injury
Haarbauer-Krupa, J. K., Pugh, M. J., Prager, E. M., Harmon, N., Wolfe, J., & Yaffe, K. S. (2021) · Journal of Neurotrauma · doi:10.1089/neu.2021.0062 · Cited by 380
Stein, M. B., Jain, S., Giacino, J. T., Levin, H., Dikmen, S., Nelson, L. D., Vassar, M. J., Okonkwo, D. O., Diaz-Arrastia, R., Robertson, C. S., et al. (2019) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2018.4288 · Cited by 308
Self-citationMild TBI and risk of Parkinson disease
Gardner, R. C., Byers, A. L., Barnes, D. E., Li, Y., Boscardin, W. J., & Yaffe, K. S. (2018) · Neurology · doi:10.1212/wnl.0000000000005522 · Cited by 297
A systematic review of sex differences in concussion outcome: What do we know?
Merritt, V. C., Padgett, C. R., & Jak, A. J. (2019) · The Clinical Neuropsychologist · doi:10.1080/13854046.2018.1508616 · Cited by 157
Metadata
- Authors
- Mac Donald, C. L., Barber, J., Jordan, M., Johnson, A. M., Dikmen, S., Fann, J. R., & Temkin, N.
- Affiliations
- Department of Neurological Surgery, University of Washington, Seattle
- University of Washington (US)
- Washington University in St. Louis (US)
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2017-07-01
- Volume
- 74
- Issue
- 7
- Pages
- 821
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC5732492
- OpenAlex
- W2611287086
- Cited by
- 142
- References
- 70
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 12 · 2023: 10 · 2022: 14 · 2021: 18 · 2020: 21 · 2019: 21 · 2018: 19 · 2017: 7
- FWCI
- 14.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense (W81XWH1320095, W81XWH, W81XWH-13-2-, W81XWH-13)
- National Institutes of Health (W81XWH)
- National Institute of Neurological Disorders and Stroke (R01NS091618)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Physical Sciences › Engineering › Biomedical Engineering › Automotive and Human Injury Biomechanics
- Keywords
- mild traumatic brain injury, military personnel, long-term disability, risk factors, neurobehavioral symptoms, sleep disorders, psychiatric symptoms, life satisfaction, cognitive function, Glasgow Outcome Scale-Extended, functional outcome prediction, neuropsychological performance, motor strength, verbal fluency, war-related brain injury, Afghanistan deployment
- MeSH terms
- Adult, Behavioral Symptoms, Blast Injuries, Brain Concussion, Female, Humans, Longitudinal Studies, Male, Migraine Disorders, Military Personnel, Prognosis, Risk Factors, United States, Case-Control Studies, Outcome Assessment, Health Care, Glasgow Outcome Scale, Afghan Campaign 2001-, Cognitive Dysfunction
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