Evidence-based Synthesis Program 

(ESP)

Complications of mild traumatic brain 

injury in Veterans and military 

personnel: A Systematic Review

Maya O’Neil, PhD, MS

Kathleen Carlson, PhD, MS

Daniel Storzbach, PhD

David Cifu, MD

Robert Ruff, MD, PhD

Joel Scholten, MD

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Evidence-based Synthesis Program 

(ESP)

Acknowledgements

Report Authors 

o Maya O’Neil, PhD, MS

o Kathleen Carlson, PhD, MS

o Daniel Storzbach, PhD

o Lisa Brenner, PhD

o Michele Freeman, MPH

o Ana R. Quiñones, PhD, MS

o Makalapua Motu’apuaka, BS

o Megan Ensley, PsyD

o Devan Kansagara, MD, MCR

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Presenters & Discussants

o Maya O’Neil, PhD, MS

o Kathleen Carlson, PhD, MS

o Daniel Storzbach, PhD

o David Cifu, MD

o Robert Ruff, MD, PhD

o Joel Scholten, MD
Evidence-based Synthesis Program 

(ESP)

Disclosure

This report is based on research conducted by the Evidence-based 

Synthesis Program (ESP) Center located at the Portland VA Medical Center 

funded by the Department of Veterans Affairs, Veterans Health 

Administration, Office of Research and Development, Health Services 

Research and Development. The findings and conclusions in this 

document are those of the author(s) who are responsible for its contents; 

the findings and conclusions do not necessarily represent the views of the 

Department of Veterans Affairs or the United States government. 

Therefore, no statement in this article should be construed as an official 

position of the Department of Veterans Affairs. No investigators have any 

affiliations or financial involvement (e.g., employment, consultancies, 

honoraria, stock ownership or options, expert testimony, grants or patents 

received or pending, or royalties) that conflict with material presented in 

the report. 3 
Evidence-based Synthesis Program 

(ESP)

VA Evidence-based Synthesis (ESP)

Program Overview

• Sponsored by VA QUERI Program.

• Established to provide timely and accurate 

syntheses/reviews of healthcare topics identified by VA 

clinicians, managers and policy-makers, as they work to 

improve the health and healthcare of Veterans. 

• Builds on staff and expertise already in place at the 

Evidence-based Practice Centers (EPC) designated by AHRQ. 

Four of these EPCs are also ESP Centers: 

o Durham VA Medical Center; VA Greater Los Angeles Health Care 

System; Portland VA Medical Center; and Minneapolis VA Medical 

Center. 4 
Evidence-based Synthesis Program 

(ESP)

• Provides evidence syntheses on important clinical practice 

topics relevant to Veterans, and these reports help:

o develop clinical policies informed by evidence, 

o the implementation of effective services to improve patient 

outcomes and to support VA clinical practice guidelines and 

performance measures, and 

o guide the direction for future research to address gaps in 

clinical knowledge.

• Broad topic nomination process – e.g. VACO, VISNs, field – 

facilitated by ESP Coordinating Center (Portland) through 

online process: 

 http://www.hsrd.research.va.gov/publications/esp/TopicNomination.cfm

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Evidence-based Synthesis Program 

(ESP)

• Steering Committee representing research and operations 

(PCS, OQP, ONS, and VISN) provides oversight and guides 

program direction.

• Technical Advisory Panel (TAP)

o Recruited for each topic to provide content expertise.

o Guides topic development; refines the key questions.

o Reviews data/draft report.

• External Peer Reviewers & Policy Partners

o Reviews and comments on draft report

• Final reports posted on VA HSR&D website and disseminated 

widely through the VA. 

http://www.hsrd.research.va.gov/publications/esp/reports.cfm

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Evidence-based Synthesis Program 

(ESP)

Recent Reports:

• Complications of Mild Traumatic Brain Injury in Veterans 

and Military Personnel: A Systematic Review (January, 2013) 

intranet only

• Group Visits Focusing on Education for the Management of 

Chronic Conditions in Adults (December, 2012) intranet only

• Mobile Applications and Internet-based Approaches for 

supporting Non-professional Caregivers (November, 2012) 

intranet only

Full-length reports available on ESP website:

http://www.hsrd.research.va.gov/publications/esp/reports.cfm 7
Evidence-based Synthesis Program 

(ESP)

Overview of Today’s Presentation

• Background

• Why is this topic of interest, and what was the purpose of the report?

• Scope of the reviews and methods

• Synthesizing the best available and most relevant evidence

• Results

• Cognitive functioning

• Physical health

• Mental health

• Functional/Social

• Service Utilization/Costs

• Discussion

• Limitations of the body of literature and of this review

• Future research needs

• Clinical considerations

• VA mTBI policy

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Evidence-based Synthesis Program 

(ESP)

Background

• 12% to 23% of service members returning from Operations 

Enduring Freedom, Iraqi Freedom, and New Dawn 

(OEF/OIF/OND) experienced a TBI while deployed, the 

majority of which are classified as mild (mTBI)

• Differing accounts of mTBI recovery:

o Some researchers suggest most individuals recover within three months

o Others estimate that 10% to 20% of individuals continue to experience 

post-concussive symptoms (e.g., headaches, dizziness, balance 

problems) beyond this time

• Recovery may be unique for OEF/OIF/OND service members

o Multiple mTBIs; mechanism of injury; other physical and mental health concerns

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Evidence-based Synthesis Program 

(ESP)

Key Questions

• Goal of the review: Examine complications of mTBI unique 

to members and Veterans of the military

o 1. What is the prevalence of health problems, cognitive deficits, 

functional limitations, and mental health symptoms that develop or 

persist following mTBI?

o 2. What factors affect outcomes for Veteran/military patients with 

mTBI? 

 2A: Are there pre-injury (premorbid) risk/protective factors that 

affect outcomes for those with mTBI? 

 2B: Are there post-injury risk/protective factors that affect outcomes 

for those with mTBI?

o 3. What is the resource utilization over time for Veteran/military 

patients with mTBI? 10
Evidence-based Synthesis Program 

(ESP)

Methods

• Search: Medline, PsychINFO and Cochrane Register of Controlled 

Trials (OVID), from database inception to October 3rd, 2012

• Reviewed 2,667 titles and abstracts from the electronic and hand 

searches, 353 articles were identified for full-text review

o 31 primary studies met inclusion criteria.

o All included studies were observational and had methodological limitations

• Dual quality assessment of all primary studies and systematic 

reviews

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Evidence-based Synthesis Program 

(ESP)

Inclusion Criteria

• Population: Veterans or members of the military who have 

experienced mTBI as defined by the VA/DoD

o Studies that did not differentiate between adult and child populations, or between 

Veteran/military and civilian populations, were excluded. 

• Outcomes: Health problems, cognitive deficits, functional 

limitations, mental health symptoms, and cost/resource utilization

• Study design: Systematic reviews, meta-analyses, randomized 

controlled trials, prospective and retrospective cohort studies, case 

control studies, case series, and cross-sectional studies

• Sample size: Minimum of 30 mTBI cases

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Evidence-based Synthesis Program 

(ESP)

Overview of Results: 

• 31 studies meeting inclusion criteria

• Very low strength of evidence for all outcomes

o Methodological shortcomings, observational study design

o Diverse outcomes and populations

o Findings are very tentative

• Cognitive, physical, and mental health symptoms are 

commonly reported following mTBI

o Not significantly more common in those with mTBI than those 

without mTBI, with few exceptions. 

• No consistent patterns of potential risk or protective factors 

were identified

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Evidence-based Synthesis Program 

(ESP)

Cognitive Functioning Results 

• 17 studies reported mean scores (not proportions with impairment)

• Mean scores were within normal limits for all reported domains: 

language abilities/general fund of verbal knowledge, visuospatial

abilities, memory, attention/concentration, and executive functioning

• Non-significant differences in cognitive performance compared to 

similar populations without mTBI for all reported domains: language 

abilities/general fund of verbal knowledge, visuospatial abilities, 

memory, attention/concentration, processing speed, and executive 

functioning with few exceptions

o Significantly worse performance on tests of memory, attention/concentration, 

and processing speed was limited to one assessment tool, and these differences 

in performance were only present 72 hours-5 days following injury

• Subjective cognitive complaints were common

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Evidence-based Synthesis Program 

(ESP)

Physical Health Results 

• 17 studies met inclusion criteria

• One study reported average self-reported headache, vision, hearing, 

numbness/tingling, nausea, appetite, and vestibular symptoms in 

the mild-moderate range on the Neuropsychological Symptom 

Inventory

• One study reported prevalence of neurology referrals for headaches 

in a population with mTBI was 33.3%

• Single studies reported significantly worse pain and vestibular 

symptoms for those with mTBI compared to those without mTBI

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Evidence-based Synthesis Program 

(ESP)

Mental Health Results 

• 20 studies met inclusion criteria

• Mean scores on measures of PTSD and anxiety suggested clinically 

significant impairment; studies suggested mixed results (impaired and 

normal range scores) for depression

• One study reported that 45% of those with mTBI experience clinically 

significant impairment from PTSD

• Veterans post-deployment with and without mTBI experience similar levels 

of PTSD and depression

• Two studies reported drug abuse/dependence in 9% of cases and another 

reported alcohol abuse/dependence in 28% of cases

• Prevalence of suicidal ideation (25%), suicidal intent (7%), and past suicide 

attempts (4%) was not significantly different from controls in one study

• Axis I disorder prevalence was 50-78% (two studies); one study reported 

significantly higher prevalence estimates compared to controls

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Evidence-based Synthesis Program 

(ESP)

Functional/Social Outcome Results 

• 12 included studies

• Employment:

o 20% rate of unemployment not significantly different than controls (1 study)

o Significantly worse odds of missing more than 2 days of work, difficulty carrying 

a heavy load in the past month, and difficulty performing physical training in the 

past month for those with mTBI (1 study)

• Sleep: 

o Three studies described similar, and three described significantly worse, sleep 

difficulties for those with versus without mTBI

o One study reported prevalence of sleep difficulties between 13-23%

o One study reported sleep difficulties ranging from mild to very severe depending 

on comorbid PTSD

• Emotional support:

o One study reported prevalence of lack of emotional support to be 26%.

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Evidence-based Synthesis Program 

(ESP)

Service Utilization/Cost Results 

• 7 studies described service utilization; no studies described costs

• Non-significant differences in rates of service utilization compared to 

controls (4 studies)

o However, one study reported that those with mTBI were prescribed an average 

of 18 medications compared to 5 for those without mTBI, though statistical 

significance was not reported

• Prevalence of current counseling reported to be 4-6% and current 

mental health medications 4-5% in one study

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Evidence-based Synthesis Program 

(ESP)

Overall Findings

• Very low strength of evidence for all outcomes

• Cognitive complaints, physical and mental health problems 

are common among those with mTBI

o Objective cognitive deficits and mental health problems are not 

significantly worse compared to similar Veteran groups without 

mTBI

• Little to no evidence for functional, social, service 

utilization, and cost outcomes

• Findings are relatively consistent with civilian literature:

o Though some cognitive impairment within a week of injury is 

common, these effects are no longer present after seven days and 

most functional impairment resolves within a month

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Evidence-based Synthesis Program 

(ESP)

Limitations of the Body of Evidence

• Observational studies with methodological flaws

• Number and mechanism of injuries often not accounted for

• Time since injury not accounted for in most cases

• Lack of prevalence estimates limits accurate population description and 

service utilization/cost estimates

• Cognitive results did not report prevalence of impairment

• Diversity of populations, outcomes, assessment tools

• Potential for selective reporting bias

• Lack of assessor blinding to mTBI status

• Lack of patient blinding to study hypotheses; self-reported outcomes

• Potential confounders (e.g., effort and motivation) not included

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Evidence-based Synthesis Program 

(ESP)

Limitations of this Review

• Limited inclusion to studies using VA/DoD mTBI definition

• Did not apply imaging exclusion criteria as recommended 

by the VA/DoD

• Due to diversity in outcomes, we report statistically 

significant results within studies rather than mathematically 

combining results across studies

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Evidence-based Synthesis Program 

(ESP)

Future Research Needs

• Clear, consistent reporting of mTBI definition/criteria including imaging results

• Validated assessment tools, replication studies, common data elements 

(http://www.commondataelements.ninds.nih.gov/TBI.aspx#tab=Data_Standards and 

http://www.ncbi.nlm.nih.gov/pubmed/21044708), for meta-analytic purposes

• Report and analyze impact of multiple mTBI events, mechanism of injury, and 

time since injury, as well as other potential moderating/mediating factors such 

as demographic characteristics and comorbid health problems

• Adjust for the effects of possible confounders such as PTSD, effort/motivation

• Report prevalence estimates as well as clinically significant impairment rather 

than only mean scores

• Reduce risk of bias by using blinded outcome assessors, patient blinding to 

study hypotheses, and a priori reporting of included outcomes

• Large, prospective cohort studies, though challenging, are needed to improve 

the quality of evidence for Veterans and members of the military 22
Evidence-based Synthesis Program 

(ESP)

Implications for Clinical Care

• Some symptoms that patients ascribe to mTBI may be related to 

comorbid mental or physical health concerns, or to other factors such 

as combat stress, and post-deployment readjustment

• Engagement in services to identify potential health problems and 

appropriate, evidence-based treatment for these concerns (e.g., 

treatment for PTSD, sleep disorders, etc.)

• Because objective cognitive deficits are not common, particularly after 

three months, individuals experiencing ongoing cognitive deficits 

following first-line treatment for co-occurring symptoms and disorders 

may need further testing (e.g., neuropsychological or neurological 

evaluation, imaging)

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Evidence-based Synthesis Program 

(ESP)

Discussants:

David Cifu, Robert Ruff, Joel Scholten

• Overview of mTBI policy in the VA • VA/DoD Clinical Practice Guidelines: 

http://www.healthquality.va.gov/mtbi/concussion_mtbi_full_1_0.pdf

• How can the current, limited evidence guide best 

practices in policy, research, and clinical care?

• What do clinicians need to know now to treat those with mTBI (PCPs, 

neurologists, neuropsychologists, etc.)?

• How should we design research to address the gaps in our knowledge?

• What does VA leadership need to do to encourage VA work that builds the 

evidence base in important and meaningful ways?

• What mTBI research is ongoing in VA/military settings?

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Evidence-based Synthesis Program 

(ESP)

Questions?

If you have further questions, 

feel free to contact:

Maya O’Neil, PhD, MS

maya.oneil@va.gov

The full report and cyberseminar presentation is available on the ESP website: 

http://www.hsrd.research.va.gov/publications/esp/

(currently intranet only, soon full release)

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