Evidence-based Synthesis Program Department of Veterans Affairs

Health Services Research & Development Service

January 2013

Prepared for:

Department of Veterans Affairs

Veterans Health Administration

Quality Enhancement Research Initiative

Health Services Research & Development Service

Washington, DC 20420

Prepared by:

Evidence-based Synthesis Program (ESP) Center

Portland VA Medical Center

Portland, OR

Devan Kansagara, M.D., M.C.R., Director

Investigators:

Principal Investigator: 

Maya Elin O’Neil, Ph.D., M.S.

Co-Investigators and Research Associates: 

Kathleen Carlson, Ph.D., M.S.

Daniel Storzbach, Ph.D.

Lisa Brenner, Ph.D.

Michele Freeman, M.P.H.

Ana Quiñones, Ph.D.

Makalapua Motu’apuaka, B.S.

Megan Ensley, Psy.D.

Devan Kansagara, M.D., M.C.R.

Complications of Mild Traumatic 

Brain Injury in Veterans and Military 

Personnel: A Systematic Review

EXECUTIVE SUMMARY
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Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

PREFACE

Quality Enhancement Research Initiative’s (QUERI) Evidence-based Synthesis Program 

(ESP) was established to provide timely and accurate syntheses of targeted healthcare topics 

of particular importance to Veterans Affairs (VA) managers and policymakers, as they work to 

improve the health and healthcare of Veterans. The ESP disseminates these reports throughout 

VA.

QUERI provides funding for four ESP Centers and each Center has an active VA affiliation. The 

ESP Centers generate evidence syntheses on important clinical practice topics, and these reports 

help:

• develop clinical policies informed by evidence,

• guide the implementation of effective services to improve patient outcomes 

and to support VA clinical practice guidelines and performance measures, 

and 

• set the direction for future research to address gaps in clinical knowledge.

In 2009, the ESP Coordinating Center was created to expand the capacity of QUERI Central 

Office and the four ESP sites by developing and maintaining program processes. In addition, 

the Center established a Steering Committee comprised of QUERI field-based investigators, 

VA Patient Care Services, Office of Quality and Performance, and Veterans Integrated Service 

Networks (VISN) Clinical Management Officers. The Steering Committee provides program 

oversight, guides strategic planning, coordinates dissemination activities, and develops 

collaborations with VA leadership to identify new ESP topics of importance to Veterans and the 

VA healthcare system.

Comments on this evidence report are welcome and can be sent to Nicole Floyd, ESP 

Coordinating Center Program Manager, at nicole.floyd@va.gov.

Recommended citation: O’Neil ME, Carlson KF, Storzbach D, Brenner LA, Freeman M, 

Quiñones A, Motu’apuaka M, Ensley M, Kansagara D. Complications of Mild Traumatic Brain 

Injury in Veterans and Military Personnel: A Systematic Review. VA-ESP Project #05-225; 2012

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

(ESP) Center located at the Portland VA Medical Center, Portland, OR funded by the 

Department of Veterans Affairs, Veterans Health Administration, Office of Research and 

Development, Quality Enhancement Research Initiative. 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.
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Complications of Mild Traumatic Brain Injury in Veterans

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TABLE OF CONTENTS

Executive summary

Background......................................................................................................................................................1

Methods...........................................................................................................................................................1

Results .............................................................................................................................................................2

Limitations and Future Research.....................................................................................................................4

Abbreviations Table.........................................................................................................................................5

Introduction ............................................................................................................................................................8

Methods

Topic Development..........................................................................................................................................9

Search Strategy................................................................................................................................................9

Study Selection..............................................................................................................................................10

Data Abstraction ............................................................................................................................................ 11

Quality Assessment ....................................................................................................................................... 11

Data Synthesis...............................................................................................................................................12

Rating the Body of Evidence.........................................................................................................................12

Peer Review...................................................................................................................................................12

Results

Methodologic Considerations........................................................................................................................13

Literature Flow ..............................................................................................................................................13

Summary of Findings....................................................................................................................................23

Cognitive Functioning Results......................................................................................................................23

Physical Health Results.................................................................................................................................30

Mental Health Results ...................................................................................................................................34

Functional/Social Outcome Results ..............................................................................................................38

Service Utilization/Costs Results..................................................................................................................40

Summary And Discussion

Summary of Evidence ...................................................................................................................................42

Limitations and Recommendations for Future Research ..............................................................................46

Conclusions ...................................................................................................................................................48

References..............................................................................................................................................................49

Tables

Table 1. Descriptive Characteristics of Studies of U.S. Veterans and Members of the U.S. 

Military with mTBI.......................................................................................................................15

Table 2. Summary of Evidence for Cognitive Functioning Outcomes Associated with mTBI in 

Veteran and Military Populations .................................................................................................24

Table 3. Summary of Evidence for Physical Health Outcomes Associated with mTBI in Veteran 

and Military Populations...............................................................................................................31
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Complications of Mild Traumatic Brain Injury in Veterans

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Table 4. Summary of Evidence for Mental Health Outcomes Associated with mTBI in Veteran 

and Military Populations...............................................................................................................35

Table 5. Summary of Evidence for Functional/Social Outcomes Associated with mTBI in 

Veteran and Military Populations .................................................................................................39

Table 6. Summary of Evidence for Service Utilization/Costs Associated with mTBI in Veteran 

and Military Populations...............................................................................................................41

Figure

Figure 1. Literature Flow Diagram ..............................................................................................................14

Appendix A. Search Strategies...................................................................................................................55

Appendix B. Study Selection Form...........................................................................................................59

Appendix C. Definition of Mtbi from the VA/DOD Clinical Practice Guideline

for Management of Concussion/Mild Traumatic Brain Injury (2009)...........61

Appendix D. Excluded Studies That Did Not Meet MTBI Definition Criteria ...................63

Appendix E. Results of Included Studies...............................................................................................79

Cognitive Functioning

Table 1a. Language abilities and general fund of verbal knowledge measures in studies of U.S. 

Veterans and members of the U.S. military with mild TBI ..........................................................79

Table 1b. Visuospatial function in studies of U.S. Veterans and members of the U.S. military with 

mild TBI........................................................................................................................................80

Table 1c. Memory functioning in studies of U.S. Veterans and members of the U.S. military with 

mild TBI........................................................................................................................................81

Table 1d. Attention/concentration measures in studies of U.S. Veterans and members of the U.S. 

military with mTBI.......................................................................................................................84

Table 1e. Cognitive processing speed in studies of U.S. Veterans and members of the U.S. military 

with mild TBI................................................................................................................................86

Table 1f. Executive functioning in studies of U.S. Veterans and members of the U.S. military 

with mild TBI................................................................................................................................88

Table 1g. Effort and motivation measures in a study of U.S. Veterans with mild TBI evaluated in 

a research versus forensic context ................................................................................................89

Table 1h. Total and cross-domain composite scores in studies of U.S. Veterans and members 

of the U.S. military with mild TBI................................................................................................90

Table 1i. Self-reported cognitive deficits in studies of U.S. Veterans and members of the U.S. 

military with mild TBI..................................................................................................................91

Physical Health Outcomes

Table 2a. Headache outcomes in studies of U.S. Veterans and members of the U.S. military with 

mild TBI........................................................................................................................................93

Table 2b. Pain outcomes in studies of U.S. Veterans and members of the U.S. military with 

mild TBI........................................................................................................................................95

Table 2c. Vestibular outcomes in studies of U.S. Veterans and members of the U.S. military with 

mild TBI........................................................................................................................................95

Table 2d. Vision outcomes in studies of U.S. Veterans and members of the U.S. military with 

mild TBI........................................................................................................................................96
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Complications of Mild Traumatic Brain Injury in Veterans

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Table 2e. Hearing outcomes in studies of U.S. Veterans and members of the U.S. military with 

mild TBI........................................................................................................................................96

Table 2f. Neurological outcomes in studies of U.S. Veterans and members of the U.S. military 

with mild TBI................................................................................................................................97

Table 2g. Nausea/appetite outcomes in studies of U.S. Veterans and members of the U.S. military 

with mild TBI................................................................................................................................97

Mental Health Outcomes

Table 3a. PTSD outcomes in studies of U.S. Veterans and members of the U.S. military with 

mild TBI........................................................................................................................................98

Table 3b. Measures of anxiety in studies of U.S. Veterans and members of the U.S. military with 

mild TBI......................................................................................................................................101

Table 3c. Measures of depression in studies of U.S. Veterans and members of the U.S. military 

with mild TBI..............................................................................................................................102

Table 3d. Substance use disorders in studies of U.S. Veterans and members of the U.S. military 

with mild TBI..............................................................................................................................102

Table 3e. Suicide-related outcomes in studies of U.S. Veterans and members of the U.S. military 

with mild TBI..............................................................................................................................103

Table 3f. Other mental health outcomes in studies of U.S. Veterans and members of the U.S. 

military with mild TBI................................................................................................................103

Functional/Social Outcomes

Table 4a. Employment outcomes in studies of U.S. Veterans and members of the U.S. military 

with mild TBI..............................................................................................................................104

Table 4b. Sleep outcomes in studies of U.S. Veterans and members of the U.S. military with mild TBI .........105

Table 4c. Social outcomes in studies of U.S. Veterans and members of the U.S. military with mild TBI ........106

Service Utilization/Costs

Table 5. Service utilization outcomes in studies of U.S. Veterans and members of the U.S. military 

with mild TBI..............................................................................................................................106

Appendix F. List of Excluded Studies Grouped by Reason for Exclusion.........................107

Appendix G. Peer Review Comments and Responses......................................................................125
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Complications of Mild Traumatic Brain Injury in Veterans

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EXECUTIVE SUMMARY

BACKGROUND

Traumatic brain injury (TBI) is a common condition, especially among military members. 

Twelve to 23 percent of service members returning from Operations Enduring Freedom, Iraqi 

Freedom, and New Dawn (OEF/OIF/OND) experienced a TBI while deployed. Although various 

criteria are used to define TBI severity, the majority of documented TBI events among OEF/OIF/

OND service members may be classified as mild in severity, or mTBI, according to the definition 

used by the Veterans Health Administration and Department of Defense (VA/DoD).

While some researchers suggest most individuals recover within three months of an mTBI, 

others estimate that 10 to 20 percent of individuals continue to experience post-concussive 

symptoms (e.g., headaches, dizziness, balance problems) beyond this time fame. This estimate 

may be higher among OEF/OIF service members given the frequency of multiple TBI events, 

concomitant mental health conditions such as depression and posttraumatic stress disorder 

(PTSD), and other factors unique to combat deployments. As such, deployment-related mTBI is 

a significant issue for the VA, as patients who report ongoing mTBI symptoms may require the 

attention from a range of health care professionals. This evidence synthesis review will be used 

by the VHA TBI Advisory Committee to develop strategies to identify those at-risk for long-term 

mTBI effects, inform clinical practice, determine resource allocation, and identify future research 

priorities. 

The key questions were:

Key Question #1. For Veteran/military populations, what is the prevalence of health problems 

(such as pain, seizure disorders, headaches, migraines, and vertigo), cognitive deficits, functional 

limitations (such as employment status, changes in marital status/family dynamics), and mental 

health symptoms (such as PTSD and depression) that develop or persist following mTBI?

Key Question #2. What factors affect outcomes for Veteran/military patients with mTBI? Key 

Question 2A: For Veteran/military populations, are there pre-injury (premorbid) risk/protective 

factors (e.g., pre-injury mental health factors, genetic factors, or prior concussions) that affect 

outcomes for mTBI? Key Question 2B: For Veteran/military populations, are there post-injury 

risk/protective factors (e.g., PTSD) that affect outcomes for mTBI?

Key Question #3. What is the resource utilization over time for Veteran/military patients with 

mTBI?

METHODS

We searched Medline, PsychINFO and Cochrane Register of Controlled Trials (OVID), from 

database inception to October 3, 2012. We adapted the search strategy developed by the World 

Health Organization (WHO) Collaborating Centre for Neurotrauma Prevention, Management 

and Rehabilitation Task Force for a recent systematic review of prognosis after mTBI, and we 

included terms to identify articles specific to Veterans and military personnel. We obtained 
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Complications of Mild Traumatic Brain Injury in Veterans

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additional articles from systematic reviews, reference lists of pertinent studies, reviews, 

editorials, and by consulting clinical and research experts in the area of mTBI. 

We included studies reporting outcomes in Veterans or military personnel who had suffered 

an mTBI using a case definition consistent with definitions in the VA/DoD Clinical Practice 

Guideline for Management of Concussion/Mild Traumatic Brain Injury. Reviewers trained in 

the critical analysis of literature assessed the titles and abstracts for relevance, and retrieved 

full-text articles for further review. We compiled a narrative synthesis of findings. We assessed 

individual study quality using criteria based on the Newcastle-Ottawa quality assessment tools 

for observational studies. We assessed the overall strength of evidence for the body of included 

literature according to criteria developed by the GRADE Working Group.

A draft version of this report was reviewed by 11 technical experts, as well as clinical leadership. 

Reviewer comments were addressed and our responses were incorporated in the final report 

(Appendix G).

RESULTS

From 2,668 titles and abstracts, we identified 354 articles for full-text review. Of these, 31 

primary studies met inclusion criteria. In general, we found that though self-reported cognitive, 

physical, and mental health symptoms were common in the Veteran/military population, there 

was little evidence that symptoms were more common in those with mTBI than those without 

mTBI. However, the evidence base is weakened by inconsistent findings, methodologic 

shortcomings of many studies, and variation in outcomes considered and outcome measurement 

approaches. The following sections detail findings by symptom category. 

Summary of Cognitive Functioning Results

We found 17 studies reporting cognitive outcomes for those with mTBI. Overall, few studies 

found an association between mTBI and cognitive deficits. The strength of evidence is low 

overall because of poor and incomplete reporting of data and sampling procedures, lack of timesince-injury information, and because most studies were unblinded and single-center.

There were studies that found mTBI patients had deficits in visuospatial abilities, attention/

concentration, and total/cross-domain composite scores as compared to patients without mTBI. 

However, even within each of these subdomains, findings were inconsistent across studies. 

In nearly all studies, scores for each of the subscales fell within normal limits, suggesting no 

clinically significant impairment in the group as a whole. Because studies did not report the 

proportion of patients scoring below normal range for each of the subscales, it is unclear whether 

there may have been subgroups of mTBI patients with cognitive deficits.

It is difficult to draw overall conclusions about which factors, in addition to mTBI, are 

independently associated with cognitive test performance since studies evaluated a variety 

of different factors and there were inconsistent findings among studies. Impaired cognitive 

test performance was associated with comorbid mental health diagnosis, time since injury of 

less than 10 days, self-reported cognitive complaints, and experiencing loss or alteration of 

consciousness at the time of injury.
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Complications of Mild Traumatic Brain Injury in Veterans

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Self-reported cognitive complaints were common, both in Veterans with and without mTBI. 

Correlates of more severe self-reported cognitive problems include having an additional injury, 

loss of consciousness (LOC) or post-traumatic amnesia (PTA) at the time of injury versus only 

experiencing alteration of consciousness (AOC), being service connected, and having an Axis I 

mental health disorder. 

Summary of Physical Health Results

We found 17 studies reporting physical health outcomes for those with mTBI. Low strength 

evidence suggests that self-reported physical symptoms are associated with mTBI. This body of 

evidence is comprised entirely of low quality studies generally limited by poor and incomplete 

reporting of data and sampling procedures, by lack of time-since-injury information, and because 

most studies were unblinded and single-center. 

Studies included in this report suggest that symptoms commonly reported by those with mTBI 

include headaches, pain, vestibular symptoms, hearing and vision problems, nausea or loss 

of appetite, and neurologic symptoms. One study reported that the prevalence of neurology 

referrals for headaches was 33.3% for Veterans with mTBI, though no other physical health 

studies reported prevalence estimates for these outcomes. It is also unclear whether mTBI 

directly contributes to the prevalence or severity of physical health symptoms as only two studies 

included a comparison group of participants without mTBI. Symptom severity ranged widely 

across individuals and many of the physical health outcomes were based solely on responses 

to an individual item from the Neurobehavioral Symptom Inventory (NSI), a general postconcussive symptom inventory. Additionally, inconsistent information on risk and protective 

factors provided insufficient evidence to make strong conclusions about potentially moderators 

of physical health outcomes.

Summary of Mental Health Results

Twenty studies reported mental health outcomes for Veterans or members of the military with 

mTBI. Mental health outcomes varied greatly in terms of methods of assessment, ranging from 

lengthy clinical interviews based on diagnostic criteria, to single-item, self-report screeners. 

Overall, this body of literature provides low strength evidence, as it is based on low quality 

studies with many methodological limitations.

Studies included in this review suggest that there are high rates of mental health disorders and 

symptoms reported by Veterans and members of the military who have a history of mTBI. 

Prevalence of Axis I mental health disorders ranged from 50-78% in two studies; single studies 

reported that the rate of PTSD was 45%, alcohol abuse/dependence was 28%, drug abuse/

dependence was 9%, suicidal ideation was 25%, suicidal intent was 7%, and past suicide 

attempts was 4% for Veterans with mTBI. Notably, however, the majority of included studies 

suggest that there are few, if any, significant differences in mental health outcomes for those with 

mTBI compared to Veteran/military participants without mTBI. Finally, though many individual 

studies investigated potential moderating factors for mental health outcomes, no clear risk or 

protective factors were identified.
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Complications of Mild Traumatic Brain Injury in Veterans

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Summary of Functional/Social Outcome Results

We found 12 studies, all low quality, reporting functional/social outcomes for Veterans or members 

of the military with mTBI. Due to methodologic limitations as well as small sample size and 

inadequate reporting of and accounting for time since injury, the strength of evidence for this group 

of studies is low. One study reported that approximately 20% of Veterans with mTBI experience 

unemployment. One of two studies comparing participants with and without mTBI found higher 

unemployment among those with mTBI. Another study found that 26% of those with mTBI had 

difficulties with interpersonal relationships, though this was not significantly different in comparison 

to individuals without mTBI. Ten studies examined sleep disturbance: two found an overall 

prevalence of 13-23%, and seven found that sleep disturbances, when present, were moderate to 

severe. One of two studies found that sleep disturbance was more common in those with mTBI 

compared to those without. No clear patterns of risk or protective factors emerged from studies 

examining potential moderators of associations between mTBI and functional or social outcomes. 

Summary of Service Utilization/Cost Results

We found seven low quality studies that described service utilization by those with mTBI, but 

no studies that reported costs associated with mTBI. The overall strength of evidence was low 

because of the small number and methodologic shortcomings of studies. The available literature 

suggests that there are few differences in service utilization for those with mTBI compared to 

similar controls; no significant associations with risk or protective factors were identified.

Conclusion

Overall, given the low strength of evidence, it is difficult to draw firm conclusions about the 

effects of mTBI in Veteran and military populations. The literature reviewed here is relatively 

consistent with findings from the more methodologically rigorous, prospective, longitudinal 

studies conducted in civilian populations. Both bodies of literature suggest that though some 

negative outcomes occur for a significant portion of individuals who have mTBI, most objective 

results (e.g., objective cognitive test results) are not significantly different from control 

participants, and deficits that are present shortly following injury most often resolve within days 

to months. The literature on Veterans and members of the military suggests that many have 

physical and mental health symptoms, but it is not clear that those with mTBI experience more or 

higher severity symptoms than those without mTBI suggesting that outcomes may be influenced 

by other deployment-related conditions such as PTSD. The studies included in this report were 

low quality, cross sectional studies which did not provide consistent evidence for potential 

moderators of mTBI outcomes.

LIMITATIONS AND FUTURE RESEARCH

One of the major limitations of this literature is the inadequate reporting of and accounting for 

time since injury. Future research on Veterans and members of the military should not only report 

time since injury for their research populations, but specifically account for time since injury in 

their analyses so that outcomes can be analyzed over time.

Few studies presented data on all outcomes of interest to the stakeholders of this review, and 

few studies reported their outcome reporting rationale. Most studies relied on clinical datasets, 
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Complications of Mild Traumatic Brain Injury in Veterans

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rather than research databases or registries. It is likely that many studies only included outcomes 

of relevance to the authors’ particular study questions, though it is impossible to know whether 

some studies did not report outcomes given a lack of association with mTBI. There is a pressing 

need for large cohort studies of Veterans with and without mTBI that prospectively collect data 

on all risk and protective factors, and all outcomes of interest. Such studies would be relatively 

costly but would result in higher-quality evidence on which more definitive conclusions could be 

based.

Very few studies reported the actual prevalence of symptoms or conditions; most studies simply 

reported mean scores for the entire study group. Future research should report proportions of 

individuals with clinically significant impairment for each outcome.

Although a strength of this review was that many of the included studies relied on well-validated 

measures commonly used with Veteran/military populations, many of the clinical outcomes 

relied solely on self-reported symptoms, often obtained from single items on questionnaires. 

Results from this review and from the civilian literature suggest that self-reported deficits are 

more likely to be reported by individuals with mTBI compared to similar individuals without 

mTBI, particularly when associated with potential financial compensation. Future research 

should use objective and validated assessments, blinded outcome assessors, patient blinding to 

study hypotheses, and accounting for compensation factors whenever possible in order to reduce 

potential bias associated with outcome assessment. Additionally, future research should employ 

commonly used outcome assessment tools in order to facilitate the combination of results across 

studies for meta-analytic purposes. 

A final strength of this review was the use of clear criteria for defining mTBI, as established 

by the VA and DoD. However, because the majority of studies did not assess or report imaging 

results, a key component of the VA/DoD criteria for mTBI, we were unable to use positive 

imaging results as an exclusion criteria. Future primary research should clearly report criteria 

used to define mTBI, including assessment and reporting of imaging results when available, and 

should consider examination of differences in outcomes based on definitional criteria for mTBI, 

as it is possible that less stringent criteria could be associated with different results.

ABBREVIATIONS TABLE

ACRM American Congress of Rehabilitation Medicine

AFB Air Force Base

AIS Abbreviated Injury Scale

AMC Army Medical Center

ANAM Automated Neuropsychological Assessment Metrics

AOC Alteration of Consciousness/Mental State

BAMC Brooke Army Medical Center

BDI-II Beck Depression Inventory 2nd Edition

BTBIS Brief Traumatic Brain Injury Screen

BVMT-R Brief Visuospatial Memory Test Revised

C&P Compensation and Pension

CAPS Clinician Administered PTSD Scale
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Complications of Mild Traumatic Brain Injury in Veterans

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CDC Centers for Disease Control and Prevention

CDD ANAM - code substitution delayed

CDS ANAM - code substitution

CI Confidence Interval

COWA Controlled Oral Word Association

CT Computed tomography

CTE Chronic Traumatic Encephalopathy

CVAMC Cleveland Veterans Affairs Medical Center

CVLT-II California Verbal Learning Test Second Edition

DHI Dizziness Handicap Inventory

D-KEFS Delis-Kaplan Executive Function System Trail Making subtests

DoD Department of Defense

DTI Diffusion Tensor Imaging

DVBIC Defense and Veterans Brain Injury Center

DVAT Dynamic Visual Acuity Test

EFP Explosively Formed Projectile

ESS Epworth Sleepiness Scale 

FCES Full Combat Exposure Scale

FrSBe Frontal Systems Behavioral Scale

FSIQ Estimated Full Scale IQ

GED General Educational Development

GCS Glasgow Coma Scale

HADS Hospital Anxiety and Depression Scale

HIT-6 Headache Impact Test-6

HS High School

ICU Average days in ICU

IED Improvised explosive device

IQR Interquartile range

ISS Injury Severity Scale

LOC Loss of consciousness

LOS Length of stay

MACE Military Acute Concussion Evaluation

mBIAS Mild brain injury atypical symptoms scale

MIDAS Migraine Disability Assessment Score

MIRECC Mental Illness Research, Education and Clinical Center

MOCA Montreal Cognitive Assessment

MRI Magnetic Resonance Imaging

MSP ANAM - matching to sample

mTBI Mild traumatic brain injury

MTH ANAM - mathematical processing

MVA Motor vehicle accident

NA Not applicable

NR Not Reported

NSI Neurobehavioral Symptom Inventory

OEF Operation Enduring Freedom

OIF Operation Iraqi Freedom
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Complications of Mild Traumatic Brain Injury in Veterans

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OND Operation New Dawn

OR Odds Ratio

PCL PTSD Checklist

PCL-C PTSD Checklist, Civilian version

PCL-M PTSD Checklist, Military version

PCL-S PTSD Checklist Stressor Specific Version

PCS Postconcussive symptoms

PHQ-15 Patient Health Questionnaire—15

PI Principal Investigator

PM&R Physical Medicine and Rehabilitation

PRT Procedural reaction time

PT Physical training

PTA Post-traumatic amnesia

PTSD Posttraumatic Stress Disorder

RBANS Repeatable Battery for the Assessment of Neuropsychological Status

RCFT Rey Complex Figure Test

Rey FIT Rey 15 Item test

ROCFT Rey Osterlith Complex Figure Test

RPG Rocket propelled grenade

SAC Standardized assessment of concussion

SCID-I Structured Clinical Interview for DSM-IV Axis I Disorders

SD Standard deviation

SR Systematic review

SRT Simple reaction time

TBI Traumatic brain injury

TOMM Test of Memory Malingering

VACO Veterans Affairs Central Office

VAMC Veterans Affairs Medical Center

VBIED Vehicle borne improvised explosive device

VHA Veterans Health Administration

VISN Veterans Integrated Service Network

VSVT Victoria Symptom Validity Test

WAIS-III Wechsler Adult Intelligence Scale Third Edition

WAIS-IV Wechsler Adult Intelligence Scale Version IV

WASI Wechsler Abbreviated Scale of Intelligence

WHO World Health Organization

WMS-III Wechsler Memory Scale Third Edition

WRAMC Walter Reed Army Medical Center

WTAR Wechsler Test of Adult Reading
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Complications of Mild Traumatic Brain Injury in Veterans

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EVIDENCE REPORT

INTRODUCTION

Traumatic brain injury (TBI) is a common condition, especially among military members. 

Twelve to 23 percent of service members returning from Operations Enduring Freedom, Iraqi 

Freedom, and New Dawn (OEF/OIF/OND) experienced a TBI while deployed. Although various 

criteria are used to define TBI severity, the majority of documented TBI events among OEF/OIF/

OND service members may be classified as mild in severity, or mTBI, according to the definition 

used by the Veterans Health Administration and Department of Defense (VA/DoD).1

While some researchers suggest most individuals recover within three months of an mTBI, 

others estimate that 10 to 20 percent of individuals continue to experience post-concussive 

symptoms (e.g., headaches, dizziness, balance problems) beyond this time fame.2 This estimate 

may be higher among OEF/OIF service members given the frequency of multiple TBI events, 

concomitant mental health conditions such as depression and posttraumatic stress disorder 

(PTSD), and other factors unique to combat deployments. As such, deployment-related mTBI is 

a significant issue for the VA, as patients who report ongoing mTBI symptoms may require the 

attention from a range of health care professionals.3

 This evidence synthesis review will be used 

by the VHA TBI Advisory Committee to develop strategies to identify those at-risk for long-term 

mTBI effects, inform clinical practice, determine resource allocation, and identify future research 

priorities.
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Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

METHODS

TOPIC DEVELOPMENT

This project was nominated by Dr. Stuart Hoffman, Scientific Program Manager for the Brain 

Injury portfolio, Rehabilitation Research & Development Service. Operational partners include 

David X. Cifu, MD, Chair, VHA TBI Advisory Committee and National Director of Physical 

Medicine and Rehabilitation (PM&R) Program Office; Robert L. Ruff, MD, PhD, National 

Director for Neurology and Acting-Director of Rehabilitation Research and Development; Joel 

Scholten, MD, Associate Chief of Staff for Rehabilitation Services, Washington DC VA Medical 

Center Director of Special Projects, PM&R Program Office, Veterans Affairs Central Office 

(VACO); and Alexander Ommaya, DSc, Director of Translational Research, Office of Research 

and Development. We also received input from a technical expert panel.

Anticipated report usage:

The evidence synthesis review will be used by the VHA TBI Advisory Committee to develop 

strategies to determine which sub-groups are most at risk for long-term effects of mTBI. The 

review will be used to inform clinical practice and to identify how best to allocate future 

resources for effective screening for late complications of mTBI. The review will also identify 

gaps in evidence that warrant further research.

The final key questions are:

Key Question #1. For Veteran/military populations, what is the prevalence of health problems 

(such as pain, seizure disorders, headaches, migraines, and vertigo), cognitive deficits, functional 

limitations (such as employment status, changes in marital status/family dynamics), and mental 

health symptoms (such as PTSD and depression) that develop or persist following mTBI?

Key Question #2. What factors affect outcomes for Veteran/military patients with mTBI? Key 

Question 2A: For Veteran/military populations, are there pre-injury (premorbid) risk/protective 

factors (e.g., pre-injury mental health factors, genetic factors, or prior concussions) that affect 

outcomes for mTBI? Key Question 2B: For Veteran/military populations, are there post-injury 

risk/protective factors (e.g., PTSD) that affect outcomes for mTBI?

Key Question #3. What is the resource utilization over time for Veteran/military patients with 

mTBI?

SEARCH STRATEGY

We searched Medline, PsychINFO and Cochrane Register of Controlled Trials (OVID) for 

observational studies, clinical trials, systematic reviews, and cost studies, from database 

inception to October 3rd, 2012. We limited the search to articles involving human subjects and 

published in the English language. We adapted the search strategy developed by the WHO 

Collaborating Centre for Neurotrauma Prevention, Management and Rehabilitation Task Force 

for a recent systematic review of prognosis after mTBI, which included the terms ‘traumatic 

brain injury,’ ‘craniocerebral trauma,’ ‘prognosis,’ and ‘recovery of function.’4

 The full details 
10

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

of the search strategy are provided in Appendix A. The preliminary WHO Collaborating Centre 

for Neurotrauma Prevention, Management and Rehabilitation Task Force search strategy was 

reviewed by a library scientist and by our team of investigators with clinical expertise in order to 

assure comprehensiveness of the search. The search was expanded to include additional mTBI 

search terminology following the discovery of a relevant article which was not identified in the 

preliminary search. After review, we expanded the WHO Collaborating Centre for Neurotrauma 

Prevention, Management and Rehabilitation Task Force search with additional TBI terms and 

also limited the search to Veteran/military population studies by using terms including military, 

VA, and Veteran (Appendix A). We obtained additional articles from systematic reviews, 

reference lists of pertinent studies, reviews, editorials, and by consulting clinical and research 

experts. All citations were imported into an electronic database (EndNote X4).

STUDY SELECTION

We included studies reporting outcomes in Veterans or military personnel who had suffered 

an mTBI using a case definition consistent with definitions in the VA/DoD Clinical Practice 

Guideline for Management of Concussion/Mild Traumatic Brain Injury. Abstracts of citations 

identified from literature searches were reviewed by the PI to assess for relevance to the key 

questions; a portion of the abstracts were dual reviewed by at least one additional member of 

the team to assure accuracy and consistency of coding. Full-text articles of potentially relevant 

abstracts were retrieved for further review, and reviewed by the PI and at least one additional 

reviewer. Full-text articles for which there was disagreement by two reviewers were reviewed 

by the team of investigators and included or excluded based on team consensus. Each article 

was reviewed using the eligibility criteria in Appendix B. A list of excluded studies grouped by 

reason for exclusion is reported in Appendix F. Eligible articles had English-language abstracts 

and provided data relevant to the key questions. Articles also had to report outcomes for 

members of the U.S. armed forces or Veterans.

Diagnostically, to have sustained a TBI one must have experienced an event (e.g., motor vehicle 

crash, fall) which resulted in a structural injury to the brain or a physiological disruption of 

brain function (e.g., alteration of consciousness,5 loss of consciousness [LOC], or post-traumatic 

amnesia6). TBI severity is classified according to the extent of harm to the brain or altered 

consciousness associated with the injury. Severity of residual symptoms reported or observed 

should not be used to classify TBI severity. Therefore, to apply consistent criteria to define 

mTBI and compare similar populations with mTBI, all included studies had to use a definition 

of mTBI consistent with the VA/Department of Defense (DoD) Clinical Practice Guideline for 

Management of Concussion/Mild Traumatic Brain Injury described in Appendix C. Articles that 

described their populations as having mTBI but used definitions of mTBI differing from the 

VA/DoD criteria were excluded from this evidence synthesis but are described in Appendix D. 

Due to the frequent lack of reporting or obtaining imaging results (e.g., MRI, CT scan), the only 

variation from this definition in included studies relates to positive imaging results: we included 

studies regardless of whether they reported or included participants with positive imaging results 

as long as the rest of their mTBI inclusion criteria were consistent with the VA/DoD criteria. 

Finally, we did not limit study eligibility based on number of mTBI incidents or the presence of 

comorbid conditions.
11

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

We published our key questions and abstract online so that they were available for public review. 

A summary of article inclusion criteria is as follows:

Population(s): Veterans or members of the military who have experienced mTBI. Studies that do 

not differentiate between adult and child populations, or between Veteran/military and civilian 

populations, will be excluded. Studies must state a clear case definition for mTBI that falls 

within the definitions provided by the VA/DoD Clinical Practice Guideline for Management of 

Concussion/Mild Traumatic Brain Injury (Appendix C). 

Intervention(s): Not applicable to the proposed key questions. 

Comparator(s): Similar populations that have not been diagnosed with mTBI or concussion; 

comparison group not required for inclusion.

Outcome(s): Health problems (e.g., pain, seizure disorders, chronic headaches, migraines, 

vertigo, etc.), cognitive deficits, functional limitations (e.g., employment status, marital status 

changes/family dynamic changes), mental health symptoms (e.g., diagnosis of PTSD or 

depression), and cost/resource utilization (ER visits, hospitalizations, outpatient appointments). 

Outcomes diagnosed post-mortem will be included (e.g., Chronic Traumatic Encephalopathy 

[CTE]).

Timing: No limitations based on time since injury. 

Setting: No limitations based on study setting.

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: All included studies must include a minimum of 30 mTBI cases, so that a better 

level of precision and confidence in the results can be achieved.

DATA ABSTRACTION

We abstracted the following data for each included study: sample selection, population 

characteristics, subject eligibility and exclusion criteria, number of subjects, comparison(s), and 

outcome(s) (See Table 1 and Appendix E). Data was abstracted by one investigator and reviewed 

for accuracy by at least one additional investigator.

QUALITY ASSESSMENT

We assessed the quality of included studies pertaining to all of the key questions. We found 

no randomized trials meeting inclusion criteria, and our entire sample of included studies is 

comprised of observational studies of various designs, primarily retrospective cohort, case 

control, and case series. Issues of quality, particularly in observational studies, are often unique 

to the condition and outcomes of interest. Therefore, though we assessed quality using criteria 

based on the Newcastle-Ottawa quality assessment tools for observational studies7

 the criteria 

that specifically related to this body of literature included the following: accurate definition of 

condition of interest, consecutive sample selection, use of validated assessment tools, blinding 
12

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

of outcome assessors, blinding of patients and assessors to study hypotheses, adjustment for 

known confounders including mental health condition, comparability of controls, response rate, 

attrition, and reduced risk of reporting bias. These indicators of study quality and potential for 

bias were abstracted by one investigator and reviewed for accuracy by at least one additional 

investigator who was not blinded to the original assessment. In cases of disagreement, the team 

of investigators reviewed the study and came to consensus on quality assessment. In addition to 

quality rating of individual studies, we evaluated the overall quality of the evidence for each key 

question as proposed by the GRADE Working Group.8

DATA SYNTHESIS

We constructed evidence tables showing the study characteristics and results for all included 

studies organized by outcome. We critically analyzed studies to compare their characteristics, 

methods, and findings. We compiled a summary of findings for each outcome category and 

key question, and drew conclusions based on qualitative synthesis of the findings. We did not 

combine the studies in a quantitative manner via meta-analysis because of the heterogeneity of 

outcomes and study characteristics. The synthesis was conducted by the principal investigator, 

though all results were reviewed with the team of investigators to review and obtain consensus 

on the reported findings.

RATING THE BODY OF EVIDENCE

We assessed the overall quality of evidence for outcomes using a method developed by the 

GRADE Working Group,8 which classified the grade of evidence across outcomes according to 

the following criteria:

•	 High = Further research is very unlikely to change our confidence on the estimate of 

effect.

•	 Moderate = Further research is likely to have an important impact on our confidence in 

the estimate of effect and may change the estimate.

•	 Low = Further research is very likely to have an important impact on our confidence in 

the estimate of effect and is likely to change the estimate.

•	 Very Low = Any estimate of effect is very uncertain.

PEER REVIEW

A draft version of this report was reviewed by 11 technical experts as well as clinical leadership. 

Their comments and our responses are presented in Appendix G.
13

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

RESULTS

METHODOLOGIC CONSIDERATIONS

The strengths of included studies include using well-validated assessment tools, comparing 

similar populations with and without mTBI, and applying a clearly reported definition of mTBI 

consistent with VA/DoD criteria. In spite of these strengths, however, all of the included studies 

were rated as having high risk of bias for the following reasons: The included studies often did 

not adequately account for time since injury (the only exception being two studies reporting 

results from a single population), or other quality factors such as assessor blinding to the 

presence of mTBI, participant and assessor blinding to study hypotheses, or clearly reporting 

sampling procedures. This body of observational literature did not, in general, report results in 

a manner consistent with reduced reporting bias, and it is possible that studies emphasized or 

only reported statistically significant or otherwise selected results. Because outcomes and risk/

protective factors are often described in single studies without replication by other research 

teams, this body of literature is not strengthened by adequate replication and confirmation of 

preliminary results. Therefore, the overall body of literature providing evidence on outcomes for 

those with mTBI is from low quality observational studies, and the overall strength of evidence 

is low for all outcomes reported in this review. Because all individual studies were rated as 

having high risk of bias, no studies were differentially weighted based on quality in the data 

synthesis.

LITERATURE FLOW

We reviewed 2,664 titles and abstracts from the electronic search, and identified an additional 4 

studies from reviewing reference lists and conducting manual searches. After applying inclusion/

exclusion criteria at the abstract level, 354 full-text articles were reviewed, as shown in Figure 

1. Of the full-text articles, we excluded 323 that did not meet inclusion criteria. We grouped the 

studies by outcome and key question. Figure 1 details the exclusion criteria and the number of 

references related to each of the key questions. We identified 31 primary studies that addressed 

the key questions. All studies were conducted in U.S. Veterans or active-duty service members of 

the U.S. military. Table 1 shows the characteristics of the 31 primary studies, and the following 

sections detail findings according to symptom category. 
14

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Figure 1. Literature Flow Diagram

2,984 Citations identified from

 electronic database searches:

1,977 from MEDLINE®

46 from Cochrane library

961 from PsycINFO

4 Citations identified from reference lists

 of review articles, and manual searches 

 for recent, unpublished or ongoing

 studies

320 Duplicate citations excluded

2,668 Citations identified for review of title and abstract

2,314 Citations excluded due to

 lack of relevance in title or

 abstract

354 Potentially relevant articles identified for further review

31 Primary studies

Total excluded articles = 323

Population does not meet criteria 

for adult, human subjects who are 

Veterans or members of the military 

from any country = 28

No primary data and not a SR of 

primary studies = 73

Does not distinguish mild TBI from 

moderate or severe = 131

Sample includes fewer than 30 mTBI 

cases = 28

Does not report outcomes that 

address key questions = 3

Does not meet VA DoD definition for 

mTBI = 60
15

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

istics of Studies of U.S. Veterans and Members of the U.S. Military with Mild Traumatic Brain Injury

 sample selection mTBI definition and associated citation reported in the study

Sample 

size:

Total, 

mTBI

Demographics of mTBI group

Time since injury for mTBI 

group, Mean (SD); Mechanism 

of injury; 

Prior TBI

outpatient PTSD treatment 

t a Midwestern Veterans 

 patients served in OEF and/

 criteria for PTSD due to 

xcluded: LOC >30 mins or 

•	 Definition: AOC, LOC, PTA.•	 Positive imaging: NR •	 Citation: Holm, Cassidy, Carroll, & Borg, 2005 •	 How assessed: Chart review, clinical interview

92, 46 (data reported only for entire sample)

•	 Age: 30.3 (8.2)•	 Gender: 100% male•	 Race/Ethnicity: 93.3% Caucasian, 

4.4% African American, 2.2% Native American

•	 Education: NR

•	 Time since injury: NR•	 Mechanism of Injury: NR•	 Prior TBI: NR

mitted to Tampa VAMC or 

fied.

•	 Definition: PTA, LOC•	 Positive Imaging: Excluded•	 Citation: Kay et al., 1993•	 How assessed: Self report, chart review

225, 134 •	 Age: 30.7 (9.5) 

•	 Gender: 97% male•	 Race/Ethnicity: NR•	 Education: NR

•	 Time since injury: 703.5 (1064.1) 

days

•	 Mechanism of Injury: 67% blast, 

25% MVA, 7% other mechanism of injury

•	 Prior TBI: 14/134 with prior mTBI

consecutive brain injury 

 neuropsychological 

Durham VAMC post

tients; and “selected 

 Mid-Atlantic MIRECC.

alingering based on clinical 

 failed certain measures of 

gical disorders; brain injury 

•	 Definition: LOC and PTA •	 Positive Imaging: Included (n = 6 blast, n = 3 

non-blast)

•	 Citation: Kay et al., 1993•	 How assessed: Self-report, chart review

102, 51 •	 Age: 30.9 (9.2) 

•	 Gender: NR* (4/102 female for entire 

aggregate sample)

•	 Race/Ethnicity: NR* (76 Caucasian, 16 

African American; 8 Hispanic; 2 Other for entire aggregate sample)

•	 Education: 13.1 (2.2) yrs

•	 Time since injury: 1021.4 

(1730.0) days

•	 Mechanism of Injury: For total 

sample: 49 = blast only; 12 = blast plus MVA; 41 = non-blast

•	 Prior TBI: NR* (n = 20 for entire 

aggregate sample)

MCs and WRAMC. 10% 

 included in the Belanger, 

 French, 2010 analyses.

•	 Definition: DoD Criteria•	 Positive Imaging: Excluded•	 Citation: Kay et al., 1993•	 How assessed: Clinical interview chart review

390 •	 Age: 28.3 (7.9) for blast exposed; 30.0 

(9.1) for non-blast exposed

•	 Gender: 94% male•	 Race/Ethnicity: NR•	 Education: NR

•	 Time since injury: 6 months 

(WRAMC); 52 months (VA)

•	 Mechanism of Injury: 298 = blast, 

92 = non-blast cause

•	 Prior TBI: NR

 polytrauma team. 

vere brain injury; skull 

•	 Definition: Identifying a mechanism of injury 

and endorsing at least one of the following symptoms: LOC, PTA, or feeling dazed for <24 hrs after the injury.

•	 Positive imaging: NR•	 Citation: Defense and Veterans Brain Injury 

Center, 2006

•	 How assessed: Chart review

345 •	 Age: 30.4 (7.5)

•	 Gender: 96.2% male•	 Race/Ethnicity: 11.6% African 

American, 66.4% White, 18.6% Hispanic, 3.5% other

•	 Education: 55.9% HS diploma or 

equivalent, 37.1% some college, 5.8% college graduate, 1.2% other

•	 Time since injury: 3.0 (1.6) yrs 

(most recent injury)

•	 Mechanism of Injury: 64.6% 

report at least one blast injury, 29.9 report at least one motor vehicle accident, 25.5 report at least one fall

•	 Prior TBI: NR
16

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

 sample selection mTBI definition and associated citation reported in the study

Sample 

size:

Total, 

mTBI

Demographics of mTBI group

Time since injury for mTBI 

group, Mean (SD); Mechanism 

of injury; 

Prior TBI

9, U.S. Army soldiers 

e within 72 hrs of suffering 

. Included: 18-50 years, 

a concussion, free of 

no significant psychiatric 

g therapy, reporting pain 

ale of I to 10, consenting to 

nd controls were enrolled 

x, Joint Base Balad, and 

ntrols were patients in the 

controls were volunteers 

cluded: any history of severe 

he previous 3 yrs, or of any 

 of current injury.

•	 Definition: DoD criteria•	 Positive imaging: NR•	 Citation: DoD diagnostic criteria, no citation 

given

•	 How assessed: Clinical interview

237, 71 Cases vs. controls:

•	 Age: 26.5 vs. 27.3 (SD not reported), 

p = 0.44

•	 Gender: 96% vs. 88% male, p = 0.07•	 Race/Ethnicity: NR•	 Education (yrs): 12.5 vs. 13.1 (SD not 

reported), p = 0.02

•	 Time since injury: within 72 hrs•	 Mechanism of Injury: NR•	 Prior TBI: Excluded moderate 

or severe TBI within 3 yrs, and concussion within 90 days of current injury.

ng to an outpatient medical 

oncussion between January 

ition altering medication 

nosis requiring ongoing 

1-10 scale, no severe TBI, 

e past 3 yrs, no concussion 

•	 Definition: DoD criteria•	 Positive imaging: NR•	 Citation: NR•	 How assessed: NR

235, 69 •	 Age: 18-20 (9%), 21-25 (45%), 26-30 

(26%), 31-40 (17%), 41-55( 4%) 

•	 Gender: 96% male•	 Race/Ethnicity: Caucasian (72%), Black 

(4%), Hispanic (19%), other (4%)

•	 Education: HS (4%), HS graduate 

(57%), some college (38%), college graduate (0%)

•	 Time since injury: 0 (2%), 1 

(47%), 2 (29%), 3 (22%) days

•	 Mechanism of Injury: blast 45%, 

blow 26%, mixed 11%, unknown 19%

•	 Prior TBI: none in past 90 days

f OEF/OIF military service 

BI clinic at BAMC for 

g between January 2008 

icipants were over 18 years 

ntly, and were injured while 

articipants had major body 

utations, were missing key 

d below cutoffs indicating 

psychological measures. No 

ria were applied.

•	 Definition: ACRM and VA/DoD criteria•	 Positive imaging: Excluded•	 Citation: ACRM, 1993•	 How assessed: Clinical interview and chart 

review

60 Blast exposed vs. non-blast exposed:

•	 Age: 29.5 (7.73) vs. 29.43 (7.95)•	 Gender: 100% vs. 78.6% male•	 Race/Ethnicity: NR•	 Education: NR

Blast exposed vs. non-blast exposed:•	 Time since injury: 192.29 

(167.46), 148.69 (150.98) days

•	 Mechanism of Injury: Blast 53% 

non-blast 47%

•	 Prior TBI: NR
17

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

 sample selection mTBI definition and associated citation reported in the study

Sample 

size:

Total, 

mTBI

Demographics of mTBI group

Time since injury for mTBI 

group, Mean (SD); Mechanism 

of injury; 

Prior TBI

ers, including activated 

f the National Guard, 

military medical treatment 

dical Center (BAMC) 

ment to Iraq or Afghanistan 

ve injury during their 

e identified for this study 

ncluding inpatient care, 

care clinics, specialty care 

in Injury Service) and case 

id not sustain a TBI, 87 

 severe TBI or penetrating 

ubjects with PCL-C scores 

o maximize the dispersion 

ble (i.e., excluded medium

compare low vs. high).

•	 Definition: ACRM criteria.•	 Positive imaging: NR•	 Citation: ACRM, 1993•	 How assessed: Clinical interview

240 Low combat stress vs. high combat 

stress:•	 Age: 26.4 (6.5) vs. 27.8 (6.9)•	 Gender: 99.2% vs. 94.4%•	 Race/Ethnicity: NR•	 Education: NR

Low combat stress vs. high combat stress:•	 Time since injury: 3.8 (5.8) vs. 

7.3 (11.0) months

•	 Mechanism of Injury: Blast 84% 

vs. 85%

•	 Prior TBI: NR

embers with burn injuries 

s treated at BAMC 

ct 2007. Service members 

ry were referred to the 

as part of routine screening 

neurocognitive testing. 

due to length of PTA 

 brain injury than ACRM 

se they could not complete 

ropsychological testing due 

nd/or amputations.

•	 Definition: ACRM criteria; and GCS score ≥ 13•	 Positive imaging: NR•	 Citation: ACRM, 1993•	 How assessed: Clinical interview and chart 

review

167, 50 TBI+ (n = 50) vs. TBI- (n = 117):

•	 Age: 25.06 (5.818) vs. 25.67 (5.537), 

p = 0.524

•	 Gender: 44 (88.0%) male 114 vs. 

(97.4%) male, p = 0.013

•	 Race/Ethnicity: NR•	 Education (presumably years): 12.54 

(1.073) vs. 12.52 (1.454), p = 0.935

TBI+ vs. TBI-•	 Weeks since injury: 8.12 (7.763) 

vs. 7.76 (8.181), p = 0.792

•	 Mechanism of Injury: All subjects 

had burn injuries due to explosive munitions

•	 Prior TBI: NR

 Brain Injury clinic, 

uspected mTBI and 

s. The sample was primarily 

ervice members including 

embers of the National 

d operating procedure, 

he clinic completed 

tionnaires on a computer 

ncounter with a medical 

mpleting all three self-report 

NSI; mBIAS) were included 

an initial archival set of 443 

e excluded for incomplete 

sures of interest.

•	 Definition: ACRM criteria; GCS score ≥ 13. 

Consistent with the current DoD guidance ...individuals with positive neuroimaging findings, who otherwise met criteria for mTBI, were classified as moderate TBl.

•	 Positive imaging: Excluded•	 Citation: Casscells, 2007; ACRM, 2003•	 How assessed: Clinical interview, chart review

403, 268 •	 Age: 32 (9)

•	 Gender: 93% male•	 Race/Ethnicity: NR•	 Education: NR

•	 Time since injury: N (%) 

1 yr: N = 148 (62%) 1-3 yrs: N = 53 (22%)>3 yrs: N = 35 (15%)

•	 Mechanism of Injury: NR•	 Prior TBI: NR
18

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

 sample selection mTBI definition and associated citation reported in the study

Sample 

size:

Total, 

mTBI

Demographics of mTBI group

Time since injury for mTBI 

group, Mean (SD); Mechanism 

of injury; 

Prior TBI

e VA Ann Arbor Healthcare 

ple. 

ng a mTBI; C and P 

cutoff on Digit Span; scored 

5; incomplete data; scored 

y Vocabulary test.

•	 Definition: LOC; PTA; “alteration in mental 

state” at time of injury; focal neurological deficit

•	 Positive imaging: NR•	 Citation: Kay et al., 1993•	 How assessed: Self-report screening tool and 

structured clinical interview

167 •	 Age: 29.47 (7.28) 

•	 Gender: 163 (M), 4 (F)•	 Race/Ethnicity: NR•	 Education: 12.89 (1.63) yrs

•	 Time since injury: 41.93 (34.06) 

months

•	 Mechanism of Injury: NR•	 Prior TBI: NR

uded 360 service members 

urn Center for burn and 

g 2004 to Aug 2006. 146 

reated at the USAISR Burn 

 PTSD during Sep 2005 

e, 80 were also assessed 

uded in the study if they 

 blast injury and were 

nd TBI (n = 80). Two 

or moderate and severe 

wo subjects were excluded 

ured in OEF or OIF. Subjects 

BI (as defined by GCS <12 

rs) were excluded from the 

•	 Definition: ACRM criteria; and a GCS score ≥ 

13. 

•	 Positive imaging: NR•	 Citation: ACRM, 1993•	 How assessed: Clinical interview

76, 31 •	 Age: 25.5. (6) 

mTBI plus PTSD 25, mTBI no PTSD 28.9

•	 Gender: 96% male

mTBI plus PTSD male .93, mTBI no PTSD 1.0

•	 Race/Ethnicity: NR•	 Education: NR

•	 Time since injury: NR, but the 

admission date for included subjects ranged from Aug 2004-2006, and the sample included subjects assessed for both PTSD and TBI during Sept 2005-Aug 2006. 

•	 Mechanism of Injury: Mechanism 

for burn injury not specified. Blast injury: sustaining a combat injury caused by explosive munitions, such as an IED, RPG, Explosively Formed Projectile (EFP), mortar rounds, VBIED, and conventional grenades. 

•	 Prior TBI: NR

one a neuropsychological 

 Veterans Health Care 

earch database.

an invalid TOMM score.

•	 Definition: LOC; PTA; normal CT and/or MRI•	 Positive imaging: Excluded; state 

“uncomplicated.”

•	 Citation: Kay et al., 1993•	 How assessed: Self-report survey, clinical 

interview

82 •	 Age: 49.8 (11.9) 

•	 Gender: 88% male•	 Race/Ethnicity: non-Hispanic White 

(52%); Hispanic (33%); African Americans (10%); Asian Americans (4%); Native Americans (1%)

•	 Education: 12.9 (2.4) yrs

•	 Time since injury: 20.1 (14.7) 

months

•	 MVA (27%); falls (20%); sports 

injuries (12%); industrial accidents (11%); miscellaneous accidents (11%); assaults (10%); and explosions (9%). “Most (89%) were not sustained during combat.”

•	 Prior TBI: NR

00, 99 male subjects were 

eton Concussion Clinic 

uded 53 cases plus 46 

bjects were active duty and 

of psychiatric or substance 

uals with mild TBI and a 

•	 Definition: American Academy of Neurology 

mTBI definition,

•	 Positive imaging: NR•	 Citation: Schubert, Herdman, & Tusa, 2001; 

Kay et al., 1993

•	 How assessed: Chart review

99, 53 •	 Age: 22 (SD, NR) 

•	 Gender: 100% male•	 Race/Ethnicity: NR•	 Education: 98% completed HS; 

32% had taken some college-level courses; 4% graduated from college

•	 Time since injury: mean of 84 hrs 

post injury (range 2 hrs to 6 days, with the exception of one patient who was not seen until 10 days).

•	 Mechanism of Injury: NR•	 Prior TBI: NR
19

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

 sample selection mTBI definition and associated citation reported in the study

Sample 

size:

Total, 

mTBI

Demographics of mTBI group

Time since injury for mTBI 

group, Mean (SD); Mechanism 

of injury; 

Prior TBI

aq presenting for medical 

cussive event, from January 

8–50, meet DoD criteria for 

on altering medication; have 

nosis requiring ongoing 

ication management by a 

ot more than 7 of 10, and 

rior severe TBI, moderate 

yrs, or any concussion within 

cases after demonstrating 

women due to small number 

•	 Definition: DoD criteria •	 Positive imaging: NR•	 Citation: DoD, 2007•	 How assessed: Self-report survey, clinical 

interview

212, 66 Cases (n = 66) vs. controls (n = 146)

•	 Age median (IQR): 25 (22,30) vs. 25 

(22,31), p = ns 

•	 Gender: 100% male•	 Race/Ethnicity, (%): p = ns

white 74 vs. 70; black 6 vs. 16; Hispanic 17 vs. 8; Asian 0 vs. 1; American Indian 0 vs. 1; Pacific Islander 0 vs. 1; Other 8 vs. 6

•	 Education (%): p = 0.03; HS: 9 vs. 3; 

HS graduate 48 vs. 55; Some college 39 vs. 29; College graduate 3 vs. 12

•	 Time since injury: NR. Cases 

were admitted within 72 hrs of injury; neuropsych testing administered after a full night’s rest.

•	 Mechanism of Injury (%, cases 

only): Blast: 53%, Blow: 27%, Mixed: 9%, Unknown: 11%

•	 Prior TBI: p<0.01

0: 68 vs. 86; 1: 20 vs. 10; 2: 9 vs. 1

m Jan 2007-Apr 2009 at 

ston, Lackland AFB referred 

erate, severe, or penetrating 

eployed to OEF; more than 3 

 non-blast injury mechanism; 

months after injury.

•	 Definition: ACRM criteria; and GCS of 13-15•	 Positive imaging: NR•	 Citation: ACRM, 1993•	 How assessed: Clinical interview

274 •	 Age: 28.15 (7.1) mTBI only; 25.40 (5.5) 

mTBI mTBI plus at least one other AIS coded injury

•	 Gender: 100% male•	 Race/Ethnicity: NR•	 Education: NR

•	 Time since injury: 12.95 (12.9), 

12.63(13.4) wks

•	 Mechanism of Injury: Blast or 

explosion

•	 Prior TBI: NR

bers who were evaluated 

at the San Antonio Military 

23, 2005 to August 31, 

ts who had incomplete data 

 with more severe TBI, and 

ury.

•	 Definition: ACRM criteria•	 Positive imaging: NR•	 Citation: Kay et al., 1993•	 How assessed: Clinical interview

724, 586 •	 Age: 27.9 (7.4)

•	 Gender: 96.7% male•	 Race/Ethnicity: NR•	 Education: NR

•	 Time since injury: 

Total mTBI sample: 31.3 (47.1) wks; Blast: 30.6 (45.4) wks; Nonblast: 34.1 (54.0) wks

•	 Mechanism of Injury: non-blast 

mTBI group: deployment-related events such as MVAs, assaults and falls and not as a direct result of a blast explosion.

•	 Prior TBI: NR

o screened positive for 

m screen, referred to 

c, and completed 2nd level 

ation in VA polytrauma 

from n = 327 who were seen 

 site between 1/1/08 and 

•	 Definition: Positive 4-item VA TBI screen and 

subsequently diagnosed with TBI based on 2nd level comprehensive TBI evaluation including severity rating.

•	 Positive imaging: NR•	 Citation: GAO, 2008 & VHA, 2007 cited for 

screening; Kay et al., 1993 cited for secondary clinical evaluation.

•	 How assessed: Self-report screen and follow-up 

clinical evaluation 

200, 131 Note: Only age reported for mTBI sample; 

all other demographics reported for whole sample

•	 Age: 31.02 (9.14) •	 Gender: 94% male•	 Race/Ethnicity: NR•	 Education: pre-military education = 

71.7% HS or less

•	 Time since injury: NR•	 Mechanism of Injury: NR•	 Prior TBI: NR
20

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

 sample selection mTBI definition and associated citation reported in the study

Sample 

size:

Total, 

mTBI

Demographics of mTBI group

Time since injury for mTBI 

group, Mean (SD); Mechanism 

of injury; 

Prior TBI

BI symptoms referred for 

 TBI screening process. 

BI criteria.

•	 Definition: LOC, or disorientation < 24 hrs•	 Positive imaging: NR•	 Citation: CDC, 2003•	 How assessed: Self-report

339 •	 Age: 30.28 (7.59) 

•	 Gender: 96.2% male•	 Race/Ethnicity: 13.3% African 

American; 62.8% Caucasian; 20.1% Hispanic; 3.8% Other

•	 Education: 55.8% HS Diploma or 

equivalent; 37.5% some college; 5.6% college graduate; 1.2% other

•	 Time since injury: 36.72 (19.5) for 

last reported injury

•	 Mechanism of Injury: Blast (n = 

138), non-blast (n = 56), or both (n = 145)

•	 Prior TBI: Some participants had 

multiple TBIs

om a Brigade Combat Team 

rans from VA polytrauma 

inics n = 61. Excluded: 

 current/past substance 

han alcohol/caffeine/

s prior to deployment, 

e deployment, current/

medical condition that 

nctioning, significant risk of 

r, and history of TBI greater 

ficient effort testing.

•	 Definition: LOC, any loss of memory for events 

surrounding the event, any alteration in mental state, and focal neurologic deficits, PTA 

•	 Positive imaging: NR•	 Citation: Kay et al., 1993•	 How assessed: Participant self-reported 

symptoms evaluated by psychological consensus team.

104 * 67 participants included in Nelson et 

al., 2010•	 Age: VA = 29.3 (6.3), National Guard = 

35.5 (8.7) 

•	 Gender: 93.3% male•	 Race/Ethnicity: 97.1% Caucasian•	 Education: 14.4 (2.2) yrs

•	 Time since injury: 177.2 (85.5) 

weeks since most recent blast exposure

•	 Mechanism of Injury: 84.6% blast 

exposed overall (regardless of mechanism of mTBI); 50% of overall sample had blast-related concussions

•	 Prior TBI: Included history of 

mild; 10.5 (21.7) mean number of blast exposures

Midwestern region of the 

participants were recruited 

eapolis VA Medical Center. 

eet mTBI criteria.

•	 Definition: ACRM definition•	 Positive imaging: NR•	 Citation: Kay et al., 2003•	 How assessed: Clinical interview

119 •	 Age: 35.5 (10.2) 

•	 Gender: 93.3% male•	 Race/Ethnicity: 93.3% Caucasian•	 Education: 13.7 (2.3) yrs

•	 Time since injury: 327.0 (425.6) 

days (most recent concussion)

•	 Mechanism of Injury, n: Forensic 

or compensation context: OEF/OIF blast, 19; non-blast, 5; OEF/OIF non-blast, 1; non-blast n, 11; other, 8; Research context OEF/OIF blast, 38; OEF/OIF non-blast, 37

•	 Prior TBI: NR

mbat Veterans with diagnosis 

June 2007-July 2009. 

logy appointment for 

che; mechanism of injury 

•	 Definition: Based on VA/DoD Consensus-based 

Classification of Closed TBI Severity

•	 Positive imaging: Included. 45/56 veterans seen 

in neurology clinic had CT, MR or both. 40% of these with white matter changes, 30% with sinus polyps/cysts, 25% with arachnoid cysts/vascular malformations/masses, 5% atrophy

•	 Citation: Defense and Veterans Brain Injury 

Center, 2006

•	 How assessed: Clinical interview, chart review

n/a, 246 •	 Age: 27.9 (6.3)

•	 Gender: 92.3% male•	 Race/Ethnicity: 85% White•	 Education: >99% completed HS or 

GED

•	 Time since injury: NR•	 Mean time between mTBI event 

and neurology visit: 3.1 yrs (data missing in 24/56 patients)

•	 Mechanism of Injury: 65% blastexposure•	 Prior TBI: NR
21

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

 sample selection mTBI definition and associated citation reported in the study

Sample 

size:

Total, 

mTBI

Demographics of mTBI group

Time since injury for mTBI 

group, Mean (SD); Mechanism 

of injury; 

Prior TBI

t care from the VHA, Louis 

: moderate or penetrating 

hree groups: combat 

at Veterans without LOC, 

vilian mTBI.

•	 Definition: An episode of TBI with LOC, AOC, 

and/or PTA

•	 Positive imaging: NR•	 Citation: Malec, Brown, Liebson, et al., 2007•	 How assessed: clinical interview

163 

*does not 

include 5 

veterans 

with 

“probable” 

mTBI

Combat Veterans with LOC; combat 

Veterans without LOC; and then Veterans with civilian mTBI.

•	 Age: 29.2 (2.6); 30.0 (1.6); 35.1 (2.2) •	 Gender: 92.1, 90.5, 90.5% male•	 Race/Ethnicity: NR•	 Education: 100% HS graduates; 8.7, 5, 

9.5% college graduates

•	 Time since injury: NR•	 Mechanism of Injury: Military and 

civilian incidents

•	 Prior TBI: NR

ted at the VHA, Louis 

AMC. Exclusions: the initial 

ve because a veteran did 

; the veteran had moderate 

ained penetrating TBI; TBI 

o an explosion; and the 

he second-level evaluation.

•	 Definition: LOC, any alteration in mental state 

following the TBI < 24 hrs, PTA

•	 Positive imaging: NR•	 Citation: Ruff, 2005; Malec, Brown, Liebson, et 

al., 2007; Esselman & Uomoto, 1995; Kay et al., 1993

•	 How assessed: self-report screening tool and 

clinical interview

126 •	 Age: NR

•	 Gender: NR•	 Race/Ethnicity: NR•	 Education: NR

•	 Time since injury: NR•	 Mechanism of Injury: Explosion•	 Prior TBI: NR

ted at the VHA, Louis 

AMC. Same exclusions as 

above. Included veterans 

ho had “abnormalities on 

neuropsychological testing, 

ches.”

•	 Definition: LOC, the duration of any alteration in 

mental state following the TBI < 24 hrs, PTA

•	 Positive imaging: NR•	 Citation: Kushner, 1998; Ruff, 2005; Malec, 

Brown, Liebson, et al., 2007; Esselman & Uomoto, 1995; Kay et al., 1993

•	 How assessed: self-report screening tool and 

clinical interview

74 Note: Subpopulation from the Ruff et al., 

2008 study also reported•	 Age: 29.4 (2.9) •	 Gender: 95% male•	 Race/Ethnicity: NR•	 Education: NR

•	 Time since injury: NR•	 Mechanism of Injury: Explosion•	 Prior TBI: NR

ondeployed service 

ecruited thru local DVBIC; 

ures not specified

•	 Definition: LOC; GCS score between 13 and 

15; and/or PTA

•	 Positive imaging: Excluded (classified as 

moderate TBI)

•	 Citation: NR•	 How assessed: “Self-report”

66, 44 Note: mild and moderate TBI populations 

combined•	 Age: NR•	 Gender: NR•	 Race/Ethnicity: NR•	 Education: NR

•	 Time since injury: 38.3 (11.8) 

days

•	 Mechanism of Injury: Blunt force•	 Prior TBI: Excluded

 at the VA Ann Arbor Health 

omprehensive medical 

 a neuropsych assessment. 

ort on neuropsych testing as 

 or below on the Rey 15-item 

t of a C and P; exceeded 

•	 Definition: screened positive for possible 

head injury on standard VA clinical reminder consisting of PCS

•	 Positive imaging: NR•	 Citation: NR•	 How assessed: Clinical Interview

105 •	 Age: 29.8 (8.2) 

•	 Gender: NR•	 Race/Ethnicity: NR•	 Education: 12.9 (1.4) yrs

•	 Time since injury: NR•	 Mechanism of Injury: NR•	 Prior TBI: NR
22

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

 sample selection mTBI definition and associated citation reported in the study

Sample 

size:

Total, 

mTBI

Demographics of mTBI group

Time since injury for mTBI 

group, Mean (SD); Mechanism 

of injury; 

Prior TBI

ed with PTSD. Controls 

rough advertisements.

cal disease, severe 

h as schizophrenia or bipolar 

e abuse, visual deficits, or 

al events.

•	 Definition: VA/DoD Clinical Practice Guidelines •	 Positive imaging: NR•	 Citation: The Management of Concussion/mTBI 

Working Group, 2009

•	 How assessed: Clinical interview

73, 30 •	 Age: 32.3 (7.5) 

•	 Gender: 97% male•	 Race/Ethnicity: NR•	 Education: 13.6 (1.2) yrs

•	 Time since injury: 3.8 (1.5) yrs 

postdeployment; time since injury NR

•	 Mechanism of Injury: NR•	 Prior TBI: Yes, some

re evaluated between Jan 

rology Clinic at Madigan 

hronic headaches following 

 Iraq. Soldiers were eligible 

ches during deployment 

ce headaches for 3 or more 

m Iraq.

•	 Definition: DVBIC Working Group on the Acute 

Management of Mild Traumatic Brain Injury in Military Operational Settings criteria

•	 Positive imaging: NR•	 Citation: DVBIC Working Group on the Acute 

Management of Mild Traumatic Brain Injury in Military Operational Settings Clinical Practice Guideline and Recommendations, ND

•	 How assessed: Chart review

81, 33 •	 Age: 29.1 

•	 Gender: 80% male•	 Race/Ethnicity: NR•	 Education: NR

•	 Time since injury: NR•	 Mechanism of Injury: Of the n 

= 33 (41%) with head or neck trauma: 15% blunt trauma, 18% other explosive, 67% blast

•	 Prior TBI: Multiple head or neck 

injuries occurred in 6 soldiers

try brigade combat teams 

eployment during Nov-Dec 

Afghanistan for at least one 

 from participating units 

tment phase. Excluded: 10 

derate or severe TBI 

•	 Definition: Combat injury was grouped into no 

injury, non-mTBI injury, mTBI with AOC but no LOC, and mTBI with LOC. 

•	 Positive imaging: NR•	 Citation: Hoge et al., 2008•	 How assessed: Self-report survey

1522, NR •	 Age: NR

•	 Gender: NR•	 Race/Ethnicity: NR•	 Education: NR

•	 Time since injury: NR•	 Mechanism of Injury: NR•	 Prior TBI: NR
23

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Summary of Findings

In general, we found that, though cognitive, physical, and mental health symptoms were 

frequently reported by Veterans/military members following mTBI, there was little evidence 

that symptoms were more common in those with mTBI than those without mTBI. However, the 

evidence base is weakened by inconsistent findings, methodologic shortcomings of many studies, 

and variation in outcomes considered and outcome measurement approaches. We grouped 

findings into categories according to our key questions; though some outcomes could have been 

included in multiple categories (e.g., sleep), we chose to categorize outcomes as commonly 

reported in the literature, and report specific outcomes within each category individually for 

clarity. Findings by outcome categories are reported in detail in the following sections.

Cognitive Functioning Results

Summary of Cognitive Functioning Results

We found 17 studies reporting cognitive outcomes for those with mTBI. Overall, few studies 

found an association between mTBI and cognitive deficits. The strength of evidence is very low 

because of poor and incomplete reporting of data and sampling procedures, lack of time-sinceinjury information, and because most studies were unblinded and single-center. 

The studies reporting cognitive outcomes reported mean scores rather than proportions of 

individuals with impaired scores, making estimates of prevalence of cognitive impairment 

impossible. The best approximation of prevalence of impairment comes from studies reporting 

standardized scores which can be associated with impairment below certain cutoffs, and cognitive 

results should ideally be adjusted for pre-morbid functioning since the most accurate assessment of 

impairment reflects intra-individual change over time. We report estimates of impairment based on 

mean standardized scores, when available, and none of the included studies provided information 

on pre-morbid functioning such that change from baseline could be assessed at the intra-individual 

level. Though the majority of studies reported mean standardized scores within normal limits, the 

nature of mean score reporting is such that individuals comprising those means may have scored 

significantly above or below the mean. Therefore, though overall scores may be within normal 

limits, it is likely that some individuals obtained scores indicative of impairment, and individual 

variation should be kept in mind when interpreting findings. 

There were studies that found mTBI patients had deficits in visuospatial abilities, attention/

concentration, and total/cross-domain composite scores as compared to patients without mTBI. 

However, even within each of these subdomains, findings were inconsistent across studies. 

In nearly all studies, scores for each of the subscales fell within normal limits, suggesting no 

clinically significant impairment in the group as a whole. Because studies did not report the 

proportion of patients scoring below normal range for each of the subscales, it is unclear whether 

there may have been subgroups of mTBI patients with cognitive deficits. Of note, single studies 

reported that mTBI patients within 10 days of injury and those undergoing disability evaluation 

had low processing speed scores.

It is difficult to draw overall conclusions about which factors, in addition to mTBI, are 

independently associated with cognitive test performance since studies evaluated a variety of 
24

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

different factors and there were inconsistent findings among them. Individual studies suggested 

that impaired cognitive test performance was associated with comorbid mental health diagnosis, 

time since injury of less than 10 days, self-reported cognitive complaints, and experiencing 

loss or alteration of consciousness at the time of injury. One study found that Veterans who 

participated in a headache intervention demonstrated better overall cognitive functioning postintervention than those who did not participate in the intervention. 

Prevalence estimates of self-reported cognitive complaints were not reported in the included 

studies. Potential risk factors for more severe self-reported cognitive problems include having an 

additional injury, LOC or PTA at the time of injury, being service connected, and having an Axis 

I mental health disorder. 

The following table summarizes the evidence on cognitive outcomes, which is then followed by 

detailed results descriptions for each cognitive domain.

Table 2. Summary of Evidence for Cognitive Functioning Outcomes Associated with mTBI in 

Veteran and Military Populations

Domain (number of 

studies)

Key Question 1:

Estimates of 

Prevalence and 

Impairment (number 

of studies)

Key Question 1:

Statistically 

Significant Deficits 

Compared to 

Controls (number of 

studies)

Key Question 2: Statistically 

Significant Potential Risk or 

Protective Factors (number of 

studies)

Language Abilities and 

General Fund of Verbal 

Knowledge (8)

Mean scores were 

within normal limits (7)

No (3) No: Axis I disorder (2)

No: Blast exposure (1)

No: Disability/C&P Evaluation (1)

No: LOC or PTA (1)

Visuospatial Abilities (6) Mean scores were 

within normal limits (2)

Yes (1)

No (1)

Yes Risk: Axis I disorder (1)

No: Axis I disorder (3)

No: Blast exposure (1)

No: Self-reported cognitive problems (1)

Memory (11) Mean scores were 

within normal limits (5)

No (3)

Yes (2 studies on same 

population; differences 

only significant within 5 

days of injury)

Yes Risk: Time since injury 72 hours (1)

Yes Risk: Axis I disorder (1)

Mixed Risk: Axis I disorder (2)

Mixed Risk: Self-reported cognitive 

problems (1)

Mixed Risk: Time since injury 5 days (1)

No: Axis I disorder (1)

No: Blast exposure (2)

No: Disability/C&P Evaluation (1)

No: LOC or PTA (1)

No: Service connection (1)

No: Time since injury 10 days (1)

Attention/Concentration 

(8)

Mean scores were 

within normal limits (2)

No (2)

Yes (3)

Yes Risk: Time since injury 72 hours (1)

Mixed Risk: Axis I disorder (1)

No: Axis I disorder (1)

No: Blast exposure (1)

No: Disability/C&P Evaluation (1)

No: LOC or AOC (1)

No: Service connection (1)

No: Self-reported cognitive problems (1)

No: Time since injury 5-10 days (1)
25

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Domain (number of 

studies)

Key Question 1:

Estimates of 

Prevalence and 

Impairment (number 

of studies)

Key Question 1:

Statistically 

Significant Deficits 

Compared to 

Controls (number of 

studies)

Key Question 2: Statistically 

Significant Potential Risk or 

Protective Factors (number of 

studies)

Processing Speed (9) Mean scores were 

within normal limits; 

exceptions were 

scores below expected 

limits for some 

participants evaluated 

for disability/C&P and 

< 10 days since injury. 

(4)

No (5) Yes Risk: Disability/C&P Evaluation (1)

Yes Risk: Time since injury 5 days (1)

No: Axis I disorders (3)

No: Blast exposure (1)

No: LOC or PTA (1)

No: Time since injury 10 days (1)

Executive Functioning 

(7)

Mean scores were 

within normal limits (4)

No (2) No: Axis I disorder (3)

No: Blast exposure (1)

No: Disability/C&P Evaluation (1)

No: LOC or PTA (1)

Effort/Motivation (1) Mean scores were 

within normal limits (1)

No (1) Yes Risk: Disability/C&P Evaluation (1)

Total and Cross-Domain 

Composite Scores (9)

Mean scores were 

within normal limits (2)

No (2)

Yes (1)

Yes Protective: Participation in 

headache intervention (1)

Yes Risk: Disability/C&P Evaluation (1)

Yes Risk: LOC or AOC (1)

No: Blast exposure (1)

Self-reported Cognitive 

Deficits (7)

NR NR Yes Protective: Additional injury (1)

Yes Risk: LOC or PTA (1)

Yes Risk: Service Connection (1)

Yes Risk: Axis I disorder (4)

No: Axis I disorder (1)

No: Blast exposure (1)

Note. The impairment summary is based on average scores for groups with mTBI, and does not reflect individual 

variation in scores which could include some impairment for a certain proportion of participants. “Mixed” results 

indicate both significant and non-significant results for multiple assessments of the same outcome in a single study.

Language Abilities and General Fund of Verbal Knowledge

Key Question 1: We found eight primary studies that assessed this domain of cognitive 

functioning using the Repeatable Battery for the Assessment of Neuropsychological Status 

(RBANS): Language subtest, the Shipley Institute of Living Scale Vocabulary subtest, the 

Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) Information subtest, and the 

Wechsler Adult Test of Adult Reading (WTAR).10,11,16,18,20,22,29,30 The results abstracted from these 

studies are found in Appendix E, Table 1a. Three studies examined outcomes compared to a nonTBI group from the same population, describing similar performance across groups.18,29,30 All 

of the three studies reported standardized scores, and all of the mean scores fell within normal 

limits for language abilities and general fund of verbal knowledge, suggesting that, on average, 

clinically significant impairment in this domain is not associated with mTBI. None of the studies 

reported proportions of patients who obtained impaired scores on tests of language abilities and 

general fund of verbal knowledge.

Key Question 2: One study examined differences between Veterans with a history of mTBI who 

were obtaining testing as part of a C and P evaluation (i.e., a disability evaluation associated with 

potential financial gain) versus those recruited in a research context, and reported no significant 
26

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

differences between the groups.30 A study by the same group of authors examined the effect of 

having an Axis I disorder on two different tests assessing language abilities and general fund 

of verbal knowledge, and both tests indicated non-significant differences between groups.29

Similarly, studies examining the possible effect of PTSD diagnosis or mental health diagnosis 

other than PTSD22 and LOC and/or PTA at the time of injury (compared to solely experiencing 

alteration of consciousness)20 both reported non-significant group differences. One study reported 

non-significant differences between Veterans with mTBI who were exposed to blast versus those 

who were not exposed to blast.16

Visuospatial Abilities

Key Question 1: Six primary studies reported visuospatial outcomes using the RBANS: 

Visuospatial/Constructional subscale; Rey Complex Figure Test (RCFT); a study-specific Visual 

Organization/Processing factor; and the WAIS-III: Block Design subtest (Appendix E, Table 

1b).16,18,20,22,29,36 In the studies that directly compared mTBI with non-TBI participants from the 

same population, groups performed similarly on two measures of visuospatial abilities (WAIS-III 

Block Design and RCFT Figure Copy), though the mTBI group performed significantly worse than 

participants without mTBI on the RBANS Visuospatial/Constructional subscale.18,29 All of the mean 

standardized scores reported in these studies are within normal limits for visuospatial abilities.

Key Question 2: Studies examining the effects of Axis I disorders,29 PTSD diagnosis,22 or 

mental health diagnosis other than PTSD22 reported equivalent results across groups. Contrary to 

these results, another research group examined the association between mental health variables 

including PTSD, depression, and anxiety with a visual organization/processing factor score, and 

reported significant negative correlations between visuospatial abilities and both self-reported 

PTSD and depression symptoms, but non-significant differences for service connection and 

LOC or PTA at the time of injury.20 One study reported non-significant differences based on 

blast exposure.16 Finally, a study examining self-reported cognitive deficits found no significant 

association with objective visuospatial test results.36

Memory

Key Question 1: We found 11 primary studies that assessed this domain of cognitive functioning 

using the Automated Neuropsychological Assessment Metrics (ANAM): Code Substitution 

Delayed (CDD) and Matching to Sample (MSP) subtests; Brief Visuospatial Memory Test 

Revised (BVMT-R): Total Recall and Delayed Recall subtests; the California Verbal Learning 

Test Second Edition (CVLT-II): Trials 1-5, Short Delay Free Recall, and Long Delay Free Recall 

subscales; a study-specific Memory Composite Score; a study-specific Memory Factor; the 

RBANS Story Memory Immediate Recall, Story Memory Delayed Recall, Immediate Memory, 

and Delayed Memory subtests; the RCFT: Immediate Recall and Delayed Recall subtests; and 

the WAIS-III: Digit Symbol Coding subtest (Appendix E, Table 1c).11,15,16,18,20,22,24,29,30,35,36 Five 

studies examined outcomes compared to a non-TBI group from the same population, reporting 

similar results across groups in most cases.15,18,24,29,30 The notable exception was from two studies 

by the same group of authors and the same patient population which reported significant group 

differences on both 72 hour assessments, one of the two 5 day assessments, and neither of the 10 

day assessments.15,24 In these two studies, the participants were assessed by the ANAM subtests, 

and the assessments were conducted within 72 hours, 5 days, and 10 days of injury; the rest of 
27

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

the comparisons were between populations with longer time since injury, and using assessment 

tools other than the ANAM. Of the studies which reported standardized scores on assessments, 

all of the mean scores fell within normal limits for memory functioning; none of the studies 

reported proportions of patients who obtained impaired scores on tests of memory.11,18,20,29,30

Key Question 2: As noted above, two studies reported ANAM outcomes at specific times following 

mTBI event; these studies report significant deficits in memory on the majority of ANAM subtests 

at 72 hours and 5 days following injury.15,24 These same studies also report comparisons with 

controls after 10 days following injury, and notably these latter results are both non-significant. 

One study reported non-significant differences between Veterans with mTBI who were exposed 

to blast versus those who were not exposed to blast in terms of their immediate and delayed 

memory test performance.16 One study examined differences between Veterans with mTBI who 

were obtaining testing as part of a C and P evaluation versus those recruited in a research context, 

reporting non-significant differences between groups.30 A study by the same group of authors 

examined the effect of having an Axis I disorder on three tests assessing memory, and two out 

of three assessment results indicated non-significant differences between individuals with mTBI 

who did and did not have an Axis I disorder.29 One study examined the effect of mental health 

diagnosis other than PTSD on memory outcomes, and found similar results across groups.22 Two 

studies examined the effect of PTSD on memory outcomes. One of these studies did not report 

p-values, though results for four out of five memory tests were worse for those with a diagnosis of 

PTSD.22 The other study reported a significant negative relationship between scores on a self-report 

PTSD symptom inventory and a composite memory score.20 This latter study also reported a nonsignificant association for self-reported depression and service connection with memory test results, 

though self-reported anxiety was significantly related to memory functioning.20 A study examining 

self-reported cognitive deficits found no significant correlation between memory test results and 

self-reported cognitive deficits for two out of three tests.36 One study examined the impact of blast 

exposure and reported no significant differences between groups.11 Finally, one study reported 

similar results across groups based on mTBI with LOC and/or PTA at the time of injury compared 

to those with mTBI who only reported alteration of consciousness at the time of the mTBI event.20

Attention/Concentration

Key Question 1: We found eight primary studies that assessed this domain of cognitive functioning 

using the ANAM: Mathematical Processing (MTH) subtest; the RBANS: Attention subscale; 

study-specific Visual and Verbal Attention factor scores; and the WAIS-III and WAIS-IV: Digit 

Span subtest scores (Appendix E, Table 1d).15,16,18,20,24,29,30,36 In five studies that compared mTBI 

directly with non-mTBI controls, findings varied with the metric used. The mTBI group performed 

similarly to a non-TBI comparison group on the WAIS-IV Digit Span measures of attention in 

two studies,29,30 In other studies, participants with mTBI performed worse on the RBANS subtest 

and on the ANAM subtest, but deficits noted at 72 hours diminished with time.15,18,24 As with other 

outcomes, mean scores fell within normal limits for attention/concentration abilities.29,30

Key Question 2: Seven studies reported results separately for mTBI groups with and without 

potential risk or protective factors.15,16,20,24,29,30,36 As noted with other cognitive outcomes, 

significant deficits in attention/concentration at 72 hours following injury diminished to nonsignificant differences 5 and 10 days following injury.15,24 One study reported non-significant 
28

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

differences in attention based on blast exposure.16 The study that compared mTBI participants 

in a research setting with a forensic setting (i.e., a setting in which patients were evaluated for 

potential compensation) found non-significant differences in attention/concentration, in contrast 

with other outcomes for which participants in the forensic setting performed worse.30 Having 

an Axis I disorder in addition to mTBI did not emerge as a significant factor on attention/

concentration outcomes.29 A study that examined the possible effects of PTSD, anxiety, and 

depression on attention and concentration outcomes reported significant associations between 

worse visual, but not verbal attention for depression and anxiety, and significant negative 

associations between both visual and verbal attention for PTSD.20 Service connection was nonsignificantly associated with verbal and visual attention.20 Participants with LOC and/or PTA 

following TBI had similar results on attention/concentration compared with those who did 

not have these immediate sequelae.20 WAIS-IV Digit Span test results were not significantly 

correlated with self-reported cognitive deficits in one study.36

Processing Speed

Key Question 1: We found nine primary studies that assessed processing using the ANAM: Code 

Substitution (CDS), Procedural Reaction Time (PRT) subtest, and Simple Reaction Time (SRT) 

subtest; reaction time on a Go/NoGo task; Stroop Color & Word Test: Color and Word subtests; 

the Trail Making Test Part A; and the WAIS-III: Digit Symbol Coding subtest (Appendix E, 

Table 1e).11,15,20,22,24,29,30,36,37 Five studies examined outcomes compared to a non-TBI group from 

the same population.15,24,29,30,37 In three of these studies, the mTBI group performed similarly to 

a non-TBI comparison group on multiple measures of processing speed.29,30,37 By contrast, two 

studies conducted in the same patient population using the ANAM observed processing speed 

deficits soon after injury (72 hours and 5 days), although statistically significant differences 

between cases and controls were not detected upon longer term follow-up (10 days after 

injury).15,24

Key Question 2: As noted above, two studies report significant deficits in processing speed on 

the majority of ANAM subtests at 72 hours and 5 days following injury, but non-significant 

differences 10 days after injury.15,24 One study examined differences between Veterans with 

mTBI who were obtaining testing as part of a C and P evaluation compared with Veterans with 

mTBI who were recruited in a research context, describing worse processing speed performance 

on all four tests examined by those obtaining a C & P evaluation.30 Studies examining Axis I 

disorders,29 PTSD diagnosis,22 mental health problems other than PTSD,22 self-reported cognitive 

deficits,36 blast exposure,11 and LOC and/or PTA20 all reported equivalent results across compared 

groups.

Executive Functioning

Key Question 1: We found seven primary studies that assessed this domain of cognitive 

functioning using the Controlled Oral Word Association (COWA) test, the Stroop Color and 

Word Test Color-Word subscale, the Trail Making Test Part B, and an Executive Functioning 

Composite test score (Appendix E, Table 1f).11,20,22,29,35,36 Two studies by the same group of 

authors examined outcomes compared to a non-TBI group from the same population.29,30 In 

these studies, the mTBI group performed similarly to a non-TBI comparison group on multiple 

measures of executive functioning. Of the four studies reporting standardized scores, all of the 
29

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

mean scores fell within normal limits for executive functioning; none of the studies reported 

proportions of patients who obtained impaired scores on tests of executive functioning.

Key Question 2: One study examined differences between mTBI Veterans who were obtaining 

testing as part of a C and P evaluation (i.e., a disability evaluation associated with potential 

financial gain) versus those recruited in a research context, reporting no significant differences 

between groups.30 One study examined the effect of having an Axis I disorder, and all results 

were non-significant.29 Similarly, another study examined the possible effect of PTSD diagnosis 

or mental health diagnosis other than PTSD on executive functioning outcomes, and found 

non-significant differences between groups.22 A study examining self-reported cognitive deficits 

found no significant association with executive functioning test results.36 One study on blast 

exposure reported no significant group differences.11 Finally, one study reported non-significant 

group differences based on mTBI with LOC and/or PTA at time of injury compared to those with 

mTBI who did not have these immediate sequelae.20

Effort/Motivation

Key Question 1: We found one primary study that assessed effort and motivation on cognitive 

tests using the CVLT-II: Forced Choice subtest, an Effort Failures composite; the Rey 15 Item 

test (Rey FIT): Combination test, the Victoria Symptom Validity Test (VSVT); and the WAISIII: Reliable Digit Span subtest (Appendix E, Table 1g).30 This study did not report comparisons 

between those with and without mTBI (Appendix E, Table 1g).30

Key Question 2: The same study also examined differences between Veterans with mTBI who 

were obtaining testing as part of a C and P evaluation (i.e., a disability evaluation associated 

with potential financial gain; n = 24) versus those with mTBI who were recruited in a research 

context (n = 38).30 Veterans tested in the context of a disability evaluation scored worse on every 

measure of effort and motivation administered, and five out of the seven outcomes reported were 

statistically significant.30

Total and Cross-Domain Composite Scores

Key Question 1: We found nine primary studies that assessed cognitive functioning across 

domains using an Attention/Processing Speed composite score; “positive neurological and/

or neuropsychological findings,” Montreal Cognitive Assessment (MOCA); Overall Test 

Battery Mean; RBANS: Total Score; WAIS-III: Vocabulary, Information, Matrix Reasoning, 

Block Design Subscales; and WAIS-IV: all subtests (Appendix E, Table 1h).16,18,22,29,30,32-35 Three 

studies examined outcomes compared to a non-TBI group.18,29,30 In two of these studies,29,30

there were no significant differences between mTBI and non-mTBI participants on Overall Test 

Battery Mean scores, though one study18 reported significantly lower RBANS total scores for 

mTBI participants. Of the two studies reporting standardized scores on assessments, all of the 

mean scores fell within normal limits for cognitive functioning; none of the studies reported 

proportions of patients who obtained total or composite scores indicative of impaired cognitive 

functioning.29,30

Key Question 2: One study reported non-significant differences in RBANS total score between 

Veterans with mTBI who were exposed to blast versus those who were not exposed to blast.16

One study examined differences between Veterans with mTBI who were obtaining testing as 
30

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

part of a C and P evaluation (i.e., a disability evaluation associated with potential financial gain) 

versus those with mTBI who were recruited in a research context, reporting significantly lower 

Overall Test Battery Mean scores for evaluations linked to potential financial gain.30 A study by 

the same group of authors examined the effect of having an Axis I disorder, and results indicated 

non-significant differences between the groups.29 Similarly, another group of authors investigated 

the effect of having PTSD or a mental health diagnosis other than PTSD, and reported similar 

cognitive functioning across groups.22 Another study examined the possible effects of a 

headache intervention involving sleep hygiene, Prazosin, headache and pain education, and 

group therapy.34 This study indicated that completion of the intervention was associated with 

significantly higher MOCA scores. The same group of authors also reported that MOCA scores 

were significantly lower for Veterans who experienced LOC compared to those who did not 

experience LOC.32 Finally, another study by this same groups of authors reported a significant 

association between obtaining positive neurological or neuropsychological test results and the 

number of blast exposures resulting in LOC, as well as an association with the number of blast 

exposures resulting in either LOC or AOC.33

Self-Reported Cognitive Problems

Key Question 1: Seven primary studies examined self-reported cognitive problems including 

self-reported blackouts; confusion; Frontal Systems Behavioral Scale (FrSBe): Subjective 

Executive Dysfunction pre- to post-injury change; memory problems; and Neurobehavioral 

Symptom Inventory (NSI): concentration, decision-making, memory, and slowed thinking/

organization items and cognitive cluster score (Appendix E, Table 1i).12,13,17,20,25,29,35 We found no 

studies reporting prevalence estimates or comparisons with a non-mTBI control group.

Key Question 2: One study examining the effects of Axis I disorders reported non-significant 

differences between groups,29 and another described non-significant differences for those with 

and without blast exposure.12 Four studies examined self-reported cognitive problems on the NSI 

and their relationship to anxiety,20 depression,20 PTSD,12,17,20 service connection,20 and presence 

of LOC and/or PTA at the time of injury,20 and all describe significantly worse symptoms 

reported by participants with mTBI with these potential risk factors. Finally, one study described 

having an additional injury being significantly correlated with fewer self-reported cognitive 

complaints.25

Physical Health Results

Summary of Physical Health Results

We found 17 studies reporting physical health outcomes for those with mTBI. Low strength 

evidence suggests that self-reported physical symptoms are associated with mTBI. This body of 

evidence is comprised entirely of low quality studies generally limited by poor and incomplete 

reporting of data and sampling procedures, lack of time-since-injury information, and lack of 

blinding of those conducting outcomes assessments; most studies were also single-center. 

Studies included in this report suggest that symptoms reported by those with mTBI include 

headaches, pain, vestibular symptoms, hearing and vision problems, nausea or loss of appetite, 

and neurologic symptoms. One study reported that the prevalence of neurology referrals for 
31

Complications of Mild Traumatic Brain Injury in Veterans

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headaches was 33.3% for Veterans with mTBI, though no other physical health studies reported 

prevalence estimates for these outcomes. It is also unclear whether mTBI directly contributes 

to the prevalence or severity of physical health symptoms, as only two studies included a 

comparison group of participants without mTBI. Self-reported symptom severity ranges widely 

across individuals and many of the reported physical health outcomes are based solely on 

responses to an individual item from the NSI, a general post-concussive symptom inventory. 

Additionally, inconsistent information on risk and protective factors provides insufficient 

evidence to make strong conclusions about potentially moderating factors for self-reported 

physical health outcomes.

The following table summarizes the evidence on physical health outcomes, which is then 

followed by detailed results descriptions for each physical health domain.

Table 3. Summary of Evidence for Physical Health Outcomes Associated with mTBI in Veteran and 

Military Populations

Domain (number of 

studies)

Key Question 1:

Estimates of 

Prevalence and 

Impairment (number 

of studies)

Key Question 1: 

Statistically Significant 

Deficits Compared to 

Controls (number of 

studies)

Key Question 2: Statistically 

Significant Potential Risk or 

Protective Factors (number of 

studies)

Headaches (10) Prevalence of neurology 

referrals for headache = 

33.3%. (1)

Average self-reported 

headache severity = 

“moderate-severe” (1)

Average headache pain 

= 4.33 on a scale of 

0-10 (1)

NR Yes Protective: Additional injury (1)

Yes Protective: Headache intervention 

(1)

Mixed Risk: Axis I disorder (2)

No: Blast exposure (2)

Yes Risk: Positive neurological or 

neuropsychological findings (1)

Yes Risk: Referral to neurology clinic for 

headaches (1)

Pain (2) Median pain = 3.5 on a 

scale of 0-10 (1)

Yes: Average pain 

severity (1)

NR

Vestibular (6) Average vestibular 

symptom severity = 

mild-moderate (1)

Mixed (1) Yes Risk: 1-3 weeks following injury (1)

Mixed Risk: 4 weeks following injury (1)

Mixed Risk: Axis I disorders (2)

Yes Protective: Additional injury (1)

No: Blast exposure (1)

Vision (5) Average vision-related 

symptom severity = 

mild-moderate (1)

NR Mixed Risk: Axis I disorders (3)

Yes Protective: Additional injury (1)

No: Blast exposure (1)

Hearing (5) Average hearing-related 

symptom severity = 

moderate (1)

NR Mixed Risk: Axis I disorders (3)

Mixed Protective: Additional injury (1)

Mixed Risk: Blast exposure (1)

Nausea/Appetite (5) Average appetite/

nausea-related 

symptom severity = 

mild-moderate (1)

NR Mixed Risk: Axis I disorders (3)

Mixed Protective: Additional injury (1)

No: Blast exposure (1)

Neurological (5) Average numbness or 

tingling severity = mildmoderate (1)

NR Yes Risk: PTSD (2)

No: Additional injury (1)

No: Blast exposure (1)

Yes Risk: LOC (1)

Note. The impairment summary is based on average scores for groups with mTBI, and does not reflect individual 

variation in scores which could include some impairment for a certain proportion of participants. “Mixed” results 

indicate both significant and non-significant results for multiple assessments of the same outcome in a single study.
32

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Headaches

Key Question 1: We found 10 primary studies that reported headache outcomes for Veterans and 

members of the military including self-reported headaches, headache days per month, headache 

duration, headache frequency, headache pain level or severity, headache type, time since injury 

of initiation of headaches, worsening of pre-trauma headaches, headache referral, headache 

medication overuse, Migraine Disability Assessment Score (MIDAS), Headache Impact Test 

(HIT-6) score, and NSI: Headache item (Appendix E, Table 2a).12,13,16,17,25,29,31,33,34,38 One study 

without a comparison group reported prevalence of neurology referrals for headache in an mTBI 

population was 33.3%.31 Another study reported an average NSI headache item scores between 

1.45-2.71, corresponding to a self-report of headache severity in the moderate range.25 Finally, 

one study reported average headache pain of 4.33 on a scale of 0-10 for Veterans with mTBI.33

All other prevalence estimates and comparisons with a non-mTBI population reported in the 

included studies were based on populations selected because they experienced headaches, and 

therefore prevalence estimates are not accurate for a general mTBI population. 

Key Question 2: A study comparing a similar population of Veterans with history of mTBI who 

also had at least one additional injury reported that additional injury is, in fact, a protective factor 

for experiencing headaches, reporting that those with additional injuries reported significantly 

lower NSI headache item severity than those without.25 Another study investigating the effects 

of a headache intervention found that following completion of this intervention, Veterans 

reported decreased headache frequency and severity compared to a comparison group who did 

not complete the intervention.34 One study reported non-significant differences in headache 

impact based on blast exposure.16 One study reported a non-significant relationship between 

Axis I disorder and headaches.29 All other studies investigating possible risk and protective 

factors reported statistically significant risk associated with blast exposure,12 PTSD,12,17 positive 

neurological or neuropsychological findings,33 and referral to neurology clinic for headaches.31

Pain

Key Question 1: We found only two studies documenting outcomes related to pain using selfreported pain in the past 30 days, and self-reported pain on a 0-10 scale (Appendix E, Table 

2b).9,27 Only one study compared pain to a non-mTBI population, describing statistically 

significant differences in median pain scores of 3.5/10 for the participants with mTBI and 2.0/10 

for those without mTBI.9

Key Question 2: Neither included study provided data related to this key question.

Vestibular

Key Question 1: We found six primary studies reporting vestibular outcomes including 

disorientation, dizziness, Dizziness Handicap Inventory (DHI) scores, Dynamic Visual Acuity 

Test (DVAT) scores, imbalance, and NSI: Feeling Dizzy, Loss of Balance, and Poor Coordination 

item scores (Appendix E, Table 2c).12,13,17,23,25,29 Ranges of mean scores on vestibular NSI 

items ranged from 1.32-1.47 for mTBI populations, corresponding to mild-moderate symptom 

severity.13 One study compared DHI and DVAT scores to non-mTBI populations, reporting 

significantly more vestibular symptoms in mTBI groups at 1, 2, 3, and 4 weeks following injury 

for DHI and 1 week but not 4 weeks following injury for DVAT.23
33

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Key Question 2: As noted above, one study reported that significantly worse DVAT scores for 

the mTBI group became non-significantly different from those of non-mTBI controls after 4 

weeks following injury.23 Two studies reported non-significant differences in vestibular outcomes 

for those with Axis I disorders29 or blast exposure.12 Three studies reported that PTSD12,17 and 

additional injury were significantly associated with worse self-reported vestibular symptoms in 

Veterans with mTBI.

Vision

Key Question 1: We found five primary studies reporting vision-related outcomes including 

“photophobia” and NSI: Vision Problems and Sensitivity to Light item scores (Appendix E, 

Table 2d).12,13,17,25,29 Ranges of mean scores on vision-related NSI items ranged from 1.51-1.72 for 

mTBI populations, corresponding to mild-moderate symptom severity.13 No studies compared 

mTBI to non-mTBI populations.

Key Question 2: Two studies reported non-significant differences for those exposed to blast,12

and those with Axis I disorders.29 Four studies reported significantly worse self-reported visionrelated outcomes for those with PTSD12,17 and additional injury.25

Hearing

Key Question 1: We found five primary studies reporting hearing-related outcomes including 

tinnitus, “phonophobia,” and NSI: Hearing Difficulty and Sensitivity to Noise item scores 

(Appendix E, Table 2e).12,13,17,25,29 Average self-reported hearing difficulty and sensitivity to noise 

were in the moderate range.13 No studies compared mTBI to non-mTBI populations.

Key Question 2: Two studies investigating the association of blast exposure12 and additional 

injury25 with hearing-related outcomes reported significant findings for sensitivity to noise, but 

not for hearing difficulty. One study reported non-significant differences for those with Axis I 

disorders.29 Two studies reported significantly worse self-reported hearing-related outcomes for 

those with PTSD.12,17

Neurological

Key Question 1: We found five primary studies reporting neurological outcomes including 

neurological deficits based on examination, and NSI: Numbness or Tingling item score 

(Appendix E, Table 2f).12,13,17,25,32 Average self-reported numbness or tingling was of mildmoderate severity.13 No studies compared populations with mTBI to those without mTBI.

Key Question 2: One study investigating the association of blast exposure with the NSI item 

score described non-significant group differences,12 as did a study on presence of additional 

injury.25 Two studies reported significantly worse NSI numbness or tingling score for those 

with PTSD.12,17 Finally, one study reported that Veterans with LOC at the time of injury were 

significantly more likely to obtain positive neurological exam findings than those without LOC.32

Nausea/Appetite

Key Question 1: We found five primary studies reporting outcomes related to appetite and nausea 

including self-reported nausea, and NSI: Loss of Appetite, Change in Taste or Smell, and Nausea 
34

Complications of Mild Traumatic Brain Injury in Veterans

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item scores (Appendix E, Table 2g).12,13,17,25,29 Average self-reported change in taste or smell, 

nausea, and loss of appetite ranged from mild to moderate in severity.13 No studies compared 

populations with mTBI to those without mTBI.

Key Question 2: One study reported that having an additional injury was a protective factor on 

two NSI items, but non-significantly related to the NSI item assessing change in taste or smell.25

Two studies investigating the association of blast exposure12 and presence of an Axis I disorder 

reported non-significant group differences for items assessing nausea, appetite, and changes in 

taste and smell.29 Two studies reported significantly worse self-reported appetite and nausearelated outcomes for those with PTSD.12,17

Mental Health Results

Summary of Mental Health Results

Twenty studies reported mental health outcomes for Veterans or members of the military with 

mTBI. Mental health outcomes varied greatly in terms of methods of assessment, ranging from 

lengthy clinical interviews based on diagnostic criteria, to single-item, self-report screeners. 

Overall, this body of literature provides low strength evidence, as it is based on studies with 

many methodological limitations.

Studies included in this review suggest that there are high rates of comorbid mental health 

disorders and symptoms for those with mTBI. Notably, studies examined different, sometimes 

overlapping mental health outcomes (e.g., some studies examined only PTSD, while others 

reported combined mental health outcomes such as “any Axis I disorder.” Rates of Axis I 

disorders ranged from 50-78% in two studies; single studies reported that reported that the rate 

of PTSD was 45%, alcohol abuse/dependence was 28%, drug abuse/dependence was 9% suicidal 

ideation was 25%, suicidal intent was 7%, and past suicide attempts was 4% for Veterans with 

mTBI. Notably, however, the majority of included studies suggest that there are few, if any, 

significant differences in mental health outcomes for those with mTBI compared to Veteran/

military participants without mTBI). Finally, though many individual studies investigated 

potential moderating factors for mental health outcomes, no clear risk or protective factors were 

identified; however, studies often reported an association multiple mental health outcomes (e.g., 

depression, anxiety, and PTSD symptoms were reported to be significantly correlated for those 

with and without mTBI).

The following table summarizes the evidence on mental health outcomes, which is then followed 

by detailed results descriptions for specific areas of mental health.
35

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Table 4. Summary of Evidence for Mental Health Outcomes Associated with mTBI in Veteran and 

Military Populations

Domain (number of 

studies)

Key Question 1:

Estimates of 

Prevalence and 

Impairment (number 

of studies)

Key Question 1:

Statistically 

Significant Deficits 

Compared to Controls 

(number of studies)

Key Question 2: Statistically 

Significant Potential Risk or 

Protective Factors (number of 

studies)

PTSD (17) Yes: Mean scores 

indicated impairment 

(4); No: (1)

Proportion with PTSD = 

45% (1)

Mixed (1)

No (3)

Yes Protective: Additional injury (1)

Yes Risk: Anxiety (1)

Yes Risk: Blast exposure (2)

Yes Risk: Depression (1)

Yes Risk: LOC and/or AOC or PTA (3)

Yes Risk: Positive neurological or 

neuropsychological assessment 

results (1)

Yes Risk: Self-reported cognitive 

complaints (1)

No: Referral to neurology clinic for 

headaches (1)

No: Blast exposure (1)

Anxiety (6) Average anxiety = 

“moderate-severe” (1)

Yes: Mean scores 

indicated impairment 

(2)

NR Yes Protective: Additional injury (1)

Yes Risk: Depression (1)

Yes Risk: LOC and/or PTA (1)

Yes Risk: PTSD (2)

Yes Risk: Self-reported cognitive 

complaints (1)

No: Blast exposure (1)

Depression (8) Mixed: Mean scores 

indicated impairment 

(2)

No (2) Yes Risk: LOC and/or PTA (1)

Yes Risk: PTSD (2)

Yes Risk: Self-reported cognitive 

complaints (1)

No: Additional injury (1)

No: Blast exposure (1)

Substance Use 

Disorders (2)

Prevalence of alcohol 

abuse/dependence = 

28% (2)

Prevalence of drug 

abuse/dependence = 

9% (1)

No (2) Yes Risk: Axis I disorder (1)

Suicide (1) Prevalence of suicidal 

ideation = 25% (1)

Prevalence of suicidal 

intent = 7% (1)

Prevalence of past 

suicide attempts = 4% 

(1)

No (1) NR

Other (6) Prevalence of Axis I 

disorder = 50-78% (2)

Self-reported irritability/

frustration = “moderatesevere” (2)

Yes: Any Axis I disorder 

(1)

No: Any Axis I disorder 

(1)

Yes Protective: Additional injury (1)

Yes Risk: PTSD (2)

No: Blast exposure (1)

Note. The impairment summary is based on average scores for groups with mTBI, and does not reflect individual 

variation in scores which could include some impairment for a certain proportion of participants. “Mixed” results 

indicate both significant and non-significant results for multiple assessments of the same outcome in a single study.
36

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

PTSD

Key Question 1: There were 17 studies that met inclusion criteria and reported PTSD outcomes 

(Appendix E, Table 3a).9-13,16,19-21,25,27,28,31-33,36,38 These studies used the following assessment 

tools to measure PTSD: Clinician Administered PTSD Scale (CAPS): Total Score and Reexperiencing subscale; PTSD diagnosis; PTSD Checklist - Civilian Version (PCL-C) Total Score, 

Avoidance subscale, Hyper-Arousal subscale, Re-experiencing subscale, and individual item 

scores; PTSD Checklist - Military Version (PCL-M); and the PTSD Checklist - Stressor Specific 

Version (PCL-S). Mean scores on the PCL measures for those with mTBI ranged from 34.638 to 

61.9,9 suggesting clinically significant impairment for many with mTBI. Similarly, the one study 

reporting proportion of patients obtaining scores indicative of clinically significant impairment 

reported that 45% of individuals with mTBI obtained such scores.21 Of the studies comparing 

PTSD in those with mTBI to similar populations without, three reported non-significant 

differences between groups,19,21,38 and one provided mixed results.9

Key Question 2: One study examined individual items on the PCL-C, and found that all but 

one (the item asking about disturbing memories) were significantly lower for those who had at 

least one additional injury.25 The same study examined the association between PTSD and blast 

exposure for those with LOC or AOC at the time of injury, describing non-significant findings 

for all PCL symptom clusters and total scores with the one exception of higher scores on the PCL 

re-experiencing cluster.25 Three additional studies examined the association with blast exposure, 

reporting significantly worse symptoms for those with blast exposure in two of the studies12,28 and 

non-significant differences in one study.16 One study reported significant, positive associations 

among PTSD, depression, and anxiety symptoms.20 Two studies reported significantly worse 

PTSD symptom reports by those with LOC at the time of injury32 and LOC and/or PTA.20 One 

study reported a significant association between PTSD and obtaining positive neurological 

or neuropsychological test results.33 One study reported non-significant differences in PTSD 

between those who were and were not referred to neurology clinics for headache treatment.31

Finally, one study reported a significant association between self-reported cognitive complaints 

and PTSD symptoms.36

Anxiety

Key Question 1: We found six primary studies reporting anxiety outcomes including the Hospital 

Anxiety and Depression Scale (HADS): Anxiety assessment and the NSI: Feeling Anxious item 

score (Appendix E, Table 3b).12,13,17,20,25,36 Average self-reported anxiety symptoms were in the 

moderate-severe range on the NSI and in the clinically significant range on the HADS.13,36 No 

studies compared mTBI to non-mTBI populations.

Key Question 2: One study investigating the association of blast exposure with self-reported 

anxiety resulted in non-significant findings.12 Four studies reported significantly worse selfreported anxiety for those with PTSD,12,17 LOC and/or PTA immediate sequelae,20 self-reported 

depression, 20 and self-reported slowed thinking, attention deficits, and memory deficits. 36 One 

study reported that having at least one additional injury was negatively associated with selfreported anxiety.25
37

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Depression

Key Question 1: We found eight primary studies reporting depression outcomes including 

Beck Depression Inventory 2nd Edition (BDI-II) score, a single-item hopelessness assessment, 

Hospital Anxiety and Depression Scale (HADS): Depression subscale score, Neurobehavioral 

Symptom Inventory (NSI): Depression item score, and Structured Clinical Interview for 

DSM-IV Axis I Disorders (SCID-I): Major Depressive Disorder diagnosis (Appendix E, Table 

3c).9,12,13,17,20,25,36,37 Average self-reported depression severity was in the moderate range on the 

NSI,13 though average scores did not fall within the clinically significant range on the HADS.36

Of the two studies comparing depression symptoms for those with and without mTBI,9,37 neither 

reported significantly worse depression symptoms for mTBI participants. 

Key Question 2: Two studies investigating the association of blast exposure12 and additional 

injury25 with depression reported non-significant findings. One study investigated presence of 

LOC and/or PTA20, two studies investigated PTSD,12,17 and one study investigated self-reported 

cognitive problems36; all reported that these were statistically significantly associated with worse 

depression in those with mTBI.

Substance Use Disorders

Key Question 1: We found only two primary studies reporting substance use outcomes, both 

using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) to establish drug 

or alcohol use/dependence (Appendix E, Table 3d).9,29 The studies reported that the prevalence of 

substance use disorders in this population ranged from 9% for drug abuse/dependence9 to 28% 

for alcohol abuse/dependence.9,29 Both studies reported non-significant differences in prevalence 

compared to controls.

Key Question 2: One of the studies described having another Axis I disorder as significantly 

associated with increased prevalence of alcohol abuse/dependence.29

Suicide

Key Question 1: We found only one primary study reporting outcomes related to suicide 

(Appendix E, Table 3e).9

 This study used the following single item assessments of suicide-related 

outcomes: Suicidal Ideation (Have you had thoughts about death or about killing yourself?), 

Suicidal Intent (Have you ever intended to commit suicide?), and Past Suicide Attempts (Have 

you ever attempted suicide?). This single study reported that the prevalence of suicidal ideation 

in this population was 25%, suicidal intent was 7%, and past suicide attempts was 4%. The 

authors report non-significant differences when comparing these outcomes to results from nonmTBI controls. 

Key Question 2: We did not find any evidence related to this key question.

Other Mental Health Outcomes

Key Question 1: We found six primary studies reporting other mental health outcomes and 

summary scores (Appendix E, Table 3f).9,12,13,18,25,35 The outcomes investigated in these studies 

included Frontal Systems Behavioral Scale (FrSBe): Apathy pre- to post-injury change and 

Behavioral Disinhibition pre- to post-injury change subscales, Neurobehavioral Symptom 
38

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Inventory (NSI): Affective Cluster, Neurobehavioral Symptom Inventory (NSI): Irritability and 

Frustration items, Psychiatric Diagnosis, and Structured Clinical Interview for DSM-IV Axis 

I Disorders (SCID-I): Axis I Disorder diagnosis. The prevalence of Axis I disorder in mTBI 

populations was reported to range from 50-78% based on two studies, though these same studies 

report mixed results in terms of whether these prevalence estimates are significantly higher 

compared to non-mTBI controls.9,18 Self-reported irritability and frustration were both within the 

moderate to severe range as assessed by the NSI in one study.13

Key Question 2: One study reported a non-significant association between blast exposure and 

frustration severity.12 One study reported a significant negative association between having an 

additional injury and NSI affective cluster, frustration, and irritability scores. 25 Finally, two 

studies reported that PTSD was significantly associated with poor NSI frustration and irritability 

item scores12,18 as well as the NSI affective cluster score.18

Functional/Social Outcome Results

Summary of Functional/Social Outcome Results

We found 12 studies, all low quality, reporting functional/social outcomes for Veterans or 

members of the military with mTBI. Due to methodologic limitations as well as small sample 

size and inadequate reporting of and accounting for time since injury, the strength of evidence for 

this group of studies is low. One study reported that approximately 20% of Veterans with mTBI 

experience unemployment. One of two studies comparing participants with mTBI to participants 

without mTBI found higher unemployment among those with mTBI. Another study found that 

26% of those with mTBI had difficulties with interpersonal relationships, though this was not 

significantly different in comparison to individuals without mTBI. Ten studies examined sleep 

disturbance: two found an overall prevalence of 13-23% in those with a history of mTBI, and 

seven found that sleep disturbances, when present, were moderate to severe. One of two studies 

found that sleep disturbance was more common in those with mTBI compared to those without a 

history of mTBI. No clear patterns of risk or protective factors emerged from studies examining 

potential moderators of mTBI history for functional or social outcomes. 

The following table summarizes the evidence on functional/social outcomes, which is then 

followed by detailed results descriptions for each functional/social domain.
39

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Table 5. Summary of Evidence for Functional/Social Outcomes Associated with mTBI in Veteran 

and Military Populations

Domain (number of 

studies)

Key Question 1:

Estimates of 

Prevalence and 

Impairment (number 

of studies)

Key Question 1:

Statistically 

Significant Deficits 

Compared to Controls 

(number of studies)

Key Question 2: Statistically 

Significant Potential Risk or 

Protective Factors (number of 

studies)

Employment (2) Prevalence of 

unemployment = 20% 

(1)

Yes (1)

No (1)

No: LOC (1)

Sleep (10) Mixed results related 

to impairment: Mean 

self-reported sleep 

disturbance and 

fatigue ranged from 

approximately “mild” to 

“very severe.” (7)

Prevalence < 4 hours of 

sleep per night: 13% (1)

Prevalence of > 2 hours 

sleep loss per night: 

23% (1)

Yes (1)

No (1)

Yes Protective: Additional injury (1)

No: Blast exposure (1)

Yes Risk: PTSD (2)

Yes Risk: Positive neurological or 

neuropsychological findings (1)

Yes Protective: Participation in a 

headache intervention (1)

No: Referral to neurology clinic for 

headaches(1)

Relationships (1) Prevalence of lack of 

emotional support = 

26% (1)

No (1) NR

Note. The impairment summary is based on average scores for groups with mTBI, and does not reflect individual 

variation in scores which could include some impairment for a certain proportion of participants. “Mixed” results 

indicate both significant and non-significant results for multiple assessments of the same outcome in a single study.

Employment

Key Question 1: We found only two studies documenting outcomes related to employment status 

using self-reported unemployment, two or more missed workdays in the past month, difficulty 

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

as indicators of employment outcomes (Appendix E, Table 4a).9,39 One study described a nonsignificant comparison to a non-mTBI population, and reported that the rate of unemployment 

for the mTBI population was 20%.9

 Another study reported that the odds of missing more than 2 

days of work ranged from 1.4-1.8, odds of difficulty carrying a heavy load in past month ranged 

from 2.2-3.0, and odds of difficulty performing physical training in the past month as indicators 

of employment outcomes ranged from 1.6-1.9 when compared to a non-mTBI reference group.39

Key Question 2: One study examined the potential impact of LOC on employment outcomes for 

Veterans with mTBI, and reported equivalent results across groups for all outcomes assessed. 39

Sleep

Key Question 1: We found 10 primary studies that reported sleep outcomes for Veterans and 

members of the military including the Epworth Sleepiness Scale (ESS); Neurobehavioral 

Symptom Inventory (NSI): Fatigue and Sleep items; hours per night of sleep; hours per 

night of sleep lost; and sleep disturbance in the past 30 days.12,13,15,17,24,25,27,31,33,34 Of the two 

studies comparing participants with and without mTBI, three out of six sleep outcomes were 

significantly worse for those with mTBI, and the others were approximately equivalent across 
40

Complications of Mild Traumatic Brain Injury in Veterans

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groups.15,24 Only one study reported prevalence of sleep disturbance, estimated at 13% (less than 

four hours of sleep per night) to 23% (more than 2 hours sleep loss per night) for active duty 

military personnel within 10 days of injury.15 Notably, self-reported sleep disturbance and fatigue 

on the NSI ranged from approximately “mild” (0.86) to approximately “very severe” (3.45) 

depending on the sub-population with mTBI (e.g., those with and without PTSD), indicating 

clinically significant impaired sleep for at least some Veterans and members of the military with 

mTBI.12,13,17,25,31,33,34

Key Question 2: One study examining differences between Veterans referred to the neurology 

clinic for headaches versus those not referred noted non-significant differences between 

groups on mean NSI sleep item score.31 Studies examining additional injury,25 blast exposure,12

PTSD,12,17 and positive neurological or neuropsychological findings33 all suggest that participants 

with mTBI with these potential risk factors endorse significantly worse sleep disturbance than 

those without these factors. Similarly, a study investigating a headache intervention described 

significantly less sleep disturbance endorsed by participants with mTBI who were randomly 

assigned to the intervention condition compared to the control group of participants with mTBI 

who were not offered the intervention.34

Social

Key Question 1: We found only one study reporting social outcomes as indicated by lack of 

emotional support and marital status (Appendix E, Table 4b).9

 This study reported non-significant 

differences between mTBI compared to non-mTBI participants for both outcomes. The 

prevalence of lack of emotional support was reported to be 26% for Veterans with mTBI.

Key Question 2: No studies addressed this key question related to social outcomes.

Service Utilization/Costs Results

Summary of Service Utilization/Costs Results

We found seven studies that described service utilization by Veterans with mTBI, and no studies 

reported costs associated with mTBI. The overall strength of evidence was low because of the 

small number and methodologic shortcomings of studies. The available literature suggests that 

there are few differences in service utilization for those with mTBI compared to similar controls, 

and no significant associations with potential risk or protective factors were identified. The 

following table summarizes the evidence on service utilization/cost outcomes, which is then 

followed by a detailed results description of results.
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Complications of Mild Traumatic Brain Injury in Veterans

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Table 6. Summary of Evidence for Service Utilization/Costs Associated with mTBI in Veteran and 

Military Populations

Domain (number of 

studies)

Key Question 1:

Estimates of 

Prevalence and 

Impairment (number 

of studies)

Key Question 1:

Statistically 

Significant Deficits 

Compared to Controls 

(number of studies)

Key Question 2: Statistically 

Significant Potential Risk or 

Protective Factors (number of 

studies)

Service Utilization (7) No mean scores 

indicating impairment 

(e.g., diagnosis), with 

the exception of a 

broad range of results 

reported for number of 

prescribed medications. 

(2)

Prevalence of current 

counseling = 4-6%. (1)

Prevalence of 

current mental health 

medications = 4-5%. (1)

No (4) No: LOC (1)

Costs (0) NR NR NR

Note. The impairment summary is based on average scores for groups with mTBI, and does not reflect individual 

variation in scores which could include some impairment for a certain proportion of participants.

Service Utilization/Costs

Key Question 1: Table 6 describes the seven primary studies reporting service utilization by 

Veterans and members of the military including current counseling, current mental health 

medication, current pain medication, narcotic pain medication, number of medications overall, 

length of hospital stay, length of intensive care unit stay, and medical utilization as indicated 

by more than two sick calls within the past month.10,15,18,21,24,37,39 None of the studies comparing 

participants with mTBI to those without mTBI15,18,21,24 or to those with moderate/severe TBI10

reported statistically significant differences on any service utilization outcomes. One study which 

did not report a p-value, however, reported that participants with mTBI were prescribed an 

average of 18 medications, compared to a control group without mTBI, who were prescribed an 

average of five medications.37 Prevalence of current counseling by those with mTBI was reported 

to be approximately 4-6% and current mental health medication was 4-5% in two studies of the 

same population.15,24

Key Question 2: One study examined whether or not LOC at the time of injury was related to 

having two or more sick call visits in the past month, and reported similar odds ratios for mTBI 

participants with and without LOC.
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Complications of Mild Traumatic Brain Injury in Veterans

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SUMMARY AND DISCUSSION

SUMMARY OF EVIDENCE

We found 31 studies examining the effects of mTBI in Veteran and military populations. In 

general, though cognitive, physical, and mental health symptoms were commonly reported 

by Veterans and members of the military following an mTBI, there was little evidence that 

symptoms were more commonly reported by study participants with mTBI than similar 

participants without mTBI. However, the evidence base is weakened by inconsistent findings, 

methodologic shortcomings of many studies, and variation in outcomes considered and outcome 

measurement approaches. Therefore, conclusions drawn from this body of literature are 

uncertain, likely to change given additional research in the future, and should be interpreted with 

caution.

Mental health problems are a serious concern for Veterans and members of the military 

with mTBI, though the extent to which these outcomes are uniquely related to mTBI versus 

other deployment-related illnesses are not clear. Posttraumatic stress disorder (PTSD) is one 

of the most common mental health disorders among Veterans of wartime service, affecting 

approximately 15% of Veterans of all eras.40 A recent systematic review estimated the overall 

prevalence of comorbid TBI and PTSD among OIF/OEF Veterans at 5-7%,41 and among Veterans 

with histories of TBI, rates of PTSD range from 33-65%.41-44 Furthermore, having both PTSD 

and TBI may adversely affect functionality more than suffering from either disorder alone.45

The high prevalence of comorbid PTSD and mTBI are likely related to both event-related 

factors and neuropsychiatric symptom overlap between disorders.46 Modern warfare involving 

multiple deployments and high rates of blast exposure has greatly increased service members’ 

risk of TBI and PTSD.47 In addition, there is evidence from neuroimaging studies that PTSD 

and TBI affect similar areas of the brain, including the prefrontal cortex, hippocampus, and 

amygdala.47,48 Regardless of etiology, the overlap in the presentation of mTBI and PTSD can be 

accounted for at least in part by shared symptoms. In particular, core symptoms of both PTSD 

and postconcussive syndrome include problems with concentration/attention and memory, sleep 

disturbance, and irritability.49,50 Moreover, cognitive complaints and objective neurocognitive 

deficits are common among individuals with PTSD, even in the absence of a history of TBI,48,51-54

including problems with memory, concentration/attention, and problem-solving.

We found a very limited evidence base examining functional and social outcomes suggesting that 

one fifth to one quarter of Veterans with mTBI experienced unemployment, sleep disturbance, 

or lack of emotional support. Whereas more severe levels of TBI are identified immediately 

post-trauma, cases of mTBI are often unidentified and untreated until after military discharge, 

at which point Veterans may begin to recognize problems like trouble reintegrating into work 

or school or difficulties maintaining familial or social relationships. Longitudinal studies have 

found impairments ranging from difficulty maintaining leisure interests and friendships, to 

vocational instability, poor life satisfaction, and poor quality of life among individuals who 

have incurred mTBI.55,56 Individuals’ social and physical environments can either help or hinder 

recovery of full functional capacity after mTBI. Research has found factors like social support, 

family adjustment and cohesion, life stressors, and receipt of compensation for disability to be 
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associated with functional outcomes among individuals with mTBI.57

The VA will be providing life-long care for a large number of OEF/OIF/OND Veterans who 

have sustained mTBI. In some cases, the VA will also provide care for the Veterans’ informal/

family caregivers.58 The long-term resource needs of OEF/OIF/OND Veterans are likely 

substantial; however, these resource needs are possibly related to a variety of factors including 

comorbid conditions and other consequences of deployment and not uniquely related to having 

experienced an mTBI. The majority of data on costs and resource utilization of individuals with 

TBI comes from civilian studies and examines those with moderate-to-severe TBI, for which 

follow-up care and rehabilitation needs are great and disability is common. Little is known 

about long-term costs and needs for those with mTBI, particularly military members or Veterans 

with deployment-related mTBI. Although most outcomes studies of civilians have found that 

symptoms and sequelae of mTBI resolve within one year after the injury,59 different contextual 

factors including mechanism of injury provide only indirect comparisons to Veteran/military 

outcomes. It is likely that complicating deployment-related factors such as repeat mTBI events 

or concomitant mental health disorders such as PTSD could result in very different long-term 

outcomes and resource utilization for this population.

Findings from Civilian Populations

Though the overall strength of evidence evaluating outcomes following mTBI in Veteran 

or military populations is low, it is noteworthy that the findings are remarkably consistent 

with higher quality civilian literature.59 Both bodies of research suggest that many health 

consequences resolve within the first few months following injury, if not sooner.

A systematic review of literature in children and adults found objective cognitive deficits 

associated with mTBI resolve within 2-3 months and the physical consequences of mTBI are 

likely limited to those which resolve within the first few days following injury.

59 The authors note 

that though objective cognitive impairment resolves quickly, subjective cognitive complaints 

may linger for years for some individuals who experience mTBI. They also found that litigation 

or evaluation for compensation was a risk factor for worse cognitive test performance, a finding 

echoed by another review.60

Other systematic reviews reported similar findings. One review described insufficient and 

inadequate evidence for any cognitive effects of mTBI greater than 6 months following injury.61 A 

meta-analysis of sports-related concussion suggests that though some impairment in memory and 

global cognitive functioning may be present for individuals with mTBI within a week of injury, 

these effects are no longer present after 7 days post-injury.60 These authors also found cognitive 

deficits were no longer present by 3 months after injury in unselected, consecutive samples.60

A systematic review of civilian literature related to functional impairment suggests that there 

is not a significant impact for children with mTBI, and most functional impairment resolves 

within a month for adults with mTBI.59 However, this review also points out that self-reported 

functional impairment may last longer, up to years, in some instances, particularly when 

individuals are involved in litigation or compensation related to the mTBI, and when individuals 

experience the mTBI event as psychologically traumatic. 

Pertab and colleagues conducted a re-analysis of studies included in earlier meta-analyses. This 
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group of authors suggests that time since injury and the use of different cognitive assessment 

tools may have a potentially moderating effect on cognitive outcomes.62 The authors describe a 

range in summary effect sizes based on cognitive domain and time since injury, suggesting the 

possibility that some subgroups of those with mTBI may experience some objective cognitive 

deficits for a limited period of time following injury. 

Of note, the WHO Collaborating Centre for Neurotrauma Prevention, Management and 

Rehabilitation Task Force has recently completed an updated systematic review examining the 

effects of mTBI in civilian populations. Results are likely to be reported within the next year and 

should further add to our understanding. 

Even though the strength of evidence in civilian populations is higher, there is not enough 

information in that body of literature either to identify how factors such as time since injury, 

mechanism of injury, or number of mTBIs influence long-term outcomes.

Use of Imaging and Biomarkers in mTBI Research

Although beyond the scope of this review, since imaging and biomarker technologies are a 

rapidly evolving area of research of interest to stakeholders, we will briefly summarize recent 

relevant research here.

Although biomarkers are increasingly being used as prognostic tools among those with moderate 

or severe TBI, research among those with less severe injuries has been limited.63 Efforts are 

focused on evaluating serum and cerebral spinal fluid during different stages of the brain injury 

cascade (e.g., inflammation, neuronal injury).64 As no single biomarker with discriminative 

characteristics has been indentified, Sharma and Laskowitz (2012) suggest that combining 

biomarkers may increase sensitivity and specificity.64 For further information regarding 

biomarkers and mTBI see Jeter et al. (2012), and Sharma and Laskowitz (2012).64,65

Recent interest has emerged regarding the possibility that returning military personnel with 

a history of TBI are at risk for developing chronic traumatic encephalopathy (CTE).66 CTE 

refers to persistent cognitive and neuropsychiatric symptoms (e.g., executive dysfunction, 

memory impairment, depression, poor impulse control, and dementia) secondary to chronic 

neurodegeneration thought to be caused at least in part by multiple TBIs.67 At present, CTE can 

only be identified by direct tissue examination; as such, full autopsies and immunohistochemical 

brain analyses are necessary for definitive diagnosis. Despite much speculation regarding 

blast exposed individuals being at risk for CTE, limited data currently exists in support 

of this relationship. Current efforts pertaining to increasing understanding regarding CTE 

include: creating clinical diagnostic criteria, identifying objective biomarkers, and increasing 

understanding regarding additional risk factors and underlying mechanisms.68

Recent literature reviews of neuroimaging in mTBI including DTI, functional,69 and metabolic 

imaging,70 have examined the association of imaging findings with neuropathology.

71 Although 

brain changes resulting from mTBI are often not discernible with conventional clinical structural 

CT and MRI, there is a growing body of evidence that they are more readily detectible with 

advanced research imaging technologies, particularly DTI,72 which measures the functional 

integrity of white matter interconnections within the brain. A rapidly growing body of DTI 

investigation indicates that DTI is more sensitive to white matter injury than conventional MRI 
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Complications of Mild Traumatic Brain Injury in Veterans

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and CT, with DTI consistently detecting more abnormalities than conventional CT or MRI 

across multiple mTBI studies. As would be expected from the animal model and neurocognitive 

assessment literature,71 acute and subacute structural and functional imaging changes are 

demonstrated. However, abnormalities have also been demonstrated at chronic stages, 

suggesting that some patients experience long-term brain changes as well. The most common 

abnormalities have been shown for long association pathways including the corticospinal 

tract, corpus callosum, corona radiata, internal capsule, uncinate fasciculus, and the superior 

longitudinal fasciculus. Further, in some studies, DTI abnormalities correlate with cognitive 

performance in patients with mTBI, with general aggregate DTI abnormality correlated with 

executive function, memory, and cognitive processing speed. Locally specific structure-function 

relationships have sometimes been observed in mTBI, with damage to frontal white matter 

associated with executive function and attentional performance, and temporal tract changes 

associated with decreases in memory performance. Some more recent imaging studies support 

the notion of persistent postconcussive symptoms (PCS), with observable pathophysiological 

findings correlated with PCS. Supportive of these DTI findings, many fMRI studies found 

activation differences between individuals with mTBI and individuals in the control group during 

cognitive and behavioral tasks consistent with DTI findings, although many studies failed to 

show associated significant differences in task performance.69 The various metabolic imaging 

techniques are less well investigated in mTBI, but initial results suggest that these techniques 

show promise as investigative and diagnostic tools.70

Although rapidly growing, there remain several limitations for mTBI neuroimaging research. It is 

largely made up of cross-sectional studies with small samples, and there is a great deal of method 

and design variability with respect to such factors as time period of scanning post-injury, brain 

regions examined, magnet strength, non-imaging outcome variables, and methods of analyses, 

resulting in differences across studies in both anatomical location of observed brain alterations 

and the nature of these alterations. Despite considerable consistency in its main findings, this 

body of research is still relatively new and there remain as-yet unresolved discrepancies. For 

instance, some DTI studies show increased fractional anisotropy (FA), while others show 

decreased FA. Also, many fMRI studies failed to show associated significant differences in task 

performance associated with significant task-related activation differences between patients and 

control participants.69 Imaging studies nonetheless are consistent in providing evidence of small 

and subtle brain injuries in mTBI that are often, although not always, associated with symptoms 

and cognitive performance. This evidence would not be possible if conventional MRI and CT 

scans alone were used to establish and characterize brain injury; it requires more advanced and 

sophisticated imaging methods such as DTI and fMRI that are sensitive to the effects of diffuse 

axonal injury and altered metabolic function to delineate these abnormalities.

Clinical Considerations

The best available evidence, which is of low quality, suggests that many symptoms that 

patients ascribe to mTBI may be related to comorbid mental or physical health concerns, or to 

other factors such as readjustment to civilian life following deployment or injury beliefs and 

perceptions.73 Difficulties related to post-deployment adjustment underscores the need to engage 

recently returned Veterans and members of the military quickly in efforts to identify physical 

and mental health problems and provide appropriate re-integration services. Patients should be 
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Complications of Mild Traumatic Brain Injury in Veterans

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encouraged to engage in treatment for these comorbid concerns with the best available evidencebased treatments (e.g., evidence-based psychotherapy to treat PTSD).

Administrators setting policy for treatment of military-related mTBI should be cautioned to treat 

the available evidence as limited and subject to change depending on findings from future, more 

methodologically rigorous studies. Policy based on the best available evidence should likely 

encourage the treatment of comorbid conditions that commonly occur for Veterans and members 

of the military who have experienced deployment (e.g., treatment for PTSD, substance use 

disorders, headaches, sleep disorders, and other post-deployment concerns). 

Given the lack of large, good-quality observational studies with adequate follow-up it is very 

difficult to estimate the long-term cognitive effects of mTBI. However, the current evidence base 

suggests that cognitive deficits are not common, particularly more than three months after injury. 

Therefore, should individuals with mTBI continue to experience ongoing cognitive deficits 

following first-line treatment for co-occurring symptoms and disorders such as PTSD, further 

testing such as neuropsychological or neurological evaluations or imaging might be warranted.

LIMITATIONS AND RECOMMENDATIONS FOR FUTURE RESEARCH

The available literature reporting consequences of mTBI in Veteran and military populations 

is based on low quality observational studies and provides low strength evidence for the 

associations synthesized in this systematic review. Notably, not all outcomes of potential 

interest to stakeholders were found in the literature base (e.g., costs). There is insufficient data 

to determine the presence or absence of an effect for these outcomes, and further research is 

warranted.

One of the major limitations of this literature is the inadequate reporting of and accounting 

for time since injury among Veterans and military members, and therefore it is not possible to 

construct an accurate picture of mTBI consequences over time for this population. This body of 

literature is also likely subject to participant recall bias due to the cross-sectional, retrospective 

nature of almost all included studies. Participants are likely unable to accurately recall symptoms 

and timeframes so long after one (or more) mTBI events. Future research should take advantage 

of available VA and DoD databases that have time since injury information and include this 

variable in the analysis of mTBI consequences on an individual participant level. Similarly, such 

databases should be used to examine the possible effect of multiple mTBI events as this is a 

common occurrence for many individuals who were part of OEF/OIF conflicts. Additionally, a 

large prospective cohort study would be better able to identify factors associated with outcomes 

in mTBI populations.

A related limitation of the body of literature relates to how data is presented in included studies. 

Very few studies reported the actual prevalence of symptoms or conditions; most studies 

simply reported mean scores for the entire study group. This latter approach can provide useful 

information for determining whether there is a unique contribution of mTBI versus outcomes 

being affected by more general deployment or combat exposure factors. However, a lack of 

prevalence estimates limits an accurate description of the population, particularly when a goal 

of stakeholders is to estimate numbers of Veterans who will be affected by specific outcomes 
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Complications of Mild Traumatic Brain Injury in Veterans

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and utilize related treatment services. Future research should not only report mean scores for 

subgroups, but also report proportions of individuals with clinically significant impairment for 

each outcome. This recommendation is particularly relevant to the body of research on cognitive 

outcomes, as the vast majority of this literature describes differences based on means rather than 

reporting the proportion of individuals who obtain scores indicating impaired functioning. For 

cognitive outcomes in particular, impairment is ideally determined not only by standardized 

scores within a certain range, but also by comparison to pre-injury (baseline) functioning. Studies 

should report this intra-individual change as part of any cognitive findings so that accurate 

estimates of mTBI-related cognitive impairment are reported.

Few studies presented data on all outcomes of interest to the stakeholders of this review, and few 

studies reported their outcome reporting rationale. Most studies relied on clinical datasets, which 

are generally not maintained for research purposes, rather than research databases or registries. 

The use of these datasets can be efficient relative to primary data collection but typically do not 

contain all variables of interest in a given scientific inquiry. It is likely that many studies only 

included outcomes of relevance to the authors’ particular study questions, though it is impossible 

to know whether some studies did not report outcomes given a lack of association with mTBI. 

There is a pressing need for large cohort studies of Veterans with and without mTBI that 

prospectively collect data on all risk and protective factors, and all outcomes of interest. Such 

studies would be relatively costly but would result in higher-quality evidence on which more 

definitive conclusions could be based.

Although a strength of this review was that many of the included studies relied on well-validated 

measures commonly used with Veteran/military populations, many of the clinical outcomes 

relied solely on self-reported outcomes, often obtained from single questionnaire items. Selfreport data is often the only way to assess certain outcomes such as pain. However, some 

notable results from this review and a review of the civilian literature59 suggest that self-reported 

deficits are more likely to be reported by individuals with mTBI. Assessment for mTBI is often 

associated with potential financial compensation, which in turn has been commonly associated 

with worse outcomes. Because participants are not often blinded to study hypotheses, selfreported outcomes should be interpreted with greater caution than objective findings evaluated 

by blinded outcome assessors. Thus, future research should consider using objective and 

validated assessments, blinded outcome assessors, patient blinding to study hypotheses, and 

accounting for compensation factors whenever possible in order to reduce bias associated with 

outcome assessment.

Additionally, future research should employ commonly used outcome assessment tools in 

order to facilitate the combination of results across studies for meta-analytic purposes. One 

of the limitations of this body of literature was the wide variety of tools used to assess each 

outcome. Though we reported statistically significant results from included studies, it is possible 

that combining studies mathematically would increase power, and effects could be detected 

in aggregate which were not apparent at the individual study level. In the case of this review, 

diversity in outcome assessment tools precluded mathematical combination of results.74

A final strength of this review was the use of clear criteria for defining mTBI. However, 

because the majority of studies did not assess or report imaging results, and those that did were 
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Complications of Mild Traumatic Brain Injury in Veterans

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inconsistent in their inclusion of participants with positive imaging results, we were not able to 

apply exclusion criteria based on positive imaging as is recommended by the VA/DoD definition 

of mTBI. Additionally, because of our reliance on stringent definitional criteria, we excluded 

many studies that purported to study mTBI populations, but did not meet the criteria for this 

report. The scope of this report focused explicitly on OEF/OIF/OND Veterans and members of 

the military meeting VA/DoD mTBI criteria; consequently, this report provides a narrow window 

of information on mTBI and should not be viewed as comprehensive. Findings from other 

systematic reviews on mTBI in civilian populations should be considered for a more complete 

understanding of mTBI consequences. Future primary research should clearly report criteria used 

to define mTBI, including assessment and reporting of imaging results. Future research should 

investigate the possible impact of number of mTBI events, as many studies noted that Veterans 

experienced multiple mTBIs, though few examined this variable as a possible moderator of 

outcomes. Additionally, future reviews should consider examination of differences in outcomes 

based on definitional criteria for mTBI, as it is possible that less stringent criteria could be 

associated with different results.

CONCLUSIONS

Overall, given the low strength of evidence, it is difficult to draw firm conclusions about the 

effects of mTBI in Veteran and military populations. The literature reviewed here is relatively 

consistent with findings from the more methodologically rigorous, prospective, longitudinal 

studies conducted in civilian populations. Both bodies of literature suggest that though some 

negative outcomes occur for a significant portion of individuals who have mTBI, most objective 

results (e.g., objective cognitive test results) are not significantly different from control 

participants, and deficits that are present shortly following injury most often resolve within days 

to months. The literature on Veterans and members of the military suggests that many have 

physical and mental health symptoms, but it is not clear that those with mTBI experience more or 

higher severity symptoms than those without mTBI suggesting that outcomes may be influenced 

by other deployment-related conditions such as PTSD. The studies included in this report were 

low quality, cross sectional studies which did not provide consistent evidence for potential 

moderators of mTBI outcomes.
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24. Kelly MP, Coldren RL, Parish RV, Dretsch MN, Russell ML. Assessment of acute 

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25. Kennedy JE, Cullen MA, Amador RR, Huey JC, Leal FO. Symptoms in military service 

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Complications of Mild Traumatic Brain Injury in Veterans

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26. Kennedy JE, Leal FO, Lewis JD, Cullen MA, Amador RR. Posttraumatic stress 

symptoms in OIF/OEF service members with blast-related and non-blast-related mild 

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27. Lew HL, Pogoda TK, Hsu P-T, et al. Impact of the “polytrauma clinical triad” on sleep 

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28. Lippa SM, Pastorek NJ, Benge JF, Thornton GM. Postconcussive symptoms after blast 

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29. Nelson WN, Hoelzle JB, Doane BM, et al. Neuropsychological Outcomes of U.S. 

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Sponheim SR. Evaluation context impacts neuropsychological performance of OEF/

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31. Patil VK, St Andre JR, Crisan E, et al. Prevalence and treatment of headaches in veterans 

with mild traumatic brain injury. Headache. Jul-Aug 2011;51(7):1112-1121.

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whether neurological deficits and PTSD in combat veterans are related to episodes of 

mild TBI. BMJ Open. 2012;2(2):e000312.

33. Ruff RL, Ruff SS, Wang X-F. Headaches among Operation Iraqi Freedom/Operation 

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explosions. J Rehabil Res Dev. 2008;45(7):941-952.

34. Ruff RL, Ruff SS, Wang X-F. Improving sleep: initial headache treatment in OIF/

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35. Schiehser DM, Delis DC, Filoteo JV, et al. Are self-reported symptoms of executive 

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36. Spencer RJ, Drag LL, Walker SJ, Bieliauskas LA. Self-reported cognitive symptoms 

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performance in OIF/OEF veterans. J Rehabil Res Dev. 2010;47(6):521-530.

37. Swick D, Honzel N, Larsen J, Ashley V, Justus T. Impaired response inhibition in 

veterans with post-traumatic stress disorder and mild traumatic brain injury. J Int 

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38. Theeler BJ, Erickson JC. Mild head trauma and chronic headaches in returning US 

soldiers. Headache. Apr 2009;49(4):529-534.

39. Toblin RL, Riviere LA, Thomas JL, Adler AB, Kok BC, Hoge CW. Grief and 

physical health outcomes in U.S. soldiers returning from combat. J Affect Disord. Feb 

2012;136(3):469-475.

40. Wagner A, Jakupcak M. Combat-related stress reactions among U.S. veterans of wartime 

service. In: Matthews JHLMD, ed. The Oxford Handbook of Military Psychology. New 

York: Oxford University Press; 2012:15-28.

41. Carlson KF, Kehle SM, Meis LA, et al. Prevalence, assessment, and treatment of mild 

traumatic brain injury and posttraumatic stress disorder: a systematic review of the 

evidence. J Head Trauma Rehabil. Mar-Apr 2011;26(2):103-115.

42. Cohen B, Gima K, Bertenthal D, Kim S, Marmar C, Seal K. Mental Health Diagnoses 

and Utilization of VA Non-Mental Health Medical Services Among Returning Iraq and 

Afghanistan Veterans. J Gen Intern Med. 2010;25(1):18-24.

43. Lew HL, Otis JD, Tun C, Kerns RD, Clark ME, Cifu DX. Prevalence of chronic pain, 

posttraumatic stress disorder, and persistent postconcussive symptoms in OIF/OEF 

veterans: polytrauma clinical triad. J Rehabil Res Dev. 2009;46(6):697-702.

44. Pietrzak RH, Johnson DC, Goldstein MB, Malley JC, Southwick SM. Posttraumatic 

stress disorder mediates the relationship between mild traumatic brain injury and health 

and psychosocial functioning in veterans of Operations Enduring Freedom and Iraqi 

Freedom. J Nerv Ment Dis. Oct 2009;197(10):748-753.

45. Uomoto JM, Williams RM, Randa LA. Neurobehavioral consequences of combat-related 

blast injury and polytrauma. Ashley, Mark J [Ed]. 2010:63-95.

46. Vasterling JJ, Bryant RA, Keane TM. Understanding the interface of traumatic stress and 

mild traumatic brain injury: Background and conceptual framework. Vasterling, Jennifer 

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47. Bogdanova Y, Verfaellie M. Cognitive sequelae of blast-induced traumatic brain injury: 

recovery and rehabilitation. Neuropsychol Rev. Mar 2012;22(1):4-20.

48. Dolan S, Martindale S, Robinson J, et al. Neuropsychological sequelae of PTSD and 

TBI following war deployment among OEF/OIF veterans. Neuropsychol Rev. Mar 

2012;22(1):21-34.

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51. Brewin CR, Kleiner JS, Vasterling JJ, Field AP. Memory for emotionally neutral 

information in posttraumatic stress disorder: A meta-analytic investigation. Journal of 

Abnormal Psychology. Aug 2007;116(3):448-463.

52. Leskin LP, White PM. Attentional networks reveal executive function deficits in 

posttraumatic stress disorder. Neuropsychology. May 2007;21(3):275-284.

53. Vasterling JJ, Brailey K, Constans JI, Sutker PB. Attention and memory dysfunction in 

posttraumatic stress disorder. Neuropsychology. Jan 1998;12(1):125-133.

54. Vasterling JJ, Proctor SP. Understanding the neuropsychological consequences of 

deployment stress: a public health framework. J Int Neuropsychol Soc. Jan 2011;17(1):1-

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55. High WMJ, Sander AM, Struchen MA, Hart KA. Rehabilitation for Traumatic Brain 

Injury. New York, NY: Oxford University Press; 2005.

56. Crooks CY, Zumsteg JM, Bell KR. Traumatic Brain Injury: A Review of Practice 

Management and Recent Advances. Physical medicine and rehabilitation clinics of North 

America. 2007;18(4):681-710.

57. McCrea M. Functional Outcome after mTBI. In: Series OW, ed. Mild Traumatic Brain 

Injury and Postconcussion Syndrome: The New Evidence Base for Diagnosis and 

Treatment. New York, NY: Oxford University Press; 2008.

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States Government Printing Office; 2010.

59. Carroll LJ, Cassidy JD, Peloso PM, et al. Prognosis for mild traumatic brain injury: 

results of the who collaborating centre task force on mild traumatic brain injury. J 

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60. Belanger HG, Vanderploeg RD. The neuropsychological impact of sports-related 

concussion: a meta-analysis. J Int Neuropsychol Soc. Jul 2005;11(4):345-357.

61. Dikmen SS, Corrigan JD, Levin HS, Machamer J, Stiers W, Weisskopf MG. Cognitive 

outcome following traumatic brain injury. J Head Trauma Rehabil. Nov-Dec 

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acute phase of mild traumatic brain injury. Neurology. May 1 2012;78(18):1428-1433.

64. Sharma R, Laskowitz DT. Biomarkers in traumatic brain injury. Curr Neurol Neurosci 

Rep. Oct 2012;12(5):560-569.
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65. Jeter CB, Hergenroeder GW, Hylin MJ, Redell JB, Moore AN, Dash PK. Biomarkers for 

the diagnosis and prognosis of mild traumatic brain injury/concussion. J Neurotrauma. 

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66. Goldstein LE, Fisher AM, Tagge CA. Chronic traumatic encephalopathy in blastexposed military veterans and a blast neurotrauma mouse model. Sci Transl Med. 

2012;4(134):134ra160.

67. Omalu B, I., Bailes J, Hammers JL, Fitzsimmons RP. Chronic Traumatic Encephalopathy, 

Suicides and Parasuicides in Professional American Athletes: The Role of the Forensic 

Pathologist. American Journal of Forensic Medicine & Pathology June. 2010;31(2):130-

132.

68. Baugh CM, Stamm JM, Riley DO, et al. Chronic traumatic encephalopathy: 

neurodegeneration following repetitive concussive and subconcussive brain trauma. 

Brain imaging behav. Jun 2012;6(2):244-254.

69. McDonald BC, Saykin AJ, McAllister TW. Functional MRI of mild traumatic brain injury 

(mTBI): progress and perspectives from the first decade of studies. Brain imaging behav. 

Jun 2012;6(2):193-207.

70. Lin AP, Liao HJ, Merugumala SK, Prabhu SP, Meehan WP, 3rd, Ross BD. Metabolic 

imaging of mild traumatic brain injury. Brain imaging behav. Jun 2012;6(2):208-223.

71. Bigler ED, Maxwell WL. Neuropathology of mild traumatic brain injury: relationship to 

neuroimaging findings. Brain imaging behav. Jun 2012;6(2):108-136.

72. Shenton M, Hamoda H, Schneiderman J, et al. A review of magnetic resonance imaging 

and diffusion tensor imaging findings in mild traumatic brain injury. Brain Imaging and 

Behavior. Jun 2012;6(2):137-192.

73. Whittaker R, Kemp S, House A. Illness perceptions and outcome in mild head injury: a 

longitudinal study. J Neurol Neurosurg Psychiatry. 2007;78(6):644-646.

74. Wilde EA, Whiteneck GG, Bogner J, et al. Recommendations for the Use of Common 

Outcome Measures in Traumatic Brain Injury Research. Archives of physical medicine 

and rehabilitation. 2010;91(11):1650-1660.e1617.

75. Morissette SB, Woodward M, Kimbrel NA, et al. Deployment-related TBI, persistent 

postconcussive symptoms, PTSD, and depression in OEF/OIF veterans. Rehabil Psychol. 

Nov 2011;56(4):340-350.
55

Complications of Mild Traumatic Brain Injury in Veterans

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APPENDIX A. SEARCH STRATEGIES

Database: Ovid MEDLINE(R) and Ovid OLDMEDLINE(R) <1946 to September Week 3 2012>, 

Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations <October 02, 2012>

Search Strategy:

--------------------------------------------------------------------------------

1 exp Brain edema/ (11605)

2 exp cerebrovascular trauma/ (4960)

3 exp craniocerebral trauma/ (113847)

4 exp coma/ (17150)

5 exp glasgow outcome scale/ (1042)

6 exp glasgow coma scale/ (6068)

7 ((brain* or capitis or cerebr* or crani* or hemispher* or inter-crani* or intra-crani* or 

skull*) adj4 (contusion* or damag* or fractur* or injur* or trauma* or wound*)).ab,ti. 

(77042)

8 ((brain or crani* or cerebr* or head or inter-cran* or intra-cran*) adj4 (bleed* or 

haematoma* or haemorrhag* or hematoma* or hemorrhag* or pressure)).ti,ab. (23995)

9 (Glasgow adj (coma or outcome) adj (scale* or score*)).ab,ti. (7439)

10 ‘Rancho Los Amigos Scale’.ti,ab. (31)

11 diffuse axonal injur*.ti,ab. (755)

12 ((brain or cerebral or intracranial) adj3 (edema or oedema or swell*)).ab,ti. (11389)

13 ((coma* or concuss* or unconscious* or ‘persistent vegetative state’) adj2 (damag* or 

fractur* or injur* or trauma* or wound*)).ti,ab. (1686)

14 (mtbi or “mild trauma* injur*”).tw. or “minor trauma* injur*”.mp. (639)

15 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 (209513)

16 exp cohort studies/ (1212058)

17 exp prognosis/ (967036)

18 exp morbidity/ (328065)

19 exp mortality/ (255922)

20 exp survival analysis/ (158174)

21 exp models, statistical/ (230839)

22 prognos*.tw. (324957)

23 course*.tw. (428896)

24 diagnosed.tw. (303319)

25 cohort*.tw. (221535)

26 death.tw. (417341)

27 predict*.tw. (808663)

28 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 (3743025)

29 diagnosed.tw. (303319)

30 cohort:.mp. (281196)

31 (predictor: or death).tw. (578864)

32 exp models, statistical/ (230839)

33 prognosis/ (327999)
56

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

34 29 or 30 or 31 or 32 or 33 (1494750)

35 28 or 34 (3743144)

36 15 and 35 (67135)

37 exp rehabilitation, vocational/ (8852)

38 exp employment/ (49891)

39 exp work/ (12406)

40 sick leave/ (3365)

41 absenteeism/ (6861)

42 exp occupational health/ (23070)

43 exp occupational medicine/ (21574)

44 exp disabled persons/ (43220)

45 “recovery of function”/ (25824)

46 exp human activities/ (291441)

47 exp self care/ (36358)

48 activities of daily living.tw. (13206)

49 (dressing or feeding or eating or toilet$ or bathing or mobil$ or driving or public 

transport$).tw. (409253)

50 ((daily or domestic or house or home) adj5 (activit$ or task$ or skill$ or chore$)).tw. 

(34321)

51 (“work status” or “work capacity”).tw. (4948)

52 (unemployment or re-employment or underemployment or “job retention”).ti,ab. (6217)

53 (return* adj2 school).tw. (428)

54 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 or 51 or 52 

or 53 (884984)

55 15 and 54 (12268)

56 exp dementia/ (109281)

57 Delirium/ or exp Delirium, Dementia, Amnestic, Cognitive Disorders/ (165121)

58 dement*.mp. or alzheimer*.tw. (137451)

59 exp Parkinsonian Disorders/ (53442)

60 parkinson*.tw. (67897)

61 56 or 57 or 58 or 59 or 60 (263117)

62 15 and 61 (10666)

63 36 or 55 or 62 (80547)

64 animals/ not (humans/ and animals/) (3693774)

65 63 not 64 (72473)

66 limit 65 to (danish or english or french or norwegian or spanish or swedish) (62699)

67 limit 66 to yr=”2001 -Current” (36478)

68 exp “Outcome Assessment (Health Care)”/ (605282)

69 (intervention* adj3 stud*).tw. (23915)

70 68 or 69 (626005)

71 15 and 70 (12781)

72 71 not 64 (12055)

73 limit 72 to (yr=”2001 -Current” and (danish or english or french or norwegian or swedish)) 

(8537)

74 67 or 73 (36658)
57

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

75 randomized controlled trial.pt. (337763)

76 Randomized controlled trial/ (337763)

77 Randomized Controlled Trials as Topic/ (83241)

78 Double-Blind Method/ (117191)

79 clinical trial.pt. (474276)

80 “double blind:”.mp. (143695)

81 placebos/ (31353)

82 placebo:.mp. (158293)

83 random:.mp. (788646)

84 75 or 76 or 77 or 78 or 79 or 80 or 81 or 82 or 83 (1069355)

85 15 and 84 (10248)

86 review/ (1739065)

87 (medline or medlars or pubmed or grateful med or CINAHL or scisearch or psychinfo 

or psycinfo or psychlit or psyclit or handsearch* or hand search* or manual* search* or 

electronic database* or bibliographic database* or embase or lilacs or scopus or web of 

science).mp. (74569)

88 86 and 87 (48085)

89 meta-analysis.mp. (59484)

90 meta-analysis as topic/ (12450)

91 meta-analysis/ (36480)

92 systematic review*.tw. (38103)

93 cochrane database*.jn. (9039)

94 88 or 89 or 90 or 91 or 92 or 93 (112607)

95 15 and 94 (1435)

96 exp brain neoplasms/ (111650)

97 (cancer* or neoplasm* or tumor* or malign*).mp. and brain.tw. (75605)

98 exp Glioma/ (55756)

99 96 or 97 or 98 (164154)

100 15 and 99 (9656)

101 exp pain/ (283152)

102 exp chronic disease/ (210066)

103 101 and 102 (20005)

104 (chronic* adj3 pain*).mp. (32890)

105 103 or 104 (40897)

106 15 and 105 (366)

107 exp sports/ (100542)

108 exp recreation/ (116143)

109 (return* adj3 play*).tw. (803)

110 107 or 108 or 109 (116607)

111 15 and 110 (3782)

112 exp mental disorders/ (880032)

113 15 and 112 (15929)

114 exp disability evaluation/ (35932)

115 exp “Outcome Assessment (Health Care)”/ (605282)

116 disab:.tw. (119042)
58

Complications of Mild Traumatic Brain Injury in Veterans

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117 114 or 115 or 116 (728782)

118 15 and 117 (17459)

119 74 or 85 or 95 or 100 or 106 or 111 or 113 or 118 (68980)

120 limit 119 to (english language and yr=”2001 -Current” and (danish or english or french or 

norwegian or swedish)) (43016)

121 animals/ not (humans/ and animals/) (3693774)

122 120 not 121 (39793)

123 exp “United States Department of Veterans Affairs”/ or exp Veterans Health/ or exp 

Hospitals, Veterans/ or exp Veterans Disability Claims/ or exp Veterans/ (15311)

124 veteran.mp. (2331)

125 veterans.mp. (23349)

126 VA.mp. (16805)

127 VA.in. (58986)

128 VAMC.mp. (285)

129 VAMC.in. (2086)

130 exp Military Medicine/ or exp “United States Department of Defense”/ or exp Naval 

Medicine/ (30814)

131 exp Hospitals, Military/ (3861)

132 exp Military Facilities/ (3901)

133 (army or navy or air force or marines or coast guard).mp. [mp=title, abstract, original title, 

name of substance word, subject heading word, protocol supplementary concept, rare 

disease supplementary concept, unique identifier] (15842)

134 military.mp. or exp Military Personnel/ (22947)

135 soldier.mp. (1480)

136 soldiers.mp. (5245)

137 123 or 124 or 125 or 126 or 127 or 128 or 129 or 130 or 131 or 132 or 133 or 134 or 135 or 

136 (151164)

138 122 and 137 (1170)

139 traumatic brain injury.mp. or exp Brain Injuries/ (48119)

140 tbi.mp. (10831)

141 139 or 140 (51178)

142 137 and 141 (1468)

143 138 or 142 (1977)

144 from 143 keep 1-1977 (1977)

***************************

The above search strategy was applied to two additional databases on Oct. 3, 2012, with the 

following yield:

PsycINFO=961

Cochrane Register of Controlled Trials (OVID)=46
59

Complications of Mild Traumatic Brain Injury in Veterans

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APPENDIX B. STUDY SELECTION FORM 

1. Language: Is the full text of the article in English?

Yes........................................................................................................Proceed to #2

No.....................................................................................................Code X1. STOP

2. Population: Is the population adult, human participants who are Veterans or members of 

the military from any country? Studies that do not differentiate between adult and child 

populations, or between Veteran/military and civilian populations, will be excluded.

Yes........................................................................................................Proceed to #3

No..................Code X2. Add code B if retaining for background/discussion. STOP

3. Publication type: Does the article present original study data, or is it a systematic-review or 

meta-analysis? Narrative or non-systematic reviews, letters, editorials, and commentaries will 

be excluded.

Yes........................................................................................................Proceed to #4

No..................Code X3. Add code B if retaining for background/discussion. STOP

4. Case definition: Does the article stratify/examine mTBI separately from moderate to severe 

TBI cases? Participants can consist of a mixed group of TBI severity (mild, moderate or 

severe) only if the results are stratified by severity and the mTBI subjects can be clearly 

identified. Studies that include mixed groups of TBI severity and do not differentiate between 

mild, moderate and severe TBI in their analysis will be excluded. Patients must be clearly 

described as having mTBI, Post-Concussive Syndrome, or concussion; if none of these terms 

are used, patients must be clearly defined as falling within the definition of mTBI from the 

VA/DoD Clinical Practice Guideline for Management of Concussion/Mild Traumatic Brain 

Injury (2009) listed below.

Yes........................................................................................................Proceed to #5

No..................Code X4. Add code B if retaining for background/discussion. STOP

5. Systematic review: Is the article a systematic review or meta-analysis of primary studies? 

Yes................................................................Code ISR (systematic review). STOP

No.........................................................................................................Proceed to #6

6. Sample size: Is the article a primary study with a sample size of at least 30 mTBI cases?

Yes...............................................................................Proceed to #7

No .............Code X6. Add code B if retaining for background/discussion. STOP

7. Applicability: Does the study report outcomes addressed in our Key Questions (e.g., health, 

cognitive, etc. for KQ1; or factors associated with outcomes in KQ1; or cost/utilization)?

Yes........................................................................................................Proceed to #8

No..................Code X7. Add code B if retaining for background/discussion. STOP

8. Intervention studies: Is the study an intervention study?

Yes........................................................................................................Proceed to #9

No.......................................................................................................Proceed to #10
60

Complications of Mild Traumatic Brain Injury in Veterans

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9. Intervention outcomes: Does the intervention study report outcomes not influenced by 

intervention participation (e.g., baseline and/or control group outcome data)?

Yes......................................................................................................Proceed to #10

No..................Code X8. Add code B if retaining for background/discussion. STOP

10. VA/DoD mTBI definition: Does the study define mTBI participants as meeting the VA/

DoD Clinical Practice Guideline for Management of Concussion/Mild Traumatic Brain 

Injury (2009) definition of mTBI (listed below) with the exception of including/excluding/

not reporting positive imaging results? Studies may use a different mTBI definition, but all 

criteria with the exception of positive imaging must fall within the VA/DoD definition.

Yes......................................................................Code IPS (primary study). STOP

No................Code X10. Add code B if retaining for background/discussion. STOP
61

Complications of Mild Traumatic Brain Injury in Veterans

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APPENDIX C. Definition of mTBI from the VA/DoD 

Clinical Practice Guideline for Management of

Concussion/Mild Traumatic Brain Injury (2009) 

1.1 Definition of Traumatic Brain Injury 

A traumatically induced structural injury and/or physiological disruption of brain function as 

a result of an external force that is indicated by new onset or worsening of at least one of the 

following clinical signs, immediately following the event:

•	 Any period of loss of or a decreased level of consciousness (LOC) 

•	 Any loss of memory for events immediately before or after the injury (post-traumatic 

amnesia6

) 

•	 Any alteration in mental state at the time of the injury (confusion, disorientation, slowed 

thinking, etc.) (Alteration of consciousness/mental state5)

•	 Neurological deficits (weakness, loss of balance, change in vision, praxis, paresis/plegia, 

sensory loss, aphasia, etc.) that may or may not be transient

•	 Intracranial lesion 

External forces may include any of the following events: the head being struck by an object, the 

head striking an object, the brain undergoing an acceleration/deceleration movement without 

direct external trauma to the head, a foreign body penetrating the brain, forces generated from 

events such as a blast or explosion, or other forces yet to be defined. 

The above criteria define the event of a TBI. Not all individuals exposed to an external force will 

sustain a TBI, but any person who has a history of such an event with immediate manifestation 

of any of the above signs and symptoms can be said to have had a TBI. 

1.2 Severity of Brain Injury Stratification 

TBI is further categorized as to severity into mild, moderate, or severe based on the length of 

LOC, AOC, or PTA (see Table A-1). Acute injury severity is determined at the time of the injury.

•	 The patient is classified as mild/moderate/severe if s/he meets any of the criteria in 

Table A-1 within a particular severity level. If a patient meets criteria in more than one 

category of severity, the higher severity level is assigned. 

•	 If it is not clinically possible to determine the brain injury level of severity because 

of medical complications (e.g., medically induced coma), other severity markers are 

required to make a determination of the severity of the brain injury. 

•	 Abnormal structural imaging (e.g., Magnetic Resonance Imaging or Computed 

Tomography Scanning) attributed to the injury will result in the individual being 

considered clinically to have greater than mild injury. 

In addition to traditional imaging studies, other imaging techniques such as functional magnetic 

resonance imaging, diffusion tensor imaging, positron emission tomography scanning; 

electrophysiological testing such as electroencephalography; and neuropsychological or other 

standardized testing of function have been used in the evaluation of persons with TBIs, but are 
62

Complications of Mild Traumatic Brain Injury in Veterans

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not considered in the currently accepted criteria for measuring severity at the time of the acute 

injury outlined in Table A -1.

The severity level has prognostic value, but does not necessarily predict the patient’s ultimate 

level of functioning. There is substantial evidence that the epidemiology, pathophysiology, 

natural history, and prognosis for concussion/mTBI are different than for moderate and severe 

TBI. For example, moderate and severe TBI are often associated with objective evidence of 

brain injury on brain scan or neurological examination (e.g., neurological deficits) and objective 

deficits on neuropsychological testing, whereas these evaluations are frequently not definitive in 

persons with concussion/mTBI. The natural history and prognosis of moderate and severe TBI 

are much more directly related to the nature and severity of the injury in moderate and severe 

TBI, whereas factors unrelated to the injury (such as co-existing mental disorders) have been 

shown to be the strong predictors of symptom persistence after a concussion/mTBI. 

Table A-1. Classification of TBI Severity

Criteria Mild Moderate Severe 

Structural imaging Normal Normal or abnormal Normal or abnormal 

Loss of Consciousness 

(LOC) 

0–30 min > 30 min and < 24 

hrs 

> 24 hrs 

Alteration of consciousness/

mental state (AOC) 

a moment up to 24 

hrs

> 24 hours. Severity based on other criteria

Post-traumatic amnesia 

(PTA) 

0-1 day > 1 and < 7 days > 7 days 

Glasgow Coma Scale (best 

available score in first 24 

hours) 

13-15 9-12 < 9 
63

Complications of Mild Traumatic Brain Injury in Veterans

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APPENDIX D. Excluded studies that did not meet

mTBI definition criteria

Author, Year Definition

Patients 

with 

Abnormal 

Imaging

Citation How 

Assessed

Adams, Larson, 

Corrigan, et al., 

20121

Length of LOC classified as < 1 minute, 

1-20 minutes, or > 20 minutes. Used the 

Health Related Behaviors Among Active 

Duty Military Personnel Survey response 

categories: “The HRB Survey symptom 

response groups permit recoding LOC 

as up to 20 minutes and greater than 

20 minutes. This provides insufficient 

information to code LOC using the 

American Congress of Rehabilitation 

Medicine’s definition of mild TBI.”

NR Kay, Harrington, 

Adams, et al., 1993

Self-report 

survey

Arbisi, Polusny, 

Erbes, et al., 20112

Adapted from the Defense and Veterans 

Brain Injury Center screening tool: yes 

to last item “dazed, confused, see stars, 

get knocked out or lose consciousness” 

classified as mTBI. No participants 

reported “receiving treatment while in 

Iraq for a TBI or were removed from 

assigned duties as a result of exposure to 

blast or other form of head trauma.”

NR Schwab et al., 2007 Self-report 

mailed questionnaire

Armistead-Jehle, 

20103

“Screened positive on the VHA TBI 

screens” for “possible mTBI.” “All 

patients suffered at most a mild TBI..., 

as none reported loss of consciousness of 

more than 30 minutes or posttraumatic 

amnesia of 24 hours or more.”

NR US Department of 

Veterans Affairs, 

2007

Self-report

Bazarian, 

Donnelly, Peterson, 

et al., 20124

“Mild TBI diagnosis was determined 

by in-person interview using a 22-item 

questionnaire developed to establish 

the nature, probability, and severity of 

deployment-related TBI among OEF/OIF 

veterans. The interview followed previously 

published TBI diagnostic criteria, which 

include confirmation of a possible 

TBI event, confirmation of alteration 

of consciousness, and confirmation of 

postconcussion symptoms. On the basis 

of the standardized clinical interview, 

interviewers rated the likelihood of mild 

TBI according to a 6-point scale: “not at 

all likely,” “very unlikely,” “somewhat 

unlikely,” “somewhat likely,” “very likely,” 

and “almost certainly.” These likelihood 

categories were used in all analyses. 

However, for descriptive purposes, 

subjects were defined as having mild TBI 

if interviewers rated them “very likely” or 

“almost certainly.””

NR Lew, Poole, & 

Vanderploeg, 2007

Clinical 

interview
64

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Author, Year Definition

Patients 

with 

Abnormal 

Imaging

Citation How 

Assessed

Booth-Kewley, 

Highfill-McRoy, 

Larson, et al., 

20125

“Mild TBI symptoms were assessed using 

a set of questions that asked participants 

whether they had received an injury to the 

head during their most recent deployment 

that involved ‘being dazed, confused, or 

‘seeing stars’’ or ‘not remembering the 

injury, or losing consciousness (knocked 

out).’ A participant was classified as having 

a positive TBI screen if any of the three 

questions elicited a positive response.”

NR Centers for Disease 

Control and 

Prevention & World 

Health Organization 

definitions adapted 

by the Defense and 

Veterans Brain Injury 

Center working group 

for military use

Self-report 

survey

Brenner, Terrio, 

Homaifar, et al., 

20106

Warrior Administered Retrospective 

Casualty Assessment Tool (WARCAT) and 

Brief Trauma Brain Injury Screen. “All 45 

participants whose test scores were included 

in analyses had a history of blast exposure 

with alteration of or loss of consciousness 

(LOC).” “The nature of the most serious 

mTBIs reported were: n = 30, altered 

consciousness only; n = 12, up to 1-min 

LOC; and n = 3, one to 20-min LOC.”

NR Soldier Readiness 

Process, 2007; 

Schwab et al., 2007

Chart 

review, 

self-report 

survey, and 

clinical 

interview

Brenner, Ivins, 

Schwab, Warden, 

Nelson, Jaffee, & 

Terrio, 20107

As described in Terrio et al., 2009: Warrior 

Administered Retrospective Casualty 

Assessment Tool (WARCAT) and Brief 

Trauma Brain Injury Screen

NR Soldier Readiness 

Process, 2007; 

Schwab et al., 2007

Chart 

review, 

self-report 

survey, and 

clinical 

interview

Cameron, 

Marshall, 

Sturdivant, & 

Lincoln, 20118

“Incident cases of mTBI were operationally 

defined according to the administrative 

case definition proposed by the Centers 

for Disease Control and Prevention (CDC) 

for research purposes... and include ICD9-CM codes for skull fracture (800.00, 

800.5, 801.0, 801.5, 803.0, 803.5, 804.0, 

and 804.5), concussion (850.0, 850.1, 

850.5, and 850.9), intracranial injury of 

unspecified nature (854.0), and head injury 

unspecified (959.01). In addition to the four 

digit codes listed, all subordinate five-digit 

codes were also included.”

NR Centers for Disease 

Control and 

Prevention, 2003

Chart review

Carlson, Kehle, 

Meis, et al., 20119

“Included studies must have assessed 

participants for a “probable” TBI (identified 

using self-report screening instruments) or 

diagnosed TBI history.”

NR NR NA

Clement & 

Kennedy, 200310

LOC<60 minutes with no neurological 

findings

Excluded NR Chart review
65

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Author, Year Definition

Patients 

with 

Abnormal 

Imaging

Citation How 

Assessed

Dougherty, 

MacGregor, Han, 

et al., 201111

International Classification of Diseases, 9th

Revision (ICD-9) codes 800.0-801.9, 803.0-

804.9, 850.0-854.1. “The Abbreviated 

Injury Scale (AIS) was used to describe 

the severity of brain injury... Due to a 

small number of TBI observations with 

scores of 4 (severe injury) and 5 (critical 

injury) in the present study, TBI severity 

was classified as follows: 0 = No TBI, 1 = 

minor, 2 = moderate and 3-5 = serious to 

critical. Service members with AIS scores 

of 6 were not eligible for inclusion in the 

study.”

NR Gennarelli & Wodzin, 

2005

Chart review

Drake, Gray, 

Yoder, et al., 200012

“Subjects were consecutive MTBI 

patients... meeting specific inclusion 

criteria... a documented TBI classified by 

accepted criteria as a mild TBI.” No specific 

mTBI definition noted.

NR NR Self-report 

and chart 

review

Eskridge, 201113 “Clinical diagnosis codes from the 

International Classification of Diseases, 9th

Revision (ICD-9) were assigned to each 

injury... In addition to the assigning of 

diagnosis codes, severity of each injury is 

accessed with two different standardized 

measures of injury severity; the Abbreviated 

Injury Scale (AIS) and the Injury Severity 

Scale (ISS)... The ISS for each blast 

episode was documented and categorized 

into one of four severity levels; mild (ISS 

1-3), moderate (ISS 4-8), serious (ISS 9-15) 

and severe (ISS 16 and higher).”

NR NR Chart review

Fear, Jones, 

Groom, et al., 

200914

“Criteria for identification include 

confusion or disorientation, loss of 

consciousness lasting less than 30 min or 

post-traumatic amnesia lasting less than 

24 h.” However, description of population 

studied only states, “we have examined 

the prevalence of symptoms thought to 

be a consequence of mTBI,” with unclear 

description of how mTBI was determined.

NR Holm, et al., 2005 Chart review

Ferrier-Auerbach, 

Erbes, Polusny, et 

al., 200915

“Three items adapted from the Defense 

and Veterans Brain Injury Center (DVBIC) 

Blast Exposure Screening Questionnaire... 

(1) Were you ever so close to a blast that 

you could feel the blast wave (such as 

heat or pressure) or afterward had trouble 

hearing or problems with attention or 

memory?... (2) Did you have any injuries 

from a blast, vehicle crash, bullet/shrapnel 

or fall?... (3) Did any injury cause you to 

be dazed/confused, ‘see stars,’ get knocked 

out, or lose consciousness?”

NR Schwab et al., 2007 Self-report 

survey
66

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Author, Year Definition

Patients 

with 

Abnormal 

Imaging

Citation How 

Assessed

French, Lange, 

Iverson, Ivins, et 

al., 201216

LOC < 15 mins; PTA < 24 hours; absence 

of intracranial abnormality on computed 

tomography or magnetic resonance imaging 

scan

Excluded Used VA/DoD 

criteria, but data 

limited to LOC < 15 

minute categories.

Chart review

Gottshall, Gray, 

Drake, et al., 

200717

Definition: GCS 13-15. One patient 

identified as having an open head injury. 

LOC categorized as 31-60 (1 patient), and 

> 60 minutes (one patient), and up to 20 

minutes (all remaining patients).

NR American Academy 

of Neurology, 1997

Clinical 

presentation 

(to ED or 

Battalion Aid 

Station)

Helfer, Jordan, 

Lee, et al., 201118

ICD-9CM codes 850.0, 850.11, 850.12, 

850.2, 850.3, 850.4, 850.5, 850.9, 959.01, 

V15.52

NR US Dept of Health 

and Human Services, 

2008

Chart review

Heltemes, 

Dougherty, 

MacGregor, & 

Galarneau, 201119

International Classification of Diseases, 

9th Revision, Clinical Modification (ICD9-CM) codes 800.0-801.9, 803.0-804.9, 

850.0-854.1.

NR Centers for Disease 

Control and 

Prevention, 2003

Chart review

Hoffer, Balaban, 

Gottshall, et al., 

201020

“Definitive diagnosis of mild traumatic 

brain as defined by the 2007 Joint Service 

Surgeon General’s Definition”

NR Assistant Secretary 

of Defense: 

Memorandum on 

Traumatic Brain 

Injury: Definition and 

Reporting. Available 

at http://www.

pdhealth.mil/TBI.asp

In theater 

clinical 

evaluation

Hoffer, Donaldson, 

Gottshall, et al., 

200921

No specific mTBI definition listed. NR NR Clinical 

interview

Hoge, McGurk, 

Thomas, et al., 

200822

Positive response to three questions: LOC, 

being dazed and confused, seeing stars or 

not remembering the injury. However, “four 

Soldiers reported LOC lasting longer than 

30 minutes. Although technically they were 

considered to have a moderate TBI they 

were not excluded because the number was 

low and it was not possible to verify the 

self-report data on any of the subjects”.

NR DVBIC, 2006; CDC, 

2003

Self-report

Ivins, Schwab, 

Baker, & Warden, 

200323

“Head injury for which any LOC or any 

alteration of mental state without LOC 

was reported.” Reports rates of concussion 

grades separately, though the categories are 

divided by LOC < 20 minutes and LOC 

between 20-59 minutes.

NR Kay et al., 1993 Chart review

Ivins, Schwab, 

Baker, & Warden, 

200624

ICD-9CM codes 800.00-801.99, 803.00-

804.99, and 850.0-854.19 and AIS severity 

codes of minor or moderate.

NR Kay et al., 1993; 

Thurman & Guerrero, 

1999

Chart review
67

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Author, Year Definition

Patients 

with 

Abnormal 

Imaging

Citation How 

Assessed

Ivins, Kane, & 

Schwab, 200925

Brief Traumatic Brain Injury Screen 

(BTBIS); LOC criteria < 20 mins. 

Additional computerized survey 

administered; however, it appears that 

only those with LOC < 20 minutes were 

included in the further assessment.

Brief Traumatic Brain Injury Screen 

(BTBIS); Patients who screened positive 

for TBI and had LOC< = 20 minutes and/or 

possible PTA< = 24 hours were identified 

as having MTBI with LOC or possible PTA

NR Kay et al., 1993; 

Thurman & Guerrero, 

1999

Chart review

Ivins, 201026 Mapped ICD-9 CM diagnoses to the 

Abbreviated Injury Scale (AIS): ICD-9CM 

codes 800.00-801.99, 803.00-804.99, and 

850.0-854.19 and AIS severity codes of 

minor or moderate. Combines mild and 

moderate into one category.

NR Kay et al., 1993; 

Thurman & Guerrero, 

1999

Chart review

Lange, Pancholi, 

Bhagwat, et al., 

201227

“PTA < 24 hours and LOC < 15 minutes.” 

“It was our preference to use a LOC 

criterion of < 30 minutes, consistent with 

commonly used diagnostic criteria... 

However, the available information 

regarding LOC was limited to categorical 

data that did not allow us to differentiate 

between LOC greater or lower than 30 

min.”

Included Carroll et al., 2004; 

Management of 

Concussion/mTBI 

Working Group, 

2009; ACRM, 1993

Chart review

Lange, Pancholi, 

Brickell, et al., 

201228

LOC < 15 mins; PTA < 24 hours Included Used VA/DoD 

criteria, but data 

limited to LOC < 15 

minute categories.

Chart review 

and clinical 

interview

Lange, Brickell, 

French, et al., 

201229

Uncomplicated: PTA<24 hours, LOC < 

15 mins, negative imaging; complicated: 

positive imaging. “It was our preference to 

use an LOC criterion of 30 min to classify 

MTBI consistent with commonly used 

military and civilian diagnostic criteria. 

However, the available information 

regarding LOC was limited to categorical 

data that did not allow us to differentiate 

between LOC greater or less than 30 min 

(i.e., available data = LOC < 15 min and 

LOC 16–60 min).”

Excluded Used VA/DoD 

criteria, but data 

limited to LOC < 15 

minute categories.

Routine 

comprehensive clinical 

evaluation

Lew, Garvert, 

Pogoda, et al., 

200930

Mild TBI was defined as an initial GCS 

score of 13 to 15, PTA duration of <1 day, 

or LOC duration of <1 hour

NR NR Chart review 

and clinical 

evaluation
68

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Author, Year Definition

Patients 

with 

Abnormal 

Imaging

Citation How 

Assessed

Luis, Venderploeg, 

& Curtiss, 200331

“During the interview, participants were 

asked, among many others, the following 

three questions: 1) since your discharge 

from active duty, have you been injured in a 

MVA? 2) Since your discharge from active 

duty have you injured your head (HI)? and 

(3) Did you lose consciousness as a result 

of the head injury?”

Analysis by LOC group but time of LOC 

not specified.

NR NR Self-report

MacGregor, 200732 “An ICD-9 code in the following ranges 

was defined as a TBI (n = 124): 800.0- 

801.9 (fractures of the vault or base of the 

skull); 803.0-804.9 (other and unqualified 

and multiple fractures of the skull); and 

850.0-854.1 (intracranial injury, including 

concussion, contusion, laceration, and 

hemorrhage)... Severity of TBI was 

indicated with the Abbreviated Injury Scale 

(AIS). The AIS ranges from 1 (relatively 

minor) to 6 (currently untreatable), 

and is determined separately for each 

different body region. Severity of TBI was 

determined by maximum AIS score for the 

head region – head AIS 1-2 indicated mild 

TBI, head AIS 3-5 indicated moderatesevere TBI. A majority of TBI identified via 

CHAMPS did not have a head AIS score 

present; in this case the TBI was assumed 

to be of mild severity due to a closed head 

injury.”

NR ICD-9-CM, 2005 Chart review

MacGregor, 

Dougherty, & 

Galarneau, 201133

International Classification of Diseases, 9th

Revision (ICD-9) codes 800.0-801.9, 803.0-

804.9, 850.0-854.1. “The AIS was used to 

describe the severity of these injuries and 

the injuries were scored according to the 

following scale: 0, no injury; 1 minor; 2, 

moderate; 3, serious; 4, severe; 5, critical; 6, 

fatal injury. As per previous literature, each 

participant was categorized by the severity 

of their highest (or maximum) AIS Head 

score as mild (AIS score = 1-2), moderate 

(AIS score = 3), or severe (AIS score = 

4-6).

NR Ommaya, Ommaya, 

Dannenberg, et al., 

1996

Chart review

MacGregor, 

Dougherty, 

Morrison, et al., 

201134

“A concussion was defined by the ICD9-CM code of 850.0-850.9. Severity of 

concussion was defined using the AIS.”

NR NR Chart review 

MacGregor, 

Shaffer, Dougherty, 

et al. 201035

ICD-9 codes 800-801.9, 803-804.9, and 

850-854.1; Abbreviated Injury Scale (AIS) 

score 1-2 = “mild,” 3-5 = “moderate to 

severe”

NR Ommaya et al., 1996 Chart review
69

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Author, Year Definition

Patients 

with 

Abnormal 

Imaging

Citation How 

Assessed

McGuire, 

Marsh, Sowin, & 

Robinson, 201236

“LOC less than 30 min or amnesia less than 

60 min”

NR Annegers et al., 1998 NR

Mora, Ritenour, 

Wade, et al., 200937

“Consciousness status to determine mTBI 

was queried using both codes from ICD and 

Abbreviated Injury Scale for indications of 

trauma to the head, concussive injuries, and 

indications of consciousness at the time of 

injury. A loss of consciousness served as the 

definition for mTBI.

NR NR Chart review

Morgan, 

Lockwood, 

Steinke, et al., 

201238

No clear mTBI definition. NR NR Self-report 

screening 

and clinical 

interview

Nelson, Weiser, 

Giford, et al., 

201139

“The Brief Traumatic Brain Injury Screen 

was used to identify cases (probable mTBl) 

and controls (no mTBI). Individuals were 

placed in the “probable mTBl” group if 

they endorsed an injury (reported at least 

one injury on the BTBIS) and indicated that 

they had lost consciousness for a defined 

period of time (ranging from less than 1 

minute to longer than 20 minutes) following 

the injury.

Those who did not report an injury or a loss 

of consciousness (LOC) for any amount of 

time following an injury acted as the control 

group.”

NR Defense and Veterans 

Brain Injury Center 

(DVBIC)

Chart review

Olson-Madden, 

Forster, Huggins, 

& Schneider, 

201240

“Injury severity data were coded as either 

mild (alteration in consciousness or loss 

of consciousness </ = 30 minutes) or 

moderate/severe (loss of consciousness > 

30 minutes).”

NR Kay et al., 1993 Clinical 

interview

Ommaya, 

Ommaya, 

Dannenberg, et al., 

199641

“Head-injury-related discharge diagnosis 

(800.00-801.99, 803.00-804.99, and 

850.0-854.19).” Injury Severity Scale and 

Abbreviated Injury Scale were calculated.

NR NR Chart review

Ommaya, Salazar, 

Dannenberg, et al., 

199642

“Records with a head-injury hospitalrelated discharge diagnosis (800.00-801.99, 

803.00-804.99, and 850.0-854.19) were 

identified as described in a previous study.”

“Maximum Abbreviated Injury Score (AIS) 

head and Injury Severity Score (ISS) were 

computed using the ICD-9 map. Mild TBI 

was defined as maximum AIS head equal 

to 1 or 2”

NR NR Clinical 

records

Pietrzak, Johnson, 

Goldstein, Malley, 

Southwick 

200943

“Positive mTBI screen” based on 

endorsement of all 4 items on the DVBIC 

questionnaire

NR GAO, 2008 & 

DVBIC, 2006

Self-report 

survey
70

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Author, Year Definition

Patients 

with 

Abnormal 

Imaging

Citation How 

Assessed

Plassman, Havlik, 

Steffens, et al., 

200044

“1) mild injury = loss of consciousness 

or posttraumatic amnesia for less than 

30 minutes, with no skull fracture; 2) 

moderate injury = loss of consciousness or 

post-traumatic amnesia for more than 30 

minutes but less than 24 hours, and/or a 

skull fracture; and 3) severe injury = loss of 

consciousness or post-traumatic amnesia for 

more than 24 hours.”

NR Frankowski, 

Annengers, & 

Whitman, 1985

Chart review

Polusny, Kehle, 

Nelson, Erbes, 

Arbisi, Thuras, 

201145

Injury with altered mental status or LOC 

(items 1-3 on DVBIC screen)

NR Schwab et al., 2007 Self-report 

in theater, 1 

month prior 

to return 

home

Roebuck-Spencer, 

Vincent, Twille, et 

al., 201246

“Although data on recency and severity of 

injury were not available in this dataset, 

TBIs reported in this study are presumed 

to be mild in nature given that Service 

Members were still on active duty. Mild 

TBI was defined as such when individuals 

reported an injury event accompanied 

by an alteration of consciousness. This 

included endorsement of at least one of 

the following: feeling dazed or confused, 

experiencing loss of consciousness (LOC), 

or experiencing loss of memory for the 

injury or posttraumatic amnesia (PTA) for 

the event.”

NR NR Self-report 

screening 

tool

Romesser, Shen, 

Reblin, Kircher, 

Allen, Roberts, & 

Marchand, 201147

“History of military-related concussion 

during a VHA TBI secondary evaluation.” 

Excluded if “self-report suggested a history 

of a moderate or severe TBI (i.e., if they 

endorsed loss of consciousness more than 

30 minutes).”

NR NR Clinical 

interview

Rona, Jones, Fear, 

et al., 201248

“Possible mTBI was assessed using a 

modified version of the BTBIS... A second 

item asked about possible symptoms 

associated with the injury. These were 

losing consciousness; being dazed or 

confused; not remembering the injury; 

concussion (e.g., headache, dizziness); head 

injury, and none of these. Participants were 

asked to tick all that applied. Self-report of 

the duration of any loss of consciousness 

was also obtained, we eliminated one 

participant from the analysis who reported 

prolonged loss of consciousness... 

Participants who endorsed at least one of 

these symptoms were classified as having 

mTBI.”

NR Iverson, Langlois, 

McCrea, & Kelly, 

2009

Self-report 

questionnaire
71

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Author, Year Definition

Patients 

with 

Abnormal 

Imaging

Citation How 

Assessed

Rona, Jones, Fear, 

et al., 201249

“Possible mTBI was assessed using a 

modified version of the BTBIS, which 

included an item exploring possible causes 

of injury (blast, shrapnel fragments, bullet, 

fall, and vehicle accident and other). 

Participants could state that they had not 

suffered an injury during deployment. 

A second item asked about possible 

symptoms associated with the injury. These 

were losing consciousness; being dazed 

or confused; not remembering the injury; 

concussion (e.g., headache, dizziness); head 

injury; and none of these. Participants were 

asked to tick all that applied. Self-report of 

the duration of any loss of consciousness 

was also obtained, we eliminated 1 

participant from the analysis who reported 

prolonged loss of consciousness (which 

would be classified traumatic brain injury, 

not mTBI). Participants who endorsed at 

least one of these symptoms were classified 

as having mTBI.”

NR Iverson, Langlois, 

McCrea, & Kelly, 

2009

Self-report 

questionnaire

Schneiderman, 

Braver & Kang, 

200850

Three-item Brief Traumatic Brain Injury 

Screen

NR Defense and Veterans 

Brain Injury Center

Self-report 

survey

Skopp, 

Trofimovich, 

Grimes, et al., 

201251

mild TBI (subset of all TBI codes): 

310.2, 800.00-800.02, 800.06, 800.09, 

800.50, 800.52, 801.00, 801.01,801.02, 

801.06, 801.09, 801.50, 801.51, 801.52, 

803.00-803.02, 803.06, 803.09, 803.50, 

803.51, 803.52, 804.00, 804.01, 804.02, 

804.06, 804.09, 804.50, 804.51, 804.52, 

850.0, 805.1, 850.11, 850.9, 959.01, 

V15.52, V15.5_7, V15.5_C, V15.52_2, 

V15.52_2,V15.52_7, V15.52_C

NR DoD standard TBI 

surveillance case 

definition to ascertain 

TBI status and 

severity

Chart review
72

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Author, Year Definition

Patients 

with 

Abnormal 

Imaging

Citation How 

Assessed

Theeler, Flynn, & 

Erickson, 201052

“2-question screen followed by a 

10-question screen... The first question 

asks if, while deployed, the soldier was 

exposed to or near a blast, improvised 

explosive device (IED) explosion, car 

bomb, suicide explosion, or exposed to 

any other combat event or resulted in 

a blow or jolt to the head. The second 

question asks if the soldier was involved 

in a motor vehicle accident, a fall, a sports 

accident, or any other event that caused 

a blow to the head or resulted in a neck 

whiplash. If the soldier answers yes to 

either question 1 or 2, 10 more questions 

asking about loss of consciousness, dazed 

sensation after the event, and neurologic or 

behavioral sequelae following the event are 

administered. This questionnaire is scored 

in a standardized manner from 0 to 39.The 

case definition for concussion constituted 

a score of 5 or greater on the 2-plus-10 

questionnaire.”

NR NR Self-report 

survey

Theeler, Flynn, & 

Erickson, 201253

No specific criteria: 2-question followed by 

a 10-question screen if the soldier answers 

yes to either of the first 2 questions. This 

questionnaire is scored in a standardized 

manner from 0 to 39; the score from the 

2-plus-10 questionnaire will herein be 

called the TBI Score

NR Theeler, Flynn, & 

Erickson, 2010

Self-report 

survey

Vanderploeg, 

Belanger, & 

Curtiss, 200954

“Have you injured your head?... Did you 

lose consciousness as a result of the head 

injury?” “those individuals who required 

hospitalization after their head injury (n 

= 40) were excluded.” “head injury with 

altered consciousness” were classified as 

mild TBI.

NR NR Clinical 

interview

Vanderploeg, 

Curtiss & 

Belanger, 200555

“During the interview, participants were 

asked, among many others, the following 

three questions: 1) Since your discharge 

from active duty, have you been injured in a 

MVA? 2) Since your discharge from active 

duty have you injured your head (HI)? and 

3) Did you lose consciousness as a result of 

the head injury?”

NR NR Self-report

Vanderploeg, 

Curtiss, Duchnick, 

Luis, 200356

Positive responses to following questions: 

“Since discharge from active duty, have you 

been injured in a MVA?”; “Since discharge 

from active duty, have you injured your 

head (from any cause)?”; and “Did you 

lose consciousness as a result of the head 

injury?”

NR NR Self-report 

survey
73

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Author, Year Definition

Patients 

with 

Abnormal 

Imaging

Citation How 

Assessed

Vasterling, Brailey, 

Proctor, et al., 

201257

“Congruent with reports showing stronger 

associations between clinical outcomes 

and TBI following loss of consciousness 

v. altered consciousness, only those pre- to 

post-deployment interval injuries resulting 

in loss of consciousness were queried.”

NR NR Self-report 

survey

Wilk, Herrell, 

Wynn, Riviere, & 

Hoge, 201258

“Injury resulted in being dazed, confused, 

or seeing stars, not remembering the injury, 

or losing consciousness (knocked out).”

NR DoD/VA Brain 

Injury Center Brief 

Traumatic Brain 

Injury Screen

Self-report 

survey

Wilk, Thomas, 

McGurk, et al., 

201059

“Injury resulted in being dazed, confused, 

or seeing stars, not remembering the injury, 

or losing consciousness (knocked out).”

NR DoD/VA Brain 

Injury Center Brief 

Traumatic Brain 

Injury Screen

Self-report 

survey

Yurkiewicz, 

Lappan, Neely, et 

al., 201260

“Defense and Veterans Brain Injury Center 

(DVBIC) assesses TBI severity after a 

blast event or motor vehicle accident, 

answers questions about evacuation and 

in-theater clinical care and medication, and 

provides recommendations on headache 

management and vision, hearing, vestibular, 

and neurologic issues. Successes of the 

program include a stratified headache 

protocol for primary care providers and 

an early management protocol for mild 

TBI and posttraumatic headache stratified 

headache protocol.” 

“We reviewed consults sent to the 

neurology group from October 2006 to 

December 2010 and consults sent to the 

TBI group from March 2008 to December 

2010. Microsoft Excel spreadsheets were 

constructed to organize and analyze data 

regarding number of consultations, response 

times, location of origin, branch of service, 

clinical images transmitted, anatomic 

location of complaint, type of injury, 

workup recommended, and treatment and 

evacuation recommendations.”

NR DVBIC Brief 

Traumatic Brain 

Injury Screen

Chart review

Note. None of the studies reported information on assessor blinding of study hypotheses when assessing mTBI.
74

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

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prevalence and character. J Trauma. Oct 2003;55(4):617-621.

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27. Lange RT, Pancholi S, Bhagwat A, Anderson-Barnes V, French LM. Influence of poor effort 

on neuropsychological test performance in U.S. military personnel following mild traumatic 

brain injury. J Clin Exp Neuropsychol. 2012;34(5):453-466.

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versus Non-blast: Mild Traumatic Brain Injury in U.S. Military Service Members. J Int 

Neuropsychol Soc. May 2012;18(3):595-605.

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Uncomplicated Mild, Complicated Mild, and Moderate Traumatic Brain Injury in US 

Military Personnel. Arch Clin Neuropsychol. 2012;27(5):480-494.

30. Lew HL, Garvert DW, Pogoda TK, et al. Auditory and visual impairments in patients 

with blast-related traumatic brain injury: Effect of dual sensory impairment on Functional 

Independence Measure. J Rehabil Res Dev. 2009;46(6):819-826.

31. Luis CA, Vanderploeg RD, Curtiss G. Predictors of postconcussion symptom complex in 

community dwelling male veterans. J Int Neuropsychol Soc. Nov 2003;9(7):1001-1015.

32. Macgregor AJ. Physical injury and psychological outcomes among United States combat 

veterans. Dissertation Abstracts International: Section B: The Sciences and Engineering. 

2007;68(6-B):3665.

33. MacGregor AJ, Dougherty AL, Galarneau MR. Injury-specific correlates of combatrelated traumatic brain injury in Operation Iraqi Freedom. The Journal of Head Trauma 

Rehabilitation. Jul-Aug 2011;26(4):312-318.

34. MacGregor AJ, Dougherty AL, Morrison RH, Quinn KH, Galarneau MR. Repeated 

concussion among U.S. military personnel during Operation Iraqi Freedom. J Rehabil Res 

Dev. 2011;48(10):1269-1278.

35. MacGregor AJ, Shaffer RA, Dougherty AL, et al. Prevalence and psychological correlates 

of traumatic brain injury in operation iraqi freedom. J Head Trauma Rehabil. Jan-Feb 

2010;25(1):1-8.

36. McGuire SA, Marsh RW, Sowin TW, Robinson AY. Aeromedical decision making and 

seizure risk after traumatic brain injury: longitudinal outcome. Aviat Space Environ Med. 

Feb 2012;83(2):140-143.

37. Mora AG, Ritenour AE, Wade CE, Holcomb JB, Blackbourne LH, Gaylord KM. 

Posttraumatic stress disorder in combat casualties with burns sustaining primary blast and 

concussive injuries. J Trauma. Apr 2009;66(4 Suppl):S178-185.

38. Morgan M, Lockwood A, Steinke D, Schleenbaker R, Botts S. Pharmacotherapy regimens 

among patients with posttraumatic stress disorder and mild traumatic brain injury. 

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39. Nelson C, St, Weiser M, Gifford S, Gallimore J, Morningstar A. Knowledge gained from the 

Traumatic Brain Injury Screen-Implications for treating Canadian military personnel. Mil 

Med. Feb 2011;176(2):156-160.
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and Military Personnel: A Systematic Review Evidence-based Synthesis Program

40. Olson-Madden JH, Forster JE, Huggins J, Schneider A. Psychiatric diagnoses, mental health 

utilization, high-risk behaviors, and self-directed violence among veterans with comorbid 

history of traumatic brain injury and substance use disorders. J Head Trauma Rehabil. Sep 

2012;27(5):370-378.

41. Ommaya AK, Ommaya AK, Dannenberg AL, Salazar AM. Causation, incidence, and 

costs of traumatic brain injury in the U.S. military medical system. J Trauma. Feb 

1996;40(2):211-217.

42. Ommaya AK, Salazar AM, Dannenberg AL, Chervinsky AB, Schwab K. Outcome after 

traumatic brain injury in the U.S. military medical system. J Trauma. Dec 1996;41(6):972-

975.

43. Pietrzak RH, Johnson DC, Goldstein MB, Malley JC, Southwick SM. Posttraumatic stress 

disorder mediates the relationship between mild traumatic brain injury and health and 

psychosocial functioning in veterans of Operations Enduring Freedom and Iraqi Freedom. J 

Nerv Ment Dis. Oct 2009;197(10):748-753.

44. Plassman BL, Havlik RJ, Steffens DC, et al. Documented head injury in early adulthood 

and risk of Alzheimer’s disease and other dementias. Neurology. Oct 24 2000;55(8):1158-

1166.

45. Polusny MA, Kehle SM, Nelson NW, Erbes CR, Arbisi PA, Thuras P. Longitudinal 

effects of mild traumatic brain injury and posttraumatic stress disorder comorbidity on 

postdeployment outcomes in national guard soldiers deployed to Iraq. Arch Gen Psychiatry. 

Jan 2011;68(1):79-89.

46. Roebuck-Spencer TM, Vincent AS, Twillie DA, et al. Cognitive change associated with selfreported mild traumatic brain injury sustained during the OEF/OIF conflicts. The Clinical 

Neuropsychologist. Apr 2012;26(3):473-489.

47. Romesser J, Shen S, Reblin M, et al. A preliminary study of the effect of a diagnosis of 

concussion on PTSD symptoms and other psychiatric variables at the time of treatment 

seeking among veterans. Mil Med. Mar 2011;176(3):246-252.

48. Rona RJ, Jones M, Fear NT, et al. Mild traumatic brain injury in UK military personnel 

returning from Afghanistan and Iraq: cohort and cross-sectional analyses. J Head Trauma 

Rehabil. Jan-Feb 2012;27(1):33-44.

49. Rona RJ, Jones M, Fear NT, Sundin J, Hull L, Wessely S. Frequency of mild traumatic brain 

injury in Iraq and Afghanistan: are we measuring incidence or prevalence? J Head Trauma 

Rehabil. Jan-Feb 2012;27(1):75-82.

50. Schneiderman AI, Braver ER, Kang HK. Understanding sequelae of injury mechanisms and 

mild traumatic brain injury incurred during the conflicts in Iraq and Afghanistan: persistent 

postconcussive symptoms and posttraumatic stress disorder. Am J Epidemiol. Jun 15 

2008;167(12):1446-1452.

51. Skopp NA, Trofimovich L, Grimes J, Oetjen-Gerdes L, Gahm GA. Relations between 

suicide and traumatic brain injury, psychiatric diagnoses, and relationship problems, active 

component, U.S. Armed Forces, 2001-2009. Msmr. Feb 2012;19(2):7-11.
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52. Theeler BJ, Flynn FG, Erickson JC. Headaches after concussion in US soldiers returning 

from Iraq or Afghanistan. Headache. Sep 2010;50(8):1262-1272.

53. Theeler BJ, Flynn FG, Erickson JC. Chronic Daily Headache in U.S. Soldiers After 

Concussion. Headache. 2012;52(5):732-738.

54. Vanderploeg RD, Belanger HG, Curtiss G. Mild traumatic brain injury and posttraumatic 

stress disorder and their associations with health symptoms. Arch Phys Med Rehabil. Jul 

2009;90(7):1084-1093.

55. Vanderploeg RD, Curtiss G, Belanger HG. Long-term neuropsychological outcomes 

following mild traumatic brain injury. J Int Neuropsychol Soc. May 2005;11(3):228-236.

56. Vanderploeg RD, Curtiss G, Duchnick JJ, Luis CA. Demographic, medical, and psychiatric 

factors in work and marital status after mild head injury. J Head Trauma Rehabil. Mar-Apr 

2003;18(2):148-163.

57. Vasterling JJ, Brailey K, Proctor SP, Kane R, Heeren T, Franz M. Neuropsychological 

outcomes of mild traumatic brain injury, post-traumatic stress disorder and depression in 

Iraq-deployed US Army soldiers. Br J Psychiatry. Sep 2012;201:186-192.

58. Wilk JE, Herrell RK, Wynn GH, Riviere LA, Hoge CW. Mild traumatic brain injury 

(concussion), posttraumatic stress disorder, and depression in U.S. soldiers involved in 

combat deployments: association with postdeployment symptoms. Psychosom Med. Apr 

2012;74(3):249-257.

59. Wilk JE, Thomas JL, McGurk DM, Riviere LA, Castro CA, Hoge CW. Mild traumatic brain 

injury (concussion) during combat: lack of association of blast mechanism with persistent 

postconcussive symptoms. J Head Trauma Rehabil. Jan-Feb 2010;25(1):9-14.

60. Yurkiewicz IR, Lappan CM, Neely ET, et al. Outcomes from a US military neurology and 

traumatic brain injury telemedicine program. Neurology. Sep 18 2012;79(12):1237-1243.
79

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

esults of included studies

nd general fund of verbal knowledge measures in studies of U.S. Veterans and members of the U.S. military with mild TBI

mparison group description Outcome measure Subscale or test component mTBI group Mean (SD) Comparison group Mean (SD) p value for comparison Magnitude of effect

xis I disorder WTAR scaled score --- 106.7 (10.1) 105.4 (5.7) “NS” NR

WAIS-III Information scaled score 12.8 (1.7) 11.8 (2.1) “NS” NR

ensic context WAIS-III Information scaled score 11.97 (1.92) 11.58 (1.82) “NS” NR

ast exposed RBANS Language 97.43 (12.42) 92.81 (14.10) p = 0.187 NR

C and/or PTA Shipley Institute of Living 

Scale

Vocabulary Subtest 49.15 (7.50) 49.15 (6.20) NR NR

 Health Diagnosis 

her than PTSD

WTAR --- 96.8 (10.8) 101.7 (12.3) NR NR

SD Diagnosis WTAR --- 96.8 (10.8) 99.0 (11.2) NR NR

 population with 

erate/severe TBI

WTAR Estimated Full Scale IQ 

(FSIQ)

98.3 (9.3) 97.6 (9.1) p = .67 NR

 population with 

erate/severe TBI

WTAR Estimated Full Scale IQ 

(FSIQ)

98.1 (14.6) 96.1 (12.8) p = .35 NR

opulation without 

mTBI

RBANS Language 92.90 (15.586) 93.66 (11.873) p = 0.732 NR

opulation without 

 none with poor 

effort

WAIS-III Information scaled score 12.21 (2.01) 12.26 (2.25) “NS” d = .22

opulation without 

 none have Axis I

WAIS-III Information scaled score 12.8 (1.7) 11.9 (2.6) “NS” NR

WTAR scaled score 106.7 (10.1) 106.0 (9.2) “NS” NR
80

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

n in studies of U.S. Veterans and members of the U.S. military with mild TBI

mparison group 

description Outcome measure Subscale or test component mTBI group Mean (SD) Comparison group Mean (SD) p value for comparison Magnitude of effect

NA RCFT Figure Copy 33.6 (2.9) NA NA NA

Figure Orientation 3.6 (1.7) NA NA NA

Time to Copy 158.7 (63.5) NA NA NA

opulation without 

mTBI

RBANS Visuospatial/ 

Constructional

104.06 (13.382) 109.29 (10.47) p = 0.007 NR

opulation without 

 none have Axis I

RCFT Figure Copy 31.3 (3.2) 32.0 (2.1) “NS” NR

WAIS-III Block Design scaled score 12.2 (2.6) 13.0 (2.9) “NS” NR

xis I disorder RCFT Figure Copy 31.3 (3.2) 31.5 (3.0) “NS” NR

WAIS-III Block Design scaled score 12.2 (2.6) 12.2 (3.1) “NS” NR

ast exposed RBANS Visuospatial/ Constructional 112.11 (9.70) 108.09 (11.80) p = 0.159 NR

ADS Anxiety Visual Organization/ 

Processing Factor

--- NR NR p > .05 r = -.12

DS Depression Visual Organization/ 

Processing Factor

--- NR NR p < .001 r = -.25

C and/or PTA Visual Organization/ 

Processing Factor

--- 49.08 (9.98) 50.46 (10.12) p = .30 NR

RCFT Figure Copy 33.72 (2.64) 33.78 (2.38) NR NR

Organization 3.64 (1.74) 3.99 (1.81) NR NR

Time to Copy 170.51 (63.07) 166.17 (74.91) NR NR

 Health Diagnosis 

her than PTSD

RCFT Figure Copy 32.6 (4.9) 32.7 (4.7) NR NR

CL-M score Visual Organization/ 

Processing Factor

--- NR NR p < .05 r = -.18

SD Diagnosis RCFT Figure Copy 32.6 (4.9) 32.1 (6.0) NR NR

eported slowed 

ng/organization

RCFT Figure Copy NR NR “NS” r = -.13

Figure Orientation NR NR “NS” r = -.02

Time to Copy NR NR “NS” r = -.14

vice connected Visual Organization/ 

Processing Factor

--- NR NR p = .57 NR
81

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

 in studies of U.S. Veterans and members of the U.S. military with mild TBI

mparison group description Outcome measure Subscale or test component mTBI group Mean (SD) or Median (IQR) Comparison group Mean (SD) or Median (IQR) p value for comparison Magnitude of effect

xis I disorder CVLT-II Long Delay Free Recall 

z-score

0.5 (0.9) -0.1 (1.1) “Significant” NR

Trials 1-5 z-score 0.6 (0.9) 0.1 (1.0) “NS” NR

RCFT Delayed Recall z-score -0.1 (1.3) -0.5 (.98) “NS” NR

ast exposure BVMT-R Delayed Recall t score 48.6 (12.8) 50.7 (10.7) “NS” NR

Total Recall t score 45.2 (12.3) 50.1 (10.1) “NS” NR

CVLT-II Long Delay Free Recall 

t-score

48.3 (9.1) 50.5 (11.4) p = .38 NR

Total Trials 1-5 t-score 52.8 (10.5) 54.0 (8.1) p = .38 NR

ast exposure RBANS Immediate Memory 91.70 (11.0) 91.81 (15.67) P = 0.994 NR Delayed Memory 96.96 (16.59) 95.12 (16.04) P = 0.664 NR

ensic context CVLT-II Long Delay Free Recall 

z-score

0.03 (0.99) -0.73 (1.12) “NS” NR

Trials 1-5 t-score 52.82 (8.61) 46.33 (9.23) “NS” NR

ADS Anxiety Memory Factor --- NR NR p < .001 r = -.29

DS Depression Memory Factor --- NR NR p > .05 r = -.15

C and/or PTA Memory Factor --- 49.22 (9.89) 49.61 (10.36) NR NR

RBANS Story Memory Immediate 

Recall

44.99 (10.19) 48.10 (10.36) NR NR

Story Memory Delayed 

Recall

45.41 (10.49) 44.98 (10.71) NR NR

RCFT Immediate Recall 44.43 (12.72) 44.50 (13.65) NR NR

 Health Diagnosis 

her than PTSD

CVLT-II Long Delay Free Recall 8.9 (3.7) 8.9 (3.9) NR NR

Short Delay Free Recall 8.3 (3.5) 8.6 (3.9) NR NR

CVLT-II Total Trials 1-5 43.7 (12.0) 44.6 (13.7) NR NR

RCFT Immediate Recall 16.4 (7.7) 17.4 (7.2) NR NR

Delayed Recall 16.0 (7.9) 17.4 (7.2) NR NR
82

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

mparison group description Outcome measure Subscale or test component mTBI group Mean (SD) or Median (IQR) Comparison group Mean (SD) or Median (IQR) p value for comparison Magnitude of effect

mparison group RBANS Story Memory Immediate 

Recall

17.2 (3.4) NA NA NA

Story Memory Delayed 

Recall

8.4 (2.3) NA NA NA

RCFT Immediate Recall 19.9 (6.2) NA NA NA

MSP subtest Baseline: 51 (43-53) 

≤ 72 hours: 44 (38.5-

51)

Baseline: 50 (45-55)

≤ 72 hours: 50 (44-

56)

Baseline: p = .57

≤ 72 hours: p 

<.001

NR

CL-M score Memory Factor --- NR NR p < .05 r = -.34

SD Diagnosis CVLT-II Long Delay Free Recall 8.9 (3.7) 7.6 (3.2) NR NR

Short Delay Free Recall 8.3 (3.5) 7.0 (3.4) NR NR

Total Trials 1-5 43.7 (12.0) 38.7 (11.1) NR NR

RCFT Immediate Recall 16.4 (7.7) 15.7 (8.5) NR NR

Delayed Recall 16.0 (7.9) 16.1 (7.1) NR NR

e population of 

 participants, none 

th poor effort

CVLT-II Long Delay Free Recall 

z-score

0.27 (0.91) 0.45 (0.81) “NS” d = 0.21

Trials 1-5 t-score 54.43 (8.95) 57.16 (8.04) “NS” d = 0.32

 population with 

rate/ severe TBI

BVMT-R Delayed Recall NR NR “NS” NRBVMT-R Total Recall NR NR “NS” NR

CVLT-II Long Delay Free Recall NR NR p < .05 NR

Total Trials 1-5 NR NR p < .01 NR

 population with 

rate/ severe TBI

Memory Composite 

Score

--- 9.0 (2.4) 7.7 (2.8) p = .04 NR

opulation without 

th minor traumatic 

 not involving the 

 and noninjured 

teers from same 

population

ANAM CDD subtest Baseline: 

42.5 (36.5-50)

5+ days: 

49.5 (40-56)

10+ days: 

49.5 (40.1-53.1)

Baseline:

44 (37-52)

5+ days: 

50.3 (44.1-57.8)

10+ days: 

50.3 (44.1-57.8)

Baseline: 

p = 0.47

5+ days: p = 0.07

10+ days: 

p = 0.17

NR

MSP subtest Baseline: 

51 (43-53)

5+ days: 

50.5 (44-58)

10+ days: 

51.8 (43.5-57.9)

Baseline: 

52 (44.5-57.8)

5+ days: 

51.5 (44.5-57.6)

10+ days: 

51.5 (44.5- 57.6)

Baseline: 

p = 0.29

5+ days: p = 0.47

10+ days: 

p = 0.77

NR

opulation without 

TBI

RBANS Immediate Memory 95.14 (14.181) 96.49 (14.445) p = .589 NR
83

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

mparison group description Outcome measure Subscale or test component mTBI group Mean (SD) or Median (IQR) Comparison group Mean (SD) or Median (IQR) p value for comparison Magnitude of effect

opulation without 

th minor traumatic 

 not involving the 

 and noninjured 

teers from same 

population

ANAM CDD subtest Baseline: 

42.5 (35-50) 

≤ 72 hours: 

42 (35-49.5)

Baseline: 

45 (38-52) 

≤ 72 hours: 

44.75 (39-51)

Baseline: 

p = .20

≤ 72 hours: 

p = .04

NR

opulation without 

 none have Axis I

CVLT-II Long Delay Free Recall 

z-score

0.5 (0.9) 0.6 (0.8) “NS” NR

Trials 1-5 z-score 0.6 (0.9) 0.8 (0.8) “NS” NR

RCFT Delayed Recall z-score -0.1 (1.3) -0.3 (1.3) “NS” NR

Delayed Memory 96.48 (12.998) 100.42 (12.854) p = 0.072 NR

eported memory 

deficits

RBANS Story Memory Immediate 

Recall

NR NR “NS” r = -.05

Story Memory Delayed 

Recall

NR NR p < .05 r = -.20

RCFT Immediate Recall NR NR “NS” r = .08

vice connected Memory Factor --- NR NR p = .17 NR
84

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

ion measures in studies of U.S. Veterans and members of the U.S. military with mTBI

mparison group description Outcome measure Subscale or test component mTBI group Mean (SD) or Median (IQR) Comparison group Mean (SD) or Median (IQR) p value for comparison Magnitude of effect

xis I disorder WAIS-III Digit Span scaled score 9.9 (2.8) 9.9 (2.1) “NS” NR

ensic context WAIS-III Digit Span scaled score 9.61 (2.55) 8.42 (2.77) “NS” NR

ast exposure RBANS Attention 98.89 (16.64) 94.78 (14.51) p = 0.311 NA

ADS Anxiety Verbal Attention Factor --- NR NR p < .05 r = -.24

Visual Attention Factor --- NR NR p > .05 r = -.12

DS Depression Verbal Attention Factor --- NR NR p < .05 r = -.24

Visual Attention Factor --- NR NR p > .05 r = -.13

C and/or PTA Verbal Attention Factor --- 49.69 (10.91) 49.87 (9.69) p = .91 NR

Visual Attention Factor --- 50.67 (9.61) 49.61 (10.36) p = .50 NR

C and/or PTA WAIS-IV Digit Sequencing 9.30 (2.76) 9.41 (2.27) NR NR

Digit Span Backward 9.23 (2.54) 8.92 (2.18) NR NR

Digits Forward 8.39 (2.63) 8.64 (2.70) NR NR

mparison group WAIS-IV Digit Sequencing 8.0 (1.9) NA NA NA

Digits Backward 7.8 (2.1) NA NA NA

Digits Forward 9.6 (2.1) NA NA NA

CL-M score Verbal Attention Factor --- NR NR p < .05 r = -.21

Visual Attention Factor --- NR NR p < .05 r = -.20

Digit Span scaled score 9.9 (2.8) 10.9 (2.4) “NS” NR

opulation without 

BI; with minor 

matic injuries not 

ng the head and 

jured volunteers 

same population

ANAM Mathematical Processing 

(MTH) subtest

Baseline: 

51 (42-57.3)

5+ days: 

50.5 (43-56)

10+ days: 

50.8 (46.3-55.8)

Baseline: 

50 (42-55)

5+ days: 

52 (44-59.8)

10+ days: 

52 (44-59.8)

Baseline: 

p = 0.71

5+ days: 

p = 0.29

10+ days: 

p = 0.51

NR

opulation without 

mTBI

RBANS Attention 84.06 (15.013) 89.74 (14.898) p = 0.026 NR
85

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

mparison group description Outcome measure Subscale or test component mTBI group Mean (SD) or Median (IQR) Comparison group Mean (SD) or Median (IQR) p value for comparison Magnitude of effect

opulation without 

BI; with minor 

matic injuries not 

ng the head and 

jured volunteers 

same population

ANAM Mathematical Processing 

(MTH) subtest

Baseline: 

47 (42-57) 

≤ 72 hours: 

46.7 (40.5-52.5)

Baseline: 

52 (42-55) 

≤ 72 hours: 

50 (44-56.6)

Baseline: 

p = .57

≤ 72 hours: 

p = .03

NR

opulation without 

 none with poor 

effort

WAIS-III Digit Span scaled score 10.50 (2.29) 10.65 (2.37) “NS” d = .06

ported attention 

deficits

WAIS-IV Digit Sequencing NR NR “NS” r = -.15

Digits Backward NR NR “NS” r = -.11

Digits Forward NR NR “NS” r = -.15

Digit Sequencing NR NR “NS” r = .00

Digits Backward NR NR “NS” r = -.14

vice connected Verbal Attention Factor --- NR NR p = .42 NR

Visual Attention Factor --- NR NR p = .17 NR

 speed in studies of U.S. Veterans and members of the U.S. military with mild TBI

roup 

n Outcome measure Subscale or test component mTBI group Mean (SD) or Median (IQR) Comparison group Mean (SD) or Median (IQR) p value for comparison Magnitude of effect

er Stroop Color and 

Word Test

Color t-score 49.5 (6.9) 45.8 (7.8) “NS” NR

Word t-score 49.4 (9.8) 46.2 (8.6) “NS” NR

Trail Making Test Part A t-score 50.0 (11.7) 50.5 (9.7) “NS” NR

WAIS-III Digit Symbol Coding 

scaled score

10.9 (2.0) 9.8 (2.4) “NS” NR

re Trail Making Test Part A t-score 45.8 (14.8) 46.2 (11.6) all p values > .10 NR

WAIS-III Digit Symbol Coding 

scaled score

8.3 (2.7) 8.9 (2.5) all p values > .10 NR
86

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

roup 

n Outcome measure Subscale or test component mTBI group Mean (SD) or Median (IQR) Comparison group Mean (SD) or Median (IQR) p value for comparison Magnitude of effect

ext Stroop Color and 

Word Test

Color t-score 45.29 (8.60) 40.04 (7.00) “NS” NR

Word t-score 45.47 (9.01) 39.12 (7.54) “NS” NR

Trail Making Test Part A t-score 48.71 (10.44) 39.96 (9.78) “Significant” NR

WAIS-III Digit Symbol Coding 

scaled score

9.92 (2.53) 7.12 (2.53) “Significant” NR

PTA Trail Making Test Part A 48.93 (10.83) 47.99 (11.04) NR NR

agnosis 

TSD

Stroop Color & 

Word Test

Color 58.8 (12.1) 54.1 (11.2) NR NR

Word 76.2 (16.5) 77.0 (17.7) NR NR

Trail Making Test Part A 41.8 (15.8) 41.9 (19.1) NR NR

group Trail Making Test Part A 29.6 (13.1) NA NA NA

Procedural Reaction 

Time (PRT) subtest

Baseline: 52 (43-53) 

≤ 72 hours: 46 (34.5-54.5)

Baseline: 50 (47-58) 

≤ 72 hours: 52.5 (46.5-59)

Baseline: p = .60

≤ 72 hours: p < .001

NR

Simple Reaction Time 

(SRT) subtest

Baseline: 53 (48-55)

≤ 72 hours: 44.5 (34.5-52)

Baseline: 52 (47-55)

≤ 72 hours: 52 (47-55.5)

Baseline: p = .24

≤ 72 hours: p < .001

NR

sis Stroop Color & 

Word Test

Color 58.8 (12.1) 60.8 (15.3) NR NR

Word 76.2 (16.5) 79.6 (18.2) NR NR

Trail Making Test Part A 41.8 (15.8) 40.1 (15.0) NR NR

tion 

with 

njuries 

the 

jured 

 same 

n

ANAM Code Substitution (CDS) 

subtest

Baseline: 46 (39.5-48.5)

5+ days: 52.5 (46.5-58)

10+ days: 53 (47-60)

Baseline: 48 (43-55)

5+ days: 57 (50-63)

10+ days: 57 (50-63)

Baseline: p = 0.04

5+ days: p = 0.03

10+ days: p = 0.14

NR

Procedural Reaction 

Time (PRT) subtest

Baseline: 52 (43-57)

5+ days: 52 (44.5-58.5)

10+ days: 48.8 (42-62.1)

Baseline: 52 (47-58)

5+ days: 54 (47-62.5)

10+ days: 54 (47-62.5)

Baseline: p = 0.77

5+ days: p = 0.13

10+ days: p = 0.20

NR

Simple Reaction Time 

(SRT) subtest

Baseline: 53 (52-55)

5+ days: 54 (48-56.5)

10+ days: 54.5 (46.6-57.6)

Baseline: 52 (47-58)

5+ days: 53.5 (48.8-56.5)

10+ days: 53.5 (48.8-56.5)

Baseline: p = .23

5+ days: p = .97

10+ days: p = .71

NR

tion 

with 

njuries 

the 

jured 

 same 

n

ANAM Code Substitution (CDS) 

subtest

Baseline: 44 (37-50) 

≤ 72 hours: 44 (38.5-51)

Baseline: 48 (43-55) 

≤ 72 hours: 52 (45-57)

Baseline: p = .02

≤ 72 hours: p < .001

NR
87

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

roup 

n Outcome measure Subscale or test component mTBI group Mean (SD) or Median (IQR) Comparison group Mean (SD) or Median (IQR) p value for comparison Magnitude of effect

tion 

none 

ort

Stroop Color and 

Word Test

Color t-score 46.00 (8.88) 47.26 (6.90) “NS” d = 0.16

Word t-score 46.29 (9.10) 48.58 (8.64) “NS” d = 0.26

Trail Making Test Part A t-score 48.89 (9.89) 49.61 (11.66) “NS” d = 0.10

WAIS-III Digit Symbol Coding 

scaled score

10.46 (2.52) 10.35 (2.47) “NS” d = 0.04

tion 

none 

Stroop Color and 

Word Test

Color t-score 49.5 (6.9) 48.9 (6.7) “NS” NR

tion 

BI; 

 PTSD

Reaction time on a 

Go/NoGo task

--- NR NR p > .7 NR

n with 

re TBI

Trail Making Test Part A NR NR all p values > .10 NR

WAIS-III Digit Symbol Coding NR NR all p values > .10 NR

Word t-score 49.4 (9.8) 48.3 (6.6) “NS” NR

Trail Making Test Part A t-score 50.0 (11.7) 51.8 (12.1) “NS” NR

WAIS-III Digit Symbol Coding 

scaled score

10.9 (2.0) 11.1 (2.7) “NS” NR

ention 

Trail Making Test Part A NR NR “NS” r = -.03

owed 

zation

Trail Making Test Part A NR NR “NS” r = -.09
88

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

g in studies of U.S. Veterans and members of the U.S. military with mild TBI

mparison group description Outcome measure Subscale or test component mTBI group Mean (SD) Comparison group Mean (SD) p value for comparison Magnitude of effect

ast exposure Trail Making Test Part B t-score 49.1 (15.0) 45.6 (9.4) all p values > .10 NR

 population with 

erate/severe TBI

Trail Making Test Part B NR NR all p values > .10 NR

C and/or PTA Trail Making Test Part B t-score 49.96 (8.35) 48.80 (8.65) NR NR

 Health Diagnosis 

her than PTSD

Stroop Color & Word Test Color Word 32.9 (7.9) 30.3 (9.0) NR NR

Trail Making Test Part B 93.0 (38.8) 106.1 (73.2) NR NR

SD Diagnosis Stroop Color & Word Test Color Word 32.9 (7.9) 30.5 (8.5) NR NR

Trail Making Test Part B 93.0 (38.8) 95.2 (34.5) NR NR

xis I disorder COWA t-score --- 46.4 (11.0) 42.7 (9.5) “NS” NR

Stroop Color and Word Test Color-Word t-score 51.1 (9.5) 48.3 (9.5) “NS” NR

Trail Making Test Part B t-score 51.0 (12.1) 48.4 (10.8) “NS” NR

opulation without 

 none have Axis I

COWA t-score --- 46.4 (11.0) 48.9 (9.7) “NS” NR

Stroop Color and Word Test Color-Word t-score 51.1 (9.5) 52.6 (7.0) “NS” NR

Trail Making Test Part B t-score 51.0 (12.1) 53.6 (7.5) “NS” NR

ensic context COWA t-score --- 44.79 (10.43) 42.83 (8.52) “NS” NR

Stroop Color and Word Test Color-Word t-score 46.95 (9.09) 43.78 (8.10) “NS” NR

Trail Making Test Part B t-score 51.45 (10.25) 44.71 (10.22) “NS” NR

opulation without 

ne with poor effort

COWA t-score 47.04 (8.94) 46.97 (9.69) “NS” d = 0.01

Stroop Color and Word Test Color-Word t-score 48.86 (9.35) 50.52 (9.22) “NS” d = 0.18

Trail Making Test Part B t-score 52.21 (10.20) 52.77 (5.83) NS d = 0.07

 population with 

erate/severe TBI

Executive Function 

Composite Score

--- 10.4 (2.2) 9.5 (3.0) p = .13 NR

None Trail Making Test Part B 72.8 (34.8) NA NA NA

ported attention 

deficits

Trail Making Test Part B NR NR “NS” r = -.01

eported slowed 

ng/organization

Trail Making Test Part B NR NR “NS” r = -.01
89

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

n measures in a study of U.S. Veterans with mild TBI evaluated in a research versus forensic context

come measure Portion or subscale Research context Mean (SD) Forensic context Mean (SD) p value for comparison Magnitude of effect

CVLT-II Forced Choice 15.87 (0.41) 15.50 (1.18) “NS” NR

Failures raw score --- 0.32 (0.58) 1.17 (0.87) “Significant” NR

Rey FIT Combination 28.84 (2.06) 26.13 (3.72) “Significant” NR

VSVT Easy Items 23.90 (0.31) 22.92 (2.00) “Significant” NR

Difficult Items 22.11 (2.87) 15.63 (6.25) “Significant” NR

Total Items 46.00 (3.08) 38.54 (7.43) “Significant” NR

WAIS-III Reliable Digit Span 9.63 (1.98) 8.38 (1.71) “NS” NR
90

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

ain composite scores in studies of U.S. Veterans and members of the U.S. military with mild TBI

mparison group description Outcome measure Subscale or test component mTBI group Mean (SD) Comparison group Mean (SD) p value for comparison Magnitude of effect

ast exposure RBANS Total Score 98.61 (9.33) 94.88 (12.92) p = 0.211 NR

opulation without 

mTBI

RBANS Total Score 92.16 (11.932) 96.71 (11.672) p = 0.023 NR

opulation without 

ne with poor effort

Overall Test Battery Mean 

z-score

--- 0.00 (0.55) 0.11 (0.42) “NS” d = 0.22

opulation without 

 none have Axis I

Overall Test Battery Mean 

z-score

--- 0.14 (0.69) 0.26 (0.38) “NS” d = .23

 population with 

erate/severe TBI

Attention/Processing Speed 

Composite Score

--- 9.8 (1.9) 8.5 (2.0) p < .01 NR

xis I disorder Overall Test Battery Mean 

z-score

--- 0.14 (0.69) -.14 (.45) “NS” NR

ensic context Overall Test Battery Mean 

z-score

--- -0.15 (0.55) -0.75 (0.52) “Significant” NR

che intervention 

ng sleep hygiene, 

in, headache and 

ucation, and group 

therapy

MOCA --- 24.50 (.49) 28.60 (.59) p < .001 NR

LOC MOCA --- 28.9 (.32) 25.1 (.18) p < .001 NR

 Health Diagnosis 

her than PTSD

WAIS-III (73 participants 

administered);

WAIS-IV (9 participants 

administered)

WAIS-III Vocabulary, 

Information, Matrix 

Reasoning, Block Design 

Subscales; 

WAIS-IV: all subtests 

97.4 (11.0) 100.2 (15.4) NR NR

 neurological and/

uropsychological 

findings

Number of blast exposures 

associated with LOC or AOC

--- 2.65 (.18) 4.42 (.23) p < .001 NR

Number of blast exposures 

associated with LOC only

--- 1.46 (.09) 3.91 (.20) p < .001 NR

SD Diagnosis WAIS-III (73 participants 

administered);

WAIS-IV: (9 participants 

administered)

WAIS-III Vocabulary, 

Information, Matrix 

Reasoning, Block Design 

Subscales;

WAIS-IV: all subtests

97.4 (11.0) 95.6 (13.3) NR NR
91

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

ve deficits in studies of U.S. Veterans and members of the U.S. military with mild TBI

mparison group description Outcome measure Subscale or test component mTBI group Mean (SD) Comparison group Mean (SD) p value for comparison Magnitude of effect

one additional AIS 

code

NSI Cognitive Cluster 10.01 (4.90) 6.88 (5.25) p < 0.001 NR

Concentration 2.16 (1.17) 1.40 (1.32) p < 0.001 NR

Decision-Making 1.74 (1.22) 1.04 (1.15) p < 0.001 NR

Memory 2.36 (1.16) 1.81 (1.34) p < 0.001 NR

Slowed Thinking/

Organization

1.89 (1.18) 1.11 (1.21) p < 0.001 NR

xis I disorder Memory --- 1 (5.6) 4 (11.8) “NS” NR

ast exposure NSI Decision-Making NR NR p > .002 NR

Memory NR NR p > .002 NR

Slowed Thinking/

Organization

NR NR p > .002 NR

ADS Anxiety NSI Concentration NR NR p < .001 r = .56

Decision-Making NR NR p < .001 r = .52

Memory NR NR p < .001 r = .49

Slowed Thinking/

Organization

NR NR p < .001 r = .58

DS Depression NSI Concentration NR NR p < .001 r = .55

Decision-Making NR NR p < .001 r = .57

Memory NR NR p < .001 r = .51

Slowed Thinking/

Organization

NR NR p < .001 r = .62

C and/or PTA NSI Concentration 2.08 (1.21) 2.71 (1.12) NR NR

Decision-Making 1.59 (1.365) 2.05 (1.36) NR NR

Memory 2.17 (1.16) 2.86 (1.18) NR NR

Slowed Thinking/

Organization

1.80 (1.32) 2.38 (1.29) NR NR

NA NSI Concentration 2.31 (1.08) NA NA NA

Decision-Making 1.72 (1.12) NA NA NA

Memory 2.50 (1.04) NA NA NA

Slowed Thinking/

Organization

1.96 (1.18) NA NA NA
92

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

mparison group description Outcome measure Subscale or test component mTBI group Mean (SD) Comparison group Mean (SD) p value for comparison Magnitude of effect

CL score > 50 NSI Decision-Making NR NR p < .002 NR

Memory NR NR p < .002 NR

Slowed Thinking/

Organization

NR NR p < .002 NR

≥60 (controls had 

PCL-C ≤30)

NSI Cognitive Cluster 3.04 (3.40) 13.32 (3.90) p < .0001 NR

Concentration 0.47 (0.79) 2.87 (0.88) p < .0001 NR

Decision-Making 0.33 (0.73) 2.28 (1.13) p < .0001 NR

Memory 0.95 (1.14) 3.00 (0.91) p < .0001 NR

Slowed Thinking/

Organization

0.42 (0.81) 2.57 (0.98) p < .0001 NR

CL-M score NSI Concentration NR NR p < .001 r = .59

Decision-Making NR NR p < .001 r = .63

Memory NR NR p < .001 r = .53

Slowed Thinking/

Organization

NR NR p < .001 r = .68

 population with 

erate/severe TBI

FrSBe Subjective Executive 

Dysfunction pre- to postinjury change

10.8 (14.2) 21.6 (18.3) p = .01 NR

vice connected NSI Concentration NR NR p < .05 NR

Decision-Making NR NR p < .05 NR

Memory NR NR p < .001 NR

Slowed Thinking/

Organization

NR NR p < .05 NR
93

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

s

in studies of U.S. Veterans and members of the U.S. military with mild TBI

ison group description Outcome measure

mTBI group

Mean (SD) or 

% of subjects

Comparison 

group

Mean (SD) or 

% of subjects

p value for 

comparison

Magnitude of 

effect

one additional AIS code NSI: Headaches 2.71 (1.10) 1.45 (1.30) p < 0.001 NR

Axis I disorder Headache 6 (33.3) 12 (35.3) “NS” NR

Blast exposure NSI: Headaches NR NR p < .002 NRBlast exposure HIT-6 54.32 (9.44) 56.03 (9.54) p = 0.489 NR

e intervention involving 

p hygiene, Prazosin, 

he and pain education, 

nd group therapy

Headache frequency (number per month) 12.40 (.94) 4.77 (.19) p < .001 NR

Headache pain level (scale 0-10) 7.28 (.27) 4.08 (.19) p < .001 NR

NA NSI: Headaches 2.29 (1.04) NA NA NANA Neurology referral for headaches 82/246 = 33.3% NA NA NA

Neurology referral for headaches, Chronic daily type 11/246 = 4.47% NA NA NA

Neurology referral for headaches, Cluster type 1/246 = 0.41% NA NA NA

Neurology referral for headaches, Migraine type 25/246 = 10.16% NA NA NA

Neurology referral for headaches, Mixed type 8/246 = 3.25% NA NA NA

Neurology referral for headaches, Other type 1/246 = 0.41% NA NA NA

Neurology referral for headaches, Post-traumatic type 4/246 = 1.63% NA NA NA

Neurology referral for headaches, Tension type 6/246 = 2.44% NA NA NA

NA Headaches started < 1 week after trauma 12/33 = 36% NA NA NA

Headaches started > 1 month after trauma 3/33 = 9% NA NA NA

Headaches started 1 week to 1 month after trauma 1/33 = 3% NA NA NA

Unspecified onset of headache after trauma 5/33 = 15% NA NA NA

Worsening of pre-existing headaches 12/33 = 36% NA NA NA

PCL score > 50 NSI: Headaches NR NR p < .002 NR

60 (controls had PCL-C 

≤30)

NSI: Headaches 1.01 (1.15) 2.79 (1.18) p < .0001 NR
94

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

ison group description Outcome measure

mTBI group

Mean (SD) or 

% of subjects

Comparison 

group

Mean (SD) or 

% of subjects

p value for 

comparison

Magnitude of 

effect

e neurological and/or 

psychological findings

Headache frequency: > 10 per month 0/0 = 0% 31/74 = 42% p < .001 NR

Headache frequency: > 4 per month 2/6 = 33% 71/74 = 96% p < .001 NR

Headache frequency: Daily 0/0 = 0% 10/14 = 14% p < .001 NR

Headache pain level (scale 0-10) 4.33 (.27) 7.28 (.27) p < .001 NR

Headache: Migraine type 0/0 = 0% 14/74 = 19% p < .001 NR

Headache: Mixed type 0/0 = 0% 30/74 = 41% p < .001 NR

Headache: Tension type 6/6 = 100% 30/74 = 41% p < .001 NR

 to Neurology clinic for 

headaches

NSI: Headache 1.97 (0.91) 2.87 (0.80) p < .01 NR

opulation without mTBI Headache days per month after deployment 

(days/month)

11.9 (10.0) 10.3 (8.0) NR NR

Headache days per month during deployment 

(days/month)

14.5 (11.7) 9.4 (9.4) NR NR

Headache duration (hours) 8.8 (7.3) 7.5 (5.2) NR NR

Headache NOS 7/33 = 21% 7/48 = 14% NR NR

Headache severity (0-10 scale) 7.1 (1.5) 7.1 (1.2) NR NR

Medication overuse headache 4/33 = 12% 0/48 = 0% NR NR

MIDAS 30.8 (44.3) 26.8 (27.5) NR NR

Migraine with aura 8/33 = 24% 3/48 = 6% NR NR

Migraine without aura 15/33 = 45% 30/48 = 62% NR NR

Multiple headache types 10/33 = 30% 16/48 = 33% NR NR

Occipital headache 5/33 = 15% 3/48 = 6% NR NR

Probable migraine 3/33 = 9% 5/48 = 10% NR NR

Tension-type headache 5/33 = 15% 13/48 = 27% NR NR
95

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

dies of U.S. Veterans and members of the U.S. military with mild TBI

mparison group description Outcome measure mTBI group Comparison group p value for comparison Magnitude of effect

me population 

ithout mTBI

Pain (On a scale of 0 to 10, with 0 as no 

pain and 10 as the worst pain possible, how 

would you rate your current pain?)

Median = 3.5 Median = 2.0 p = .18 Cohen’s d = .30

 population with 

erate/severe TBI

Pain in the past 30-days 112/125 = 90% 6/6 = 100% p = .53 NR

in studies of U.S. Veterans and members of the U.S. military with mild TBI

mparison group description Outcome measure mTBI group Mean (SD) Comparison group Mean (SD) p value for comparison Magnitude of effect

Blast exposure NSI: Feeling Dizzy NR NR p > .002 NR

NSI: Loss of Balance NR NR p > .002 NR

NSI: Poor Coordination NR NR p > .002 NR

PCL score > 50 NSI: Feeling Dizzy NR NR p < .002 NR

NSI: Loss of Balance NR NR p < .002 NR

NSI: Poor Coordination NR NR p < .002 NR

NA NSI: Feeling Dizzy 1.47 (.86) NA NA NA

NSI: Loss of Balance 1.32 (.92) NA NA NA

NSI: Poor Coordination 1.32 (.93) NA NA NA

 ≥60 (controls had PCL-C ≤30) NSI: Feeling Dizzy 0.52 (0.81) 1.88 (1.13) p < .0001 NR

NSI: Loss of Balance 0.45 (0.66) 1.89 (1.04) p < .0001 NR

NSI: Poor Coordination 0.30 (0.55) 1.98 (1.04) p < .0001 NR

 volunteer subjects without TBI. 

plicitly stated whether controls 

m the same population as cases, 

 controls were evaluated at the 

same time and place.

DHI NR NR p < .01 for weeks 1, 2, 

3, & 4 following injury

NR

 volunteer subjects without TBI. 

plicitly stated whether controls 

m the same population as cases, 

 controls were evaluated at the 

same time and place.

DVAT NR NR p < .01 for week 1

p > .01 for week 4

NR

east one additional AIS code NSI: Feeling Dizzy 1.44 (1.09) 0.94 (1.05) p < 0.001 NR

NSI: Loss of Balance 1.30 (1.08) 0.92 (0.98) p = 0.002 NR

NSI: Poor Coordination 1.71 (1.05) 0.92 (1.03) p < 0.001 NR

Axis I disorder Disorientation 7 (38.9) 13 (38.2) “NS” NR

Dizziness 5 (27.8) 8 (23.5) “NS” NR

Imbalance 2 (11.1) 4 (11.8) “NS” NR
96

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

tudies of U.S. Veterans and members of the U.S. military with mild TBI

Comparison group description Outcome measure mTBI group Comparison group p value for comparison Magnitude of effect

At least one additional AIS code NSI: Sensitivity to Light 1.56 (1.26) 0.85 (1.22) p < 0.001 NR

NSI: Vision Problems 1.18 (1.16) 0.86 (1.16) p = 0.022 NR

Axis I disorder Photophobia 4 (22.2) 6 (17.6) “NS” NR

Blast exposure NSI: Sensitivity to Light NR NR p > .002 NR

NSI: Vision Problems NR NR p > .002 NR

NA NSI: Sensitivity to Light 1.72 (1.17) NA NA NA

NSI: Vision Problems 1.51 (1.07) NA NA NA

PCL score > 50 NSI: Sensitivity to Light NR NR p < .002 NR

NSI: Vision Problems NR NR p < .002 NR

PCL-C ≥60 (controls had PCL-C 

≤30)

NSI: Sensitivity to Light 0.65 (0.99) 2.06 (1.44) p < .0001 NR

NSI: Vision Problems 0.51 (0.99) 1.68 (1.23) p < .0001 NR

 studies of U.S. Veterans and members of the U.S. military with mild TBI

Comparison group description Outcome measure mTBI group Mean (SD) Comparison group Mean (SD) p value for comparison Magnitude of effect

Blast exposure NSI Hearing Difficulty NR NR p < .002 NR

Sensitivity to Noise NR NR p > .002 NR

PCL score > 50 NSI Hearing Difficulty NR NR p < .002 NR

Sensitivity to Noise NR NR p < .002 NR

NA NSI Hearing Difficulty 1.88 (1.06) NA NA NA

Sensitivity to Noise 1.85 (1.11) NA NA NA

PCL-C ≥60 (controls had PCL-C 

≤30)

NSI Sensitivity to Noise 0.48 (0.87) 2.50 (1.09) p < .0001 NR

Hearing Difficulty 0.70 (1.02) 2.06 (1.11) p < .0001 NR

At least one additional AIS code NSI Sensitivity to Noise 1.86 (1.17) 1.29 (1.41) p < 0.001 NR

Hearing Difficulty 1.46 (1.12) 1.39 (1.28) p = 0.620 NR

Axis I disorder Tinnitus 8 (44.4) 13 (38.2) “NS” NR

Phonophobia 4 (22.2) 4 (11.8) “NS” NR
97

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

es in studies of U.S. Veterans and members of the U.S. military with mild TBI

Comparison group description Outcome measure mTBI group Mean (SD) or % of subjects Comparison group Mean (SD) or % of subjects p value for comparison Magnitude of effect

At least one additional 

AIS code

NSI: Numbness or Tingling 1.02 (1.08) 1.22 (1.32) p = 0.157 NR

 

Blast exposure NSI: Numbness or Tingling NR NR p > .002 NR

LOC Neurological deficits based on 

examination

0/16 = 0% 65/125 = 52% p < .001 NR

NA NSI: Numbness or Tingling 1.61 (1.19) NA NA NA

 

PCL score > 50 NSI: Numbness or Tingling NR NR p < .002 NR

PCL-C ≥60 (controls had 

PCL-C ≤30)

NSI: Numbness or Tingling 0.76 (0.96) 1.83 (1.26) p < .0001 NR

omes in studies of U.S. Veterans and members of the U.S. military with mild TBI

Comparison group description Outcome measure mTBI group Mean (SD) Comparison group Mean (SD) p value for comparison Magnitude of effect

 

Blast exposure NSI Change in Taste or Smell NR NR p > .002 NR

Loss of Appetite NR NR p > .002 NR

Nausea NR NR p > .002 NR

PCL score > 50 NSI Change in Taste or Smell NR NR p < .002 NR

Loss of Appetite NR NR p < .002 NR

Nausea NR NR p < .002 NR

NA NSI Change in Taste or Smell 0.82 (1.03) NA NA NA

Loss of Appetite 1.53 (1.13) NA NA NA

Nausea 1.13 (1.01) NA NA NA

PCL-C ≥60 (controls had 

PCL-C ≤30)

NSI Change in Taste or Smell 0.15 (0.60) 1.14 (1.14) p < .0001 NR

Loss of Appetite 0.50 (0.84) 2.05 (1.10) p < .0001 NR

Nausea 0.31 (0.70) 1.57 (1.12) p < .0001 NR

At least one additional 

AIS code

NSI Change in Taste or Smell 0.54 (0.92) 0.49 (0.90) p = 0.681 NR

Loss of Appetite 1.44 (1.11) 1.13 (1.16) p = 0.026 NR

Nausea 1.12 (1.07) 0.60 (0.94) p < 0.001 NR

Axis I disorder Nausea 3 (16.7) 4 (11.8) “NS” NR
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tudies of U.S. Veterans and members of the U.S. military with mild TBI

Comparison group description Outcome measure mTBI group Mean (SD) Comparison group Mean (SD) p value for comparison Magnitude of effect

1025 At least one additional AIS code PCL-C Arousal With Reminder 3.02 (1.39) 2.17 (1.36) p < 0.001 NR

Avoid Activities 2.50 (1.39) 2.03 (1.28) p = 0.004 NR

Avoid Thoughts 2.92 (1.42) 2.31 (1.36) p < 0.001 NR

Avoidance Cluster 17.72 (7.54) 13.93 (6.61) p < 0.001 NR

Disturbing Dreams 3.10 (1.42) 2.74 (1.47) p = 0.042 NR

Disturbing Memories 3.32 (1.32) 3.03 (1.43) p = 0.086 NR

Feeling Distant 2.97 (1.43) 2.10 (1.22) p < 0.001 NR

Feeling Numb 2.31 (1.41) 1.85 (1.19) p = 0.004 NR

Future Cut Short 2.29 (1.40) 1.85 (1.24) p = 0.006 NR

Hyper-Arousal Cluster 17.47 (4.91) 13.65 (5.58) p < 0.001 NR

Irritability 3.18 (1.32) 2.51 (1.40) p < 0.001 NR

Jumpy, Easily Startled 3.34 (1.30) 2.72 (1.41) p < 0.001 NR

Loss of Interest 2.55 (1.41) 2.01 (1.19) p = 0.001 NR

Poor Sleep 4.11 (1.16) 3.36 (1.48) p < 0.001 NR

Re-experiencing Cluster 14.95 (5.74) 12.07 (5.92) p < 0.001 NR

Reliving Experience 2.54 (1.29) 1.99 (1.26) p < 0.001 NR

Super-Alert, Watchful 3.44 (1.28) 2.67 (1.39) p < 0.001 NR

Total Score 50.14 (16.66) 39.64 (16.72) p < 0.001 NR

Trouble Concentrating 3.41 (1.26) 2.46 (1.39) p < 0.001 NR

Trouble Remembering 2.48 (1.42) 2.05 (1.32) p = 0.009 NR

Upset When Reminded 2.98 (1.34) 2.42 (1.36) p = 0.001 NR

229 Axis I disorder CAPS 9.8 (12.1) 54.2 (52.5) “Significant” NR

SCID-I: PTSD 0 (0.0) 24 (70.6) “NS” NR

t al., 

Blast exposure PCL 37.3 (17.6) 41.5 (17.4) p = .047 NR

201216 Blast exposure PCL-M 36.29 (14.72) 37.88 (16.42) p = .696 NR
99

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comparison group description Outcome measure mTBI group Mean (SD) Comparison group Mean (SD) p value for comparison Magnitude of effect

26 Blast exposure PCL-C Avoidance All: 15.6 (7.0)

AOC: 14.8 (6.9)

LOC: 16.1 (7.1)

All: 15.8 (7.4)

AOC: 14.9 (7.1)

LOC: 16.3 (7.5)

All: p = .826

AOC: “NS”

LOC: “NS”

NR

Hyper-Arousal All: 14.5 (5.7)

AOC: 14.0 (5.6)

LOC: 14.8 (5.8)

All: 15.2 (5.6)

AOC: 14.6 (5.4)

LOC: 15.6 (5.7)

All: p = .202

AOC: “NS”

LOC: “NS”

NR

Re-experiencing All: 12.0 (5.7)

AOC: 11.8 (5.8)

LOC: 12.2 (5.8)

All: 13.3 (5.9)

AOC: 12.6 (5.7)

LOC: 13.7 (5.9)

All: p = .020

AOC: “NS”

LOC: “NS”

NR

Total Score All: 42.7 (16.9)

AOC: 40.6 (17.0)

LOC: 43.1 (17.0)

All: 44.3 (17.6)

AOC: 42.0 (16.8)

LOC: 45.7 (17.9)

All: p = .198

AOC: “NS”

LOC: “NS”

NR

201028 Blast exposure PCL: Civilian and Military versions 49.75 (15.11) 54.45 (14.98) p = .005 NR

20 HADS Anxiety PCL-M NR NR p < .001 r = .76

HADS Depression PCL-M NR NR p < .001 r = .76

32 LOC PTSD diagnosis (based on PCL-M as 

well as clinical interview)

1/16 = 6.25% 83/125 = 66% p < .001 NR

20 LOC and/or PTA PCL-M 50.61 (16.24) 56.74 (14.61) p < .05 NR

913 NA PCL-C: Total Score 53.5 (15.6) NA NA NA

NA PCL-M 52.4 (15.0) NA NA NA

Positive neurological and/or 

neuropsychological findings

PTSD diagnosis: (PCL score > 50 and 

meeting DSM-IV criteria)

11/46 = 24% 72/80 = 90% p < .001 NR

131 Referral to neurology clinic for 

headaches

PTSD (clinician confirmed or selfreported symptoms) 116/164 = 70.7% 66/82 = 80.5% p = .10 NR

ench, 

Same population with moderate/

severe TBI

PCL 35.4 (16.8) 23.5 (13.7) p < .0001 NR

ett, & 

Same population with moderate/

severe TBI

PCL 45.5 (17.2) 30.1 (15.5) p < .0001 NR

owles, 

Same population with moderate/

severe TBI

PCL-M 42 (1) 37 (3) NR NR

Same population with moderate/

severe TBI

PTSD diagnosis 91/125 = 73% 5/6 = 83% p = .49 NR

owles, 

Same population without mTBI PCL-M 42 (1) 31 (4) NR NRSame population without mTBI PCL-M: Score </= 44 14/31 = 45% 10/45 = 22% p = .0345 NRSame population without mTBI PCL-C 34.6 (13.3) 36.0 (14.0) NR NR
100

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comparison group description Outcome measure mTBI group Mean (SD) Comparison group Mean (SD) p value for comparison Magnitude of effect

Same population without mTBI CAPS: B – Re-experiencing Subscale 20.02 (7.03) 17.53 (6.06) p = .08 Cohen’s d = 

0.38

CAPS: Total Score 74.02 (16.21) 67.20 (13.21) p = .03 Cohen’s d = 

0.46

PCL-S 61.86 (11.04) 58.19 (12.89) p = .17 Cohen’s d = 

0.30

owles, 

Same population, neurologic 

patients (tumor, stroke, electrical, 

subarachnoid hemorrhage, anoxia, 

encephalitis, Parkinson’s disease, 

fronto-temporal dementia)

PCL-M 42 (1) 35 (5) NR NR

Self-reported attention deficits PCL-M NR NR p < .001 r = .60

Self-reported memory deficits PCL-M NR NR p < .001 r = .48

Self-reported slowed thinking/

organization

PCL-M NR NR p < .001 r = .54
101

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

in studies of U.S. Veterans and members of the U.S. military with mild TBI

Comparison group description Outcome measure mTBI group Mean (SD) Comparison group Mean (SD) p value for comparison Magnitude of effect

Blast exposure NSI: Feeling Anxious NR NR “NS” NR

PCL score > 50 NSI: Feeling Anxious NR NR p < .002 NR

NA NSI: Feeling Anxious 2.58 (1.08) NA NA NA

PCL-C ≥60 (controls had 

PCL-C ≤30)

NSI: Feeling Anxious 0.48 (0.82) 2.96 (0.91) p < .0001 NR

LOC and/or PTA HADS: Anxiety 11.56 (4.06) 13.16 (3.92) p < .05 NR

HADS Depression HADS: Anxiety NR NR p < .001 r = .56

At least one additional 

AIS code

NSI: Feeling Anxious 1.99 (1.24) 1.49 (1.34) p = 0.001 NR

NA HADS: Anxiety 11.9 (4.5) NA NA NA

Self-reported slowed 

thinking/organization

HADS: Anxiety NR NR p < .001 r = .39

Self-reported attention 

deficits

HADS: Anxiety NR NR p < .001 r = .48

Self-reported memory 

deficits

HADS: Anxiety NR NR p < .001 r = .33
102

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

on in studies of U.S. Veterans and members of the U.S. military with mild TBI

mparison group description Outcome measure Subscale or test component mTBI group Mean (SD) or % of subjects Comparison group Mean (SD) or % of subjects p value for comparison Magnitude of effect

t one additional AIS 

code

NSI Feeling Depressed or Sad 1.16 (1.26) 1.08 (1.19) p = 0.566 NR

last exposure NSI Feeling Depressed or Sad NR NR “NS” NR

OC and/or PTA HADS Depression 7.95 (4.61) 10.34 (4.013) p < .001 NR

NA NSI Feeling Depressed or Sad 2.09 (1.20) NA NA NANA HADS Depression 8.7 (4.3) NA NA NA

CL score > 50 NSI Feeling Depressed or Sad NR NR p < .002 NR

0 (controls had PCL-C 

≤30)

NSI Depression 0.30 (0.64) 2.44 (1.19) p < .0001 NR

population without 

all participants had 

PTSD.

BDI-II --- 20.0 (12.3) 20.8 (9.2) NR NR

population without 

mTBI

BDI-II --- 31.56 (11.06) 29.17 (10.53) p = .29 Cohen’s d = 0.23

Hopelessness (Who or what 

gives you strength and 

hope?)

--- 6/46 = 13% 6/46 = 13% NR NR

SCID-I Major Depressive Disorder 25/46 = 54% 18/46 = 39% p = .14 φ = .15

eported attention 

deficits

HADS Depression NR NR p < .001 r = .45

rted memory deficits HADS Depression NR NR p < .001 r = .36

reported slowed 

king/organization

HADS Depression NR NR p < .001 r = .52

orders in studies of U.S. Veterans and members of the U.S. military with mild TBI

mparison group description Outcome measure Subscale or test component mTBI group % of subjects Comparison group % of subjects p value for comparison Magnitude of effect

xis I disorder SCID-I Alcohol Abuse/Dependence 5/18 = 27.8% 12/34 = 35.3% “Significant” NR

opulation without 

 none have Axis I

Alcohol Abuse/Dependence 5/18 = 27.8% 5/28 = 17.9% “NS” NR

opulation without 

mTBI

SCID-I Alcohol Problem 13/46 = 28% 17/46 = 37% p = .37 φ = .09

Drug Problem 4/46 = 9% 7/46 = 15% p = .34 φ = .10
103

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

mes in studies of U.S. Veterans and members of the U.S. military with mild TBI

Comparison group description Outcome measure mTBI group % of subjects Comparison group % of subjects p value for comparison Magnitude of effect

Same population without 

mTBI

Suicidal ideation (Have 

you had thoughts about 

death or about killing 

yourself?)

11/44 = 25% 5/44 = 11% p = .10 φ = .18

Suicidal Intent (Have you 

ever intended to commit 

suicide?)

3/46 = 7% 1/46 = 2% NR NR

Past Suicide Attempts 

(Have you ever attempted 

suicide?)

2/46 = 4% 2/46 = 4% NR NR

outcomes in studies of U.S. Veterans and members of the U.S. military with mild TBI

mparison group description Outcome measure Subscale or test component mTBI group Comparison group p value for comparison Magnitude of effect

one additional AIS 

code

NSI Affective Cluster 7.21 (4.21) 5.43 (4.54) p < 0.001 NR

Frustration 1.86 (1.22) 1.24 (1.29) p < 0.001 NR

Irritability 2.19 (1.23) 1.62 (1.32) p < 0.001 NR

ast exposure NSI Frustration NR NR “NS” NR

NA NSI Frustration 2.41 (1.17) NA NA NA

Irritability 2.76 (1.06) NA NA NA

CL score > 50 NSI Frustration NR NR p < .002 NR

≥60 (controls had 

PCL-C ≤30)

NSI Affective Cluster 2.97 (2.93) 14.64 (3.48) p < .0001 NR

Frustration 0.31 (0.68) 2.82 (0.95) p < .0001 NR

Irritability 0.63 (0.89) 2.95 (0.90) p < .0001 NR

 population with 

erate/severe TBI

FrSBe Apathy, pre- to post-injury 

change

14.7 (17.2) 27.8 (16.8) p < .01 NR

Behavioral Disinhibition, 

pre- to post-injury change

5.3 (7.8) 5.5 (11.2) p = .98 NR

opulation without 

mTBI

SCID-I Any Co-Morbid Axis I 

Disorder

34/46 = 78% 29/46 = 63% p = .14 φ = .12

opulation without 

mTBI

Psychiatric Diagnosis --- 25 (50.0%) 26 (22.2%) p = 0.001 NR
104

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

mes

es in studies of U.S. Veterans and members of the U.S. military with mild TBI

mparison group description Outcome measure

mTBI group

% of subjects or

OR (95% CI) compared to 

non-mTBI control

Comparison group

% of subjects or

OR (95% CI) compared to 

non-mTBI control

p value for 

comparison

Magnitude of 

effect

opulation without 

mTBI

Unemployment 

(% who responded ‘No’ to ‘Are you 

employed?’)

9/45 = 20% 14/45 = 31% p = .23 φ = .13

LOC Missed work: ≥2 missed workdays 

in the past month

1.8 (95% CI 0.9-3.5) 1.4 (95% CI 0.5-3.6) NR NR

Occupational Impairment, Heavy 

Load: 

Difficulty carrying a heavy load in 

past month

2.2 (95% CI 1.3-3.5) 3.0 (95% CI 1.5-5.7) NR NR

Occupational Impairment, Physical 

Training: 

Difficulty performing physical 

training (PT) in past month

1.9 (95% CI 1.2-2.9) 1.6 (95% CI 0.8-3.0) NR NR
105

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

udies of U.S. Veterans and members of the U.S. military with mild TBI

son group description Outcome measure Subscale or test component

mTBI group

Mean (SD),

Median (IQR), or

% of subjects

Comparison group

Mean (SD), 

Median (IQR), or

% of subjects

p value for 

comparison

Magnitude of 

effect

st one additional AIS 

code

NSI Fatigue 1.85 (1.11) 1.51 (1.14) p = 0.009 NR

Sleep 2.73 (1.10) 2.15 (1.33) p < 0.001 NR

Blast exposure NSI Fatigue NR NR p < .002 NR

dache intervention 

ving sleep hygiene, 

n, headache and pain 

on, and group therapy

ESS --- 16.10 (0.28) 7.28 (0.34) p < .001 NR

NA NSI Fatigue 2.10 (1.11) NA NA NA

Sleep 2.72 (1.17) NA NA NA

population without 

with minor traumatic 

not involving the head 

oninjured volunteers 

m same population

Sleep hours per night < 4 6/47 = 13% 7/108 = 7% p = 0.21 for sleep 

hours overall

NR

hours per night ≥4 40/47 = 87% 99/108 = 93% p = 0.21 for sleep 

hours overall

NR

Sleep Change < 2 hour loss 10/47 = 23% 4/108 = 6% p = 0.02 for sleep 

change overall

NR

> 2 hour loss 33/47 = 77% 62/108 = 94% p = 0.02 for sleep 

change overall

NR

population without 

with minor traumatic 

not involving the head 

oninjured volunteers 

m same population

Sleep hours per night Median = 6 (5-7) Median = 6 (5-7) p = .22 NR

Sleep Change (negative 

value = hours lost)

--- Median = 0 (-2.5-0) Median = 0 (0-0) p < 0.001 NR

PCL score > 50 NSI Fatigue NR NR p < .002 NR

60 (controls had PCL-C 

≤30)

NSI Fatigue 0.86 (0.91) 2.60 (1.04) p < .0001 NR

Sleep 1.24 (1.17) 3.45 (0.70) p < .0001 NR

e neurological and/or 

sychological findings

NSI Sleep 5/46 = 11% 66/80 = 82.5% p < .001 NR

to Neurology clinic for 

headaches

NSI Sleep 2.53 (1.17) 2.78 (1.12) p = .11 NR

e population with 

derate/severe TBI

Sleep disturbance in 

the past 30 days

--- 2.72 (1.24) 3.17 (.75) p = .38 NR
106

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udies of U.S. Veterans and members of the U.S. military with mild TBI

mparison group description Outcome measure mTBI group % of subjects Comparison group % of subjects p value for comparison Magnitude of effect

opulation without 

mTBI

Lack of emotional support 

(% who responded ‘No’ to 

‘Do you have an emotional 

support system?’)

9/35 = 26% 6/35 = 17% p = .38 φ = .10

Marital status (Are you 

married?)

NR NR p = .72 φ = .04

comes in studies of U.S. Veterans and members of the U.S. military with mild TBI

omparison group description Outcome Measure

mTBI group

OR (95% CI) compared to 

non-mTBI control, 

% of subjects, or 

Mean (SD)

Comparison group

OR (95% CI) compared to 

non-mTBI control, 

% of subjects, or 

Mean (SD)

p value for 

comparison

Magnitude 

of effect

LOC Medical utilization: ≥2 “sick 

call” visits in past month

2.0 (95% CI 1.3-3.1) 1.9 (95% CI 1.04-3.6) NR NR

me population without mTBI; 

th minor traumatic injuries not 

olving the head and noninjured 

unteers from same population

Current Counseling 2/47 = 4% 4/108 = 4% p >0.99 NR

Current Mental Health 

Medication

2/47 = 4% 9/108 = 9% p = 0.50 NR

me population without mTBI; 

th minor traumatic injuries not 

olving the head and noninjured 

unteers from same population

Current Counseling 4/66 = 6% 5/146 = 3% p = .46 NR

Current Mental Health 

Medication

3/66 = 5% 8/146 = 6% p = .99 NR

me population with moderate/

severe TBI

Currently taking pain 

medications

24/44 = 55% 37/64 = 57% p = .44 NR

ame population without mTBI Length of Hospital Stay (days) PTSD: 13.6 (9.8) 

No PTSD: 19.0 (20.9)

PTSD: 16.0 (26.6) 

No PTSD: 14.1 (22.2)

NR NR

Length of Intensive Care Unit 

Stay (days)

PTSD: 2.0 (6.7) 

No PTSD: 12.1 (12.1)

PTSD: 1.6 (3.9) 

No PTSD: 2.8 (8.9)

NR NR

me population without mTBI; all 

participants had PTSD.

Number of medications 18 5 NR NR

ame population without mTBI Pain Medication (Narcotic) 32 (64.0%) 85 (72.6%) p = 0.264 NR
107

Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

APPENDIX F. LIST OF EXCLUDED STUDIES GROUPED BY 

REASON FOR EXCLUSION

Population does not meet criteria for adult, human subjects who are Veterans or members of 

the military from any country

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Complications of Mild Traumatic Brain Injury in Veterans

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Schneiderman AI, Braver ER, Kang HK. Understanding sequelae of injury mechanisms and mild 

traumatic brain injury incurred during the conflicts in Iraq and Afghanistan: persistent postconcussive 

symptoms and posttraumatic stress disorder. Am J Epidemiol. Jun 15 2008;167(12):1446-1452.
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Complications of Mild Traumatic Brain Injury in Veterans

and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Skopp NA, Trofimovich L, Grimes J, Oetjen-Gerdes L, Gahm GA. Relations between suicide and 

traumatic brain injury, psychiatric diagnoses, and relationship problems, active component, U.S. Armed 

Forces, 2001-2009. Msmr. Feb 2012;19(2):7-11.

Theeler BJ, Flynn FG, Erickson JC. Chronic Daily Headache in U.S. Soldiers After Concussion. Headache. 

2012;52(5):732-738.

Theeler BJ, Flynn FG, Erickson JC. Headaches after concussion in US soldiers returning from Iraq or 

Afghanistan. Headache. Sep 2010;50(8):1262-1272.

Vanderploeg RD, Belanger HG, Curtiss G. Mild traumatic brain injury and posttraumatic stress disorder 

and their associations with health symptoms. Arch Phys Med Rehabil. Jul 2009;90(7):1084-1093.

Vanderploeg RD, Curtiss G, Belanger HG. Long-term neuropsychological outcomes following mild 

traumatic brain injury. J Int Neuropsychol Soc. May 2005;11(3):228-236.

Vanderploeg RD, Curtiss G, Duchnick JJ, Luis CA. Demographic, medical, and psychiatric factors in work 

and marital status after mild head injury. J Head Trauma Rehabil. Mar-Apr 2003;18(2):148-163.

Vasterling JJ, Brailey K, Proctor SP, Kane R, Heeren T, Franz M. Neuropsychological outcomes of mild 

traumatic brain injury, post-traumatic stress disorder and depression in Iraq-deployed US Army 

soldiers. Br J Psychiatry. Sep 2012;201:186-192.

Wilk JE, Herrell RK, Wynn GH, Riviere LA, Hoge CW. Mild traumatic brain injury (concussion), 

posttraumatic stress disorder, and depression in U.S. soldiers involved in combat deployments: 

association with postdeployment symptoms. Psychosom Med. Apr 2012;74(3):249-257.

Wilk JE, Thomas JL, McGurk DM, Riviere LA, Castro CA, Hoge CW. Mild traumatic brain injury 

(concussion) during combat: lack of association of blast mechanism with persistent postconcussive 

symptoms. J Head Trauma Rehabil. Jan-Feb 2010;25(1):9-14.

Yurkiewicz IR, Lappan CM, Neely ET, et al. Outcomes from a US military neurology and traumatic brain 

injury telemedicine program. Neurology. Sep 18 2012;79(12):1237-1243.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

R REVIEW COMMENTS AND RESPONSES

Comment Response

 scope, and methods for this review clearly described?

Noted.

n the background of Executive Summary more rationale (e.g., 

standing OEF/OIF cohort vis-à-vis mTBI for planning etc). 

We have made this addition.

ing the criteria that were used for inclusion/exclusion at the 

document.

Due to space limitations, we have left reference to inclusion/exclusion criteria in the body of the report and appendices; however, this information will be presented earlier in the planned article publication of the results.

ore specific when mentioning comparison to controls (e.g., on 

y injured controls, postdeployed controls?)

We have included this information in the data abstraction tables.

Noted.

 review are clearly described. 

 review is clearly described. 

Noted.

k detail. Expectations for reporting methodological detail have 

ally over the past few years, and although this would expand the 

, I highly recommend that this be done. 

Noted. We have expanded this discussion.

ommend that the report follow the most recent PRISMA 

porting systematic reviews. I recognize that this is not primarily 

ument. However, adherence to the PRISMA guidelines would 

dibility of the review.

Noted. We have expanded our reporting to be in line with PRISMA guidelines as you suggest.

no online protocol was published, but if so, that should be 

We have updated this information in the report.

ria: The study designs included were mentioned. I have a few 

control studies are not listed in the inclusion criteria. Were case 

xcluded from the search? I assume that case series and case 

luded, but this is not explicit. Under the criteria “Timing: No 

 on timing” – my question – timing of what? Please clarify

Noted. Case control studies were not excluded. Timing has been updated to reflect time since injury. The inclusion criteria have been updated accordingly.

ources: This is well covered. However, if study authors were 

ditional information, this information should be included. If they 

ed, it is fine to leave the section as it is.

Correct – no authors were contacted for additional information about studies included in this review.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

ectronic search is included in appendix A. This is very good. Also, 

andard practice to clarify that the search was developed by a 

xperienced in database searches of this sort. It has also recently 

ended practice for a search strategy to be peer reviewed by a 

 Was this done? What measures were taken to ensure that the 

prehensive?

We have added this description of procedures.

n: This section is nicely detailed. Including the study selection 

ul. Other information to consider adding: What procedures were 

PI and the other reviewer disagreed on relevance at the point 

ning? What procedures were undertaken where the reviewers 

evance at the point of full article screening? A detailed definition 

d in Appendix C. This requires a Mild TBI to have normal CT/MRI. 

d in the methods section (or someplace else in the document) 

universally agreed upon criteria – many definitions of MTBI 

malities on imaging, differentiating these by classifying them as 

ncomplicated mild TBI. Of course it is important to adhere to the 

but it is a possible point of discrepancy from other criteria that 

tly noted.

Thank you. We have included this additional information in the updated report.

on: Good tables. It would be useful to have details about the data 

ess. It has become the standard to have at least two independent 

– was this done? Who did the data abstraction? How was this 

where data were missing or ambiguous in the report, were 

d? It would also be helpful to include study design in the tables.

We have updated the report with this additional information. We chose not to include study design in the tables because the designs were often inaccurately reported in the published studies and because all studies were observational in nature. Specific study design criteria related to quality/potential for bias were abstracted in the tables (e.g., sample selection, comparison group, etc.)

ment: In this section, you state that case control and case series 

uded. This should be consistent with the statement of study 

criteria. More details should be provided. Who did the quality 

 standard practice to have two independent quality assessments 

nd to report the procedures undertaken when there is no 

ality. How (specifically) was the assessment of quality used in 

s process? How specifically was this linked to rating the body of 

performed this linkage?

This discrepancy has been corrected. We have added this information.

have provided a reasonable way of grouping the studies and no 

s conducted – I see this decision as appropriate. However, details 

nthesis was conducted would be very good to add. This includes who 

nthesis, was this discussed in a larger group, were the conclusions 

working group, and what processes were used to reach agreement.

We have added this information.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

 literature flow chart. This is very good. Noted.

well-formulated summary statements, and in your detailed 

you link findings to your citations. But it might also be useful to 

he particular studies in your summary statements as well. This is 

esent it as worth considering.

Due to the lengthiness of the report, we decided not to link findings to particular studies in the summary section. However, we linked findings in the results section to the citations of included studies should readers be interested in these specifics.

nkage between particular studies and their study quality 

more importantly, their assessed risk of bias. This does not 

y the need for an overall score, and the use of an overall additive 

widely criticized. But the reader should be able to see which 

 of which biases. There is some reference to overall study 

tions reporting summary of findings, but most recent standards 

 this be reported in a more study-specific way. When you say 

what specifically do you mean? I also wonder whether studies 

bias in their methodological quality can usefully contribute to our 

I in the military?

We have updated our description of study quality and risk of bias to specifically describe each study as being of low quality due to the high risk of bias. We have also provided additional cautionary, interpretive statements in the summary section related to the strength of evidence from a body of low quality studies.

ectional studies included in sections related to risk or prognostic 

no information provided about the restriction of study designs 

estions. Obviously, cross-sectional studies are appropriate for 

prevalence of symptoms, but not for making causal inferences 

ptoms. Could this be clarified in the report?

We have clarified the inclusion of various types of study designs, highlighted findings from the only prospective study, and noted limitations of interpretation based solely on cross sectional studies reporting association rather than causal inferences.

have done a good job in discussing limitations of the literature 

t section. Would it be useful to be even more specific about 

itations and Recommendations section? E.g., providing concrete 

ll bias; of incidence-prevalence bias (where it might exist), etc.

We have added additional discussion of these points.

Noted.

Noted.

ection of the Executive Summary is missing important 

ut inclusion/exclusion criteria and how quality and strength of 

. This latter point is particularly important as it makes it very 

eader to understand why the authors consider the strength of the 

ow. 

We have added this information to the executive summary section of the report.

r when the authors state that no clear pattern of risk and 

s emerge whether the studies were designed to look at risk and s.

We have noted this in the discussion.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

ve Summary Conclusions section (and elsewhere in the report) 

 to “objective results” (p.4). It would be helpful if they discussed 

re “objective” and what is meant by “objective”.

We have updated this section to describe results not based on self-report.

o me why the authors are including the headache intervention 

rticipating in a headache intervention a protective factor? What 

 protective factor? Do the authors mean that the sample referred 

ervention was different than those not referred? Why is that 

Qs? In general, the information presented on this particular study 

ughout the report and relevance is not clear.

We have clarified references to this intervention throughout the report.

o me why studies focused on biomarkers are included. I do not 

kers are “impairments” (KQ 1) according to any definition of 

 not see how biomarkers address either KQ2A (pre-injury factors) 

y factors) if they not include a focus on outcomes, given the way 

d. How does this study meet criteria for the outcomes listed on 

We agree and have moved information from this section to the discussion rather than including it in the evidence synthesis.

the mTBI definition column confusing. What do the authors mean 

at do the authors mean when they list “LOC, AOC and PTA” given 

 requires DOD/VA/ACRM definition of mTBI? A note to the table 

We have clarified this column label.

g tables summarizing strength of evidence per study. This 

rticularly important given the conclusions. It would also make it 

der to refer to specific studies when reviewing the report. In the 

nformation, it is difficult to interpret statements like, “Strength of 

s low because of ....”. If I missed something that was included in 

ogize.

We have clarified this information in the text of the report. All included studies were rated as low quality due to high risk of bias, without exception.

would have liked to see the pertinent studies referenced rather 

n addition to the number of studies listed in parentheses. 

 be as important as quality, in my opinion. Question based on 

dies find that mean scores for processing speed were within 

h possible exceptions of those getting C&Ps and <10 days since 

s is what the Table suggests, unless I am not reading it correctly.

We have referenced individual citations in the text, and due to the low quality rating of all included studies, have not identified individual studies or study quality in the table for reasons of space. You are correct in your interpretation of the presented information in the table.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

hors make statements like “most research reported no significant 

 factors,” it would be helpful to know the number/percent of 

king at risk/protective factors.

We have noted this information in the discussion as an overall commentary on the body of literature given that only one included study was prospective in nature, and the rest were not designed to assess risk/protective factors. We have also clarified these sentences in the report to reflect studies of association rather than implying that studies were designed to assess risk/protective factors.

that readers who are not neuropsychologists will understand 

 are distinguishing between cognitive and physical health 

ample, it may not be clear why visuospatial abilities falls in the 

n but vision is in the physical health results section. It is not clear 

review “effort and motivation” at all. It is not clear why studies 

 are in the functional/social outcomes section. I suggest that the 

 describe the rationale for their groupings.

We have provided additional description of these decisions in the report.

tive Summary Limitation section, the authors state that the 

in the review relied on well-validated assessment tools. Are they 

SI as well-validated? Perhaps this statement can be more precise. 

We have made this statement more accurate and non-specific to individual tools. We refer to well-validated assessment tools being a strength of the overall body of literature, and report specific tools in the data abstraction. However, we did not to an individual literature search or other method of assessment to determine validation of each tool used in the included studies. We do also note limitations of some of the tools (e.g., the NSI) used to assess single-item, self-report outcomes.

ation and Costs: For this section, it does not make sense to 

cross Veteran and active duty samples given differences in the 

ms. I recommend that the authors clearly state which findings are 

ns using VA and which are specific to active duty.

We have added a clarifying statement noting that all included studies investigated Veterans.

Noted.

Noted.

ention cognitive “disability” as an outcome, but based on the 

ed in the literature, cognitive “deficits” may be a better term. The 

ng mental health outcomes could also be clarified. The objectives 

oms” but the operational definition is later given as diagnoses. 

ation of the measures in the studies included suggests that 

uld be the more accurate term.

We have changed the wording to “deficits.”

Noted.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

escribed. Noted.

Noted.

ectives clearly described, but missing some information. 

cussion of how common features of mTBI, e.g. the presence of 

d multiple TBIs, were handled in inclusion criteria. 

We have clarified these criteria in the report.

” was a major factor in exclusion (p.14) but no further 

ided on how this criterion was applied.

Study relevance simply implies that the study must provide information included in the KQs and meet inclusion/exclusion criteria. No additional relevance criteria were applied.

s in discussion of physical and neuroimaging outcomes. The 

 by the key questions does not include imaging or biomarkers 

s not clear whether these topics were adequately searched 

search strategy presented. However, I am not familiar with the 

d formatting used to detail the search strategy, so this was a bit 

n explanation or reference would be helpful.

We agree and have moved the imaging/biomarker information to the discussion section and removed it from the results/evidence synthesis.

ment, scope is very large and each element (e.g. cognitive 

 the subject of a report.

Noted.

Noted.

es and methodology are sound. Noted.

Noted.

ing to: Key Question # 1:

vice Members who suffer a mTBI and develop acute and or 

e of mTBI symptoms what is the prevalence of health conditions 

ches, insomnia, vertigo, or seizure disorder), functional 

return to work/duty, marital status/family dynamics), cognitive 

 attention, concentration or memory) and or associated mental 

s ( e.g. PTSD, depression or anxiety disorder ). Key Question # 

ffect outcomes for Veterans/service members with mTBI? Key 

r Veteran/military populations, are there pre-injury (premorbid) 

 pre-injury mental health factors, genetic factors, or prior 

protective factors ??) that affect outcomes for mTBI? Key 

 Veteran/military populations, are there post-injury risk factors 

ession or anxiety) or protective factors that affect outcomes for 

We have changed the wording of the key questions slightly.Noted.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

as in our synthesis of the evidence?

Noted.

Noted.

dication of bias, although it is always useful to discuss possible 

and how this might impact on the synthesis. However, a synthesis 

biased studies can bias a synthesis. Where studies were highly 

ty), can it be estimated what direction those methodological 

e biased the study’s findings? (toward or away from the null, for 

ay impact on the interpretation of study findings.

Noted. We have added these points to the discussion.

Noted.

Noted.

tes that TBI is THE leading cause of morbidity and disability in 

 believe that this is accurate. More important, one needs to 

een TBI history and TBI-related disability. The prevalence of 

ility is unknown and some evidence suggests that persistent 

y individuals who suffered TBI in OEF/OIF result from mental 

ties

Noted. We have changed the introductory paragraphs to better reflect these distinctions.

ummary Conclusions section, the authors state that “It is likely 

nce....is largely influenced by factors other than deployment 

g uniquely associated with mTBI.” They do NOT however describe 

is conclusion. This reviewer suggests that the authors clearly 

s based on the literature reviewed otherwise the sentence 

nion. The statement in the Executive Summary Conclusions 

e most likely exceptions are...evaluation linked with potential 

s particularly troubling as it seems to be based on the one study 

mpensation effects (#34). In the Executive Summary Limitation 

ors state “...self-reported deficits are more likely to persist for 

mTBI particularly when associated with compensation (p.40.” 

ment seems too strong if only one study (#34) reviewed looked at 

ffects unless that study was of very high quality

These conclusions are based on consistent findings across Veteran/military and civilian literature, though we agree that the conclusions could have been interpreted as basing conclusions on solely the Veteran/military literature, which would not have been warranted. These concluding statements have been tempered and clarified to more accurately reflect the results available from the body of literature.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

ry and Discussion section the authors conclude, “The body 

gest that many health consequences resolve within the first 

wing injury, if not sooner” (p.49). I am not clear about what 

e using the draw that conclusion given the design of the studies 

ch specific studies/findings are the authors referring when they 

 cognitive impairment most often resolves within a few weeks 

 I suggest that authors be very clear about the findings and 

using to make that claim. That claim also seems to be in direct 

eir statement in the Background section that “TBI is the leading 

ty and disability...” It also contradicts the statement in the 

n/Costs that “The long-term resource needs of recent Iraq and 

 Veterans who sustained mTBI are likely substantial”. (p.52). Why 

e case?

We have clarified the studies on which these conclusions are based, as sometimes the quotes were in direct reference to the Carroll et al, 2004 review findings that we were summarizing. We have also tempered the introductory statements relating to the potential effects of TBI.

so state in Summary and Discussion, “This report documents that 

uation for compensation as being a risk factor...(p.49)” Is this the 

 one study referred to in multiple sections of this report (#34) or 

tudies? The basis for this statement was not clear to me.

This statement was in reference to findings from the Carroll et al, 2004 review, and this citation has been clarified.

Noted.

o with studies included versus excluded. Your criteria are clear 

e bottom of page 9, of which the DoD/VA criteria are one 

ition of those criteria. 

Noted.

nuscript includes studies that don’t meet that criteria because 

Noted.

rates and “unclassified” severity patients [Morrisette, Woodward, 

 201175, Schiehser, Delis, Filoteo, et al., 201135] or, 

Thank you for catching this error. Though this paper reports findings for the mTBI only group separately from those with moderate or unclassified TBI, the specific finding we reported in our review was a combined group finding; therefore, this study has been excluded.

e where TBI was not verified (“probably TBI) [Ruff, Riechers, 

232], or 

Though this paper reports some findings for a combined TBI group, the findings that we reported in this review are reported separately for the mTBI only group.

rently written in the tables, state criteria at variance to the DoD/

h as the GCS > 13 was used or GCS = 13 (when it should be > 13) 

per, Mercado, et al., 200821, Cooper, Mercado-Couch, Richfield, et 

You are correct that this was inaccurately stated in the table. It should be > 13, as reported in the article, and therefore these studies remain included.
133

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

ded, that in my view meet the DoD/VA criteria at least as well, 

n some of the included studies. Of course I am biased, but I’m 

tudies:

Noted. We have reviewed all the suggested studies and agree that they provide useful information; however, we have scoped the review to include a specific subset of papers meeting VA/DoD mTBI criteria, and the papers you suggest do not fit within those pre-specified criteria and are therefore not included in the review.

loeg RD, Curtiss G. Predictors of postconcussion symptom 

ommunity dwelling male veterans. J Int Neuropsychol Soc. Nov 

01-1015.

Reviewed, not included due to not meeting inclusion criteria.

 Belanger HG, Curtiss G. Mild traumatic brain injury and 

c stress disorder and their associations with health symptoms. 

ed Rehabil. Jul 2009;90(7):1084-1093.

Reviewed, not included due to not meeting inclusion criteria.

 Curtiss G, Belanger HG. Long-term neuropsychological 

lowing mild traumatic brain injury. J Int Neuropsychol Soc. May 

28-236.

Reviewed, not included due to not meeting inclusion criteria.

 Curtiss G, Duchnick JJ, Luis CA. Demographic, medical, and 

ctors in work and marital status after mild head injury. J Head 

abil. Mar-Apr 2003;18(2):148-163.

Reviewed, not included due to not meeting inclusion criteria.

OC is not reliable because individuals do not know if they actually 

mply a memory gap (i.e., PTA). Our studies used alteration of 

efined as “loss consciousness or ‘black out’”. That is, either a 

C or a self-reported Alteration of consciousness. It is possible, 

y, that my studies included a few folks who had moderate injuries. 

 the data was collected in the 1970s at which time those with 

han a mild TBI would be hospitalized overnight at least, and no 

italized. In addition, the bias come in because other studies were 

d moderate or “unclassified” TBI severity subjects. 

See above comments; we have re-reviewed all noted studies and the inclusion/exclusion criteria have been appropriately applied. Thank you for noting the possible discrepancies as one of the studies was inappropriately included in the first draft of the report and has now been excluded (Morrisette).

ld change findings, but my studies do address things the 

 have not been addressed – frequencies of different medical 

oms and psychosocial outcomes, as well as frequencies of 

cal impairments, in addition to comparison with an injury control 

ost other studies do not have) and controlling for comorbid or 

cal and mental health conditions.

See above response re: included studies.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

findings of these studies have been replicated in a new sample 

t you would likely agree does meet the DoD/VA criteria for mild 

so not included, is:

D., Belanger, H.G., Horner, R.D., Spehar, A.M., Powell-Cope, 

cott, S.G., (2012). Health Outcomes Associated With Military 

d Traumatic Brain Injury, Blast, Trauma, and Combat Associations 

tional Guard. Archives of Physical Medicine and Rehabilitation, 

We have reviewed this study and it does not quite meet VA/DoD criteria, and therefore is not included in the review.

Noted.

studies is straightforward, but given the large number excluded, 

ul to summarize in the table of excluded studies, the specific 

sion. Without knowing how close these studies came to being 

ion in the paper, it’s difficult to assess whether the eligibility 

es may have incidentally introduced a bias. For example, are war

ore likely to be excluded than veteran samples due to contextual 

somehow limited the information gathered? I’m not suggesting 

bility criteria, but instead suggesting assessing potential 

” (for inclusion in the review) based on the possible identification 

istently associated with failure to use the DoD/VA definition.

We had similar concerns, and this was the rationale for including a table of studies meeting all inclusion criteria except for VA/DoD mTBI definition so that we were transparent about exclusions and readers could examine the list for possible bias in the included/excluded studies. We have also added a table of all the full-text study citations and exclusion codes. 

Noted.

bsent of bias, and was appropriately critical of the lack of 

ology, TBI severity description, and appropriate controls that 

 throughout the literature on TBI in U.S. service members and 

Noted.

Noted.

 introduced biases that should be discussed. Use of VA/DoD 

could time-limit the literature to after 2007; indeed, all included 

m within the last 3 years. These criteria may also limit to military 

 researchers and to US researchers. It is possible that exclusion of 

 reporting of LOC and PTA led to unnecessary loss of data, as the 

ese is usually based on self-report and is unreliable. 

We agree that any scoping decisions, this one included, introduce potential for bias. This decision was agreed upon by stakeholders for this review in order to obtain the most accurate description of a specific population of interest: Members of the US military/Veterans with mTBI meeting VA/DoD criteria. Therefore, though the report is limited in these ways, the stakeholders agreed that other, broader reports (e.g., the Carroll et al, 2004 WHO mTBI report) could address broader/different questions. In response to your comment, we have broadened the discussion of this point in the discussion.
135

c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

 for an mTBI sample size of at least 30 will bias the type of 

es that are used. Because of expense and other limitations, few 

udies will fulfill this requirement. Large studies can be limited in 

form in-depth testing, and so the report may be biased toward 

estionnaire data and easier-to-administer testing protocols (e.g. 

ning measure designed for dementia). Large studies also may 

resentation of individual results, which as you note, can be 

 objective evaluations of physical outcomes (e.g. audiology) were 

severely limits interpretation of this domain.

We agree, and have moved the neuroimaging information to the discussion section because of the likelihood that it is not comprehensive since we did not design the search to focus on these outcomes. We have also now added a table of excluded studies so that authors can review studies that were excluded based on sample size to gather additional information as needed.

ved as sources across outcome domains (e.g. Nelson et al., 

 potentially perpetuate any biases or limitations present in the 

ss domains (e.g. recruitment setting, inadequate power).

We agree and have noted this limitation in the discussion.

Noted.Noted.Noted.

npublished studies that we may have overlooked?

Noted.

ck, & Yan, 2012 (published in Work) This study does not meet our inclusion criteria because of 

unclearly reported definition of mTBI and because results are not reported separately for those with mTBI versus moderate/severe TBI.

Noted.

nk of. Noted.

Noted.

nalysis of US Veterans Health Administration comprehensive 

raumatic brain injury in Operation Enduring Freedom and 

reedom Veterans. Brain Inj 2012

We have reviewed this study and it does not meet inclusion criteria due to the mTBI definition used to define the cohort of participants.

Noted.

s reviewed the CBO report: The Veterans Health Administration’s 

SD and Traumatic Brain Injury Among Recent Combat Veterans?

We have reviewed this report and agree that though it provides important information and guidance, it does not meet our criteria for inclusion in this review.

Noted.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

D., Belanger, H.G., Horner, R.D., Spehar, A.M., Powell-Cope, 

cott, S.G., (2012). Health Outcomes Associated With Military 

d Traumatic Brain Injury, Blast, Trauma, and Combat Associations 

tional Guard. Archives of Physical Medicine and Rehabilitation, 

We have reviewed this study and agree that though it provides important information, it does not meet VA/DoD mTBI definitional criteria and is therefore not included in this review.

Noted.

e, the report captures all of the military/military veteran studies. 

discussion of meta-analytic studies from the civilian literature, it 

ant to balance the discussion with the Pertab et al., meta-analysis 

data from previous meta-analytic studies and reveals a potential 

rior findings.

This review has been added to the report.

Noted.

y come out with a TBI sensory and communications disorders 

ssue 7, 2012). Even though this journal is published after Oct. 3, 

les cover deployment-related experiences (e.g., blast, TBI), and 

 the following senses, conditions, and patterns: vestibular, visual, 

TSD, and referrals. This compendium fits well with the focus of 

Thank you for this suggestion. We have reviewed all studies from this special issue none meet criteria for inclusion in this report.

studies that were not included, though would be excluded for 

BI criteria, are:

., Hendricks, A., Kimerling, R., Krengel, M., Meterko, M., Stolzmann, 

Pogoda, T.K., Vasterling, J., & Lew, H.L. (2011). Psychiatric diagnoses 

havioral symptom severity among OEF/OIF VA patients with 

related TBI. Women’s Health Issues, 2(4S), S210-S217.

We have reviewed this study and agree that though it provides important information, it does not meet VA/DoD criteria and is therefore not included in this review.

aft, M., Pogoda, T.K., Amick, M.M., Woods, P., & Cifu, D.X. (2011). 

nd Characteristics of Driving Difficulties in Operation Enduring 

eration Iraqi Freedom Combat Returnees. JRRD, 48(8), 913-926. 

We have reviewed this study and agree that though it provides important information, it does not meet VA/DoD criteria and is therefore not included in this review.

goda, T.K., Baker, E., Meterko, M., Stolzmann, K.L., Cifu, D.X., 

& Hendricks, A.M. (2011). Prevalence of dual sensory impairment 

iation with traumatic brain injury and blast exposure in OEF/OIF 

urnal of Head Trauma & Rehabilitation, 26(6):489-96.

We have reviewed this study and agree that though it provides important information, it does not meet VA/DoD criteria and is therefore not included in this review.

M, Amara J, Baker E, Charns MP, Gardner JA, Iverson KM, et al. 

eening for mild traumatic brain injury in OEF-OIF deployed US 

empirical assessment of VHA’s experience. Brain Injury

We were not able to obtain a copy of this study for review.

Noted.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

010. Comparison of Concussive Symptoms, Cognitive 

d Psychological Symptoms Between Acute Blast-Versus 

d Mild Traumatic Brain Injury. Journal of the International 

cal Society (2011), 17, 36–45.

We reviewed this study and it did not meet inclusion criteria.

9 Traumatic Brain Injury Screening: Preliminary Findings in a US 

mbat Team. J Head Trauma Rehabil Vol. 24, No. 1, pp. 14–23.

We reviewed this study and it did not meet inclusion criteria.

0 The Structure of Postconcussive Symptoms in 3 US Military 

Trauma Rehabil Vol. 25, No. 6, pp. 447–458.

We reviewed this study and it did not meet inclusion criteria.

9. Eye and visual function in traumatic brain injury. J Rehab 

ume 46, Number 6, 2009 Pages 811–818.

We reviewed this study and it did not meet inclusion criteria.

ne, 2011. Head Injury and Blast Exposure: Vestibular 

Otolaryngol Clin N Am 44 (2011) 323–334.

We reviewed this study and it did not meet inclusion criteria.

12. Multisensory Impairment Reported by Veterans with and 

tic Brain Injury History. J Rehab Research Dev Volume 49, Number 

.

This study has been included in the report. Thank you for the suggestion.

2012. Neuropsychological outcomes of mild traumatic brain 

matic stress disorder and depression in Iraq-deployed US Army 

hiatry 201, 186-192

We reviewed this study and it did not meet inclusion criteria.

2012 Altered brain activation in military personnel with one 

tic brain injuries following blast. J Int Neuropsychol Soc. 2012 

We have moved the discussion of imaging and biomarkers to the discussion section of the report since it falls outside the scope of our key questions.

2 Effects of chronic mild traumatic brain injury on white matter 

nd Afghanistan war veterans. Hum Brain Mapp. 2012 Jun 15

We have moved the discussion of imaging and biomarkers to the discussion section of the report since it falls outside the scope of our key questions.

t al.,2011. Neuroimaging Correlates of Traumatic Brain Injury and 

r J Head Trauma Rehabil Vol. 26, No. 4, pp. 276–289

We reviewed this study and it did not meet inclusion criteria.

 Evidence of disrupted functional connectivity in the brain after 

blast injury. NeuroImage 54 (2011) S21–S29

We have moved the discussion of imaging and biomarkers to the discussion section of the report since it falls outside the scope of our key questions.

11. Cerebrocerebellar hypometabolism associated with repetitive 

ild traumatic brain injury in 12 Iraq war Veterans with persistent 

symptoms. NeuroImage 54 (2011) S76–S82.

We reviewed this study and it did not meet inclusion criteria.

y that have been excluded that meet criteria for inclusion. Please 

ing Vision data.

Noted.Noted.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

Relationship between mechanism of injury and neurocognitive 

EF/OIF service members with mild traumatic brain injuries. Mil 

77(10):1157-60.

This study has been included in the report. Thank you for the suggestion.

 Analysis of US Veterans Health Administration comprehensive 

raumatic brain injury in Operation Enduring Freedom and 

reedom Veterans. Brain Inj. 2012;26(10):1177-84. 

We have reviewed this study and it does not meet inclusion criteria due to the mTBI definition used to define the cohort of participants.

oss of Consciousness, Depression, Posttraumatic Stress Disorder, 

Among Deployed Military Personnel With Mild Traumatic Brain 

uma Rehabil. 2012 Oct 16. 

This study has been added to the included studies for this report. Thank you for the suggestion.Noted.

 call you had mentioned that another group (I believe IOM) was 

ew of mTBI literature. It would be helpful to note this since non

were not included in the literature review and could have been 

 the comparison to the Veteran based studies.

Agreed. The WHO group lead by Dr. Linda Carroll is updating the 2004 mTBI prognosis review, and we have included this information in our report for reader reference.

gestions or comments below. If applicable, please indicate the page and line numbers from the draft report.

se define “old learning.” More specificity in general would be 

ample, for ‘memory studies’, were delayed recall, trial-by-trial 

tion all examined? On page 48 in the summary of results, to what 

roups were mTBI compared? On page 53, suggest adding the 

s as a future area for investigation. On page 54, suggest being 

e use of the word “persistent” since it is unclear if symptoms 

gitudinal sense.

We have changed “old learning” to be “language abilities and general fund of verbal knowledge.” We have included additional information on specific tests and on comparison groups in the appendix tables. We have added a statement in the discussion relating to future research of the number of TBIs. We have clarified and limited use of the term persistent throughout the report.

other reviews are cited, it would be useful to explicitly indicate 

were published, since early systematic reviews might simply be 

udy citation is included, of course, but inclusion of the year of 

e body of this section would highlight that point.

We have included the year in text in this section.

ent evidence review. Noted. Thank you.

hasized for all domains that major shortcomings in the literature 

on-mTBI comparison groups and lack of adequate pre-mTBI 

.

Agreed, and we have added this point to the discussion.

ntal disorders, some controlled civilian studies do show higher 

isorders after mTBI compared with non-TBI controls (e.g., 

Gen Psychiatry 2004). Presence of prior psychiatric conditions 

ctor. Data from this same cohort showed higher health care 

g those with mTBI compared with non-TBI controls (Rockhill et al, 

012).

We have clarified that some civilian literature indicates higher rates of mental disorders after mTBI, as noted in the Carroll et al 2004 review.
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Comment Response

pecific comments about organization and note some areas 

 used where not clear to me. Please disregard if not helpful in 

 the report.

Thank you for the suggestions. Some will be included in this report, though some will be included in the planned article publication rather than in this full report.

the authors orient the reader at the beginning to their overall 

marizing the findings. It took this reviewer a few reads to 

the authors were presenting the material. It was a bit confusing 

e summary before the sections describing findings per domain 

 cognitive functioning in general before description in each 

n). Sometimes the summaries seem completely unnecessary 

e study is reviewed. In general, there was considerable repetition 

ructure of this report, which made the report difficult to read. 

eads to know what is new information versus a restating of what 

 summarized. 

Because some parts of this report are purposely repetitive (e.g., the executive summary), we plan to make the suggested change for the published article.

suggests the authors state reason time since injury is important 

ming the reader already has this information. 

Noted, and this has been added.

ader understand the “cognitive function” section, I suggest the 

eader that x# studies are based on neuropsychological testing 

n. It would be helpful to have an appendix in which the function 

es is described – otherwise, I am not sure how helpful it is to list 

yms in Appendix E. I did not find it useful to have the names of 

 the text – in fact, I think it makes the narrative harder to read. 

We have made some of these changes, including shortening the acronyms listed in the results section of the report.

ry of Findings for Cognitive Function Results the author state 

ed scores are scores associated with impairment below a certain 

t quite right and I do not think the sentence expresses what they 

We have corrected this sentence.

when the authors state that risk factors include “LOC and PTA” 

 that they are using the DoD/VA/ACRM definition of mTBI. As 

?

We have clarified that LOC and PTA were compared to just alteration of consciousness.

ore accurate on p.39 to state that the PCL scores suggest clinically 

oms rather than “impairment” as stated in the report

We have chosen to use the term impairment across measures to use similar terminology describing scores above a clinically significant cutoff.

 sequelae” as used here is confusing. For example, on p. 28 

 that one study reported “...based on mTBI with LOC and PTA 

se with mTBI who did not have these immediate sequelae.” What 

If these individuals did not have these “sequelae”, how was mTBI 

s is probably a matter of simple clarification.

We have changed this sentence to clarify.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

Conclusions: This section is largely devoted to discussion of the 

. The subsection on Physical Health Outcomes (p.49) does not 

Veteran/military studies. I suggest switching the focus so that the 

y discuss the literature they reviewed for this report.

Noted. We have updated the physical health section to focus the discussion on a comparison.

e that references are used inconsistently. Why are there no 

e summaries? Why are the “one study” referred to on p. 26 and 

es” on .34 not referenced What are the “some studies” (p.30 

r cognitive function for those not evaluated in forensic settings? I 

as just one study that examined this issue (#34). In some sections, 

 to identify which studies are forming the basis of the authors’ 

Noted. We have made the suggested corrections to text. The format for this report is such that summaries do not contain citations; however, citations will be used consistently throughout the published article.

SD is an AXIS I disorder (p.35). I do not understand the statement, 

many individual studies...general association between specific 

tcomes with other mental health diagnoses and symptoms”.

We have clarified that some studies looked at only PTSD, some examined “any Axis I disorder” which would include PTSD. We have clarified the confusing sentence.

 made without any supporting reference, that I do not believe the 

ports. 

 the leading cause of morbidity and disability among OEF/OIF 

ers.” I’m not sure about “morbidity” (but I think chronic pain and 

 are higher), but I’m quite sure there is no evidence to support 

” claim. This statement is repeated several times throughout the 

This has been corrected throughout the manuscript.

 (and elsewhere) “One or more studies have found . . . [problems 

riencing loss or alteration of consciousness at the time of the 

ms to me that everyone included in every study meets this criteria 

s the criteria for TBI. So, that statement it seems problematic. If 

 all subjects with an immediate event-related “loss or alteration 

ess” how can “loss or alteration of consciousness at the time of 

nique factor?

We have clarified that this refers only to patients who have PTA but not LOC or AOC, as described by the primary study authors.

ewhere): If you include my studies (or the one you inadvertently 

use it was recently published), the statement “Similar to objective 

lts, prevalence of self-reported cognitive deficits was not 

e included studies” would be inaccurate.

We have updated all summary statements to reflect the final list of articles meeting inclusion criteria.
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Comment Response

atement “. . . self-reported deficits are more likely to persist for 

th mTBI” is inaccurate. There is a difference between “persistence 

 and “symptoms reported in the chronic phase” which may come

-and-wane. Studies have not demonstrated persistence. What 

monstrated is problems/symptoms reported in the post-acute 

ase. The studies do not document that these began at the time 

nd persisted over time to the time of assessment. Other civilian 

rly documents that symptoms and problems are not persistent, 

t they come-and-go or wax-and-wane, but are generally higher in 

mild TBI subjects. We don’t know if they were also higher prior to 

ut we do know that they are not persistent. 

We have made this change throughout the report.

guage and Old Learning” is a term no one uses, and as a result 

nitially I thought you were referring to “Verbal Learning and 

ould suggest using the term “Language Abilities and General Fund 

wledge” or something like that. 

Thank you for this suggestion. We have made this change.

e review you refer to “statistical significance” or lack thereof. 

ct size would seem to better capture the important issue. If 

re somewhat small (or there are is lot of variability across 

 moderate effect size could be non-significant, but a moderate 

uld be clinically important. 

We agree entirely. We report effect sizes in the tables whenever available; however, authors frequently did not report effect sizes or data with which effect sizes could be calculated.

 to that above, is that studies may compare a mild TBI group 

TBI control group and find differences (as some studies did). 

se two groups may differ on other important factors as well that 

group differences (e.g., education, race, age, degree of comorbid 

 or medical health conditions). It seems to me that you would 

ss this issue if you can for those studies that reported group 

n example of this is on the bottom of page 26. 

Agreed. We highlighted any statistical adjustment or other adjustment for variation across groups in the text and tables; unfortunately, most studies did not provide this information, and this lack of adjustment for potential confounders is a contributing factor to the low study quality ratings for this body of literature.

erm “associated with mTBI” is used in talking about mental 

ers and symptoms. This implies some actual association, when it 

that they are simply comorbid factors both due to deployment

-related) experiences that are risk factors for both mTBI and 

ntal health conditions.

st using the term “comorbid” rather than “associated”.

We have made this change to the paper.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

g mean cognitive performance scores are criticized within 

se they cannot provide prevalence estimates of impairment. 

plication that report of percentage of participants scoring 

ment cut-off or below a certain standard score would yield a 

 estimate of cognitive impairment does not take into account 

ognitive abilities of participants. Clinically relevant cognitive 

pically thought of as an intra-individual decline. Scores normally 

ow average may not indicate acquired impairment but instead 

e potential of the individuals; similarly, above average scores 

ognitive decline (i.e., impairment) in an individual with superior 

al. Thus, the suggestion in the report does not go far enough. To 

e prevalence of cognitive impairment following a TBI, prospective, 

surement would be necessary. This is typically not feasible, 

ould nevertheless avoid implications that use of normative 

ard to the individual’s baseline potential would yield accurate 

ates of cognitive decline. The paper states this in the Summary 

ection, but it is also important to mention it earlier when 

rment cut-offs based on standardized scores.

Noted. We have included this discussion both within the section on cognitive outcomes, and within the discussion section.

ts: The synthesis was very well written and took a comprehensive 

mining the extant literature on mTBI in U.S. service members 

 synthesis was inconsistent with respect to its use of citations 

ts repetition of acronyms and abbreviations. Other editorial and 

ments (line numbers not included in reviewed drafts):

Noted. Thank you.

 OEF/OIF should be defined. Also, what about OND? This change has been made. No studies reported outcomes 

for OND Veterans and the information we describe in the background is specific to OEF/OIF Veterans.

efine WHO This change has been made.

 PTA This change has been made.

uction of NSI – Neurobehavioral Symptoms (no S) Inventory This change has been made.

ast paragraph, two instances of “reported that” – delete one This change has been made.

ast paragraph – “mTBI).” ß no reference to an open parentheses, 

This change has been made.

MRI This change has been made.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

ph: the recommendation to include imaging results is noted; 

recommendation is not feasible in terms of equipment, 

cipant willingness to participate (might lead to biased self

g, and costs. This recommendation also needs to be reconciled 

 Clinical Practice Guidelines (see excerpt below). Though, the 

at if imaging studies, especially functional fMRI or DTI, were 

 frequently, then perhaps there would be notable distinctions 

l” and “mild TBI” states.

. 16)

Noted, and we have changed this recommendation slightly to be more consistent with this comment.

ditional imaging studies, other imaging techniques such 

gnetic resonance imaging, diffusion tensor imaging, 

n tomography scanning; electrophysiological testing such as 

ography; and neuropsychological or other standardized testing 

been used in the evaluation of persons with TBIs, but are not 

e currently accepted criteria for measuring severity at the time of 

outlined in Table A -1

Noted, and the criteria presented are consistent with the VA/DoD criteria.

ble: There were some abbreviations throughout the text that 

ly” defined before their first use, so these are included along 

AOC = Alteration of consciousness/mental state 5 (based on 

es) p.5; (b) BAMC (last row) = Brooke Army Medical Center, 

Compensation & Pension , p. 21; (d) CTE = Chronic Traumatic 

 p. 10; (e) EFP = Explosively formed penetrator (?) – used on p. 17 

AS – “symptoms” misspelled, p. 6; (g) NSI = I = Inventory, p. 6; (h) 

estigator, p. 9 (or just say “Principal Investigator on p. 9); (i) VHA = 

Administration (like on p. 8), p. 7; (j) For SCID, indicate Axis I, not 

efine/include VACO and PM&R, as introduced on p. 8; (l) define 

entioned on p. 8)

These changes have been made.

dies from which the “12 to 23 percent” are derived. Also 

endricks et al. (in press, Brain Injuries), who examined VA 

TBI evaluation (CTBIE) data and found: “In the study population, 

positive for potential TBI and 54.6% of these had an electronic 

. Of those with CTBIE records, evaluators confirmed TBI in 57.7%, 

stimate that 6.8% of all those screened were confirmed to have 

This citation has been added.

agraph: “fame” should be “frame” This change has been made.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

agraph: “factors unique to combat deployments.” I would take out 

e replace with “military,” but not sure if that’s necessary), since 

ted conditions (e.g., noise in the general military environment), 

mbat, may uniquely account for experiencing post-concussive 

since women are restricted from some combat roles, the use of 

may minimize what women potentially experience.

This change has been made.

semi-colon in second paragraph, This change has been made.

Veterans Health Administration” as VHA; This change has been made.

R and VACO This change has been made.

gy – can now call it “mTBI” This change has been made.

ph – why not include “post-traumatic amnesia” along with AOC, 

This change has been made.

aph, discussion about “severity of sequelae” gets a little 

se TBI sequelae can be defined as either AOC, LOC, or PTA (which 

 be primed for, since there was just discussion about these in 

tence), or TBI residual symptoms (e.g., headache, vestibular, 

sual, etc. impairment). I don’t know if “the Severity of sequelae” 

o be here, but I understand that it makes the point that very 

re used to categorize TBI severity, and it’s important to note that 

ental/physical symptoms following a TBI event are not used to 

I would replace “sequelae” with “symptoms,” and then provide a 

toms to orient the reader. It might also be helpful to briefly state 

 on the duration of LOC, AOC, or PTA. You can then list the criteria 

in), or refer to the reader to a more detailed description, as you 

This change has been made.

D in first paragraph This change has been made.

TE in “Outcomes” paragraph This change has been made.

ullet points in the last box to the right would help the criteria 

We left out bullet points for space reasons.

rnes et al., spell out “medical” We have corrected this mistake.

Mercado-Couch, et al. – BAMC should be defined earlier (e.g., 

al. citation above it in the table); Should American “College” be 

s not clear about 10 participants excluded due to PTA suggesting 

BI... Is it that the duration of PTA was longer than the criteria for 

d by ACRM?

This change has been made.
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Comment Response

define “C and P,” also, in mTBI definition, why not just call it 

This change has been made.

al., American College or Congress?; defined “EFP,” as previously 

This change has been made.

l., Time since Injury – define unit of time. This change has been made.

eal et al., last column, just say MVA instead of spelling it out This change has been made.

 et al., use “TBI” consistently – sometimes it’s spelled out (see 

mns)

This is a quote so it is spelled out as in the original text.

et al., spell “through,” not “thru.” This change has been made.

l., reference 34: define what “forensic” context is. This change has been made.

Based on “VA”/DoD Consensus definition (reversed as written). This change has been made.

rs et al., “Department of CVAMC” needs editing; also, in 

hree groups of Veterans, for the first two indicate “deployment

ot sure what “combat Veterans without “LOC” means – is this a 

did they have AOC or PTA?; In the mTBI definition column, not 

finition is referring to – did Veterans have to have LOC or AOC 

, PLUS PTA?

These changes have been made.

t al., mTBI definition column – delete © This change has been made.

al., C&P needs to be defined earlier This change has been made.

 Combat Veterans diagnosed, not “diagnoses” This change has been made.

l., mTBI definition column – use DVBIC acronym This change has been made.

ast paragraph – can abbreviate LOC and AOC – make clear, if this 

participants demonstrated better overall cognitive functioning 

on?”

This change has been made.

ar in 2nd to last paragraph – second line: Should this be “NOT” 

uld “NOT” be deleted?

We have clarified this sentence.

 speed row, Key Question #1 column, not sure why “possible” 

re – delete that word?

This change has been made.

aph – could you cite the 7 studies here? We are providing summary paragraphs without citations for 

each section, which are followed by the cited results sections by key question. This will be consolidated for the published article version of the report.
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Comment Response

aph, 2nd line, instead of “with” TBI, replace “with” with 

 indicate “with mTBI history.” Also make this correction in Key 

graph, first line.

This change has been made.

al abilities, first sentence, cite the 5 studies here. We are providing summary paragraphs without citations for 

each section, which are followed by the cited results sections by key question. This will be consolidated for the published article version of the report.

agraph: Just give the abbreviations/acronyms, no need to spell 

ychological test names.

This change has been made.

aph, 3rd line: instead of saying “significant correlations,” indicate 

ce it seems like visuospatail abilities and MH conditions would be 

ated.

This change has been made.

ory” paragraph, mid-way through, again report direction of 

This change has been made.

on 1 paragraph: just report abbreviations This change has been made.

on 1 paragraph, 5th from last row, use “longer” instead of “much 

This change has been made.

ast row, use (C&P) for compensation and pension, since this 

 introduced previously.

This change has been made.

ph, second from last row: Use LOC and PTA instead of spelling 

This change has been made.

Concentration paragraph, cite the 7 studies after mentioning 

We are providing summary paragraphs without citations for each section, which are followed by the cited results sections by key question. This will be consolidated for the published article version of the report.

Concentration paragraph, last line can read “....OR PTSD was not 

ciated with outcomes.”

This change has been made.

on 1 paragraph, do not spell out neuropsychological test names. This change has been made.

aph, “forensic” mentioned a couple of times – define what exactly 

This change has been made.

aph, indicate direction of associations; do not spell out LOC, PTA This change has been made.

on 1 paragraph (here the 9 studies are cited, very helpful!); , do 

ropsychological test names.

This change has been made.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

estion 2 paragraphs for each page, can say C&P instead of spelling 

no need to define what a C&P evaluation is here, define it when 

This change has been made.

vation paragraph – regarding “with mTBI,” see comment #41 This change has been made.

on 2 paragraph, see comments #56, 58 This change has been made.

on 1 paragraph, do not spell out neuropsychological test names. This change has been made.

on 1 paragraph: There is discussion about “non-mTBI” 

e these participants who never experienced a TBI (non-mTBI 

o not currently have mTBI (symptoms resolved?)

This has been clarified

on 2 paragraph: compensation and pension evaluation can be 

This change has been made.

ed Cognitive Problems paragraph. I’m wondering if “service 

uld be considered a “risk factor,” as it’s really a proxy for a 

hat was sustained or aggravated during military service. The point 

vice connection” is a short-hand for the latter, so this might be a 

tics.

Agreed, and this is how it is described in the primary study.

– instead of saying “control,” say “control group.” This change has been made.

of Physical health results first paragraph – it would be helpful to 

es here.

We are providing summary paragraphs without citations for each section, which are followed by the cited results sections by key question. This will be consolidated for the published article version of the report.

of Physical health results first paragraph – to be consistent, 

rom time-since-injury.

This change has been made.

om last paragraph, no need to spell out NSI – already introduced. This change has been made.

first row, similar to comment 63, “referral to neurology clinic 

s listed as a risk factor, but is likely a proxy for headache 

cy. Again, this might just be a matter of semantics and readers 

he implication. Without reviewing the article, not sure if any 

ven for why a patient might be referred to a neurology clinic, so I 

this might be the only unit of measurement.

Agreed—and this is how it was described in the primary study.

ome articles from JRRD 49(7) would be relevant here (if you 

e frame of your search)

We have added these articles.

graph – when describing the pain level scale, please provide 

ain at all?) to 10 (very severe pain?) scale.

This change has been made.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

raph for “Headaches,” last line about referral to neurology clinic 

ee comment #68.

Noted.

tion 1 paragraph – here, the 9 studies being alluded to are 

od!).

“NSI” here, no need to spell it out.

This change has been made.

tion 2 paragraph: Provide more detail in the first sentence – 

ps being compared

This change has been made.

tion 2 paragraph, last sentence – see comment #68. Noted.

aragraph: cite the one study being discussed We are providing summary paragraphs without citations for 

each section, which are followed by the cited results sections by key question. This will be consolidated for the published article version of the report.

Appetite” first paragraph - cite the specific studies you highlight, 

y describing mild to moderate effects of mTBI population, PTSD 

sults study

We are providing summary paragraphs without citations for each section, which are followed by the cited results sections by key question. This will be consolidated for the published article version of the report.

mary of Mental Health Results section – cite the studies where you 

es, two studies, PTSD, alcohol abuse, etc.

We are providing summary paragraphs without citations for each section, which are followed by the cited results sections by key question. This will be consolidated for the published article version of the report.

e comment #68 Noted.

tions, 17 studies are alluded to in the first paragraph, and then 

n the Key Question paragraph, and then cited. Just make sure 

ncy between the sections throughout the report in terms of when 

Noted.

estion 2, could you add specifics? For example, for study #27, 

ociation between the PCL re-experiencing cluster and blast

This change has been made.

nxiety paragraph, cite the studies that are being alluded to. We are providing summary paragraphs without citations for 

each section, which are followed by the cited results sections by key question. This will be consolidated for the published article version of the report.

tion 1 – just say “NSI” This change has been made.

tion 1 – abbreviations This change has been made.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

e Use disorders first paragraph – cite studies alluded to We are providing summary paragraphs without citations for 

each section, which are followed by the cited results sections by key question. This will be consolidated for the published article version of the report.

st paragraph - cite studies alluded to We are providing summary paragraphs without citations for 

each section, which are followed by the cited results sections by key question. This will be consolidated for the published article version of the report.

ntal Health Outcomes first paragraph – cite studies alluded to We are providing summary paragraphs without citations for 

each section, which are followed by the cited results sections by key question. This will be consolidated for the published article version of the report.

ntal Health Outcomes first paragraph – aren’t “frustration” and 

e NSI affective cluster (e.g., Meterko et al., 2012, Journal of Head 

ation, 27(1), 55-62 Psychometric assessment of the Neurobehavioral 

ry-22: the structure of persistent postconcussive symptoms 

ment-related mild traumatic brain injury among veterans.)

Yes, and we would consider these part of the mental health related outcomes section for this report.

on 1 – abbreviations This change has been made.

on 1, second to last sentence – period before 12,20 citations. This change has been made.

 of functional/social outcome results: cite studies alluded to We are providing summary paragraphs without citations for 

each section, which are followed by the cited results sections by key question. This will be consolidated for the published article version of the report.

 of functional/social outcome results – make clear throughout 

hether patients with mTBI, patients without mTBI, or results 

both groups are being discussed.

This change has been made.

oduction paragraph – what are “positive neurological findings?” This change has been made.

 Question 1 – abbreviations This change has been made.

sults” paragraph: Throughout the paragraph, the word 

ed several times. I think a better word here would be “exhibiting.”

This section has been removed and edited.

on 1: Abbreviations This section has been removed and edited.

on 1: I found the first sentence difficult to follow – please add 

punctuation and clarifying language.

This section has been removed and edited.

tion 2: the tense was different in this paragraph than in others. 

tead of “obtain.”

This section has been removed and edited.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

 of service utilization/costs results: Please cite studies alluded to. We are providing summary paragraphs without citations for 

each section, which are followed by the cited results sections by key question. This will be consolidated for the published article version of the report.

tion 1: Table X = Table 7? This change has been made.

al health outcomes, it’s acknowledged that PTSD is a focus for 

I’m wondering if this section could be rounded out by also 

other mental health conditions that are typically of interest: 

PTSD anxiety, and substance use disorders? As a starting point, 

lister has published on mild TBI in civilian populations and its 

, cognitive, mental health conditions; Silver JM, McAllister TW, 

epression and cognitive complaints following mild traumatic brain 

hiatry. 2009; 166: 653-61.)

Agreed, and due to space limitations, we provided an expanded discussion of PTSD at the request of our stakeholders, but have not provided an expanded discussion of other outcomes, instead referring readers to other reviews and studies.

raph of the MH Outcomes section: instead of “causal factors,” 

erm “event-related?”

This change has been made.

ot Surprisingly” paragraph, cite the “aforementioned” literature 

 last sentence of this paragraph, it might be more clear to say, 

BI versus other factors, such as those that are deployment

clear.”

This change has been made.

al paragraph at top, “When individuals experience the mTBI as 

der replacing “experience” with “perceive,” since, by definition, 

f mTBI is traumatic, at least physiologically/functionally.

This sentence has been clarified.

agraph, starting with “The results,” I think more detail could be 

h as citations, especially when you cite specific figures. Consider 

st sentence as:

high prevalence estimates may differ from results observed in 

ns, as they may be related to unique deployment-related factors, 

rather than, specifically, to the presence of mTBI. 

This change has been made.

biomarkers paragraph: cite the one study here. We are providing summary paragraphs without citations for 

each section, which are followed by the cited results sections by key question. This will be consolidated for the published article version of the report.

 biomarkers” sentence: Do you mean “as prognostic tools among 

vere” TBI or with “moderate to severe” TBI? (not sure if severe 

s a category, or if this was meant as “not mild.”

This change has been made.
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 biomarkers” paragraph: after introducing chronic traumatic 

 put “(CTE)”

This change has been made.

ph, 2nd sentence, put “imaging” after “functional”; 5th sentence, 

d of spelling it out; instead of “demonstrated” throughout this 

observed;” Cite

This change has been made.

raph, 2nd sentence; add “patients with” mTBI. This change has been made.

raph, 6th sentence, should be an “in” between “decreases 

This change has been made.

aph, 9th sentence, reword: differences between “individuals with 

iduals without mTBI” or “individuals in the control group.” 

This change has been made.

aph, 9th sentence – reword, such as “fMRI studies found 

nces between individuals with mTBI and individuals in the 

ring cognitive and behavioral tasks consistent with....”

This change has been made.

ragraph, first sentence, reverse last two words so that it reads: 

ng; cite which studies found increased vs. decreased FA; instead 

 “control participants.”

This change has been made.

raph, first sentence, say “universal” limitation (instead of across 

This has been re-worded.

raph, what is the evidence that participants aren’t blinded to 

s? It’s my sense that patients are told that the purpose of the 

ine differences,” “observe,” etc., and aren’t informed about 

al hypotheses until after study completion, if at all.

No studies reported that patients were blinded, and therefore we cannot assume that any were blinded.

ragraph, 3rd-4th sentences; “wide variety of tools used to assess 

 interest.”

This change has been made.

ns, 2nd sentence, I would say, “The literature reviewed here,” This change has been made.

ns, 4th sentence, instead of saying “negative outcomes,” 

gh a significant portion of individuals who have experienced an 

-term mental and physical health symptoms” .....”not significantly 

dividuals who “did not experience mTBI” or “served as controls.”

This section has been re-worded.

s, 7th sentence, I would stay away from “outcomes,” and say 

mptoms,” because we don’t know whether symptoms/conditions 

n “outcome”) by the mTBI.

This change has been made.

ns, 8th sentence from last – instead of “do not have mTBI,” I 

have not experienced mTBI” or “who do not have mTBI history”

This change has been made.
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Comment Response

ns, 7th sentence from last, “instead of saying “is largely influenced 

can be accounted for” by other factors that are deployment

an....”

This change has been made.

et al., “five-difit”, should be “five-digit” This change has been made.

., “seeking starts” should be “seeing stars” This change has been made.

“loose” should be “lose” This change has been made.

n et al. – why aren’t the p-values listed? We have listed results according to what was reported in the 

primary studies and have put labels used by study authors in quotes to indicate a direct quote in our tables.

mitation of non-reporting of impaired subgroups is emphasized. Noted. Thank you.

t repetitive and disorganized with regards to reporting of the 

hed. For example, conclusions are reported on p.13 within a 

erature Flow. 

We have re-ordered the presentation of findings.

esults needs revision. Tables contain a great deal of text and no 

rs are occasionally presented without units (e.g. p.18 Gordon et 

ury: 20.1 (weeks?)). Table 1 should include each study’s outcome 

eferably study hypothesis. It was good to see that effect sizes 

he tables in the appendices, but effect sizes are missing for most 

ported, these can be calculated). Also, in cases where significance 

n corrected for multiple comparisons (e.g. Table 5), this should 

We have made these corrections to the table. For space reasons, we have presented some information in appendix tables rather than in text. We report the data as reported in the studies without calculating effect sizes when the authors did not provide this information; however, we are considering providing this calculated information in the article version of the report.

aging and biomarkers, p.51: it is mentioned twice that functional 

have “failed” to show differences in performance along with 

ain function, and this point would benefit from clarification. One 

ported by activation patterns, is that mTBI patients are able 

milar test performance to uninjured controls through greater 

eural resources. (e.g. McAllister, 2001, Neuroimage. 2001 

12.Differential working memory load effects after mild traumatic 

We have moved all discussion of imaging results to the discussion due to searching limitations and refer readers to more comprehensive reviews of this literature.

tle “Verbal and Old Learning” inappropriate as the tests 

section measure vocabulary and knowledge, not learning 

arning and memory).

We have changed this title.

5: “...without mTBI on the RBANS Visuospatial/Constructional 

entence does not match information presented in table 1b for 

We have made sure these results are correct and consistent with the table.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

 E, some information in the “comparison group description 

t appear to describe a comparison group, but rather a covariate 

Yes, this indicates continuous variables rather than comparison groups, and as such, correlation results are presented for these studies.

ments: Noted as below.

“...and its associated post-concussion symptoms is...” should be 

Refers to mTBI, not the symptoms, therefore left as “is.”

 “...a TBI while deployed).” The parenthesis does not have a 

This change has been made.

and p.8 paragraph 2: “...balance problems) beyond this time 

e “frame” 

This change has been made.

 “...often require the attention from a range of health care 

should remove “the”

This change has been made.

“lengthly” should be “lengthy” This change has been made.

 “...Veteran/military participants without mTBI).” The parenthesis 

partner.

This change has been made.

 “disruption of brain function (e.g. altered of consciousness...)” 

tion”

This change has been made.

4: “six studies reporting...” Should be “reported” This change has been made.

3: “Axis 1” should be “Axis I” This change has been made.

3: “...we excluded many studies which proported to study mTBI” 

orted”

This change has been made.

Cockerham and Goodrich might be beneficial in the section 

dresses occult visual deficits in this patient population. This 

flated with self-reported complaints, as previously established 

ssessment were deemed not sensitive in detecting these 

dditionally, as this data is prospectively collected at all Polytrauma 

data be incorporated in the analyses.

We have reviewed this literature and though it provides important information related to vision outcomes, we did not find studies meeting our inclusion criteria for this report due to the populations examined.

mmend additional references regarding TBI incidence—pg #8 

e point could be substantiated by and WHO data or CDC Data.

We have re-worked the introduction for the report.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

umber of veterans and service members who have incurred a 

t related mTBI have lead to persistent or chronic post-concussion 

Multiple studies have reported PCS-like symptoms among 

ears after mTBI. Agree that published studies to date has been 

y all the potential risk factors and a major causative role other 

0 and DSM-4 criteria have been established for diagnosing PCS 

what. There continues to be a lack of consensus regarding PCS, 

s limit the symptoms to within 4 weeks of injury, while DSM-4 

symptom onset shortly after injury, but persistence at least 3 

these diagnostic guidelines, evidence suggests that symptoms 

ediately, or weeks to months after the initial injury (Ryan et 

ent studies have reported PCS-like symptoms among Veterans 

 mTBI. ( Scholten et al.2012). While these persistent symptoms 

mplicate return to work/duty and negatively affect quality of life, 

 and time courses are not understood and diagnosis remains 

relies mostly on self-report of complex symptomatology rather 

uantitative or biological measures. The reasons why people 

r fail to recover fully from mTBIs is not known and there are no 

logies for diagnosis or prognosis of PCS. Identifying the cognitive, 

m biomarkers that accurately diagnose veterans or service 

ersistent symptoms is critical to our understanding of long-term 

 patient population and needs to explored further.

We have expanded the discussion section to include some of these ideas.

nging area with limited available published studies. I would 

ating in the early overview section that there are no prospective 

.

We have stated this in the executive summary and the body of the report.

o seems somewhat contradictory when you report that imaging 

w strength of evidence yet your recommendations indicate that 

es should be designed to report imaging findings.

We have rearranged and clarified the imaging findings and recommendations.

mplementation Questions

formance measures, programs, quality improvement measures, patient care services, or conferences that will be directly 

lease provide detail.

 new information here. Conclusions are consistent with 

owever, making this available to national Polytrauma calls or 

 Mental Health/PTSD calls and conferences would help reinforce 

Noted. We plan to make the report findings available in a variety of formats, including VA intranet, a published article, presentation at a national neuropsychology conference, and through a VA cyber-seminar. We will consider how to expand the audience as you recommend.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

aise the question of the context in which mTBI may be best 

A. The results also have implications for compensation and 

s regarding mTBI.

Noted, though we caution our readers not to make strong inferences based on the low quality literature available for synthesis in this report. Relying on these report findings in conjunction with related research on civilian populations with mTBI will provide the strongest available foundation for such weighty decisions.

nce injury” was cited throughout the document as being related 

ut also noted to be missing in many studies, I think it would 

nt to capture this variable in national VA databases, such as the 

TBI Evaluation database. If this information is available in any DoD 

efense Manpower Data Center (DMDC), then a data exchange 

d VA would benefit studies by having these data located in one 

hus reducing the risk of error through patient self-report.

We have added this to the discussion.

d nature and low quality of literature, it is not possible to reach 

 There is nothing to be implemented at this time.

Noted, and we encourage readers of this report to consider the results in conjunction with findings from civilian literature in order to make conclusions based on the best available evidence.

in the Inpatient/Polytrauma Units might be affected. Noted.

 TBI System of Care. Noted.

em of Care, can be disseminated on one of the national calls and 

rs with link to report

Noted.

endations on how this report can be revised to more directly address or assist implementation needs.

er adding review of any studies that looked at multiple mTBI’s. It 

mplication” 

’d suggest clearly delineating the difference between cognitive 

d symptom complaints. While it’s true that the literature 

te cognitive performance recovery by 3 months (or even 7 days 

re), there is a difference between performance and symptoms. 

e civilian literature suggests that PCS symptoms in fact do 

e Meares et al) and such the use of the term ‘persist’ may be 

nce” may be more accurate.

We have made these changes throughout the report.

What” section. However, one could potentially make the 

ince outcomes do not differ following mTBI, that all the DoD/VHA 

d attention devoted to this matter may be a less than ideal use 

 example: Do we really need to continue to screen for mTBI? Are 

mprehensive TBI Evaluations following a positive TBI screen, really 

od use of resources?

Noted, and we have expanded our discussion of these points in the report.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

ways to meet the needs of those symptomatic returning service 

terans than focusing on mTBI, when mTBI does not appear to be 

ning the symptoms and problems?

Noted, and we have expanded our discussion of this point in the report.

tions. This is a thorough report with well-reasoned conclusions. Noted. Thank you.

ates that many of the mTBI studies performed with service 

terans are methodologically limited and provide low strength 

se implementation should be based on strong evidence, it doesn’t 

report should make any health services related recommendations 

on, but should recommend that VA leaders prioritize 

 to ensure high quality research, and develop mechanisms 

standard communications between DoD and VA) that assist 

btaining reliable data.

We agree that ideally, recommendations should be made based on strong evidence. However, in the absence of strong evidence, then the best available evidence should be the basis on which treatment and policy decisions are made. We have made cautious recommendations consistent with the best available evidence for treatment and policy as well as making strong recommendations for further high quality research as you suggest.

ypographical errors should be addressed. Presentation of results 

d. Consider other data presentation modes in addition to tables. 

markers could possibly be removed and examined in a separate 

tion criteria that are more appropriate for these kinds of studies. 

Noted, and we have incorporated your suggested edits.

 in the TBI clinics is the CHRONIC effects of mTBI 3-10 years post 

ed sequale of the initial injury which does not completely follow 

ern of the civilian mTBI population. In the civilian population the 

nsient and self-limiting, with apparent full recovery occurring 

everal weeks following injury (Levin et al., 1997) which is distinct 

/service member population who have persistent symptoms and/

ations (Iverson et al., 2006; Ruff et al., 1996). There needs to be 

on into the etiology and treatment of these chronic/persistent PCS 

We agree and have expanded our discussion of treatment implications.

act details of any additional individuals/stakeholders who should be made aware of this report.

A? Noted.

mmendations other than VA polytrauma staff. Noted.

R&D leaders responsible for prioritizing funding, inclusive of and 

D

D

D

, MPT

ma Clinic Directors

Noted.
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c Brain Injury in Veterans and Military Personnel: A Systematic Review Evidence-based Synthesis Program

Comment Response

ck, Deputy Director, Defense and Veterans Brain Injury Center

k@tma.osd.mil

Noted.

keholders should made aware of this report: VHA Polytrauma 

which include Polytrauma Rehabilitation Centers (PRC),Polytrauma 

bilitation Programs (PTRP), Polytrauma Network Site (PNS), 

ort Clinic Team (PSCT), and Polytrauma Point of Contact (PPOC). 

Military Heath System’s TBI clinics, Defense and Veterans Brain 

VBIC) and National Intrepid Center of Excellence (NICoE) satellite 

Noted.