Archives of Physical Medicine and Rehabilitation journal homepage: www.archives-pmr.org Archives of Physical Medicine and Rehabilitation 2014;95(3 Suppl 2):S230-7
REVIEW ARTICLE
Systematic Review of Prognosis After Mild Traumatic Brain Injury in the Military: Results of the International Collaboration on Mild Traumatic Brain Injury Prognosis Eleanor Boyle, PhD,a,b Carol Cancelliere, DC, MPH,c,d Jan Hartvigsen, PhD,a Linda J. Carroll, PhD,e Lena W. Holm, DrMedSc,f J. David Cassidy, PhD, DrMedSca,b,c,d From the aInstitute of Sports Science and Clinical Biomechanics, Faculty of Health, University of Southern Denmark, Odense, Denmark; b Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; cDivision of Health Care and Outcomes Research, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada; d Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; eSchool of Public Health and Alberta Centre for Injury Control and Research, University of Alberta, Edmonton, Alberta, Canada; and fDivision of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Abstract Objective: The World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury (MTBI) published its findings on the prognosis of MTBI in 2004. This is an update of that review with a focus on deployed military personnel. Data Sources: Relevant literature published between January 2001 and February 2012 listed in MEDLINE and 4 other databases. Study Selection: Controlled trials and cohort and case-control studies were selected according to predefined criteria. After 77,914 titles and abstracts were screened, 13 articles were rated eligible for this review and 3 (23%) with a low risk of bias were accepted. Two independent reviewers critically appraised eligible studies using a modification of the Scottish Intercollegiate Guidelines Network criteria. Data Extraction: The reviewers independently extracted data from eligible studies and produced evidence tables. Data Synthesis: The evidence was synthesized qualitatively and presented in evidence tables. Our findings are based on 3 studies of U.S. military personnel who were deployed in Iraq or Afghanistan. We found that military personnel with MTBI report posttraumatic stress disorder and postconcussive symptoms. In addition, reporting of postconcussive symptoms differed on the basis of levels of combat stress the individuals experienced. The evidence suggests a slight decline in neurocognitive function after MTBI, but this decline was in the normal range of brain functioning. Conclusions: We found limited evidence that combat stress, posttraumatic stress disorder, and postconcussive symptoms affect recovery and prognosis of MTBI in military personnel. Additional high-quality research is needed to fully assess the prognosis of MTBI in military personnel. Archives of Physical Medicine and Rehabilitation 2014;95(3 Suppl 2):S230-7 ª 2014 by the American Congress of Rehabilitation Medicine
Injuries sustained in combat today differ from the injuries sustained in previous wars.1,2 The proportion of head and neck wounds has doubled from the Vietnam War, whereas thoracic and Supported by the Ontario Neurotrauma Foundation (grant reference 2010-ABI-MTBIWHO871). The funder was involved neither in the design or preparation of the study protocol nor in the management of the project, analysis or interpretation of data, or the preparation of the final article. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. The findings and conclusions in this research are those of the authors alone and do not necessarily represent the official views or policies of the Centers for Disease Control and Prevention or any agency of the United States government. Inclusion of individuals, programs, or organizations in this article does not constitute endorsement by the United States government.
abdominal injuries have declined.3 This change can be explained by various factors including the use of body armor and Kevlar helmets, which have reduced life-threatening injuries to the head, chest, and abdomen. Also, advances in in-theater medical care have reduced the killed-wounded ratio to less than 1 in 10.4 Furthermore, the use of mine-resistant ambush-protected vehicles that diminish the effects of improvised explosive devices has resulted in a reduction in fatalities from roadside explosives.3 Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are being referred to as the “signature” injuries in the current U.S. conflicts.5 One of the most common causal agents for injuries is exposure to blasts, which can result in TBIs with
0003-9993/14/$36 - see front matter ª 2014 by the American Congress of Rehabilitation Medicine http://dx.doi.org/10.1016/j.apmr.2013.08.297
Review of prognosis after mild TBI in the military different degrees of severity.6 Based on the mechanism by which blast-related injuries are produced, these are classified into 4 groups.7,8 A primary blast injury occurs when the injury is sustained from the explosive materials. A secondary blast injury results from being hit by matter thrown by the explosion or by the fragments of the weapon casing. A tertiary blast injury is the result of the individual’s being thrown by the explosive blast and hitting another object such as a wall or the ground. Last, a quaternary blast injury can occur from burns, toxic fumes, and other causes not covered in the previous 3 definitions. It has been estimated that 60% to 80% of the military personnel who are exposed to a blast acquire a TBI.5,9 From 2000 to the first quarter of 2012, 244,217 cases of TBIs were reported among U.S. military personnel by the Defense Medical Surveillance System and the Theater Medical Data Store.10 Slightly over 75% of the TBIs were classified as mild, and only 1.6% were penetrating head injuries. Approximately 58% of these injuries occurred in U.S. Army personnel, and the remaining injuries occurred evenly in the Navy, Marines, and Air Force. According to the Defense Medical Surveillance System, the incidence rate of mild traumatic brain injury (MTBI) between 1997 and 2007 in the U.S. military was approximately 6.6 per 1000 person-years.11 This incidence rate significantly varies by age groups (younger have higher rates), sex (men higher than women), race (white higher than other races), rank (enlisted higher than officer), and branch of service (Army and Marines higher than other branches). The cost of care for TBI in the U.S. military population has risen from $21 million in 2003 to approximately $646 million in 2010.12 The majority of the prognostic research in MTBI has been conducted in the civilian population. For example, the World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury published the first systematic review on MTBI prognosis in 2004. It accepted only 1 article involving a military population.13 In that study, conducted 1 year after the Gulf War, the authors found a 1.8 times greater risk of a behavioral-related discharge in military personnel who had an MTBI than in persons who were discharged without a brain injury.14 The majority of the head injuries in that study were related to falls (31.8%) and motor vehicle collisions (30.4%); these mechanisms are similar to those seen in civilian injuries. It is unclear whether these results of the study would be generalizable to MTBIs that occurred in-theater.15 There are inherent differences in the combat military population and civilian population.2 Depending on the country, military personnel might have been evaluated with predeployment health screens and physical fitness standards. All military personnel are employed at the time of injury, which may not be true in the civilian population. The prevalence of MTBI is higher in the military population than in civilian populations living in noncombat zones, and in particular, blast TBIs are higher.16 Depending on the length of deployment and the probability of being exposed to improvised explosive devices, there is a greater chance that military personnel may experience repeated TBIs.17 Last, standardized triage and care is provided to military personnel throughout the recovery period.18
List of abbreviations: ICoMP MTBI PCL-C PTSD TBI
International Collaboration on MTBI Prognosis mild traumatic brain injury Posttraumatic Stress Disorder Check ListeCivilian posttraumatic stress disorder traumatic brain injury
www.archives-pmr.org
S231 In the present study, we aimed to update and expand on the original World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury on the prognosis of MTBI by focusing solely on the military population. The specific objective of this study was to synthesize the best available evidence on the course and prognosis of MTBI in the military population.
Methods The literature search and synthesis strategy has been outlined in detail elsewhere and in this issue.19,20 In brief, using a detailed search strategy, MEDLINE, PsycINFO, Embase, CINAHL, and SPORTDiscus were searched from January 1, 2001, to February 10, 2012. In addition, the reference lists of eligible articles were screened for potentially relevant articles and members of the International Collaboration on MTBI Prognosis (ICoMP) provided titles of articles that were not found in the search strategy. Using predefined inclusion and exclusion criteria, articles were screened for eligibility. Inclusion criteria were as follows: controlled trials, cohort studies, or case-control studies; published in peer-reviewed journals; written in English, French, Swedish, Norwegian, Danish, or Spanish; and included a minimum of 30 MTBI cases of military personnel that were independent of duty status at the time of injury (ie, active duty, reservist, or veteran). Cross-sectional studies and case reports and series were excluded. In addition, cadaveric studies, biomechanical studies, and laboratory studies were excluded. Systematic reviews and meta-analyses reference lists were checked for relevant studies, but these designs were not included in our review. MTBI was defined using criteria established by the World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury and the U.S. Centers for Disease Control and Prevention. It was defined as follows: (1) 1 or more of the following symptoms: confusion or disorientation, loss of consciousness for 30 minutes or less, posttraumatic amnesia for less than 24 hours, and/or other transient neurological abnormalities such as focal signs, seizure, and intracranial lesion not requiring surgery; and (2) Glasgow Coma Scale score of 13 to 15 thirty minutes postinjury or later on presentation for health care. These symptoms of MTBI must not be due to drugs, alcohol, or medications; caused by other injuries or treatment for other injuries (eg, systemic injuries, facial injuries, or intubation); caused by other problems (eg, psychological trauma, language barrier, or coexisting medical conditions); or caused by penetrating craniocerebral injury.21 Persons with fractured skulls were included if they fit this case definition. The causal agent could not be bullet(s) and/or fragment(s) because this may have resulted in a penetrating brain injury. The Centers for Disease Control and Prevention provides an additional definition based on clinical records data. MTBI is recognized if an Abbreviated Injury Severity scale score of 2 for the head region is documented.7 An administrative data definition for surveillance or research is also provided. Specifically, cases of MTBI are recognized among persons who are assigned certain International Classification of Diseases, Ninth Revision, Clinical Modification, diagnostic codes.20 Two reviewers independently appraised each study using a modification of the Scottish Intercollegiate Guidelines Network criteria.22 A third reviewer was consulted if any disagreements arose between the 2 reviewers. Data from the accepted articles were extracted by 2 reviewers independently and placed into evidence tables (table 1). The evidence on prognostic factors was categorized into phases on the basis of study designs as described by Coˆte´ et al.23 Phase I studies are hypothesis-generating
S232 investigations that explore the associations between potential prognostic factors and disease outcomes in a descriptive or univariate way. Phase II studies are extensive exploratory analyses that focus on particular sets of prognostic factors or attempt to discover which factors have the highest prognostic value. Last, phase III studies are large confirmatory studies of explicit prestated hypotheses that allow for a focused examination of the strength, direction, and independence of the proposed relation between a prognostic factor and the outcome of interest. Information from accepted phase III studies is considered the strongest evidence for a prognostic factor, followed by evidence from accepted phase II studies. Phase I studies do not consider confounding factors and are considered more limited evidence.
Results After applying the inclusion and exclusion criteria to 77,914 titles and abstracts for our entire review, 69 full-text articles related to TBI in the military were screened and 13 deemed eligible for review. Of these, only 3 (23%) were found to be at low risk of bias, as determined by modified Scottish Intercollegiate Guidelines Network criteria, and these form the basis of our findings. All 3 are retrospective cohort studies that involve U.S. military personnel who were deployed in either Iraq or Afghanistan (2 phase III24,25 and 1 phase II26; see table 1). These studies came from 2 different military health facilities within the state of Texas. Two studies24,26 examined the type of symptoms military personnel may experience after an MTBI. Kennedy et al26 found that military personnel who only had blast-related MTBI, and did not sustain concurrent injuries, presented with significantly more postconcussive symptoms, as measured on the Neurobehavioural Symptom Inventory, than did military personnel who had blast-related MTBI and another Abbreviated Injury Severity scaleecoded concurrent injury. The assessment occurred, on average, 13 weeks postinjury for both groups. Furthermore, the “blast-related only MTBI” group had significantly higher severity scores in each of the 4 domains of the Neurobehavioural Symptom Inventory, with the sensory domain having an average score 1.6 times higher than that of the other group. Specifically, those with sensitivity to light and noise, headache, and sleep problems had significantly higher scores in the sensory domain. Kennedy et al also examined the difference between these 2 groups at about 13 weeks postinjury with respect to posttraumatic stress symptoms as measured by the Posttraumatic Stress Disorder Check ListeCivilian (PCL-C). On average, the blast-related only MTBI group reported significantly more symptoms than did those who had blast-related MTBI and concurrent injuries. In addition, scores on the 3 domains of the PCL-C were significantly higher in those who had blast-related only MTBI. The 2 groups were similar regarding the length of time since injury, rank, branch of military, loss of consciousness, and alteration of consciousness, but differed on age, with those having blast-related only MTBI being older. After adjusting for age, the blast-related only MTBI group remained significantly higher on postconcussive symptoms and posttraumatic stress than did the blast-related MTBI and concurrent injuries group. Cooper et al24 examined postconcussive symptoms in a cohort of military personnel who experienced MTBI. The authors divided the MTBI cohort into 2 groups on the basis of their posttraumatic stress, as scored on the PCL-C. They hypothesized that the coexistence of stress would have an impact on postconcussive symptoms. The “high combat stress” group scored 60 or more on the PCL-C, and the “low combat stress” group scored 30 or less on the PCL-C. MTBI
E. Boyle et al cohort members who scored between 31 and 59 points were excluded from the analysis. The 2 groups differed on sex, rank, and time since MTBI. The low combat stress group was examined on average 4 months postinjury, and the high combat stress group was examined on average 7 months postinjury. The authors controlled for these characteristics using multivariable analysis and found that the high combat stress group reported significantly more postconcussive symptoms, as measured by the Neurobehavioural Symptom Inventory, than did the low combat stress group. The average scores on the 4 domains were 3 to 5 times higher in the high combat stress group. Overall, the low combat stress group reported few postconcussive symptoms, and their most prevalent symptoms were sleep disturbances, headache, and memory problems. The final article examined neurocognitive performance in military personnel who had a blast-related MTBI or other blast-related injury.25 The authors hypothesized that psychiatric comorbidity (in particular, PTSD) would be more highly associated with cognitive performance than with having an MTBI. They also hypothesized that narcotic pain medication usage would be more associated with cognitive performance. Cognitive performance was measured with the Repeatable Battery for the Assessment of Neuropsychological Status, which consists of 5 domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. The authors used information from medical records to define the presence/absence of psychiatric comorbid and narcotic pain medication usage. The MTBI group had significantly more women and significantly more military personnel who had a psychiatricrelated comorbidity. The groups did not differ with regard to age, education, weeks since blast injury, total body surface area burned, injury severity score, and the usage of narcotic pain medication. Overall, the MTBI group had significantly lower unadjusted total cognitive function scores than did the non-MTBI group, but on average, the scores were within the normal range. Specifically, the MTBI group had significantly lower unadjusted scores in the visuospatial/constructional and attention domains. The authors found that both psychiatric-related comorbidity and narcotic pain medication usage explained little of the variance in the difference between the 2 groups for the attention domain of the Repeatable Battery for the Assessment of Neuropsychological Status.
Discussion This systematic review of the prognosis of military personnel who had an MTBI identified 3 articles with a low risk of bias that were published between 2001 and February 2012. Two of the studies examined symptoms, and 1 study examined cognitive functioning after having an MTBI during deployment. There was an increased association of PTSD and having postconcussive symptoms after an MTBI if the service member did not have a concurrent injury.26 PTSD, depression, substance abuse, and chronic pain can exhibit similar symptoms as someone with postconcussive symptoms. Therefore, 1 phase III study stratified on combat stress and found that those who were classified with “high stress” had more postconcussive symptoms than did service members with “low stress.”24 They also found that having an MTBI was associated with a decline in neurocognitive function; however, the authors were unable to confirm their hypotheses that neurocognitive decline could be explained by either coexisting psychiatric conditions or use of narcotic pain medication(s).25 To put these findings into perspective, it should be noted that PTSD is common in military personnel. An American www.archives-pmr.org
Evidence table
Author, Year, and Country
Source Population, Study Size, Participation, Follow-Up
Inclusion/Exclusion Criteria
MTBI Case Definition
Cohort studies Phase III studies Consecutive admissions of OIF and Inclusion: Age at least 18y, English LOC3 OIF following: LOC
REVIEW ARTICLE
Systematic Review of Prognosis After Mild Traumatic Brain Injury in the Military: Results of the International Collaboration on Mild Traumatic Brain Injury Prognosis Eleanor Boyle, PhD,a,b Carol Cancelliere, DC, MPH,c,d Jan Hartvigsen, PhD,a Linda J. Carroll, PhD,e Lena W. Holm, DrMedSc,f J. David Cassidy, PhD, DrMedSca,b,c,d From the aInstitute of Sports Science and Clinical Biomechanics, Faculty of Health, University of Southern Denmark, Odense, Denmark; b Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; cDivision of Health Care and Outcomes Research, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada; d Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; eSchool of Public Health and Alberta Centre for Injury Control and Research, University of Alberta, Edmonton, Alberta, Canada; and fDivision of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Abstract Objective: The World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury (MTBI) published its findings on the prognosis of MTBI in 2004. This is an update of that review with a focus on deployed military personnel. Data Sources: Relevant literature published between January 2001 and February 2012 listed in MEDLINE and 4 other databases. Study Selection: Controlled trials and cohort and case-control studies were selected according to predefined criteria. After 77,914 titles and abstracts were screened, 13 articles were rated eligible for this review and 3 (23%) with a low risk of bias were accepted. Two independent reviewers critically appraised eligible studies using a modification of the Scottish Intercollegiate Guidelines Network criteria. Data Extraction: The reviewers independently extracted data from eligible studies and produced evidence tables. Data Synthesis: The evidence was synthesized qualitatively and presented in evidence tables. Our findings are based on 3 studies of U.S. military personnel who were deployed in Iraq or Afghanistan. We found that military personnel with MTBI report posttraumatic stress disorder and postconcussive symptoms. In addition, reporting of postconcussive symptoms differed on the basis of levels of combat stress the individuals experienced. The evidence suggests a slight decline in neurocognitive function after MTBI, but this decline was in the normal range of brain functioning. Conclusions: We found limited evidence that combat stress, posttraumatic stress disorder, and postconcussive symptoms affect recovery and prognosis of MTBI in military personnel. Additional high-quality research is needed to fully assess the prognosis of MTBI in military personnel. Archives of Physical Medicine and Rehabilitation 2014;95(3 Suppl 2):S230-7 ª 2014 by the American Congress of Rehabilitation Medicine
Injuries sustained in combat today differ from the injuries sustained in previous wars.1,2 The proportion of head and neck wounds has doubled from the Vietnam War, whereas thoracic and Supported by the Ontario Neurotrauma Foundation (grant reference 2010-ABI-MTBIWHO871). The funder was involved neither in the design or preparation of the study protocol nor in the management of the project, analysis or interpretation of data, or the preparation of the final article. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. The findings and conclusions in this research are those of the authors alone and do not necessarily represent the official views or policies of the Centers for Disease Control and Prevention or any agency of the United States government. Inclusion of individuals, programs, or organizations in this article does not constitute endorsement by the United States government.
abdominal injuries have declined.3 This change can be explained by various factors including the use of body armor and Kevlar helmets, which have reduced life-threatening injuries to the head, chest, and abdomen. Also, advances in in-theater medical care have reduced the killed-wounded ratio to less than 1 in 10.4 Furthermore, the use of mine-resistant ambush-protected vehicles that diminish the effects of improvised explosive devices has resulted in a reduction in fatalities from roadside explosives.3 Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are being referred to as the “signature” injuries in the current U.S. conflicts.5 One of the most common causal agents for injuries is exposure to blasts, which can result in TBIs with
0003-9993/14/$36 - see front matter ª 2014 by the American Congress of Rehabilitation Medicine http://dx.doi.org/10.1016/j.apmr.2013.08.297
Review of prognosis after mild TBI in the military different degrees of severity.6 Based on the mechanism by which blast-related injuries are produced, these are classified into 4 groups.7,8 A primary blast injury occurs when the injury is sustained from the explosive materials. A secondary blast injury results from being hit by matter thrown by the explosion or by the fragments of the weapon casing. A tertiary blast injury is the result of the individual’s being thrown by the explosive blast and hitting another object such as a wall or the ground. Last, a quaternary blast injury can occur from burns, toxic fumes, and other causes not covered in the previous 3 definitions. It has been estimated that 60% to 80% of the military personnel who are exposed to a blast acquire a TBI.5,9 From 2000 to the first quarter of 2012, 244,217 cases of TBIs were reported among U.S. military personnel by the Defense Medical Surveillance System and the Theater Medical Data Store.10 Slightly over 75% of the TBIs were classified as mild, and only 1.6% were penetrating head injuries. Approximately 58% of these injuries occurred in U.S. Army personnel, and the remaining injuries occurred evenly in the Navy, Marines, and Air Force. According to the Defense Medical Surveillance System, the incidence rate of mild traumatic brain injury (MTBI) between 1997 and 2007 in the U.S. military was approximately 6.6 per 1000 person-years.11 This incidence rate significantly varies by age groups (younger have higher rates), sex (men higher than women), race (white higher than other races), rank (enlisted higher than officer), and branch of service (Army and Marines higher than other branches). The cost of care for TBI in the U.S. military population has risen from $21 million in 2003 to approximately $646 million in 2010.12 The majority of the prognostic research in MTBI has been conducted in the civilian population. For example, the World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury published the first systematic review on MTBI prognosis in 2004. It accepted only 1 article involving a military population.13 In that study, conducted 1 year after the Gulf War, the authors found a 1.8 times greater risk of a behavioral-related discharge in military personnel who had an MTBI than in persons who were discharged without a brain injury.14 The majority of the head injuries in that study were related to falls (31.8%) and motor vehicle collisions (30.4%); these mechanisms are similar to those seen in civilian injuries. It is unclear whether these results of the study would be generalizable to MTBIs that occurred in-theater.15 There are inherent differences in the combat military population and civilian population.2 Depending on the country, military personnel might have been evaluated with predeployment health screens and physical fitness standards. All military personnel are employed at the time of injury, which may not be true in the civilian population. The prevalence of MTBI is higher in the military population than in civilian populations living in noncombat zones, and in particular, blast TBIs are higher.16 Depending on the length of deployment and the probability of being exposed to improvised explosive devices, there is a greater chance that military personnel may experience repeated TBIs.17 Last, standardized triage and care is provided to military personnel throughout the recovery period.18
List of abbreviations: ICoMP MTBI PCL-C PTSD TBI
International Collaboration on MTBI Prognosis mild traumatic brain injury Posttraumatic Stress Disorder Check ListeCivilian posttraumatic stress disorder traumatic brain injury
www.archives-pmr.org
S231 In the present study, we aimed to update and expand on the original World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury on the prognosis of MTBI by focusing solely on the military population. The specific objective of this study was to synthesize the best available evidence on the course and prognosis of MTBI in the military population.
Methods The literature search and synthesis strategy has been outlined in detail elsewhere and in this issue.19,20 In brief, using a detailed search strategy, MEDLINE, PsycINFO, Embase, CINAHL, and SPORTDiscus were searched from January 1, 2001, to February 10, 2012. In addition, the reference lists of eligible articles were screened for potentially relevant articles and members of the International Collaboration on MTBI Prognosis (ICoMP) provided titles of articles that were not found in the search strategy. Using predefined inclusion and exclusion criteria, articles were screened for eligibility. Inclusion criteria were as follows: controlled trials, cohort studies, or case-control studies; published in peer-reviewed journals; written in English, French, Swedish, Norwegian, Danish, or Spanish; and included a minimum of 30 MTBI cases of military personnel that were independent of duty status at the time of injury (ie, active duty, reservist, or veteran). Cross-sectional studies and case reports and series were excluded. In addition, cadaveric studies, biomechanical studies, and laboratory studies were excluded. Systematic reviews and meta-analyses reference lists were checked for relevant studies, but these designs were not included in our review. MTBI was defined using criteria established by the World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury and the U.S. Centers for Disease Control and Prevention. It was defined as follows: (1) 1 or more of the following symptoms: confusion or disorientation, loss of consciousness for 30 minutes or less, posttraumatic amnesia for less than 24 hours, and/or other transient neurological abnormalities such as focal signs, seizure, and intracranial lesion not requiring surgery; and (2) Glasgow Coma Scale score of 13 to 15 thirty minutes postinjury or later on presentation for health care. These symptoms of MTBI must not be due to drugs, alcohol, or medications; caused by other injuries or treatment for other injuries (eg, systemic injuries, facial injuries, or intubation); caused by other problems (eg, psychological trauma, language barrier, or coexisting medical conditions); or caused by penetrating craniocerebral injury.21 Persons with fractured skulls were included if they fit this case definition. The causal agent could not be bullet(s) and/or fragment(s) because this may have resulted in a penetrating brain injury. The Centers for Disease Control and Prevention provides an additional definition based on clinical records data. MTBI is recognized if an Abbreviated Injury Severity scale score of 2 for the head region is documented.7 An administrative data definition for surveillance or research is also provided. Specifically, cases of MTBI are recognized among persons who are assigned certain International Classification of Diseases, Ninth Revision, Clinical Modification, diagnostic codes.20 Two reviewers independently appraised each study using a modification of the Scottish Intercollegiate Guidelines Network criteria.22 A third reviewer was consulted if any disagreements arose between the 2 reviewers. Data from the accepted articles were extracted by 2 reviewers independently and placed into evidence tables (table 1). The evidence on prognostic factors was categorized into phases on the basis of study designs as described by Coˆte´ et al.23 Phase I studies are hypothesis-generating
S232 investigations that explore the associations between potential prognostic factors and disease outcomes in a descriptive or univariate way. Phase II studies are extensive exploratory analyses that focus on particular sets of prognostic factors or attempt to discover which factors have the highest prognostic value. Last, phase III studies are large confirmatory studies of explicit prestated hypotheses that allow for a focused examination of the strength, direction, and independence of the proposed relation between a prognostic factor and the outcome of interest. Information from accepted phase III studies is considered the strongest evidence for a prognostic factor, followed by evidence from accepted phase II studies. Phase I studies do not consider confounding factors and are considered more limited evidence.
Results After applying the inclusion and exclusion criteria to 77,914 titles and abstracts for our entire review, 69 full-text articles related to TBI in the military were screened and 13 deemed eligible for review. Of these, only 3 (23%) were found to be at low risk of bias, as determined by modified Scottish Intercollegiate Guidelines Network criteria, and these form the basis of our findings. All 3 are retrospective cohort studies that involve U.S. military personnel who were deployed in either Iraq or Afghanistan (2 phase III24,25 and 1 phase II26; see table 1). These studies came from 2 different military health facilities within the state of Texas. Two studies24,26 examined the type of symptoms military personnel may experience after an MTBI. Kennedy et al26 found that military personnel who only had blast-related MTBI, and did not sustain concurrent injuries, presented with significantly more postconcussive symptoms, as measured on the Neurobehavioural Symptom Inventory, than did military personnel who had blast-related MTBI and another Abbreviated Injury Severity scaleecoded concurrent injury. The assessment occurred, on average, 13 weeks postinjury for both groups. Furthermore, the “blast-related only MTBI” group had significantly higher severity scores in each of the 4 domains of the Neurobehavioural Symptom Inventory, with the sensory domain having an average score 1.6 times higher than that of the other group. Specifically, those with sensitivity to light and noise, headache, and sleep problems had significantly higher scores in the sensory domain. Kennedy et al also examined the difference between these 2 groups at about 13 weeks postinjury with respect to posttraumatic stress symptoms as measured by the Posttraumatic Stress Disorder Check ListeCivilian (PCL-C). On average, the blast-related only MTBI group reported significantly more symptoms than did those who had blast-related MTBI and concurrent injuries. In addition, scores on the 3 domains of the PCL-C were significantly higher in those who had blast-related only MTBI. The 2 groups were similar regarding the length of time since injury, rank, branch of military, loss of consciousness, and alteration of consciousness, but differed on age, with those having blast-related only MTBI being older. After adjusting for age, the blast-related only MTBI group remained significantly higher on postconcussive symptoms and posttraumatic stress than did the blast-related MTBI and concurrent injuries group. Cooper et al24 examined postconcussive symptoms in a cohort of military personnel who experienced MTBI. The authors divided the MTBI cohort into 2 groups on the basis of their posttraumatic stress, as scored on the PCL-C. They hypothesized that the coexistence of stress would have an impact on postconcussive symptoms. The “high combat stress” group scored 60 or more on the PCL-C, and the “low combat stress” group scored 30 or less on the PCL-C. MTBI
E. Boyle et al cohort members who scored between 31 and 59 points were excluded from the analysis. The 2 groups differed on sex, rank, and time since MTBI. The low combat stress group was examined on average 4 months postinjury, and the high combat stress group was examined on average 7 months postinjury. The authors controlled for these characteristics using multivariable analysis and found that the high combat stress group reported significantly more postconcussive symptoms, as measured by the Neurobehavioural Symptom Inventory, than did the low combat stress group. The average scores on the 4 domains were 3 to 5 times higher in the high combat stress group. Overall, the low combat stress group reported few postconcussive symptoms, and their most prevalent symptoms were sleep disturbances, headache, and memory problems. The final article examined neurocognitive performance in military personnel who had a blast-related MTBI or other blast-related injury.25 The authors hypothesized that psychiatric comorbidity (in particular, PTSD) would be more highly associated with cognitive performance than with having an MTBI. They also hypothesized that narcotic pain medication usage would be more associated with cognitive performance. Cognitive performance was measured with the Repeatable Battery for the Assessment of Neuropsychological Status, which consists of 5 domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. The authors used information from medical records to define the presence/absence of psychiatric comorbid and narcotic pain medication usage. The MTBI group had significantly more women and significantly more military personnel who had a psychiatricrelated comorbidity. The groups did not differ with regard to age, education, weeks since blast injury, total body surface area burned, injury severity score, and the usage of narcotic pain medication. Overall, the MTBI group had significantly lower unadjusted total cognitive function scores than did the non-MTBI group, but on average, the scores were within the normal range. Specifically, the MTBI group had significantly lower unadjusted scores in the visuospatial/constructional and attention domains. The authors found that both psychiatric-related comorbidity and narcotic pain medication usage explained little of the variance in the difference between the 2 groups for the attention domain of the Repeatable Battery for the Assessment of Neuropsychological Status.
Discussion This systematic review of the prognosis of military personnel who had an MTBI identified 3 articles with a low risk of bias that were published between 2001 and February 2012. Two of the studies examined symptoms, and 1 study examined cognitive functioning after having an MTBI during deployment. There was an increased association of PTSD and having postconcussive symptoms after an MTBI if the service member did not have a concurrent injury.26 PTSD, depression, substance abuse, and chronic pain can exhibit similar symptoms as someone with postconcussive symptoms. Therefore, 1 phase III study stratified on combat stress and found that those who were classified with “high stress” had more postconcussive symptoms than did service members with “low stress.”24 They also found that having an MTBI was associated with a decline in neurocognitive function; however, the authors were unable to confirm their hypotheses that neurocognitive decline could be explained by either coexisting psychiatric conditions or use of narcotic pain medication(s).25 To put these findings into perspective, it should be noted that PTSD is common in military personnel. An American www.archives-pmr.org
Evidence table
Author, Year, and Country
Source Population, Study Size, Participation, Follow-Up
Inclusion/Exclusion Criteria
MTBI Case Definition
Cohort studies Phase III studies Consecutive admissions of OIF and Inclusion: Age at least 18y, English LOC3 OIF following: LOC
