In the first such study to be conducted, Mac Donald et al. assess US military personnel 0–7 days after blast-related concussion in Afghanistan and 6–12 months later in the United States. Military personnel who remain on duty after concussion frequently show poor outcomes, driven largely by impaired mental health.

In the first such study to be conducted, Mac Donald et al. assess US military personnel 0–7 days after blast-related concussion in Afghanistan and 6–12 months later in the United States. Military personnel who remain on duty after concussion frequently show poor outcomes, driven largely by impaired mental health.

## Abstract

High rates of adverse outcomes have been reported following blast-related concussive traumatic brain injury in US military personnel, but the extent to which such adverse outcomes can be predicted acutely after injury is unknown. We performed a prospective, observational study of US military personnel with blast-related concussive traumatic brain injury (n = 38) and controls (n = 34) enrolled between March and September 2012. Importantly all subjects returned to duty and did not require evacuation. Subjects were evaluated acutely 0–7 days after injury at two sites in Afghanistan and again 6–12 months later in the United States. Acute assessments revealed heightened post-concussive, post-traumatic stress, and depressive symptoms along with worse cognitive performance in subjects with traumatic brain injury. At 6–12 months follow-up, 63% of subjects with traumatic brain injury and 20% of controls had moderate overall disability. Subjects with traumatic brain injury showed more severe neurobehavioural, post-traumatic stress and depression symptoms along with more frequent cognitive performance deficits and more substantial headache impairment than control subjects. Logistic regression modelling using only acute measures identified that a diagnosis of traumatic brain injury, older age, and more severe post-traumatic stress symptoms provided a good prediction of later adverse global outcomes (area under the receiver-operating characteristic curve = 0.84). Thus, US military personnel with concussive blast-related traumatic brain injury in Afghanistan who returned to duty still fared quite poorly on many clinical outcome measures 6–12 months after injury. Poor global outcome seems to be largely driven by psychological health measures, age, and traumatic brain injury status. The effects of early interventions and longer term implications of these findings are unknown.

## Introduction

In the US military, it is estimated that ∼20% of the deployed force suffered a head injury (Taniellian and Jaycox, 2008) in the wars in Iraq and Afghanistan. Of these, 83.3% endured a mild, uncomplicated traumatic brain injury (TBI) or concussion (Casscells, 2007; DVBIC, 2013), the long-term impact of which is just beginning to be appreciated. Previous studies have reported that 78% of all combat casualties can be accounted for by explosive mechanisms (Owens et al., 2008) and 88% of all patients referred to second echelon treatment centres for further care were due to blast exposure (Warden, 2006).

Previous work has attempted to understand the sequelae of these blast-related ‘mild’/concussive brain injuries but it has been predominantly limited to later stage evaluations (Verfaellie et al., 2013; Fischer et al., 2014), retrospective review (Galarneau et al., 2008; Cooper et al., 2011; Eskridge et al., 2013; Kontos et al., 2013) or biased towards patients requiring medical evacuation (Mac Donald et al., 2014a, b), which may not be representative of the larger population of concussive TBI patients treated directly in the combat theatre. Few studies have prospectively examined patients acutely in theatre (Luethcke et al., 2011; Coldren et al., 2012; Norris et al., 2013), but none to our knowledge, have completed longitudinal evaluations to elucidate the relationship between acute characteristics and long-term outcomes. The objective of the current study was to clinically assess service members from the point of injury in Afghanistan and follow them to 6–12 month outcome back in the United States to determine if acute clinical measures could be used to predict brain injury sequelae and overall outcome.

## Materials and methods

Participants were initially enrolled at Kandahar Air Field and Camp Leatherneck in Afghanistan between March and September 2012 as part of a prospective, observational, research study. Through this ongoing collaborative effort, a subset of these subjects were also enrolled in a 6–12 month follow-up at Washington University in Saint Louis, Missouri (Principal Investigator: D. Brody). This group was randomly selected from the larger cohort enrolled in Afghanistan from those who consented to participate in a long-term follow-up examination back in the USA. In total, 72 subjects, 34 controls and 38 TBI subjects completed both the initial study in Afghanistan and the follow-up evaluation at Washington University in Saint Louis 6–12 months later. Demographic characteristics were similar but not identical between groups (Table 1). Within each group, there were no significant differences in demographic information comparing those who followed up to those who only completed the initial study (Supplementary Table 1).

Table 1

Participant characteristics

Characteristic Control (n = 34) TBI (n = 38) P-value
Age in years: median (range) 28 (19–44) 26 (20–41) 0.02a
Education in years: median (range) 15 (12–24) 13 (12–18) 0.0003a
Gender no (%)
Male 27 (79%) 36 (95%) 0.05c
Female 7 (21%) 2 (5%)
Race/ethnicity no (%)
White 22 (65%) 29 (77%) 0.28b
African American 5 (15%) 2 (5%)
Hispanic/Latino 7 (20%) 7 (18%)
Asian
Branch of Service no (%)
US Army 13 (38%) 32 (84%) 0.0001b
US Air Force 2 (6%)
US Marine Corps 3 (9%) 6 (16%)
US Navy 16 (47%)
Military Rank no (%)
Enlisted 24 (71%) 35 (92%) 0.018c
Officer 10 (29%) 3 (8%)
Enrolment Site (%)
Kandahar Airfield 31 (91%) 30(79%) 0.15c
Camp Leatherneck 3 (7%) 8 (21%)
Previous Deployments
median (range) 2 (0–7) 2 (0–8) 0.99a
Previous Blast Exposures
median (range) 0 (0–2) 0 (0–6) 0.0031a
Previous Concussions
median (range) N/A 2 (0–11)
Characteristic Control (n = 34) TBI (n = 38) P-value
Age in years: median (range) 28 (19–44) 26 (20–41) 0.02a
Education in years: median (range) 15 (12–24) 13 (12–18) 0.0003a
Gender no (%)
Male 27 (79%) 36 (95%) 0.05c
Female 7 (21%) 2 (5%)
Race/ethnicity no (%)
White 22 (65%) 29 (77%) 0.28b
African American 5 (15%) 2 (5%)
Hispanic/Latino 7 (20%) 7 (18%)
Asian
Branch of Service no (%)
US Army 13 (38%) 32 (84%) 0.0001b
US Air Force 2 (6%)
US Marine Corps 3 (9%) 6 (16%)
US Navy 16 (47%)
Military Rank no (%)
Enlisted 24 (71%) 35 (92%) 0.018c
Officer 10 (29%) 3 (8%)
Enrolment Site (%)
Kandahar Airfield 31 (91%) 30(79%) 0.15c
Camp Leatherneck 3 (7%) 8 (21%)
Previous Deployments
median (range) 2 (0–7) 2 (0–8) 0.99a
Previous Blast Exposures
median (range) 0 (0–2) 0 (0–6) 0.0031a
Previous Concussions
median (range) N/A 2 (0–11)

aMann-Whitney U-test.

bChi-square.

cFisher’s exact test.

### Subjects

Inclusion criteria for the TBI group were as follows: (i) clinical diagnosis of ‘mild’/concussive TBI from a blast exposure within the past 7 days made by a trained, board-certified neurologist or neurosurgeon based on the criteria from the American Congress of Rehabilitation Medicine 1993; (ii) injury from blast exposure within 7 days of enrolment; (iii) US military; (iv) ability to provide informed consent in person; (v) no contraindications to MRI such as retained metallic fragments; (vi) no prior history of moderate to severe TBI based on Department of Defense criteria; and (vii) agreement to communicate by telephone or email and then travel to Washington University in Saint Louis for in-person follow-up. Inclusion criteria for the control group were the same except for a negative assessment for TBI and no history of blast exposure.