Mild traumatic brain injury and its long-term consequences

It is currently being debated as to whether mild traumatic brain injury has enduring consequences in terms of post-concussion symptoms in the military. ^{Reference Hoge, Goldberg and Castro8} The case that mild traumatic brain injury may lead to long-term disability was recently made by a study that used diffusion tensor imaging and found an association between blast-related mild traumatic brain injury and imaging abnormalities which persist in some individuals. ^{Reference MacDonald, Johnson, Cooper, Nelson, Werner and Shimony9} However, these researchers did not relate their finding to post-concussion symptoms and the studied group represented a highly selected sample of personnel with mild traumatic brain injury who were evacuated to Germany, while the great majority was not. ^{Reference Hoge and Castro10} Structural and functional studies have not clearly established causality with persistent post-concussion symptoms. ^{Reference Lange, Iverson and Rose7} The consequences of mild traumatic brain injury during deployment have been particularly difficult to study so far because the symptoms associated with mild traumatic brain injury as a result of a blast are usually reported many months after the event, so are subject to reporting bias. In addition, post-concussion symptoms are non-specific, ^{Reference Hoge, McGurk, Thomas, Cox, Engel and Castro4,Reference Rona, Jones, Fear, Hull, Murphy and Machell5,Reference Hoge, Goldberg and Castro8} many of the symptoms are common to depression, PTSD and other conditions, and people who report non-specific post-concussion symptoms also report an excess of other physical symptoms. ^{Reference Hoge, McGurk, Thomas, Cox, Engel and Castro4,Reference Rona, Jones, Fear, Hull, Murphy and Machell5} In contrast to studies in athletes in which the presence of trained healthcare staff during sports events can ensure reliable information on mild traumatic brain injury, ^{Reference McCrea11} epidemiological studies of deployed personnel rely on self-report of injury events. The level of reliability of these reports is uncertain, as shown in a longitudinal study in which mild traumatic brain injury had a prevalence of 9% when assessed a month before the end of deployment, but 22% a year after returning from deployment in the same personnel. ^{Reference Polusny, Kehle, Nelson, Erbes, Arbisi and Thuras12} The great majority of self-reported cases of mild traumatic brain injury do not access medical services soon after the event, which further increases the level of uncertainty.

Analytical approaches to the debate so far

The statistical strategy to assess post-concussion symptoms following mild traumatic brain injury in military studies has been to compare each non-specific concussion symptom in mild traumatic brain injury cases and in controls (who had injuries but not mild traumatic brain injury) and adjust for concomitant PTSD, other physical symptoms and depression. ^{Reference Hoge, McGurk, Thomas, Cox, Engel and Castro4,Reference Rona, Jones, Fear, Hull, Murphy and Machell5} Some studies have used, as controls, individuals without mild traumatic brain injury but not restricted to those with other injuries. ^{Reference Polusny, Kehle, Nelson, Erbes, Arbisi and Thuras12} Other studies have not adjusted for PTSD, but considered that a greater joint effect of PTSD and mild traumatic brain injury on post-concussion symptoms was sufficient to demonstrate the long-term effect of mild traumatic brain injury. ^{Reference Brenner, Ivins, Schwab, Warden, Nelson and Jaffee13} Most studies, including a longitudinal study, have shown that for most symptoms there is no association between mild traumatic brain injury and post-concussion symptoms after adjustments for PTSD ^{Reference Hoge, McGurk, Thomas, Cox, Engel and Castro4,Reference Polusny, Kehle, Nelson, Erbes, Arbisi and Thuras12} or adjustment for multiple physical symptoms and PTSD. ^{Reference Rona, Jones, Fear, Hull, Murphy and Machell5} However, headaches and dizziness remained associated with mild traumatic brain injury. ^{Reference Hoge, McGurk, Thomas, Cox, Engel and Castro4,Reference Rona, Jones, Fear, Hull, Murphy and Machell5} Brenner and colleagues reported that mild traumatic brain injury and PTSD together are more strongly associated with post-concussion symptoms than either condition separately. ^{Reference Brenner, Ivins, Schwab, Warden, Nelson and Jaffee13} Such results would be expected in a group of individuals with both mild traumatic brain injury and PTSD. Their view would have been more appealing had they shown an interaction between PTSD and mild traumatic brain injury on post-concussion symptoms. On the other hand, one should be aware of the dangers of adjusting for PTSD, as some post-concussion symptoms such as sleeping difficulties, fatigue and lack of concentration are also symptoms of PTSD. This leaves researchers in a dilemma as to whether to disregard these symptoms when assigning individuals to PTSD in the analysis.

New contribution to the debate

Vasterling and colleagues’ article in the current issue of the Journal is to be welcomed because they explore the possible neuropsychological consequences of mild traumatic brain injury rather than a list of non-specific possible symptoms of concussion. ^{Reference Vasterling, Brailey, Proctor, Kane, Heeren and Franz14} They assessed the consequences of mild traumatic brain injury and its interrelation with PTSD and depression using an objective battery of neuropsychological tests in 760 US personnel deployed to Iraq. The battery of measurements included several aspects of memory, sustained attention, aspects of learning and cognitive inhibition, and reaction time. They included measures to assess processing speed, which has been previously found to be diminished in those who had sustained mild traumatic brain injury with or without PTSD. ^{Reference Vasterling, Brailey, Proctor, Kane, Heeren and Franz14} Neuropsychological tests were administered before and after returning from deployment. Thus, the researchers were able to account in the analysis for pre-deployment neuropsychological status and therefore account for the pre-deployment estimate of the neuropsychological outcomes.

The results were that out of the 13 neuropsychological outcomes in the follow-up assessment, mild traumatic brain injury was associated only with visual reproductions (immediate recall), even before adjusting for PTSD or depression, whereas PTSD and depression were associated with several neuropsychological outcomes, including processing speed, even after adjusting for mild traumatic brain injury.

There are some limitations to Vasterling et al's study. ^{Reference Vasterling, Brailey, Proctor, Kane, Heeren and Franz14} The study included as cases of mild traumatic brain injury only individuals with loss of consciousness following blast-related injury. Cases of mild traumatic brain injury with altered mental state but no loss of consciousness may have been included as part of the control group in the analysis. This might reduce the contrast between mild traumatic brain injury and controls. This is important because those who sustained mild traumatic brain injury with altered mental status only are not proper controls and are potentially liable to represent a group with neuropsychological symptoms. The control group comprised anyone without mild traumatic brain injury (loss of consciousness), whereas other studies include in the control group only individuals who suffered injury but not mild traumatic brain injury. This has been considered necessary in studies of mild traumatic brain injury because some of the post-concussion symptoms could be related to injury in the absence of mild traumatic brain injury and would be more appropriate to discount ‘background noise’. Vasterling et al's approach is understandable because it increased the statistical power and had they restricted the analysis to those who reported injury, the study would have been underpowered. However, such a limitation would have increased the chance of finding differences between the two groups and reduced the chance of false negative findings.

The remaining problem in studies of mild traumatic brain injury in deployed populations is that they rely on individuals’ self-reports using a poorly validated tool. Further progress could be achieved if these reports were accredited by trained healthcare staff near to the time of the event. However, this is the counsel of perfection in an operational environment.

Overall, Vasterling and colleagues add to the evidence that mild traumatic brain injury, as reported by military personnel following deployment, has minimal lasting consequences for the majority, even if it can still not exclude such an effect for a small number, admittedly rather fewer than claimed elsewhere. The advice of Vasterling et al is appropriate – healthcare providers should pay attention to symptoms of depression and PTSD in any veterans reporting mild traumatic brain injury. Healthcare staff can also reassure those who report having sustained mild traumatic brain injury in a blast-related event of a good long-term prognosis.