To avoid system errors, if Chrome is your preferred browser, please update to the latest version of Chrome (81 or higher) or use an alternative browser.
Click here to login if you're an NAE Member
Recover Your Account Information
Author: Robert L. Ruff
Mild traumatic brain injury (mTBI), with or without loss of consciousness, is the most frequent form of TBI in US troops serving in Iraq and Afghanistan (Warden 2006). In 2006, as the director of neurology for the Department of Veterans Affairs, I was involved in setting up TBI care networks in Ohio and in mTBI screening for veterans returning from these two wars. The results described here are from a case-controlled study of Afghanistan/Iraq veterans with mTBI treated at the VA Medical Center in Cleveland.
VA Study of mTBI Effects in Veterans
Studies of combat-related mTBI have revealed a high frequency of posttraumatic stress disorder (PTSD), although the diagnosis of PTSD in veterans has not always been causally related to combat mTBI (Hoge et al. 2008). To investigate possible links between the two, we studied the presence of mTBI (revealed by physical examination) and of neurological deficits (revealed by a structured neurological examination) in US veterans of the wars in Iraq and Afghanistan. We also examined the relationship between the number of episodes of combat mTBI and the presence of neurological deficits and PTSD.
One of the challenges at the time was to evaluate people quickly. To achieve this we assembled a protocol consisting of a 50-element neurological examination, a battery of neuropsychological tests (Ruff et al. 2008), a cognition test (the Montreal Cognitive Assessment, MoCA), a quantitative olfaction test, and a PTSD symptom severity index (PTSD Checklist–Military Version) (Ruff et al. 2008, 2012a).
There were six study groups of veterans, both military and civilian, based on type of injury: combat-acquired mTBI with loss of consciousness (LOC) (126 subjects); combat mTBI without LOC (52 subjects); combat without TBI (21 subjects); civilian mTBI with LOC (21 subjects); civilian mTBI without LOC (21 subjects); and civilian veterans without TBI (21 subjects).
Link between mTBI and PTSD
We observed the following correlations:
In addition, impaired sleep in servicemembers who have experienced combat mTBI is associated with PTSD, and heightens the likelihood and frequency of both headaches and behavioral and cognitive problems (Ruff et al. 2009, 2012b). Insomnia in persons with mTBI is associated with disruption of hypothalamic-pituitary-adrenal function (Theeler et al. 2013); specifically, pituitary adenylate cyclase-activating peptide (PACAP) and the PACAP receptor may prove to be a link between PTSD and migraine, as PACAP is upregulated by stress and triggers the vasodilation associated with migraine (Theeler et al. 2013).
We continued to study these subjects, typically for 2 or more years, and found that among the 80 veterans who had abnormalities on neurological examination, neuropsychological testing, or both, 37 (46 percent) were married when they left military service. Among them the divorce rate was 86 percent in a narrow window of about 1½ years. This is an impact of enormous personal cost. The biggest problem reported was a personality and behavioral change: their families noted that they looked like the same person, but they were not the same person.
Link between PTSD and Impaired Olfaction
The 126 military veterans who had combat-related mTBI with loss of consciousness had a high frequency of deficits on the neurological exam. These deficits were reduced olfaction (65 subjects; 52 percent), impaired balance (14 subjects), abnormal eye movements (13), motor asymmetry (2), and sensory changes (2). Twenty-nine of these veterans had more than one deficit.
An olfaction deficit was the finding of greatest frequency. Among the 65 veterans with impaired olfaction, this was the only neurological deficit for 36 (55 percent), although most did not entirely lose their sense of smell and in fact were not aware that they had a deficit in olfaction. Hence olfactory tests that evaluate only whether an individual can smell are inadequate.
We found that olfaction deficits correlated with PTSD severity in the group with both mTBI and LOC, and that the likelihood of PTSD increases with the number of LOC episodes. Impaired olfaction with mTBI and loss of consciousness may thus be a biomarker for damage to the olfactory bulb and/or the adjacent ventromedial prefrontal cortex, which inhibits the amygdale. The prefrontal cortex and amygdale have different responses to physical injury. In the prefrontal cortex the dendritic tree becomes pruned, whereas the amygdale architecture becomes more elaborate (Radley et al. 2004; Vyas et al. 2002). The ventromedial prefrontal cortex provides inhibition to the amygdale, and its pruning becomes an operational mechanism for PTSD. The proposal is that an uninhibited or overactive amygdale results in an excessive state of fear and anticipation of fear, thus triggering PTSD (Koenigs et al. 2008; Pitman et al. 2012).
We have previously argued that mTBI, not other factors such as smoking, produced impaired olfaction in combat veterans (Ruff et al. 2012a). It has been determined that PTSD itself does not compromise olfaction (Vermetten et al. 2007), and we found that olfactory impairment did not correlate solely with PTSD severity (Ruff et al. 2012a). We conclude that repeated mTBI episodes with loss of consciousness likely reduced olfaction scores.
Further investigation is needed to determine whether our findings linking PTSD and neurological deficits with episodes of loss of consciousness generalize to other populations of military personnel, and to examine how repeated combat mTBI events are linked to both impaired olfaction and the genesis of PTSD.
Hoge CW, McGurk D, Thomas JL, Cox AL, Engel CC, Castro CA. 2008. Mild traumatic brain injury in US soldiers returning from Iraq. New England Journal of Medicine 358(5):453–463.
Koenigs M, Huey ED, Raymont V, Cheon B, Solomon J, Wassermann E, Grafman J. 2008. Focal brain damage protects against post-traumatic stress disorder in combat veterans. Nature Neuroscience 11(2):232–237.
Pitman RK, Rasmusson AM, Koenen KC, Shin LM, Orr SP, Gilbertson MW, Milad MR, Liberzon I. 2012. Biological studies of post-traumatic stress disorder. Nature Reviews Neuroscience 13(11):769–787.
Radley JJ, Sisti HM, Hao J, Rocher AB, McCall T, Hof PR, McEwen BS, Morrison JH. 2004. Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience 125(1):1–6.
Ruff RL, Ruff SS, Wang X-F. 2008. Headaches among veterans of Operations Iraqi Freedom and Enduring Freedom with mild traumatic brain injury associated with exposures to explosions. Journal of Rehabilitation Research & Development 45:941–953.
Ruff RL, Ruff SS, Wang X-F. 2009. Improving sleep: Initial headache treatment in OIF/OEF veterans with blast-induced mild TBI. Journal of Rehabilitation Research & Development 46(9):1071–1084.
Ruff RL, Riechers RG, Wang X-F, Piero T, Ruff SS. 2012a. A case-control study examining whether neurological deficits and PTSD in combat veterans are related to episodes of mild TBI. BMJ Open 2:e000312.
Ruff RL, Riechers RG, Wang X-F, Piero T, Ruff SS. 2012b. For veterans with mild traumatic brain injury, improved posttraumatic stress disorder severity and sleep correlated with symptomatic improvement. Journal of Rehabilitation Research & Development 49(9):1305–1320.
Theeler BJ, Lucas S, Riechers RG 2nd, Ruff RL. 2013. Post-traumatic headaches in civilians and military personnel: A comparative, clinical review. Headache: Journal of Head and Face Pain 53(6):881–900.
Vermetten E, Schmahl C, Southwick SM, Bremner JD. 2007. Positron tomographic emission study of olfactory induced emotional recall in veterans with and without combat-related posttraumatic stress disorder. Psychopharmacology Bulletin 40(1):8–30.
Vyas A, Mitra R, Shankaranarayana Rao BS, Chattarji S. 2002. Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. Journal of Neuroscience 22(15):6810–6818.
Warden DL. 2006. Military TBI during the Iraq and Afghanistan wars. Journal of Head Trauma Rehabilitation 21:398–402.