Neuroimaging and advanced research techniques may lead to improved outcomes in military members suffering from traumatic brain injury

Recent military conflicts in Iraq and Afghanistan have resulted in the significant increase in blast-related traumatic brain injury (TBI), leading to increased Department of Defense interest in its potential long-term effects ranging from the mildest head injuries termed subconcussive trauma to the most debilitating termed chronic traumatic encephalopathy (CTE). Most patients with mild TBI will recover quickly while others report persistent symptoms called postconcussive syndrome. Repeated concussive and subconcussive head injuries result in neurodegenerative conditions that may hinder the injured for years. Fundamental questions about the nature of these injuries and recovery remain unanswered. Clinically, patients with CTE present with either affective changes or cognitive impairment. Genetically, there have been no clear risk factors identified. The discovery that microglia of the cerebral cortex discharged small extracellular vesicles in the injured and adjacent regions to a TBI may soon shed light on the immediate impact injury mechanisms. The combination of neuroimaging and advanced research techniques may, one day, fill critical knowledge gaps and lead to significant TBI research and treatment advancements.

Fluid Biomarkers for Chronic Traumatic Encephalopathy

Chronic traumatic encephalopathy (CTE) is a neuropathological condition that has been described in individuals who have been exposed to repetitive head impacts, including concussions and subconcussive trauma. Currently, there is no fluid or imaging biomarker for diagnosing CTE during life. Based on retrospective clinical data, symptoms of CTE include changes in behavior, cognition, and mood, and may develop after a latency phase following the injuries. However, these symptoms are often nonspecific, making differential diagnosis based solely on clinical symptoms unreliable. Thus, objective biomarkers for CTE pathophysiology would be helpful in understanding the course of the disease as well as in the development of preventive and therapeutic measures. Herein, we review the literature regarding fluid biomarkers for repetitive concussive and subconcussive head trauma, postconcussive syndrome, as well as potential candidate biomarkers for CTE. We also discuss technical challenges with regard to the current fluid biomarkers and potential pathways to advance the most promising biomarker candidates into clinical routine.

Exosomal neurofilament light

ObjectiveTo measure exosomal and plasma levels of candidate blood biomarkers in veterans with history of mild traumatic brain injury (mTBI) and test their relationship with chronic symptoms.MethodsExosomal and plasma levels of neurofilament light (NfL) chain, tumor necrosis factor (TNF)–α, interleukin (IL)–6, IL-10, and vascular endothelial growth factor (VEGF) were measured using an ultrasensitive assay in a cohort of 195 veterans, enrolled in the Chronic Effects of Neurotrauma Consortium Longitudinal Study. We examined relationships between candidate biomarkers and symptoms of postconcussive syndrome (PCS), posttraumatic stress disorder (PTSD), and depression. Biomarker levels were compared among those with no traumatic brain injury (TBI) (controls), 1–2 mTBIs, and repetitive (3 or more) mTBIs.ResultsElevated exosomal and plasma levels of NfL were associated with repetitive mTBIs and with chronic PCS, PTSD, and depression symptoms. Plasma TNF-α levels correlated with PCS and PTSD symptoms. The total number of mTBIs correlated with exosomal and plasma NfL levels and plasma IL-6. Increased number of years since the most recent TBI correlated with higher exosomal NfL and lower plasma IL-6 levels, while increased number of years since first TBI correlated with higher levels of exosomal and plasma NfL, as well as plasma TNF-α and VEGF.ConclusionRepetitive mTBIs are associated with elevated exosomal and plasma levels of NfL, even years following these injuries, with the greatest elevations in those with chronic PCS, PTSD, and depression symptoms. Our results suggest a possible neuroinflammatory and axonal disruptive basis for symptoms that persist years after mTBI, especially repetitive.

Interaction Between Psychiatric Symptoms and History of Mild TBI When Evaluating Postconcussion Syndrome in Veterans

Introduction: Symptoms of postconcussive syndrome (PCS) after mild TBI (mTBI) have been shown to resolve quickly, yet new research raises questions about possible long-term effects of this condition. It is not clear how best to address assessment and treatment when someone reports lingering symptoms of PCS. One self-report measure used by the VA and the DoD is the Neurobehavioral Symptom Inventory (NSI), but this measure may be affected by underlying psychiatric symptoms. We investigated whether the NSI is sensitive to mTBI after considering a number of psychiatric and demographic factors. Methods: This study examined which factors are associated with NSI scores in a Veteran sample (n = 741) that had recently returned from deployment. Results: Post-traumatic stress disorder (PTSD) and depression accounted for most of the variance on the NSI. Although history of mTBI was initially related to NSI, this association was no longer significant after other covariates were considered. Conclusions: The NSI score was primarily explained by symptoms of PTSD and depression, suggesting that the NSI is not specific to the experience of a brain injury. We recommend cautious interpretation when this measure is used in the chronic phase after mTBI, especially among patients with comorbid depression or PTSD.

PTSD and Traumatic Brain Injury

One of the more hotly debated issues in the field of post-traumatic stress disorder (PTSD) is the role of traumatic brain injury (TBI), and particularly mild traumatic brain injury (mTBI). This topic became increasingly the focus of attention in the context of recent wars in Iraq and Afghanistan, where many troops suffered PTSD and mTBIs. Over three-quarters of injuries sustained in these conflicts arose from encounters with explosive devices, and accordingly it was often claimed that the “signature injuries” of the wars in Iraq and Afghanistan were both PTSD and mTBI. Clinicians and researchers have thus given renewed attention to the interplay of these two conditions. This chapter reviews definitional issues of PTSD and mTBI, how PTSD can develop after mTBI, the impact mTBI may have on stress responses, the distinctive role of postconcussive syndrome, and how to manage PTSD following mTBI.