The US Department of Defense (DoD) and US Department of Veterans Affairs (VA) have invested millions of dollars toward gaining knowledge about the basic science of traumatic brain injury (TBI) and its effects on service members in order to identify the most effective treatment, as well as its long-term chronic effects. Since my blog on chronic traumatic encephalopathy in April 2015, a new study published by the National Institute of Nursing Research (NINR) shows that ultrahigh-sensitive technology can identify blood biomarkers that are linked to TBI.
Total tau (T-tau or tau) is an abnormal protein that accumulates in the brain and is linked to killing the brain cells associated with memory, emotions and other functions. Tau levels can be detected through the cerebrospinal fluid because this biofluid is in direct contact with the parenchyma (or lining) of the brain. Elevated levels of tau correlate with the severity of the brain damage following TBI.
However, the difficulty in identifying tau concentrations is that central nervous system-derived markers are in extremely low concentration when measured in the blood. The concentrations necessary for a definite diagnosis can only be obtained by lumbar puncture (extraction of cerebrospinal fluid) or posthumously through brain biopsy. These invasive procedures are not suitable to implement in routine evaluations and follow-up of TBI patients. Specifically, those of service members that sustain an injury while still in theatre of operations. Thus, the DoD and VA funding of research have hoped to develop technology that would be able to identify tau biomarkers in the blood.
After a TBI or concussion, the brain needs rest to recover properly. This is especially important because even a mild TBI is in danger of developing chronic or even progressive symptoms if not treated appropriately. The development of tools that can detect injury to the central nervous system, including the brain, in the blood due to TBI and concussions could objectively inform physicians of the severity of the injury, and ultimately charter a course of treatment needed for long-term recovery.
Reports show that nearly 20% of the more than 2.5 million service members deployed since 2003 to Operation Enduring Freedom, Operation Iraqi Freedom and Operation New Dawn have sustained at least one traumatic brain injury. (http://dvbic.dcoe.mil/dod-worldwide-numbers-tbi) The overwhelming majority of TBIs are related to explosive munitions. However, a TBI can be sustained by a service member through other means, such as a fall, blow to the head during training, or an occupational injury to the head. For the veteran to be eligible for compensation benefits the injury must have occurred or sustained during active duty service.
The recent NINR study involved a relatively large number of service members. The participants included 70 service members with mild TBI and 28 deployed control service members with no TBI injuries. The strength in this study is that 86% of participants with mild TBI had samples that were obtained at least 18 months after the last reported brain injury, and thus, mostly reflected the chronic post-concussive state. Most veterans that sustain a brain injury during combat are not afforded, if any, adequate time off duty for the brain to rest. The majority of veterans with a mild or moderate TBI seek help once they return stateside or until their symptoms are not abating. Furthermore, the tau concentrations in service members were correlated with the severity of the self-reported symptoms, providing evidence that the elevated plasma tau concentrations are clinically meaningful. Veterans’ subjective symptoms are oftentimes minimized by VA examiners – frequently labeling them as “malingerers”. Unsympathetic Compensation & Pension examiners go as far as stating in their opinion that the veteran was found to be over reporting and exaggerating their symptoms. This study will assist veterans in supporting their subjective symptoms associated with a TBI despite non-apparent gross structural brain damage. The study also found evidence of increased tau concentration in the blood of service members who had more than three mild TBIs. Most of the veterans returning from Iraq and Afghanistan report mild, but frequent brain injuries. The veterans who sustain a moderate to severe TBI are in obvious distress and are given immediate attention, but not the ones sustaining mild injuries. This is supportive evidence that repetitive mild TBIs can cause long-term effects on veterans returning from war. Tauopathy-related neurodegeneration and dementia is a pressing concern for DoD and VA. Therefore, this study and ongoing investigations funding development of ultrahigh-sensitivity technology will be a game changer for identifying blood biomarkers of mild TBI.