Traumatic Brain Injury and the Need for Accurate Biomarkers

Overview of Traumatic Brain Injury

Each year, approximately 3.5 million Americans seek medical care for traumatic brain injuries (TBI). Despite the prevalence of these injuries, advancements in therapeutic options are hampered by a lack of precise biomarkers that could enhance the diagnosis and classification of TBIs.

Understanding Biomarkers

A biomarker is defined as a biological indicator that can be quantified and utilized to assess physical health. An example of this is blood pressure, which serves as a biomarker for stroke risk. Biomarkers can also encompass various chemicals or proteins found in blood, cerebrospinal fluid, or other bodily organs. Effective biomarkers allow healthcare professionals to accurately differentiate between patients with a disease and those without, playing a crucial role in the advancement of medical treatments and drug therapies. In the context of TBI, the absence of reliable biomarkers has significantly restricted treatment development.

Current Diagnostic Methods for TBI

Traditionally, TBIs have been diagnosed and classified using neurological assessment tools, such as the Glasgow Coma Scale, or through neuroimaging methods like computed tomography (CT) scans and magnetic resonance imaging (MRIs). However, these methods have notable limitations, including the tendency to overestimate injury severity and difficulty in isolating confounding factors like the presence of alcohol or drugs. Notably, 90% of TBIs fall into the mild to moderate categories, where these diagnostic techniques are least effective.

Potential of Biomarkers in TBI Diagnosis

Research on Plasma Biomarkers

Recent research published in JAMA Neurology explored the efficacy of three plasma biomarkers for accurately distinguishing between acute mild and chronic TBI. The biomarkers investigated were:
– Hypophosphorylated tau protein (P-tau)
– Total tau (T-tau) protein
– The ratio of P-tau to T-tau

Between April 2010 and June 2012, plasma samples were collected from 196 patients admitted to three level 1 trauma centers within 24 hours of their injury. Additionally, 21 patients with TBI who were admitted to rehabilitation units within six months of their injury were included in the study. Of the 217 TBI patients, around 74% were men, with a mean age of 42.5 years. For comparative analysis, plasma samples were also obtained from healthy individuals of similar age and sex. The samples were analyzed for P-tau and T-tau levels using advanced immunoassay techniques.

Findings from the Study

The study revealed that plasma samples from patients with chronic TBI exhibited elevated P-tau levels and significantly higher P-tau to T-tau ratios compared to healthy controls. Furthermore, both P-tau levels and the P-tau to T-tau ratios more effectively distinguished patients with chronic TBI and those with poor outcomes than T-tau levels alone.

Currently, no clinical methods exist for accurately assessing the severity of injury and potential outcomes in TBI patients, particularly in cases of mild TBI, where symptoms can be subtle.

Importance of Further Research

Understanding the relationship between measurable biological proteins, such as P-tau and T-tau, is crucial for enhancing treatment options for traumatic brain injury. However, when considering the implementation of these biomarkers in clinical settings, it will be important to evaluate the costs associated with blood biomarker analysis in comparison to traditional methods like CT scans or structural MRIs.

Reference

Rubenstein, R., Chang, B., Yue, J. K., Chiu, A., Winkler, E. A., Puccio, A. M., … & Gordon, W. A. “Comparing plasma phospho tau, total tau, and phospho tau–total tau ratio as acute and chronic traumatic brain injury biomarkers.” JAMA Neurology. 2016 July 24. doi:10.1001/jamaneurol.2017.0655