Eval, Pathogenesis, Outcome of Subjects with or Suspected Traumatic Brain Injury

National Institute Of Neurological Disorders And Stroke

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Linked publications & trials

Abstract

Each year, at least 1.4 million people sustain TBI, with over 1.1 million treated and released from the emergency department (ED). Approximately 125,000 patients with TBI, typically those more severely injured, experience permanent disability as a result of damage to the brain. On the other hand, mild TBI, accounting for at least 75% of all TBI, results in more subtle functional and cognitive deficits that often go undetected in the acute setting. These patients can experience drastic changes in their quality of life, have difficulties returning to daily activities and may be unable to return to work for weeks or months. It is estimated that mild TBI alone costs the United States more than $17 billon per year in long-term care and lost productivity. Lack of objective criteria for diagnosing TBI presents a significant impediment to developing therapies and improving clinical outcomes. Patients with a history of head injury often receive a screening brain scan using computed tomography (CT) in the ED despite a low sensitivity for detecting mild injury. The objective of this project is to generate natural history data for cohort-based comparisons to serve as the basis for future hypothesis-driven protocols and to contribute to the clinical and physiological understanding of traumatic brain injury (TBI) through the description of manifestations of the injury and the relationship among radiological, hematological, clinical variables and standard functional/cognitive outcome measures. In particular, the use of MRI to identify biomarkers, diagnose acute TBI, and predict outcome is being study. This is a prospective study of subjects with known and suspected non-penetrating acute traumatic brain injury who are enrolled in one of two IRB approved protocols. Subjects presenting to the emergency department or trauma service at participating hospitals with a history of recent head injury were studied during their hospital stay and after discharge using radiological, hematological, clinical and functional/cognitive outcome measures. In addition to patients presenting to our local hospitals for acute care, there was an option to recruit subjects from beyond the local hospitals to be brought to the NIH Clinical Center for a more comprehensive battery of assessments and referral to other studies. Nearly 2000 adult subjects with history of recent head injury with or suspected non-penetrating acute TBI have been enrolled in one of two protocols. Subjects having varying degrees of TBI severity have been recruited from the collaborative programs between NIH and non-NIH hospitals. Approximately 80% of subjects are classified as mild TBI, concussion, or no injury, with approximately one half of subjects enrolled being discharged directly from the emergency department. Subjects were offered the option of coming to the NIH Clinical Center to be imaged at very high fields (7T), imaged with positron emission tomography (PET), and some have been followed for up to 5 years under a collaborative project The project was part of the NIH Uniform Services University - Center for Neuroscience and Regenerative Medicine (CNRM) and supported through the CNRM Acute Studies core. In 2019, support for the core was discontinued, enrollment was halted, and data was cleaned and locked. Work continues to analyze and publish data as part of the NINDS effort and through continued collaboration with CNRM, now renamed to MTBI (https://mtbi2.usuhs.edu). During the past year, we have focused on the following areas: Traumatic microbleeds, a marker of traumatic vascular injury: We have demonstrated the prevalence and persistence of small hemorrhagic lesions: traumatic microbleeds or TMB. They are found in up to 20% of patients with mild TBI we have studied and are suggestive of microvascular injury based on our pathology work. They are predictive of worse outcome. We have demonstrated an association between TMBs and areas of cytotoxic edema, essentially small, stroke-like appearing lesions. Independent of other baseline factors, evidence of cytotoxic edema seen on acute MRI is predictive of persistent deficits at 30-90 days. This past year we published a follow-up study further showing these peri-microbleed areas later progress to vasogenic edema in analogy to stroke. Preliminary analysis of high-resolution imaging data obtained at 7T demonstrate that permanent, chronic injury occurs in the cortex adjacent to injured vasculature. Traumatic meningeal enhancement (TME): We have discovered one of the most common neuroimaging findings after mild TBI is injury to the meninges in the form of a newly formed subdural space evident on post-contrast MRI. Multiple manuscripts have been published. Our largest study of approximately 650 patients is complete the manuscript is currently undergoing revision. To strengthen the work, we added data from four blood-based biomarkers purportedly sensitive and specific for TBI. We have shown that the levels of these markers is tightly coupled to the severity of TME at baseline and largely independent of CT findings in mild TBI patients. A second analysis of the blood marker data is complete and the manuscript at draft stage. Most recently we have discovered anomalously high mobility of water in the areas of TME and a project has been initiated to describe the phenomena. Collaborative science: As part of the Department of Defense CNRM, now renamed to MTBI2, we continue to make data available through direct collaboration, particularly work involving blood-based biomarkers. A collaborative project was funded through MTBI2 to study extracellular vesicles in our acute patient population.