Mild Traumatic Brain Injury Prognosis Research Articles

A Kinetic Model for Blood Biomarker Levels After Mild Traumatic Brain Injury.

Traumatic brain injury (TBI) imposes a significant economic and social burden. The diagnosis and prognosis of mild TBI, also called concussion, is challenging. Concussions are common among contact sport athletes. After a blow to the head, it is often difficult to determine who has had a concussion, who should be withheld from play, if a concussed athlete is ready to return to the field, and which concussed athlete will develop a post-concussion syndrome. Biomarkers can be detected in the cerebrospinal fluid and blood after traumatic brain injury and their levels may have prognostic value. Despite significant investigation, questions remain as to the trajectories of blood biomarker levels over time after mild TBI. Modeling the kinetic behavior of these biomarkers could be informative. We propose a one-compartment kinetic model for S100B, UCH-L1, NF-L, GFAP, and tau biomarker levels after mild TBI based on accepted pharmacokinetic models for oral drug absorption. We approximated model parameters using previously published studies. Since parameter estimates were approximate, we did uncertainty and sensitivity analyses. Using estimated kinetic parameters for each biomarker, we applied the model to an available post-concussion biomarker dataset of UCH-L1, GFAP, tau, and NF-L biomarkers levels. We have demonstrated the feasibility of modeling blood biomarker levels after mild TBI with a one compartment kinetic model. More work is needed to better establish model parameters and to understand the implications of the model for diagnostic use of these blood biomarkers for mild TBI.

Relationship of Circulating CXCR4+ EPC with Prognosis of Mild Traumatic Brain Injury Patients

To investigate the changes of circulating endothelial progenitor cells (EPCs) and stromal cell-derived factor-1α (SDF-1α)/CXCR4 expression in patients with mild traumatic brain injury (TBI) and the correlation between EPC level and the prognosis of mild TBI. 72 TBI patients (57 mild TBI, 15 moderate TBI patients) and 25 healthy subjects (control) were included. The number of circulating EPCs, CD34+, and CD133+ cells and the percentage of CXCR4+ cells in each cell population at 1,4,7,14,21 days after TBI were counted by flow cytometer. SDF-1α levels in serum were detected by ELISA assay. The patients were divided into poor and good prognosis groups based on Extended Glasgow Outcome Scale and Activity of Daily Living Scale at 3 months after TBI. Correlation analysis between each detected index and prognosis of mild TBI was performed. Moderate TBI patients have higher levels of SDF-1α and CXCR4 expression than mild TBI patients (P < 0.05). The percentage of CXCR4+ EPCs at day 7 post-TBI was significantly higher in mild TBI patients with poor prognosis than the ones with good prognosis (P < 0.05). HAMA and HAMD scores in mild TBI patients were significantly lower than moderate TBI patients (P < 0.05) in early term. The percentage of CXCR4+ EPCs at day 7 after TBI was significantly correlated with the prognosis outcome at 3 months. The mobilization of circulating EPCs can be induced in mild TBI. The expression of CXCR4+ in EPCs at 7 days after TBI reflects the short-term prognosis of brain injury, and could be a potential biological marker for prognosis prediction of mild TBI.

Does the cause of the mild traumatic brain injury affect the expectation of persistent postconcussion symptoms and psychological trauma?

ABSTRACTIntroduction: A controlled experiment of the effect of injury cause on expectations of outcome from mild traumatic brain injury (TBI) was conducted. Method: Ninety-three participants were randomly assigned to one of four conditions. The participants read a vignette that described a mild TBI (with fixed injury parameters) from a different cause (sport, domestic assault, fall, or motor vehicle accident). The effect of the manipulation on expectations of persistent postconcussion symptoms and psychological trauma was assessed with standard measures and a novel “threat-to-life” measure. Results: The Kruskal–Wallis H test for group differences revealed a significant but selective effect of group on symptom and trauma outcomes (ŋ2s ≥ .10; large effects). Post hoc pairwise tests showed that, in most cases, there was an expectation of a worse outcome following mild TBI from a domestic assault than from the other causes (small-to-medium effects). Conclusion: Expectations were selectively altered by an experimental manipulation of injury cause. Given that expectations of outcome are known to affect mild TBI prognosis, the findings suggest the need for greater attention to injury cause.

Summary of the findings of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

In 2004, the WHO Collaborating Centre for Neurotrauma, Prevention, Management and Rehabilitation Task Force published the first large systematic review and best evidence synthesis on the clinical course and prognosis for recovery after MTBI. Ten years later, the International Collaboration on Mild Traumatic Brain Injury Prognosis (ICoMP) formed to update the original WHO Task Force results. This summary review highlights important clinical findings from the full ICoMP results including the current evidence on the course and prognosis of recovery after MTBI in diverse patient populations (e.g., adults, athletes and children) and injury environments (e.g., motor vehicle collisions) as well as on the risk of long-term outcomes after MTBI, such as Parkinson’s disease and dementia. Additional clinical areas of interest in MTBI are also discussed including the similarities between MTBI and other traumatic injuries and the risk of Second Impact Syndrome after sport concussion. Clinicians can use this information to help inform patients on the likely course of recovery after MTBI/concussion and guide better decision-making in the care of these patients.

Comparison of Outcome Measures for Studying Mild Traumatic Brain Injury Prognosis in Older Adults

To identify clinically meaningful outcomes for older adults with mild traumatic brain injury (MTBI).

Methodological Issues and Research Recommendations for Prognosis After Mild Traumatic Brain Injury: Results of the International Collaboration on Mild Traumatic Brain Injury Prognosis

The International Collaboration on Mild Traumatic Brain Injury (MTBI) Prognosis performed a comprehensive search and critical review of the literature from 2001 to 2012 to update the 2002 best-evidence synthesis conducted by the World Health Organization Collaborating Centre for Neurotrauma, Prevention, Management and Rehabilitation Task Force on the prognosis of MTBI. Of 299 relevant studies, 101 were accepted as scientifically admissible. The methodological quality of the research literature on MTBI prognosis has not improved since the 2002 Task Force report. There are still many methodological concerns and knowledge gaps in the literature. Here we report and make recommendations on how to avoid methodological flaws found in prognostic studies of MTBI. Additionally, we discuss issues of MTBI definition and identify topic areas in need of further research to advance the understanding of prognosis after MTBI. Priority research areas include but are not limited to the use of confirmatory designs, studies of measurement validity, focus on the elderly, attention to litigation/compensation issues, the development of validated clinical prediction rules, the use of MTBI populations other than hospital admissions, continued research on the effects of repeated concussions, longer follow-up times with more measurement periods in longitudinal studies, an assessment of the differences between adults and children, and an account for reverse causality and differential recall bias. Well-conducted studies in these areas will aid our understanding of MTBI prognosis and assist clinicians in educating and treating their patients with MTBI.

Introduction to the Findings of the International Collaboration on Mild Traumatic Brain Injury Prognosis: What is a Prognostic Study?

Prognostic studies of mild traumatic brain injury (MTBI) can serve many purposes. First, they are used to describe paths and outcomes of patients with MTBI. Second, they provide information on which characteristics are associated with the occurrence of outcomes. Third, they provide insight into the causation of poor or favorable course of the disease. Finally, they can assess how differences in the probability of outcomes can help predict the course of patients. In this article, we summarize methodologic principles used by the International Collaboration on MTBI Prognosis to appraise the prognostic literature. Differentiating prognostic factors (causally linked with outcome), prognostic markers (associated but not causally), and predictors is important to guide interventions, public health policy, and research. Ideally, prognostic studies need a clear statement of the type of question (hypothesis-generating descriptive, exploration of possible prognostic variables, confirmatory modeling of prognosis); a cohort study design with standardized follow-up of a representative population of patients with MTBI; a standardized data collection using reliable and accurate tools to capture clinically, biologically, psychologically, or socially relevant variables and outcomes; and an analysis of data based on survival methods. Interpretation of prognostic studies should consider biases related to differential inclusion of nonrepresentative samples of patients, poor measurements of outcomes, and poor control for confounders. Transferring prognostic results into clinical practice should be based on estimates of the predictive performance of models and on a demonstration that patient outcomes can be improved by the use of prediction rules.

Summary of the findings of the International Collaboration on Mild Traumatic Brain Injury Prognosis

In 2004, the WHO Collaborating Centre for Neurotrauma, Prevention, Management and Rehabilitation Task Force published the first large systematic review and best evidence synthesis on the clinical course and prognosis for recovery after MTBI. Ten years later, the International Collaboration on Mild Traumatic Brain Injury Prognosis (ICoMP) formed to update the original WHO Task Force results. This summary review highlights important clinical findings from the full ICoMP results including the current evidence on the course and prognosis of recovery after MTBI in diverse patient populations (e.g., adults, athletes and children) and injury environments (e.g., motor vehicle collisions) as well as on the risk of long-term outcomes after MTBI, such as Parkinsons disease and dementia. Additional clinical areas of interest in MTBI are also discussed including the similarities between MTBI and other traumatic injuries and the risk of Second Impact Syndrome after sport concussion. Clinicians can use this information to help inform patients on the likely course of recovery after MTBI/concussion and guide better decision-making in the care of these patients.

Traumatic Brain Injury and Chronic Traumatic Encephalopathy: A Forensic Neuropsychiatric Perspective

Recent scientific reports and popular press describing chronic traumatic encephalopathy (CTE) collectively link this condition to a broad array of neuropsychiatric symptoms, including extremely rare and multi-determined behaviors such as murder-suicide. These reports are difficult to reconcile with several decades of research on the science of traumatic brain injury (TBI) and its consequences, especially the natural history and prognosis of mild TBI. This article attempts to reconcile these sources by reviewing the state of the science on CTE, with particular attention to case definitions and neuropathological criteria for this diagnosis. The evidence for links between TBI, CTE, and catastrophic clinical events is explored, and the complexity of attributing rare frequency behavioral events to CTE is highlighted. The clinical and medicolegal implications of the best available evidence are discussed, concluding with a cautionary note against prematurely generalizing current findings on CTE to entire populations of persons with, or at risk for, concussion exposures.