Background: Uncertainty continues to surround mild traumatic brain injury (mTBI) diagnosis, symptoms, prognosis, and outcome due in part to a lack of objective biomarkers of injury and recovery. As mTBI gains recognition as a serious public health epidemic, there is need to identify risk factors, diagnostic tools, and imaging biomarkers to help guide diagnosis and management.
Methods: One hundred and eleven patients (15–50 years old) were enrolled acutely after mTBI and followed with up to four standardized serial assessments over 3 months. Each encounter included a clinical exam, neuropsychological assessment, and magnetic resonance imaging (MRI). Chi-square and linear mixed models were used to assess changes over time and determine potential biomarkers of mTBI severity and outcome.
Results: The symptoms most frequently endorsed after mTBI were headache (91%), not feeling right (89%), fatigue (86%), and feeling slowed down (84%). Of the 104 mTBI patients with a processed MRI scan, 28 (27%) subjects had white matter changes which were deemed unrelated to age, and 26 of these findings were deemed unrelated to acute trauma. Of the neuropsychological assessments tested, 5- and 6-Digit Backward Recall, the modified Balance Error Scoring System (BESS), and Immediate 5-Word Recall significantly improved longitudinally in mTBI subjects and differentiated between mTBI subjects and controls. Female sex was found to increase symptom severity scores (SSS) at every time point. Age ≥ 25 years was correlated with increased SSS. Subjects aged ≥ 25 also did not improve longitudinally on 5-Digit Backward Recall, Immediate 5-Word Recall, or Single-Leg Stance of the BESS, whereas subjects < 25 years improved significantly. Patients who reported personal history of depression, anxiety, or other psychiatric disorder had higher SSS at each time point.
Conclusions: The results of this study show that 5- and 6-Digit Backward Recall, the modified BESS, and Immediate 5-Word Recall should be considered useful in demonstrating cognitive and vestibular improvement during the mTBI recovery process. Clinicians should take female sex, older age, and history of psychiatric disorder into account when managing mTBI patients. Further study is necessary to determine the true prevalence of white matter changes in people with mTBI.
Mild traumatic brain injury (mTBI) is defined as a traumatically induced physiological disruption of brain function (1). Although mTBI accounts for at least 75% of traumatic brain injuries and imposes an excessive societal burden (2, 3), mTBI diagnosis continues to lack objective clinical and imaging biomarkers. As of now, the best marker for severity and recovery is a subjective assessment of acute symptom burden (4). Uncertainty continues to surround mTBI diagnosis, symptoms, prognosis, and outcome for physicians and patients as reliable biomarkers remain elusive. As injury rates increase and mTBI becomes a serious public health epidemic (5), there is an increasing role for identification of potential imaging biomarkers, specific neuropsychological assessments, and validated risk factors to help guide prognoses and return to play decisions.
Given the current subjective nature of symptom burden assessment, there is a role for neuropsychological assessments in evaluating the cognitive impairment of patients after injury. The sport concussion assessment tool (SCAT) has been demonstrated as an effective tool to differentiate between mTBI subjects and controls in non-athlete populations and is widely used in mTBI studies (6–8). Tests of memory, balance, and cognition are incorporated into the SCAT (9, 10), but research has not demonstrated their effectiveness as longitudinal assessments (11). Separately, 3-word recall is commonly employed in patients with mTBI to assess memory function (12). This test is usually normal and is probably inadequate for assessing these patients.
The risk factors for mTBI severity are debated in the literature. Demographic factors commonly explored include sex, age, previous concussions, learning disability, psychiatric history, and migraine/headache history (13). Although each of these preinjury characteristics has been studied in numerous protocols, a consensus has not been reached. Further research is needed to establish the risk factors for mTBI severity so that they may be incorporated into clinical care.
Moreover, routine imaging techniques are limited in their value of serving as biomarkers of severity or prognosis in the mTBI population, and the extent of incidental magnetic resonance imaging (MRI) findings in mTBI patients also remains unclear. Conventional structural MR imaging is felt to be limited in its yield of disease severity or prognosis. Further research is necessary to investigate the anatomical characteristics of the mTBI population that present to medical attention. Better characterization of the specific abnormalities in anatomic imaging in this population is necessary.
The aim of this study was to incorporate patient history, clinical exams, imaging, and multiple neurological assessments into a prospective longitudinal study of patients presenting with an acute mild traumatic brain injury to provide guidance for hypothesis generation and future study design of mTBI research. Traditional neuropsychological assessments were developed to further attempt to detect abnormalities in patients with mTBI. Although MR imaging is not routinely performed for acute mTBI, recent advances in MRI based techniques have allowed researchers to incorporate imaging into mTBI trials. This study specifically investigated the presence of white matter hyperintensities on structural imaging. This combination of assessments and time points provided a more comprehensive and detailed assessment of symptoms and outcomes of mTBI patients than found in previous studies. This allows for identification of previously elusive potential risk factors which may influence outcome measures for mTBI populations.[…]