Targeted Intervention Improves Symptoms and Impairments in Patients With Mild Traumatic Brain Injury With Chronic Symptom: A Prospective, Multiple Interventional Research Trial.

BACKGROUND: Mild traumatic brain injury (mTBI) and its potential long-term consequences is a primary concern for the US military. The purpose of the study is to evaluate if participants improved in anxiety/mood symptoms, sleep quality, and vestibular/ocular symptoms following a 6-month active intervention, and to explore the effect of targeted treatment for those with specific symptoms/impairments (e.g., psychological, sleep, ocular, vestibular). MATERIALS AND METHODS: A multidisciplinary clinical team adjudicated participants (n=72, 35.8±8.6 years old, 19% female) to have one of the following primary clinical trajectories: psychological (PSYCH; n=34), sleep (SLEEP; n=25) and vestibular/ocular (VESTIB/OCULAR; n=18). Participants returned for follow-up assessment 6 months later. Assessments included the Post-Concussion Symptom Scale [PCSS], Generalized Anxiety Disorder-7 [GAD-7], Pittsburgh Sleep Quality Index [PSQI], and Dizziness Handicap Inventory [DHI]. Change in concussion symptoms and primary outcome for the given trajectory (i.e., PSYCH=GAD-7, SLEEP=PSQI, VESTIB/OCULAR=DHI) was assessed. RESULTS: Following the 6-month intervention, participants reduced PCSS Score (-14.5±2.4; p<.001; η2=0.34), GAD-7 (-3.1±0.5; p<.001; η2=0.34), PSQI (-2.7±0.5; p<.001; η2=0.34) and DHI (-9.2±2.0; p<.001; η2=0.23). PSYCH (n=34) reduced PCSS score (-17.9±3.6; p<.001; η2=0.45) and GAD-7 (-3.1±0.7; p<.001; η2=0.38). SLEEP (n=25) reduced PCSS score (-8.8±4.4; p=.06; η2=0.15) and PSQI (-3.6±0.9; p<.001; η2=0.45) scores. VESTIB/OCULAR (n=18) reduced PCSS score (-16.7±4.8; p=.03; η2=0.45), and DHI (-15.7±5.5; p=.012; η2=0.35). CONCLUSIONS: Large effects were observed for concussion, anxiety, sleep, and dizziness symptom reduction over 6-month treatment. Each primary outcome demonstrated a larger treatment effect for the given trajectory than the overall sample, indicating that targeted treatment can reduce symptom burden in patients with mTBI with chronic symptoms.

Impact of Multi-Disciplinary Care and Clinical Coach Coordinators on Participant Satisfaction and Retention in TBI Clinical Trials: A TEAM-TBI Study.

BACKGROUND: Targeted Evaluation Action and Monitoring of Traumatic Brain Injury (TEAM-TBI) is a monitored, multiple interventional research identifying clinical profiles and assigns individualized, evidence-based treatment program. The objective of the current study was to assess overall participant satisfaction of the multi-disciplinary care team and approach. METHODS: Between 2014 and 2017, 90 participants completed the 4-day TEAM-TBI clinical intake evaluation resulting in individualized treatment recommendations followed by a six-month intervention phase follow-up. Inclusion criteria were: age 18-60, history of chronic TBI (>6 months post-injury) with refractory clinical sequelae at screening (Post-Concussion Symptom Scale [PCSS] score >30). RESULTS: A total of 85/90 (94%) participants completed the survey at baseline focusing on intake evaluation and approach; 90% of eligible participants also completed the follow-up time-point. Hundred percent of participants had a mean score of >4 across all questions at the initial time point." CONCLUSIONS: The multi-disciplinary care approach and individualized treatment plans of the TEAM-TBI study yielded high participant retention and satisfaction scores. The Clinical Coach component of the trial was one of the highest rated aspects of the program and was associated with participant motivation and high retention rates.

[18F]FDG, [11C]PiB, and [18F]AV-1451 PET Imaging of Neurodegeneration in Two Subjects With a History of Repetitive Trauma and Cognitive Decline.

Background: Trauma-related neurodegeneration can be difficult to differentiate from multifactorial neurodegenerative syndromes, both clinically and radiographically. We have initiated a protocol for in vivo imaging of patients with suspected TBI-related neurodegeneration utilizing volumetric MRI and PET studies, including [18F]FDG indexing cerebral glucose metabolism, [11C]PiB for Aß deposition, and [18F]AV-1451 for tau deposition. Objective: To present results from a neuroimaging protocol for in vivo evaluation of TBI-related neurodegeneration in patients with early-onset cognitive decline and a history of TBI. Methods: Patients were enrolled in parallel TBI studies and underwent a comprehensive neuropsychological test battery as well as an imaging protocol of volumetric MRI and PET studies. Findings from two patients were compared with two age-matched control subjects without a history of TBI. Results: Both chronic TBI patients demonstrated cognitive deficits consistent with early-onset dementia on neuropsychological testing, and one patient self-reported a diagnosis of probable early-onset AD. Imaging studies demonstrated significant [18F]AV-1451 uptake in the bilateral occipital lobes, substantial [11C]PiB uptake throughout the cortex in both TBI patients, and abnormally decreased [18F]FDG uptake in the posterior temporoparietal areas of the brain. One TBI patient also had subcortical volume loss. Control subjects demonstrated no appreciable [18F]AV-1451 or [11C]PiB uptake, had normal cortical volumes, and had normal cognition profiles on neuropsychological testing. Conclusions: In the two patients presented, the [11C]PiB and [18F]FDG PET scans demonstrate uptake patterns characteristic of AD. [11C]PiB PET scans showed widespread neocortical uptake with less abnormal uptake in the occipital lobes, whereas there was significant [18F]AV-1451 uptake in both occipital lobes.

Preliminary Evidence for Improvement in Symptoms, Cognitive, Vestibular, and Oculomotor Outcomes Following Targeted Intervention with Chronic mTBI Patients.

Introduction: To determine if targeted, active interventions would improve symptoms and impairment in previously intractable patients with chronic mild traumatic brain injury (mTBI). Materials and Methods: Twenty-six (20 males; 6 females) out of 51 (51%) former military and civilian patients with chronic (1-3 yr) mTBI enrolled in the TEAM traumatic brain injury (TBI) study completed both an initial and 6-mo post-intervention comprehensive mTBI assessment including symptoms (Post-concussion Symptom Scale [PCSS], Dizziness Handicap Inventory [DHI]), cognitive (Immediate Post-concussion Assessment and Cognitive Testing [ImPACT]), vestibular/oculomotor (Vestibular/Ocular Motor Screening [VOMS]), balance (Activities-specific Balance Confidence [ABC] scale, Balance Error Scoring System [BESS]), and cervical (Neck Disability Index [NDI]). Patients were prescribed progressive, targeted interventions and therapies (e.g., behavioral, vestibular, vision, and exertion) that matched their mTBI clinical profile. A series of paired t-tests adjusted for multiple corrections were used to compare pre- and post-intervention assessment scores. Results: Patients demonstrated significant improvement from pre- to post-intervention on total symptoms (t = 2.69, p = 0.01), verbal memory (t = -1.96, p = 0.05), ABC balance score (t = -2.05, p = 0.05), smooth pursuits (t = 2.32, p = 0.04), near-point convergence distance (t = -3.58, p = 0.01), vestibular ocular reflex (t = 2.31, p = 0.03), and visual motion sensitivity (t = 2.43, p = 0.03). Conclusions: Previously recalcitrant patients with chronic complex mTBI demonstrated significant improvement in symptoms, cognitive, vestibular, oculomotor, and balance function following targeted interventions.

Quantifying white matter structural integrity with high-definition fiber tracking in traumatic brain injury.

There is an urgent, unmet demand for definitive biological diagnosis of traumatic brain injury (TBI) to pinpoint the location and extent of damage. We have developed High-Definition Fiber Tracking, a 3 T magnetic resonance imaging-based diffusion spectrum imaging and tractography analysis protocol, to quantify axonal injury in military and civilian TBI patients. A novel analytical methodology quantified white matter integrity in patients with TBI and healthy controls. Forty-one subjects (23 TBI, 18 controls) were scanned with the High-Definition Fiber Tracking diffusion spectrum imaging protocol. After reconstruction, segmentation was used to isolate bilateral hemisphere homologues of eight major tracts. Integrity of segmented tracts was estimated by calculating homologue correlation and tract coverage. Both groups showed high correlations for all tracts. TBI patients showed reduced homologue correlation and tract spread and increased outlier count (correlations>2.32 SD below control mean). On average, 6.5% of tracts in the TBI group were outliers with substantial variability among patients. Number and summed deviation of outlying tracts correlated with initial Glasgow Coma Scale score and 6-month Glasgow Outcome Scale-Extended score. The correlation metric used here can detect heterogeneous damage affecting a low proportion of tracts, presenting a potential mechanism for advancing TBI diagnosis.

A high-definition fiber tracking report for patients with traumatic brain injury and their doctors.

We have developed a tablet-based application, the High-Definition Fiber Tracking Report App, to enable clinicians and patients in research studies to see and understand damage from Traumatic Brain Injury (TBI) by viewing 2-dimensional and 3-dimensional images of their brain, with a focus on white matter tracts with quantitative metrics. The goal is to visualize white matter fiber tract injury like bone fractures; that is, to make the "invisible wounds of TBI" understandable for patients. Using mobile computing technology (iPad), imaging data for individual patients can be downloaded remotely within hours of a magnetic resonance imaging brain scan. Clinicians and patients can view the data in the form of images of each tract, rotating animations of the tracts, 3-dimensional models, and graphics. A growing number of tracts can be examined for asymmetry, gaps in streamline coverage, reduced arborization (branching), streamline volume, and standard quantitative metrics (e.g., Fractional Anisotropy (FA)). Novice users can learn to effectively navigate and interact with the application (explain the figures and graphs representing normal and injured brain tracts) within 15 minutes of simple orientation with high accuracy (96%). The architecture supports extensive graphics, configurable reports, provides an easy-to-use, attractive interface with a smooth user experience, and allows for securely serving cases from a database. Patients and clinicians have described the application as providing dramatic benefits in understanding their TBI and improving their lives.

An exploratory analysis linking neuropsychological testing to quantification of tractography using High Definition Fiber Tracking (HDFT) in military TBI.

To realize the potential value of tractography in traumatic brain injury (TBI), we must identify metrics that provide meaningful information about functional outcomes. The current study explores quantitative metrics describing the spatial properties of tractography from advanced diffusion imaging (High Definition Fiber Tracking, HDFT). In a small number of right-handed males from military TBI (N = 7) and civilian control (N = 6) samples, both tract homologue symmetry and tract spread (proportion of brain mask voxels contacted) differed for several tracts among civilian controls and extreme groups in the TBI sample (high scorers and low scorers) for verbal recall, serial reaction time, processing speed index, and trail-making. Notably, proportion of voxels contacted in the arcuate fasciculus distinguished high and low performers on the CVLT-II and PSI, potentially reflecting linguistic task demands, and GFA in the left corticospinal tract distinguished high and low performers in PSI and Trail Making Test Part A, potentially reflecting right hand motor response demands. The results suggest that, for advanced diffusion imaging, spatial properties of tractography may add analytic value to measures of tract anisotropy.