Quantitative Volumetric Imaging and Clinical Outcome Characterization of Symptomatic Concussion in 10- to 14-Year-Old Adolescent Athletes.

OBJECTIVE: Prior work suggests that younger athletes may be more vulnerable to postconcussive syndrome. We investigated measures of clinical outcome and quantitative volumetric imaging in 10- to 14-year-old adolescent athletes to better understand the impact of concussion on this younger population. SETTING: Outpatient clinics. PARTICIPANTS: Ten- to 14-year-old symptomatic pediatric sports concussion patients and typically developing active controls. DESIGN: Prospective, observational multiclinic study. MAIN MEASURES: Demographics, magnetic resonance imaging, clinical assessments (neurocognitive function, postconcussive symptoms, mental health symptoms, quality of life). RESULTS: Neuropsychological performance was comparable between groups while symptoms of mental health were discriminating and comprised the top regression model describing factors related to overall health behavior impairment. Concussion patients had smaller total brain volume as well as total intracranial volume in comparison with controls even though there was no difference on measures of natural development (age, height, weight, education, gender, and handedness). CONCLUSIONS: Findings indicate that 10- to 14-year-old concussion patients symptomatic at 1 month more likely exhibit mental health symptoms impairing health behavior than cognitive dysfunction. There may be a vulnerability for those with smaller brain volumes at the time of the exposure. The study provides new data to support further investigation into risk factors for prolonged symptoms in this younger athlete population.

Longitudinal neuroimaging following combat concussion: sub-acute, 1 year and 5 years post-injury.

Questions remain regarding the long-term impact of combat concussive blast exposure. While efforts have begun to highlight the clinical impact, less is known about neuroimaging trajectories that may inform underlying pathophysiological changes post-injury. Through collaborative efforts in combat, following medical evacuation, and at universities in the USA, this study followed service members both with and without blast concussion from the sub-acute to 1-year and 5-year outcomes with quantitative neuroimaging. The following two primary and two exploratory groups were examined: combat-deployed controls without blast exposure history 'non-blast control' and concussive blast patients (primary) and combat concussion arising not from blast 'non-blast concussion' and combat-deployed controls with blast exposure history 'blast control' (exploratory). A total of 575 subjects were prospectively enrolled and imaged; 347 subjects completed further neuroimaging examination at 1 year and 342 subjects completed further neuroimaging examination at 5 years post-injury. At each time point, MRI scans were completed that included high-resolution structural as well as diffusion tensor imaging acquisitions processed for quantitative volumetric and diffusion tensor imaging changes. Longitudinal evaluation of the number of abnormal diffusion tensor imaging and volumetric regions in patients with blast concussion revealed distinct trends by imaging modality. While the presence of abnormal volumetric regions remained quite stable comparing our two primary groups of non-blast control to blast concussion, the diffusion tensor imaging abnormalities were observed to have varying trajectories. Most striking was the fractional anisotropy 'U-shaped' curve observed for a proportion of those that, if we had only followed them to 1 year, would look like trajectories of recovery. However, by continuing the follow-up to 5 years in these very same patients, a secondary increase in the number of reduced fractional anisotropy regions was identified. Comparing non-blast controls to blast concussion at each time point revealed significant differences in the number of regions with reduced fractional anisotropy at both the sub-acute and 5-year time points, which held after adjustment for age, education, gender, scanner and subsequent head injury exposure followed by correction for multiple comparisons. The secondary increase identified in patients with blast concussion may be the earliest indications of microstructural changes underlying the 'accelerated brain aging' theory recently reported from chronic, cross-sectional studies of veterans following brain injury. These varying trajectories also inform potential prognostic neuroimaging biomarkers of progression and recovery.

Longitudinal Clinical and Neuroimaging Evaluation of Symptomatic Concussion in 10- to 14-year-old Youth Athletes.

This study longitudinally assessed 10- to 14-year-old patients with sports and recreational concussion (n = 22) who remained symptomatic 3 to 4weeks post-injury compared with typically developing controls (n = 24). Examination by multi-modal magnetic resonance imaging (MRI) and multi-domain clinical outcome measures was completed at 1-month and 6-months post-injury. Concussion patients showed evidence of improvement by 6-month follow-up in domains of cognitive function, whereas measures of psychological health were less resolved with patients exhibiting sustained symptoms of depression, behavior impairment, and concussion symptoms. Quantitative neuroimaging measures identified measures indicative of chronic injury with regional reductions observed by both volumetric segmentation and white matter fractional anisotropy (FA) from diffusion tensor imaging (DTI). Volumetric reductions (p < 0.01) were observed in the middle anterior and posterior portions of the corpus callosum, and right caudal anterior cingulate cortex of patients, although none held after strict correction. Examination of the FA data identified significant reductions in the left middle frontal gyrus white matter (p = 0.0003). Linear regression analysis on the 6-month depression outcome variable using the initial clinical, demographic, and imaging measures identified the top predictive models to include concussion diagnosis, and initial symptoms of depression, concussion symptoms, and sleep impairment with additional contribution from other measures of mental health, behavior impairment, and quality of life depending on the model (adjusted r-squared = 0.69 indicating strong predictive ability). This study supports further inclusion of mental health rehabilitation and imaging supplementing traditional cognitive rehabilitation strategies employed in these young athletes.

5-Year imaging sequelae of concussive blast injury and relation to early clinical outcome.

Current imaging diagnostic techniques are often insensitive to the underlying pathological changes following mild traumatic brain injury (TBI) or concussion so much so that the explicit definition of these uncomplicated mild brain injuries includes the absence of radiological findings. In the US military, this is complicated by the natural tendency of service members to down play symptoms for fear of removal from their unit particularly in combat making it challenging for clinicians to definitively diagnose and determine course of treatment. Questions remain regarding the long-term impact of these war-time brain injuries. The objective of the current study was to evaluate the long-term imaging sequelae of blast concussion in active-duty US military and leverage previous longitudinal data collected in these same patients to identify predictors of sustained DTI signal change indicative of chronic neurodegeneration. In total, 50 blast TBI and 44 combat-deployed controls were evaluated at this 5-year follow up by advanced neuroimaging techniques including diffusion tensor imaging and quantitative volumetry. While cross-sectional analysis of regions of white matter on DTI images did not reveal significant differences across groups after statistical correction, an approach flexible to the heterogeneity of brain injury at the single-subject level identified 74% of the concussive blast TBI cohort to have reductions in fractional anisotropy indicative of chronic brain injury. Logistic regression leveraging clinical and demographic data collected in the acute/sub-acute and 1-year follow up to determine predictors of these long-term imaging changes determined that brain injury diagnosis, older age, verbal memory and verbal fluency best predicted the presence of DTI abnormalities 5 years post injury with an AUC of 0.78 indicating good prediction strength. These results provide supporting evidence for the evolution not resolution of this brain injury pathology, adding to the growing body of literature describing imaging signatures of chronic neurodegeneration even after mild TBI and concussion.