The goal of the current investigation was to detect clinically important axonal damage in cerebral white matter after mild traumatic brain injury (TBI) using diffusion tensor imaging (DTI). To this end, we evaluated a prospective, pilot study of six subjects with isolated mild TBI and six matched orthopedic controls. All subjects underwent DTI scanning, post-concussive symptom (PCS) assessment, and neurobehavioral testing within 72 h of injury. Fractional anisotropy (FA) and trace values in white matter voxels of whole brain and five preslected regions of interest (ROI) were compared in mild TBI and control subjects using a quantile approach. In addition, whole brain images were analyzed using voxel-based morphometry. All subjects underwent quality of life and repeat PCS assessment at 1 month. Whole brain images revealed significantly lower 1^st percentile trace values (mean 0.465 vs. 0.488, p = 0.049) among mild TBI subjects. These trace values correlated with PCS scores at both 72 h (r = −0.57, p = 0.05) and 1 month (r = −0.61, p = 0.04). Analysis of ROIs showed mild TBI subjects to have significantly lower mean trace in the left anterior internal capsule (0.536 vs. 0.574, p = 0.007) and higher maximum ROI-specific median FA values (mean 0.801 vs. 0.756, p = 0.035) in the posterior corpus callosum. These FA values correlated with 72-h PCS score (r = −0.63, p = 0.03), and two neurobehavioral tests (visual motor speed [r = 0.63, p = 0.03] and impulse control [r = 0.59, p = 0.04]). Collectively, DTI detected significantly lower trace and elevated FA values in mild TBI subjects compared to controls. These abnormalities correlated to poor clinical outcome. We believe these findings represent axonal swelling, an early step in the process of axonal injury.

Primary objective: To determine the incidence and epidemiology of emergency department (ED)-attended mild traumatic brain injury (mTBI) in the US. Research design: Secondary analysis of ED visits for mTBI in the National Hospital Ambulatory Medical Care Survey for 1998–2000. Methods and procedures: MTBI defined by International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for ‘skull fracture’, ‘concussion’, ‘intracranial injury of unspecified nature’ and ‘head injury, unspecified’. Main outcome and results: The average incidence of mTBI was 503.1/100 000, with peaks among males (590/100 000), American Indians/Alaska Natives (1,026/100 000) and those <5 years of age (1,115.2/100 000). MTBI incidence was highest in the Midwest region (578.4/10 000) and in non-urban areas (530.9/100 000) of the US. Bicycles and sports accounted for 26.4% of mTBI in the 5–14 age group. Conclusions: The national burden of mTBI is significant and the incidence higher than that reported by others. Possible explanations are discussed. Bicycle and sports-related injuries are an important and highly preventable cause of mTBI underscoring the need to promote prevention programmes on a national level.

The objective of this study was to estimate the independent association of sex with outcome after mild traumatic brain injury (mTBI). We performed an analysis of a subset of an established cohort involving 1425 mTBI patients presenting to an academic emergency department (ED). The associations between sex and three outcomes determined 3 months after the initial ED visit were examined: post-concussive symptom (PCS) score (0, 1–5, 6–16, and >16), the number of days to return of normal activities (0, 1–7, and >7), and the number of days of work missed (0, 1–7,and >7). Logistic regression analyses were used to determine the relationship between sex and each outcome after controlling for 12 relevant subject-level variables. Of the 1425 subjects, 643 (45.1%) were female and 782 (54.9%) were male. Three months after mTBI, males had significantly lower odds of being in a higher PCS score category (odds ratio [OR] 0.62, 95% confidence interval [CI]: 0.50, 0.78); this association appeared to be more prominent during child-bearing years for females. Males and females did not significantly differ with respect to the odds of poorer outcome as defined by the number of days to return of normal activities or the number of days of work missed. Female sex is associated with significantly higher odds of poor outcome after mTBI, as measured by PCS score, after control for appropriate confounders. The observed pattern of peak disability for females during the child-bearing years suggests disruption of endogenous estrogen or progesterone production. Attempts to better understand how mTBI affects production of these hormones acutely after injury and during the recovery period may shed light on the mechanism behind poorer outcome among females and putative therapeutic interventions.

Repetitive head impacts (RHI) sustained in contact sports are thought to be necessary for the long-term development of chronic traumatic encephalopathy (CTE). Our objectives were to: 1) characterize the magnitude and persistence of RHI-induced white matter (WM) changes; 2) determine their relationship to kinematic measures of RHI; and 3) explore their clinical relevance. Prospective, observational study of 10 Division III college football players and 5 non-athlete controls during the 2011-12 season. All subjects underwent diffusion tensor imaging (DTI), physiologic, cognitive, and balance testing at pre-season (Time 1), post-season (Time 2), and after 6-months of no-contact rest (Time 3). Head impact measures were recorded using helmet-mounted accelerometers. The percentage of whole-brain WM voxels with significant changes in fractional anisotropy (FA) and mean diffusivity (MD) from Time 1 to 2, and Time 1 to 3 was determined for each subject and correlated to head impacts and clinical measures. Total head impacts for the season ranged from 431–1,850. No athlete suffered a clinically evident concussion. Compared to controls, athletes experienced greater changes in FA and MD from Time 1 to 2 as well as Time 1 to 3; most differences at Time 2 persisted to Time 3. Among athletes, the percentage of voxels with decreased FA from Time 1 to 2 was positively correlated with several helmet impact measures. The persistence of WM changes from Time 1 to 3 was also associated with changes in serum ApoA1 and S100B autoantibodies. WM changes were not consistently associated with cognition or balance. A single football season of RHIs without clinically-evident concussion resulted in WM changes that correlated with multiple helmet impact measures and persisted following 6 months of no-contact rest. This lack of WM recovery could potentially contribute to cumulative WM changes with subsequent RHI exposures.

Objective : To determine if clinical variables or neurobehavioural test (NBT) scores obtained in the ED within 24 hours of minor head injury (MHI) predict the development of postconcussive syndrome (PCS). Methods : Prospective, observational study of 71 MHI patients and 60 orthopaedic controls. MHI defined as loss of consciousness < 10 minutes or amnesia, GCS 15, no skull fracture or new neurologic focality on PE, and no brain injury on CT (if done). All patients received a seven part NBT battery in the ED. Telephone follow-up was done at 1, 3 and 6 months to determine if patients met the DSM IV definition of PCS. Analysis : Stepwise, multivariate, logistic regression. Results : Predictors of PCS at 1 month were female gender (OR 7.8; 95% CI 41.6, 1.98), presence of both retrograde and anterograde amnesia (OR 0.055; CI 0.002, 0.47), Digit Span Forward Scores (OR 0.748; CI 0.52, 1.03) and Hopkins Verbal Learning A scores (OR 0.786; CI 0.65, 0.91); at 3 months, presence of both retrograde and anterograde amnesia (OR 0.13; CI 0.0, 0.93), Digit Span Forward Scores (OR 0.744; CI 0.58, 0.94). No variables fit the model at 6 months. 92% of males scoring > 25 on Hopkins Verbal Learning A did not have PCS at 1 month, and 89% of females scoring < 9 on Digit Span Forward did have PCS at 1 month. Conclusions : Gender and two NBTs can help predict PCS after MHI.