Jeffrey J. Bazarian

Mild traumatic brain injury in the United States, 1998--2000.

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.

Epidemiology and predictors of post-concussive syndrome after minor head injury in an emergency population

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.

Subject-specific changes in brain white matter on diffusion tensor imaging after sports-related concussion

BACKGROUND AND PURPOSE Current approaches to diffusion tensor imaging (DTI) analysis do not permit identification of individual-level changes in DTI indices. We investigated the ability of wild bootstrapping analysis to detect subject-specific changes in brain white matter (WM) before and after sports-related concussion. MATERIALS AND METHODS A prospective cohort study was performed in nine high school athletes engaged in hockey or football and six controls. Subjects underwent DTI pre- and postseason within a 3-month interval. One athlete was diagnosed with concussion (scanned within 72 h), and eight suffered between 26 and 399 subconcussive head blows. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in each WM voxel. Bootstrap samples were generated, and a permuted t test was used to compare voxel-wise FA/MD changes in each subject pre- vs. postseason. RESULTS The percentage of WM voxels with significant (p<.05) pre-post FA changes was highest for the concussion subject (3.2%), intermediary for those with subconcussive head blows (mean 1.05%±.15%) and lowest for controls (mean 0.28%±.01%). Similarly, the percentage of WM voxels with significant MD changes was highest for the concussion subject (3.44%), intermediary for those with subconcussive head blows (mean 1.48%±.17%) and lowest for controls (mean 0.48%±.05%). Significantly changed FA and MD voxels colocalized in the concussion subject to the right corona radiata and right inferior longitudinal fasciculus. CONCLUSIONS Wild bootstrap analysis detected significantly changed WM in a single concussed athlete. Athletes with multiple subconcussive head blows had significant changes in a percentage of their WM that was over three times higher than controls. Efforts to understand the significance of these WM changes and their relationship to head impact forces appear warranted.

Predicting Postconcussion Syndrome After Mild Traumatic Brain Injury in Children and Adolescents Who Present to the Emergency Department

OBJECTIVE To determine the acute predictors associated with the development of postconcussion syndrome (PCS) in children and adolescents after mild traumatic brain injury. DESIGN Retrospective analysis of a prospective observational study. SETTING Pediatric emergency department (ED) in a childrens hospital. PARTICIPANTS Four hundred six children and adolescents aged 5 to 18 years. MAIN EXPOSURE Closed head trauma. MAIN OUTCOME MEASURES The Rivermead Post Concussion Symptoms Questionnaire administered 3 months after the injury. RESULTS Of the patients presenting to the ED with mild traumatic brain injury, 29.3% developed PCS. The most frequent PCS symptom was headache. Predictors of PCS, while controlling for other factors, were being of adolescent age, headache on presentation to the ED, and admission to the hospital. Patients who developed PCS missed a mean (SD) of 7.4 (13.9) days of school. CONCLUSIONS Adolescents who have headache on ED presentation and require hospital admission at the ED encounter are at elevated risk for PCS after mild traumatic brain injury. Interventions to identify this population and begin early treatment may improve outcomes and reduce the burden of disease.

Consequences of repeated blood-brain barrier disruption in football players

The acknowledgement of risks for traumatic brain injury in American football players has prompted studies for sideline concussion diagnosis and testing for neurological deficits. While concussions are recognized etiological factors for a spectrum of neurological sequelae, the consequences of sub-concussive events are unclear. We tested the hypothesis that blood-brain barrier disruption (BBBD) and the accompanying surge of the astrocytic protein S100B in blood may cause an immune response associated with production of auto-antibodies. We also wished to determine whether these events result in disrupted white matter on diffusion tensor imaging (DT) scans. Players from three college football teams were enrolled (total of 67 volunteers). None of the players experienced a concussion. Blood samples were collected before and after games (n = 57); the number of head hits in all players was monitored by movie review and post-game interviews. S100B serum levels and auto-antibodies against S100B were measured and correlated by direct and reverse immunoassays (n = 15 players; 5 games). A subset of players underwent DTI scans pre- and post-season and after a 6-month interval (n = 10). Cognitive and functional assessments were also performed. After a game, transient BBB damage measured by serum S100B was detected only in players experiencing the greatest number of sub-concussive head hits. Elevated levels of auto-antibodies against S100B were elevated only after repeated sub-concussive events characterized by BBBD. Serum levels of S100B auto-antibodies also predicted persistence of MRI-DTI abnormalities which in turn correlated with cognitive changes. Even in the absence of concussion, football players may experience repeated BBBD and serum surges of the potential auto-antigen S100B. The correlation of serum S100B, auto-antibodies and DTI changes support a link between repeated BBBD and future risk for cognitive changes.

Sex differences in outcome after mild traumatic brain injury.

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.

Long-term Neurologic Outcomes After Traumatic Brain Injury

ObjectiveTo determine the relations between traumatic brain injury (TBI) and several neurologic outcomes 6 months or more after TBI. ParticipantsNot applicable. DesignSystematic review of the published, peer-reviewed literature. Primary MeasuresNot applicable. ResultsWe identified 75 studies that examined the relations between TBI and neurologic outcomes. Unprovoked seizures are causally related to penetrating TBI as well as to moderate and severe TBI. There was only limited evidence of an association between seizures and mild TBI. Dementia of the Alzheimers type (DAT) was associated with moderate and severe TBI, but not with mild TBI unless there was loss of consciousness (LOC); the evidence for the latter was limited. Parkinsonism was associated with moderate and severe TBI, but there was only modest evidence of a link with mild TBI without LOC. Dementia pugilistica was associated with professional boxing. There was insufficient evidence to support an association between TBI and both multiple sclerosis and amyotrophic lateral sclerosis. TBI appeared to produce a host of postconcussive symptoms (eg, memory problems, dizziness, and irritability). Moderate and severe TBI were associated with endocrine problems such as hypopituitarism and growth hormone deficiency and possibly with diabetes insipidus. There was only limited evidence of an association between mild TBI and the development of ocular/visual motor deterioration. ConclusionTBI is strongly associated with several neurologic disorders 6 months or more after injury. Clinicians caring for TBI patients should monitor them closely for the development of these disorders. While some of these disorders can be treated after they arise (eg, seizures), a greater public health benefit would be achieved by preventing them before they develop. Research efforts to develop therapies aimed at secondary prevention are currently underway.

Serum S-100B and cleaved-tau are poor predictors of long-term outcome after mild traumatic brain injury

Primary objective: To determine the relationship of serum S-100B and C-tau levels to long-term outcome after mild traumatic brain injury (mild TBI). Research design: A prospective study of 35 mild TBI subjects presenting to the emergency department. Methods and procedures: Six hour serum S-100B and C-tau levels compared to 3-month Rivermead Post Concussion Questionnaire (RPCQ) scores and post-concussive syndrome (PCS). Main outcomes and results: The linear correlation between marker levels and RPCQ scores was weak (S-100B: r = 0.071, C-tau: r = −0.21). There was no statistically significant correlation between marker levels and 3-month PCS (S-100B: AUC = 0.589, 95%CI. 038, 0.80; C-tau: AUC = 0.634, 95%CI 0.43, 0.84). The sensitivity of these markers ranged from 43.8–56.3% and the specificity from 35.7–71.4%. Conclusions: Initial serum S-100B and C-tau levels appear to be poor predictors of 3-month outcome after mild TBI.

Persistent, long-term cerebral white matter changes after sports-related repetitive head impacts

Introduction 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. Methods 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. Results 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. Conclusions 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.

The Relationship Between Gender and Postconcussion Symptoms After Sport-Related Mild Traumatic Brain Injury

The authors sought to define the relationship between gender and postconcussion symptoms (PCSx) at 3 months after sport‐related mild traumatic brain injury (mTBI) and, further, to examine whether age (minors vs. adults), source of PCSx reporting (self‐reported vs. proxy), previous head injury or loss of consciousness, or the sport type in which the mTBI was incurred explain any observed gender differences in PCSx.