Context: Evidence suggests that athletes engaging in high-intensity activities after concussion have more difficulties with cognitive recovery. Objective: To examine the role postinjury activity level plays in postconcussive symptoms and performance on neurocognitive tests in a population of student-athletes. Design: Retrospective cohort study with repeated measures of neurocognitive performance and symptom reporting. Setting: University-based sports concussion clinic. Patients or Other Participants: Ninety-five student-athletes (80 males, 15 females: age = 15.88 ± 1.35 years) were retrospectively assigned to 1 of 5 groups based on a postinjury activity intensity scale. Main Outcome Measure(s): We employed a regression analysis for repeated measures to evaluate the relationship of activity intensity to symptoms and neurocognitive outcome up to 33 days after concussion. Postconcussion symptom scores and neurocognitive (verbal memory, visual memory, visual motor speed, and reaction time) scores served as the primary outcome measures. Results: Level of exertion was significantly related to all outcome variables (P < .02 for all comparisons). With multivariate analysis, activity intensity remained significant with respect to visual memory (P = .003) and reaction time (P < .001). Conclusions: Activity level after concussion affected symptoms and neurocognitive recovery. Athletes engaging in high levels of activity after concussion demonstrated worse neurocognitive performance. For these tasks, those engaging in moderate levels of activity demonstrated the best performance.

As an astrocytic protein specific to the central nervous system, S100b is a potentially useful marker in outcome prediction after traumatic brain injury (TBI). Some studies have questioned the validity of S100b, citing the extracerebral origins of the protein as reducing the specificity of the marker. This study evaluated S100b as a prognostic biomarker in adult subjects with severe TBI (sTBI) by comparing outcomes with S100b temporal profiles generated from both cerebrospinal fluid (CSF) ( n =138 subjects) and serum ( n =80 subjects) samples across a 6-day time course. Long-bone fracture, Injury Severity Score (ISS), and isolated head injury status were variables used to assess extracerebral sources of S100b in serum. After TBI, CSF and serum S100b levels were increased over healthy controls across the first 6 days post-TBI ( p ≤0.005 and p ≤0.031). Though CSF and serum levels were highly correlated during early time points post-TBI, this association diminished over time. Bivariate analysis showed that subjects who had temporal CSF profiles with higher S100b concentrations had higher acute mortality ( p <0.001) and worse Glasgow Outcome Scale (GOS; p =0.002) and Disability Rating Scale (DRS) scores ( p =0.039) 6 months post-injury. Possibly as a result of extracerebral sources of S100b in serum, as represented by high ISS scores ( p =0.032), temporal serum profiles were associated with acute mortality ( p =0.015). High CSF S100b levels were observed in women ( p =0.022) and older subjects ( p =0.004). Multivariate logistic regression confirmed CSF S100b profiles in predicting GOS and DRS and showed mean and peak serum S100b as acute mortality predictors after sTBI.

Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples ( n =536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls ( n =14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global outcome for both men and women. These findings represent a paradigm shift when thinking about the role of sex steroids in neuroprotection clinically after TBI.

Objective: Examine associations between chronic inflammatory profiles and outcome 6 to 12 months following severe traumatic brain injury (TBI). Setting: University-affiliated level 1 trauma center and community. Participants: Adults with severe TBI (n = 87); healthy controls (n = 7). Design: Prospective cohort study. Main Measures: Glasgow Outcome Scale; serum cytokines (interleukin [IL]-1β, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, tumor necrosis factor α), 2 weeks to 3 months, 4- to 6-month averages, 6- and 12-month levels. Results: Serum levels of IL-1β, IL-6, IL-8, IL-10, and tumor necrosis factor α were elevated over 3 months following TBI. Multivariate analysis showed that increased cytokine load score was associated with a 1.21 (95% confidence interval, 1.06-1.38) and 1.18 (95% confidence interval, 1.02-1.37) increase in odds of unfavorable Glasgow Outcome Scale score at 6 and 12 months, respectively. Also, elevated IL-6/IL-10 ratios were associated with increased odds of unfavorable outcomes at 6 months (adjusted odds ratio = 1.76; 95% confidence interval, 1.08-2.88). Conclusions: Chronic inflammation has not been well characterized following TBI. Our subacute cytokine load score classifies individuals at risk for unfavorable outcomes following injury. Higher proinflammatory burden with IL-6, relative to the anti-inflammatory marker IL-10, is significantly associated with outcome. Further research should examine whether inflammatory genes and other inflammatory biomarkers affect risk for unfavorable outcomes and TBI complications.