Subclinical brain manifestations of repeated mild traumatic brain injury are changed by chronic exposure to sleep loss, caffeine, and sleep aids.

INTRODUCTION: After mild traumatic brain injury (mTBI), the brain is labile for weeks and months and vulnerable to repeated concussions. During this time, patients are exposed to everyday circumstances that, in themselves, affect brain metabolism and blood flow and neural processing. How commonplace activities interact with the injured brain is unknown. The present study in an animal model investigated the extent to which three commonly experienced exposures-daily caffeine usage, chronic sleep loss, and chronic sleep aid medication-affect the injured brain in the chronic phase. METHODS: Subclinical trauma by repeated mTBIs was produced by our head rotational acceleration injury model, which causes brain injury consistent with the mechanism of concussion in humans. Forty-eight hours after a third mTBI, chronic administrations of caffeine, sleep restriction, or zolpidem (sedative hypnotic) began and were continued for 70 days. On Days 30 and 60 post injury, resting state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were performed. RESULTS: Chronic caffeine, sleep restriction, and zolpidem each changed the subclinical brain characteristics of mTBI at both 30 and 60 days post injury, detected by different MRI modalities. Each treatment caused microstructural alterations in DTI metrics in the insular cortex and retrosplenial cortex compared with mTBI, but also uniquely affected other gray and white matter regions. Zolpidem administration affected the largest number of individual structures in mTBI at both 30 and 60 days, and not necessarily toward normalization (sham treatment). Chronic sleep restriction changed local functional connectivity at 30 days in diametrical opposition to chronic caffeine ingestion, and both treatment outcomes were different from sham, mTBI-only and zolpidem comparisons. The results indicate that commonly encountered exposures modify subclinical brain activity and structure long after healing is expected to be complete. CONCLUSIONS: Changes in activity and structure detected by fMRI are widely understood to reflect changes in the functions of the affected region which conceivably underlie mTBI neuropathology and symptomatology in the chronic phase after injury.

Sleep loss, caffeine, sleep aids and sedation modify brain abnormalities of mild traumatic brain injury.

Little evidence exists about how mild traumatic brain injury (mTBI) is affected by commonly encountered exposures of sleep loss, sleep aids, and caffeine that might be potential therapeutic opportunities. In addition, while propofol sedation is administered in severe TBI, its potential utility in mild TBI is unclear. Each of these exposures is known to have pronounced effects on cerebral metabolism and blood flow and neurochemistry. We hypothesized that they each interact with cerebral metabolic dynamics post-injury and change the subclinical characteristics of mTBI. MTBI in rats was produced by head rotational acceleration injury that mimics the biomechanics of human mTBI. Three mTBIs spaced 48 h apart were used to increase the likelihood that vulnerabilities induced by repeated mTBI would be manifested without clinically relevant structural damage. After the third mTBI, rats were immediately sleep deprived or administered caffeine or suvorexant (an orexin antagonist and sleep aid) for the next 24 h or administered propofol for 5 h. Resting state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) were performed 24 h after the third mTBI and again after 30 days to determine changes to the brain mTBI phenotype. Multi-modal analyses on brain regions of interest included measures of functional connectivity and regional homogeneity from rs-fMRI, and mean diffusivity (MD) and fractional anisotropy (FA) from DTI. Each intervention changed the mTBI profile of subclinical effects that presumably underlie healing, compensation, damage, and plasticity. Sleep loss during the acute post-injury period resulted in dramatic changes to functional connectivity. Caffeine, propofol sedation and suvorexant were especially noteworthy for differential effects on microstructure in gray and white matter regions after mTBI. The present results indicate that commonplace exposures and short-term sedation alter the subclinical manifestations of repeated mTBI and therefore likely play roles in symptomatology and vulnerability to damage by repeated mTBI.

Assessing photoreceptor structure in patients with traumatic head injury.

OBJECTIVE: Previous work using adaptive optics scanning light ophthalmoscopy (AOSLO) imaging has shown photoreceptor disruption to be a common finding in head and ocular trauma patients. Here an expanded trauma population was examined using a novel imaging technique, split-detector AOSLO, to assess remnant cone structure in areas with significant disruption on confocal AOSLO imaging and to follow photoreceptor changes longitudinally. METHODS AND ANALYSIS: Eight eyes from seven subjects with head and/or ocular trauma underwent imaging with spectral domain optical coherence tomography, confocal AOSLO and split-detector AOSLO to assess foveal and parafoveal photoreceptor structure. RESULTS: Confocal AOSLO imaging revealed hyporeflective foveal regions in two of eight eyes. Split-detector imaging within the hyporeflective confocal areas showed both remnant and absent inner-segment structure. Both of these eyes were imaged longitudinally and showed variation of the photoreceptor mosaic over time. Four other eyes demonstrated subclinical regions of abnormal waveguiding photoreceptors on multimodal AOSLO imagery but were otherwise normal. Two eyes demonstrated normal foveal cone packing without disruption. CONCLUSION: Multimodal imaging can detect subtle photoreceptor abnormalities not necessarily detected by conventional clinical imaging. The addition of split-detector AOSLO revealed the variable condition of inner segments within confocal photoreceptor disruption, confirming the usefulness of dual-modality AOSLO imaging in assessing photoreceptor structure and integrity. Longitudinal imaging demonstrated the dynamic nature of the photoreceptor mosaic after trauma. Multimodal imaging with dual-modality AOSLO improves understanding of visual symptoms and photoreceptor structure changes in patients with head and ocular trauma.

Acute Clinical Predictors of Symptom Recovery in Emergency Department Patients with Uncomplicated Mild Traumatic Brain Injury or Non-Traumatic Brain Injuries.

There is a subset of patients with mild traumatic brain injury (mTBI) who report persistent symptoms that impair their functioning and quality of life. Being able to predict which patients will experience prolonged symptom recovery would help clinicians target resources for clinical follow-up to those most in need, and would facilitate research to develop precision medicine treatments for mTBI. The purpose of this study was to investigate the predictors of symptom recovery in a prospective sample of emergency department trauma patients with either mTBI or non-mTBI injuries. Subjects were examined at several time points from within 72 h to 45 days post-injury. We quantified and compared the value of a variety of demographic, injury, and clinical assessment (symptom, neurocognitive) variables for predicting self-reported symptom duration in both mTBI (n = 89) and trauma control (n = 73) patients. Several injury-related and neuropsychological variables assessed acutely (< 72 h) post-injury predicted symptom duration, particularly loss of consciousness (mTBI group), acute somatic symptom burden (both groups), and acute reaction time (both groups), with reasonably good model fit when including all of these variables (area under the receiver operating characteristic curve [AUC] = 0.76). Incorporating self-reported litigation involvement modestly increased prediction further (AUC = 0.80). The results highlight the multifactorial nature of mTBI recovery, and injury recovery more generally, and the need to incorporate a variety of variables to achieve adequate prediction. Further research to improve this model and validate it in new and more diverse trauma samples will be useful to build a neurobiopsychosocial model of recovery that informs treatment development.

Prospective, Head-to-Head Study of Three Computerized Neurocognitive Assessment Tools Part 2: Utility for Assessment of Mild Traumatic Brain Injury in Emergency Department Patients.

OBJECTIVES: The aim of this study was to evaluate the reliability and validity of three computerized neurocognitive assessment tools (CNTs; i.e., ANAM, DANA, and ImPACT) for assessing mild traumatic brain injury (mTBI) in patients recruited through a level I trauma center emergency department (ED). METHODS: mTBI (n=94) and matched trauma control (n=80) subjects recruited from a level I trauma center emergency department completed symptom and neurocognitive assessments within 72 hr of injury and at 15 and 45 days post-injury. Concussion symptoms were also assessed via phone at 8 days post-injury. RESULTS: CNTs did not differentiate between groups at any time point (e.g., M 72-hr Cohen's d=-.16, .02, and .00 for ANAM, DANA, and ImPACT, respectively; negative values reflect greater impairment in the mTBI group). Roughly a quarter of stability coefficients were over .70 across measures and test-retest intervals in controls. In contrast, concussion symptom score differentiated mTBI vs. control groups acutely), with this effect size diminished over time (72-hr and day 8, 15, and 45 Cohen's d=-.78, -.60, -.49, and -.35, respectively). CONCLUSIONS: The CNTs evaluated, developed and widely used to assess sport-related concussion, did not yield significant differences between patients with mTBI versus other injuries. Symptom scores better differentiated groups than CNTs, with effect sizes weaker than those reported in sport-related concussion studies. Nonspecific injury factors, and other characteristics common in ED settings, likely affect CNT performance across trauma patients as a whole and thereby diminish the validity of CNTs for assessing mTBI in this patient population. (JINS, 2017, 23, 293-303).

Activity-Related Symptom Exacerbations After Pediatric Concussion.

IMPORTANCE: Recovery from concussion generally follows a trajectory of gradual improvement, but symptoms can abruptly worsen with exertion. This phenomenon is poorly understood. OBJECTIVES: To characterize the incidence, course, and clinical significance of symptom exacerbations (spikes) in children after concussion. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of clinical trial data analyzes 63 eligible participants prospectively recruited from an emergency department who were asked to complete a postconcussion symptom scale and record their activities in a structured diary for the next 10 days. They completed standardized assessments of symptoms (postconcussion symptom scale), cognition (Immediate Post-Concussion Assessment and Cognitive Testing), and balance (Balance Error Scoring System) 10 days following the injury. Eligible participants were aged 11 to 18 years and sustained a concussion (according to the Centers for Disease Control and Prevention criteria) that did not result in an abnormal computed tomography scan or require hospital admission. The trial was conducted from May 2010 to December 2012, and the analysis was conducted from November 2015 to February 2016. MAIN OUTCOME AND MEASURE: The occurrence of symptom spikes, defined as an increase of 10 or more points on the postconcussion symptom scale over consecutive days. RESULTS: Of the 63 participants, there were 41 boys (65.1%) and 22 girls (34.9%), and the mean (SD) age was 13.8 (1.8) years. Symptom spikes occurred in one-third of the sample (20 participants [31.7%]). Symptom spikes tended to partially resolve within 24 hours. An abrupt increase in mental activity (ie, returning to school and extracurricular activities) from one day to the next increased the risk of a symptom spike (relative risk, 0.81; 95% CI, 0.21-3.21), but most symptom spikes were not preceded by a documented increase in physical or mental activity. Patients with symptom spikes were initially more symptomatic in the emergency department and throughout the observation period but did not differ from the group without symptom spikes on cognition or balance 10 days following injury. CONCLUSIONS AND RELEVANCE: Certain patients appeared susceptible to high and variable symptom reporting. Symptom spikes may not themselves be detrimental to recovery. The present findings support clinical guidelines for adolescents to return to school and activities gradually after concussion. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01101724.

Preinjury somatization symptoms contribute to clinical recovery after sport-related concussion.

OBJECTIVE: To determine the degree to which preinjury and acute postinjury psychosocial and injury-related variables predict symptom duration following sport-related concussion. METHODS: A total of 2,055 high school and collegiate athletes completed preseason evaluations. Concussed athletes (n = 127) repeated assessments serially (<24 hours and days 8, 15, and 45) postinjury. Cox proportional hazard modeling was used to predict concussive symptom duration (in days). Predictors considered included demographic and history variables; baseline psychological, neurocognitive, and balance functioning; acute injury characteristics; and postinjury clinical measures. RESULTS: Preinjury somatic symptom score (Brief Symptom Inventory-18 somatization scale) was the strongest premorbid predictor of symptom duration. Acute (24-hour) postconcussive symptom burden (Sport Concussion Assessment Tool-3 symptom severity) was the best injury-related predictor of recovery. These 2 predictors were moderately correlated (r = 0.51). Path analyses indicated that the relationship between preinjury somatization symptoms and symptom recovery was mediated by postinjury concussive symptoms. CONCLUSIONS: Preinjury somatization symptoms contribute to reported postconcussive symptom recovery via their influence on acute postconcussive symptoms. The findings highlight the relevance of premorbid psychological factors in postconcussive recovery, even in a healthy athlete sample relatively free of psychopathology or medical comorbidities. Future research should elucidate the neurobiopsychosocial mechanisms that explain the role of this individual difference variable in outcome following concussive injury.

Age Differences in Recovery After Sport-Related Concussion: A Comparison of High School and Collegiate Athletes.

CONTEXT: Younger age has been hypothesized to be a risk factor for prolonged recovery after sport-related concussion, yet few studies have directly evaluated age differences in acute recovery. OBJECTIVE: To compare clinical recovery patterns for high school and collegiate athletes. DESIGN: Prospective cohort study. SETTING: Large, multicenter prospective sample collected from 1999-2003 in a sports medicine setting. SUBJECTS: Concussed athletes (n = 621; 545 males and 76 females) and uninjured controls (n = 150) participating in high school and collegiate contact and collision sports (79% in football, 15.7% in soccer, and the remainder in lacrosse or ice hockey). MAIN OUTCOME MEASURE(S): Participants underwent evaluation of symptoms (Graded Symptom Checklist), cognition (Standardized Assessment of Concussion, paper-and-pencil neuropsychological tests), and postural stability (Balance Error Scoring System). Athletes were evaluated preinjury and followed serially at several time points after concussive injury: immediately, 3 hours postinjury, and at days 1, 2, 3, 5, 7, and 45 or 90 (with neuropsychological measures administered at baseline and 3 postinjury time points). RESULTS: Comparisons of concussed high school and collegiate athletes with uninjured controls suggested that high school athletes took 1 to 2 days longer to recover on a cognitive (Standardized Assessment of Concussion) measure. Comparisons with the control group on other measures (symptoms, balance) as well as direct comparisons between concussed high school and collegiate samples revealed no differences in the recovery courses between the high school and collegiate groups on any measure. Group-level recovery occurred at or before 7 days postinjury on all assessment metrics. CONCLUSIONS: The findings suggest no clinically significant age differences exist in recovery after sport-related concussion, and therefore, separate injury-management protocols are not needed for high school and collegiate athletes.

Prospective, Head-to-Head Study of Three Computerized Neurocognitive Assessment Tools (CNTs): Reliability and Validity for the Assessment of Sport-Related Concussion.

Limited data exist comparing the performance of computerized neurocognitive tests (CNTs) for assessing sport-related concussion. We evaluated the reliability and validity of three CNTs-ANAM, Axon Sports/Cogstate Sport, and ImPACT-in a common sample. High school and collegiate athletes completed two CNTs each at baseline. Concussed (n=165) and matched non-injured control (n=166) subjects repeated testing within 24 hr and at 8, 15, and 45 days post-injury. Roughly a quarter of each CNT's indices had stability coefficients (M=198 day interval) over .70. Group differences in performance were mostly moderate to large at 24 hr and small by day 8. The sensitivity of reliable change indices (RCIs) was best at 24 hr (67.8%, 60.3%, and 47.6% with one or more significant RCIs for ImPACT, Axon, and ANAM, respectively) but diminished to near the false positive rates thereafter. Across time, the CNTs' sensitivities were highest in those athletes who became asymptomatic within 1 day before neurocognitive testing but was similar to the tests' false positive rates when including athletes who became asymptomatic several days earlier. Test-retest reliability was similar among these three CNTs and below optimal standards for clinical use on many subtests. Analyses of group effect sizes, discrimination, and sensitivity and specificity suggested that the CNTs may add incrementally (beyond symptom scores) to the identification of clinical impairment within 24 hr of injury or within a short time period after symptom resolution but do not add significant value over symptom assessment later. The rapid clinical recovery course from concussion and modest stability probably jointly contribute to limited signal detection capabilities of neurocognitive tests outside a brief post-injury window. (JINS, 2016, 22, 24-37).

Attention-Deficit/Hyperactivity Disorder in a VA Polytrauma Clinic.

A large-scale study suggests that veterans with attention-deficit/hyperactivity disorder may benefit from structured treatment interventions focused on developing compensatory skills for their attention and impulsivity issues.

Rehabilitation from postconcussion syndrome: nonpharmacological treatment.

Following mild traumatic brain injury (mTBI), one or more symptoms commonly occur that are known as the postconcussion syndrome (PCS). While PCS typically resolves within a few weeks of injury for most concussed patients, some patients have a more prolonged or otherwise adverse recovery course. There is relatively little systematic research on the treatment of PCS. This report offers strategies for nonpharmacological treatment of PCS during the acute, subacute, and chronic stages of recovery following mTBI. The treatment strategies are supported by clinical consensus and the limited evidence-based research wherever possible. Core treatment strategies emphasize (1) education about mTBI, PCS, and the natural recovery course, (2) reassurance of a good outcome, (3) reduction in activity level and refrain from hazardous behaviors during the acute phase, (4) gradual return to lifestyle activities as symptoms permit, (5) careful monitoring and early intervention for adverse emotional responses, (6) symptom-specific treatment when needed, and (7) ready access to providers during acute and subacute recovery periods.

Enhancement of functional connectivity, working memory and inhibitory control on multi-modal brain MR imaging with Rifaximin in Cirrhosis: implications for the gut-liver-brain axis.

UNLABELLED: Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE. HYPOTHESIS: Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks. METHODS: Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. RESULTS were compared before/after rifaximin. RESULTS: 20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92% medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia(p = 0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial. A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE.

Acute and subacute changes in neural activation during the recovery from sport-related concussion.

To study the natural recovery from sports concussion, 12 concussed high school football athletes and 12 matched uninjured teammates were evaluated with symptom rating scales, tests of postural balance and cognition, and an event-related fMRI study during performance of a load-dependent working memory task at 13 h and 7 weeks following injury. Injured athletes showed the expected postconcussive symptoms and cognitive decline with decreased reaction time (RT) and increased RT variability on a working memory task during the acute period and an apparent full recovery 7 weeks later. Brain activation patterns showed decreased activation of right hemisphere attentional networks in injured athletes relative to controls during the acute period with a reversed pattern of activation (injured > controls) in the same networks at 7 weeks following injury. These changes coincided with a decrease in self-reported postconcussive symptoms and improved cognitive test performance in the injured athletes. Results from this exploratory study suggest that decreased activation of right hemisphere attentional networks mediate the cognitive changes and postconcussion symptoms observed during the acute period following concussion. Conversely, improvement in cognitive functioning and postconcussive symptoms during the subacute period may be mediated by compensatory increases in activation of this same attentional network.

Naming outcome prediction in patients with discordant Wada and fMRI language lateralization.

OBJECTIVE: Investigations of the validity of fMRI as an alternative to Wada language testing have yielded Wada/fMRI discordance rates of approximately 15%, but almost nothing is known regarding the relative accuracy of Wada and fMRI in discordant cases. The objective of this study was to determine which of the two (the Wada test or the language fMRI) is more predictive of postoperative naming outcome following left anterior temporal lobectomy in discordant cases. METHODS: Among 229 patients with epilepsy who prospectively underwent Wada and fMRI language testing, ten had discordant language lateralization results, underwent left anterior temporal lobectomy, and returned for postoperative language testing. The relative accuracy of Wada and fMRI for predicting language outcome was examined in these cases. RESULTS: Functional magnetic resonance imaging provided a more accurate prediction of language outcome in seven patients, Wada was more accurate in two patients, and the two tests were equally accurate in one patient. CONCLUSIONS: In cases of discordance, fMRI predicted postsurgical naming outcome with relatively better accuracy compared to the Wada test.

Language lateralization by fMRI and Wada testing in 229 patients with epilepsy: rates and predictors of discordance.

PURPOSE: To more definitively characterize Wada/functional magnetic resonance imaging (fMRI) language dominance discordance rates with the largest sample of patients with epilepsy to date, and to examine demographic, clinical, and methodologic predictors of discordance. METHODS: Two hundred twenty-nine patients with epilepsy underwent both a standardized Wada test and a semantic decision fMRI language protocol in a prospective research study. Language laterality indices were computed for each test using automated and double-blind methods, and Wada/fMRI discordance rates were calculated using objective criteria for discordance. Regression analyses were used to explore a range of variables that might predict discordance, including subject variables, Wada quality indices, and fMRI quality indices. KEY FINDINGS: Discordant results were observed in 14% of patients. Discordance was highest among those categorized by either test as having bilateral language. In a multivariate model, the only factor that predicted discordance was the degree of atypical language dominance on fMRI. SIGNIFICANCE: fMRI language lateralization is generally concordant with Wada testing. The degree of rightward shift of language dominance on fMRI testing is strongly correlated with Wada/fMRI discordance, suggesting that fMRI may be more sensitive than Wada to right hemisphere language processing, although the clinical significance of this increased sensitivity is unknown. The relative accuracy of fMRI versus Wada testing for predicting postsurgical language outcome in discordant cases remains a topic for future research.

Incidence, clinical course, and predictors of prolonged recovery time following sport-related concussion in high school and college athletes.

Sport-related concussion (SRC) is typically followed by clinical recovery within days, but reports of prolonged symptoms are common. We investigated the incidence of prolonged recovery in a large cohort (n = 18,531) of athlete seasons over a 10-year period. A total of 570 athletes with concussion (3.1%) and 166 controls who underwent pre-injury baseline assessments of symptoms, neurocognitive functioning and balance were re-assessed immediately, 3 hr, and 1, 2, 3, 5, 7, and 45 or 90 days after concussion. Concussed athletes were stratified into typical (within 7 days) or prolonged (> 7 days) recovery groups based on symptom recovery time. Ten percent of athletes (n = 57) had a prolonged symptom recovery, which was also associated with lengthier recovery on neurocognitive testing (p < .001). At 45-90 days post-injury, the prolonged recovery group reported elevated symptoms, without deficits on cognitive or balance testing. Prolonged recovery was associated with unconsciousness [odds ratio (OR), 4.15; 95% confidence interval (CI) 2.12-8.15], posttraumatic amnesia (OR, 1.81; 95% CI, 1.00-3.28), and more severe acute symptoms (p < .0001). These results suggest that a small percentage of athletes may experience symptoms and functional impairments beyond the typical window of recovery after SRC, and that prolonged recovery is associated with acute indicators of more severe injury.

A comparison of two fMRI methods for predicting verbal memory decline after left temporal lobectomy: language lateralization versus hippocampal activation asymmetry.

PURPOSE: Language lateralization measured by preoperative functional magnetic resonance imaging (fMRI) was shown recently to be predictive of verbal memory outcome in patients undergoing left anterior temporal lobe (L-ATL) resection. The aim of this study was to determine whether language lateralization or functional lateralization in the hippocampus is a better predictor of outcome in this setting. METHODS: Thirty L-ATL patients underwent preoperative language fMRI, preoperative hippocampal fMRI using a scene encoding task, and pre- and postoperative neuropsychological testing. A group of 37 right ATL (R-ATL) surgery patients was included for comparison. RESULTS: Verbal memory decline occurred in roughly half of the L-ATL patients. Preoperative language lateralization was correlated with postoperative verbal memory change. Hippocampal activation asymmetry was strongly related to side of seizure focus and to Wada memory asymmetry but was unrelated to verbal memory outcome. DISCUSSION: Preoperative hippocampal activation asymmetry elicited by a scene encoding task is not predictive of verbal memory outcome. Risk of verbal memory decline is likely to be related to lateralization of material-specific verbal memory networks, which are more closely correlated with language lateralization than with overall asymmetry of episodic memory processes.

An integrated review of recovery after mild traumatic brain injury (MTBI): implications for clinical management.

The diagnosis and treatment of mild traumatic brain injury (MTBI)have historically been hampered by an incomplete base of scientific evidence to guide clinicians. One question has been most elusive to clinicians and researchers alike: What is the true natural history of MTBI? Fortunately, the science of MTBI has advanced more in the last decade than in the previous 50 years, and now reaches a maturity point at which the science can drive an evidence-based approach to clinical management. In particular, technological advances in functional neuroimaging have created a powerful bridge between the clinical and basic science of MTBI in humans. Collectively, findings from clinical, basic science, and functional neuroimaging studies now establish a foundation on which to build integrative theories and testable hypotheses around a comprehensive model of MTBI recovery. We review the current scientific literature on postconcussion symptom recovery, neuropsychological outcome, and neurophysiological healing after MTBI. Special emphasis is placed on how the new evidence base can help guide clinicians in the evaluation and management of military-related MTBI.

Effects of a symptom-free waiting period on clinical outcome and risk of reinjury after sport-related concussion.

OBJECTIVE: This study is the first to investigate the influence of a symptom-free waiting period (SFWP) on clinical outcome and risk of repeat injury after sport-related concussion. METHODS: This was a prospective, nonrandomized study of 16 624 player seasons from 1999 to 2004, including a cohort of 635 concussed high school and college athletes grouped on the basis of an SFWP or no SFWP observed after their concussion. Clinical outcome in symptoms, cognitive functioning, and postural stability 45 and 90 days postinjury was compared with preinjury baseline. Data on SFWP and same-season repeat concussion were recorded. RESULTS: An SFWP was observed in 60.3% of cases. There were no significant differences between the SFWP and no SFWP groups in acute injury characteristics or clinical outcome with respect to symptom recovery or postinjury performance on formal neuropsychological and balance testing. Most repeat concussions (79.2%) occurred within 10 days of the initial injury. The rate of repeat concussion was actually higher in the SFWP group (6.49%) than the no SFWP group (0.90%) (P < 0.005), but the repeat concussion subgroup's SFWP was 2.82 days shorter (95% confidence interval, 0.61-5.03; P < 0.01) and these athletes resumed participation 3.55 days sooner (95% confidence interval, 0.06-7.04; P < 0.05) than those in the SFWP group in which there was no repeat concussion. CONCLUSION: Our findings suggest that an SFWP did not intrinsically influence clinical recovery or reduce risk of a repeat concussion. The overall risk of same-season repeat concussion seems to be relatively low, but there may be a period of vulnerability that increases risk of repeat concussion during the first 7 to 10 days postinjury. Further study is required to investigate this preliminary finding and help determine whether this risk can be reduced further with specific injury-management strategies.

Concussion symptom inventory: an empirically derived scale for monitoring resolution of symptoms following sport-related concussion.

Self-report post-concussion symptom scales have been a key method for monitoring recovery from sport-related concussion, to assist in medical management, and return-to-play decision-making. To date, however, item selection and scaling metrics for these instruments have been based solely upon clinical judgment, and no one scale has been identified as the "gold standard". We analyzed a large set of data from existing scales obtained from three separate case-control studies in order to derive a sensitive and efficient scale for this application by eliminating items that were found to be insensitive to concussion. Baseline data from symptom checklists including a total of 27 symptom variables were collected from a total of 16,350 high school and college athletes. Follow-up data were obtained from 641 athletes who subsequently incurred a concussion. Symptom checklists were administered at baseline (preseason), immediately post-concussion, post-game, and at 1, 3, and 5 days post-injury. Effect-size analyses resulted in the retention of only 12 of the 27 variables. Receiver-operating characteristic analyses were used to confirm that the reduction in items did not reduce sensitivity or specificity. The newly derived Concussion Symptom Inventory is presented and recommended as a research and clinical tool for monitoring recovery from sport-related concussion.