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The Brain Trauma Foundation (BTF) Guidelines for the Management of Severe Head Injury were the first clinical practice guidelines published by any surgical specialty. These guidelines have earned a reputation for rigor and have been widely adopted around the world. Implementation of these guidelines has been associated with a 50% reduction in mortality and reduced costs of patient care. Over their 25-yr history the traumatic brain injury (TBI) guidelines have been expanded, refined, and made increasingly more rigorous in conjunction with new clinical evidence and evolving methodologic standards. Here, we discuss the history and accomplishments of BTF guidelines for TBI as well as their limitations. We also discuss planned changes to future TBI guidelines intended to increase their utility and positive impact in an evolving medical landscape. Perhaps the greatest limitation of TBI guidelines now is the lack of high-quality clinical research as well as novel diagnostics and treatments with which to generate substantially new recommendations.

When the fourth edition of the Brain Trauma Foundation's Guidelines for the Management of Severe Traumatic Brain Injury were finalized in late 2016, it was known that the results of the RESCUEicp (Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension) randomized controlled trial of decompressive craniectomy would be public after the guidelines were released. The guideline authors decided to proceed with publication but to update the decompressive craniectomy recommendations later in the spirit of “living guidelines,” whereby topics are updated more frequently, and between new editions, when important new evidence is published. The update to the decompressive craniectomy chapter presented here integrates the findings of the RESCUEicp study as well as the recently published 12-mo outcome data from the DECRA (Decompressive Craniectomy in Patients With Severe Traumatic Brain Injury) trial. Incorporation of these publications into the body of evidence led to the generation of 3 new level-IIA recommendations; a fourth previously presented level-IIA recommendation remains valid and has been restated. To increase the utility of the recommendations, we added a new section entitled Incorporating the Evidence into Practice. This summary of expert opinion provides important context and addresses key issues for practitioners, which are intended to help the clinician utilize the available evidence and these recommendations. The full guideline can be found at: https://braintrauma.org/guidelines/guidelines-for-the-management-of-severe-tbi-4th-ed#/.

OBJECTIVE Female athletes may be more likely to sustain a concussion and may vary in symptom presentation and neurocognitive impairments as compared with males. Scientific literature is limited by subjective assessments and underproportioned representation of women-the scope and etiology of sex-based differences are unknown. This study investigates sex-based differences in sports concussion assessments among college varsity athletes. DESIGN AND SETTING Retrospective study of an institution's athletic head injury database. PARTICIPANTS Acute postinjury and baseline data from 111 college athletes sustaining concussions between 2016 and 2018, diagnosed by a concussion specialist physician. MAIN OUTCOME MEASURES Concussion assessments examined included the Sports Concussion Assessment Tool (SCAT5) and Vestibular Oculomotor Screening (VOMS) performed within 3 days (24-72 hours) of injury. RESULTS No significant difference by sex was observed in the SCAT5 total symptom evaluation scores or severity scores, Standardized Assessment of Concussion, or Balance Error Scoring System (P > .05) within 3 days of head injury. Females did report more "pressure in the head" severity scores from baseline to postconcussion (2.7 ± 1.5 increased symptomatology in females vs 1.8 ± 1.3 increase in males, P = .007). The VOMS test resulted in significant sex differences in smooth pursuit [0.6 ± 1.4 increase in females (P < .001) vs 0.2 ± 0.6 increase in males (P = .364)], horizontal saccades [0.6 ± 1.2 increase in females (P < .001) vs 0.2 ± 0.5 increase in males (P = .149)], and vertical saccades [0.9 ± 1.9 increase in females (P < .001) vs 0.3 ± 0.7 increase in males (P = .206)]. CONCLUSION Our study did not show sex-based differences in baseline or acute postconcussive symptom reporting in most concussion assessment parameters, challenging previous research suggesting that females report more symptoms than males. Females did have significant differences in symptom provocation using the VOMS.

BACKGROUND: Hypertonic saline (HTS) and mannitol are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their simultaneous effect on the cerebral perfusion pressure (CPP) and ICP has not been studied rigorously. OBJECTIVE: To determine the difference in effects of HTS and mannitol on the combined burden of high ICP and low CPP in patients with severe TBI. METHODS: We performed a case–control study using prospectively collected data from the New York State TBI-trac® database (Brain Trauma Foundation, New York, New York). Patients who received only 1 hyperosmotic agent, either mannitol or HTS for raised ICP, were included. Patients in the 2 groups were matched (1:1 and 1:2) for factors associated with 2-wk mortality: age, Glasgow Coma Scale score, pupillary reactivity, hypotension, abnormal computed tomography scans, and craniotomy. Primary endpoint was the combined burden of ICP(high) (> 25 mm Hg) and CPP(low) (

Sport-related concussion has garnered increasing scientific attention and research over the last decade. Collegiate student-athletes represent an important cohort in this field. As such, the Pac-12 CARE-Affiliated Program (CAP) was formed in 2017 as a regional hub of the Concussion Assessment, Research and Education (CARE) consortium. CAP is multisite, prospective, longitudinal study that aims to improve student-athlete health by identifying factors associated with concussion incidence and recovery and using this knowledge to inform best clinical practices and policy decisions. CAP employed a staggered rollout across the Pac-12, with the first four institutions enrolling in fall 2018. After receiving institutional review board (IRB) approval, these institutions began consenting student-athletes to share clinical concussion and baseline data for research purposes. Athletes completed baseline testing that included a medical questionnaire, concussion history and a battery for clinical concussion assessments. Concussed student-athletes were given the same battery of assessments in addition to full injury and return to play reports. Clinicians at each university worked with a data coordinator to ensure appropriate reporting, and the Pac-12 Concussion Coordinating Unit at the University of Colorado Boulder provided oversight for quality control of the data study wide. During year 1, CAP consented 2181 student-athletes and tracked 140 concussions. All research was conducted with the appropriate IRB approval across the participating Pac-12 institutions. Data security and dissemination are managed by the Presagia Sports Athlete Electronic Health Record software (Montreal, Quebec, Canada) and QuesGen Systems (San Francisco, California, USA).

It is widely appreciated that the spectrum of traumatic brain injury (TBI), mild through severe, contains distinct clinical presentations, variably referred to as subtypes, phenotypes, and/or clinical profiles. As part of the Brain Trauma Blueprint TBI State of the Science, we review the current literature on TBI phenotyping with an emphasis on unsupervised methodological approaches, and describe five phenotypes that appear similar across reports. However, we also find the literature contains divergent analysis strategies, inclusion criteria, findings, and use of terms. Further, whereas some studies delineate phenotypes within a specific severity of TBI, others derive phenotypes across the full spectrum of severity. Together, these facts confound direct synthesis of the findings. To overcome this, we introduce PhenoBench, a freely available code repository for the standardization and evaluation of raw phenotyping data. With this review and toolset, we provide a pathway toward robust, data-driven phenotypes that can capture the heterogeneity of TBI, enabling reproducible insights and targeted care.

Context Concussion underreporting leads to delays in diagnosis and treatment, prolonging recovery time. Athletes' self-reporting of concussion symptoms, therefore, reduces risk. Objective To evaluate the effectiveness of 3 concussion-education programs in improving concussion-reporting intention. Design Randomized controlled clinical trial. Setting Three high schools in California. Patients or Other Participants A total of 118 male football players (age = 14.88 ± 1.19 years). Intervention(s) Participants were randomly assigned to receive concussion education via CrashCourse (CC), Centers for Disease Control and Prevention (CDC) video education materials (CDC-Vi), or CDC written education materials (CDC-Wr). Main Outcome Measure(s) The primary outcome was concussion-reporting intention, which was assessed at baseline, immediately after education, and at 1-month follow-up. Secondary outcomes were concussion knowledge, concussion-reporting attitudes, perceived concussion-reporting norms, and perceived behavioral control. Results Across all education formats, a total sample of athletes improved in concussion-reporting intention at immediate and 1-month follow-ups (mean improvements = 6.8% and 11.4%, respectively; F4,224 = 11.1, P < .001). Similar findings were observed across all education formats in secondary analyses examining knowledge, attitudes, and perceived behavioral control. However, we noted differences in concussion-reporting intention by education format and time (F4,224 = 2.8, P = .03). Post hoc analysis showed that athletes who received CC had increased concussion-reporting intentions at immediate and 1-month follow-ups (baseline = 4.7, immediate follow-up = 6.1, 1-month follow-up = 6.0; F16,61.1 = 6.1, P = .007) compared with increases only at 1-month follow-up for CDC-Vi (baseline = 4.3, immediate follow-up = 5.2, 1-month follow-up = 5.8; F1.6,61.6 = 8.4, P = .001) and no improvement for CDC-Wr (P = .10). Secondary analyses indicated differences between CC and both CDC interventions in concussion knowledge and attitudes at immediate and 1-month follow-ups. We identified no differences in perceived behavioral control among interventions (F4,216 = 0.2, P = .93) or perceived concussion-reporting norms across (F4,224 = 0.3, P = .73) or among (F4,224 = 1.7, P = .15) interventions. Conclusions All athletes exhibited an improved intent to report concussions, increased concussion knowledge, better concussion attitudes, and more perceived behavioral control at both immediate and 1-month follow-ups. However, athletes randomized to receive CC reported a greater intent to report concussion, more knowledge, and improved concussion-reporting attitudes when compared with those who received CDC-Vi and CDC-Wr.

Injuries and illnesses can alter the normal bilateral symmetry of the brain, and determining the extent of this disruption may be useful in characterizing the pathology. One way of quantifying brain symmetry is in terms of bilateral correlation of diffusion tensor metrics between homologous white matter tracts. With this approach, we hypothesized that the brains of patients with a concussion are more asymmetrical than those of healthy individuals without a history of a concussion. We scanned the brains of 35 normal individuals and 15 emergency department patients with a recent concussion. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were determined for regions of interest (ROI) defined by a standard white-matter atlas that included 21 bilateral ROIs. For each ROI pair, bilateral correlation coefficients were calculated and compared between the two subject groups. A symmetry index, defined as the ratio between the difference and the sum of bilateral measures, was also calculated for each ROI pair and compared between the groups. We found that in normal subjects, the extent of symmetry varied among regions and individuals, and at least subtle forms of structural lateralization were common across regions. In patients, higher asymmetry was found overall as well as in the corticospinal tract specifically. Results indicate that a concussion can manifest in brain asymmetry that deviates from a normal state. The clinical utility of characterizing post-concussion pathology as abnormal brain asymmetry merits further exploration.

Background: There is heterogeneity in neurosensory alterations following mild traumatic brain injury. Commonly assessed neurosensory symptoms following head injury include symptom reports and measures of oculomotor impairment, auditory changes, and vestibular impairment. Hypothesis/Purpose: Neurosensory alterations are prevalent acutely following mild traumatic brain injury secondary to blunt head trauma during collegiate varsity sports and may vary by sex and sport. Study Design: Retrospective study of a large collegiate athletic database. Methods: Analyses were performed using an established single University dataset of 177 male and female collegiate varsity athletes who were diagnosed with concussion/mild traumatic brain injury between September 2013 and October 2019. Descriptive and comparative analyses were performed on individual and grouped acute concussion assessments pertaining to neurosensory alterations obtained within 72 h of injury using components of the Sports Concussion Assessment Tool Version 5 and Vestibular/Ocular-Motor Screening. Results: Females had significantly more abnormal smooth pursuit (p-value: 0.045), convergence (p-value: 0.031), and visual motion sensitivity tests results (p-value: 0.023) than males. There were no differences in neurosensory alterations when grouped by overall auditory, vestibular, or oculomotor impairments. The majority of sports-related concussions occurred during football (50, 28.25%), wrestling (21, 11.86%), water polo (15, 8.47%), and basketball (14, 7.91%). Abnormal vestibular assessments were high in these top four sports categories, but statistically significant differences in overall auditory, vestibular, or oculomotor impairments were not reached by individual sport. However, water polo players had higher abnormal individual assessments related to balance reports on the sideline (60.00%, p-value: 0.045) and in the clinic setting (57.14%, p-value: 0.038) as compared to all other sports. Conclusion: While neurosensory alterations are prevalent in both male and female athletes acutely post-concussion, females have a higher incidence of abnormalities in smooth pursuit, convergence, and visual motion sensitivity and may benefit from early rehabilitation.

Background Traumatic brain injury (TBI) often results in elevations in intracranial pressure (ICP) that are refractory to standard therapies. Several studies have investigated the utility of external lumbar drainage (ELD) in this setting. Objective To evaluate the safety and efficacy of ELD or lumbar puncture with regard to immediate effect on ICP, durability of the effect on ICP, complications, and neurological outcomes in adults with refractory traumatic intracranial hypertension. Methods A systematic review and meta-analysis were conducted beginning with a comprehensive search of PubMed/EMBASE. Two investigators reviewed studies for eligibility and extracted data. The strength of evidence was evaluated using GRADE methodology. Random-effects meta-analyses were performed to calculate pooled estimates. Results Nine articles detailing 6 studies (N = 110) were included. There was moderate evidence that ELD has a significant immediate effect on ICP; the pooled effect size was -19.5 mmHg (95% CI -21.0 to -17.9 mmHg). There was low evidence to indicate a durable effect of ELD on ICP up to at least 24 h following ELD. There was low evidence to indicate that ELD was safe and associated with a low rate of clinical cerebral herniation or meningitis. There was very low evidence pertaining to neurological outcomes. Conclusion Given preliminary data indicating potential safety and feasibility in highly selected cases, the use of ELD in adults with severe TBI and refractory intracranial hypertension in the presence of open basal cisterns and absence of large focal hematoma merits further high-quality investigation; the ideal conditions for potential application remain to be determined.

Background Current guidelines for the treatment of adult severe traumatic brain injury (sTBI) consist of high-quality evidence reports, but they are no longer accompanied by management protocols, as these require expert opinion to bridge the gap between published evidence and patient care. We aimed to establish a modern sTBI protocol for adult patients with both intracranial pressure (ICP) and brain oxygen monitors in place. Methods Our consensus working group consisted of 42 experienced and actively practicing sTBI opinion leaders from six continents. Having previously established a protocol for the treatment of patients with ICP monitoring alone, we addressed patients who have a brain oxygen monitor in addition to an ICP monitor. The management protocols were developed through a Delphi-method-based consensus approach and were finalized at an in-person meeting. Results We established three distinct treatment protocols, each with three tiers whereby higher tiers involve therapies with higher risk. One protocol addresses the management of ICP elevation when brain oxygenation is normal. A second addresses management of brain hypoxia with normal ICP. The third protocol addresses the situation when both intracranial hypertension and brain hypoxia are present. The panel considered issues pertaining to blood transfusion and ventilator management when designing the different algorithms. Conclusions These protocols are intended to assist clinicians in the management of patients with both ICP and brain oxygen monitors but they do not reflect either a standard-of-care or a substitute for thoughtful individualized management. These protocols should be used in conjunction with recommendations for basic care, management of critical neuroworsening and weaning treatment recently published in conjunction with the Seattle International Brain Injury Consensus Conference. Electronic supplementary material The online version of this article (10.1007/s00134-019-05900-x) contains supplementary material, which is available to authorized users.

BACKGROUNDThe Brain Trauma Foundation has developed treatment guidelines for the care of patients with acute traumatic brain injury. The Adam Williams Initiative is a program established to provide education and resources to encourage hospitals across the United States to incorporate the guidelines into practice.OBJECTIVETo explore the relationship in hospitals between participation in the Adam Williams Initiative and adherence to the Brain Trauma Foundation guidelines for patients with acute traumatic brain injury.METHODHospitals that participated in the Adam Williams Initiative entered data into an online tracking system of patients with traumatic brain injury for at least 2 years after the initial site training. Data included baseline hospital records and daily records on hospital care of patients with traumatic brain injury, including blood pressure, intracranial pressure, cerebral perfusion pressure, oxygenation, and other data relevant to the 15 key metrics in the Brain Trauma Foundation guidelines.RESULTSThe 16 hospitals funded by the Adam Williams Initiative had good overall adherence to the 15 key metrics of the recommendations detailed in the Brain Trauma Foundation guidelines. Variability in results was primarily due to data collection methods and analysis.CONCLUSIONSThe Adam Williams Initiative helps promote adherence to the Brain Trauma Foundation guidelines for hospital care of patients with traumatic brain injury by providing a platform for developing and standardizing best practices. Participation in the initiative is associated with high adherence to clinical guidelines, a situation that may subsequently improve care and outcomes for patients with traumatic brain injury.

Aim: Postconcussion symptom-rating scales are frequently used concussion assessment tools that do not align directly with new expert, consensus-based concussion subtype classification systems. This may result in delays in concussion diagnosis, subspecialty referral and rehabilitative strategies. Objective: To determine the representation of subtype-directed symptomatology in common postconcussion symptom-rating scales. Methods: Literature review and expert consensus were used to compile commonly used concussion symptom-rating scales. Statistics were generated to describe the degree of representation of the consensus symptom set. Results: The percentage of symptoms representing each subtype/associated condition is low overall (15–26%). The ocular-motor (11%) and vestibular subtypes (19%) and cervical strain (5%)-associated condition were the most under-represented and also had the greatest unmet needs. Conclusion: Concussion subtypes do not have equal representation on commonly used concussion symptom-rating scales. There is a need for a subtype-directed symptom assessment to allow for increased accuracy of diagnosis and to guide management.

Brain injury; Head trauma; Algorithm Daño cerebral; Trauma en la cabeza; Algoritmo Lesió cerebral; Trauma al cap; Algoritme Background: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation’s sTBI Management Guidelines, as they were not evidence-based. Methods: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists’ decision tendencies were the focus of recommendations. Results: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination. Conclusions: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management. We thank our financial supporters who include Adler/Geirsch Attorney at Law, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Neurotrauma and Critical Care, Bard, the Brain Trauma Foundation, DePuy, Hemedex, Integra, the Neurointensive Care Section of the European Society of Intensive Care Medicine, Neurosurgical Society of Australasia, Medtronic, Moberg Research, Natus, Neuroptics, Raumedic, Sophysa, Stryker, and Zoll.

BACKGROUND Concussion is a heterogeneous mild traumatic brain injury (mTBI) characterized by a variety of symptoms, clinical presentations, and recovery trajectories. By thematically classifying the most common concussive clinical presentations into concussion subtypes (cognitive, ocular-motor, headache/migraine, vestibular, and anxiety/mood) and associated conditions (cervical strain and sleep disturbance), we derive useful definitions amenable to future targeted treatments. OBJECTIVE To use evidence-based methodology to characterize the 5 concussion subtypes and 2 associated conditions and report their prevalence in acute concussion patients as compared to baseline or controls within 3 d of injury. METHODS A multidisciplinary expert workgroup was established to define the most common concussion subtypes and their associated conditions and select clinical questions related to prevalence and recovery. A literature search was conducted from January 1, 1990 to November 1, 2017. Two experts abstracted study characteristics and results independently for each article selected for inclusion. A third expert adjudicated disagreements. Separate meta-analyses were conducted to do the following: 1) examine the prevalence of each subtype/associated condition in concussion patients using a proportion, 2) assess subtype/associated conditions in concussion compared to baseline/uninjured controls using a prevalence ratio, and 3) compare the differences in symptom scores between concussion subtypes and uninjured/baseline controls using a standardized mean difference (SMD). RESULTS The most prevalent concussion subtypes for pediatric and adult populations were headache/migraine (0.52; 95% CI = 0.37, 0.67) and cognitive (0.40; 95% CI = 0.25, 0.55), respectively. In pediatric patients, the prevalence of the vestibular subtype was also high (0.50; 95% CI = 0.40, 0.60). Adult patients were 4.4, 2.9, and 1.7 times more likely to demonstrate cognitive, vestibular, and anxiety/mood subtypes, respectively, as compared with their controls (P

Concussion, or mild traumatic brain injury (mTBI), is a major public health concern, linked with persistent post-concussive syndrome, and chronic traumatic encephalopathy. At present, standard clinical imaging fails to reliably detect traumatic axonal injury associated with concussion and post-concussive symptoms. Diffusion tensor imaging (DTI) is an MR imaging technique that is sensitive to changes in white matter microstructure. Prior studies using DTI did not jointly investigate white matter microstructure in athletes, a population at high risk for concussive and subconcussive head traumas, with those in typical emergency room (ER) patients. In this study, we determine DTI scalar metrics in both ER patients and scholastic athletes who suffered concussions and compared them to those in age-matched healthy controls. In the early subacute post-concussion period, athletes demonstrated an elevated rate of regional decreases in axial diffusivity (AD) compared to controls. These regional decreases of AD were especially pronounced in the cerebellar peduncles, and were more frequent in athletes compared to the ER patient sample. The group differences may indicate differences in the mechanisms of the concussive impacts as well as possible compound effects of cumulative subconcussive impacts in athletes. The prevalence of white matter abnormality in cerebellar tracts lends credence to the hypothesis that post-concussive symptoms are caused by shearing of axons within an attention network mediated by the cerebellum, and warrant further study of the correlation between cerebellar DTI findings and clinical, neurocognitive, oculomotor, and vestibular outcomes in mTBI patients.

Classifying concussion in key subtypes according to presenting symptomatology at an early post-injury stage is an emerging approach that may allow prediction of clinical trajectories and delivery of targeted treatments. The Rivermead Post-concussion Symptoms Questionnaire (RPQ) is a simple, freely available, and widely used tool for assessment of the presence and severity of various post-concussion symptoms. We aimed to probe the prevalence among athletes of symptom classes associated with identified concussion phenotypes using the RPQ at baseline and acutely after a concussion. Participants of organized sports aged 12-30 years were baseline-assessed with the expectation that some would experience a concussion during the study period. Concussed athletes were re-assessed within 2 weeks of their injuries. The RPQ was supplemented with three specific questions and reworded for baseline assessment. A binomial test was used to contrast the prevalence of an attribute in the concussed cohort against the probability established by the baseline observation. Three thousand and eighty-eight athletes were baseline-assessed and eighty-nine were re-assessed post-concussion. All concussed athletes endorsed having some elevated symptoms in the RPQ, and such endorsements were more prevalent than those among normal athletes. Moderate-to-severe post-concussion symptoms of specific classes tended to be endorsed with few additional symptoms of other classes of similar intensities. Elevated symptoms detected with the RPQ within as short as 2 weeks after a concussion may help delineate patients' clinical subtypes and guide their treatment. Further refinement of symptom questionnaires and use of objective measures will be needed to properly populate the concussion subtype classification.

Attention impairment may provide a cohesive neurobiological explanation for clusters of clinical symptoms that occur after a concussion; therefore, objective quantification of attention is needed. Visually tracking a moving target is an attention-dependent sensorimotor function, and eye movement can be recorded easily and objectively to quantify performance. Our previous work suggested the utility of gaze-target synchronization metrics of a predictive visual tracking task in concussion screening and recovery monitoring. Another objectively quantifiable performance measure frequently suggested for concussion screening is simple visuo-manual reaction time (simple reaction time, SRT). Here, we used visual tracking and SRT tasks to assess changes between pre- and within-2-week post-concussion performances and explore their relationships to post-concussion symptomatology. Athletes participating in organized competitive sports were recruited. Visual tracking and SRT records were collected from the recruited athlete pool as baseline measures over a 4-year period. When athletes experienced a concussion, they were re-assessed within 2 weeks of their injury. We present the data from a total of 29 concussed athletes. Post-concussion symptom burden was assessed with the Rivermead Post-Concussion Symptoms Questionnaire and subscales of the Brain Injury Screening Questionnaire. Post-concussion changes in visual tracking and SRT performance were examined using a paired t-test. Correlations of changes in visual tracking and SRT performance to symptom burden were examined using Pearson's coefficients. Post-concussion changes in visual tracking performance were not consistent among the athletes. However, changes in several visual tracking metrics had moderate to strong correlations to symptom scales (r up to 0.68). On the other hand, while post-concussion SRT performance was reduced (p < 0.01), the changes in the performance metrics were not meaningfully correlated to symptomatology (r ≤ 0.33). Results suggest that visual tracking performance metrics reflect clinical symptoms when assessed within 2 weeks of concussion. Evaluation of concussion requires assessments in multiple domains because the clinical profiles are heterogeneous. While most individuals show recovery within a week of injury, others experience prolonged recovery periods. Visual tracking performance metrics may serve as a biomarker of debilitating symptoms of concussion implicating attention as a root cause of such pathologies.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality throughout the world. Mild TBI, which is typically defined by Glasgow Coma Scale score ≥13, accounts for the vast majority of all TBIs, particularly in the setting of sports-related injuries. The terms concussion and TBI are often used interchangeably, both in the medical literature and in clinical care of this patient population. However, the lack of clearly defined definitions of these terms often leads to confusion, and this confusion may lead to delayed diagnosis and inconsistent management of affected patients. Here, we review the current terminology and classification of mild TBI and concussion. We will also discuss recent efforts to stratify these injuries into clinically relevant subtypes or profiles that are both diagnostic- and treatment-targeted.

OBJECT Increased intracranial pressure (ICP) in patients with traumatic brain injury (TBI) is associated with a higher mortality rate and poor outcome. Mannitol and hypertonic saline (HTS) have both been used to treat high ICP, but it is unclear which one is more effective. Here, the authors compare the effect of mannitol versus HTS on lowering the cumulative and daily ICP burdens after severe TBI. METHODS The Brain Trauma Foundation TBI-trac New York State database was used for this retrospective study. Patients with severe TBI and intracranial hypertension who received only 1 type of hyperosmotic agent, mannitol or HTS, were included. Patients in the 2 groups were individually matched for Glasgow Coma Scale score (GCS), pupillary reactivity, craniotomy, occurrence of hypotension on Day 1, and the day of ICP monitor insertion. Patients with missing or erroneous data were excluded. Cumulative and daily ICP burdens were used as primary outcome measures. The cumulative ICP burden was defined as the total number of days with an ICP of > 25 mm Hg, expressed as a percentage of the total number of days of ICP monitoring. The daily ICP burden was calculated as the mean daily duration of an ICP of > 25 mm Hg, expressed as the number of hours per day. The numbers of intensive care unit (ICU) days, numbers of days with ICP monitoring, and 2-week mortality rates were also compared between the groups. A 2-sample t-test or chi-square test was used to compare independent samples. The Wilcoxon signed-rank or Cochran-Mantel-Haenszel test was used for comparing matched samples. RESULTS A total of 35 patients who received only HTS and 477 who received only mannitol after severe TBI were identified. Eight patients in the HTS group were excluded because of erroneous or missing data, and 2 other patients did not have matches in the mannitol group. The remaining 25 patients were matched 1:1. Twenty-four patients received 3% HTS, and 1 received 23.4% HTS as bolus therapy. All 25 patients in the mannitol group received 20% mannitol. The mean cumulative ICP burden (15.52% [HTS] vs 36.5% [mannitol]; p = 0.003) and the mean (± SD) daily ICP burden (0.3 ± 0.6 hours/day [HTS] vs 1.3 ± 1.3 hours/day [mannitol]; p = 0.001) were significantly lower in the HTS group. The mean (± SD) number of ICU days was significantly lower in the HTS group than in the mannitol group (8.5 ± 2.1 vs 9.8 ± 0.6, respectively; p = 0.004), whereas there was no difference in the numbers of days of ICP monitoring (p = 0.09). There were no significant differences between the cumulative median doses of HTS and mannitol (p = 0.19). The 2-week mortality rate was lower in the HTS group, but the difference was not statistically significant (p = 0.56). CONCLUSIONS HTS given as bolus therapy was more effective than mannitol in lowering the cumulative and daily ICP burdens after severe TBI. Patients in the HTS group had significantly lower number of ICU days. The 2-week mortality rates were not statistically different between the 2 groups.

A moving target is visually tracked with a combination of smooth pursuit and saccades. Human visual tracking eye movement develops through early childhood and adolescence, and declines in senescence. However, the knowledge regarding performance changes over the life course is based on data from distinct age groups in isolation using different procedures, and thus is fragmented. We sought to describe the age-dependence of visual tracking performance across a wide age range and compare it to that of simple visuo-manual reaction time. We studied a cross-sectional sample of 143 subjects aged 7-82 years old (37% male). Eye movements were recorded using video-oculography, while subjects viewed a computer screen and tracked a small target moving along a circular trajectory at a constant speed. For simple reaction time (SRT) measures, series of key presses that subjects made in reaction to cue presentation on a computer monitor were recorded using a standard software. The positional precision and smooth pursuit velocity gain of visual tracking followed a U-shaped trend over age, with best performances achieved between the ages of 20 and 50 years old. A U-shaped trend was also found for mean reaction time in agreement with the existing literature. Inter-individual variability was evident at any age in both visual tracking and reaction time metrics. Despite the similarity in the overall developmental and aging trend, correlations were not found between visual tracking and reaction time performances after subtracting the effects of age. Furthermore, while a statistically significant difference between the sexes was found for mean SRT in the sample, a similar difference was not found for any of the visual tracking metrics. Therefore, the cognitive constructs and their neural substrates supporting visual tracking and reaction time performances appear largely independent. In summary, age is an important covariate for visual tracking performance, especially for a pediatric population. Since visual tracking performance metrics may provide signatures of abnormal neurological or cognitive states independent of reaction time-based metrics, further understanding of age-dependent variations in normal visual tracking behavior is necessary.

Background: Data evaluating the role of exercise in patients with a concussion are contradictory. Studies have reported improvement in the Post-Concussion Symptom Scale (PCSS) score, whereas others showed no effect on the PCSS score. Purpose: To conduct a systematic review and meta-analysis on the role of physical exercise on different outcomes in patients with a concussion. Study Design: Systematic review and meta-analysis. Methods: A search of 5 databases from the earliest available date to September 30, 2016, and a hand search of a few articles were performed. Trial registries were reviewed, and authors of multiple studies were contacted to find additional published or unpublished studies. Randomized controlled trials (RCTs), cohort studies, and before and after (pre-post) studies evaluating the effect of physical exercise, compared with control, in patients with a concussion or mild traumatic brain injury were included. Results: The search generated 1096 studies. Of these, 14 studies (5 RCTs, 1 propensity score matching study, 3 cohort studies, and 5 before and after studies) met our inclusion criteria. Exercise significantly decreased the PCSS score (mean difference, −13.06; 95% CI, −16.57 to −9.55; P < .00001; I2 = 44%), percentage of patients with symptoms of a concussion (risk ratio, 0.74; 95% CI, 0.63 to 0.86; P = .0001; I2 = 0%), and days off work (17.7 days vs 32.2 days, respectively; P < .05) compared with control. Exercise improved the reaction time (standard mean difference, –0.43; 95% CI, −0.80 to −0.06; P = .02) component of the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) score without affecting the Balance Error Scoring System (BESS) score and neuropsychological parameters. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) scores were moderate for the PCSS, symptoms, ImPACT, BESS, and neuropsychological tests. Conclusion: Physical exercise appears to improve the PCSS score and symptoms in patients with a concussion. A high-quality RCT evaluating different intensities of exercise at different time points, for different durations after a concussion, for different races/ethnicities, and for sex needs to be conducted to evaluate a clear effect of exercise in patients with a concussion.

Human visual tracking performance is known to be reduced with an increase of the target's speed and oscillation frequency, but changes in brain states following a concussion may alter these frequency responses. The goal of this study was to characterize and compare frequency-dependent smooth pursuit velocity degradation in normal subjects and patients who had chronic postconcussion symptoms, and also examine cases of acutely concussed patients. Eye movements were recorded while subjects tracked a target that moved along a circular trajectory of 10° radius at 0.33, 0.40, or 0.67 Hz. Performance was characterized by the gain of smooth pursuit velocity, with reduced gain indicating reduced performance. The difference between normal and chronic patient groups in the pattern of decrease in the gain of horizontal smooth pursuit velocity as a function of the stimulus frequency reflected patients performing more poorly than normal subjects at 0.4 Hz while both groups performing similarly at 0.33 or 0.67 Hz. The performance of acute patients may represent yet another type of frequency response. The findings suggest that there may be ranges of stimulus frequencies that differentiate the effects of concussion from normal individuals.

BACKGROUND: Currently, there is no evidence-based definition for concussion that is being uniformly applied in clinical and research settings. OBJECTIVE: To conduct a systematic review of the highest-quality literature about concussion and to assemble evidence about the prevalence and associations of key indicators of concussion. The goal was to establish an evidence-based foundation from which to derive, in future work, a definition, diagnostic criteria, and prognostic indicators for concussion. METHODS: Key questions were developed, and an electronic literature search from 1980 to 2012 was conducted to acquire evidence about the prevalence of and associations among signs, symptoms, and neurologic and cognitive deficits in samples of individuals exposed to potential concussive events. Included studies were assessed for potential for bias and confound and rated as high, medium, or low potential for bias and confound. Those rated as high were excluded from the analysis. Studies were further triaged on the basis of whether the definition of a case of concussion was exclusive or inclusive; only those with wide, inclusive case definitions were used in the analysis. Finally, only studies reporting data collected at fixed time points were used. For a study to be included in the conclusions, it was required that the presence of any particular sign, symptom, or deficit be reported in at least 2 independent samples. RESULTS: From 5437 abstracts, 1362 full-text publications were reviewed, of which 231 studies were included in the final library. Twenty-six met all criteria required to be used in the analysis, and of those, 11 independent samples from 8 publications directly contributed data to conclusions. Prevalent and consistent indicators of concussion are (1) observed and documented disorientation or confusion immediately after the event, (2) impaired balance within 1 day after injury, (3) slower reaction time within 2 days after injury, and/or (4) impaired verbal learning and memory within 2 days after injury. CONCLUSION: The results of this systematic review identify the consistent and prevalent indicators of concussion and their associations, derived from the strongest evidence in the published literature. The product is an evidence-based foundation from which to develop diagnostic criteria and prognostic indicators.

We tested whether reduced cognitive function associated with mild traumatic brain injury (mTBI) and sleep deprivation can be detected and distinguished using indices of predictive visual tracking. A circular visual tracking test was given to 13 patients with acute mTBI (recruited within 2 weeks of injury), 127 normal control subjects, and 43 healthy subjects who were fatigued by 26-hour sleep deprivation. Eye movement was monitored with video-oculography. In the mTBI-related portion of the study, visual tracking performance of acute mTBI patients was significantly worse than normal subjects (p0.001). In the sleep-deprivation-related portion of the study, no change was detected between the two baseline measures separated by 2 to 3 weeks, but the 26-hour sleep deprivation significantly degraded the visual tracking performance (p0.001). The mTBI subjects had substantially worse visual tracking than sleep-deprived subjects that could also be identified with different visual tracking indices, indicating possible different neurophysiological mechanisms. Results suggest that cognitive impairment associated with mTBI and fatigue may be triaged with the aid of visual tracking measures.

BACKGROUND: Fatigue due to sleep restriction places individuals at elevated risk for accidents, degraded health, and impaired physical and mental performance. Early detection of fatigue-related performance decrements is an important component of injury prevention and can help to ensure optimal performance and mission readiness. This study used a predictive visual tracking task and a computer-based measure of attention to characterize fatigue-related attention decrements in healthy Army personnel during acute sleep deprivation. METHODS: Serving as subjects in this laboratory-based study were 87 male and female service members between the ages of 18 and 50 with no history of brain injury with loss of consciousness, substance abuse, or significant psychiatric or neurologic diagnoses. Subjects underwent 26 h of sleep deprivation, during which eye movement measures from a continuous circular visual tracking task and attention measures (reaction time, accuracy) from the Attention Network Test (ANT) were collected at baseline, 20 h awake, and between 24 to 26 h awake. RESULTS: Increases in the variability of gaze positional errors (46-47%), as well as reaction time-based ANT measures (9-65%), were observed across 26 h of sleep deprivation. Accuracy of ANT responses declined across this same period (11%). DISCUSSION: Performance measures of predictive visual tracking accurately reflect impaired attention due to acute sleep deprivation and provide a promising approach for assessing readiness in personnel serving in diverse occupational areas, including flight and ground support crews. Language: en

Objectives Evidence-based traumatic brain injury guidelines support cerebral perfusion pressure thresholds for adults at a class 2 level, but evidence is lacking in younger patients. The purpose of this study is to identify the impact of age-specific cerebral perfusion pressure thresholds on short-term survival among patients with severe traumatic brain injury.

Object In spite of evidence that use of the Brain Trauma Foundation Guidelines for the Management of Severe Traumatic Brain Injury (Guidelines) would dramatically reduce morbidity and mortality, adherence to these Guidelines remains variable across trauma centers. The authors analyzed 2-week mortality due to severe traumatic brain injury (TBI) from 2001 through 2009 in New York State and examined the trends in adherence to the Guidelines. Methods The authors calculated trends in adherence to the Guidelines and age-adjusted 2-week mortality rates between January 1, 2001, and December 31, 2009. Univariate and multivariate logistic regression analyses were performed to evaluate the effect of time period on case-fatality. Intracranial pressure (ICP) monitor insertion was modeled in a 2-level hierarchical model using generalized linear mixed effects to allow for clustering by different centers. Results From 2001 to 2009, the case-fatality rate decreased from 22% to 13% (p < 0.0001), a change that remained significant after adjusting for factors that independently predict mortality (adjusted OR 0.52, 95% CI 0.39–0.70; p < 0.0001). Guidelines adherence increased, with the percentage of patients with ICP monitoring increasing from 56% to 75% (p < 0.0001). Adherence to cerebral perfusion pressure treatment thresholds increased from 15% to 48% (p < 0.0001). The proportion of patients having an ICP elevation greater than 25 mm Hg dropped from 42% to 29% (p = 0.0001). Conclusions There was a significant reduction in TBI mortality between 2001 and 2009 in New York State. Increase in Guidelines adherence occurred at the same time as the pronounced decrease in 2-week mortality and decreased rate of intracranial hypertension, suggesting a causal relationship between Guidelines adherence and improved outcomes. Our findings warrant future investigation to identify methods for increasing and sustaining adherence to evidence-based Guidelines recommendations.

The scope and purpose of this work is 2-fold: to synthesize the available evidence and to translate it into recommendations. This document provides recommendations only when there is evidence to support them. As such, they do not constitute a complete protocol for clinical use. Our intention is that these recommendations be used by others to develop treatment protocols, which necessarily need to incorporate consensus and clinical judgment in areas where current evidence is lacking or insufficient. We think it is important to have evidence-based recommendations to clarify what aspects of practice currently can and cannot be supported by evidence, to encourage use of evidence-based treatments that exist, and to encourage creativity in treatment and research in areas where evidence does not exist. The communities of neurosurgery and neuro-intensive care have been early pioneers and supporters of evidence-based medicine and plan to continue in this endeavor. The complete guideline document, which summarizes and evaluates the literature for each topic, and supplemental appendices (A-I) are available online at https://www.braintrauma.org/coma/guidelines.

To aid a clear and unified visual perception while tracking a moving target, both eyes must be coordinated, so the image of the target falls on approximately corresponding areas of the fovea of each eye. The movements of the two eyes are decoupled during sleep, suggesting a role of arousal in regulating binocular coordination. While the absence of visual input during sleep may also contribute to binocular decoupling, sleepiness is a state of reduced arousal that still allows for visual input, providing a context within which the role of arousal in binocular coordination can be studied. We examined the effects of sleep deprivation on binocular coordination using a test paradigm that we previously showed to be sensitive to sleep deprivation. We quantified binocular coordination with the SD of the distance between left and right gaze positions on the screen. We also quantified the stability of conjugate gaze on the target, i.e., gaze-target synchronization, with the SD of the distance between the binocular average gaze and the target. Sleep deprivation degraded the stability of both binocular coordination and gaze-target synchronization, but between these two forms of gaze control the horizontal and vertical components were affected differently, suggesting that disconjugate and conjugate eye movements are under different regulation of attentional arousal. The prominent association found between sleep deprivation and degradation of binocular coordination in the horizontal direction may be used for a fit-for-duty assessment.

Object Evidence-based guidelines recommend intracranial pressure (ICP) monitoring for patients with severe traumatic brain injury (TBI), but there is limited evidence that monitoring and treating intracranial hypertension reduces mortality. This study uses a large, prospectively collected database to examine the effect on 2-week mortality of ICP reduction therapies administered to patients with severe TBI treated either with or without an ICP monitor. Methods From a population of 2134 patients with severe TBI (Glasgow Coma Scale [GCS] Score Results Age, initial GCS score, hypotension, and CT scan findings were associated with 2-week mortality. In addition, patients of all ages treated with an ICP monitor in place had lower mortality at 2 weeks (p = 0.02) than those treated without an ICP monitor, after adjusting for parameters that independently affect mortality. Conclusions In patients with severe TBI treated for intracranial hypertension, the use of an ICP monitor is associated with significantly lower mortality when compared with patients treated without an ICP monitor. Based on these findings, the authors conclude that ICP-directed therapy in patients with severe TBI should be guided by ICP monitoring.

This clinical policy provides evidence-based recommendations on select issues in the management of adult patients with mild traumatic brain injury (TBI) in the acute setting. It is the result of joint efforts between the American College of Emergency Physicians and the Centers for Disease Control and Prevention and was developed by a multidisciplinary panel. The critical questions addressed in this clinical policy are: (1) Which patients with mild TBI should have a noncontrast head computed tomography (CT) scan in the emergency department (ED)? (2) Is there a role for head magnetic resonance imaging over noncontrast CT in the ED evaluation of a patient with acute mild TBI? (3) In patients with mild TBI, are brain specific serum biomarkers predictive of an acute traumatic intracranial injury? (4) Can a patient with an isolated mild TBI and a normal neurologic evaluation result be safely discharged from the ED if a noncontrast head CT scan shows no evidence of intracranial injury? Inclusion criteria for application of this clinical policy's recommendations are nonpenetrating trauma to the head, presentation to the ED within 24 hours of injury, a Glasgow Coma Scale score of 14 or 15 on initial evaluation in the ED, and aged 16 years or greater. The primary outcome measure for questions 1, 2, and 3 is the presence of an acute intracranial injury on noncontrast head CT scan; the primary outcome measure for question 4 is the occurrence of neurologic deterioration.

Prehospital management of traumatic brain injury (TBI) and trauma system development and organization are aspects of TBI care that have the potential to significantly impact patient outcome. This multi-center study was conducted to explore the effect of prehospital management decisions on early mortality after severe TBI.This report is based on 1449 patients with severe TBI (GCS9) treated at 22 trauma centers enrolled in a New York State quality improvement (QI) program between 2000 and 2004. The prehospital data collected on these patients include time of injury, time of arrival to the trauma center, mode of transport, type of EMS provider, direct or indirect transport, blood pressure and pulse oximetry values, GCS score, pupillary assessment, and airway management procedures.After exclusion criteria were applied, a total of 1,123 patients were eligible for analysis. The majority of patients were male (75%) with a mean age of 36 years. After controlling for arterial hypotension, age, pupillary status, and initial GCS score, direct transport was found to result in significantly lower mortality than indirect transport. Transport mode, time to admission, and prehospital intubation were not found to be related to 2-week mortality.The present study provides class II evidence that demonstrates a 50% increase in mortality associated with indirect transfer of TBI patients. Patients with severe TBI should be transported directly to a Level I or Level II trauma center with capabilities as delineated in the Guidelines for the Prehospital Management of Traumatic Brain Injury, even if this center may not be the closest hospital.

INDICATIONS FOR SURGERY An acute subdural hematoma (SDH) with a thickness greater than 10 mm or a midline shift greater than 5 mm on computed tomographic (CT) scan should be surgically evacuated, regardless of the patient's Glasgow Coma Scale (GCS) score. All patients with acute SDH in coma (GCS score less than 9) should undergo intracranial pressure (ICP) monitoring. A comatose patient (GCS score less than 9) with an SDH less than 10-mm thick and a midline shift less than 5 mm should undergo surgical evacuation of the lesion if the GCS score decreased between the time of injury and hospital admission by 2 or more points on the GCS and/or the patient presents with asymmetric or fixed and dilated pupils and/or the ICP exceeds 20 mm Hg. TIMING In patients with acute SDH and indications for surgery, surgical evacuation should be performed as soon as possible. METHODS If surgical evacuation of an acute SDH in a comatose patient (GCS < 9) is indicated, it should be performed using a craniotomy with or without bone flap removal and duraplasty.

Indications for surgery An epidural hematoma (EDH) greater than 30 cm3 should be surgically evacuated regardless of the patient's Glasgow Coma Scale (GCS) score. An EDH less than 30 cm3 and with less than a 15-mm thickness and with less than a 5-mm midline shift (MLS) in patients with a GCS score greater than 8 without focal deficit can be managed nonoperatively with serial computed tomographic (CT) scanning and close neurological observation in a neurosurgical center. Timing It is strongly recommended that patients with an acute EDH in coma (GCS score Methods There are insufficient data to support one surgical treatment method. However, craniotomy provides a more complete evacuation of the hematoma.

INDICATIONS: Patients with parenchymal mass lesions and signs of progressive neurological deterioration referable to the lesion, medically refractory intracranial hypertension, or signs of mass effect on computed tomographic (CT) scan should be treated operatively. Patients with Glasgow Coma Scale (GCS) scores of 6 to 8 with frontal or temporal contusions greater than 20 cm3 in volume with midline shift of at least 5 mm and/or cisternal compression on CT scan, and patients with any lesion greater than 50 cm3 in volume should be treated operatively. Patients with parenchymal mass lesions who do not show evidence for neurological compromise, have controlled intracranial pressure (ICP), and no significant signs of mass effect on CT scan may be managed nonoperatively with intensive monitoring and serial imaging. TIMING AND METHODS: Craniotomy with evacuation of mass lesion is recommended for those patients with focal lesions and the surgical indications listed above, under Indications. Bifrontal decompressive craniectomy within 48 hours of injury is a treatment option for patients with diffuse, medically refractory posttraumatic cerebral edema and resultant intracranial hypertension. Decompressive procedures, including subtemporal decompression, temporal lobectomy, and hemispheric decompressive craniectomy, are treatment options for patients with refractory intracranial hypertension and diffuse parenchymal injury with clinical and radiographic evidence for impending transtentorial herniation.

In 1995, evidence-based guidelines for the management of severe traumatic brain injury (TBI) were published and disseminated. Information regarding their implementation is limited.During 1999 to 2000, we contacted all designated U.S. trauma centers caring for adults with severe TBI to determine the degree of guideline compliance and to identify predictors.Of 924 centers identified, 828 participated (90%). Four hundred thirty-three with intensive care units caring for severe TBI were surveyed. Three hundred ninety-five centers transferring patients were excluded. Full guideline compliance was rare (n = 68 [16%]). In multivariate analyses, treatment protocols (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.9-6.6), neurosurgery residency program (OR, 5.0; 95% CI, 2.6-9.8), and state (OR, 2.7; 95% CI, 0.62-12) or American College of Surgeons (OR, 5.1; 95% CI, 1.1-23) designation increased the likelihood of full compliance versus noncompliance.Although evidence-based guidelines were published and disseminated in 1995, implementation is infrequent. Focus must turn to changing physician practice and transport decisions to provide guideline-compliant care and improve patient outcome.

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate significant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.

Objective To conduct a systematic review and meta-analysis evaluating the role of exercise or rest in patients with concussion or mild traumatic brain injury. Design Systematic review and meta-analysis. Data sources Medline, PsychInfo, Scopus, Cochrane Controlled Trials Registers and Sport Discus, till March 2016 and hand search of some articles. Study selection Randomised controlled trials (RCTS) and observational studies (OBS) comparing the effect of exercise or rest in patients with concussion, on different outcomes. Participants Children and adults with concussion or mild traumatic brain injury. Intervention Exercise or Rest. Outcomes Post concussive symptoms (PCCS), balance error scoring system (BESS), immediate post concussion assessment and cognitive testing (ImPACT). Main results Our search generated 921 studies. Of these, 5 RCTs and 12 OBS met our inclusion criteria. Methodological quality of most of the studies was poor. Meta-analysis of 6 studies involving more than 556 patients showed statistical significant decrease in PCCS with exercise compared to control, Mean Difference (MD) [95% Confidence Interval (CI)], −14.6 [−17.8, −11.3], p There was not effect of rest on total symptoms in patients with concussion and number of patients with symptoms. Conclusion Our systematic review and meta-analysis showed clear benefits of exercise in PCCS. However, the evidence was based on poor quality studies that vary in duration, frequency and intensity of exercise. A good quality RCT needs to be conducted to evaluate a clear effect of exercise and rest in patients with concussion. Competing interests None.

INTRODUCTION Treatment of patients with traumatic brain injury (TBI) should be based upon the strongest evidence to achieve optimal patient outcomes. Given the challenges, efforts involved, and delays in uptake of evidence into practice, priorities for knowledge translation (KT) should be chosen carefully. An international workshop was convened to identify KT priorities for acute and rehabilitation care of TBI and develop KT projects addressing these priorities. METHODS An expert panel of 25 neurotrauma clinicians, researchers, and KT scientists representing 4 countries examined 66 neurotrauma research topics synthesized from 2 neurotrauma evidence resources: Evidence Based Review of Acquired Brain Injury and Global Evidence Mapping projects. The 2-day workshop combined KT theory presentations with small group activities to prioritize topics using a modified Delphi method. RESULTS Four acute care topics and 3 topics in the field of rehabilitation were identified. These were focused into 3 KT project proposals: optimization of intracranial pressure and nutrition in the first week following TBI; cognitive rehabilitation following TBI; and vocational rehabilitation following TBI. CONCLUSION Three high-priority KT projects were developed: the first combined 2 important topics in acute TBI management of intracranial pressure management and nutrition, and the other projects focused on cognitive rehabilitation and vocational rehabilitation.

An attention-based biomarker may be useful for concussion screening. A key role of attention is to generate time-based expectancies of specific sensory information, and it is postulated that postconcussion cognitive impairments and symptoms may stem from a primary deficit in this predictive timing mechanism. There is a close relationship between gaze and attention, but in addressing predictive timing, there is a need for an appropriate testing paradigm and methods to quantify oculomotor anomalies. We have utilized a continuous predictive visual tracking paradigm because human visual tracking requires predicting the temporal course of a stimulus and dynamically synchronizing the required action with the stimulus. We have shown that concussion patients often show disrupted gaze-target synchronization characterized by large gaze position error variability and overall phase advancement. Various attention components interact with visual tracking, and thus there is a possibility that different neurological and physiological conditions produce identifiable visual tracking characteristics. Analyzing neuromotor functions, specifically oculomotor synchronization, can provide a fast, accurate, and reliable assessment of cognitive functions.

¶ The authors retrospectively analysed two groups of consecutive patients who were similarly matched for brain injury severity. From a total of 39 severe head injury patients, 23 were treated according to the Guidelines for the Management of Severe Head Injury with intracranial pressure (ICP) monitoring (“Guidelines group”). Such an approach allowed the maintenance of ICP within normal values, especially in patients with intraventricular ICP monitoring allowing the release of cerebrospinal fluid (CSF) from the ventricular system. In the Guidelines group only two patients were administered barbiturates, after all other means of ICP lowering had been exhausted. The second group consisted of 16 patients who were not monitored for ICP (“non-Guidelines group”). In this group, management consisted of the prophylactic administration of barbiturates, high dose osmotic diuretics and hyperventilation usually at levels below 25 mm Hg. In the Guidelines group the mortality rate was 30% compared to 44% in the non-Guidelines group. Almost twice as many patients achieved a “favourable” (good recovery and moderate disability) outcome (49%) compared to the non-Guidelines treated patients (25%). Furthermore, there was a 32% decrease in severe neurological disabilities in those patients in the Guidelines group. It seems that the implementation of “Guidelines” in the treatment of severe head injury, based on the result of our clinical study, reduces death and disability rates in patients with severe head injury. The administration of therapy based on the “Guidelines principles” and monitoring of ICP, can minimise the application of those therapeutic modalities (barbiturate coma and prolonged hyperventilation) which, in addition to favourable effects, may also have harmful effects on patients with severe head injury.

Increasing clinical and experimental evidence suggests that traumatic brain injury (TBI) elicits an acute inflammatory response. In the present study we investigated whether white blood cells (WBC) are activated in the cerebral microcirculation early after TBI and whether WBC accumulation affects the posttraumatic cerebrovascular response. Twenty-four anesthetized rabbits had chronic cranial windows implanted 3 weeks before experimentation. Animals were divided into four experimental groups and were studied for 7 hours (groups I, IIa, and III) or 2 hours (group IIb). Intravital fluorescence videomicroscopy was used to visualize WBC (rhodamine 6G, intravenously), pial vessel diameters, and blood–brain barrier (BBB) integrity (Na+-fluorescein) at 6 hours (groups I, IIa, and III) or 1 hour (group IIb) after TBI. Group I (n = 5) consisted of sham-operated animals. Groups IIa (n = 7) and IIb (n = 5) received fluid-percussion injury at 1 hour. Group III (n = 7) received fluid-percussion injury and 1 mg/kg anti–adhesion monoclonal antibody (MoAb) “IB4” 5 minutes before injury. Venular WBC sticking, intracranial pressure (ICP), and arterial vessel diameters increased significantly for 6 hours after trauma. IB4 reduced WBC margination and prevented vasodilation. Intracranial pressure was not reduced by treatment with IB4. Blood–brain barrier damage occurred at 1 hour but not at 6 hours after TBI and was independent of WBC activation. This first report using intravital videomicroscopy to study the inflammatory response after TBI reveals upregulated interaction between WBC and cerebral endothelium that can be manipulated pharmacologically. White blood cell activation is associated with pial arteriolar vasodilation. White blood cells do not induce BBB breakdown less than 6 hours after TBI and do not contribute to posttraumatic ICP elevation. The role of WBC more than 6 hours after TBI should be investigated further.

The temporal delay between sensory input and motor execution is a fundamental constraint in interactions with the environment. Predicting the temporal course of a stimulus and dynamically synchronizing the required action with the stimulus are critical for offsetting this constraint, and this prediction-synchronization capacity can be tested using visual tracking of a target with predictable motion. Although the role of temporal prediction in visual tracking is assumed, little is known of how internal predictions interact with the behavioral outcome or how changes in the cognitive state influence such interaction. We quantified and compared the predictive visual tracking performance of military volunteers before and after one night of sleep deprivation. The moment-to-moment synchronization of visual tracking during sleep deprivation deteriorated with sensitivity changes greater than 40 %. However, increased anticipatory saccades maintained the overall temporal accuracy with near zero phase error. Results suggest that acute sleep deprivation induces instability in visuomotor prediction, but there is compensatory visuomotor adaptation. Detection of these visual tracking features may aid in the identification of insufficient sleep.