Addressing the needs of traumatic brain injury with clinical proteomics.

BackgroundNeurotrauma or injuries to the central nervous system (CNS) are a serious public health problem worldwide. Approximately 75% of all traumatic brain injuries (TBIs) are concussions or other mild TBI (mTBI) forms. Evaluation of concussion injury today is limited to an assessment of behavioral symptoms, often with delay and subject to motivation. Hence, there is an urgent need for an accurate chemical measure in biofluids to serve as a diagnostic tool for invisible brain wounds, to monitor severe patient trajectories, and to predict survival chances. Although a number of neurotrauma marker candidates have been reported, the broad spectrum of TBI limits the significance of small cohort studies. Specificity and sensitivity issues compound the development of a conclusive diagnostic assay, especially for concussion patients. Thus, the neurotrauma field currently has no diagnostic biofluid test in clinical use.ContentWe discuss the challenges of discovering new and validating identified neurotrauma marker candidates using proteomics-based strategies, including targeting, selection strategies and the application of mass spectrometry (MS) technologies and their potential impact to the neurotrauma field.SummaryMany studies use TBI marker candidates based on literature reports, yet progress in genomics and proteomics have started to provide neurotrauma protein profiles. Choosing meaningful marker candidates from such 'long lists' is still pending, as only few can be taken through the process of preclinical verification and large scale translational validation. Quantitative mass spectrometry targeting specific molecules rather than random sampling of the whole proteome, e.g., multiple reaction monitoring (MRM), offers an efficient and effective means to multiplex the measurement of several candidates in patient samples, thereby omitting the need for antibodies prior to clinical assay design. Sample preparation challenges specific to TBI are addressed. A tailored selection strategy combined with a multiplex screening approach is helping to arrive at diagnostically suitable candidates for clinical assay development. A surrogate marker test will be instrumental for critical decisions of TBI patient care and protection of concussion victims from repeated exposures that could result in lasting neurological deficits

Concussion-related Alterations in Neural Activity During Emotion Recognition: Case Studies of Short-term and Residual Effects

Concussions have recently become an area of concern among the general public, but a clear understanding of their total consequence is still being developed. Symptoms of concussions are wide-ranging, encapsulating a plethora of cognitive and emotional abilities that could be affected. Concussions transiently disrupt neural activation as well as behavioral responses across multiple categories. Skills pertaining to various aspects of emotions are often affected yet have rarely been studied after concussions. We present two case studies of collegiate athletes with a history of multiple concussions. This paper highlights the case of a collegiate athlete who had obtained two previous concussions with the most recent being sustained sixteen days prior to neuroimaging. A second athlete with two lifetime concussions was tested one year after the most recent injury. The current study utilized a novel emotional recognition task to assess the behavioral and neural effects of this injury. A group of five controls responded with high accuracy rates and quick response times to the task. They showed activation in regions of the frontal lobe as well as facial recognition areas of the occipital lobe. The 16-day case subject was impaired in recognizing emotions relative to controls and showed little to no overlap in brain activity for regions involved in emotional face processing. The athlete with a longer post-concussion period also showed residual effects of neural activity alteration when compared to controls with few overlapping active regions. Specific brain regions were activated in this group but not in controls including the sensorimotor cortex, supramarginal gyrus, and lateral occipital cortex. By taking a more individual approach in examination of neural activity post-concussion, we may be able to gain a better understanding of this heterogeneous injury

The Sport Concussion Assessment Tool (SCAT2) for evaluating civilian mild traumatic brain injury

Post-concussion symptoms; SCAT2; Head injurySíntomas posteriores a la conmoción cerebral; SCAT2; Lesión cranealSímptomes posteriors a la commoció cerebral; SCAT2; Lesió cranialSelf-report measures, particularly symptom inventories, are critical tools for identifying patients with persistent post-concussion symptoms and their follow-up. Unlike in military or sports-related assessment, in general civilian settings pre-injury levels of concussion-like symptoms are lacking. Normative data are available in adolescent and college populations, but no reference data exist to guide clinical adult explorations. The purpose of this study was to use the second edition of the Sport Concussion Assessment Tool (SCAT2) to profile a cohort of 60 healthy community volunteers who had not sustained a head injury. Participating volunteers underwent MRI scanning and were evaluated with the Hospital Anxiety and Depression Scale (HADS). Participants reported a median of 3 concussion-like symptoms and the 97.5 percentile score was found at 10.5 symptoms, out of a total of 22. The median severity score was 4.9 points, and 28.9 was the upper limit of the reference interval. Only 10 participants (16.7%) did not endorse any symptom. The most frequently endorsed symptom was feeling difficulty in concentrating, with 41.7% of the sample reporting it. Age, sex and general distress, anxiety and depressive symptoms were not associated with concussion-like symptoms. Our data yielded elevated cut-offs scores for both the number of symptoms and the symptom severity. In conclusion, postconcussive-like symptoms are frequent in the general non-concussed adult population and it should be taken into account in any future models developed for screening patients at risk of developing physical, cognitive, and psychological complaints following mild traumatic injury.UNINN is supported by a Grant from the Generalitat de Catalunya (SGR 2014-844, http://agaur.gencat.cat). This work has been supported in part by the Fondo de Investigacion Sanitaria (Instituto de Salud Carlos III, https://portalfis.isciii.es) with grants FIS PI11/00700 (J.S.) and grant FIS PI13/02397 (M.A.P.), which were co-financed by the European Regional Development Fund (ERDF). A.R. was a recipient of a pre-doctoral grant from the Fundacio Institut de Recerca VHIR (PRED-VHIR-2012-26, http://en.vhir.org)

Head Impact Situations in Professional Football (Soccer)

To assess head impact incidents (HIIs) and to distinguish diagnosed head injuries from other incidents, a video observation analysis of match HIIs was conducted in the German Bundesliga (2017/18 season). Video recordings of each match were screened to identify the respective events. Head injury data were identified by a prospective injury registry. HII and head injury incidence rates (IR) were calculated with 95 % CIs. The total number of HIIs was 1362 corresponding to an IR of 134.9/1000 match hours (95% CI 127.9–142.2). In 123 HII (IR 12.2, 95% CI 10.2–14.5) the contact was classified as severe. Head contact with the opponent was the most frequent cause (85%). The most frequent mechanism was in 44% (combined) the arm and elbow-to-head, followed by head-to-head and hand-to-head contacts (each 13%). In 58%, the HIIs occurred during header duels. Twenty-nine head injuries were recorded (IR 2.9, 95% CI 2.0–4.1). Concussions/traumatic brain injuries accounted for 48%, head/facial fractures 24%, head/facial contusions 21%, and lacerations/abrasions 7%. The number of HIIs not classified as concussions/more severe trauma was high. Identification of HIIs and head injury severity should be improved during on-field assessment as many head injuries might go unrecognised based on the large number of HIIs

Sport-Related Concussions: Symptom Recurrence After Return to Exercise

Background: Current guidelines dictate a gradual exercise progression after a concussion; however, it is unclear what proportion of athletes experience a recurrence of symptoms once they are symptom free at rest. Estimating the proportion of athletes and predictors of symptom recurrence would help shape return-to-play protocols. Purpose: To determine the proportion and associated risk factors of athletes who have a recurrence of concussion symptoms with exercise after being symptom free at rest. Study Design: Case-control study; Level of evidence, 3. Methods: Between October 1, 2009 and July 31, 2011, we studied patients from a sport concussion clinic located within a tertiary care regional children’s hospital. Patients were queried at every visit using a standardized questionnaire. Our main outcome variable was recurrence of symptoms with exercise after being symptom free at rest at some point in their recovery. Cofactors included age, sex, loss of consciousness with injury, prior concussion (diagnosed and undiagnosed), Post-Concussion Symptom Scale (PCSS) score, time until clinical presentation, and duration of symptoms. Results: Of the 217 patients included, 25 (12%) experienced a return of symptoms. Losing consciousness at the time of injury and a longer duration between injury and clinical presentation were associated with a decreased risk of symptoms recurring with exercise. Conversely, athletes who had sustained previously undiagnosed concussions and had suffered a longer duration of symptoms at rest were at an increased risk of symptom recurrence with exercise. Conclusion: Relatively few athletes who are symptom free at rest after a concussion will have a recurrence of symptoms when they resume exercise. The risk of symptoms recurring with exercise may be greater among those athletes who sustained previously undiagnosed concussions and had a longer period of symptoms at rest. The early identification of athletes who may be at risk of symptom recurrence will help mold treatment guidelines and exercise progression protocols