Concussion diagnosis and recovery in relation to collegiate athletic department classification: a LIMBIC MATARS consortium investigation.

PURPOSE: We investigated time to reach concussion diagnosis and recovery milestones in collegiate athletes relative to their schools' National Collegiate Athletic Association (NCAA) classification. METHODS: We retrospectively examined 849 (43.1% female) concussion cases from 11 NCAA institutions (Division I Power 5 [n = 4], Division I Non-Power 5 [n = 4], and Division II/III [n = 3]) from the 2015-16 to 2019-20 athletic seasons. Our primary outcome measures were days to reach specific clinical milestones following concussion. RESULTS: Median (IQR) time from injury to diagnosis was significantly longer at Division II/III institutions (1 [0-4] days) compared to Division I Power 5 (0 [0-1] days) and Division I Non-Power 5 (0 [0-1] days) institutions (p < 0.001). Likewise, Division II/III athletes (15 [11-22] days) took significantly longer to return to sport after concussion than Division I Power 5 (10 [7-16] days) and Division I Non-Power 5 (11 [7-18.5] days) athletes (p < 0.001). CONCLUSION: Division II/III athletes had delayed concussion diagnoses and return to sport timelines compared to Division I athletes. Our results suggest that differences in sports medicine resources across NCAA divisions may influence injury recognition and recovery in collegiate athletes with concussion.

Physical activity and recovery following concussion in collegiate athletes: a LIMBIC MATARS Consortium Investigation.

OBJECTIVE: To investigate whether routine daily activities (RDA), non-prescribed exercise (Non-ERx), or prescribed exercise (ERx) were associated with recovery from sport-related concussion (SRC) in collegiate athletes. MATERIALS AND METHODS: Data for this cross-sectional, retrospective chart review of collegiate athletes diagnosed with SRC (n = 285[39.6% female], age = 19.5 ± 1.4 years) were collected during the 2015-16 to 2019-20 athletic seasons. The independent variable was group (RDA, Non-ERx, ERx). Dependent variables included days from date of diagnosis to symptom resolution (Dx-SR) and SR to return to sport (SR-RTS). RESULTS: Those in the Non-ERx group took nearly 1.3 times longer to achieve SR (IRR = 1.28, 95% CI: 1.11, 1.46) and, 1.8 times longer for RTS (IRR = 1.82, 95% CI: 1.11, 2.71) when compared to those in the RDA group. No other comparisons were significant. CONCLUSION: Collegiate athletes in the Non-ERx group took approximately 1 week longer to achieve SR as compared to the RDA and ERx groups. Our findings suggest that if exercise is recommended following SRC, it must be clearly and specifically prescribed. If exercise parameters cannot be prescribed, or monitored, RDA appear to be similarly beneficial during recovery for collegiate athletes with concussion.

Academic adjustments and concussion recoveries in NCAA student-athletes: a LIMBIC MATARS investigation.

OBJECTIVE: The aim of this study was to investigate the association between academic adjustments and recovery from sport-related concussions (SRCs) in collegiate athletes. MATERIALS AND METHODS: A retrospective medical chart review was performed between the 2015-2016 and 2019-2020 sport seasons at 11 Long-term Impact of Military-relevant Brain Injury Consortium Military and Tactical Athlete Research Study (LIMBIC MATARS) sites. Days between injury and symptom resolution, and injury and return to sport (dependent variables) for collegiate athletes who did or did not receive academic adjustments (independent variable) were analyzed using Mann-Whitney U tests. RESULTS: The number of days between date of injury and symptom-resolution between those who did (median = 9 [interquartile range = 5,16]) and did not have (7[3,12]) academic adjustments were statistically different (z=-2.76, p < 0.01, r=-0.17). However, no differences were observed between days to return to sport among those who did (14[10,22]) and did not (13[8,20]) receive assigned academic adjustments (z= -1.66, p = 0.10, r= -.10). CONCLUSIONS: Recovery trajectories were similar between athletes diagnosed with a SRC who did or did not receive academic adjustments.. Our findings suggest academic adjustments supported recovery for those who needed academic adjustments. Clinicians and healthcare professionals should assist and support collegiate athletes after SRCs on an individual basis, including academic adjustments when appropriate based on patient presentation.

Access to athletic trainers and sex as modifiers of time to reach clinical milestones after sport-related concussion in collegiate athletes.

OBJECTIVE: Investigate whether an athlete's biological sex and exposure to a dedicated athletic trainer (AT) were related to clinical milestones after a sports-related concussion (SRC). DESIGN: Retrospective chart review. METHODS: Medical charts of collegiate athletes (n = 196 [70.9% female]) diagnosed with SRC were reviewed to extract: biological sex, dedicated AT exposure for their sport (yes/no), and time (days) to reaching clinical milestones (diagnosis, symptom resolution, unrestricted return to sport [RTS]). Mann-Whitney U tests were used to determine whether time to clinical milestones differed by sex, AT exposure, or their interaction. Proportions of same-day diagnoses and times to diagnosis, symptom resolution, and unrestricted RTS were evaluated with chi-squared and spearman's rank correlations, respectively. RESULTS: There were no significant differences in times to reaching any clinical milestone by sex, AT exposure, or their interaction (ps > 0.05). Forty-three percent of participants were diagnosed on the day of their SRC. This did not differ by sex or AT exposure (ps > 0.29). Longer times to SRC diagnosis were associated with more days to symptom resolution (ρ = 0.236, p = 0.001) and unrestricted RTS (ρ = 0.223, p < 0.001). CONCLUSIONS: Athlete sex and AT exposure were not associated with times to reach any clinical milestone; however, delayed diagnosis was associated with longer times to reach clinical recovery.

High molar ratios of tumor necrosis factor α (TNF α) soluble receptors I and II to the TNF ligand in human plasma from male veterans with comorbid posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI).

Background and Objectives: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are associated with chronic inflammation, as inferred from increased, but variable, peripheral levels of cytokines. We sought proof of concept for the notion that peripheral cytokine binding proteins and/or soluble receptors can confound measures of cytokines in those with a history of physical and psychological traumatic exposures. Efforts were focused on one of the major cytokines involved in inflammation, tumor necrosis factor-α (TNF-α). Methods: We examined blood plasma concentrations of TNF-α, its soluble receptors (TNF-soluble receptors (sR) I and TNFsRII), and C-reactive protein (CRP-1) in a cohort of US Veterans. In a previous study, CRP-1 was shown to be reduced by probiotic anti-inflammatory treatment in this patient cohort. All participants (n = 22) were diagnosed with PTSD and had a history of mild TBI with persistent post-concussive symptoms. Exclusion criteria included medications directly targeting inflammation. Results: Molar concentrations of soluble TNFsRI and II exceeded concentrations of the TNF-α ligand. TNFsRI, but not TNFsRII, was significantly associated with CRP-1 (Spearman Rho correlations = 0.518; p=.016 and 0.365; p = .104, respectively). Conclusions: TNF soluble receptors may bind to and sequester free TNF-α, suggesting that only measuring ligand concentrations may not provide a fully comprehensive view of inflammation, and potentially lead to inaccurate conclusions. TNFsRI concentration may provide a better estimate of inflammation than TNF-α for those with PTSD and post-acute mTBI with post-concussive symptoms, a hypothesis that invites further testing in larger studies.

Association between sports participation history and age of first exposure to high-risk sports with concussion history.

The purpose of this study was to examine the association between sports participation history, including estimated age of first exposure (eAFE) to high-risk sports, and concussion history in first year (i.e., freshmen) collegiate athletes. Athletes increased their odds of sustaining a pre-college concussion by 5% [odds ratio(OR) = 1.05 (95%CI:1.05-1.06)] for each additional year of contact sports participation - 24% of all student athletes reported one or more pre-college concussions. When eAFE was analysed dichotomously at age 12, a greater proportion of those who started playing football before age 12 reported a positive concussion history compared to those who started playing football at age 12 or later (Ð¥2 = 4.483, p = 0.034, Phi = 0.049). When eAFE was analysed continuously, later eAFE to women's high-risk sports was associated with a lower likelihood of sustaining a pre-college concussion [OR = 0.93 (95%CI:0.88-0.98)]. Our findings suggest that there is a relationship between eAFE to football and to women's high-risk sports and concussion history.

Evaluation of serum neurofilament light in the early management of mTBI patients.

OBJECTIVES: Serum S100B allows a one-third reduction of computed tomography (CT) scans performed for mild traumatic brain injury (mTBI) patients. In this study, we evaluated the diagnostic performance of serum NF-L in the detection of intracranial lesions induced by mTBI. METHODS: One hundred seventy-nine adult mTBI patients presenting to the emergency department of Clermont-Ferrand University Hospital with a Glasgow Coma Scale (GCS) score of 14-15 were included. S100B assays were performed for clinical routine while NF-L samples were stored at -80 °C until analysis. CT scans were performed for patients with S100B levels above the decision threshold of 0.10 µg/L. Later, NF-L and S100B levels were compared to CT scan findings to evaluate the biomarkers' performances. RESULTS: The area under the ROC curve (AUC) evaluating the diagnostic ability in the prediction of intracranial lesions was 0.72 (95% CI; 0.58-0.87) for S100B and 0.58 (95% CI; 0.45-0.71) for NF-L, the specificities (at a threshold allowing a 100% sensitivity) were 35.7% for S100B, and 28% for NF-L (p=0.096). AUCs of NF-L and S100B for the identification of patients with neurological disorders were statistically different (p<0.001). The AUCs were 0.87 (95% CI; 0.82-0.93) for NF-L and 0.57 (95% CI; 0.48-0.66) for S100B. There was a poor correlation between NF-L and S100B, and NF-L levels were correlated to patients' age (Spearman coefficient of 0.79). CONCLUSIONS: NF-L showed poor performances in the early management of mTBI patients. NF-L levels are strongly correlated to neurodegeneration, whether physiological, age-related, or pathological.

CGRP monoclonal antibody prevents the loss of diffuse noxious inhibitory controls (DNIC) in a mouse model of post-traumatic headache.

AIM: Determine the role of calcitonin-gene related peptide in promoting post-traumatic headache and dysregulation of central pain modulation induced by mild traumatic brain injury in mice. METHODS: Mild traumatic brain injury was induced in lightly anesthetized male C57BL/6J mice by a weight drop onto a closed and unfixed skull, which allowed free head rotation after the impact. We first determined possible alterations in the diffuse noxious inhibitory controls, a measure of net descending pain inhibition called conditioned pain modulation in humans at day 2 following mild traumatic brain injury. Diffuse noxious inhibitory control was assessed as the latency to a thermally induced tail-flick that served as the test stimulus in the presence of right forepaw capsaicin injection that provided the conditioning stimulus. Post-traumatic headache-like behaviors were assessed by the development of cutaneous allodynia in the periorbital and hindpaw regions after mild traumatic brain injury. We then determined if intraperitoneal fremanezumab, an anti-calcitonin-gene related peptide monoclonal antibody or vehicle administered 2 h after sham or mild traumatic brain injury induction could alter cutaneous allodynia or diffuse noxious inhibitory control responses on day 2 post mild traumatic brain injury. RESULTS: In naïve and sham mice, capsaicin injection into the forepaw elevated the latency to tail-flick, reflecting the antinociceptive diffuse noxious inhibitory control response. Periorbital and hindpaw cutaneous allodynia, as well as a loss of diffuse noxious inhibitory control, was observed in mice 2 days after mild traumatic brain injury. Systemic treatment with fremanezumab blocked mild traumatic brain injury-induced cutaneous allodynia and prevented the loss of diffuse noxious inhibitory controls in mice subjected to a mild traumatic brain injury. INTERPRETATION: Sequestration of calcitonin-gene related peptide in the initial stages following mild traumatic brain injury blocked the acute allodynia that may reflect mild traumatic brain injury-related post-traumatic headache and, additionally, prevented the loss of net descending inhibition within central pain modulation pathways. As loss of conditioned pain modulation has been linked to multiple persistent pain conditions, dysregulation of descending modulatory pathways may contribute to the persistence of post-traumatic headache. Additionally, evaluation of the conditioned pain modulation/diffuse noxious inhibitory controls response may serve as a biomarker of vulnerability for chronic/persistent pain. These findings suggest that early anti-calcitonin-gene related peptide intervention has the potential to be effective both for the treatment of mild traumatic brain injury-induced post-traumatic headache, as well as inhibiting mechanisms that may promote post-traumatic headache persistence.

Post-traumatic Headache and Mild Traumatic Brain Injury: Brain Networks and Connectivity.

PURPOSE OF REVIEW: Post-traumatic headache (PTH) consequent to mild traumatic brain injury (mTBI) is a complex, multidimensional, chronic neurological disorder. The purpose of this review is to evaluate the current neuroimaging studies on mTBI and PTH with a specific focus on brain networks and connectivity patterns. RECENT FINDINGS: We present findings on PTH incidence and prevalence, as well as the latest neuroimaging research findings on mTBI and PTH. Additionally, we propose a new strategy in studying PTH following mTBI. The diversity and heterogeneity of pathophysiological mechanisms underlying mild traumatic brain injury pose unique challenges on how we interpret neuroimaging findings in PTH. Evaluating alterations in the intrinsic brain network connectivity patterns using novel imaging and analytical techniques may provide additional insights into PTH disease state and therefore inform effective treatment strategies.

Coping with stress before and after mild traumatic brain injury: a pilot hair cortisol study.

Background: Cortisol is a crucial hormone for adaptation to challenging and stressful situations. Hair cortisol measurement is used to determine chronic stress; the growth rate of hair allows to determine averaged cortisol levels for a longer period. Objective: Pre- and post-injury measures of hair cortisol were compared in patients with mild traumatic brain injury (mTBI), and related to their coping styles.Methods: For 46 patients with mTBI, 3 cm scalp hair samples were collected 4-6 weeks post-injury, resulting in two 1 cm segments, pre- and post-injury. Hair samples were also collected for 11 healthy controls. Hair cortisol was quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Complaints, anxiety, depression and coping style were measured two weeks post-injury and long term (six-twelve months), added with measures for post-traumatic stress and functional outcome.Results: There were no differences between patients' pre- and post-injury cortisol levels, nor between cortisol levels of patients and controls. However, pre- and post-injury cortisol levels of patients were negatively correlated with both passive and an avoidant coping style.Conclusions: Our findings suggest that mTBI has no separate impact on chronic long-term cortisol levels, possibility indicating that variability in cortisol levels reflects individuals' premorbid characteristics determining coping with stress in general.

Mild traumatic brain injury affects the features of migraine.

BACKGROUND: Headache is one of the most common symptoms after concussion, and mild traumatic brain injury (mTBI) is a risk factor for chronic migraine (CM). However, there remains a paucity of data regarding the impact of mTBI on migraine-related symptoms and clinical course. METHODS: Of 2161 migraine patients who participated in the American Registry for Migraine Research between February 2016 and March 2020, 1098 completed questions assessing history of TBI (50.8%). Forty-four patients reported a history of moderate to severe TBI, 413 patients reported a history of mTBI. Patients' demographics, headache symptoms and triggers, history of physical abuse, allodynia symptoms (ASC-12), migraine disability (MIDAS), depression (PHQ-2), and anxiety (GAD-7) were compared between migraine groups with (n = 413) and without (n = 641) a history of mTBI. Either the chi-square-test or Fisher's exact test, as appropriate, was used for the analyses of categorical variables. The Mann-Whitney test was used for the analyses of continuous variables. Logistic regression models were used to compare variables of interest while adjusting for age, gender, and CM. RESULTS: A significantly higher proportion of patients with mTBI had CM (74.3% [307/413] vs. 65.8% [422/641], P = 0.004), had never been married or were divorced (36.6% [147/402] vs. 29.4% [187/636], P = 0.007), self-reported a history of physical abuse (24.3% [84/345] vs. 14.3% [70/491], P <  0.001), had mild to severe anxiety (50.5% [205/406] vs. 41.0% [258/630], P = 0.003), had headache-related vertigo (23.0% [95/413] vs. 15.9% [102/640], P = 0.009), and difficulty finding words (43.0% [174/405] vs. 32.9% [208/633], P <  0.001) in more than half their attacks, and headaches triggered by lack of sleep (39.4% [155/393] vs. 32.6% [198/607], P = 0.018) and reading (6.6% [26/393] vs. 3.0% [18/607], P = 0.016), compared to patients without mTBI. Patients with mTBI had significantly greater ASC-12 scores (median [interquartile range]; 5 [1-9] vs. 4 [1-7], P < 0.001), MIDAS scores (42 [18-85] vs. 34.5 [15-72], P = 0.034), and PHQ-2 scores (1 [0-2] vs. 1 [0-2], P = 0.012). CONCLUSION: Patients with a history of mTBI are more likely to have a self-reported a history of physical abuse, vertigo, and allodynia during headache attacks, headaches triggered by lack of sleep and reading, greater headache burden and headache disability, and symptoms of anxiety and depression. This study suggests that a history of mTBI is associated with the phenotype, burden, clinical course, and associated comorbid diseases in patients with migraine, and highlights the importance of inquiring about a lifetime history of mTBI in patients being evaluated for migraine.

Lost productivity associated with headache and depression: a quality improvement project identifying a patient population at risk.

OBJECTIVE: This quality improvement project was implemented in order to highlight the association between headache, mTBI and depression on lost productivity and resource utilization. BACKGROUND: Mood disorders, environment and traumatic brain injury are common in patients with headache, and have been shown to influence clinical course, treatment response and outcome. Although widely recognized, the association of these factors on clinical outcomes, resource utilization and productivity is not well understood. METHODS: All patients presenting to a military referral center for migraines are assessed for presence of traumatic brain injury, Headache Impact Score (HIT-6) and Patient Depression Questionnaire (PHQ-9). Based on screening, patients are offered referral to mental health and a multidisciplinary headache education course. RESULTS: 237 patients were seen for headache or migraine. 180 patients had severely disabling headaches. These patients accounted for 146 emergency room visits over the course of one year. Of headache patients, 65% met criteria for depression and 15% of patients had severe depression. Only 37% of these patients carried a formal diagnosis of depression and 38% had been seen by mental health. Lost productivity and duty limitations were significantly associated with severity of depression. In service members screening positively for mild, moderate or severe depression, duty restrictions had been placed on 8.3%, 32.5% and 53.8%, respectively. Only 3.8% of patients who did not screen for depression had similar duty limitations. A history of mTBI strongly correlated with comorbid depression. Lost productivity and duty limitations were not impacted by other headache characteristics or HIT-6 scores. CONCLUSIONS: This quality improvement project identified a practice gap for treatment of comorbid depression in patients presenting to Neurology for headache. Depression strongly correlated with productivity loss, highlighting a possible target for the economic burden of headache.

Does baseline concussion testing aid in identifying future concussion risk?

The purpose was to determine differences in pre-season baseline performance between student-athletes who suffered a future sport-related concussion (fSRC) and those who did not. Collegiate student-athletes (82 fSRC, 82 matched control, age = 18.4 ± 0.8years, height = 172.7 ± 10.3 cm, mass = 80.1 ± 20.9 kg) completed baseline Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Balance Error Scoring System (BESS), and Standardized Assessment of Concussion (SAC). Results of the independent t-tests suggested there were no differences between the fSRC and the control groups for ImPACT composite scores (95% confidence intervals, Visual Memory: fSRC 70.4-75.9, Control 73.4-78.5, p = 0.134; Verbal Memory: fSRC 83.8-87.7, Control 85.7-89.9, p = 0.155; Reaction Time: fSRC 0.562-0.591, Control 0.580-0.614, p = 0.071; Visual Motor Speed: fSRC 38.5-41.1, Control 38.2-40.9, p = 0.757), BESS total errors (fSRC 11.3-13.7, Control 11.8-14.4, p = 0.483), or SAC (fSRC 26.6-27.4, Control 26.9-27.6, p = 0.394). Receiver operating characteristic (ROC) areas-under-the-curve were 0.417-0.515. Our findings suggest that baseline concussion assessments cannot be used to predict individuals who may sustain a fSRC.

CGRP-dependent and independent mechanisms of acute and persistent post-traumatic headache following mild traumatic brain injury in mice.

BACKGROUND: Acute and persistent post-traumatic headache are often debilitating consequences of traumatic brain injury. Underlying physiological mechanisms of post-traumatic headache and its persistence remain unknown, and there are currently no approved therapies for these conditions. Post-traumatic headache often presents with a migraine-like phenotype. As calcitonin-gene related peptide promotes migraine headache, we explored the efficacy and timing of intervention with an anti- calcitonin-gene related peptide monoclonal antibody in novel preclinical models of acute post-traumatic headache and persistent post-traumatic headache following a mild traumatic brain injury event in mice. METHODS: Male, C57Bl/6 J mice received a sham procedure or mild traumatic brain injury resulting from a weight drop that allowed free head rotation while under minimal anesthesia. Periorbital and hindpaw tactile stimulation were used to assess mild traumatic brain injury-induced cutaneous allodynia. Two weeks after the injury, mice were challenged with stress, a common aggravator of migraine and post-traumatic headache, by exposure to bright lights (i.e. bright light stress) and cutaneous allodynia was measured hourly for 5 hours. A murine anti- calcitonin-gene related peptide monoclonal antibody was administered after mild traumatic brain injury at different time points to allow evaluation of the consequences of either early and sustained calcitonin-gene related peptide sequestration or late administration only prior to bright light stress. RESULTS: Mice with mild traumatic brain injury, but not a sham procedure, exhibited both periorbital and hindpaw cutaneous allodynia that resolved by post-injury day 13. Following resolution of injury-induced cutaneous allodynia, exposure to bright light stress re-instated periorbital and hindpaw cutaneous allodynia in injured, but not sham mice. Repeated administration of anti-calcitonin-gene related peptide monoclonal antibody at 2 hours, 7 and 14 days post mild traumatic brain injury significantly attenuated the expression of cutaneous allodynia when evaluated over the 14-day post injury time course and also prevented bright light stress-induced cutaneous allodynia in injured mice. Administration of anti-calcitonin-gene related peptide monoclonal antibody only at 2 hours and 7 days after mild traumatic brain injury blocked injury-induced cutaneous allodynia and partially prevented bright light stress-induced cutaneous allodynia. A single administration of anti-calcitonin-gene related peptide monoclonal antibody after the resolution of the peak injury-induced cutaneous allodynia, but prior to bright light stress challenge, did not prevent bright light stress-induced cutaneous allodynia. CONCLUSIONS: We used a clinically relevant mild traumatic brain injury event in mice along with a provocative stimulus as novel models of acute post-traumatic headache and persistent post-traumatic headache. Following mild traumatic brain injury, mice demonstrated transient periorbital and hindpaw cutaneous allodynia suggestive of post-traumatic headache-related pain and establishment of central sensitization. Following resolution of injury-induced cutaneous allodynia, exposure to bright light stress re-established cutaneous allodynia, suggestive of persistent post-traumatic headache-related pain. Continuous early sequestration of calcitonin-gene related peptide prevented both acute post-traumatic headache and persistent post-traumatic headache. In contrast, delayed anti-calcitonin-gene related peptide monoclonal antibody treatment following establishment of central sensitization was ineffective in preventing persistent post-traumatic headache. These observations suggest that mechanisms involving calcitonin-gene related peptide underlie the expression of acute post-traumatic headache, and drive the development of central sensitization, increasing vulnerability to headache triggers and promoting persistent post-traumatic headache. Early and continuous calcitonin-gene related peptide blockade following mild traumatic brain injury may represent a viable treatment option for post-traumatic headache and for the prevention of post-traumatic headache persistence. ABBREVIATIONS: CA Cutaneous allodynia CGRP Calcitonin gene-related peptide mTBI Mild traumatic brain injury PTH Post-traumatic headache APTH Acute post-traumatic headache PPTH Persistent post-traumatic headache.

A jugular vein compression collar prevents alterations of endogenous electrocortical dynamics following blast exposure during special weapons and tactical (SWAT) breacher training.

Exposure to explosive blasts places one at risk for traumatic brain injury, especially for special weapons and tactics (SWAT) and military personnel, who may be repeatedly exposed to blasts. In the current study, the effectiveness of a jugular vein compression collar to prevent alterations in resting-state electrocortical activity following a single-SWAT breacher training session was investigated. SWAT team personnel were randomly assigned to wear a compression collar during breacher training and resting state electroencephalography (EEG) was measured within 2 days prior to and two after breacher training. It was hypothesized that significant changes in brain dynamics-indicative of possible underlying neurodegenerative processes-would follow blast exposure for those who did not wear the collar, with ameliorated changes for the collar-wearing group. Using recurrence quantification analysis (RQA) it was found that participants who did not wear the collar displayed longer periods of laminar electrocortical behavior (as indexed by RQA's vertical max line measure) after breacher training. It is proposed that the blast wave exposure for the no-collar group may have reduced the number of pathways, via axonal disruption-for electrical transmission-resulting in the EEG signals becoming trapped in laminar states for longer periods of time. Longer laminar states have been associated with other electrocortical pathologies, such as seizure, and may be important for understanding head trauma and recovery.

White matter microstructural abnormalities in blast-exposed combat veterans: accounting for potential pre-injury factors using consanguineous controls.

PURPOSE: Assess the prevalence of white matter microstructural changes in combat veterans, within the context of a highly matched control group comprising unexposed close relatives. METHODS: This prospective study had institutional review board approval, included written informed consent, and is HIPAA-compliant. Diffusion tensor imaging was analyzed in 16 male blast-exposed combat veterans of Operation Iraqi Freedom/Operation Enduring Freedom (mean age 31.0 years) and 18 unexposed males (mean age 30.4 years) chosen on the basis of a consanguineous relationship to a member of the subject group. Whole-brain voxel-based comparison of fractional anisotropy (FA) was performed using both group and individual analyses. Areas where effects on FA were detected were subsequently characterized by extracting radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) from the regions of abnormal FA. RESULTS: Controls did not differ from veterans on any background demographic factor. In voxel-based group comparison, we identify high fractional anisotropy (FA) in veterans compared to controls (p < 0.01). Within individual veterans, we find multiple areas of both abnormally high and low FA (p < 0.01) in a heterogeneous distribution, consistent with multifocal traumatic axonal injury. In individualized analyses, low FA areas demonstrate high radial diffusivity, whereas high FA areas demonstrate low RD in both group and individual analyses. CONCLUSIONS: Combat-related blast exposure is associated with microstructural white matter abnormalities, and the nature of the control group decreases the likelihood that the findings reflect underlying background differences. Abnormalities are heterogeneously distributed across patients, consistent with TAI, and include areas of low and high FA.

Is Concussion a Risk Factor for Epilepsy?

BACKGROUND: Epidemiologic studies have suggested that concussion, or mild traumatic brain injury (mTBI), is associated with a twofold or greater increase in relative risk for the development of post-traumatic epilepsy. To assess the clinical validity of these findings, we analyzed the incidence of epilepsy in a large cohort of post-concussion patients in whom concussion was strictly defined according to international guidelines. METHODS: A retrospective cohort study of 330 consecutive post-concussion patients followed by a single concussion specialist. Exclusion criteria: abnormal brain CT/MRI, Glasgow Coma Scale48 hours. Independent variable: concussion. Outcome measure: epilepsy incidence (dependent variable). RESULTS: The mean number of concussions/patient was 3.3 (±2.5), mean age at first clinic visit 28 years (±14.7), and mean follow-up after first concussion 7.6 years (±10.8). Eight patients were identified whose medical records included mention of seizures or convulsions or epilepsy. Upon review by an epileptologist none met criteria for a definite diagnosis of epilepsy: four had episodic symptoms incompatible with epileptic seizures (e.g., multifocal paraesthesiae, multimodality hallucinations, classic migraine) and normal EEG/MRI investigations; four had syncopal (n=2) or concussive (n=2) convulsions. Compared with annual incidence (0.5/1000 individuals) in the general population, there was no difference in this post-concussion cohort (p=0.49). CONCLUSION: In this large cohort of post-concussion patients we found no increased incidence of epilepsy. For at least the first 5-10 years post-injury, concussion/mTBI should not be considered a significant risk factor for epilepsy. In patients with epilepsy and a past history of concussion, the epilepsy should not be presumed to be post-traumatic.

Effects of music production on cortical plasticity within cognitive rehabilitation of patients with mild traumatic brain injury.

OBJECTIVE: We explored the effects of playing the piano on patients with cognitive impairment after mild traumatic brain injury (mTBI) and, addressed the question if this approach would stimulate neural networks in re-routing neural connections and link up cortical circuits that had been functional inhibited due to disruption of brain tissue. Functional neuroimaging scans (fMRI) and neuropsychological tests were performed pre-post intervention. METHOD: Three groups participated, one mTBI group (n = 7), two groups of healthy participants, one with music training (n = 11), one baseline group without music (n = 12). The music groups participated in 8 weeks music-supported intervention. RESULTS: The patient group revealed training-related neuroplasticity in the orbitofrontal cortex. fMRI results fit well with outcome from neuropsychological tests with significant enhancement of cognitive performance in the music groups. Ninety per cent of mTBI group returned to work post intervention. CONCLUSION: Here, for the first time, we demonstrated behavioural improvements and functional brain changes after 8 weeks of playing piano on patients with mTBI having attention, memory and social interaction problems. We present evidence for a causal relationship between musical training and reorganisation of neural networks promoting enhanced cognitive performance. These results add a novel music-supported intervention within rehabilitation of patients with cognitive deficits following mTBI.

Biofluid biomarkers of traumatic brain injury.

PRIMARY OBJECTIVE: The purpose of this paper is to review the clinical and research utility and applications of blood, cerebrospinal fluid (CSF), and cerebral microdialysis biomarkers in traumatic brain injury (TBI). RESEARCH DESIGN: Not applicable. METHODS AND PROCEDURES: A selective review was performed on these biofluid biomarkers in TBI. MAIN OUTCOME AND RESULTS: Neurofilament heavy chain protein (NF-H), glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCHL1), neuron-specific enolase (NSE), myelin basic protein (MBP), tau, and s100ß blood biomarkers are elevated during the acute phase of severe head trauma but have key limitations in their research and clinical applications to mild TBI (mTBI). CSF biomarkers currently provide the best reflection of the central nervous system (CNS) pathobiological processes in TBI. Both animal and human studies of TBI have demonstrated the importance of serial sampling of biofluids and suggest that CSF biomarkers may be better equipped to characterize both TBI severity and temporal profiles. CONCLUSIONS: The identification of biofluid biomarkers could play a vital role in identifying, diagnosing, and treating the underlying individual pathobiological changes of TBI. CNS-derived exosomes analyzed by ultra-high sensitivity detection methods have the potential to identify blood biomarkers for the range of TBI severity and time course.

Diffusion imaging of mild traumatic brain injury in the impact accelerated rodent model: A pilot study.

PRIMARY OBJECTIVE: There is a need to understand pathologic processes of the brain following mild traumatic brain injury (mTBI). Previous studies report axonal injury and oedema in the first week after injury in a rodent model. This study aims to investigate the processes occurring 1 week after injury at the time of regeneration and degeneration using diffusion tensor imaging (DTI) in the impact acceleration rat mTBI model. RESEARCH DESIGN: Eighteen rats were subjected to impact acceleration injury, and three rats served as sham controls. Seven days post injury, DTI was acquired from fixed rat brains using a 7T scanner. Group comparison of Fractional Anisotropy (FA) values between traumatized and sham animals was performed using Tract-Based Spatial Statistics (TBSS), a method that we adapted for rats. MAIN OUTCOMES AND RESULTS: TBSS revealed white matter regions of the brain with increased FA values in the traumatized versus sham rats, localized mainly to the contrecoup region. Regions of increased FA included the pyramidal tract, the cerebral peduncle, the superior cerebellar peduncle and to a lesser extent the fibre tracts of the corpus callosum, the anterior commissure, the fimbria of the hippocampus, the fornix, the medial forebrain bundle and the optic chiasm. CONCLUSION: Seven days post injury, during the period of tissue reparation in the impact acceleration rat model of mTBI, microstructural changes to white matter can be detected using DTI.