Post Mild Traumatic Brain Injury Research Articles

Pre-injury psychiatric history, subacute symptoms and personality traits predict social reintegration at 3-month post-mild traumatic brain injury

ABSTRACT Background The purpose of the study was to identify whether the presence of a pre-injury psychiatric history, subacute post-concussive symptoms (PCS) and personality traits were predictive of less favorable social reintegration for 3 months following a mild traumatic brain injury (mTBI). Method A total of 76 patients with mTBI were included, and the presence of a pre-injury psychiatric history was identified from the medical chart. One-month post-accident, these patients completed the Millon Multiaxial Clinical Inventory, 3rd Edition assessing personality traits and the Rivermead Post-Concussion Symptoms Questionnaire to measure subacute PCS. Social reintegration was measured using the Mayo-Portland Adaptability Inventory, 4th Edition at 3-month post-accident. Results The presence of pre-injury psychiatric history, high levels of subacute PCS and Cluster B personality traits such as histrionic and borderline features were significant predictors of social reintegration quality at 3-month post injury. Conclusion This study provides new insights on cluster B personality traits and its influence on recovery and social reintegration at 3-month post mTBI.

Validation of a modified-composite autonomic symptom score (COMPASS-31) as an outcome measure for persistent autonomic symptoms post-concussion: an observational pilot study

ABSTRACT Objective Persistent symptoms post-mild traumatic brain injury (mTBI) includes autonomic dysregulation (AD). The composite autonomic symptoms score, (COMPASS-31), was developed to quantify AD symptom severity in the last year, which limits clinical utility. The primary aim was to determine validity of a modified-COMPASS-31 measuring symptoms in the last month compared to the original, secondarily to compare both original and modified versions to the Neurobehavioral Symptom Inventory (NSI), and tertiarily to detect change post-treatment of the modified-COMPASS-31 compared to NSI and headache intensity (HI). Participants Thirty-three military personnel with persistent headache post-mTBI. Main outcome measures Total and domain scores for COMPASS-31 (original vs. modified) NSI and HI at baseline. Change in modified-COMPASS-31. NSI, and HI. Results Baseline COMPASS-31 versions were comparable and highly correlated (r = 0.72, p < 0.001), they were moderately correlated at best to the NSI (r < 0.6), which may suggest differences in measurement metrics. The mean change in modified-COMPASS-31 scores (15.4/100, effect size 0.8) was mild to moderately correlated to the change in HI (r = 0.39) score, but not to NSI (r = 0.28). Conclusion The modified-COMPASS-31 appears to be valid, can measure change of AD symptom severity, and is recommended as an outcome measure.

Utility of Structured Oculomotor, Balance, and Exercise Testing in Civilian Adults With Mild Traumatic Brain Injury.

Assessments of oculomotor, balance, and exercise function detect different responses to mild traumatic brain injury in sports-related mild traumatic brain injury. These assessments are understudied in the adult community mild traumatic brain injury population. We evaluated level 1 trauma center patients with nonsports-related mild traumatic brain injury on oculomotor functioning (near point of convergence and accommodation), balance (Balance Error Scoring System), and exercise tolerance (Buffalo Concussion Treadmill Test). A prospective, cohort study of adults with mild traumatic brain injury ( n = 36) were assessed at 1 wk and 1-mo post-mild traumatic brain injury ( n = 26) using near point of convergence, near point of accommodation, Balance Error Scoring System, Buffalo Concussion Treadmill Test, and the Rivermead Post Concussion Symptoms Questionnaire. Prevalence of test impairment and association between performance and mild traumatic brain injury-related symptom burden (Rivermead Post Concussion Symptoms Questionnaire scores) were characterized. Participants demonstrated varying levels of impairment (e.g., 33.3% oculomotor, 44.1% balance, and 55.6% exercise impairment at 1 wk). Participants displayed diverse impairment profiles across assessments. We observed medium-to-large correlations between poorer near point of convergence and Buffalo Concussion Treadmill Test performance and greater mild traumatic brain injury symptom burden. Clinical examinations of oculomotor function, balance, and exercise adopted from sports-related concussion assessments detect impairment in adult community members with mild traumatic brain injury. While findings warrant larger-scale replication, they imply that incorporating these simple, structured examinations into the assessment of mild traumatic brain injury may facilitate more personalized management strategies.

Identification of brain areas in mice with peak neural activity across the acute and persistent phases of post-traumatic headache.

Post-traumatic headache is very common after a mild traumatic brain injury. Post-traumatic headache may persist for months to years after an injury in a substantial proportion of people. The pathophysiology underlying post-traumatic headache remains unknown but is likely distinct from other headache disorders. Identification of brain areas activated in acute and persistent phases of post-traumatic headache can provide insights into the underlying circuits mediating headache pain. We used an animal model of mild traumatic brain injury-induced post-traumatic headache and c-fos immunohistochemistry to identify brain regions with peak activity levels across the acute and persistent phases of post-traumatic headache. Male and female C57BL/6 J mice were briefly anesthetized and subjected to a sham procedure or a weight drop closed-head mild traumatic brain injury . Cutaneous allodynia was assessed in the periorbital and hindpaw regions using von Frey filaments. Immunohistochemical c-fos based neural activity mapping was then performed on sections from whole brain across the development of post-traumatic headache (i.e. peak of the acute phase at 2 days post- mild traumatic brain injury), start of the persistent phase (i.e. >14 days post-mild traumatic brain injury) or after provocation with stress (bright light). Brain areas with consistent and peak levels of c-fos expression across mild traumatic brain injury induced post-traumatic headache were identified and included for further analysis. Following mild traumatic brain injury, periorbital and hindpaw allodynia was observed in both male and female mice. This allodynia was transient and subsided within the first 14 days post-mild traumatic brain injury and is representative of acute post-traumatic headache. After this acute post-traumatic headache phase, exposure of mild traumatic brain injury mice to a bright light stress reinstated periorbital and hindpaw allodynia for several hours - indicative of the development of persistent post-traumatic headache. Acute post-traumatic headache was coincident with an increase in neuronal c-fos labeling in the spinal nucleus of the trigeminal caudalis, primary somatosensory cortex, and the nucleus accumbens. Neuronal activation returned to baseline levels by the persistent post-traumatic headache phase in the spinal nucleus of the trigeminal caudalis and primary somatosensory cortex but remained elevated in the nucleus accumbens. In the persistent post-traumatic headache phase, coincident with allodynia observed following bright light stress, we observed bright light stress-induced c-fos neural activation in the spinal nucleus of the trigeminal caudalis, primary somatosensory cortex, and nucleus accumbens. Examination of mild traumatic brain injury-induced changes in peak c-fos expression revealed brain regions with significantly increased neural activity across the acute and persistent phases of post-traumatic headache. Our findings suggest mild traumatic brain injury-induced post-traumatic headache produces neural activation along pain relevant pathways at time-points matching post-traumatic headache-like pain behaviors. These observations suggest that the spinal nucleus of the trigeminal caudalis, primary somatosensory cortex, and nucleus accumbens may contribute to both the induction and maintenance of post-traumatic headache.

Prevalence of comorbidities post mild traumatic brain injuries: a traumatic brain injury model systems study.

Traumatic brain injury (TBI) is associated with an increased risk of long-lasting health-related complications. Survivors of brain trauma often experience comorbidities which could further dampen functional recovery and severely interfere with their day-to-day functioning after injury. Of the three TBI severity types, mild TBI constitutes a significant proportion of total TBI cases, yet a comprehensive study on medical and psychiatric complications experienced by mild TBI subjects at a particular time point is missing in the field. In this study, we aim to quantify the prevalence of psychiatric and medical comorbidities post mild TBI and understand how these comorbidities are influenced by demographic factors (age, and sex) through secondary analysis of patient data from the TBI Model Systems (TBIMS) national database. Utilizing self-reported information from National Health and Nutrition Examination Survey (NHANES), we have performed this analysis on subjects who received inpatient rehabilitation at 5 years post mild TBI. Our analysis revealed that psychiatric comorbidities (anxiety, depression, and post-traumatic stress disorder (PTSD)), chronic pain, and cardiovascular comorbidities were common among survivors with mild TBI. Furthermore, depression exhibits an increased prevalence in the younger compared to an older cohort of subjects whereas the prevalence of rheumatologic, ophthalmological, and cardiovascular comorbidities was higher in the older cohort. Lastly, female survivors of mild TBI demonstrated increased odds of developing PTSD compared to male subjects. The findings of this study would motivate additional analysis and research in the field and could have broader implications for the management of comorbidities after mild TBI.

Questionnaire and structural imaging data accurately predict headache improvement in patients with acute post-traumatic headache attributed to mild traumatic brain injury

Our prior work demonstrated that questionnaires assessing psychosocial symptoms have utility for predicting improvement in patients with acute post-traumatic headache following mild traumatic brain injury. In this cohort study, we aimed to determine whether prediction accuracy can be refined by adding structural magnetic resonance imaging (MRI) brain measures to the model. Adults with acute post-traumatic headache (enrolled 0-59 days post-mild traumatic brain injury) underwent T1-weighted brain MRI and completed three questionnaires (Sports Concussion Assessment Tool, Pain Catastrophizing Scale, and the Trait Anxiety Inventory Scale). Individuals with post-traumatic headache completed an electronic headache diary allowing for determination of headache improvement at three- and at six-month follow-up. Questionnaire and MRI measures were used to train prediction models of headache improvement and headache trajectory. Forty-three patients with post-traumatic headache (mean age = 43.0, SD = 12.4; 27 females/16 males) and 61 healthy controls were enrolled (mean age = 39.1, SD = 12.8; 39 females/22 males). The best model achieved cross-validation Area Under the Curve of 0.801 and 0.805 for predicting headache improvement at three and at six months. The top contributing MRI features for the prediction included curvature and thickness of superior, middle, and inferior temporal, fusiform, inferior parietal, and lateral occipital regions. Patients with post-traumatic headache who did not improve by three months had less thickness and higher curvature measures and notably greater baseline differences in brain structure vs. healthy controls (thickness: p < 0.001, curvature: p = 0.012) than those who had headache improvement. A model including clinical questionnaire data and measures of brain structure accurately predicted headache improvement in patients with post-traumatic headache and achieved improvement compared to a model developed using questionnaire data alone.

Investigating post-mild traumatic brain injury neuromuscular function and musculoskeletal injury risk: A protocol for a prospective, observational, case–controlled study in service members and active individuals

IntroductionMusculoskeletal injury (MSKI) risk is increased following mild traumatic brain injury (mTBI). Increased MSKI risk is present up to 2 years following post-mTBI return-to-duty/activity relative to both non-mTBI peers and...

Preclinical assessment of onabotulinumtoxinA for the treatment of mild traumatic brain injury-related acute and persistent post-traumatic headache.

ObjectiveInvestigation of onabotulinumtoxinA in a murine model of acute and persistent post-traumatic headache.MethodsMild traumatic brain injury was induced with a weight drop method. Periorbital and hindpaw cutaneous allodynia were measured for 14 days. Mice were then exposed to bright light stress and allodynia was reassessed. OnabotulinumtoxinA (0.5 U) was injected subcutaneously over the cranial sutures at different post-injury time points.ResultsAfter milt traumatic brain injury, mice exhibited periorbital and hindpaw allodynia that lasted for approximately 14 days. Allodynia could be reinstated on days 14–67 by exposure to stress only in previously injured mice. OnabotulinumtoxinA administration at 2 h after mild traumatic brain injury fully blocked both transient acute and stress-induced allodynia up to day 67. When administered 72 h post-mild traumatic brain injury, onabotulinumtoxinA reversed acute allodynia, but only partially prevented stress-induced allodynia. OnabotulinumtoxinA administration at day 12, when initial allodynia was largely resolved, produced incomplete and transient prevention of stress-induced allodynia. The degree of acute allodynia correlated positively with subsequent stress-induced allodynia.ConclusionMild traumatic brain injury induced transient headache-like pain followed by long lasting sensitization and persistent vulnerability to a normally innocuous stress stimulus, respectively modeling acute and persistent post-traumatic headache.. Administration of onabotulinumtoxinA following the resolution of acute post-traumatic headache diminished persistent post-traumatic headache but the effects were transient, suggesting that underlying persistent mild traumatic brain injury-induced maladaptations were not reversed. In contrast, early onabotulinumtoxinA administration fully blocked both acute post-traumatic headache as well as the transition to persistent post-traumatic headache suggesting prevention of neural adaptations that promote vulnerability to headache-like pain. Additionally, the degree of acute post-traumatic headache was predictive of risk of persistent post-traumatic headache.

"Can differences in hospitalised mild traumatic brain injury (mTBI) outcomes at 12months be predicted?"

To identify risk factors for poor outcome one year post-mild traumatic brain injury (mTBI). This study was a prospective observational study using consecutive adult hospital admissions with mTBI. A total of 869 consecutive mTBI patients were enrolled in this study. All patients were reviewed by the specialist TBI rehabilitation team at six weeks and one year following mTBI. Demographic and injury data collected included: age, gender, TBI severity and Glasgow Coma Scale (GCS). At twelve months, global outcome was assessed by the Extended Glasgow Outcome Score (GOSE) and participation restriction by the Rivermead Head Injury Follow-up Questionnaire (RHFUQ) via semi-structured interview. An ordinal regression (OR) was used to identify associated factors for poor GOSE outcome and a linear regression for a poor RHFUQ outcome. In the GOSE analysis, lower GCS (p < 0.001), medical comorbidity (p = 0.027), depression (p < 0.001) and male gender (p = 0.008) were identified as risk factors for poor outcome. The RHFUQ analysis identified: lower GCS (p = 0.002), female gender (p = 0.001) and injuries from assault (p = 0.003) were variables associated with worse social functioning at one year. mTBI is associated with a significant impact upon the physical health and psychosocial function of affected individuals. The results of this study demonstrate that differences in mTBI outcome can be identified at twelve months post-mTBI and that certain features, particularly GCS, are associated with poorer outcomes.

Longitudinal Single Photon Emission Computed Tomography Neuroimaging as an Indication of Improvement in Psychiatric Disorders in a Community Psychiatric Practice.

In the community, there is a need to more objectively evaluate the response of common chronic psychiatric disorders to treatment. Brain single photon emission computed tomography (SPECT) indirectly measures cerebral functional activity by uptake of a radiotracer, which follows regional cerebral blood flow. Brain 3D Thresholded SPECT scans are thresholded three dimensional images derived from brain SPECT data. A retrospective community study of longitudinal (before and after treatment) brain 3D Thresholded SPECT scans of 73 patients with all-cause psychiatric disorders (most frequent diagnostic clusters: attention-deficit hyperactivity disorder, post-mild traumatic brain injury, affective disorders, psychotic disorders, post-viral chronic syndromes), shows these baseline SPECT scans predict improvement (non-worsening to large improvement) in clinical functioning with a sensitivity of 94% (95% confidence interval 86–98%) and a specificity of 67% (95% confidence interval 21–94%). In contrast, contemporaneous analysis by the same radiologist of conventional 2D reading of the same before and after treatment brain SPECT scan data of the same 73 patients, predicted improvement (non-worsening to large improvement) in clinical functioning with a sensitivity of only 26% (95% confidence interval 17–37%) although with a specificity of 100% (95% confidence interval 44–100%). These data suggest 3D Thresholded SPECT scans can provide the clinician with a more objective measure for verifying improvement in psychiatric disorders seen in the community, consistent with prior studies of SPECT as a measure of neurobiological change. Furthermore, these data suggest 3D Thresholded SPECT scans may have clinical application in guiding treatment and potentially improving outcomes.

Cervical musculoskeletal and sensorimotor impairments 4 weeks to 6 months following mild traumatic brain injury: An observational cohort study

BackgroundClinically relevant scores of neck disability have been observed in adults post mild traumatic brain injury (mTBI), even in those who initially report to be recovered. Potentially cervical musculoskeletal and/or cervical sensorimotor impairments may underlie these persistent symptoms post mTBI. ObjectiveTo determine whether cervical impairments exist beyond expected recovery times following concussion compared to healthy controls (HC). Study designObservational cohort study. MethodsParticipants aged 18–60 years consisting of 39 HC, and 72 individuals, 4 weeks to 6 months post mTBI of which 35 considered themselves asymptomatic (Asymp), and 37 symptomatic (Symp). Cervical outcome measures included range and velocity of motion, flexor muscle endurance, presence of at least one dysfunctional cervical joint, joint position error -neutral and torsion, movement accuracy, smooth pursuit neck torsion test (SPNT) and balance. ResultsIndividuals in the Symp mTBI group demonstrated significantly reduced: flexion and rotation range, rotation velocity, flexor endurance and movement accuracy as well as increased postural sway and a higher percentage had positive cervical joint dysfunction (p < 0.01]. The mTBI group who considered themselves recovered (Asymp)demonstrated significantly lower rotation range, flexor endurance, and a higher percentage had positive cervical joint dysfunction and positive SPNT (p < 0.05) compared to HCs. ConclusionIndividuals reporting symptoms post mTBI demonstrated cervical spine musculoskeletal and sensorimotor impairments beyond expected recovery times. Those not reporting symptoms had fewer but some cervical impairments. The need for a comprehensive neck assessment should be considered, perhaps even in those not reporting symptoms.

N-3 Polyunsaturated Fatty Acids Ameliorate Neurobehavioral Outcomes Post-Mild Traumatic Brain Injury in the Fat-1 Mouse Model.

Concussions and mild traumatic brain injury (m-TBI) have been identified as a consequential public health concern because of their potential to cause considerable impairments in physical, cognitive, behavioral, and social functions. Given their prominent structural and functional roles in the brain, n-3 polyunsaturated fatty acids (PUFA) have been identified as a potentially viable prophylactic agent that may ameliorate the deleterious effects of m-TBI on brain function. The purpose of the present pilot study was to investigate the effect of n-3 PUFA on neurologic function using a weight drop injury (WDI) model. Fat-1 mice, capable of synthesizing n-3 PUFA endogenously from n-6 PUFA, and their wild-type (WT) counterparts, were subjected to a mild low-impact WDI on the closed cranium, and recovery was evaluated using the neurological severity score (NSS) to assess the motor and neurobehavioral outcomes. In comparison to the WT mice, the fat-1 mice had a significantly (p ≤ 0.05) lower NSS at all time points post-WDI, and significantly greater neurological restoration measured as the time to first movement. Overall, these findings demonstrate the protective effect of n-3 PUFA against mild brain injury.

Screening for Poor Self-Reported Sleep Quality at 12 Weeks in Post-Mild Traumatic Brain Injury Patients Using the HF-Age-Gender (HAG) Index.

To identify a screening tool for poor self-reported sleep quality at 12 weeks according to non-invasive measurements and patients’ characteristics in the first week after mild traumatic brain injury (mTBI), data from 473 mTBI participants were collected and follow-ups were performed at 12 weeks. Patients with previous poor self-reported sleep quality prior to the injury were excluded. Patients were then divided into two groups at 12 weeks according to the Pittsburgh Sleep Quality Index based on whether or not they experienced poor sleep quality. The analysis was performed on personal profiles and heart rate variability (HRV) for 1 week. After analyzing the non-invasive measurements and characteristics of mTBI patients who did not complain of poor sleep quality, several factors were found to be relevant to the delayed onset of poor sleep quality, including age, gender, and HRV measurements. The HRV–age–gender (HAG) index was proposed and found to have 100% sensitivity (cut-off, 7; specificity, 0.537) to predicting whether the patient will experience poor sleep quality after mTBI at the 12-week follow-up. The HAG index helps us to identify patients with mTBI who have no sleep quality complaints but are prone to developing poor self-reported sleep quality. Additional interventions to improve sleep quality would be important for these particular patients in the future.

T1 and T2 quantification using magnetic resonance fingerprinting in mild traumatic brain injury.

To assess whether MR fingerprinting (MRF)-based relaxation properties exhibit cross-sectional and prospective correlations with patient outcome and compare the results with those from DTI. Clinical imaging, MRF, and DTI were acquired in patients (24 ± 10days after injury (timepoint 1) and 90 ± 17days after injury (timepoint 2)) and once in controls. Patient outcome was assessed with global functioning, symptom profile, and neuropsychological testing. ADC and fractional anisotropy (FA) from DTI and T1 and T2 from MRF were compared in 12gray and white matter regions with Mann-Whitney tests. Bivariate associations between MR measures and outcome were assessed using the Spearman correlation and logistic regression. Data from 22 patients (38 ± 12years; 17 women) and 18 controls (32 ± 8years; 12 women) were analyzed. Fourteen patients (37 ± 12years; 11 women) returned for timepoint 2, while two patients provided only timepoint 2 clinical outcome data. At timepoint 1, there were no differences between patients and controls in T1, T2, and ADC, while FA was lower in mTBI frontal white matter. T1 at timepoint 1 and the change in T1 exhibited more (n = 18) moderate to strong correlations (|r|= 0.6-0.85) with clinical outcome at timepoint 2 than T2 (n = 3), FA (n = 7), and ADC (n = 2). High T1 at timepoint 1, and serially increasing T1, accounted for five of the six MR measures with the highest utility for identification of non-recovered patients at timepoint 2 (AUC > 0.80). T1 derived from MRF was found to have higher utility than T2, FA, and ADC for predicting 3-month outcome after mTBI. • In a region-of-interest approach, FA, ADC, and T1 and T2 all showed limited utility in differentiating patients from controls at an average of 24 and 90days post-mild traumatic brain injury. • T1 at 24days, and the serial change in T1, revealed more and stronger predictive correlations with clinical outcome at 90days than did T2, ADC, or FA. • T1 showed better prospective identification of non-recovered patients at 90days than ADC, T2, and FA.

Report of Early Childhood Traumatic Injury Observations & Symptoms: Preliminary Validation of an Observational Measure of Postconcussive Symptoms.

To report preliminary empirical data on a novel, developmentally appropriate, observational postconcussive symptoms inventory for infants, toddlers, and preschoolers. Emergency departments of 2 tertiary, urban pediatric hospitals. Ninety-eight children (0-8 years of age; mean age at injury = 33.00, SD = 24.7 months) with mild traumatic brain injury (concussion) divided into younger (0-2 years) and older (3-8 years) age groups. Observational study. The Report of Early Childhood Traumatic Injury Observations & Symptoms (REACTIONS) documents 17 postconcussive symptoms representing observable manifestations thereof and was completed by parents in the acute (24-48 hours; n = 65), subacute (7-14 days; n = 78), and/or persistent phase (25-35 days; n = 72) post-mild traumatic brain injury. Different patterns of postconcussive symptoms were reported by age group, with behavioral manifestations particularly salient in younger children. More children younger than 2 years had sleep and comfort-seeking symptoms at each of the 3 postinjury time points. Postconcussive symptoms may manifest differently after mild traumatic brain injury sustained during early childhood. To fully understand and address their presence and evolution, developmentally sound measures such as the REACTIONS inventory are required.

Impact of Direct Access to Outpatient Physical Therapy Post Mild Traumatic Brain Injury in Reduction of Hospital Readmissions

To investigate the impact of direct access to outpatient physical therapy on hospital readmission rates for individuals post mild traumatic brain injury (mTBI). Prior to initiation of this quality improvement project, patients were recommended to follow-up with physiatry which required a three to four month wait. In 2018-2019, thirty-day ED readmission rates for mTBI were 13.61%.

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

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. 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. 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. 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.

The role of deficient pain modulatory systems in the development of persistent post-traumatic headaches following mild traumatic brain injury: an exploratory longitudinal study

BackgroundPost-traumatic headache (PTH) is one of the most common and long-lasting symptoms following mild traumatic brain injury (TBI). However, the pathological mechanisms underlying the development of persistent PTH remain poorly understood. The primary purpose of this prospective pilot study was to evaluate whether early pain modulatory profiles (sensitization and endogenous pain inhibitory capacity) and psychological factors after mild TBI predict the development of persistent PTH in mild TBI patients.MethodsAdult mild TBI patients recruited from Level I Emergency Department Trauma Centers completed study sessions at 1–2 weeks, 1-month, and 4-months post mild TBI. Participants completed the following outcome measures during each session: conditioned pain modulation to measure endogenous pain inhibitory capacity, temporal summation of pain and pressure pain thresholds of the head to measure sensitization of the head, Pain Catastrophizing Scale, Center for Epidemiological Studies – Depression Scale, and a standardized headache survey. Participants were classified into persistent PTH (PPTH) and no-PPTH groups based on the 4-month data.ResultsThe results revealed that mild TBI patients developing persistent PTH exhibited significantly diminished pain inhibitory capacity, and greater depression and pain catastrophizing following injury compared to those who do not develop persistent PTH. Furthermore, logistic regression indicated that headache pain intensity at 1–2 weeks and pain inhibitory capacity on the conditioned pain modulation test at 1–2 weeks predicted persistent PTH classification at 4 months post injury.ConclusionsOverall, the results suggested that persistent PTH is characterized by dysfunctional alterations in endogenous pain modulatory function and psychological processes in the early stages following mild TBI, which likely exacerbate risk for the maintenance of PTH.

Cognitive-communication skills and acute outcome following mild traumatic brain injury

ABSTRACT Purpose Little is known about cognitive-communication skills post mild traumatic brain injury (mTBI). We aimed to determine how performance on cognitive-communication measures in the acute recovery period relates to early outcome following complicated mTBI. Method Results of language and communication skill measures, demographic and accident-related data, length of stay (LOS), Glasgow Outcome Scale-Extended (GOSE) scores and discharge destinations were retrospectively gathered for 128 admitted patients with complicated mTBI. Results More than half of the individuals required rehabilitation services post discharge from hospital with over a third needing in-patient rehabilitation. Patients with poorer skills in auditory comprehension, verbal reasoning, confrontation naming, verbal fluency and conversational discourse were more likely to require in-patient rehabilitation. Subjects with worse skills in naming, conversational discourse and letter-category verbal fluency had a greater chance of being referred to out-patient rehabilitation services. Thus patients with both auditory comprehension and oral expression deficits were more likely to require in-patient services whereas those who had oral expression deficits but no significant difficulty in auditory comprehension were more often referred to out-patient services. Also, worse conversational discourse skills and semantic-category naming ability were related to lower GOSE scores and the chance of a longer LOS was greater when letter-category naming was poorer. Conclusion The likelihood of individuals requiring rehabilitation services post mTBI was related to performance on several oral expression and auditory comprehension measures. It is therefore important to evaluate cognitive-communication skills early to determine rehabilitation needs.

Guanosine protects against behavioural and mitochondrial bioenergetic alterations after mild traumatic brain injury

Traumatic brain injury (TBI) constitutes a heterogeneous cerebral insult induced by traumatic biomechanical forces. Mitochondria play a critical role in brain bioenergetics, and TBI induces several consequences related with oxidative stress and excitotoxicity clearly demonstrated in different experimental model involving TBI. Mitochondrial bioenergetics alterations can present several targets for therapeutics which could help reduce secondary brain lesions such as neuropsychiatric problems, including memory loss and motor impairment. Guanosine (GUO), an endogenous neuroprotective nucleoside, affords the long-term benefits of controlling brain neurodegeneration, mainly due to its capacity to activate the antioxidant defense system and maintenance of the redox system. However, little is known about the exact protective mechanism exerted by GUO on mitochondrial bioenergetics disruption induced by TBI. Thus, the aim of this study was to investigate the effects of GUO in brain cortical and hippocampal mitochondrial bioenergetics in the mild TBI model. Additionally, we aimed to assess whether mitochondrial damage induced by TBI may be related to behavioral alterations in rats. Our findings showed that 24 h post-TBI, GUO treatment promotes an adaptive response of mitochondrial respiratory chain increasing oxygen flux which it was able to protect against the uncoupling of oxidative phosphorylation (OXPHOS) induced by TBI, restored the respiratory electron transfer system (ETS) established with an uncoupler. Guanosine treatment also increased respiratory control ratio (RCR), an indicator of the state of mitochondrial coupling, which is related to the mitochondrial functionality. In addition, mitochondrial bioenergetics failure was closely related with locomotor, exploratory and memory impairments. The present study suggests GUO treatment post mild TBI could increase GDP endogenous levels and consequently increasing ATP levels promotes an increase of RCR increasing OXPHOS and in substantial improve mitochondrial respiration in different brain regions, which, in turn, could promote an improvement in behavioral parameters associated to the mild TBI. These findings may contribute to the development of future therapies with a target on failure energetic metabolism induced by TBI.