Acute Post-traumatic Headache Research Articles

Brain Iron Accumulation in Participants with Acute Post-traumatic Headache (S20.007)

Brain Iron Accumulation in Participants with Acute Post-traumatic Headache (S20.007)

Prediction of Headache Improvement Using Multimodal Machine Learning in Patients with Acute Post-traumatic Headache (P5-12.002)

Prediction of Headache Improvement Using Multimodal Machine Learning in Patients with Acute Post-traumatic Headache (P5-12.002)

Capillary blood protein markers of posttraumatic headache in children after concussion.

Posttraumatic headache (PTH) represents the most common acute and persistent symptom in children after concussion, yet there is no blood protein signature to stratify the risk of PTH after concussion to facilitate early intervention. This discovery study aimed to identify capillary blood protein markers, at emergency department (ED) presentation within 48 hours of concussion, to predict children at risk of persisting PTH at 2 weeks postinjury. Capillary blood was collected using the Mitra Clamshell device from children aged 8-17 years who presented to the ED of the Royal Children's Hospital, Melbourne, Australia, within 48 hours of sustaining a concussion. Participants were followed up at 2 weeks postinjury to determine PTH status. PTH was defined per clinical guidelines as a new or worsened headache compared with preinjury. An untargeted proteomics analysis using data-independent acquisition (DIA) was performed. Principal component analysis and hierarchical clustering were used to reduce the dimensionality of the protein dataset. A total of 907 proteins were reproducibly identified from 82 children within 48 hours of concussion. The mean participant age was 12.78 years (SD 2.54 years, range 8-17 years); 70% of patients were male. Eighty percent met criteria for acute PTH in the ED, while one-third of participants with follow-up experienced PTH at 2 weeks postinjury (range 8-16 days). Hemoglobin subunit zeta (HBZ), cystatin B (CSTB), beta-ala-his dipeptidase (CNDP1), hemoglobin subunit gamma-1 (HBG1), and zyxin (ZYX) were weakly associated with PTH at 2 weeks postinjury based on up to a 7% increase in the PTH group despite nonsignificant Benjamini-Hochberg adjusted p values. This discovery study determined that no capillary blood protein markers, measured at ED presentation within 48 hours of concussion, can predict children at risk of persisting PTH at 2 weeks postinjury. While HBZ, CSTB, CNDP1, HBG1, and ZYX were weakly associated with PTH at 2 weeks postinjury, there was no specific blood protein signature predictor of PTH in children after concussion. There is an urgent need to discover new blood biomarkers associated with PTH to facilitate risk stratification and improve clinical management of pediatric concussion.

Treatment Options for Posttraumatic Headache: A Current Review of the Literature.

We evaluate evidence-based treatments for posttraumatic headache (PTH), a secondary headache disorder resulting from traumatic brain injury (TBI), comprising nearly 4% of all symptomatic headache disorders. Utilizing recent publications, we aim to inform clinicians of current treatment methods. There is limited research on PTH treatment. A randomized controlled trial (RCT) of metoclopramide with diphenhydramine for acute PTH found that the treatment group (N = 81) experienced more significant pain improvement than placebo by 1.4 points. For persistent PTH, an open-label study of erenumab (N = 89) found that 28% of participants reported ≥ 50% reduction in moderate-to-severe headache days, but an RCT of fremanezumab showed a non-significant reduction in moderate-to-severe headache days. A randomized crossover study of 40 patients with persistent PTH found that onabotulinum toxin-A decreased cumulative number of headaches/week by 43.3% in the treatment group and increased by 35.1% among placebos. In a study of military veterans with severe posttraumatic stress disorder and persistent/delayed onset PTH (N = 193), patients who received Cognitive Behavioral Therapy reported significant improvements in headache-related disability compared to usual care (aggregate mean HIT-6, -3.4). A transcranial magnetic stimulation (N = 24) study found that 58% of participants with mild TBI-related headache experienced a 50% reduction in headache frequency. New studies indicate promise in improving clinically important outcomes of PTH. However, more research is necessary to determine the optimal treatment and whether combining pharmacologic and nonpharmacologic treatment versus a single modality is more effective.

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 and Risk Factors for Post-traumatic Headache in Civilian Patients After Mild Traumatic Brain Injury: A TRACK-TBI Study

ObjectiveTo ascertain the prevalence of and risk factors for post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI). Patients and MethodsA prospective, longitudinal, multicenter cohort study of patients with mTBI and orthopedic trauma controls who were enrolled from February 26, 2014, to August 8, 2018. The baseline assessment was conducted as soon as possible following evaluation at the emergency department. Follow-ups were scheduled at 2 weeks, 3 months, 6 months, and 12 months postinjury. Eligible patients with mTBI included those 18 years of age or older who presented to the emergency department within 24 hours of head injury warranting evaluation by noncontrast head computed tomography scan. Acute PTH was considered present when a patient reported a headache score of greater than or equal to 2 on the Rivermead Post-concussion Questionnaire at 2 weeks postinjury (ie, headache is at least a mild problem compared with pre-injury). Persistent PTH was defined when a patient with acute PTH reported a Rivermead Post-concussion Questionnaire headache score of greater than or equal to 2 at the scheduled follow-up examinations. ResultsAcute PTH was reported by 963 (60.4%) of 1594 patients with mTBI at 2 weeks postinjury. Among those with acute PTH, 439 (52.4%) of 837 patients reported persistent PTH at 3 months postinjury. This figure decreased over time and 278 (37.5%) of 742 patients continued to report persistent PTH at 6 months, whereas 187 (28.9%) of 646 patients did so as well at 12 months postinjury. Risk factors for acute PTH included younger age, female sex, fewer years of formal education, computed tomography–positive scans, alteration of consciousness, psychiatric history, and history of migraine. Risk factors for persistent PTH included female sex, fewer years of formal education, and history of migraine. ConclusionPost-traumatic headache is a prevalent sequela of mTBI that persists for at least 12 months in a considerable proportion of affected individuals. The attributable burden necessitates better patient follow-up, disease characterization, improved awareness of PTH in clinical practice, and identification of effective therapies.

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.

A Machine Learning Model Including Questionnaire and Structural Imaging Data Predicts Headache Improvement in Patients with Acute Post-traumatic Headache Attributed to Mild Traumatic Brain Injury (P8-12.002)

A Machine Learning Model Including Questionnaire and Structural Imaging Data Predicts Headache Improvement in Patients with Acute Post-traumatic Headache Attributed to Mild Traumatic Brain Injury (P8-12.002)

Cerebral blood flow in children with persisting postconcussive symptoms and posttraumatic headache at 2 weeks postconcussion.

Persisting postconcussive symptoms (pPCS), particularly headache, can significantly disrupt children's recovery and functioning. However, the underlying pathophysiology of these symptoms remains unclear. The goal in this study was to determine whether pPCS are related to cerebral blood flow (CBF) at 2 weeks postconcussion. The authors also investigated whether variations in CBF can explain the increased risk of acute posttraumatic headache (PTH) in female children following concussion. As part of a prospective, longitudinal study, the authors recruited children 5-18 years old who were admitted to the emergency department of a tertiary pediatric hospital with a concussion sustained within 48 hours of admission. Participants underwent pseudocontinuous arterial spin labeling MRI at 2 weeks postconcussion to quantify global mean gray and white matter perfusion (in ml/100 g/min). Conventional frequentist analysis and Bayesian analysis were performed. Comparison of recovered (n = 26) and symptomatic (n = 12) groups (mean age 13.15 years, SD 2.69 years; 28 male) found no differences in mean global gray and white matter perfusion at 2 weeks postconcussion (Bayes factors > 3). Although female sex was identified as a risk factor for PTH with migraine features (p = 0.003), there was no difference in CBF between female children with and without PTH. Global CBF was not associated with pPCS and female PTH at 2 weeks after pediatric concussion. These findings provide evidence against the use of CBF measured by arterial spin labeling as an acute biomarker for pediatric concussion recovery.

Developing multivariable models for predicting headache improvement in patients with acute post-traumatic headache attributed to mild traumatic brain injury: A preliminary study.

Post-traumatic headache (PTH) is a common symptom after mild traumatic brain injury (mTBI). Although there have been several studies that have used clinical features of PTH to attempt to predict headache recovery, currently no accurate methods exist for predicting individuals' improvement from acute PTH. This study investigated the utility of clinical questionnaires for predicting (i) headache improvement at 3 and 6 months, and (ii) headache trajectories over the first 3 months. We conducted a clinic-based observational longitudinal study of patients with acute PTH who completed a battery of clinical questionnaires within 0-59 days post-mTBI. The battery included headache history, symptom evaluation, cognitive tests, psychological tests, and scales assessing photosensitivity, hyperacusis, insomnia, cutaneous allodynia, and substance use. Each participant completed a web-based headache diary, which was used to determine headache improvement. Thirty-seven participants with acute PTH (mean age=42.7, standard deviation [SD]=12.0; 25 females/12 males) completed questionnaires at an average of 21.7 (SD=13.1) days post-mTBI. The classification of headache improvement or non-improvement at 3 and 6 months achieved cross-validation area under the curve (AUC) of 0.72 (95% confidence interval [CI] 0.55 to 0.89) and 0.84 (95% CI 0.66 to 1.00). Sub-models trained using only the top five features still achieved 0.72 (95% CI 0.55 to 0.90) and 0.77 (95% CI 0.52 to 1.00) AUC. The top five contributing features were from three questionnaires: Pain Catastrophizing Scale total score and helplessness sub-domain score; Sports Concussion Assessment Tool Symptom Evaluation total score and number of symptoms; and the State-Trait Anxiety Inventory score. The functional regression model achieved for modeling headache trajectory over the first 3 months. Questionnaires completed following mTBI have good utility for predicting headache improvement at 3 and 6 months in the future as well as the evolving headache trajectory. Reducing the battery to only three questionnaires, which assess post-concussive symptom load and biopsychosocialecologic factors, was helpful to determine a reasonable prediction accuracy for headache improvement.

Evidence of Chronic Complement Activation in Asymptomatic Pediatric Brain Injury Patients: A Pilot Study.

Physical insult from a mild Traumatic Brain Injury (mTBI) leads to changes in blood flow in the brain and measurable changes in white matter, suggesting a physiological basis for chronic symptom presentation. Post-traumatic headache (PTH) is frequently reported by persons after an mTBI that may persist beyond the acute period (&gt;3 months). It remains unclear whether ongoing inflammation may contribute to the clinical trajectory of PTH. We recruited a cohort of pediatric subjects with PTH who had an acute or a persistent clinical trajectory, each around the 3-month post-injury time point, as well as a group of age and sex-matched healthy controls. We collected salivary markers of mRNA expression as well as brain imaging and psychological testing. The persistent PTH group showed the highest levels of psychological burden and pain symptom reporting. Our data suggest that the acute and persistent PTH cohort had elevated levels of complement factors relative to healthy controls. The greatest change in mRNA expression was found in the acute-PTH cohort wherein the complement cascade and markers of vascular health showed a prominent role for C1Q in PTH pathophysiology. These findings (1) underscore a prolonged engagement of what is normally a healthy response and (2) show that a persistent PTH symptom trajectory may parallel a poorly regulated inflammatory response.

Headache classification and automatic biomarker extraction from structural MRIs using deep learning.

Data-driven machine-learning methods on neuroimaging (e.g. MRI) are of great interest for the investigation and classification of neurological diseases. However, traditional machine learning requires domain knowledge to delineate the brain regions first, followed by feature extraction from the regions. Compared with this semi-automated approach, recently developed deep learning methods have advantages since they do not require such prior knowledge; instead, deep learning methods can automatically find features that differentiate MRIs from different cohorts. In the present study, we developed a deep learning-based classification pipeline distinguishing brain MRIs of individuals with one of three types of headaches [migraine (n = 95), acute post-traumatic headache (n = 48) and persistent post-traumatic headache (n = 49)] from those of healthy controls (n = 532) and identified the brain regions that most contributed to each classification task. Our pipeline included: (i) data preprocessing; (ii) binary classification of healthy controls versus headache type using a 3D ResNet-18; and (iii) biomarker extraction from the trained 3D ResNet-18. During the classification at the second step of our pipeline, we resolved two common issues in deep learning methods, limited training data and imbalanced samples from different categories, by incorporating a large public data set and resampling among the headache cohorts. Our method achieved the following classification accuracies when tested on independent test sets: (i) migraine versus healthy controls-75% accuracy, 66.7% sensitivity and 83.3% specificity; (2) acute post-traumatic headache versus healthy controls-75% accuracy, 66.7% sensitivity and 83.3% specificity; and (3) persistent post-traumatic headache versus healthy controls-91.7% accuracy, 100% sensitivity and 83.3% specificity. The most significant biomarkers identified by the classifier for migraine were caudate, caudal anterior cingulate, superior frontal, thalamus and ventral diencephalon. For acute post-traumatic headache, lateral occipital, cuneus, lingual, pericalcarine and superior parietal regions were identified as most significant biomarkers. Finally, for persistent post-traumatic headache, the most significant biomarkers were cerebellum, middle temporal, inferior temporal, inferior parietal and superior parietal. In conclusion, our study shows that the deep learning methods can automatically detect aberrations in the brain regions associated with different headache types. It does not require any human knowledge as input which significantly reduces human effort. It uncovers the great potential of deep learning methods for classification and automatic extraction of brain imaging-based biomarkers for these headache types.

Observations from a prospective small cohort study suggest that CGRP genes contribute to acute posttraumatic headache burden after concussion.

IntroductionPost-traumatic headache (PTH) is commonly reported after concussion. Calcitonin gene-related peptide (CGRP) is implicated in the pathogenesis of migraine. We explored how single nucleotide polymorphisms (SNPs) from CGRP-alpha (CALCA) and the receptor activity modifying protein-1 (RAMP1) related to headache burden during the first week after concussion.MethodsA prospective study was performed in 34 collegiate athletes who sustained a concussion. Participants completed the symptom evaluation checklist from the SCAT3 within 48 h of injury (V1), and again 4 (V2) and 7 (V3) days after injury. For each visit, the self-reported score (0–6) for headache, pressure in head, blurred vision, and sensitivity to light/noise were reported and summed to calculate the headache burden. A saliva sample was obtained and genotyped for CALCA (rs3781719) and RAMP1 (rs10185142). RAMP1 (TT, TC, CC) and CALCA (AA, AG, GG) were dichotomized (A+, A- and T+, T-, respectively), and concatenated (T+A+, T+A-, T-A+, T-A-) for analyses.ResultsHeadache Burden at Visit 1 was greatest in T+A+ compared to T-A+, and trended toward a significant difference with T+A-. Repeated-measures ANOVA revealed the presence of significant visit main effects (p < 0.001, η2 = 0.404), but the group (p = 0.055) and interaction effects only trended (p = 0.094). Pearson's χ2-tests revealed that 88% of those with return-to play (RTP) exclusions ≥15 days had PTH with multi-sensory symptoms (PTH+SENS) as compared to 35% in those with RTP < 14 day.ConclusionKnowledge of RAMP1 and CALCA genotypes appear to improve an understanding the presenting features and magnitude of headache burden after concussion injury.

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.

Revisiting the ICHD-3 criteria for headache attributed to mild traumatic injury to the head: Insights from the Toronto Concussion Study Analysis of Acute Headaches Following Concussion.

BackgroundThere is limited prospective data on the prevalence, timing of onset, and characteristics of acute headache following concussion/mild traumatic brain injury.MethodsAdults diagnosed with concussion (arising from injuries not related to work or motor vehicle accidents) were recruited from emergency departments and seen within one week post injury wherein they completed questionnaires assessing demographic variables, pre-injury headache history, post-injury headache history, and the Sport Concussion Assessment Tool (SCAT-3) symptom checklist, the Sleep and Concussion Questionnaire (SCQ) and mood/anxiety on the Brief Symptom Inventory (BSI).ResultsA total of 302 participants (59% female) were enrolled (mean age 33.6 years) and almost all (92%) endorsed post-traumatic headache (PTH) with 94% endorsing headache onset within 24 hours of injury. Headache location was not correlated with site of injury. Most participants (84%) experienced daily headache. Headache quality was pressure/squeezing in 69% and throbbing/pulsing type in 22%. Associated symptoms included: photophobia (74%), phonophobia (72%) and nausea (55%). SCAT-3 symptom scores, Brief Symptom Inventory and Sleep and Concussion Questionnaire scores were significantly higher in those endorsing acute PTH. No significant differences were found in week 1 acute PTH by sex, history of migraine, pre-injury headache frequency, anxiety, or depression, nor presence/absence of post-traumatic amnesia and self-reported loss of consciousness.ConclusionsThis study highlights the very high incidence of acute PTH following concussion, the timing of onset and characteristics of acute PTH, the associated psychological and sleep disturbances and notes that the current ICHD-3 criteria for headaches attributed to mild traumatic injury to the head are reasonable, the interval between injury and headache onset should not be extended beyond seven days and could, potentially, be shorted to allow for greater diagnostic precision.

Post-traumatic headache: Pathophysiology and management - A review

Background Post-traumatic headache (PTH) is a common secondary headache due to traumatic brain injury. In the past, significant research has been conducted to understand the pathophysiology and treatment options for PTH. However, PTH still lacks evidence-based treatment, and most of the management depends on the primary phenotype observed in the patient. Objective The main objective of this review is to provide a single reference that covers the current understanding of the pathophysiology and the treatment options available for PTH. Methods A detailed literature search on PubMed was performed, and a narrative review was prepared. Results The pathophysiology of PTH is multifactorial. Acute PTH may be attributed to increased peripheral pain sensitization with impaired pain inhibiting pathways. Chronic or persistent PTH may be due to a chronic inflammatory response and peripheral as well as central sensitization. The mechanism responsible for the transition of acute to persistent PTH is unknown. The migraine-like phenotype is reported to be the most prevalent headache type seen in PTH. New targets for preventive treatment have been identified in recent years, such as neuropeptides like calcitonin-gene-related peptide (CGRP), nitric oxide, and glutamate. The preventive pharmacological and non-pharmacological strategies employed for migraine (e.g. anti-CGRP monoclonal antibodies, onabotulinumtoxinA, physical therapy, cognitive and behavioral treatment, and neurostimulation techniques) have shown in preliminary studies that they are potentially efficacious, but large, randomized, double blind, placebo controlled trials are needed to further establish these as treatment options for PTH. Conclusions The lack of evidence-based treatment for PTH has created a need for future large trials to confirm the safety and efficacy of the currently employed treatments.

Acute and chronic management of posttraumatic headache in children: A systematic review.

The goal of this paper is to provide a compilation of the evidence for the treatment of posttraumatic headache (PTH) in the pediatric population. Headache features and timing of therapy were considered. Headache is the most common symptom following mild traumatic brain injury (mTBI), affecting more than 80% of children and adolescents. It is unclear whether treatment for PTH should be tailored based on headache characteristics, particularly the presence of migraine features, and/or chronicity of the headache. Systematic literature searches of PubMed, Embase, Scopus, and Cochrane databases (1985-2021, limited to English) were performed, and key characteristics of included studies were entered into RedCAP® (Prospero ID CRD42020198703). Articles and conference abstracts that described randomized controlled trials (RCTs), cohort studies, retrospective analyses, and case series were included. Participants included youth under 18years of age with acute (<3months) and persistent (≥3months) PTH. Studies that commented on headache improvement in response to therapy were included. Twenty-seven unique studies met criteria for inclusion describing abortive pharmacologic therapies (9), preventative pharmacotherapies (5), neuromodulation (1), procedures (5), physical therapy and exercise (6), and behavioral therapy (2). Five RCTs were identified. Studies that focused on abortive pharmacotherapies were completed in the first 2weeks post-mTBI, whereas other treatment modalities focused on outcomes 1month to over 1-year post-injury. Few studies reported on migrainous features (7), personal history of migraine (7), or family history of migraine (3). There is limited evidence on the timing and types of therapies that are effective for treating PTH in the pediatric population. Prospective studies that account for headache characteristics and thoughtfully address the timing of therapies and outcome measurement are needed.

Clinical predictors of poor 30-day headache outcomes after an emergency department visit for acute post-traumatic headache.

We investigated clinical risk factors that predict poor 30-day headache outcomes among patients evaluated in the emergency department (ED) for post-traumatic headache (PTH). This was an analysis of data from a randomized, placebo-controlled study of IV metoclopramide + diphenhydramine for acute PTH. Patients were enrolled during an ED visit and received telephone follow-up with a structured questionnaire 30 days later. The primary outcome was frequency of headaches 30 days after ED discharge. We used multivariable logistic regression models to determine which clinical variables were associated with frequent headaches at 30 days. In total, 160 patients were enrolled in the study. 134 (84%) patients completed the 30-day questionnaire and were included in the analysis, including 90 females and 44 males. 30 patients (22%, 95% CI = 0.16 to 0.30) reported frequent headaches at 30-day follow-up. In the multivariable analysis, female sex (OR = 4.03, 95% CI = 1.23±13.13), patients who blamed themselves for their injury (OR = 0.13, 95% CI = 0.04±0.45), and patients who were unsure if they sustained loss of consciousness during the traumatic incident (OR = 5.63, 95% CI = 1.89±16.78) were found to be associated with poor 30-day outcomes. Medication received in the ED and age were not associated. More than 1 out of five patients treated in the ED for acute PTH experienced frequent headaches 30 days later. Women and patients who were uncertain as to whether they had experienced loss of consciousness were at increased risk of frequent PTH. Blaming oneself for the head trauma was associated with less frequent PTH.

T2* reduction in patients with acute post-traumatic headache.

Although iron accumulation in pain-processing brain regions has been associated with repeated migraine attacks, brain structural changes associated with post-traumatic headache have yet to be elucidated. To determine whether iron accumulation is associated with acute post-traumatic headache, magnetic resonance transverse relaxation rates (T2*) associated with iron accumulation were investigated between individuals with acute post-traumatic headache attributed to mild traumatic brain injury and healthy controls. Twenty individuals with acute post-traumatic headache and 20 age-matched healthy controls underwent 3T brain magnetic resonance imaging including quantitative T2* maps. T2* differences between individuals with post-traumatic headache versus healthy controls were compared using age-matched paired t-tests. Associations of T2* values with headache frequency and number of mild traumatic brain injuries were investigated using multiple linear regression in individuals with post-traumatic headache. Significance was determined using uncorrected p-value and cluster size threshold. Individuals with post-traumatic headache had lower T2* values compared to healthy controls in cortical (bilateral frontal, bilateral anterior and posterior cingulate, right postcentral, bilateral temporal, right supramarginal, right rolandic, left insula, left occipital, right parahippocampal), subcortical (left putamen, bilateral hippocampal) and brainstem regions (pons). Within post-traumatic headache subjects, multiple linear regression showed a negative association between T2* in the right inferior parietal/supramarginal regions and number of mild traumatic brain injuries and a negative association between T2* in bilateral cingulate, bilateral precuneus, bilateral supplementary motor areas, bilateral insula, right middle temporal and right lingual areas and headache frequency. Acute post-traumatic headache is associated with iron accumulation in multiple brain regions. Correlations with headache frequency and number of lifetime mild traumatic brain injuries suggest that iron accumulation is part of the pathophysiology or a marker of mild traumatic brain injury and post-traumatic headache.

Altered speech patterns in subjects with post-traumatic headache due to mild traumatic brain injury

Background/objectiveChanges in speech can be detected objectively before and during migraine attacks. The goal of this study was to interrogate whether speech changes can be detected in subjects with post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) and whether there are within-subject changes in speech during headaches compared to the headache-free state.MethodsUsing a series of speech elicitation tasks uploaded via a mobile application, PTH subjects and healthy controls (HC) provided speech samples once every 3 days, over a period of 12 weeks. The following speech parameters were assessed: vowel space area, vowel articulation precision, consonant articulation precision, average pitch, pitch variance, speaking rate and pause rate. Speech samples of subjects with PTH were compared to HC. To assess speech changes associated with PTH, speech samples of subjects during headache were compared to speech samples when subjects were headache-free. All analyses were conducted using a mixed-effect model design.ResultsLongitudinal speech samples were collected from nineteen subjects with PTH (mean age = 42.5, SD = 13.7) who were an average of 14 days (SD = 32.2) from their mTBI at the time of enrollment and thirty-one HC (mean age = 38.7, SD = 12.5). Regardless of headache presence or absence, PTH subjects had longer pause rates and reductions in vowel and consonant articulation precision relative to HC. On days when speech was collected during a headache, there were longer pause rates, slower sentence speaking rates and less precise consonant articulation compared to the speech production of HC. During headache, PTH subjects had slower speaking rates yet more precise vowel articulation compared to when they were headache-free.ConclusionsCompared to HC, subjects with acute PTH demonstrate altered speech as measured by objective features of speech production. For individuals with PTH, speech production may have been more effortful resulting in slower speaking rates and more precise vowel articulation during headache vs. when they were headache-free, suggesting that speech alterations were related to PTH and not solely due to the underlying mTBI.