Post-traumatic Headache Research Articles

Paroxysmal disorders in the long-term after traumatic brain injury in children and adolescents

Consequences of traumatic brain injury (TBI) in children and adolescents pose a major medical and social problem, as TBI interferes with neuro ontogenesis. Among these consequences, paroxysmal disorders that manifest in the long-term after TBI represent an important issue. These disorders include posttraumatic headaches, posttraumatic epilepsy and subclinical epileptiform EEG activity. In this review, clinical manifestations, pathophysiology and management of the long-term post-TBI paroxysmal disorders in children and adolescents are discussed.

Review of the Management of Pediatric Post-Concussion Syndrome-a Multi-Disciplinary, Individualized Approach.

Post-concussion syndrome (PCS), when the patient's concussion symptoms last longer than 4-6weeks, affects 10-30% of concussion patients. PCS presents a significant source of morbidity to patients and a management challenge to providers. In this review, we present the current evidence and best management approaches for pediatric PCS. There is limited high-quality evidence in pediatric PCS. There is some evidence supporting pharmaceutical management of post-traumatic headaches, cognitive symptoms, and emotional symptoms. Vestibular-ocular dysfunction should be evaluated and managed appropriately. Neuropsychological recovery is expected, but requires appropriate attention to Return to Learn. Emotional symptoms are common in PCS and the evidence supports treatment with cognitive behavioral therapy. PCS presents a unique therapeutic challenge affecting multiple domains for patients-physical, sleep, cognitive, and emotional. Successful management of PCS requires a multi-disciplinary and individualized approach. There remains a significant need for further research, specifically looking into the outcomes and effective interventions in pediatric PCS.

Amantadine Use for Postconcussion Syndrome

The development of postconcussion syndrome after traumatic brain injury can result in a wide range of potentially debilitating symptoms that includes headaches, cognitive dysfunction, and mood disorders. Unfortunately, data on helpful medications are quite limited, particularly on the treatment of persistent headaches attributed to trauma. This retrospective medical record review used data collected from patients with a diagnosis of postconcussion syndrome in Mayo Clinic's Neurology and Physical Medicine and Rehabilitation outpatient clinics to evaluate the response of postconcussive symptoms to amantadine. A complete trial of amantadine was defined as 100 mg twice per day for 2 months. Thirty-three patients were prescribed amantadine for postconcussive syndrome after traumatic brain injury. One-third of patients discontinued the medication because of adverse effects. However, posttraumatic headaches were improved in 80% of patients who completed a full trial of amantadine. Surprisingly, patients had improvement in headaches even if the medication was prescribed years after the initial trauma. Little improvement was noted in other symptoms such as poor memory, dizziness, and personality changes. Although additional research is certainly needed, amantadine may be a reasonable medication to consider for the treatment of persistent headaches attributed to trauma, even if the initial injury is remote.

Headache Trigger Sensitivity and Avoidance after Mild Traumatic Brain Injury.

Most patients with primary headache disorders identify environmental stimuli (e.g., visual glare), situational factors (e.g., stress), physiological states (e.g., hormones), or activities (e.g., exercise) as triggers that elicit or worsen headache episodes. Headache triggers have not been previously studied in post-traumatic headache (PTH). The present study explored the frequency of headache triggers and their avoidance in PTH. Participants with mild traumatic brain injury (TBI) were recruited from outpatient specialty clinics and completed questionnaires at or soon after their initial clinic visit. The research assessment included a list of 12 possible headache triggers where participants were asked to rate sensitivity (how often they get a headache when exposed to the trigger) and avoidance (how often they try to avoid the trigger). Enrolled participants were 40.6 years old (standard deviation [SD] = 11.8 years) on average, predominantly female (69.8%) and Caucasian (69.8%), and injured in a motor vehicle crash (47.2%) or fall (20.8%). They were assessed at 9.4 weeks (SD = 6.8) post-injury. Most patients with mild TBI in this consecutive series (82.7%) reported ongoing headaches. Mental exertion, stress, and lack of sleep were rated as the most potent headache triggers and among the most frequently avoided. Odors or foods, hunger, and weather conditions were rated as the least potent triggers. Headache trigger sensitivity and avoidance were moderately correlated (r = 0.736, p < 0.001). Headache severity was more associated with trigger sensitivity [F(2,49) = 13.45, p < 0.001] than trigger avoidance [F(2,47) = 2.97, p = 0.062]. In summary, the pattern of headache triggers in persistent PTH after mild TBI appears somewhat different from that in primary headache disorders, with mental exertion emerging as uniquely important. Pervasive avoidance of mental exertion to prevent headaches (cogniphobia) might be a worthwhile behavioral intervention target after mild TBI.

Intact mast cell content during mild head injury is required for development of latent pain sensitization: implications for mechanisms underlying post-traumatic headache.

Post-traumatic headache (PTH) is one of the most common, debilitating, and difficult symptoms to manage after a traumatic head injury. Although the mechanisms underlying PTH remain elusive, recent studies in rodent models suggest the potential involvement of calcitonin gene-related peptide (CGRP), a mediator of neurogenic inflammation, and the ensuing activation of meningeal mast cells (MCs), proalgesic resident immune cells that can lead to the activation of the headache pain pathway. Here, we investigated the relative contribution of MCs to the development of PTH-like pain behaviors in a model of mild closed-head injury (mCHI) in male rats. We initially tested the relative contribution of peripheral CGRP signaling to the activation of meningeal MCs after mCHI using a blocking anti-CGRP monoclonal antibody. We then used a prophylactic MC granule depletion approach to address the hypotheses that intact meningeal MC granule content is necessary for the development of PTH-related pain-like behaviors. The data suggest that after mCHI, ongoing activation of meningeal MCs is not mediated by peripheral CGRP signaling and does not contribute to the development of the mCHI-evoked cephalic mechanical pain hypersensitivity. Our data, however, also reveal that the development of latent sensitization, manifested as persistent hypersensitivity upon the recovery from mCHI-evoked acute cranial hyperalgesia to the headache trigger glyceryl trinitrate requires intact MC content during and immediately after mCHI. Collectively, our data implicate the acute activation of meningeal MCs as mediator of chronic pain hypersensitivity after a concussion or mCHI. Targeting MCs may be explored for early prophylactic treatment of PTH.

Treatment of posttraumatic headache migraine phenotype with erenumab – An observational study

Objective To report the observed effect of erenumab in mild posttraumatic headache migraine phenotype with and without aura. Background There is no clinical algorithm of pharmacotherapy for migraine following posttraumatic headache. Most migraine preventatives that are typically used are either ineffective or not tolerated. Methods Seven patients who met the clinical criteria for migraine with or without aura following posttraumatic headache who failed or were intolerant of conventional migraine preventatives were treated with erenumab 140 mg subcutaneously. Most had no history of migraine. In those patients with a history of migraine, the posttraumatic headache migraine headaches were different than the past migraine experience. Descriptive headache intensity or disability using the Head Impact Test-6 and monthly headache days were recorded before and after treatment. All patients were debilitated on presentation and demonstrated no signs of spontaneous resolution. Results Patients responded with a 95% (SD 1.22, p &lt; .001) reduction in headache days. All Head Impact Test-6 scores went from disabling to non-disabling without adverse effects. Most required only one dose of erenumab with no migraine recurrence. Onset of efficacy often became apparent within days to four weeks. Extended follow-up six months after treatment revealed no relapses. Conclusions Erenumab is effective in the treatment of posttraumatic headache with migraine phenotype in this small cohort. Large-scale studies are urgently required for this highly prevalent, disabling, condition which has no effective established treatment.

Post-traumatic headache in veterans of the Afghanistan and Iraq wars following deployment-related traumatic brain injury: long term follow-up and relation to PTSD and depression

Post-traumatic headache in veterans of the Afghanistan and Iraq wars following deployment-related traumatic brain injury: long term follow-up and relation to PTSD and depression

Banging the head and weird noise of trumpets – The enigma of Game of Thrones: No reports of post-traumatic headaches

Banging the head and weird noise of trumpets – The enigma of <i>Game of Thrones</i>: No reports of post-traumatic headaches

Cognitive and paroxysmal disorders in the long-term period of traumatic brain injury in children and adolescents

Traumatic brain injury (TBI) clinical course and outcomes in children have peculiarities as the damage impacts brain, which growth and maturation are continuing. Thus, TBI interferes into normal processes of neuroontogenesis leading to negative consequences on the cognitive functions development, school education, social skills acquisition. Cognitive and behavioral disorders in children and adolescents in the long-term period of TBI become more prominent in co-occurrence with paroxysmal disorders, including posttraumatic headaches, posttraumatic epilepsy and subclinical epileptiform activity on the EEG. Therapeutic and rehabilitation procedures in in the long-term period of TBI in children and adolescents should be conducted not only during the first 12 months after injury, when they are expected to be the most efficient, but also later on taking into consideration continuing processes of the CNS morphological and functional maturation along with the high neuroplasticity of the developing brain.

Disruption of periaqueductal grey-default mode network functional connectivity predicts persistent post-traumatic headache in mild traumatic brain injury

ObjectivePost-traumatic headache (PTH) is one of the most frequent and persistent physical symptoms following mild traumatic brain injury (mTBI) and develop in more than 50% of this population. This study...

Delta opioid receptor agonists are effective for multiple types of headache disorders

Headaches are highly disabling and are among the most common neurological disorders worldwide. Despite the high prevalence of headache, therapeutic options are limited. We recently identified the delta opioid receptor (DOR) as an emerging therapeutic target for migraine. In this study, we examined the effectiveness of a hallmark DOR agonist, SNC80, in disease models reflecting diverse headache disorders including: chronic migraine, post-traumatic headache (PTH), medication overuse headache by triptans (MOH), and opioid-induced hyperalgesia (OIH). To model chronic migraine C57BL/6J mice received chronic intermittent treatment with the known human migraine trigger, nitroglycerin. PTH was modeled by combining the closed head weight drop model with the nitroglycerin model of chronic migraine. For MOH and OIH, mice were chronically treated with sumatriptan or morphine, respectively. The development of periorbital and peripheral allodynia was observed in all four models; and SNC80 significantly inhibited allodynia in all cases. In addition, we also determined if chronic daily treatment with SNC80 would induce MOH/OIH, and we observed limited hyperalgesia relative to sumatriptan or morphine. Together, our results indicate that DOR agonists could be effective in multiple headache disorders, despite their distinct etiology, thus presenting a novel therapeutic target for headache.

Photophobia symptoms and visual pain thresholds in posttraumatic headache after mild traumatic brain injury

BackgroundLight sensitivity can be a disabling symptom in posttraumatic headache (PTH). The objective of this pilot study was to characterize photophobia symptoms and visual pain thresholds in PTH compared to healthy controls (HC).MethodsIndividuals with PTH attributed to mild traumatic brain injury (mTBI) (N = 18) and HC (N = 20), aged 18–65, were prospectively assessed using the Photosensitivity Assessment Questionnaire (PAQ), State Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI). A progressive light stimulation device was used to quantify visual pain thresholds. Visual pain thresholds were determined by the intensity of light at which subjects first noted pain. The mean of 3 trials was considered the visual pain threshold. Two sample t-test, Wilcoxon rank sum test, χ2 test and Fisher exact test was used to compare the 2 groups for their demographics, clinical characteristics, and outcomes measures.ResultsThere were no differences in demographics including age, gender, or race. The average time since onset of PTH was 50.7 (73.6) months. Those with PTH had 15.8 (9.2) headache days per month. BDI and STAI scores were significantly higher in PTH compared to HC. Photophobia was higher in PTH compared to HC, 0.64 (0.25) vs 0.24 (0.24), p &lt; 0.0001. Visual pain thresholds were lower in PTH (median 50.1 lux; quartiles 15.3 to 300.0) compared to HC (median 863.5 lux; quartiles 519.9 to 4,906.5; p = 0.0002).ConclusionPhotophobia symptoms are higher and visual pain thresholds are lower in PTH compared to HC. Light sensitivity is a well-known disabling symptom in PTH and this pilot study provides objective data through a validated photophobia scale and visual pain thresholds to characterize light sensitivity. Additional studies are needed to confirm this data, to compare acute to persistent PTH, to compare PTH to other headache disorders, and to determine if photophobia and visual pain thresholds will improve with intervention.

Narrative Review of the Pathophysiology of Headaches and Photosensitivity in Mild Traumatic Brain Injury and Concussion.

The most common symptom of post-concussive syndrome (PCS) is post-traumatic headache (PTH) accompanied by photophobia. Post-traumatic headache is currently categorized as a secondary headache disorder with a clinical phenotype described by its main features and resembling one of the primary headache disorders: tension, migraine, migraine-like cluster. Although PTH is often treated with medication used for primary headache disorders, the underlying mechanism for PTH has yet to be elucidated. The goal of this narrative literature review is to determine the current level of knowledge of these PTHs and photophobia in mild traumatic brain injury (mTBI) in order to guide further research and attempt to discover the underlying mechanism to both symptoms. The ultimate purpose is to better understand the pathophysiology of these symptoms in order to provide better and more targeted care to afflicted patients. A review of the literature was conducted using the databases CINAHL, EMBASE, PubMed. All papers were screened for sections on pathophysiology of PTH or photophobia in mTBI patients. Our paper summarizes current hypotheses. Although the exact pathophysiology of PTH and photophobia in mTBI remains to be determined, we highlight several interesting findings and avenues for future research, including central and peripheral explanations for PTH, neuroinflammation, cortical spreading depolarization and the role of glutamate excitotoxicity. We discuss the possible neuroanatomical pathways for photophobia and hypothesize a possible common pathophysiological basis between PTH and photophobia.

Symptom-based clinical profiles in the classification of post-traumatic headache

There are currently no established therapies for post-traumatic headache (PTH). One key obstacle standing in the way of meeting this unmet need is the fundamental gap in our understanding of the clinical course and functional impact of PTH. In this presentation we examine the existing schema used to characterize the clinical characteristics of PTH, including the International Classification of Headache Disorders (ICHD), and find that they leave major unresolved questions about the diagnosis, classification, and measurement of the clinical impact of PTH. Specifically, current data suggest that the ICHD classification, which is based on the extent of brain injury and the duration of condition, have limited prognostic and treatment implications. There are several challenges to the classification of PTH, as the clinical manifestations of PTH do not map well to the primary headache disorders, and the definition of the continuous and chronic daily headache require further study. Importantly, the existing classification do not provide or imply specific outcome measures for PTH, again a fundamental roadblock to testing therapeutic hypotheses for PTH. We hypothesize that a symptom-based classification is needed to begin an examination of these unresolved questions, and to establish clinically relevant endpoints for research and clinical trials for effective therapies.

Migraine with aura is the predominant phenotype among acute post-traumatic headache in sports

IntroductionHeadache is the most common symptom after traumatic brain injury (TBI), a global health concern with an estimated 2.5 million people in the United States reporting TBI in a single year. Regrettably, there is little evidence on the medical management of post-traumatic headache (PTH). Generally, treatment is approached as the primary headache disorder it most closely resembles in phenotype. In the lay public, the majority of PTHs exhibit migraine or probable migraine characteristics; however, PTH phenotypes within a sporting context have not been reported.MethodsThis cross-sectional survey evaluated the characteristics of headache in 102 student-athletes, ages 13–23 who had sustained sport-related concussion. Acute post-traumatic headache and sport-related concussion were defined by the International Classification of Headache Disorders and the Concussion in Sport Group definitions, respectively. The sample included male and female athletes from a variety of sports, with differing degrees of contact exposure. The survey collected data on personal and family history of headache, as well as specific headache characteristics.ResultsThe study included 54 males and 48 females. Migraine with aura (45.4%) was the predominant phenotype is this cross sectional cohort of sport-related acute post-traumatic headache. This was followed by migraine without aura (22.7%), tension-type headache (21.8%), and other (10.1%).ConclusionsMigraine with aura is a common phenotype among sport-related acute PTH. Further studies should evaluate for potential differences in recovery trajectories when compared to other headache phenotypes.

Feasibility of smartphone-delivered progressive muscle relaxation (PMR) therapy in post traumatic headache (PTH) management

Background Progressive muscle relaxation (PMR) has level A evidence in preventing migraine and tension-type headaches. However, there is limited research on behavioral therapy for post-traumatic headache (PTH) let alone delivered via a smartphone application. Aims/objective To gain preliminary evidence as to whether smartphone based PMR is feasible for subjects with PTH. Method(s) We performed a single-arm study of prospective patients calling our Concussion Center between June 2017 and May 2018. Subjects met ICHD-3 criteria for persistent headache secondary to mTBI, were age 18–85 and 3–12 months post injury, with no prior behavioral treatments for headache in the past year. We assessed prior and current headache and neuropsychologic histories. Using the RELAXaHEAD smartphone application, subjects were instructed to record headache symptoms daily and practice 20 minutes of PMR daily. There was a 1-month follow-up assessment. Results In our ongoing study, 21 subjects are currently enrolled, 13 female (62%) with mean age 41.4 (SD 13.1, range 20–65). Nine (43%) subjects had pre-existing headaches. Subjects' injuries were on average 6 months prior to enrollment (SD 2.6, range 4–12). Three (14%) were sports-related. In the month prior to enrollment, subjects reported 19.3 headache days (SD 8.76, median 20, range 5–30). 17 (81%) subjects reported memory problems and 18 (86%) reported impaired concentration. Of 17 subjects enrolled for at least 1 month, 9 (53%) imputed data for 20 or more days within the first month (mean 17 days, SD 12.2, median 20, range 0–31). 4 (24%) practiced PMR 2 + times/wk (mean 8.4 days, SD 8.6, median 6, range 0–31). Conclusion PTH subjects' obstacles regarding adherence to mHealth technology should be further assessed before PMR efficacy can be assessed. Notably, many subjects concurrently reported difficulties with memory and concentration, which may be contributing to poor adherence. Future work will attempt to assess for differences among users vs non-users.

Early prophylactic treatment reduces development of chronic post traumatic headache after concussion

BackgroundHeadaches after concussion are common, potentially debilitating, and long lasting. There are currently no guidelines on the treatment of post traumatic headaches (PTH). The aim of this study is to investigate the effects of early prophylactic pharmacologic treatment on the development of chronic post traumatic headaches (cPTH) in adolescent and adult concussion patients.MethodsPatients were retrospectively enrolled from the patient population at the Barrow Concussion and Brain Injury Center (Phoenix, AZ) from the previous 5 years. Males and females ages 13 and older with a diagnosis of PTH attributed to mild head injury based on ICHD2 criteria who were offered a headache prophylactic medication were included. Patients were divided into 3 groups: those who did not take treatment (Untreated), those who took nortriptyline (Nor), and those who took topiramate (Top). Groups were subdivided into those that developed cPTH and those who did not (ncPTH). The average time from injury to start of treatment (SoT) in days were analyzed using t-tests within and between groups.ResultsOne hundred twenty patients met inclusion criteria for the study (Untreated = 36, Top = 46, Nor = 38). Overall, 64 of 120 patients met criteria for cPTH (53%). SoT and development of cPTH is significant overall (35 vs 23, p&amp;lt; 0.001). SoT is significant for Untreated (NcPTH 14.4 vs cPTH 35.6, p = 0.001) and Top (NcPTH 23.9 vs cPTH 35.5, p = 0.002), but not for Nor (NcPTH 31.9 vs cPTH 34.0, p = 0.372). For NcPTH there is a significant difference between SoT for Untreated and Top (14.4 vs 23.9, p = 0.04) and Untreated vs Nor (14.4 vs 31.9, p = 0.002), but not Top and Nor (23.9 vs 31.9, p = 0.09). For cPTH there is no difference for SoT between groups.ConclusionEarly intervention with nonpharmacologic treatments and topiramate is associated with reduced development of cPTH.

Child Neurology Society survey of practitioners on management of pediatric post-traumatic headache

Background Traumatic brain injury (TBI) is a significant cause of morbidity in the pediatric population with headache being the most common post-concussive symptom. There are no established guidelines for the management of pediatric post-traumatic headache (PTH). This study aimed to better characterize common clinical practices of child neurologists in order to guide additional research in this area. Methods Members of the Child Neurology Society were surveyed. Results Ninety five practitioners responded to the survey. Respondents were heterogeneous in their experience and practice setting; 33.7% of respondents evaluated less than 25 pediatric concussion patients per year, 40.0% evaluated 25–50, and 26.3% saw >50 per year. The majority saw patients with subacute to persistent, mild TBI. 38.9% of practitioners reported that they consistently use the International Classification of Headache Disorders (ICHD) criteria to diagnose pediatric PTH, however only 18.9% correctly defined PTH as persistent at 12 weeks, as per ICHD classification. A majority of respondents recommended NSAIDs as abortive therapy after PTH, but instructions regarding timing after injury and frequency of use varied. The time-after-injury when prophylactic headache medication was recommended also varied; one-third considered prophylaxis within 1 month and one-third between 1 and 2 months. The medications most commonly used for prophylaxis were amitriptyline (93.7%), topiramate (71.6%), and vitamins/supplements (58.9%). Injection-based therapies were used by 38.0%. 93.7% recommended non-medical treatments, and 38.0% recommended injection-based therapies. Prescriptions for cognitive and physical rest and return to play were also variable; one-third of respondents recommended cognitive and physical rest for 1–3 days followed by progressive return to cognitive and physical activities, which is consistent with current guidelines. Conclusions As there are no established guidelines on management of PTH, it is not surprising that diagnosis and management varies considerably. Further studies are needed to define the best, evidence-based practices for pediatric PTH.

Migraine phenotype prolongs recovery time in traumatic brain injury (TBI)

We proposed that children and adolescents who had headache of migraine phenotype at initial neurologic assessment after mild TBI would take longer to clear for return to play than those who did not have those headache characteristics. Additionally, we predicted that those with migraine phenotype would be more likely to have comorbid mood or cognitive symptoms, which would also contribute to prolonged recovery. To test this, we assessed all new patients for the presence or absence of migraine phenotype with the Three-Item ID migraine screener (Lipton et al. 2003) at the first outpatient visit. Over the 5 months follow up interval (October 2017–February 2018), office visit data for 121 patients (ages 0–19 years) showed that 61% presented initially with a migraine phenotype. In that interval, 48% % (N = 58) were cleared for return to play. Those with migraine phenotype headache took longer to clear (99 vs 71 days respectively, p = 0.004). Neither age nor gender made a significant impact on length of recovery when only the presence or absence of migraine phenotype alone was considered. If patients had a migraine (vs non-migraine) phenotype headache and comorbid cognitive or behavioral symptoms (38% in our sample), their time to recovery was prolonged (109 vs 74 days respectively; F (1, 56) = 7.215, p = 0.009). These data suggest that early identification of migraine phenotype in assessment of post-traumatic headache can lead to aggressive treatment of headache, thus shortening the interval of disability after TBI. Cognitive and behavioral symptoms seem to have additional impact on recovery and should be addressed and supported in rehabilitation.

Posttraumatic headache in pediatrics: an update and review.

Headache following concussion and mild traumatic brain injury is very common in pediatrics. There is significant concern about appropriate management of acute and persistent headache following mild head injuries in children among affected youth, their families and care providers. The current article will review definitions and diagnoses of posttraumatic headache (PTHA), recent research regarding risk factors for persistence of postconcussion symptoms and headaches, current recommendations for the evaluation of youth with PTHA, recent data regarding efficacy of treatment options for PTHA, and current recommendations for the treatment of acute and persistent PTHA. PTHA is common following concussion in pediatrics. Some of the most consistent risk factors for persistent symptoms following concussion include female sex, adolescent age, prior concussion with prolonged recovery, prior headache history and high number of acute symptoms, particularly migrainous symptoms, following concussion. There are few prospective studies of the treatment of PTHA in pediatrics; however, a recent study found that short-term use of ibuprofen for those with acute PTHA following concussion may be associated with lower risk of symptoms and better function 1 week after injury. Currently complete rest or cocooning following concussion is not recommended as it may actually be associated with longer recovery time; a gradual return to cognitive and physical activity appears to be most effective strategy but more study is needed.