Treatment Of Post-traumatic Headache Research Articles

Onabotulinumtoxin A for the Treatment of Post-Traumatic Headache: Is It Better than Anti-CGRP Antibodies?

Post-traumatic headache (PTH) is a common and debilitating consequence of traumatic brain injury (TBI), often resembling migraine and tension-type headaches. Despite its prevalence, the optimal treatment for PTH remains unclear, with current strategies largely extrapolated from other headache disorders. This review evaluates the use of onabotulinumtoxin A (ONA) and anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the treatment of PTH. A comprehensive literature search was conducted on PubMed, including studies published up to September 2024, focusing on the efficacy, safety, and mechanisms of onabotulinumtoxin A and anti-CGRP mAbs in PTH. Both clinical trials and observational studies were reviewed. ONA, widely recognized for its efficacy in chronic migraine, has shown limited benefits in PTH with only one trial involving abobotulinumtoxin A in a cohort of 40 subjects. A phase 2 trial with fremanezumab, an anti-CGRP monoclonal antibody, failed to demonstrate significant efficacy in PTH, raising questions about the utility of targeting CGRP in this condition. ONA may offer advantages over anti-CGRP mAbs, not only in terms of its broader mechanism of action but also in cost-effectiveness and higher patient adherence. Both ONA and anti-CGRP mAbs are potential options for the management of PTH, but the current evidence is insufficient to establish clear guidelines. The negative results from the fremanezumab trial suggest that CGRP inhibition may not be sufficient for treating PTH, whereas onabotulinumtoxin A's ability to target multiple pain pathways may make it a more promising candidate.

Pilot study evaluating treatment with sumatriptan for moderate to severe post-traumatic headache: A phase 2 open-label study.

Our primary outcome was to determine the feasibility of patients with post-traumatic headache (PTH) keeping a daily headache diary and using sumatriptan as directed. Secondary outcomes include determining if sumatriptan is effective in aborting PTH and whether headache resolution is dependent on PTH phenotype. PTH is prevalent and persistent after traumatic brain injury, yet there have been few studies evaluating the effects of pharmacological treatments in individuals with PTH. This is a single-arm, prospective, non-randomized phase 2 clinical trial registered at Clinicaltrials.gov (NCT01854385) and conducted from 2013 to 2017. Data analysis was completed in 2022. Of the 299 participants screened, 40 were enrolled in the study. Participants kept a headache diary documenting headache characteristics and severity. Headache characteristics were used to determine PTH phenotypes of migraine-like, probable migraine-like, or non-migraine-like. Participants reported whether sumatriptan was used for their headache, their response to the medication, if a second dose was taken, and their response to the second dose. A total of 15 participants out of the 40 enrolled (mean [SD] age, 41.9 [14.2] years, and 53% [21/40] male), met the criteria for the use of sumatriptan, and completed all assessments. Average headache diary compliance rate for the final month of the study was 80% (372/465). While sumatriptan was used for only 19% (122/654) of all reported headaches, 72% (88/122) of those headaches resolved within 2 h of taking the medication. Resolution of headaches with sumatriptan was not significantly different among headache phenotypes (migraine-like: 22/38 [58%], probable migraine-like: 24/29 [83%], non-migraine-like: 6/15 [40%]; p = 0.154). A daily headache diary is feasible for tracking headache symptoms. Preliminary results also suggest that sumatriptan, a migraine-specific medication, may be beneficial for the treatment of PTH of different clinical phenotypes. Future studies, such as a phase 3 clinical trial with a larger sample size, are needed to better understand the efficacy of sumatriptan in the treatment of PTH.

American Headache Society white paper on treatment of post-traumatic headache from concussion in youth.

To provide healthcare professionals guidance on youth at risk for prolonged recovery and post-traumatic headache (PTH), and on pharmacologic and non-pharmacologic management of PTH due to concussion and mild traumatic brain injury. Headache is the most common persistent post-concussive symptom affecting 8% of youth for >3 months after concussion. Over the past decade, many studies have explored the treatment of PTH in youth, but there are no established guidelines. This white paper is based on a synthesis of an updated systematic review of the literature on treatment of PTH and a narrative review of the literature on risk factors for prolonged recovery and health disparities. Results were interpreted by a group of expert providers in PTH in children and adolescents through collaboration of the PTH and pediatric special interest groups of the American Headache Society. Factors that consistently were associated with prolonged recovery from concussion and persistent PTH included female sex, a high number of acute symptoms, and adolescent age. Social determinants of health also likely play an important role in PTH and deserve consideration in the clinical and research settings. A total of 33 studies met the criteria for inclusion in the systematic review of PTH treatment in youth, although most were retrospective and of fair-to-poor quality. Treatment strategies included acute and preventive pharmacologic management, procedures, neuro-modulatory devices, physical therapy, physical activity, and behavioral health support. A collaborative care approach that includes a thoughtful combination of these management strategies is likely most effective. This white paper provides a roadmap for tailoring the treatment of PTH based on factors influencing prolonged headache, the timing of therapies, and therapies with the most evidence for treating PTH in youth. We also highlight research needed for developing more definitive guidelines on PTH management in youth.

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.

Post-Traumatic Headache: A Review of Prevalence, Clinical Features, Risk Factors, and Treatment Strategies.

Post-traumatic headache (PTH) is a common and debilitating consequence of mild traumatic brain injury (mTBI) that can occur over one year after the head impact event. Thus, better understanding of the underlying pathophysiology and risk factors could facilitate early identification and management of PTH. There are several factors that could influence the reporting of PTH prevalence, including the definition of concussion and PTH. The main risk factors for PTHs include a history of migraines or headaches, female gender, younger age, greater severity of the head injury, and co-occurring psychological symptoms, such as anxiety and depression. PTH clinical profiles vary based on onset, duration, and severity: tension-type headache, migraine headaches, cervicogenic headache, occipital neuralgia, and new daily persistent headache. Pharmacological treatments often consist of analgesics and non-steroidal anti-inflammatory drugs, tricyclic antidepressants, or antiepileptic medication. Cognitive behavioral therapy, relaxation techniques, biofeedback, and physical therapy could also be used for PTH treatment. Our work highlighted the need for more rigorous studies to better describe the importance of identifying risk factors and patient-centered treatments and to evaluate the effectiveness of the existing treatment options. Clinicians should consider a multidisciplinary approach to managing PTH, including pharmacotherapy, cognitive behavioral therapy, and lifestyle changes.

Diagnosis and Treatment of Post-Traumatic Headache

Diagnosis and Treatment of Post-Traumatic Headache

Update on Non-Pharmacological Interventions for Treatment of Post-Traumatic Headache.

Post-traumatic headache (PTH) is the most common sequelae of traumatic brain injury (TBI). Its phenotypic variability, absence of formal evidence-based guidelines for treatment and underdiagnosis have made its management a challenge for clinicians. As a result, treatment of PTH has been mostly empiric. Although analgesics are the most popular drug of choice for PTH, they can present with several adverse effects and fail to address other psychosocial comorbidities associated with TBI. Non-pharmacological interventions thereby offer an intriguing alternative that can provide patients with PTH sustainable and effective care. This review article aims to: (1) provide an update on and describe different non-pharmacological interventions present in the recent literature; (2) provide clinical guidance to providers struggling with the management of patients with PTH; (3) emphasize the need for more high-quality trials examining the effectiveness of non-pharmacological treatments in patients with PTH. This review discusses 21 unique non-pharmacological treatments used for the management of PTH. Current knowledge of non-pharmacological interventions for the treatment of PTH is based on smaller scale studies, highlighting the need for larger randomized controlled trials to help establish formal evidence-based guidelines.

Effects of acupuncture treatment on posttraumatic headache after traumatic brain injury in patients: A protocol for systematic review.

Background:Posttraumatic headache (PTH) after traumatic brain injury (TBI) is a common clinical symptom, which refers to a headache that occurs after TBI. Acupuncture is often used for the treatment of such patients in China, and significant clinical effects have been achieved. However, to date, its efficacy has not been methodically evaluated. The purpose of this systematic review is to provide evidence to prove the effectiveness of acupuncture in the treatment of PTH in patients with TBI.Methods:This systematic review will be conducted in accordance with the preferred reporting items for systematic review and meta-analysis protocols. The following electronic databases will be searched from their inception to February 2022: PubMed, Web of Science, Embase, PsycINFO, the Cochrane Library, and Chinese databases such as Chinese Biomedical Literature (CBM), Chinese Medical Current Content (CMCC), Chinese Scientific Journal Database (VIP), WanFang Database, and China National Knowledge Infrastructure (CNKI). No language restrictions will be applied to the search strategy. Randomized controlled trials and cohort and case-control studies that met the inclusion and exclusion criteria will be included in this study. The meta-analysis will be performed using RevMan 5.3 software. Each session of this systematic review will be conducted independently by 2 members.Results:This review evaluates the efficacy of acupuncture in the treatment of PTH after TBI.Conclusion:This review provides substantial evidence for the clinical application of acupuncture in PTH treatment after TBI.Ethics and dissemination:Since the data in this study will be retrieved from published trials, therefore the Patient Consent Statement and Ethical Approval are not required. We will disseminate our results by publishing the research in a peer-reviewed journal.Trail registration number:The protocol was registered in INPLASY (INPLASY 202220073).

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.

A Phase 2 Study of Fremanezumab as a Treatment for Posttraumatic Headache in Adult Patients (1588)

A Phase 2 Study of Fremanezumab as a Treatment for Posttraumatic Headache in Adult Patients (1588)

The Litigation Complexity of Posttraumatic Headaches.

This review explores the workings of the legal process in posttraumatic headache (PTH) claims by discussing representative court cases, the approaches taken by both plaintiff and defense attorneys in evaluating a client with PTH, and the role of the expert witness. This discussion also examines the question of whether or not litigation prolongs the symptoms of PTH and concussion, looking at the issues of malingering and the psychological effect of litigation. Litigation prolongs recovery of PTH, primarily not from malingering but rather due to the psychological mindset of the plaintiff as created by the litigation process. Just as the medical community struggles with PTH diagnosis, mechanism, and treatment, the legal system grapples with identifying valid claims for PTH. Psychological support is an important component for PTH recovery to more effectively deal with the psychological impact of litigation and the concept of perceived injustice.

Study design for a randomized clinical trial of cognitive-behavioral therapy for posttraumatic headache

Posttraumatic headache (PTH) is a common debilitating condition arising from head injury and is highly prevalent among military service members and veterans with traumatic brain injury (TBI). Diagnosis and treatment for PTH is still evolving, and surprisingly little is known about the putative mechanisms that drive these headaches. This manuscript describes the design of a randomized clinical trial of two nonpharmacological (i.e., behavioral) interventions for posttraumatic headache. Design of this trial required careful consideration of PTH diagnosis and inclusion criteria, which was challenging due to the lack of standard clinical characteristics in PTH unique from other types of headaches. The treatments under study differed in clinical focus and dose (i.e., number of treatment sessions), but the trial was designed to balance the treatments as well as possible. Finally, while the primary endpoints for pain research can vary from assessments of pain intensity to objective and subjective functional measures, this trial of PTH interventions chose carefully to establish clinically relevant endpoints and to maximize the opportunity to detect significant differences between groups with two primary outcomes. All these issues are discussed in this manuscript.

Post-Traumatic Headache: Is It A Danger?

Post-Traumatic Headache (PTH), is the most frequent complaint after Traumatic Brain Injury (TBI). PTH affects the quality of life of the sufferer. Post-traumatic headache is defined as secondary headache within 7 days after head trauma or after regained consciousness after head trauma. PTH's definitive mechanisms are still unknown, but hypotheses can be brought from clinical findings and diagnostic tests that have been conducted. PTH can originate from peripheral or central. A multidisciplinary approach is emphasized in the treatment of PTH due to the many associated symptoms

Post-traumatic headache due to mild traumatic brain injury: Current knowledge and future directions.

Post-traumatic headache is one of the most common and persistent symptoms following mild traumatic brain injury. The objective of this narrative review is to provide an update on the diagnostic criteria, clinical presentation, epidemiology, pathophysiology, and treatment of post-traumatic headache, and to identify future research priorities. This is a narrative review of the literature regarding post-traumatic headache attributed to mild traumatic brain injury. Onset of post-traumatic headache within 7 days of injury is the only evidence for a causal relationship between the injury and the headache included in the diagnostic criteria. Post-traumatic headache often resolves within the first few days of onset, whereas it persists for at least 3 months in 30-50%. The majority of insights into post-traumatic headache pathophysiology come from pre-clinical animal studies and human imaging studies, which implicate structural, functional, metabolic, and neuroinflammatory mechanisms for post-traumatic headache. There is a paucity of quality evidence for how to best treat post-traumatic headache. Although meaningful progress has been made in the post-traumatic headache field, priorities for future research are numerous, including the optimization of diagnostic criteria, a greater understanding of post-traumatic headache pathophysiology, identifying mechanisms and predictors for post-traumatic headache persistence, and identifying safe, well-tolerated, effective therapies.

Posttraumatic headache: recent progress.

Posttraumatic headache (PTH) attributed to mild traumatic brain injury is common and debilitating. In up to one-half of those with acute PTH, the PTH becomes persistent (PTH), enduring for longer than 3 months. The high incidence and persistence of PTH necessitate research into PTH pathophysiology and treatment. In this review, recent developments regarding the diagnostic criteria for PTH, the pathophysiology of PTH, and PTH treatment are discussed. International Classification of Headache Disorders 3 diagnostic criteria for PTH attributed to head trauma require that 'a headache of any type' starts within 7 days of a head injury. PTH is considered 'persistent' when it endures for more than 3 months. Preclinical and human PTH research suggest multiple pathophysiologic mechanisms including genetic influences, neuroinflammation, increased release and inadequate clearance of neuropeptides and neurotransmitters, mast cell degranulation, and brain structural and functional remodeling. Even when it has a phenotype similar to a primary headache, data suggest that PTH is distinct from primary headaches. There is a lack of high-quality evidence for the acute or preventive treatment of PTH. However, results from published studies of conventional headache therapies and newer therapies, such as calcitonin gene-related peptide mAbs and transcranial magnetic stimulation, justify the current and future randomized controlled trials. Evidence points towards a complex pathophysiology for PTH that is at least partially distinct from the primary headaches. Although properly conducted clinical trials of PTH treatment are needed, existing work has provided important data that help to plan these clinical trials. Current and future investigations will help to identify PTH mechanisms, predictors for PTH persistence, therapeutic targets, and evidence-based treatment options.

Study of Gammacore Sapphire for the Acute and Preventive Treatment of Post-Traumatic Headache (GAP-PTH)

Study of Gammacore Sapphire for the Acute and Preventive Treatment of Post-Traumatic Headache (GAP-PTH)

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.

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.

Post traumatic headache (PTH) in a cohort of UK compensation claimants.

To explore post traumatic headache characteristics and risk factors in compensation claimants by observational retrospective cohort analysis. Medicolegal reports on 116 consecutive compensation claimants aged 41.9 ± 15.0 years were reviewed 21 ± 14 months after injury. Eighty eight had suffered head and neck injuries, 21 reported only neck injury and seven had "other injuries". Ninety four percent of the head injuries were "mild". The incidence of post traumatic headache following neck injury did not differ from that following head and neck injury, and none of the "other injuries" cases developed post traumatic headache. We anticipated that all head and neck injury claimants would seek compensation for post traumatic headache, but 25% denied developing headache. Post traumatic headache was very strongly correlated with a past history of primary headache ( p < 0.0001) but no other risk factors were identified. Post traumatic headache semiology was consistent with "migraine" or "probable migraine" in 90% of cases. Headache resolved in 30% of claimants between 3 and 24 months after injury but 70% continued to suffer headaches at the time of assessment. Forty one percent of claimants had received no treatment for post traumatic headache in primary care. Our data suggest that post traumatic headache is essentially "migraine" provoked by head or neck concussion. It is not clear why so many post traumatic headache sufferers receive poor or inadequate treatment for this condition.