Background
Post-traumatic headache (PTH) is associated with considerable disability and reduced health-related quality of life. Despite the very high prevalence of PTH, there are no evidence-based ...guidelines for PTH treatment. Thus, we found it timely to provide a systematic review of the current literature on acute and preventive pharmacological treatment of PTH using PubMed and Embase databases.
Findings
Included studies involved acute and preventive pharmacological treatment of headache attributed to traumatic injury to the head in adherence to the International Classification of Headache Disorders (ICHD) criteria. Of 1424 potentially relevant articles identified, 63 were retrieved for detailed evaluation and seven studies (one prospective and six retrospective) met the inclusion criteria. None of the seven included studies were randomized clinical trials (RCTs) or used a placebo-controlled study design.
Conclusion
We found that there is a lack of high-quality evidence-based studies on the pharmacological treatment of PTH. Future studies are highly needed and must emphasize open-label studies with rigorous methodology or RCTs with a placebo-controlled design.
Objective
To estimate the relative frequency and relative risk of post-traumatic stress disorder (PTSD) attributed to traumatic brain injury (TBI).
Data Sources
PubMed and Embase were searched from ...database inception until January 26, 2019.
Study Selection
Two independent investigators screened titles, abstracts, and full texts. We selected studies that included subjects presenting with TBI, and where the number of subjects with TBI and PTSD could be extrapolated. There were no restrictions on study design.
Data Extraction and Synthesis
Data were extracted by two independent investigators and results were pooled using random-effects meta-analysis.
Results
In civilian populations, relative frequency of PTSD following TBI was 12.2% after 3 months (CI-95 (7.6 to 16.8%)
I
2
= 83.1%), 16.3% after 6 months (CI-95 (10.2 to 22.4%),
I
2
= 88.4%), 18.6% after 12 months (CI-95 (10.2 to 26.9%),
I
2
= 91.5%), and 11.0% after 24 months (CI-95 (0.0 to 25.8%),
I
2
= 92.0%). Relative risk was 1.67 after 3 months (CI-95 (1.17 to 2.38),
P
= 0.011,
I
2
= 49%), 1.36 after 6 months (CI-95 (0.81 to 2.30),
P
= 0.189,
I
2
= 34%), and 1.70 after 12 months (CI-95 (1.16–2.50),
P
= 0.014,
I
2
= 89%). In military populations, the relative frequency of associated PTSD was 48.2% (CI-95 (44.3 to 52.1%),
I
2
= 100%) with a relative risk of 2.33 (CI-95 (2.00 to 2.72),
P
< 0.0001,
I
2
= 99.9%).
Conclusions and Relevance
TBI is a risk factor for PTSD in clinic-based civilian populations. There are insufficient data to assess the relative frequency or relative risk of PTSD in moderate to severe TBI. Due to significant between-study heterogeneity, the findings of our study should be interpreted with caution.
Objective
To investigate the association of psychiatric and cognitive comorbidities with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (TBI).
Methods
A total of ...100 patients with persistent PTH attributed to mild TBI and 100 age- and gender-matched healthy controls free of mild TBI were enrolled between July 2018 and June 2019. Quality of sleep was evaluated using the Pittsburgh Sleep Quality Index, while symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Cognitive impairment was evaluated using the Montreal Cognitive Assessment questionnaire, while post-traumatic stress disorder (PTSD) was assessed using the Harvard Trauma Questionnaire.
Results
In 100 patients with persistent PTH, 85% reported poor quality sleep, compared with 42% of healthy controls (
P
< 0.01). The relative frequency of probable to high risk of anxiety was 52% in the persistent PTH group vs. 8% in healthy controls (
P
< 0.01), while the relative frequency of probable to high risk of depression was 42% in the persistent PTH group vs. 2% in healthy controls (
P
< 0.01). Furthermore, 27% of the patients with persistent PTH had mild cognitive impairment while 10% had probable PTSD.
Conclusions
Poor quality of sleep as well as symptoms suggestive of anxiety and depression were more common in patients with persistent PTH than healthy controls. Clinicians should screen patients with persistent PTH for these comorbidities and develop treatment plans that account for their presence.
Background
The onset and duration of spontaneous migraine attacks are most often difficult to predict which, in turn, makes it challenging to study the neurobiologic underpinnings of the disease in a ...controlled experimental setting. To address this challenge, human provocation studies can be used to identify signaling molecules (e.g. calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide) that, upon intravenous or oral administration, induce migraine attacks in people with migraine and mild or no headache in healthy volunteers. This approach has proven to be valid for decades and plays an integral role in mapping signaling pathways underlying migraine pathogenesis and identification of novel drug targets. However, the question arises as to whether the pathogenic mechanisms of provoked and spontaneous migraine attacks differ. In this paper, we provide an opinionated discussion on the similarities and differences between provoked and spontaneous attacks based on the current understanding of migraine pathogenesis.
Methods
The PubMed database was searched in July 2022 for original research articles on human provocation studies that included participants with migraine. The reference lists of originally identified articles were also searched and we selected those we judged relevant.
Discussion
People with migraine describe that provoked attacks resemble their spontaneous attacks and can be treated with their usual rescue medication. From a neurobiologic standpoint, provoked and spontaneous migraine attacks appear to be similar, except for the source of migraine-inducing substances (exogenous vs. endogenous source). In addition, provoked attacks can likely not be used to study the events that precede the release of migraine-inducing signaling molecules from sensory afferents and/or parasympathetic efferents during spontaneous attacks.
Migraine is a ubiquitous neurologic disease that afflicts people of all ages. Its molecular pathogenesis involves peptides that promote intracranial vasodilation and modulate nociceptive transmission ...upon release from sensory afferents of cells in the trigeminal ganglion and parasympathetic efferents of cells in the sphenopalatine ganglion. Experimental data have confirmed that intravenous infusion of these vasoactive peptides induce migraine attacks in people with migraine, but it remains a point of scientific contention whether their site of action lies outside or within the central nervous system. In this context, it has been hypothesized that transient dysfunction of brain barriers before or during migraine attacks might facilitate the passage of migraine-inducing peptides into the central nervous system. Here, we review evidence suggestive of brain barrier dysfunction in migraine pathogenesis and conclude with lessons learned in order to provide directions for future research efforts.
Migraine is a disabling neurological disorder, diagnosis of which is based on clinical criteria. A shortcoming of these criteria is that they do not fully capture the heterogeneity of migraine, ...including the underlying genetic and neurobiological factors. This complexity has generated momentum for biomarker research to improve disease characterisation and identify novel drug targets. In this Series paper, we present the progress that has been made in the search for biomarkers of migraine within genetics, provocation modelling, biochemistry, and neuroimaging research. Additionally, we outline challenges and future directions for each biomarker modality. We also discuss the advances made in combining and integrating data from multiple biomarker modalities. These efforts contribute to developing precision medicine that can be applied to future patients with migraine.
Migraine is a highly disabling neurological disorder that directly affects more than 1 billion individuals worldwide. Available treatment options differ between countries and include acute, ...preventive, and non-pharmacological therapies. Because of major progress in the understanding of migraine pathogenesis, novel mechanism-based medications have emerged and expanded the armamentarium of treatments. We provide a comprehensive overview of the current standard of care that will enable informed clinical management. First, we discuss the efficacy, tolerability, and safety profile of various pharmacological therapies for acute and preventive treatment of migraine. Second, we review the current knowledge on non-pharmacological therapies, such as neuromodulation and biobehavioural approaches, which can be used for a multidisciplinary approach to clinical management. Third, we emphasise that any effective treatment strategy starts with building a therapeutic plan tailored to individual clinical characteristics, preferences, and needs. Finally, we explore the outlook of emerging mechanism-based treatments that could address unmet challenges in clinical management of migraine.
Purpose of Review
Post-traumatic headache is a common sequela of injury to the head and/or neck. Here, we review the current approach to pharmacologic management of post-traumatic headache and ...explore the therapeutic promise of targeting calcitonin gene–related peptide signaling to address unmet treatment needs.
Recent Findings
The scarcity of data from controlled trials has left clinicians to rely on mainly expert opinion for the pharmacologic management of post-traumatic headache. The current view is that a phenotype-guided approach should be used, in which patients are treated according to the primary headache phenotype that their clinical features resemble the most (e.g. migraine, tension-type headache). Moreover, incremental advances are being made in the field that aim to identify possible cellular and molecular drivers of headache persistence. Calcitonin gene–related peptide has emerged as a key drug target which, in turn, has prompted novel insights on the potential importance of early initiation of pharmacologic treatment following the onset of post-traumatic headache. This, in turn, might prevent subsequent persistence and chronification of headache.
Background
Calcitonin gene-related peptide (CGRP) has recently been implicated in the pathogenesis of post-traumatic headache (PTH), which raises the prospect for therapeutic use of monoclonal ...antibodies targeting CGRP or its receptor. Therefore, we decided to assess the efficacy, tolerability, and safety of erenumab for prevention of persistent PTH attributed to mild traumatic brain injury.
Methods
A single-center, non-randomized, single-arm, open-label study of erenumab for adults aged 18–65 years with persistent PTH. Patients were assigned to receive 140-mg erenumab monthly by two subcutaneous 1-mL injections, given every 4 weeks for 12 weeks. The primary outcome measure was the mean change in number of monthly headache days of moderate to severe intensity from baseline (4-week pretreatment period) to week 9 through 12. Tolerability and safety endpoints were adverse events (i.e. number and type).
Results
Eighty-nine of 100 patients completed the open-label trial. At baseline, the mean monthly number of headache days of moderate to severe intensity was 15.7. By week 9 through 12, the number was reduced by 2.8 days. The most common adverse events were constipation (n = 30) and injection-site reactions (n = 15). Of 100 patients who received at least one dose of erenumab, two patients discontinued the treatment regimen due to adverse events.
Conclusions
Among patients with persistent PTH, erenumab resulted in a lower frequency of moderate to severe headache days in this 12-week open-label trial. In addition, erenumab was well-tolerated as discontinuations due to adverse events were low. Placebo-controlled randomized clinical trials are needed to adequately evaluate the efficacy and safety of erenumab in patients with persistent PTH.
Trial registration
ClinicalTrials.Gov,
NCT03974360
. Registered on April 17, 2019 - Retrospectively registered
CGRP in human models of primary headaches Ashina, Håkan; Schytz, Henrik Winther; Ashina, Messoud
Cephalalgia,
02/2018, Volume:
38, Issue:
2
Book Review, Journal Article
Peer reviewed
Objective
To review the role of CGRP in human models of primary headaches and to discuss methodological aspects and future directions.
Discussion
Provocation experiments demonstrated a heterogeneous ...CGRP migraine response in migraine patients. Conflicting CGRP plasma results in the provocation experiments are likely due to assay variation; therefore, proper validation and standardization of an assay is needed. To what extent CGRP is involved in tension-type headache and cluster headache is unknown.
Conclusion
Human models of primary headaches have elucidated the role of CGRP in headache pathophysiology and sparked great interest in developing new treatment strategies using CGRP antagonists and antibodies. Future studies applying more refined human experimental models should identify biomarkers of CGRP-induced primary headache and reveal whether CGRP provocation experiments could be used to predict efficacy of CGRP antagonists in migraine patients.
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