Hypersensitivity to PACAP-38 in post-traumatic headache: a randomized clinical trial.

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38), known for its role in migraine pathogenesis, has been identified as a novel drug target. Given the clinical parallels between post-traumatic headache (PTH) and migraine, we explored the possible role of PACAP-38 in the pathogenesis of PTH. To this end, we conducted a randomized, double-blind, placebo-controlled, two-way crossover trial involving adult participants diagnosed with persistent PTH resulting from mild traumatic brain injury. Participants were randomly assigned to receive a 20-min continuous intravenous infusion of either PACAP-38 (10 pmol/kg/min) or placebo (isotonic saline) on two separate experimental days, with a 1-week washout period in between. The primary outcome was the difference in incidence of migraine-like headache between PACAP-38 and placebo during a 12-h observational period post-infusion. The secondary outcome was the difference in the area under the curve (AUC) for baseline-corrected median headache intensity scores during the same 12-h observational period. Of 49 individuals assessed for eligibility, 21 were enrolled and completed the trial. The participants had a mean age of 35.2 years, and 16 (76%) were female. Most [19 of 21 (90%)] had a migraine-like phenotype. During the 12-h observational period, 20 of 21 (95%) participants developed migraine-like headache after intravenous infusion of PACAP-38, compared with two (10%) participants after placebo (P < 0.001). Furthermore, the baseline-corrected AUC values for median headache intensity scores during the 12-h observational period was higher after PACAP-38 than placebo (P < 0.001). These compelling results demonstrate that PACAP-38 is potent inducer of migraine-like headache in people with persistent PTH. Thus, targeting PACAP-38 signalling might be a promising avenue for the treatment of PTH.

Hypersensitivity to CGRP as a predictive biomarker of migraine prevention with erenumab.

BACKGROUND: The present study aimed to investigate the predictive value of calcitonin gene-related peptide (CGRP)-induced migraine attacks for effectiveness to erenumab treatment in people with migraine. METHODS: In total, 139 participants with migraine underwent a single experimental day involving a 20-min infusion with CGRP. Following this, the participants entered a 24-week treatment period with erenumab. The primary endpoints were the predictive value of CGRP-induced migraine attacks on the effectiveness of erenumab, defined as ≥50% reduction in monthly migraine days, or ≥ 50% reduction in either monthly migraine or monthly headache days of moderate to severe intensity. RESULTS: Among participants with CGRP-induced migraine attacks, 60 of 99 (61%) achieved ≥50% reduction in monthly migraine days during weeks 13-24 with erenumab. Conversely, 13 of 25 (52%) where CGRP infusion did not induce a migraine achieved the same endpoint (p = 0.498). There were no significant differences between the ≥50% reduction in either monthly migraine or monthly headache days of moderate to severe intensity between CGRP-sensitive and non-sensitive participants (p = 0.625). CONCLUSIONS: Our findings suggest that the CGRP-provocation model cannot be used to predict erenumab's effectiveness. It remains uncertain whether this finding extends to other monoclonal antibodies targeting the CGRP ligand or to gepants.Trial Registration: The study was registered at ClinicalTrials.gov (NCT04592952).

The International Classification of Headache Disorders: History and future perspectives.

PURPOSE: The International Classification of Headache Disorders (ICHD) is universally accepted and forms the basis of headache management and clinical, experimental and pharmacological headache research. The present review summarizes the history of the three different editions of the classification, concentrating on aspects of general interest that are still valid today. METHODS: The article is based on the memory of the chairperson of three editions of the International Classification and on his notes in the work copies and published scientific classification studies. RESULTS: Many of the crucial issues in headache classification are discussed in the review of the different editions. Some have been resolved and some remain unresolved. The 11th edition of the World Health Organization's International Classification of Diseases (ICD) has been developed in close contact with the International Headache Society classification committee and is in fact an abbreviated version of ICHD-3. The principles of the ICHD have also been used by the International Association for Study of Pain in developing a pain classification now included in ICD-11. The many points of discussion of each of the three editions are still relevant for headache experts and all those who care for headache patients. CONCLUSION: Headache classification is a living and developing discipline of research. Here, the gradual expansion and refinement of the classification through 3 different editions are discussed with a view to present day relevance.

Are the ICHD-3 criteria for headache attributed to idiopathic intracranial hypertension valid? Headache phenotyping and field-testing in newly diagnosed idiopathic intracranial hypertension.

BACKGROUND: Headache burden is substantial in idiopathic intracranial hypertension. The classification of idiopathic intracranial hypertension headache by the International Classification of Headache Disorders (ICHD) is an important tool for research and clinical purposes. METHODS: We phenotyped headaches and tested sensitivity and specificity of the ICHD-3 criteria for idiopathic intracranial hypertension headache in a prospective cohort of patients suspected of idiopathic intracranial hypertension at two tertiary headache centers. RESULTS: Sensitivity was 93% and specificity was 100% of ICHD-3 criteria for idiopathic intracranial hypertension-related headache validated in idiopathic intracranial hypertension (n = 140) and patients in whom idiopathic intracranial hypertension was suspected but disproven (n = 103). The phenotype of new/worsened headaches related to idiopathic intracranial hypertension suspicion was equally migraine-like (p = 0.76) and tension-type-like (p = 0.08). Lumbar puncture opening pressure was higher (p < 0.0001) and pulsatile tinnitus more frequent (p < 0.0001) in idiopathic intracranial hypertension patients, but neither improved the applicability of the headache criteria, nor did papilledema. CONCLUSION: Headache phenotype is not distinct in idiopathic intracranial hypertension. ICHD-3 criteria for idiopathic intracranial hypertension headache are sensitive and specific, but simplicity can be improved without compromising accuracy. We propose that a new or worsened headache temporally related to active idiopathic intracranial hypertension is a sufficient criterion for idiopathic intracranial hypertension headache regardless of headache phenotype or accompanying symptoms, and that elements of idiopathic intracranial hypertension diagnostics (papilledema and opening pressure) be segregated from headache criteria.Trial Registration: ClinicalTrials.gov Identifier: NCT04032379.

CandeSpartan Study: Candesartan Spanish Response-prediction and Tolerability study in migraine.

INTRODUCTION: Effectiveness of candesartan in migraine prevention is supported by two randomized controlled trials. We aimed to assess the effectiveness, tolerability, and response predictors of candesartan in the preventive treatment of migraine. METHODS: Observational, multicenter, prospective cohort study. The 50%, 75% and 30% responder rates, between weeks 8-12 and 20-24, were compared with the baseline. Treatment emergent adverse effects were systematically evaluated. Response predictors were estimated by multivariate regression models. RESULTS: Eighty-six patients were included, 79.1% females, aged 39.5 (inter-quartile range [IQR] 26.3-50.3), with chronic migraine (43.0%), medication overuse headache (55.8%) and a median of two (inter-quartile range: 0.75-3) prior preventive treatments. At baseline patients had 14 (10-24) headache and 8 (5-11) migraine days per month. The 30%, 50% and 75% responder rates were 40%, 34.9% and 15.1% between weeks 8-12, and 48.8%, 36%, and 18.6% between weeks 20-24. Adverse effects were reported by 30 (34.9%) and 13 (15.1%) patients between weeks 0-12 and 12-24, leading to discontinuation in 15 (17.4%) patients. Chronic migraine, depression, headache days per month, medication overuse headache, and daily headache at baseline predicted the response between weeks 20-24. CONCLUSION: Candesartan effectiveness and tolerability in migraine prevention was in line with the clinical trials' efficacy.Trial registration: The study protocol is registered in ClinicalTrials.gov (NCT04138316).

Incidence and prevalence of headache in influenza: A 2010-2021 surveillance-based study.

BACKGROUND AND PURPOSE: Influenza is a common cause of acute respiratory infection, with headache being one of the symptoms included in the European Commission case definition. The prevalence of headache as a symptom of influenza remains unknown. We aimed to describe the incidence and prevalence of headache in patients with influenza. METHODS: All consecutive patients who met the definition criteria of influenza-like illness during the influenza seasons 2010-2011 through 2021-2022 were included. The seasonal cumulative incidence of influenza per 1000 patients at risk and the prevalence of headache as an influenza symptom were calculated, including the 95% confidence intervals (CIs). Subgroup analyses were done based on patients' sex, age group, microbiological confirmation, vaccination status, and influenza type/subtype/lineage. RESULTS: During the study period, 8171 patients were eligible. The incidence of headache in the context of influenza varied between 0.24 cases per 1000 patients (season 2020-2021) and 21.69 cases per 1000 patients (season 2017-2018). The prevalence of headache was 66.1% (95% CI = 65.1%-67.1%), varying between 49.6% (season 2021-2022) and 80.1% (season 2010-2011). The prevalence of headache was higher in women (67.9% vs. 65.7%, p = 0.03) and higher in patients between 15 and 65 years old. Headache was more prevalent in patients infected with B subtypes than A subtypes (68.7% vs. 56.9%, p < 0.001). There were no notable differences regarding vaccination status or microbiological confirmation of the infection. CONCLUSIONS: Headache is a common symptom in patients with influenza, with a prevalence higher than that observed in other viral infections.

Eating attitudes of migraine patients in Turkey: a prospective multi-center study.

BACKGROUND: Migraine is a disease characterized by headache attacks. The disease is multifactorial in etiology and genetic and environmental factors play role in pathogenesis. Migraine can also be accompanied by psychiatric disorders like neurotism and obsessive compulsive disorder. Stress, hormonal changes and certain food intake can trigger attacks in migraine. Previous studies showed that eating attitudes and disorders are prevalant in patients with migraine. Eating disorders are psychiatric disorders related to abnormal eating habits. Both migraine and eating disorders are common in young women and personality profiles of these patient groups are also similar. A possible relationship which shows that migraine and eating habits are related can lead to a better understanding of disease pathogenesis and subsequently new therapeutic options on both entities. Association of migraine in relation to severity, depression and anxiety and eating habits and disorders were aimed to be investigated in this study. METHODS: The study was designed as a prospective, multi-center, case control study. Twenty-one centers from Turkey was involved in the study. The gathered data was collected and evaluated at a single designated center. From a pool of 1200 migraine patients and 958 healthy control group, two groups as patient group and study group was created with PS matching method in relation to age, body-mass index, marital status and employment status. Eating Attitudes Test-26 (EAT-26), Beck's Depression Inventory (BDI) and Beck's Anxiety Inventory (BAI) were applied to both study groups. The data gathered was compared between two groups. RESULTS: EAT-26 scores and the requirement for referral to a psychiatrist due to symptoms related to eating disorder were both statistically significantly higher in patient group compared to control group (p = 0.034 and p = 0.0001 respectively). Patients with migraine had higher scores in both BDI and BAI compared to control group (p = 0.0001 and p = 0.0001 respectively). Severity of pain or frequency of attacks were not found to be related to eating attitudes (r:0.09, p = 0.055). CONCLUSIONS: Migraine patients were found to have higher EAT-26, BDI and BAI scores along with a higher rate of referral to a psychiatrist due to symptoms. Results of the study showed that eating habits are altered in migraine patients with higher risk of eating disorders. Depression and anxiety are also found to be common amongst migraine patients.

Readability analysis and concept mapping of PROMs used for headache disorders.

OBJECTIVE: To assess the readability and the comprehensiveness of patient-reported outcome measures (PROMs) utilized in primary headache disorders literature. BACKGROUND: As the health-care landscape has evolved toward a patient-centric model, numerous PROMs have been developed to capture treatment outcomes in patients with headache disorders. For these PROMs to advance our understanding of headache disorders and their treatment impact, they must be easy to understand (i.e., reading grade level 6 or less) and comprehensively capture what matters to patients with headache. The aim of this study was to (a) assess the readability of PROMs utilized in headache disorders literature, and (b) assess the comprehensiveness of PROMs by mapping their content to a health-related quality of life framework. METHODS: In this scoping review, recently published systematic reviews were used to identify PROMs used in primary headache disorders literature. Readability analysis was performed at the level of individual items and full PROM using established readability metrics. The content of the PROMs was mapped against a health-related quality-of-life framework by two independent reviewers. RESULTS: In total, 22 PROMs (15 headache disorders related, 7 generic) were included. The median reading grade level varied between 7.1 (interquartile range [IQR] 6.3-7.8) and 12.7 (IQR 11.8-13.2). None of the PROMs were below the recommended reading grade level for patient-facing material (grade 6). Three PROMs, the Migraine-Treatment Assessment Questionnaire, the Eurolight, and the European Quality of Life 5 Dimensions 3 Level Version, were between reading grade levels 7 and 8; the remaining 19 PROMs were above reading grade level 8. In total, the PROMs included 425 items. Most items (n = 134, 32%) assessed physical function (e.g., work, activities of daily living). The remaining items assessed physical symptoms (n = 127, 30%; e.g., pain, nausea), treatment effects on symptoms (n = 65, 15%; e.g., accompanying symptoms relief, headache relief), treatment impact (n = 56, 13%; e.g., function, side effects), psychological well-being (n = 41, 10%; e.g., anger, frustration), social well-being (n = 29, 7%; e.g., missing out on social activities, relationships), psychological impact (n = 14, 3%; e.g., feeling [not] in control, feeling like a burden), and sexual well-being (n = 3, 1%; e.g., sexual activity, sexual interest). Some of the items pertained to treatment (n = 27, 6%), of which most were about treatment type and use (n = 12, 3%; e.g., medication, botulinum toxin), treatment access (n = 10, 2%; e.g., health-care utilization, cost of medication), and treatment experience (n = 9, 2%; e.g., treatment satisfaction, confidence in treatment). CONCLUSION: The PROMs used in studies of headache disorders may be challenging for some patients to understand, leading to inaccurate or missing data. Furthermore, no available PROM comprehensively measures the health-related quality-of-life impact of headache disorders or their treatment, resulting in a limited understanding of patient-reported outcomes. The development of an easy-to-understand, comprehensive, and validated headache disorders-specific PROM is warranted.

Persistent headache attributed to past ischemic stroke: A prospective cohort study.

OBJECTIVE: To assess the incidence, characteristics, and risk factors for developing persistent headache attributed to past ischemic stroke. BACKGROUND: Although the most recent International Classification of Headache Disorders has recognized the existence of persistent headache attributed to past ischemic stroke, there has been limited research in this area. METHODS: This was a prospective cohort study. We initially assessed patients hospitalized with ischemic stroke admitted within 72 h of symptom onset. All patients underwent diffusion-weighted magnetic resonance imaging. These patients were re-interviewed by telephone 1 year after the stroke. Semi-structured questionnaires, the National Institutes of Health Stroke Scale (NIHSS), and six-item Headache Impact Test were used. RESULTS: A total of 119 participants answered the interview conducted 1 year after the stroke. The mean (standard deviation) age was 64 (13.1) years, 82/119 (68.9%) were female, and the median (interquartile range) NIHSS score was 2 (1.0-4.0). The incidence rate of persistent headache attributed to past ischemic stroke was 12/119 (10.1%; 95% confidence interval [CI] 5.3-17.0%). The most frequent pattern presented was a migraine-like pattern in seven of the 12 (58.3%) patients, which had a substantial/severe impact on five of the 12 (41.7%). For most patients this headache continued, although it began to improve. Previous migraine (odds ratio 7.1, 95% CI 1.06-50.0; p = 0.043) and headache intensity in the acute phase of stroke (odds ratio 1.75, 95% CI 1.13-2.7; p = 0.012) were associated with the occurrence of persistent headache attributed to past ischemic stroke. CONCLUSION: Persistent headache attributed to past ischemic stroke is a frequent complication after stroke. It often has a significant impact on patients' lives and presents a migraine-like pattern as its most frequent phenotype.

Daith piercing: Revisited from the perspective of auricular acupuncture systems. A narrative review.

BACKGROUND: Daith piercing is a special ear-piercing method that punctures the crus of the helix. The penetrated site at the ear's innermost point is assumed to stimulate a pressure point associated with the vagus nerve. It has been reported that the pierced spot relieves migraine and tension-type headaches by activating vagal afferents, leading to the inhibition of neurons in the caudal trigeminal nucleus via the nucleus tractus solitarii. OBJECTIVE: The objective of this narrative literature review is to summarize the current state of knowledge concerning daith piercing for the treatment of migraine and tension-type headaches from the perspectives of the Chinese and Western auricular systems. METHODS: PubMed and China National Knowledge Infrastructure databases were searched using the keywords "daith piercing," "auricular points," "headache," and "acupuncture" from database inception to September 1, 2023. Only studies on humans were eligible; otherwise, no further restrictions were applied to the study designs, type of headache, or patient population of the identified articles. Bibliographies of all eligible studies were screened for further eligible studies. The main outcome of interest was a quantitative measure of pain relief by daith piercing. Secondary outcomes were relapse time of headache and further outcomes related to daith piercing, if available. RESULTS: From a total of 186 identified articles, one retrospective study and three case reports fulfilled the inclusion criteria. No clinical trial was identified. The obtained studies describe patients experiencing chronic headaches undergoing daith piercing without changing or reducing their usual medication. In all case studies and the retrospective study, patients reported substantial reductions in pain immediately after daith piercing; however, headache symptoms recurred several weeks to months thereafter. From the perspective of the Chinese and Western auricular systems, no sufficient explanation for the described treatment effect of daith piercing was found. CONCLUSION: The available literature, combined with the reported recurrence of pain as well as the associated side effects of daith piercing, indicate that current evidence does not support daith piercing for the treatment of migraine, tension-type headaches, or other headache disorders. PLAIN LANGUAGE SUMMARY: This paper summarizes what we know about Daith piercing (DP) for chronic migraine and tension-type headache and discusses how DP might work. Current evidence does not support DP as an effective treatment of chronic migraine and tension-type headache. These findings might assist clinicians in discussing this subject with patients as well as guide future research.

Epidemiology and clinical features of paroxysmal hemicrania: A systematic review and meta-analysis.

OBJECTIVE: To assess the prevalence or relative frequency of paroxysmal hemicrania and its clinical features in the adult general population and among adult patients evaluated for headache in tertiary care. BACKGROUND: Paroxysmal hemicrania is a rare trigeminal autonomic cephalalgia with characteristic attacks of headache, associated cranial autonomic symptoms and signs, and an absolute response to indomethacin. Its epidemiological burden remains unknown in both the adult general population and among adult patients evaluated for headache in a tertiary care setting. Moreover, the frequencies of the clinical features associated with paroxysmal hemicrania have not been well established. METHODS: A literature search of PubMed and Embase was conducted from January 1, 1988, to January 20, 2023. Eligible for inclusion were observational studies reporting the point prevalence or relative frequency of paroxysmal hemicrania or its clinical features in the adult general population or among adult patients evaluated for headache in tertiary care. Two independent investigators (M.J.H. and J.G.L.) performed the title, abstract, and full-text article screening. Each included study's risk of bias was critically appraised using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Estimates of prevalence or relative frequency were calculated using a random-effects meta-analysis. The between-study heterogeneity was assessed using the I2 statistic and further explored with meta-regression. This study was pre-registered on PROSPERO (identifier: CRD42023391127). RESULTS: A total of 17 clinic-based studies and one population-based study met the eligibility criteria. Importantly, an overall high risk of bias was observed across the eligible studies. The relative frequency of paroxysmal hemicrania was estimated to be 0.3% (95% CI, 0.2%-0.5%) among adult patients evaluated for headache in tertiary care with considerable heterogeneity (I2 = 76.4%). No cases with paroxysmal hemicrania were identified among 1,838 participants in a population-based sample. Moreover, the most prevalent cranial autonomic symptoms were lacrimation (77.3% [95% Cl, 62.7%-87.3%]), conjunctival injection (75.0% [95% Cl, 60.3%-85.6%]), and nasal congestion (47.7% [95% Cl, 33.6%-62.3%]). CONCLUSIONS: Our findings suggest that paroxysmal hemicrania is a rare disorder among adults evaluated for headache in tertiary care, while its prevalence in the general population remains unknown. Further studies focusing on the clinical features of paroxysmal hemicrania are warranted.

Surgical Management of Headache Disorders - A Systematic Review of the Literature.

PURPOSE OF REVIEW: This review article critically evaluates the latest advances in the surgical treatment of headache disorders. RECENT FINDINGS: Studies have demonstrated the effectiveness of innovative screening tools, such as doppler ultrasound, pain drawings, magnetic resonance neurography, and nerve blocks to help identify candidates for surgery. Machine learning has emerged as a powerful tool to predict surgical outcomes. In addition, advances in surgical techniques, including minimally invasive incisions, fat injections, and novel strategies to treat injured nerves (neuromas) have demonstrated promising results. Lastly, improved patient-reported outcome measures are evolving to provide a framework for comparison of conservative and invasive treatment outcomes. Despite these developments, challenges persist, particularly related to appropriate patient selection, insurance coverage, delays in diagnosis and surgical treatment, and the absence of standardized measures to assess and compare treatment impact. Collaboration between medical/procedural and surgical specialties is required to overcome these obstacles.

Cognitive assessment during the phases of a spontaneous migraine: a prospective cohort study.

INTRODUCTION: Cognitive symptoms are reported commonly throughout all phases of a migraine; however, there is a paucity of objective cognitive profiling. Previous studies have been limited by practice effect, and variable populations. METHODS: Participants completed 1 month of daily testing with a computerised cognitive battery involving a simple reaction (SRT), choice reaction (CRT) and a working memory test (WM). Results were correlated with their diary to identify interictal scores, and scores during each phase of a migraine, and non-migraine headache days. RESULTS: A total of 16 patients with episodic migraine participated. During the headache phase of a migraine, responses to SRT, CRT and WM tasks were significantly slower and less accurate than interictally. During the postdrome, WM task performance was slower and less accurate. Non-migraine headache days were not associated with significant change. CONCLUSION: The headache and postdromal phase of a migraine day was associated with objective evidence of cognitive dysfunction in patients with episodic migraine.

The Association Between the Central Sensitisation Inventory and Temporomandibular Disorders Is Confounded by Migraine, Depression, Widespread Pain and Parafunction. A Cross-Sectional Telehealth Study.

BACKGROUND: Temporomandibular disorders (TMDs) are conditions that involve the temporomandibular joints, masticatory muscles, and associated tissues, causing orofacial pain. Central sensitisation (CS) is a relevant part of the TMD pathophysiology. Migraine, psychological aspects, parafunctional oral habits and widespread pain are commonly associated with both TMD and CS and could confound the association between them. OBJECTIVES: To investigate the association between painful TMD and the Central Sensitisation Inventory (CSI) score, and to assess the presence of confounders in this association. METHODS: Cross-sectional study that assessed women with and without orofacial pain complaints using telehealth. The TMD Pain Screener and an online physical examination determined the presence of painful TMD. The following questionnaires were applied: CSI, Headache Screening Questionnaire, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Oral Behavior Checklist, Jaw Functional Limitation Scale and the Nordic musculoskeletal questionnaire. A single regression investigated the association between the CSI score and TMD, and a multiple regression investigated the effect of the other outcomes as possible confounders. Confounding was considered present when the association between TMD and the CSI score changed more than 10% after adding a possible confounder to the regression model. RESULTS: Forty-two women with painful TMD and 53 without TMD were included. There was a significant association between the CSI score and the presence of painful TMD (R2 = 0.639; p < 0.001). This association changed when the following outcomes were added to the model: presence of migraine, symptoms of depression, widespread pain and parafunctional oral habits. CONCLUSION: The positive association between TMD and the CSI score was confounded by migraine, symptoms of depression, widespread pain and parafunctional oral habits.

Factors associated to the presence of headache in patients with influenza infection and its consequences: a 2010-2020 surveillance-based study.

Headache is a common symptom of influenza infection; however, its causes and consequences remain uncertain. In this manuscript, we analyzed which demographic and clinical factors were associated with the presence of headache during the course of influenza infection and whether patients with headache had a different prognosis, evaluated by need of hospitalization, sick leave or school absenteeism. The influence study (NCT05704335) was an observational study that analyzed data routinely collected from the Health Sentinel Network between 2010 and 2020. During the study period, 7832 cases were considered, among which, 5275 (67.4%) reported headache. The presence of headache was independently associated with myalgia (2.753; 95%CI: 2.456-3.087, P < 0.001), asthenia (OR: 1.958; 95%CI: 1.732-2.214, P < 0.001), shivering (OR: 1.925; 95%CI: 1.718-2.156, P < 0.001), nasopharyngeal erythema (OR: 1.505; 95%CI: 1.293-1.753, P < 0.001), fever (OR: 1.469; 95%CI: 1.159-1.861; P = 0.001), sudden onset of symptoms (OR: 1.380; 95%CI: 1.120-1.702, p = 0.004), female sex (OR: 1.134; 95%CI: 1.023-1.257, P = 0.018), and gastrointestinal symptoms (OR: 1.169; 95%CI: 1.039-1.315; P = 0.01). Patients with headache had a sex and age adjusted lower odds of being referred to the hospital (OR: 0.463; 95%CI: 0.264-0.812, P = 0.007) and a higher odd of having a sick leave and/or school absenteeism (absenteeism (OR: 1.342; 95%CI: 1.190-1.514, P < 0.001). In conclusion, the presence of headache seems associated with symptoms caused by the innate immune response. These findings support a headache pathophysiology linked with the innate immune response. Due to the potential negative consequences and its treatable nature, clinicians should systematically evaluate it and, whenever necessary, treat it too.

Frequency and predictors of headache in the first 12 months after traumatic brain injury: results from CENTER-TBI.

BACKGROUND: Headache is a prevalent and debilitating symptom following traumatic brain injury (TBI). Large-scale, prospective cohort studies are needed to establish long-term headache prevalence and associated factors after TBI. This study aimed to assess the frequency and severity of headache after TBI and determine whether sociodemographic factors, injury severity characteristics, and pre- and post-injury comorbidities predicted changes in headache frequency and severity during the first 12 months after injury. METHODS: A large patient sample from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study was used. Patients were stratified based on their clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU) in the acute phase. Headache was assessed using a single item from the Rivermead Post-Concussion Symptoms Questionnaire measured at baseline, 3, 6 and 12 months after injury. Mixed-effect logistic regression analyses were applied to investigate changes in headache frequency and associated predictors. RESULTS: A total of 2,291 patients responded to the headache item at baseline. At study enrolment, 59.3% of patients reported acute headache, with similar frequencies across all strata. Female patients and those aged up to 40 years reported a higher frequency of headache at baseline compared to males and older adults. The frequency of severe headache was highest in patients admitted to the ICU. The frequency of headache in the ER stratum decreased substantially from baseline to 3 months and remained from 3 to 6 months. Similar trajectory trends were observed in the ICU and ADM strata across 12 months. Younger age, more severe TBI, fatigue, neck pain and vision problems were among the predictors of more severe headache over time. More than 25% of patients experienced headache at 12 months after injury. CONCLUSIONS: Headache is a common symptom after TBI, especially in female and younger patients. It typically decreases in the first 3 months before stabilising. However, more than a quarter of patients still experienced headache at 12 months after injury. Translational research is needed to advance the clinical decision-making process and improve targeted medical treatment for headache. TRIAL REGISTRATION: ClinicalTrials.gov NCT02210221.

Societal and economic burden of migraine in Spain: results from the 2020 National Health and Wellness Survey.

BACKGROUND: The burden of migraine goes beyond the pain and associated symptoms. We aimed to describe the impact of migraine in healthcare resource utilization (HCRU), work productivity, and mood disorders, as well as its economic cost. METHODS: Case-control study nested in a cross-sectional analysis of patient-reported data collected between 30/12/2019 and 20/04/2020 as part of the National Health and Wellness Survey, from respondents located in Spain. Adults (≥ 18 years old) who reported a physician diagnosis of migraine and ≥ 1 monthly headache days (MHD) in the previous 30 days were included. HCRU, health-related quality-of-life, depression scores, work and activity impairment, and the associated direct and indirect costs were assessed for four cohorts of migraine patients, according to the frequency of headache (MHD: 1-3, 4-7, 8-14, ≥ 15) and compared to a no-migraine control, matched to migraine cases by a propensity score based on demographic and clinical variables. RESULTS: The survey was completed by 595 people with active migraine, of whom 461 (77.4%) experienced < 8 MHDs and 134 (22.6%) ≥ 8 MHDs, and 1,190 non-migraine matched controls. Migraine patients presented worse mental and physical health functioning (SF-12 MCS: 41.9 vs. 44.7, p < 0.001; SF-12 PCS: 48.6 vs. 51.5, p < 0.001), worse self-reported health (EQ-5D VAS: 65.8 vs. 73.5, p < 0.001), more severe depression (PHQ-9: 8.9 vs. 6.1, p < 0.001), and higher overall work impairment (WPAI: 41.4 vs. 25.5, p < 0.001). People with migraine had higher HCRU, twice higher hospitalization rates (17.0% vs. 8.3%, p < 0.001) and 1.6 higher emergency room (ER) visit rates (51.4% vs. 31.2%, p < 0.001). Having migraine translated into higher annual costs with HCRU (€894 vs. €530) and productivity losses (€8,000 vs. €4,780) per person. Respondents with more MHDs presented worse outcomes and higher costs but suffering from 1-3 MHD also increased costs by 51.3%. CONCLUSIONS: Having migraine not only causes a massive impact on patients' quality of life and ability to work, but it also generates considerable economic costs for society. In Spain, having migraine was associated to 1.7 higher costs per patient. The clinical and economic burden increases with the frequency of headaches but is higher than controls even in patients suffering from 1-3 MHD.

The burden of headache disorders in the adult population of Mongolia: estimates, and a health-care needs assessment, from a cross-sectional population-based study.

BACKGROUND: Having previously shown headache disorders to be prevalent in Mongolia, here we elaborate on headache as a public-health concern in this country, reporting symptom burden and headache-attributed impaired participation at individual and societal levels, and conducting a health-care needs assessment. METHODS: The study followed the standardized methodology developed by the Global Campaign against Headache, generating a representative general-population sample through multi-level randomized cluster sampling. Participants aged 18-65 years were interviewed at unannounced household visits by interviewers administering the HARDSHIP questionnaire. Symptom burden was established through questions on frequency, duration and intensity of headache, with proportion of time in ictal state calculated from frequency and duration. Individual impaired participation was established through the HALT questionnaire, enquiring into lost time from paid and household work and from leisure activities. Symptom burden and impaired participation yesterday were also assessed in those reporting headache yesterday. Population-level estimates were derived by factoring in prevalence. RESULTS: The total sample included 2,043 participants. Those reporting any headache in the last year (n = 1,351) spent, on average, 9.7% of all their time with headache, losing 1.3 workdays and 2.4 household days/3 months. These losses were considerably higher among those with probable medication-overuse headache (37.5%, 3.5 workdays, 6.7 household days) or other headache on ≥ 15 days/month (H15+) (21.9%, 2.4 workdays, 5.1 household days). At population-level (including those with and without headache), 6.2-7.4% of all time was spent with headache, 3.1% with H15+; 0.8 workdays and 1.4 household days/person/3 months were lost to headache, 0.3 workdays and 0.6 household days to migraine (the biggest contributor of all headache types). Our needs assessment estimated that one third (33.2%) of the adult population of Mongolia have headache (mostly migraine or H15+) likely to benefit from health care. CONCLUSION: This first population-based study on headache burden in Mongolia shows high levels of individual and societal burden, with H15 + the cause of greater burden at population level than migraine and TTH combined. Migraine, however, has the biggest impact on the nation's productivity. From a purely economic perspective, Mongolia, with limited health resources, would probably be best served by focusing on mitigating migraine-attributed burden.

The burden of headache disorders in the adult general population of the Kingdom of Saudi Arabia: estimates from a cross-sectional population-based study including a health-care needs assessment.

BACKGROUND: We have previously shown headache to be highly prevalent among adults in Saudi Arabia. Here we estimate associated symptom burden and impaired participation (impaired use of time, lost productivity and disengagement from social activity), and use these estimates to assess headache-related health-care needs in Saudi Arabia. METHODS: A randomised cross-sectional survey included 2,316 adults (18-65 years) from all 13 regions of the country. It used the standardised methodology of the Global Campaign against Headache with a culturally mandated modification: engagement by cellphone using random digit-dialling rather than door-to-door visits. Enquiry used the HARDSHIP questionnaire, with diagnostic questions based on ICHD-3 beta, questions on symptom burden, enquiries into impaired participation using the HALT index and questions about activity yesterday in those reporting headache yesterday (HY). Health-care "need" was defined in terms of likelihood of benefit. We counted all those with headache on ≥ 15 days/month, with migraine on ≥ 3 days/month, or with migraine or TTH and meeting either of two criteria: a) proportion of time in ictal state (pTIS) > 3.3% and intensity ≥ 2 (moderate-severe); b) ≥ 3 lost days from paid work and/or household chores during 3 months. RESULTS: For all headache, mean frequency was 4.3 days/month, mean duration 8.4 h, mean intensity 2.3 (moderate). Mean pTIS was 3.6%. Mean lost days from work were 3.9, from household chores 6.6, from social/leisure activities 2.0. Of participants reporting HY, 37.3% could do less than half their expected activity, 19.8% could do nothing. At population-level (i.e., for every adult), 2.5 workdays (potentially translating into lost GDP), 3.6 household days and 1.3 social/leisure days were lost to headache. According to HY data, mean total impaired participation (not distinguishing between work, household and social/leisure) was 6.8%. A total of 830 individuals (35.8%) fulfilled one or more of our needs assessment criteria. CONCLUSION: A very high symptom burden is associated with a commensurately high burden of impaired participation. The economic cost appears to be enormous. Over a third of the adult population are revealed to require headache-related health care on the basis of being likely to benefit, demanding highly efficient organization of care.

The Role of MicroRNA in Migraine: A Systemic Literature Review.

Migraine is a common primary headache disorder, affecting about 14% of the population. Importantly, it was indicated as the second cause of disability globally and the leading cause among young women. Despite the widespread prevalence, migraine remains underdiagnosed and undertreated. The possible solution may be microRNAs-small, non-coding molecules. Until now, multiple studies have shown the great value of microRNA in both the diagnosis and treatment of different human diseases. Furthermore, a significant role in neurological disorders has been suggested. Little research regarding the utility of microRNA in migraine has been conducted, however, the results so far appear to be promising. We performed an electronic article search through PubMed and Embase Database to further explore the topic. After the analysis, according to PRISMA 2020 guidelines, we included 21 studies. The dysregulation was observed in migraine in general, as well as in different types and phases; thus, miRNAs emerge as promising diagnostic biomarkers. Additionally, some studies showed the influence of the intervention with miRNA levels on neuroinflammation and the expression of peptides, which are crucial in migraine pathogenesis. This review aims to summarize the current knowledge about the role of miRNAs in migraine and encourage to further research in this field.Kindly check and confirm the edit made in the title.I checked and confirm.