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Objective: To develop a natural language processing (NLP) algorithm that can accurately extract headache frequency from free‐text clinical notes. Background: Headache frequency, defined as the number of days with any headache in a month (or 4 weeks), remains a key parameter in the evaluation of treatment response to migraine preventive medications. However, due to the variations and inconsistencies in documentation by clinicians, significant challenges exist to accurately extract headache frequency from the electronic health record (EHR) by traditional NLP algorithms. Methods: This was a retrospective cross‐sectional study with patients identified from two tertiary headache referral centers, Mayo Clinic Arizona and Mayo Clinic Rochester. All neurology consultation notes written by 15 specialized clinicians (11 headache specialists and 4 nurse practitioners) between 2012 and 2022 were extracted and 1915 notes were used for model fine‐tuning (90%) and testing (10%). We employed four different NLP frameworks: (1) ClinicalBERT (Bidirectional Encoder Representations from Transformers) regression model, (2) Generative Pre‐Trained Transformer‐2 (GPT‐2) Question Answering (QA) model zero‐shot, (3) GPT‐2 QA model few‐shot training fine‐tuned on clinical notes, and (4) GPT‐2 generative model few‐shot training fine‐tuned on clinical notes to generate the answer by considering the context of included text. Results: The mean (standard deviation) headache frequency of our training and testing datasets were 13.4 (10.9) and 14.4 (11.2), respectively. The GPT‐2 generative model was the best‐performing model with an accuracy of 0.92 (0.91, 0.93, 95% confidence interval [CI]) and R2 score of 0.89 (0.87, 0.90, 95% CI), and all GPT‐2–based models outperformed the ClinicalBERT model in terms of exact matching accuracy. Although the ClinicalBERT regression model had the lowest accuracy of 0.27 (0.26, 0.28), it demonstrated a high R2 score of 0.88 (0.85, 0.89), suggesting the ClinicalBERT model can reasonably predict the headache frequency within a range of ≤ ± 3 days, and the R2 score was higher than the GPT‐2 QA zero‐shot model or GPT‐2 QA model few‐shot training fine‐tuned model. Conclusion: We developed a robust information extraction model based on a state‐of‐the‐art large language model, a GPT‐2 generative model that can extract headache frequency from EHR free‐text clinical notes with high accuracy and R2 score. It overcame several challenges related to different ways clinicians document headache frequency that were not easily achieved by traditional NLP models. We also showed that GPT‐2–based frameworks outperformed ClinicalBERT in terms of accuracy in extracting headache frequency from clinical notes. To facilitate research in the field, we released the GPT‐2 generative model and inference code with open‐source license of community use in GitHub. Additional fine‐tuning of the algorithm might be required when applied to different health‐care systems for various clinical use cases. Plain Language Summary: We developed a novel artificial intelligence program that can automatically and accurately extract headache frequency from doctors' notes. Figuring out how often someone gets headaches is important as it helps doctors see how bad the problem is and if treatments are working. Our method, using a powerful program called Generative Pre‐Trained Transformer‐2, worked better than older ways and could make big data migraine research easier. [ABSTRACT FROM AUTHOR]

Abstract Background Migraine is a headache disorder that affects public health and reduces the patient’s quality of life. Preventive medication is necessary to prevent acute attacks and medication overuse headaches (MOH). Agomelatine is a melatonin antagonist. Aims This study aimed to determine the effectiveness of agomelatine on the severity and frequency of migraine attacks. Methods The study is a parallel randomized controlled trial with two groups of intervention and control. 400 patients were evaluated. Eligible individuals, including those with episodic migraine headaches without aura between the ages of 18 and 60 years who did not receive preventive treatment beforehand, were enrolled. Also, patients did not receive any specific medications for other diseases. Among these, 100 people met the inclusion criteria and entered the study. These subjects were randomly assigned to one of the two groups. The intervention group received 25 mg of agomelatine daily and the control group received B1. In this study, the effect of agomelatine on the frequency and severity of attacks, mean monthly migraine days (MMD), and migraine disability assessment (MIDAS), were assessed. The study was triple-blind and after three months, a post-test was performed. Data were analyzed using SPSS software. Results A total of 100 patients were randomly assigned to either intervention or control groups. The prescriber physician and the data collector did not know about the allocation of patients to groups. Before the intervention, there was no significant difference in the headache frequency per month (t=-0.182, df = 98, p = 0.85), mean MMD (p = 0.17), headache severity (p = 0.076), and MIDAS (p = 0.091). After the study, there was a significant difference between the two groups in terms of the headache frequency per month (p = 0.009), and mean of MMD (p = 0.025). There was also a significant difference between pretest and posttest in two groups in the headache severity (p

Background: Pharmacological treatment is the primary approach in chronic migraine (CM), although non-drug interventions such as physical therapy are used as adjunct treatments. We aimed to review the efficacy of physical therapy and rehabilitation approaches for CM and their impact on quality of life (QoL) and disability. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included randomized controlled trials (RCTs) in adults with CM. The primary outcomes were changes in intensity, frequency, duration of headache, disability, and QoL. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. Data synthesis and quantitative analysis were conducted on relevant studies. Results: Seven RCTs were included in the narrative review, and five of them were eligible for quantitative analysis. Aerobic exercise (AE), osteopathic manipulative treatment (OMT), occipital transcutaneous electrical stimulation (OTES), acupressure, hydrotherapy, instrument-assisted soft tissue mobilization (IASTM), facial proprioceptive neuromuscular facilitation (FPNF), and connective tissue massage (CTM) were used in CM. AE combined with pharmacological therapy reduced the frequency, duration, and intensity of headache. OMT combined with medication improved QoL and reduced disability, intensity of pain, and migraine days per month. Hydrotherapy combined with medication also resulted in improvements in the intensity of headache, frequency, and overall QoL. IASTM and OTES reduced the intensity of headache, alleviated neck pain, and improved QoL, although there were conflicting findings following OTES alone on disability and intensity of headache. Both FPNF and CTM reduced the intensity of headache. Acupressure as an adjunct to medication did not show additional benefits on the intensity of headache and QoL. Quantitative analysis of the data showed that manual physical therapy combined with medication reduced the intensity of headache (p = 0.0796), and manual or AE combined with medication reduced the headache days per month (p = 0.047). Conclusions: A limited number of RCTs investigating the efficacy of physical therapy and rehabilitation approaches show promise in improving headache symptoms, reducing disability, and enhancing QoL in CM. Metaanalysis of the data also supported favorable outcomes for both intensity and headache days per month. Further research is needed to better understand the efficacy, optimal duration, and safety of physical therapy and rehabilitation approaches for CM, and to explore alternative interventions. [ABSTRACT FROM AUTHOR]

Abstract Background Headaches are frequent neurological disorders that are yet to be unveiled and treated comprehensively worldwide. Bearing in mind that the distribution of headache subtypes in neurology clinics (NC) is essential for planning appropriate diagnostic and therapeutic approaches, the primary goals of this multi-centric study are to carry out inter-regional comparisons by using current diagnostic criteria with evaluations of neurologists to delineate headache burden. Methods A cross-sectional study between April 1 and May 16, 2022 was conducted with the participation of 13 countries from the Middle East, Asia, and Africa. Patients were included in the study on a specific day each week during five consecutive weeks. All volunteers over the age of 18 and whose primary cause for admission was headache were examined. The patients admitted to NC or referred from emergency services/other services were evaluated by neurologists by means of the International Classification of Headache Disorders (ICHD-3) criteria. Results Among the 13,794 patients encountered in NC, headache was the primary complaint in 30.04%. The headache patients’ mean age was 42.85 ± 14.89 (18–95 years), and 74.3% were female. According to the ICHD-3 criteria, 86.7% of the main group had primary headache disorders, 33.5% had secondary headaches, 4% had painful cranial neuropathies along with other facial and headaches, and 5.2% had headaches included in the appendix part showing some overlapping conditions. While the most common primary headache was migraine without aura (36.8%), the most common secondary headache was medication-overuse headache (MOH) (9.8%). Headaches attributed to COVID-19, its secondary complications, or vaccines continue to occur at rates of 1.2%-3.5% in current neurology practice. Pain severity was significantly lower in Ivory Coast and Sudan than in Türkiye, Turkish Republic of Northern Cyprus, Iran, Egypt, Senegal, Tatarstan, and Azerbaijan (p

Abstract Background In an earlier paper, we examined the relationship between headache-attributed disability, measured as proportion of time in ictal state, and lost productivity. In a linear model, we found positive and significant associations with lost paid worktime, lost household worktime and total lost productivity (paid + household), but with high variance, which was increased when headache intensity was introduced as a factor. We speculated that analyses based on headache frequency alone as the independent variable, eliminating both the subjectivity of intensity estimates and the uncertainties of duration, might show stronger associations. Methods Focusing on migraine, we used individual participant data from 16 countries surveyed either in population-based studies or in the Eurolight project. These data included frequency (headache days/month), usual attack duration (hours), usual headache intensity (“not bad”, “quite bad”, “very bad”) and lost productivity from paid and household work according to enquiries using the Headache-Attributed Lost Time (HALT) questionnaire. We used multiple linear regressions, calculating regression equations along with unstandardized and standardized regression coefficients. We made line and bar charts to visualize relationships. Results Both frequency and intensity were significant predictors of lost productivity in all multiple linear regressions, but duration was a non-significant predictor in several of the regressions. Predicted productivity in paid work decreased among males by 0.75–0.85 days/3 months for each increase of 1 headache day/month, and among females by 0.34–0.53 days/3 months. In household chores, decreases in productivity for each added day/month of headache were more similar (0.67–0.87 days/3 months among males, 0.83–0.89 days/3 months among females). Visualizations showed that the impact of duration varied little across the range of 2–24 h. The standardized regression coefficients demonstrated that frequency was a much better predictor of lost productivity than intensity or duration. Conclusion In the relationship between migraine-attributed impairment (symptom burden) and lost productivity, frequency (migraine days/month) is the dominating variable – more important than headache intensity and far more important than episode duration. This has major implications for current practice in headache care and for health policy and health-resource investment. Preventative drugs, grossly underutilized in current practice, offer a high prospect of economic benefit (cost-saving), but new preventative drugs are needed with better efficacy and/or tolerability.

Neck pain (NP) is a prevalent symptom among migraine patients, but its disability on headache impact and the contributing factors for comorbid NP are poorly understood. This study aimed to investigate NP disability on the impact of headaches among migraineurs and factors linked to comorbid NP, including sleep-related variables. This cross-sectional study was conducted at a university hospital headache center, for headache patients at their first visits. Included in the study were 295 patients with migraines (217 females; 39.0  ±  10.8 years; 101 chronic migraine). Information on NP, history of physician-diagnosed cervical spine or disc disorders, detailed parameters of headache, and sleep and mood variables were collected. Logistic analysis of the severe impact of headache and contributing factors for NP were performed. NP was present in 153 participants (51.9%) with migraine, with high NP disability observed in 28 patients, and 125 patients had low NP disability. In multivariable analysis, NP disability, medication days per month, severe disability of migraine, and excessive daytime sleepiness were significant predictors for severe impact of headache. Thirty-seven patients with physician-diagnosed cervical spine or disc disorders were excluded from the NP analysis. Higher monthly headache days, female gender, and a high likelihood of obstructive sleep apnea were positively correlated with the presence of NP among migraineurs in multivariable analysis. Overall, the study highlights the potential impact of sleep-related variables and monthly headache days on NP in these patients. The high disability of NP was also associated with severe impact of headache. [ABSTRACT FROM AUTHOR]

Background: Our prior work demonstrated that questionnaires assessing psychosocial symptoms have utility for predicting improvement in patients with acute post-traumatic headache following mild traumatic brain injury. In this cohort study, we aimed to determine whether prediction accuracy can be refined by adding structural magnetic resonance imaging (MRI) brain measures to the model. Methods: Adults with acute post-traumatic headache (enrolled 0–59 days post-mild traumatic brain injury) underwent T1-weighted brain MRI and completed three questionnaires (Sports Concussion Assessment Tool, Pain Catastrophizing Scale, and the Trait Anxiety Inventory Scale). Individuals with post-traumatic headache completed an electronic headache diary allowing for determination of headache improvement at three- and at six-month follow-up. Questionnaire and MRI measures were used to train prediction models of headache improvement and headache trajectory. Results: Forty-three patients with post-traumatic headache (mean age = 43.0, SD = 12.4; 27 females/16 males) and 61 healthy controls were enrolled (mean age = 39.1, SD = 12.8; 39 females/22 males). The best model achieved cross-validation Area Under the Curve of 0.801 and 0.805 for predicting headache improvement at three and at six months. The top contributing MRI features for the prediction included curvature and thickness of superior, middle, and inferior temporal, fusiform, inferior parietal, and lateral occipital regions. Patients with post-traumatic headache who did not improve by three months had less thickness and higher curvature measures and notably greater baseline differences in brain structure vs. healthy controls (thickness: p < 0.001, curvature: p = 0.012) than those who had headache improvement. Conclusions: A model including clinical questionnaire data and measures of brain structure accurately predicted headache improvement in patients with post-traumatic headache and achieved improvement compared to a model developed using questionnaire data alone. [ABSTRACT FROM AUTHOR]

Background: Headaches are frequent neurological disorders that are yet to be unveiled and treated comprehensively worldwide. Bearing in mind that the distribution of headache subtypes in neurology clinics (NC) is essential for planning appropriate diagnostic and therapeutic approaches, the primary goals of this multi-centric study are to carry out inter-regional comparisons by using current diagnostic criteria with evaluations of neurologists to delineate headache burden. Methods: A cross-sectional study between April 1 and May 16, 2022 was conducted with the participation of 13 countries from the Middle East, Asia, and Africa. Patients were included in the study on a specific day each week during five consecutive weeks. All volunteers over the age of 18 and whose primary cause for admission was headache were examined. The patients admitted to NC or referred from emergency services/other services were evaluated by neurologists by means of the International Classification of Headache Disorders (ICHD-3) criteria. Results: Among the 13,794 patients encountered in NC, headache was the primary complaint in 30.04%. The headache patients' mean age was 42.85 ± 14.89 (18–95 years), and 74.3% were female. According to the ICHD-3 criteria, 86.7% of the main group had primary headache disorders, 33.5% had secondary headaches, 4% had painful cranial neuropathies along with other facial and headaches, and 5.2% had headaches included in the appendix part showing some overlapping conditions. While the most common primary headache was migraine without aura (36.8%), the most common secondary headache was medication-overuse headache (MOH) (9.8%). Headaches attributed to COVID-19, its secondary complications, or vaccines continue to occur at rates of 1.2%-3.5% in current neurology practice. Pain severity was significantly lower in Ivory Coast and Sudan than in Türkiye, Turkish Republic of Northern Cyprus, Iran, Egypt, Senegal, Tatarstan, and Azerbaijan (p < 0.001). Conclusions: The study showed that migraine is still the most common motive for admissions to NC in different regions. Furthermore, MOH, an avoidable disorder, is the most common secondary headache type and appears to be a significant problem in all regions. Remarkably, pain perception differs between regions, and pain intensity is lower in Africa than in other regions. [ABSTRACT FROM AUTHOR]

Background: In an earlier paper, we examined the relationship between headache-attributed disability, measured as proportion of time in ictal state, and lost productivity. In a linear model, we found positive and significant associations with lost paid worktime, lost household worktime and total lost productivity (paid + household), but with high variance, which was increased when headache intensity was introduced as a factor. We speculated that analyses based on headache frequency alone as the independent variable, eliminating both the subjectivity of intensity estimates and the uncertainties of duration, might show stronger associations. Methods: Focusing on migraine, we used individual participant data from 16 countries surveyed either in population-based studies or in the Eurolight project. These data included frequency (headache days/month), usual attack duration (hours), usual headache intensity ("not bad", "quite bad", "very bad") and lost productivity from paid and household work according to enquiries using the Headache-Attributed Lost Time (HALT) questionnaire. We used multiple linear regressions, calculating regression equations along with unstandardized and standardized regression coefficients. We made line and bar charts to visualize relationships. Results: Both frequency and intensity were significant predictors of lost productivity in all multiple linear regressions, but duration was a non-significant predictor in several of the regressions. Predicted productivity in paid work decreased among males by 0.75–0.85 days/3 months for each increase of 1 headache day/month, and among females by 0.34–0.53 days/3 months. In household chores, decreases in productivity for each added day/month of headache were more similar (0.67–0.87 days/3 months among males, 0.83–0.89 days/3 months among females). Visualizations showed that the impact of duration varied little across the range of 2–24 h. The standardized regression coefficients demonstrated that frequency was a much better predictor of lost productivity than intensity or duration. Conclusion: In the relationship between migraine-attributed impairment (symptom burden) and lost productivity, frequency (migraine days/month) is the dominating variable – more important than headache intensity and far more important than episode duration. This has major implications for current practice in headache care and for health policy and health-resource investment. Preventative drugs, grossly underutilized in current practice, offer a high prospect of economic benefit (cost-saving), but new preventative drugs are needed with better efficacy and/or tolerability. [ABSTRACT FROM AUTHOR]

Objectives/Background: Post‐traumatic headache (PTH) is a common symptom after mild traumatic brain injury (mTBI). Although there have been several studies that have used clinical features of PTH to attempt to predict headache recovery, currently no accurate methods exist for predicting individuals' improvement from acute PTH. This study investigated the utility of clinical questionnaires for predicting (i) headache improvement at 3 and 6 months, and (ii) headache trajectories over the first 3 months. Methods: We conducted a clinic‐based observational longitudinal study of patients with acute PTH who completed a battery of clinical questionnaires within 0–59 days post‐mTBI. The battery included headache history, symptom evaluation, cognitive tests, psychological tests, and scales assessing photosensitivity, hyperacusis, insomnia, cutaneous allodynia, and substance use. Each participant completed a web‐based headache diary, which was used to determine headache improvement. Results: Thirty‐seven participants with acute PTH (mean age = 42.7, standard deviation [SD] = 12.0; 25 females/12 males) completed questionnaires at an average of 21.7 (SD = 13.1) days post‐mTBI. The classification of headache improvement or non‐improvement at 3 and 6 months achieved cross‐validation area under the curve (AUC) of 0.72 (95% confidence interval [CI] 0.55 to 0.89) and 0.84 (95% CI 0.66 to 1.00). Sub‐models trained using only the top five features still achieved 0.72 (95% CI 0.55 to 0.90) and 0.77 (95% CI 0.52 to 1.00) AUC. The top five contributing features were from three questionnaires: Pain Catastrophizing Scale total score and helplessness sub‐domain score; Sports Concussion Assessment Tool Symptom Evaluation total score and number of symptoms; and the State‐Trait Anxiety Inventory score. The functional regression model achieved R=0.64 for modeling headache trajectory over the first 3 months. Conclusion: Questionnaires completed following mTBI have good utility for predicting headache improvement at 3 and 6 months in the future as well as the evolving headache trajectory. Reducing the battery to only three questionnaires, which assess post‐concussive symptom load and biopsychosocialecologic factors, was helpful to determine a reasonable prediction accuracy for headache improvement. [ABSTRACT FROM AUTHOR]

Background: Pharmacological treatment is the primary approach in chronic migraine (CM), although non-drug interventions such as physical therapy are used as adjunct treatments. We aimed to review the efficacy of physical therapy and rehabilitation approaches for CM and their impact on quality of life (QoL) and disability. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included randomized controlled trials (RCTs) in adults with CM. The primary outcomes were changes in intensity, frequency, duration of headache, disability, and QoL. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. Data synthesis and quantitative analysis were conducted on relevant studies. Results: Seven RCTs were included in the narrative review, and five of them were eligible for quantitative analysis. Aerobic exercise (AE), osteopathic manipulative treatment (OMT), occipital transcutaneous electrical stimulation (OTES), acupressure, hydrotherapy, instrument-assisted soft tissue mobilization (IASTM), facial proprioceptive neuromuscular facilitation (FPNF), and connective tissue massage (CTM) were used in CM. AE combined with pharmacological therapy reduced the frequency, duration, and intensity of headache. OMT combined with medication improved QoL and reduced disability, intensity of pain, and migraine days per month. Hydrotherapy combined with medication also resulted in improvements in the intensity of headache, frequency, and overall QoL. IASTM and OTES reduced the intensity of headache, alleviated neck pain, and improved QoL, although there were conflicting findings following OTES alone on disability and intensity of headache. Both FPNF and CTM reduced the intensity of headache. Acupressure as an adjunct to medication did not show additional benefits on the intensity of headache and QoL. Quantitative analysis of the data showed that manual physical therapy combined with medication reduced the intensity of headache (p = 0.0796), and manual or AE combined with medication reduced the headache days per month (p = 0.047). Conclusions: A limited number of RCTs investigating the efficacy of physical therapy and rehabilitation approaches show promise in improving headache symptoms, reducing disability, and enhancing QoL in CM. Meta-analysis of the data also supported favorable outcomes for both intensity and headache days per month. Further research is needed to better understand the efficacy, optimal duration, and safety of physical therapy and rehabilitation approaches for CM, and to explore alternative interventions.

Abstract Background Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for migraine prevention in adults. Real-world data on the effectiveness of fremanezumab are limited. This retrospective, observational cohort study assessed patient-reported migraine symptoms, health care resource utilization (HCRU), and direct medical costs before and after fremanezumab treatment initiation. Methods Data were extracted from September 2018 through June 2020 from the Midwest component of EMRClaims+®, an integrated health services database containing > 20 million medical records from national commercial insurance claims, Medicare claims, and regional electronic medical records. Patients included in the cohort analysis were aged ≥ 18 years and were administered fremanezumab, with enrollment or treatment history for ≥ 6 months prior (pre-index) to initiating fremanezumab (index date) and ≥ 1 month after the index date (post-index), and without pregnancy or pregnancy-related encounters during the study period. Patient-reported headache frequency, migraine pain intensity (MPI), composite migraine symptoms, and HCRU were assessed pre-index and ≥ 1 month after fremanezumab initiation. Wilcoxon signed-rank tests were used to compare means of migraine symptoms and outcomes and HCRU before and after fremanezumab initiation. Results Overall, 172 patients were eligible for analysis. Of patients who self-reported (n = 129), 83.7% reported improvement in headache frequency or symptoms after fremanezumab treatment. Specifically, headache frequency decreased by 63% after fremanezumab initiation: mean (standard deviation) headache frequency was 22.24 (9.29) days per month pre-index versus 8.24 (7.42) days per month post-index (P

Neck pain (NP) is a prevalent symptom among migraine patients, but its disability on headache impact and the contributing factors for comorbid NP are poorly understood. This study aimed to investigate NP disability on the impact of headaches among migraineurs and factors linked to comorbid NP, including sleep-related variables. This cross-sectional study was conducted at a university hospital headache center, for headache patients at their first visits. Included in the study were 295 patients with migraines (217 females; 39.0 ± 10.8 years; 101 chronic migraine). Information on NP, history of physician-diagnosed cervical spine or disc disorders, detailed parameters of headache, and sleep and mood variables were collected. Logistic analysis of the severe impact of headache and contributing factors for NP were performed. NP was present in 153 participants (51.9%) with migraine, with high NP disability observed in 28 patients, and 125 patients had low NP disability. In multivariable analysis, NP disability, medication days per month, severe disability of migraine, and excessive daytime sleepiness were significant predictors for severe impact of headache. Thirty-seven patients with physician-diagnosed cervical spine or disc disorders were excluded from the NP analysis. Higher monthly headache days, female gender, and a high likelihood of obstructive sleep apnea were positively correlated with the presence of NP among migraineurs in multivariable analysis. Overall, the study highlights the potential impact of sleep-related variables and monthly headache days on NP in these patients. The high disability of NP was also associated with severe impact of headache.

• Current evidence is insufficient for routine clinical use of yoga therapy for migraine. Several studies have explored the efficacy of yoga therapy for migraine patients, but the results are conflicting. • The results find that compared to control group for migraine patients, yoga therapy can significantly decrease headache frequency with significant heterogeneity among the studies. • Adjuvant yoga therapy may provide additional benefit to reduce the headache frequency in patients with migraine attack. The efficacy of yoga therapy for migraine remains controversial. We conduct this meta-analysis to explore the influence of yoga therapy on the treatment efficacy of migraine. We have searched PubMed, EMbase, Web of science, EBSCO and Cochrane library databases through February 2021, and included randomized controlled trials (RCTs) assessing the efficacy of yoga therapy for migraine attack. Five RCTs involving 356 patients were included in the meta-analysis. Overall, compared with control group for migraine, yoga therapy was associated with substantially reduced headache frequency headache frequency (SMD = −1.43; 95% CI = −2.23 to −0.64; P = 0.0004) and HIT−6 score (SMD = −2.19; 95% CI = −4.09 to −0.28; P = 0.02), but revealed no obvious influence on pain intensity (SMD = −1.37; 95% CI = −2.76 to 0.01; P = 0.05) or McGill Pain Questionnaire (SMD = −2.09; 95% CI = −6.39 to 2.22; P = 0.34). Yoga therapy may benefit to reduce the headache frequency of migraine patients. [ABSTRACT FROM AUTHOR]

Primary headache disorders, such as migraine and tension-type headache (TTH), represent a significant public health concern. Besides, cognitive/mental stress was suggested to contribute to TTH and migraine physiopathology. Thus, this study aimed to evaluate the existence of a causal relationship between stress (mental/cognitive or daily stress) and headache or pain improvement in migraine and TTH patients. We developed a systematic review of the literature, including studies that utilized mental/cognitive stress tasks or daily stress by lifestyle questionnaire in migraine and TTH patients. Necessarily, these studies should have healthy patients and a pain measure (quantitative sensory tests or headache/migraine detection). PubMed, EMBASE, and SCOPUS were searched, using terms about stress and primary headaches. Both mental/cognitive stress and daily stress (perceived) were related to an increase in pain perception and related to the development of headache or enhanced transient pain intensity in migraine and TTH patients. Different factors could enrich the comprehension of the influence of stress on pain/headache induction in migraine and TTH patients, including methodological standardization, consistency of assessing, and isolating the many headache triggers in randomized controlled trial studies. [ABSTRACT FROM AUTHOR]

Background: Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for migraine prevention in adults. Real-world data on the effectiveness of fremanezumab are limited. This retrospective, observational cohort study assessed patient-reported migraine symptoms, health care resource utilization (HCRU), and direct medical costs before and after fremanezumab treatment initiation. Methods: Data were extracted from September 2018 through June 2020 from the Midwest component of EMRClaims+®, an integrated health services database containing > 20 million medical records from national commercial insurance claims, Medicare claims, and regional electronic medical records. Patients included in the cohort analysis were aged ≥ 18 years and were administered fremanezumab, with enrollment or treatment history for ≥ 6 months prior (pre-index) to initiating fremanezumab (index date) and ≥ 1 month after the index date (post-index), and without pregnancy or pregnancy-related encounters during the study period. Patient-reported headache frequency, migraine pain intensity (MPI), composite migraine symptoms, and HCRU were assessed pre-index and ≥ 1 month after fremanezumab initiation. Wilcoxon signed-rank tests were used to compare means of migraine symptoms and outcomes and HCRU before and after fremanezumab initiation. Results: Overall, 172 patients were eligible for analysis. Of patients who self-reported (n = 129), 83.7% reported improvement in headache frequency or symptoms after fremanezumab treatment. Specifically, headache frequency decreased by 63% after fremanezumab initiation: mean (standard deviation) headache frequency was 22.24 (9.29) days per month pre-index versus 8.24 (7.42) days per month post-index (P < 0.0001). Mean MPI also decreased by 18% after fremanezumab initiation: MPI was 5.47 (3.19) pre-index versus 4.51 (3.34) post-index (P = 0.014). Mean emergency room (ER) visits per month decreased from 0.72 to 0.54 (P = 0.003), and mean outpatient visits per month decreased from 1.04 to 0.81 (P < 0.001). Mean hospitalizations per month decreased, but the results did not reach statistical significance (P = 0.095). Hospitalization and ER costs decreased, while outpatient costs increased, from pre-index to post-index, but differences were not statistically significant (P ≥ 0.232). Conclusions: Significant reductions in headache frequency, MPI, and HCRU were observed after fremanezumab initiation in patients with migraine in a US real-world setting. [ABSTRACT FROM AUTHOR]

Background: Erenumab (erenumab-aooe in the US) effectively reduces monthly migraine days in episodic and chronic migraine. This traditional outcome does not capture the intensity of headache pain on days with migraine. Methods: This post hoc analysis of two pivotal randomized, placebo-controlled studies in patients with episodic migraine and chronic migraine examined the effect of erenumab 70 and 140 mg on migraine pain. Cumulative monthly migraine pain intensity is the sum of the peak pain intensity scores (0 = no migraine to 3 = migraine day with severe pain) on migraine days. Change from baseline in cumulative monthly migraine pain and average monthly pain intensity was assessed over months 4 to 6 for episodic migraine and month 3 for chronic migraine; change in average monthly pain intensity was assessed among monthly migraine days responders/non-responders. Results: Efficacy analysis included 946 patients for the episodic migraine study and 656 patients for the chronic migraine study. Cumulative monthly migraine pain decreased significantly with erenumab versus placebo (p < 0.001, for episodic migraine and chronic migraine). In addition, monthly average migraine pain intensity decreased significantly with erenumab versus placebo for episodic migraine (p < 0.01); decreases were non-significant for chronic migraine. In comparison with placebo-treated patients, a greater proportion of erenumab-treated patients were pain intensity responders regardless of threshold used. Episodic migraine and chronic migraine patients with a ≥50% reduction in monthly migraine days (responders) had a greater reduction in monthly average pain intensity than non-responders. Conclusions: Erenumab reduced cumulative monthly migraine pain in episodic migraine and chronic migraine patients and significantly reduced monthly average migraine pain in episodic migraine, demonstrating treatment benefit beyond reduction in migraine frequency. Clinical Trial Registration: ClinicalTrials.gov, NCT02456740; ClinicalTrials.gov, NCT02066415 [ABSTRACT FROM AUTHOR]

Objective: We sought to evaluate temporal response patterns to erenumab treatment in patients with episodic migraine. Background: Although many patients treated with erenumab experience onset of efficacy as early as 1 week, clinical benefits of migraine preventive therapies may accrue with continued treatment. Furthermore, details about the maintenance of clinical responses have not been reported. Methods: This was a post hoc analysis of a 6‐month, randomized, double‐blind, placebo‐controlled, phase 3 study of erenumab for the prevention of episodic migraine. We analyzed temporal responses to erenumab using a threshold of ≥50% reduction from baseline in monthly migraine days (MMDs). Results: During the 6‐month treatment period, 73.7% (230/312) and 79.6% (253/318) of patients in the erenumab 70 mg (n = 312) and 140 mg (n = 318) groups, respectively, achieved a response in at least 1 month. In this group of responders, at least half reached first monthly response (first month with ≥50% reduction from baseline in MMDs) by month 2 and at least 75% of them by month 3. The remainder responded in months 4–6. Of patients in the erenumab 70 and 140 mg groups, 35.3% (110/312) and 41.8% (133/318), respectively, responded over months 1–3 (mean response over first 3 months). Of these patients, 81.8% (90/110) and 81.9% (109/133) maintained this response over months 4–6 (mean response over last 3 months) in the 70 and 140 mg groups, respectively. Many patients who did not achieve an initial response (≥50% reduction from baseline in MMDs during month 1) responded later with continued treatment, with approximately one‐half or more of initial nonresponders responding by months 4–6. Conclusions: These results support guidelines recommending at least 3 months following the initiation of erenumab for migraine prevention before the assessment of response. [ABSTRACT FROM AUTHOR]

Objectives: The management of chronic migraine (CM) with Medication Overuse Headache (MOH) consists of withdrawal therapy, education on medications' use and prescription of prophylaxis. Little attention has been given to patients who fail in achieving a successful short‐term outcome after withdrawal: we aim to describe predictors of failure. Methods: Patients with CM and MOH were enrolled at the Neurological Institute C. Besta of Milano, and included if they completed the three months follow‐up. Withdrawal failure was defined as the situation in which patients either did not revert from chronic to episodic migraine (EM), were still overusing acute medications, or both did not revert to EM and kept overusing acute medications. Predictors of failure were addressed with a logistic regression, and for all variables, the longitudinal course in the two groups was described. Results: In 39, out of 137 patients, withdrawal was unsuccessful: the predictors included day‐hospital‐based withdrawal (OR: 2.37; 95% CI: 1.06–5.29), emergency room (ER) access before withdrawal (OR: 2.81; 95% CI: 1.13–6.94) and baseline headache frequency >69 days/three months (OR: 2.97; 95% CI: 1.32–6.65). Patients who failed withdrawal did not improve on medications intake, use of prophylactic and non‐pharmacological treatments, symptoms of anxiety and depression. Conclusions: Patients who were treated in day‐hospital, those who recently attended ER for headache, and those with more than 69 headache/3 months, as well as to those with relevant symptoms of anxiety and depression who did not improve should be closely monitored to reduce likelihood of non‐improvement after structured withdrawal. [ABSTRACT FROM AUTHOR]

This observational study aimed to assess the difference in disability, burden, and sensitization between migraine patients with low-frequency headache attack (1–8 headache days/month), high-frequency headache attack (9–14 headache days/months), and patients with chronic migraine (>14 headache days/months). Migraine patients with or without aura were divided into three groups according to headache frequency (low-frequency episodic migraine; high-frequency episodic migraine; chronic migraine). Questionnaires were used to assess the burden of headache, quality of life, phycological burden, and symptoms related to sensitization (estimated by the Central Sensitization Inventory). Differences among migraine groups were assessed using Chi-Quadro test, ANOVA, or Kruskal–Wallis as appropriate. 136 patients were included (68 low-frequency episodic migraine, 45 high-frequency episodic migraine, 23 chronic migraine). Patients with high frequency episodic migraine and chronic migraine differed from patients with low frequency episodic migraine showing a worse burden of headache (p=0.002; p=0.002), worse level of physical (p=0.001; p<0.001) and mental (p=0.002; p=0.001) quality of life, worse level of depression (p=0.008; p=0.003), and increase presence of symptoms related to sensitization (p<0.001; p=0.003). No differences were found in any variables between patients with high-frequency episodic migraine and patients with chronic migraine (p>0.05). Patients with high-frequency episodic migraine and chronic migraine could be considered in the same segment of the migraine population, with similar degrees of disability and sensitization related symptoms. [ABSTRACT FROM AUTHOR]

Abstract Background Migraine has many presumed comorbidities which have rarely been compared between samples with and without migraine. Examining the association between headache pain intensity and monthly headache day (MHD) frequency with migraine comorbidities is novel and adds to our understanding of migraine comorbidity. Methods The MAST Study is a prospective, web-based survey that identified US population samples of persons with migraine (using modified International Classification of Headache Disorders-3 beta criteria) and without migraine. Eligible migraine participants averaged ≥1 MHDs over the prior 3 months. Comorbidities “confirmed by a healthcare professional diagnosis” were endorsed by respondents from a list of 21 common cardiovascular, neurologic, psychiatric, sleep, respiratory, dermatologic, pain and medical comorbidities. Multivariable binary logistic regression calculated odds ratios (OR) and 95% confidence intervals for each condition between the two groups adjusting for sociodemographics. Modeling within the migraine cohort assessed rates of conditions as a function of headache pain intensity, MHD frequency, and their combination. Results Analyses included 15,133 people with migraine (73.0% women, 77.7% White, mean age 43 years) and 77,453 controls (46.4% women, 76.8% White, mean age 52 years). People with migraine were significantly (P

Objective: To evaluate whether the 15‐day threshold of headache days per month adequately reflects substantial differences in disability across the full spectrum of migraine. Background: The monthly frequency of headache days defines migraine subtypes and has crucial implications for epidemiological and clinical research as well as access to care. Methods: The patients with migraine (N = 836) who participated in the American Registry for Migraine Research, which is a multicenter, longitudinal patient registry, between February 2016 and March 2020, were divided into four groups based on monthly headache frequency: Group 1 (0–7 headache days/month, n = 286), Group 2 (8–14 headache days/month, n = 180), Group 3 (15–23 headache days/month, n = 153), Group 4 (≥24 headache days/month, n = 217). Disability (MIDAS), Pain intensity (NRS), Work Productivity and Activity Impairment (WPAI), Pain Interference (PROMIS‐PI), Patient Health Questionnaire‐4 (PHQ‐4), and General Anxiety Disorder‐7 (GAD‐7) scores were compared. Results: Mean (standard deviation [SD]) age was 46 (13) years (87.9% [735/836] female). The proportion of patients in each group was as follows: Group 1 (34.2% [286/836]), Group 2 (21.5% [180/836]), Group 3 (18.3% [153/836]), and Group 4 (26.0% [217/836]). There were significant relationships with increasing disability, lost productive time, and pain interference in higher headache frequency categories. There were no significant differences between Group 2 and Group 3 for most measures (NRS, all WPAI scores, PROMIS‐PI, GAD‐7, and PHQ‐4), although MIDAS scores differed (median [interquartile range (IQR)]; 38 [20–58] vs. 55 [30–90], p < 0.001). Patients in Group 1 had significantly lower MIDAS (median [IQR];16 [7–30], p < 0.001), WPAI‐% total active impairment (mean (SD): Group 1 [30.9 (26.8)] vs. Group 2 [39.2 (24.5), p = 0.017], vs. Group 3 [45.9 (24.1), p < 0.001], vs. Group 4 [55.3 (23.0), p < 0.001], and PROMIS‐PI‐T score (Group 1 [60.3 (7.3)] vs. Group 2 [62.6 (6.4), p = 0.008], vs. Group 3 [64.6 (5.6), p < 0.001], vs. Group 4 [66.8 (5.9), p < 0.001]) compared to all other groups. Patients in Group 4 had significantly higher MIDAS (median (IQR): Group 4 [90 (52–138)] vs. Group 1 [16 (7–30), p < 0.001], vs. Group 2 [38 (20–58), p < 0.001], vs. Group 3 [55 (30–90), p < 0.001], WPAI‐%Presenteeism (Group 4 [50.4 (24.4)] vs. Group 1 [28.8 (24.9), p < 0.001], vs. Group 2 [34.9 (22.3), p < 0.001], vs. Group 3 [40.9 (22.3), p = 0.048], WPAI‐% total work productivity impairment (Group 4 [55.9 (26.1)] vs. Group 1 [32.1 (37.6), p < 0.001], vs. Group 2 [38.3 (24.0), p < 0.001], vs. Group 3 [44.6 (24.4), p = 0.019]), and WPAI‐%Total activity impairment (Group 4 [55.3 (23.0)] vs. Group 1 [30.9 (26.8), p < 0.001], vs. Group 2 [39.2 (24.5), p < 0.001], vs. Group 3 [45.9 (24.1), p = 0.025]) scores compared with all other groups. Conclusion: Our data suggest that the use of a 15 headache day/month threshold to distinguish episodic and chronic migraine does not capture the burden of illness nor reflect the treatment needs of patients. These results have important implications for future refinements in the classification of migraine. [ABSTRACT FROM AUTHOR]

Background: Migraine is known to be a common neurological disorder among children. Newer anti-epileptic agents like topiramate (TPM) have shown to decrease the frequency of headache but not much work about safety and efficacy of TPM is seen in the paediatric population with migraine. This study was aimed to find out the efficacy and safety of TMP for migraine prophylaxis among children aged 5–15 years. Methods: A total of 132 children having migraine headache according to ICHD-II criterion for duration of at least 6 months, from 5–15 years of age were enrolled. Frequency of headache, severity of headache and duration of headache were compared before and after 3 months of TPM treatment. Side effects of TPM treatment were also observed. Results: In a total of 132 children, 80 (60.6%) were female and 52 (39.4%) males. Mean age was 9.52±2.5 years. Good response of TPM treatment was observed in 102 (77.3%) children. Significant decrease (p value <0.05) was noted in headache frequency, severity and duration following TPM treatment. No serious side effects of TPM treatment were noted. Conclusion: Topiramate is noted to be effective and safe for migraine prophylaxis among children. Reduction in headache frequency, severity as well as duration and disability scores are recorded after TPM treatment. [ABSTRACT FROM AUTHOR]

Background and purpose: Although erenumab has demonstrated significant reduction in migraine frequency and improved quality of life in studies lasting 3 to 12 months, little is known about long‐term therapy. Methods: This study was an open‐label, 5‐year treatment phase following a 12‐week, double‐blind, placebo‐controlled trial in adults with episodic migraine. Patients initially received open‐label erenumab 70 mg, which increased to 140 mg following a protocol amendment. Efficacy analyses included change from baseline in monthly migraine days (MMDs), monthly acute migraine‐specific medication (AMSM) days, and health‐related quality of life. Results: Of 383 patients enrolled, 250 switched to 140 mg; 215 (56.1%) completed open‐label treatment. Mean (standard error) change in MMDs from baseline of 8.7 (0.2) days was −5.3 (0.3) days; an average reduction of 62.3% at year 5. Among patients using AMSM at baseline (6.3 [2.8] treatment days), mean change in monthly AMSM days was −4.4 (0.3) days at the end of 5 years. Patient‐reported outcomes indicated stable improvements in disability, headache impact, and migraine‐specific quality of life. Exposure‐adjusted patient incidence rates of adverse events (AEs) were 123.0/100 patient‐years; AEs were most frequently nasopharyngitis, upper respiratory tract infection, and influenza. Serious AEs (SAEs) reported by 49 patients (3.8/100 patient‐years) were mostly single occurrence. Two fatal adverse events were reported. There were no increases in incidence of AEs, SAEs, or AEs leading to treatment discontinuation over 5 years of exposure. Conclusions: Treatment with erenumab was associated with reductions in migraine frequency and improvements in health‐related quality of life that were maintained for at least 5 years. No new safety signals were observed. [ABSTRACT FROM AUTHOR]

Objective: Our objective is to explore whether blood–cerebrospinal fluid (CSF) barrier biomarkers differ in episodic migraine (EM) or chronic migraine (CM) from controls. Background: Reports of blood–brain barrier and blood–cerebrospinal fluid barrier (BCSFB) disruption in migraine vary. Our hypothesis is that investigation of biomarkers associated with blood, CSF, brain, cell adhesion, and inflammation will help elucidate migraine pathophysiology. Methods: We recruited 14 control volunteers without headache disorders and 42 individuals with EM or CM as classified using the International Classification of Headache Disorders, 3rd edition, criteria in a cross‐sectional study located at our Pasadena and Stanford headache research centers in California. Blood and lumbar CSF samples were collected once from those diagnosed with CM or those with EM during two states: during a typical migraine, before rescue therapy, with at least 6/10 level of pain (ictal); and when migraine free for at least 48 h (interictal). The average number of headaches per month over the previous year was estimated by those with EM; this enabled comparison of biomarker changes between controls and three headache frequency groups: <2 per month, 2–14 per month, and CM. Blood and CSF biomarkers were determined using antibody‐based methods. Results: Antimigraine medication was only taken by the EM and CM groups. Compared to controls, the migraine group had significantly higher mean CSF–blood quotients of albumin (Qalb: mean ± standard deviation (SD): 5.6 ± 2.3 vs. 4.1 ± 1.9) and fibrinogen (Qfib mean ± SD: 1615 ± 99.0 vs. 86.1 ± 55.0). Mean CSF but not plasma soluble vascular cell adhesion molecule‐1 (sVCAM‐1) levels were significantly higher in those with more frequent migraine: (4.5 ng/mL ± 1.1 in those with <2 headache days a month; 5.5 ± 1.9 with 2–14 days a month; and 7.1 ± 2.9 in CM), while the Qfib ratio was inversely related to headache frequency. We did not find any difference in individuals with EM or CM from controls for CSF cell count, total protein, matrix metalloproteinase‐9, soluble platelet‐derived growth factor receptor β, tumor necrosis factor‐alpha, interferon‐gamma, interleukin (IL)‐6, IL‐8, IL‐10, or C‐reactive protein. Conclusions: The higher Qalb and Qfib ratios may indicate that the transport of these blood‐derived proteins is disturbed at the BCSFB in persons with migraine. These changes most likely occur at the choroid plexus epithelium, as there are no signs of typical endothelial barrier disruption. The most striking finding in this hypothesis‐generating study of migraine pathophysiology is that sVCAM‐1 levels in CSF may be a biomarker of higher frequency of migraine and CM. An effect from migraine medications cannot be excluded, but there is no known mechanism to suggest they have a role in altering the CSF biomarkers. [ABSTRACT FROM AUTHOR]

Background: Migraine has many presumed comorbidities which have rarely been compared between samples with and without migraine. Examining the association between headache pain intensity and monthly headache day (MHD) frequency with migraine comorbidities is novel and adds to our understanding of migraine comorbidity. Methods: The MAST Study is a prospective, web-based survey that identified US population samples of persons with migraine (using modified International Classification of Headache Disorders-3 beta criteria) and without migraine. Eligible migraine participants averaged ≥1 MHDs over the prior 3 months. Comorbidities "confirmed by a healthcare professional diagnosis" were endorsed by respondents from a list of 21 common cardiovascular, neurologic, psychiatric, sleep, respiratory, dermatologic, pain and medical comorbidities. Multivariable binary logistic regression calculated odds ratios (OR) and 95% confidence intervals for each condition between the two groups adjusting for sociodemographics. Modeling within the migraine cohort assessed rates of conditions as a function of headache pain intensity, MHD frequency, and their combination. Results: Analyses included 15,133 people with migraine (73.0% women, 77.7% White, mean age 43 years) and 77,453 controls (46.4% women, 76.8% White, mean age 52 years). People with migraine were significantly (P < 0.001) more likely to report insomnia (OR 3.79 [3.6, 4.0]), depression (OR 3.18 [3.0, 3.3]), anxiety (OR 3.18 [3.0 3.3]), gastric ulcers/GI bleeding (OR 3.11 [2.8, 3.5]), angina (OR 2.64 [2.4, 3.0]) and epilepsy (OR 2.33 [2.0, 2.8]), among other conditions. Increasing headache pain intensity was associated with comorbidities related to inflammation (psoriasis, allergy), psychiatric disorders (depression, anxiety) and sleep conditions (insomnia). Increasing MHD frequency was associated with increased risk for nearly all conditions and most prominent among those with comorbid gastric ulcers/GI bleeding, diabetes, anxiety, depression, insomnia, asthma and allergies/hay fever. Conclusions: In regression models controlled for sociodemographic variables, all conditions studied were reported more often by those with migraine. Whether entered into the models separately or together, headache pain intensity and MHD frequency were associated with increased risk for many conditions. Future work is required to understand the causal sequence of relationships (direct causality, reverse causality, shared underlying predisposition), the potential confounding role of healthcare professional consultation and treatment, and potential detection bias. [ABSTRACT FROM AUTHOR]

Objectives: The study aims to assess the impact of the second COVID-19 pandemic wave on migraine characteristics. Methods: This is an observational cross-sectional study conducted on migraine patients previously interviewed during the first Italian pandemic outbreak. A second structured telephone interview was conducted between 20 November 2020 and 18 January 2021. We compared migraine characteristics among T0 (before pandemic), T1 (during the first pandemic phase), and T2 (during the second pandemic phase). Results: Among the 433 patients interviewed during the first pandemic phase, 304 cases were finally considered. One hundred forty-eight patients had a control visit between March 2020 and December 2020, 120 had an in-person visit, 14 by phone, the remainder used telemedicine software provided by the hospital. Frequency of headache, number of symptomatic drugs and headache intensity worsened during T2, compared to T0 and T1, especially in episodic migraine. Headache intensity increased relating to the negative emotional impact of the pandemic. Migraine management during the pandemic did not influence the clinical outcome. Conclusion: The prolongation of the pandemic seems to have a negative impact on migraine evolution. The arousal and negative psychological behavior toward the COVID-19 outbreak seem to worsen migraine.

Background: Cutaneous allodynia is a common clinical feature of migraine that has been associated with reduced efficacy of acute migraine treatments and an increased risk of disease progression.Objective: Identify factors associated with allodynia in a sample of adults with migraine.Methods: An online survey panel was used to identify adults with migraine who averaged at least 1 monthly headache day over the previous 3 months. Data on sociodemographics, headache frequency, headache pain intensity, migraine symptom severity, medication use, depression and anxiety, and cutaneous allodynia (via the Allodynia Symptom Checklist) were obtained. Binary logistic modeling predicted the presence of allodynia. Odds ratios and 95% confidence intervals (CI) were calculated.Results: In total, 15,133 individuals with migraine met the eligibility criteria. Mean age was 43.1 years, 73.0% were female, and 81.0% were Caucasian. Allodynia was present in 39.9%. The fully adjusted model, controlling for sociodemographics and headache features, demonstrated that allodynia was significantly associated with a higher migraine symptom severity score (odds ratio 1.17, confidence interval 1.15, 1.19) and more severe pain intensity (odds ratio 1.11, confidence interval 1.08, 1.14); probable depression and/or anxiety (odds ratio 1.83, confidence interval 1.67, 2.00); and overuse of acute medication (odds ratio 1.23, confidence interval 1.09, 1.38). A higher number of monthly headache days increased the likelihood of allodynia, but the effect was attenuated in the fully adjusted model.Conclusion: In a representative sample of US adults with migraine, there were significant associations between allodynia and headache frequency and intensity, anxiety and/or depression, symptom severity, and acute medication overuse. [ABSTRACT FROM AUTHOR]

Background: Chinese herbal medicines (CHMs) are widely used to relieve headache in Asia. However, it is uncertain whether there is robust evidence on the effects of CHMs for headache.Purpose: To assess the effectiveness and safety of CHMs for headache using systematic review of high-quality randomized controlled trials (RCTs).Methods: Electronic search was conducted on six databases from inception to January 2018. We included the RCTs that met the requirement of at least 4 out of the 7 domains according to the Cochrane risk of bias tool.Results: Thirty RCTs with 3447 subjects were ultimately included for analysis and all trials were conducted in Asia. Meta-analysis showed that CHMs monotherapy were superior to placebo in reducing headache frequency [SMD -0.48 (95% CI -0.76, -0.20); p < 0.01], headache days [SMD -0.29 (95% CI -0.45, -0.13); p < 0.01], headache duration[SMD -0.58 (95% CI -0.81, -0.36); p < 0.01], headache intensity [SMD -0.42 (95% CI -0.62, -0.23); p < 0.01] and analgesic consumption [SMD -0.36 (95% CI -0.52, -0.21); p < 0.01] and improving clinical efficacy rate (p < 0.01). Similarly, CHMs monotherapy were superior to western conventional medicines (WCMs) in headache frequency [SMD -0.57 (95% CI -0.84, -0.29); p < 0.01], headache days (p < 0.01), analgesic consumption [SMD -1.63 (95% CI -1.98, -1.28); p < 0.01], headache intensity [SMD -0.81 (95% CI -1.06, -0.57); p < 0.01], and clinical efficacy rate [RR 1.24 (95% CI 1.18, 1.31); p < 0.01], except reducing headache duration (p > 0.05). CHMs adjunct therapy can improve clinical efficacy rate compared with WCMs alone [RR 1.15 (95% CI 1.09, 1.22); p < 0.01]. Meanwhile, CHMs had fewer adverse events than that of controls.Conclusion: The findings supported, at least to an extent, the use of CHM for headache patients; however, we should treat the results cautiously because the clinical heterogeneity. [ABSTRACT FROM AUTHOR]

Objective: To assess migraine epidemiology in men by examining gender differences in disease presentation, comorbidities, and prognosis.Patients and Methods: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study is a longitudinal survey of US adults with migraine identified by web questionnaire. Data were stratified by gender, collected between September 2012-November 2013, and included sociodemographics, headache features, Migraine Disability Assessment, Migraine Symptom Severity Score, Allodynia Symptom Checklist, and comorbidities. Discrete time hazard models addressed 1-year likelihood of transition from episodic to chronic migraine headache frequency.Results: Of the 16,789 migraine respondents, 4294 were men (25.6%). Compared to women, men were slightly older at onset of their headaches (mean 24.1 vs. 22.3 years) and had fewer headache days/month (4.3 vs. 5.3 days), slightly less severe attacks (Migraine Symptom Severity Score, 21.6 vs. 22.6), reduced frequencies of grade IV Migraine Disability Assessment scores (15.7% vs. 24.1%), allodynia (32.6% vs. 49.7%), chronic migraine (6.5% vs. 9.6%, each p < 0.001), and common comorbidities. Men were less likely to report consulting a doctor for their headaches and receiving a migraine diagnosis if they consulted. Men and women with episodic migraine had similar crude 1-year risk of chronic migraine onset. Controlling for known risk factors (i.e. depression, headache frequency, allodynia), men had greater likelihood of chronic migraine onset at 6, 9, and 12 months (each p < 0.05).Conclusions: Findings confirmed gender differences. Men with migraine generally have less severe attacks and disability and are less likely to receive a diagnosis than women with migraine. Prognostic factors may be better understood for women than men. [ABSTRACT FROM AUTHOR]

Objectives To estimate remission rates of chronic headache (CH), focusing on potential predictors of headache remission and medication. Methods We used data from the longitudinal population-based German Headache Consortium (GHC) Study (n = 9,944, 18-65 years). Validated questionnaires were used at baseline (t0, 2003-2007, response rate: 55.2%), first follow-up after 1.87 ± 0.39 years (t1, 37.2%) and second follow-up after 3.26 ± 0.60 years (t2, 38.8%) to assess headache type and frequency, use of analgesics and anti-migraine drugs, medication overuse, education, BMI, smoking and alcohol consumption. CH was defined as ≥ 15 headache days/month at t0 over three months. Outcomes were: CH remission (<15 headache days/month at both follow-ups), CH persistence (≥ 15 headache days/month at both follow-ups); all others were considered as partially remitted. To estimate predictors of remission, univariate and multiple logistic regression were calculated. Results At baseline, 255 (2.6%) participants were identified with CH. Of these, 158 (62.0%) participants responded at both follow-ups. Remission was observed in 58.2% of participants, partial remission in 17.7% and persistence in 24.1%. Remission was associated with female sex (adjusted odds ratio: 3.10, 95% confidence interval: 1.06-9.08) and no medication overuse (4.16, 1.45-11.94) compared to participants with persistent CH; participants with higher headache frequency at t0 were less likely to remit (0.90, 0.84-0.97). Medication, age, education, BMI, smoking and drinking showed no effects on remission. Similar results were observed for partial remission. Conclusion The majority of CH participants remitted from CH. Female sex, no overuse of pain medication and lower headache frequency were associated with remission. [ABSTRACT FROM AUTHOR]

Objectives To investigate the structural changes of hippocampus and amygdala and their relationships with migraine frequency and prognosis. Methods Hippocampus and amygdala volumes were measured by 3-T brain magnetic resonance imaging (MRI) in 31 controls and 122 migraine patients who were categorized into eight groups by headache frequency: group 1 (1-2 headache days/month), 2 (3-4), 3 (5-7), 4 (8-10), 5 (11-14), 6 (15-19), 7 (20-24), and 8 (25-30). Headache frequency was reassessed 2 years later and a frequency reduction ≥50% was regarded a good outcome. Results Hippocampus and amygdala volumes fluctuated in patient groups but did not differ from the controls. In migraine patients, the bilateral hippocampus volumes peaked in group 3. The volumes and headache frequencies correlated positively in groups 2-3 on bilateral sides (L: r = 0.44, p = 0.007; R: r = 0.35, p = 0.037), and negatively in groups 3-7 on the left side (5-24 days/month; L: r = -0.31, p = 0.004) and groups 3-8 on the right side ( r = -0.31, p = 0.002). The left amygdala volume also peaked in group 3, and correlated with headache frequency in groups 1-3 ( r = 0.34, p = 0.020) and groups 3-6 ( r = -0.30, p = 0.012). The volumetric changes of the right amygdala with headache frequency did not reach statistical significance. At 2-year follow-up, the right hippocampus volume was positively associated with a good migraine outcome after adjustment of headache frequency (OR 4.72, p = 0.024). Conclusions Hippocampus and amygdala display a structural plasticity linked to both headache frequency and clinical outcome of migraine. [ABSTRACT FROM AUTHOR]

Objective/Background To investigate the characteristics of vomiting in pediatric migraineurs and the relationship of vomiting with other migraine-related parameters. Methods The cohort included children and adolescents with migraine attending a headache clinic of a tertiary pediatric medical center from 2010 to 2016. Patients were identified by a retrospective database search. Data were collected from medical files. The presence of vomiting was associated with background and headache-related parameters. Results The study group included 453 patients, 210 boys (46.4%) and 243 girls (53.6%), of mean age 11.3 ± 3.7 years. Vomiting was reported by 161 patients (35.5%). On comparison of patients with and without vomiting, vomiting was found to be significantly associated with male gender (54% vs 42.1%, P < .018), younger age at migraine onset (8.0 ± 3. years vs 9.6 ± 3.7 years, P < .001), younger age at clinic admission (10.5 ± 3. years vs 11.6 ± 3.6 years, P = .002), higher rate of awakening headache (64.1% vs 38.7%, P < .001), lower headache frequency (10.5 ± 10.3 headaches/month vs 15.0 ± 11.7 headaches/month, P < .001), higher rate of episodic vs chronic migraine (67% vs 58.7%, P < .001), and higher rates of paternal migraine (24.1% vs 10.1%, P < .001), migraine in both parents (9.3% vs 3.1%, P = .007), and migraine in either parent (57.5% vs 45.5%, P = .02). Conclusions The higher rate of vomiting in the younger patients and the patients with awakening pain may be explained by a common underlying pathogenetic mechanism of vomiting and migraine involving autonomic nerve dysfunction/immaturity. The association of vomiting with parental migraine points to a genetic component of vomiting and migraine. It should be noted that some of the findings may simply reflect referral patterns in the tertiary clinic. [ABSTRACT FROM AUTHOR]

Cervical mobilization and manipulation are frequently used to treat patients diagnosed with cervicogenic headache (CEH), however there is conflicting evidence on the efficacy of these manual therapy techniques. The purpose of this review is to investigate the effects of cervical mobilization and manipulation on pain intensity and headache frequency, compared to traditional physical therapy interventions in patients diagnosed with CEH. A total of 66 relevant studies were originally identified through a review of the literature, and the 25 most suitable articles were fully evaluated via a careful review of the text. Ultimately, ten studies met the inclusion criteria: 1) randomized controlled trial (RCT) or open randomized controlled trial; the study contained at least two separate groups of subjects that were randomly assigned either to a cervical spine mobilization or manipulation or a group that served as a comparison, 2) subjects must have had a diagnosis of CEH; 3) the treatment group received either spinal mobilization or spinal manipulation, while the control group received another physical therapy intervention or placebo control; and 4) the study included headache pain and frequency as outcome measurements. Seven of the ten studies had statistically significant findings that subjects who received mobilization or manipulation interventions experienced improved outcomes or reported fewer symptoms than control subjects. These results suggest that mobilization or manipulation of the cervical spine may be beneficial for individuals who suffer from CEH, although heterogeneity of the studies makes it difficult to generalize the findings.