Journal of Headache and Pain最新文献

Background: Diagnosing headache disorders poses significant challenges, particularly in primary and secondary levels of care (PSLC), potentially leading to misdiagnosis and underdiagnosis. This study evaluates diagnostic agreement for migraine, tension-type headache (TTH), and cluster headache (CH) between PSLC and tertiary care (TLC) and assesses adherence to the International Classification of Headache Disorders 3rd edition (ICHD-3) guidelines.

Methods: A retrospective, cross-sectional analysis was conducted at Charité - Universitätsmedizin Berlin's tertiary headache center. The patients' self-reported diagnoses from the PSLC were compared with those in TLC and with ICHD-3 criteria. Cohen's kappa (κ) and R² were used to assess diagnostic agreement.

Results: Among 1,468 patients (43.4 ± 14.4 years; 74.5% women), 69.5% reported a diagnosis in PSLC, and 99.5% were diagnosed at their first TLC visit. Overall agreement between PSLC and TLC was 80% (κ = 0.55; R²=30%). Agreement between the PSLC and ICHD-3 was 77% for migraine, 82% for TTH, and 96% for CH (κ = 0.65; R²=41%). TLC diagnoses aligned with ICHD-3 in over 90%.

Conclusion: Our findings indicate a significant degree of diagnostic agreement across different levels of care according to the ICHD-3 guidelines. However, there remains insufficient reliability in clinical diagnostics, highlighting the need for continued efforts to improve the early recognition and diagnostic accuracy and consistency of primary headaches to optimize patient care and treatment outcomes in Germany.

Inter-individual variability in symptoms and the dynamic nature of brain pathophysiology present significant challenges in constructing a robust diagnostic model for migraine. In this study, we aimed to integrate different types of magnetic resonance imaging (MRI), providing structural and functional information, and develop a robust machine learning model that classifies migraine patients from healthy controls by testing multiple combinations of hyperparameters to ensure stability across different migraine phases and longitudinally repeated data. Specifically, we constructed a diagnostic model to classify patients with episodic migraine from healthy controls, and validated its performance across ictal and interictal phases, as well as in a longitudinal setting. We obtained T1-weighted and resting-state functional MRI data from 50 patients with episodic migraine and 50 age- and sex-matched healthy controls, with follow-up data collected after one year. Morphological features, including cortical thickness, curvature, and sulcal depth, and functional connectivity features, such as low-dimensional representation of functional connectivity (gradient), degree centrality, and betweenness centrality, were utilized. We employed a regularization-based feature selection method combined with a random forest classifier to construct a diagnostic model. By testing the models with varying feature combinations, penalty terms, and spatial granularities within a strict cross-validation framework, we found that the combination of curvature, sulcal depth, cortical thickness, and functional gradient achieved a robust classification performance. The model performance was assessed using the test dataset and achieved 87% accuracy and 0.94 area under the curve (AUC) at distinguishing migraine patients from healthy controls, with 85%, 0.97 and 84%, 0.93 during the interictal and ictal/peri-ictal phases, respectively. When validated using follow-up data, which was not included during model training, the model achieved 91%, 94%, 89% accuracies and 0.96, 0.94, 0.98 AUC for the total, interictal, and ictal/peri-ictal phases, respectively, confirming its robustness. Feature importance and clinical association analyses exhibited that the somatomotor, limbic, and default mode regions could be reliable markers of migraine. Our findings, which demonstrate a robust diagnostic performance using multimodal MRI features and a machine-learning framework, may offer a valuable approach for clinical diagnosis across diverse cohorts and help alleviate the decision-making burden for clinicians.

Background: Migraine is a common primary headache disorder, less frequently affecting men than women, and often regarded as predominantly a "women's disease." Despite this, migraine in men presents with unique characteristics in terms of symptoms, treatment responses, comorbidities, and pain perception. Historically, research has focused more on migraine in women, overlooking critical male-specific aspects.

Results: This review delves into the epidemiology, clinical presentation, and particular challenges of diagnosing and managing migraine in men. It addresses sex-specific triggers, hormonal influences, and comorbid conditions affecting migraine prevalence and severity in men. Additionally, the review evaluates current therapeutic strategies, underscoring the necessity for individualized approaches. Men with migraine often exhibit atypical symptoms compared to the ICHD-3 criteria and are less likely to report common associated symptoms. They also tend to have fewer psychological comorbidities, respond more favorably to pharmacological treatments, yet are less likely to seek medical support. The reasons for these sex disparities are complex, involving biological, psychosocial, and cultural factors, such as brain structural differences, differences in functional responses to painful stimuli, hormonal effects, and behavioral influences like adherence to masculine norms and stigma.

Conclusion: Men are underrepresented in clinical migraine research. In contrast, preclinical studies often focus solely in male animals as a result of various misconceptions. This disparity necessitates greater focus on sex-specific aspects of migraine to enhance diagnosis, treatment, and research. Addressing stigma, increasing healthcare access, and ensuring balanced sex and gender representation in future studies is crucial for a comprehensive understanding and effective management of migraine for all patients.

Background: Migraine is a disabling disorder that impacts 40 million people in the US. Zavegepant is the first calcitonin gene-related peptide (CGRP) receptor antagonist nasal-spray approved for the acute treatment of migraine with or without aura in adults. This study aimed to evaluate the proportion of patients in various pain and functional disability states over 48-h, for patients treated with zavegepant 10 mg nasal-spray versus placebo.

Methods: This post-hoc analysis included adult patients with > 1-year history of migraine from BHV3500-301 (NCT04571060): a phase 3 double-blind, randomized, placebo-controlled, single-attack study. Over 48-h, pain severity and functional disability were captured at various timepoints (pre- and post-dosing). The proportion of patients at each pain severity or functional disability state and the time spent in each category was calculated. These were analyzed for patients with complete timepoint data available and using missing not at random (MNAR) imputation for missing timepoints. Predictors of functional disability were assessed using a mixed-effects logistic regression model.

Results: There were 1,269 patients included in the MNAR imputation analysis, and between 630-641 in the complete-case analysis. As early as 15-min post-dose, a larger proportion of zavegepant patients achieved no/mild pain compared to placebo, despite balanced migraine severity pre-dose. Furthermore, zavegepant patients spent significantly more time (over 2.5-h) in pain freedom compared to placebo. Similarly, a higher proportion of patients with normal function was observed with zavegepant vs placebo, as early as 30-min post-dose. Over 48-h, patients treated with zavegepant spent an average of ~ 3-h longer with normal functioning compared to placebo. Results were similar when analyzing both analytic groups. In a regression model, treatment with zavegepant, lower pain severity, fewer baseline monthly migraine days, and absence of photophobia, phonophobia, and nausea were associated with better functioning (p < 0.05) over 48-h.

Conclusion: This post-hoc analysis demonstrates the benefit of zavegepant nasal spray over placebo on two patient-centric endpoints: time spent with pain freedom and normal functioning over 48-h post-dose. These data support the use of zavegepant for providing rapid and sustained freedom from migraine pain and freedom from migraine related disability, particularly for those who would benefit from the nasal CGRP formulation.

Part 2 explores the transformative potential of artificial intelligence (AI) in addressing the complexities of headache disorders through innovative approaches, including digital twin models, wearable healthcare technologies and biosensors, and AI-driven drug discovery. Digital twins, as dynamic digital representations of patients, offer opportunities for personalized headache management by integrating diverse datasets such as neuroimaging, multiomics, and wearable sensor data to advance headache research, optimize treatment, and enable virtual trials. In addition, AI-driven wearable devices equipped with next-generation biosensors combined with multi-agent chatbots could enable real-time physiological and biochemical monitoring, diagnosing, facilitating early headache attack forecasting and prevention, disease tracking, and personalized interventions. Furthermore, AI-driven advances in drug discovery leverage machine learning and generative AI to accelerate the identification of novel therapeutic targets and optimize treatment strategies for migraine and other headache disorders. Despite these advances, challenges such as data standardization, model explainability, and ethical considerations remain pivotal. Collaborative efforts between clinicians, biomedical and biotechnological engineers, AI scientists, legal representatives and bioethics experts are essential to overcoming these barriers and unlocking AI's full potential in transforming headache research and healthcare. This is a call to action in proposing novel frameworks for integrating AI-based technologies into headache care.

Background: We have previously shown headache disorders to be prevalent in in the adult general population of Morocco, especially migraine (30.8%) and headache on ≥ 15 days/month (H15+; 10.5%). This study, collecting data from the same population-based sample, is the first to estimate headache-attributed burden not only in Morocco but, more widely, in the Maghreb countries of North Africa.

Methods: We used the standard methodology and questionnaire developed by the Global Campaign against Headache. Cluster-based random sampling generated a sample (N = 2,575) representative of the general population aged 18-65 years. Interviews conducted face-to-face enquired into symptom burden (headache frequency, usual duration and usual intensity), and impaired participation in paid work, household work and social or leisure activities during the preceding 3 months. Further enquiry was into headache yesterday (HY). We calculated population-level estimates by factoring in prevalence. Needs assessment estimated the population proportion in need of headache-related health care based on likelihood of benefit.

Results: Participants with headache of any type spent, on average, 12.5% of their time with headache of intensity rated 2.3 on a scale of 1-3. According to age- and gender-corrected estimates, 7.2-8.4% of all time in the population (calculated by two methods) was spent with headache, H15 + accounting for well over half of this. Impaired participation measured as lost time due to headache averaged 0.5 days from paid work, 1.6 days from household work and 0.3 days from social or leisure activities during the preceding 3 months. Of those with HY (17.8% of the sample), 24.1% of males and 50.9% of females could do nothing or less than half of their planned activity yesterday. At population level this diluted to 7.0% of all activity lost to headache. At least 30% of the population were estimated to need headache-related health care.

Conclusion: Headache disorders cause much ill health in the adult population of Morocco. While this will be of obvious concern to health policy in Morocco, the call for provision of health care for almost one third of this population is challenging. On the other hand, economic policy should recognise the lost-productivity costs of inadequately treated headache, especially migraine.

Background: To describe the epidemiology and clinical characteristics of migraine and the status of treatment in Colombia. Additionally, the use of health resources by patients was measured.

Methods: This was a non-interventional, retrospective, descriptive study conducted in one Colombian Health Management Organization (HMO) from 2018 to 2022 with a follow-up period of 5 years. Migraine patients were identified using the International Code Disease 10th version G43, and the diagnosis was confirmed by a neurologist. The first recorded migraine diagnosis was defined as the index date. Medical records, claim databases and other electronic databases from the HMO were used to determine the clinical characteristics, treatments, and health care services.

Results: A total of 89,227 patients were included in the study. The mean follow-up period was 3.7 years (standard deviation 1.2). Most of them were women (84.9%). Many patients were first seen by a general practitioner (82.6%), and only 8.9% were first seen by a neurologist. The prevalence of migraine during follow-up was between 1.69 and 2.42 patients in 100 HMO affiliates in 2020, the year with the highest prevalence (2.42 [95% CI 2.41-2.44]), and the incidence ranged from 0.032 to 1.72 per 100 patient-year at risk of developing migraine. Hypertension (21.3%), arrythmia (4.1%) and structural heart disease (3.4%) were the most common cardiovascular diseases. The annual mean number of outpatient consultations in 2018 was 1.43 consultations per patient, which decreased to 0.68 in 2022. The most frequent treatments for acute events were nonsteroidal anti-inflammatory drugs (NSAIDs) (range 37-42%) in monotherapy, combinations of analgesics (range 14-35%), and corticosteroids (range 10-15%). Triptans were used in 4% of patients in the first medication record, reaching a maximum of 16% of patients. Among preventive treatments, beta-blockers (24-49%) and antiepileptics (29-41%) were the most common.

Conclusion: The prevalence of migraine in Colombia according to health electronic databases was lower than that reported in previous studies conducted in the country. The treatment patterns for acute and preventive treatment of migraine follow the recommendations of different guidelines. Cardiovascular disease is relevant for the management of migraine.

Background: People with multiple sclerosis (MS) have an increased risk of migraine. However, little is known about migraine and other headaches during the prodromal phase (before MS symptom onset). Our objective was to study the risk of migraine in women with MS before MS onset.

Methods: A nationwide, prospective cohort study of women participating in the Norwegian Mother, Father, and Child cohort study 1999-2008. The women reported the occurrence of migraine and other headaches prior to or during pregnancy. We identified women who later developed MS through data linkage with national health registries in 2018. We excluded women with an established MS diagnosis (n = 125) and women who had experienced their first clinical symptom of MS, but not yet received an MS diagnosis (n = 91). The reference group comprised all other women in the cohort (n = 85,292). We used logistic regression to estimate adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs).

Results: Two hundred and forty-six women developed MS during follow-up. Of these, 116 women had MS symptom onset after 1-5 years, 92 after 6-10 years, and 38 after 10 years. Migraine was more common among women who developed MS compared to the reference group, 18% vs 11%, aOR 1.6 (1.2-2.3), adjusted for age, smoking, socioeconomic status and overweight. The risk of other headaches was similar for women who developed MS compared to the reference group, 29% vs 27%, aOR 1.1 (0.8-1.4). Migraine was reported by 21 of 116 (18%) women with $\le$ 5 years until MS symptom onset (aOR 1.7 [1.1-2.8]) and 19 of 92 (21%) women with 6-10 years until MS symptom onset (aOR 1.9 [1.1-2.8]. Only three of 38 (8%) women with > 10 years until MS symptom onset reported migraine, aOR 0.7 (0.2-2.2).

Conclusions: Women with MS have increased risk of migraine, but not other headaches, up to a decade before the onset of classical MS symptoms. This supports that migraine can be a symptom of the MS prodrome. Special attention in people with migraine may lead to earlier recognition of MS.

The association between migraine and cognitive function has been studied during the last decade, however, this relationship is not well established. As migraine prevalence is highest between the ages of 30-40, aligning with some of our most productive years, we must understand cognitive changes within this disorder. Cognitive impairment potentially limits social and professional interactions, thus negatively impacting quality of life. Therefore, we will review the relationship between prevalent migraine and cognition. Cognitive dysfunction has been reported to be the second largest cause of disability, after pain, in migraine patients. While subjective patient reports on cognition consistently describe impairment, findings for objective neuropsychological assessments vary. Many studies report worse cognitive performance in the ictal phase compared to controls, which can persist into the postictal period, although whether this continues in the interictal period has been understudied. There is limited consensus as to whether cognition differs in migraine with aura versus migraine without aura, and while many studies do support cognitive impairment in chronic migraine, it remains uncertain as to whether this is more debilitating than the cognitive difficulties experienced by those with episodic migraine. To date, objective assessment of neurological abnormalities that may underlie cognitive impairment through neuroimaging has been underutilized. There is limited consensus as to whether cognitive impairment is a characteristic specific to migraine, whether it is driven by a combination of factors including co-morbidities such as anxiety, depression, or vascular dysfunction, treatment, or whether it is a more general characteristic of pain disorders. Overall, increasing numbers of studies support cognitive impairment in migraine patients. Future studies should consider longitudinal study designs to assess cognition across different migraine phases and subtypes of the disorder, including migraine with aura and chronic migraine, as well as controlling for important confounders such as treatment use.

Objective: The aim of this systematic review is to identify pain profiling parameters that are reliably different between patients with migraine and healthy controls, using Quantitative Sensory Testing (QST) including Temporal Summation (TS), Conditioned Pain Modulation (CPM), and Corneal Confocal Microscopy (CCM).

Methods: A comprehensive literature search was conducted (up to 23 May 2024). The quality of the research was assessed using the Newcastle-Ottawa Scale (NOS) for non-randomized studies.

Results: Twenty-eight studies were included after screening. The QST studies indicate that migraine patients exhibit lower pressure pain thresholds (PPT), particularly in the trigeminal region. A previous meta-analysis reported lower heat pain thresholds (HPT). CPM studies suggest a (mild) inhibitory or absent response in migraine patients, not different from controls. High-frequency and chronic migraine patients may exhibit a facilitatory CPM response. With repeated executions of CPM, migraine patients display a diminishing CPM response, a phenomenon not observed in control subjects. CCM investigations in migraine patients revealed conflicting outcomes, likely as a result of small sample sizes and limited characterization of migraine features.

Conclusion: Pain profiling migraine patients varies due to sensory modality, applied methods, anatomical sites, and migraine features. Understanding pain profiling offers insights into migraine pathophysiology, requiring careful selection of parameters and differentiation among migraine subtypes.