Headache disorders are among the most disabling neurological conditions, affecting over 1.5 billion people globally. Despite advances in pharmacological therapies, major inequities persist due to underdiagnosis, undertreatment and limited access to effective care, particularly in low- and middle-income countries. Social determinants of health, including cultural meanings, language and health beliefs, are increasingly recognized as key drivers of disparities in burden, diagnosis and treatment outcomes. Traditional medicine, used by more than 80% of the global population, remains first-line care in many regions and continues to influence therapeutic choices in high-income settings. Major systems such as Ayurveda, Traditional Chinese Medicine, Unani and Tibetan medicine, as well as diverse indigenous traditions, emphasize holistic approaches that integrate mental and physical symptoms into diagnosis and management. Additionally, religious and spiritual practices are commonly used to relieve suffering and pain. These culturally grounded explanatory models not only strongly shape health-seeking behavior, treatment adherence and patient narratives, but also may delay biomedical care when misconceptions or unsafe practices predominate. This paper introduces Transcultural Headache Medicine as an emerging framework that integrates cultural contexts, linguistic diversity and traditional practices into headache research, clinical care and policy. We review global traditions and therapeutic modalities including herbal, physical, mental and spiritual approaches, and propose a research agenda combining ethnography, culturally adapted diagnostic tools, experimental studies and clinical trials to evaluate benefits, risks, and contextual effects. We conclude with a call to action from the International Headache Society, aiming to map and evaluate culturally embedded practices, strengthen rigorous evidence and build a global learning network that supports culturally safe integration of effective, affordable and safe headache care.

This study aimed to identify mesocorticolimbic functional abnormalities in cluster headache (CH) patients, disentangling the roles of chronification and affective symptoms. Using the monetary incentive delay fMRI task to directly engage these pathways, we investigated functional alterations in key regions of this network in chronic (n = 23) and episodic CH patients (n = 49) compared to a control group (n = 32). After processing the fMRI data, we extracted beta values from selected regions and for contrasts of interest and entered them into logistic regression models adjusted for potential confounders (such as depressive and anxiety symptoms and smoking habit) to test their association with the diagnoses (chronic CH and control subjects, episodic CH and control subjects). Results showed that chronic CH patients exhibited reduced ventral tegmental area (VTA) activity and a tendency towards significance (p = 0.056) for an increased medial prefrontal cortex (mPFC) responsiveness during reward anticipation, alongside a significant decrease in mPFC activity during reward outcomes. Episodic patients displayed abnormal mPFC activity across both reward phases, but coupled with intact VTA responses. Importantly, these functional abnormalities were not correlated to depressive and anxiety symptoms and smoking habits. These findings suggest that chronic CH patients experience an imbalance in the VTA-mPFC pathway, while episodic patients may show early signs of this emerging dysfunction. Moreover, the observed reward processing alterations seem distinct from those associated with affective disorders, possibly highlighting unique mechanisms underlying the pathophysiology of CH.

The WHO Intersectoral Global Action Plan (2022–2031) emphasises the importance of scaling up healthcare services to enhance access to care for patients with neurologic diseases. In Sub-Saharan Africa, most patients with neurological conditions, including headache, receive care in primary healthcare services. Here, they are often underdiagnosed and poorly managed, primarily due to the inadequate training of healthcare providers. Through its Regional Outreach Programme (ROPE), the International Headache Society (IHS) partnered with a local primary healthcare programme – the Disease Relief through Excellent and Advanced Means (DREAM) programme – to deliver two structured, in-person training courses to local clinicians in Blantyre, Malawi (in 2022 and 2025). These courses provided primary care providers with practical skills in diagnosing and managing primary and secondary headaches. The programme also included local field-based mentorship periods and a ‘train-the-trainer’ model. The training output indicates that partnerships between international scientific societies, such as the IHS, and established local healthcare programmes, like DREAM, facilitate effective task shifting among primary healthcare providers. This helps to bridge the huge diagnostic and treatment gap for headaches in Sub-Saharan Africa. ROPE represents a successful, replicable model for improving access to care for people with headaches in underserved regions.

INTRODUCTION:Headache disorders are the largest contributor to all years lived with disability attributed to neurological disorders. In sub-Saharan Africa (SSA), with 1.2 billion inhabitants, headache prevalence is similar to that of Western countries but with widely inadequate access to care. Cost of transport to healthcare facilities hampers access to care, leading to abandonment and low retention. The aim of this observational study in Malawi was to investigate cost of transport and its likely impact on implementation of WHO's-Intersectoral Global Action Plan (IGAP) in an HIV+ population also complaining of, and requiring treatment for, an active headache disorder. METHODS:The study was conducted at the Disease Relief through Excellent and Advanced Means (DREAM) centre in Blantyre, Malawi, in collaboration with the Global Campaign against Headache as an extension of a previous study. Enquiries about distance and costs of travel were added to the previously published questionnaire. RESULTS:We included 495 consecutive HIV+ patients aged 6-65 years who had been followed for at least 1 year. One-year prevalence of any headache was 76.6%; 28.7% missed at least one appointment because of transport costs. Higher costs of transport were associated with higher probability of missing visits (p < 0.001), while costs were higher for those living in rural areas than for those in urban (p < 0.001). CONCLUSIONS:Awareness of cost and affordability of transport in SSA may suggest strategies to improve access to headache care. Given the disability attributable to headache, this is necessary if the IGAP strategic objectives and targets are to be achieved.

Background Despite hypothalamus has long being considered to be involved in the pathophysiology of cluster headache, the inconsistencies of previous neuroimaging studies and a limited understanding of the hypothalamic areas involved, impede a comprehensive interpretation of its involvement in this condition. Methods We used an automated algorithm to extract hypothalamic subunit volumes from 105 cluster headache patients (57 chronic and 48 episodic) and 59 healthy individuals; after correcting the measures for the respective intracranial volumes, we performed the relevant comparisons employing logist regression models. Only for subunits that emerged as abnormal, we calculated their correlation with the years of illness and the number of headache attacks per day, and the effects of lithium treatment. As a post-hoc approach, using the 7 T resting-state fMRI dataset from the Human Connectome Project, we investigated whether the observed abnormal subunit, comprising the paraventricular nucleus and preoptic area, shows robust functional connectivity with the mesocorticolimbic system, which is known to be modulated by oxytocin neurons in the paraventricular nucleus and that is is abnormal in chronic cluster headache patients. Results Patients with chronic (but not episodic) cluster headache, compared to control participants, present an increased volume of the anterior–superior hypothalamic subunit ipsilateral to the pain, which, remarkably, also correlates significantly with the number of daily attacks. The post-hoc approach showed that this hypothalamic area presents robust functional connectivity with the mesocorticolimbic system under physiological conditions. No evidence of the effects of lithium treatment on this abnormal subunit was found. Conclusions We identified the ipsilateral-to-the-pain antero-superior subunit, where the paraventricular nucleus and preoptic area are located, as the key hypothalamic region of the pathophysiology of chronic cluster headache. The significant correlation between the volume of this area and the number of daily attacks crucially reinforces this interpretation. The well-known roles of the paraventricular nucleus in coordinating autonomic and neuroendocrine flow in stress adaptation and modulation of trigeminovascular mechanisms offer important insights into the understanding of the pathophysiology of cluster headache.

BACKGROUND AND PURPOSE:Cluster headache is a relatively rare, disabling primary headache disorder with a major impact on patients' quality of life. This work presents evidence-based recommendations for the treatment of cluster headache derived from a systematic review of the literature and consensus among a panel of experts. METHODS:The databases PubMed (Medline), Science Citation Index, and Cochrane Library were screened for studies on the efficacy of interventions (last access July 2022). The findings in these studies were evaluated according to the recommendations of the European Academy of Neurology, and the level of evidence was established using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). RECOMMENDATIONS:For the acute treatment of cluster headache attacks, there is a strong recommendation for oxygen (100%) with a flow of at least 12 L/min over 15 min and 6 mg subcutaneous sumatriptan. Prophylaxis of cluster headache attacks with verapamil at a daily dose of at least 240 mg (maximum dose depends on efficacy and tolerability) is recommended. Corticosteroids are efficacious in cluster headache. To reach an effect, the use of at least 100 mg prednisone (or equivalent corticosteroid) given orally or at up to 500 mg iv per day over 5 days is recommended. Lithium, topiramate, and galcanezumab (only for episodic cluster headache) are recommended as alternative treatments. Noninvasive vagus nerve stimulation is efficacious in episodic but not chronic cluster headache. Greater occipital nerve block is recommended, but electrical stimulation of the greater occipital nerve is not recommended due to the side effect profile.

INTRODUCTION:Cluster headache (CH) is usually comorbid to mood spectrum disorders, but the psychopathological aspects are poorly explored. We aimed at identifying discrete profiles of personality traits and their association with clinical features.METHODS:Based on the personality scales of the Millon Clinical Multiaxial Inventory-III, principal component analysis (PCA) identified psychological patterns of functioning of 56 CH patients. PCA outcomes were used for hierarchical cluster analysis (HCA) for sub-groups classification.RESULTS:Eighty-seven percent of patients had personality dysfunctions. PCA found two bipolar patterns: (i) negativistic, sadic-aggressive, borderline, and compulsive traits were distinctive of the psychological dysregulation (PD) dimension, and (ii) narcissistic, histrionic, avoidant, and schizoid traits loaded under the social engagement (SE) component. PD was associated with disease duration and psychopathology. SE was related to educational level and young age. HCA found three groups of patients, and the one with high PD and low SE had the worst psychological profile.CONCLUSIONS:Personality disorders are common in CH. Our data-driven approach revealed distinct personality patterns which can appear differently among patients. The worst combination arguing against mental health is low SE and high PD. Linking this information with medical history may help clinicians to identify tailored-based therapeutic interventions for CH patients.

Background Converging evidence suggests that anatomical and functional mesocorticolimbic abnormalities support the chronicization of pain disorders. Methods We mapped structural and functional alterations of the mesocorticolimbic system in a sample of chronic cluster headache patients (n = 28) in comparison to age and sex-matched healthy individuals (n = 28) employing structural MRI and resting-state functional MRI. Results Univariate logistic regression models showed that several of the examined structures/areas (i.e., the bilateral nucleus accumbens, ventral diencephalon, hippocampus, and frontal pole, and the right amygdala) differentiated chronic cluster headache patients from healthy individuals (p < 0.05, uncorrected). Specifically, all the significant structures/areas had increased volumes in chronic cluster headache patients compared to healthy individuals. The examination of the groups suffering from left and right-sided cranial attacks showed a lateralization effect: ipsilateral to the pain ventral diencephalic regions and contralateral to the pain nucleus accumbens discriminated chronic cluster headache patients from healthy individuals. The resting-state functional MRI data analyses showed that chronic cluster headache patients compared to CTRL individuals present robust reduced functional connectivity in the right frontal pole-right amygdala pathway (p < 0.05, FDR-corrected) Conclusion Our results showed that chronic cluster headache patients present anatomical and functional maladaptation of the mesocorticolimbic system, with functional data indicating a possible prefrontal areas' failure to modulate the mesolimbic structures. These results were opposite to what we hypothesized based on the previous literature on chronic pain conditions. Future studies should assess whether the observed mesocorticolimbic abnormalities are due to the neuroprotective effects of the assumed medications, or to the frequent comorbidity of CH with neuropsychiatric disorders or if they are a genuine neural signature of CH and/or chronic cluster headache condition.