Cephalalgia最新文献

Migraine is increasingly understood as a disorder of brain network dysfunction, where attack-related cognitive symptoms (attention deficits, slowed processing speed and executive dysfunction) can be as disabling as pain and may persist into the interictal period. Such symptoms are associated with functional and structural changes across the migraine cycle, involving the prefrontal cortex, thalamus, hypothalamus, hippocampus and cerebellum. Interictal deficits in working memory, visuospatial processing, verbal fluency and executive function are also documented. Rodent models show impairments in learning and memory, while humans studies suggest that cortical hyperresponsiveness and deficient sensory habituation contribute to altered attentional processing, reflecting thalamocortical dysfunction and abnormal synaptic plasticity as underlying mechanisms. Cognitive performance is modulated by disease severity, chronification, hormonal fluctuations, psychiatric comorbidities, sleep disturbances and medication use. Anxiety, depression and sleep disorders negatively affect working memory, executive function and attention, while medication overuse further impairs visuospatial skills and orientation. Dementia risk appears heightened in migraine patients with frequent and severe attacks, as clinic-based studies consistently report cognitive deficits in this cohorts, unlike population-based studies. While longitudinal cohorts find no increased dementia risk, meta-analyses suggest a modest risk elevation. Differences are likely due to methodological differences in cognitive testing and diagnostic approaches. Cognitive dysfunction in migraine is multidimensional, involving intrinsic neuronal mechanism and external modulators, supporting the need for rational management strategies and treatment interventions.

BackgroundThe impact of psychiatric comorbidities in children and adolescents with headache disorders can be more comprehensively understood through a biopsychosocial perspective, which examines the dynamic interplay of factors beyond headache attacks. Resilience and executive function emerge within this framework, playing a central role in development psychopathology and other critical domains.MethodsThis narrative review aimed to examine the impact of psychiatric comorbidity on migraine and/or high-frequency headaches (HFH) in children and adolescents through a biopsychosocial perspective centered on the role of resilience and executive function (EF), exploring their potential clinical implications. PubMed was searched for English language articles of human participants, from birth to 18 years, published up to 10 April 2025.ResultsClinical and population-based studies suggest that children and adolescents with migraine and/or HFH are at an increased risk of low resilience and EF impairments. Preliminary interaction and multivariate analyses suggest that high vulnerability (the counterpart to resilience) exerts a moderating role in the psychiatric comorbidity of migraine, as well as a mediating effect in the association of HFH with psychiatric symptoms and disorders. Candidate predictors of psychiatric comorbidity in youths with migraine and/or HFH include EF impairment, high vulnerability, female sex, low socioeconomic status, prenatal exposure to tobacco, poor academic performance and headache attacks accompanied by nausea and vomiting.ConclusionsThe multidimensional impact of psychiatric comorbidities on children and adolescents with headache disorders is clearly demonstrated by consistent evidence of their adverse effects on headache severity and chronification, as well as negative outcomes in quality of life, cognitive performance, academic achievement and overall patient well-being, leading to long-term continuity across childhood, adolescence and adulthood. Most of this impact is probably due to the interactions between reduced resilience, increased vulnerability and EF impairment. This narrative review underscore the relevance of routinely assessing psychiatric symptoms, resilience, executive function skills and school functioning in children and adolescents with headache disorders. Future studies should examine whether early interventions focused on resilience, vulnerability and EF can prevent psychiatric comorbidities and improve headache outcomes in children and adolescents with migraine and/or HFH.

AimTo prospectively determine subtype shift, relapse rate and risk factors of frequent relapse in cluster headache (CH).MethodsThis multicenter cohort study recruited patients with CH at baseline visits between September 2016 and January 2019 and planned to prospectively follow them up for up to five years. The subtype (episodic vs. chronic) was reassessed at baseline visit 2 (2-4 weeks) and serial follow-up visits if unremitted. We assessed the subtype shift of the index bout (i.e. the bout at the baseline visit) in all patients and relapse rates in those with episodic CH who were in an active bout at the time of recruitment. Relapse (i.e. bout recurrence) was prospectively collected via clinic visit or telephone interview at 3 ± 1 months, 1, 2, 3, 4 and 5 years (each ±6 months) after the baseline visit. Risk factors of frequent relapse were analyzed by comparing the incidence rate ratio (IRR) of relapse using Poisson regression analysis (model 1, static variables in all patients; model 2, time-related variables in patients with two or more lifetime bouts) accounted for different follow-up periods using an offset term.ResultsIn 295 patients (58 with first-ever bouts) enrolled, CH subtypes were episodic, chronic and unclassified in 252, 11 and 32 at baseline. At baseline V2, CH subtype was re-determined to be chronic in seven (12.1%) of 58 patients with first-onset CH ("primary chronic CH") and nine (3.8%) of 237 with a history of episodic CH ("secondary chronic CH"). When excluding known chronic CHs at baseline, the incidence of chronic CH newly found during a prospective observation was 3.8% in patients with first-onset CH and 1.4% in those with a history of episodic CH. In 244 patients with episodic CH in an active bout at the time of recruitment, the relapse rate was 0.29 (95% confidence interval (CI) = 0.27-0.32; p < 0.001) per person-year after 5.9 ± 1.37 follow-up visits over a mean duration of 4.2 ± 1.32 years. Models 1 and 2 indicated that age (adjusted IRR = 0.97; 95% CI = 0.95-0.98), longer disease duration (adjusted IRR = 0.97; 95% CI = 0.95-1.00), first-ever bout (adjusted IRR = 0.35; 95% CI = 0.20-0.57), regular (one or more per week) alcohol consumption (adjusted IRR = 0.60; 95% CI = 0.45-0.81), and longer between-bout interval of previous bouts (adjusted IRR = 0.72; 95% CI = 0.60-0.87) were associated with less relapse. Seasonal rhythmicity (adjusted IRR = 1.66; 95% CI = 1.20-2.33) and increasing attack intensity across bouts (adjusted IRR = 1.66; 95% CI = 1.06-2.59) were associated with frequent relapse.ConclusionsThe present study provides data on the subtype shift and relapse rate of CH based on the prospective observation. Although our observation is only limited to a five-year time frame, our findings may suggest that disease activity increases after onset and then regress with age and time, and that seasonal rhythmicity and increasing attack intensity across bouts indicate higher propensity to relapse.

AimCortical spreading depression (CSD), the neural correlate of migraine aura, has been shown to cause activation of dural nociceptive neurons as well as immune cells, among which macrophages (MPs) are the most abundant and reactive. OnabotulinumtoxinA (onbotA) is used to treat chronic migraine but the mechanism of action is not fully understood. Here we investigate the role of meningeal MPs in a model of migraine activation and evaluate whether onabotA has an effect on their response.MethodsWe use our previously developed method to determine meningeal MP activation based on shape changes using time-lapse in vivo multiphoton microscopy.ResultsWe found that a small subset (∼10%) of MPs contracted their processes in response to CSD induction, but only in female mice. A similar subset of MPs contracted with lipopolysaccharide injection, suggesting that this is an M1-like response. Together this may provide insight into the phenotypic differences of migraine across males and females. We also found a small subset of MPs (∼10%) that expanded their processes in response to IL-10 (presumably an M2-like response), but were not affected by CSD. In female mice, pre-treatment with onabotA (i) reduces overall MP number in the dura, (ii) reduces pro-inflammatory M1 MP response and (iii) increases anti-inflammatory M2 response post-CSD compared to pretreatment with saline.ConclusionThis suggests that the mechanism of action of onabotA may not be simply due to its effects on nociceptors, but also due to an additional anti-inflammatory effect on the environment of the dura.

BackgroundThe stigma associated with migraine impacts patients' quality of life, mental health and their willingness to seek treatment. The present study aimed to gain insights into the stigma from the patient's perspective and to assess migraine knowledge among people without the condition.MethodsThis cross-sectional descriptive, quantitative study used two surveys (survey 1, open April 2023 to July 2023; survey 2, September 2023 to November 2023). The surveys were distributed to local patient organisations across 26 European countries and nine countries in South and North America, Asia and Oceania.ResultsSurvey 1 received 3712 answers. Most respondents were women (3444; 92.8%), 45-54 years (1090; 29.4%) and experienced severe migraine (2047; 55.1%). Most participants viewed their migraine as disabling (2655; 71.5%) and felt that medical professionals only partially understood (2135; 57.5%). Survey 2 gathered 774 responses, with most of the participants being partners (202; 26.1%), friends (196; 25.3%) or other relatives (110; 14.2%) of individuals with migraine. The significant majority of respondents demonstrated a high understanding of migraine (573; 74.0%) and predominantly recognised migraine as disabling and impacting personal and professional life. Responders felt a high degree of stigma, more from work colleagues and medical professionals than from their social network.ConclusionsThe disabling nature of migraine, combined with the associated stigma, aggravates the challenges faced by patients. There is an urgent need for improved medical education, public awareness campaigns and possible revisions in medical terminology to better support people with migraine and mitigate the stigma they encounter. Importantly, medical professionals need to re-double efforts to check their behaviour to avoid adding to the burden of our patients.

Headache disorders are among the most common neurological conditions in children and adolescents, often continuing into adulthood and causing substantial personal and societal burdens. Yet, the transition from childhood to adult headache care remains under-addressed, with critical clinical practice, policy, and research gaps. This narrative review synthesizes existing evidence and expert perspectives to highlight the urgent need for structured, developmentally appropriate transition models in headache care. It explores the evolving clinical features of headache in adolescence, increased vulnerability to different comorbidities, and changing health system expectations. We present a needs assessment reflecting the educational, emotional, and practical demands of patients and families. We identify provider- and system-level barriers, such as insufficient training, limited structured protocols, and inequitable access to specialized care, as significant obstacles to effective continuity. Drawing from established transition of care frameworks in other neurological conditions (e.g., epilepsy), we propose a dual-pathway model for headache care. We suggest key recommendations for clinicians and policymakers to promote anticipatory, patient-centered, and equitable developmental care strategies. International collaboration is essential to establish standardized guidelines and research priorities supporting optimal long-term outcomes and sustained quality of life for young people with headache disorders.

Generative artificial intelligence (AI) chatbots, powered by large language models, are emerging as transformative tools with diverse applications in healthcare. This narrative review aims to explore their unique potential for addressing significant gaps in headache education and research, with a main focus on primary headache disorders, a substantial global health burden. In headache education, chatbots can provide tailored, individual information to patients. This improved accessibility could increase the adherence to treatment, reducing the risk of chronification, resulting in a better quality of life. Similarly, clinicians, particularly non-headache specialists, can access a wealth of up-to-date information on headache disorders, including clinical training simulations, which would facilitate reaching a correct diagnosis and optimize treatment. In headache research, generative chatbots can assist by streamlining data collection and analysis, aiding complex experimental setups, and supporting clinical trials, thus accelerating the discovery pipeline. While generative chatbots have demonstrated significant promise for revolutionizing the headache field, challenges persist, with the most important being ensuring data accuracy and privacy. Future developments should focus on pre-training with headache-specific curated databases, multimodal integration, and establishing robust regulatory and ethical frameworks among users (patients, researchers, clinicians), and AI developers to address its limitations. With responsible development, generative chatbots hold the potential to bridge current gaps in headache education and meaningfully advance medical research from bench to bedside, and beyond.

AimTo evaluate the effectiveness and tolerability of non-invasive vagus nerve stimulation (nVNS) as acute or preventive treatment, or both, in a cohort of trigeminal autonomic cephalalgia (TAC) patients.MethodsA service evaluation retrospectively included patients with TACs between January 2014 and February 2025 who had used, or currently use, nVNS. Data were collected from clinical letters. Data are presented as descriptive statistics analysis and non-parametric tests were performed.ResultsIn total, 108 patients were included, 74 patients with cluster headache (CH), 10 with paroxysmal hemicrania, 15 with hemicrania continua, four with short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), three with short-lasting unilateral neuralgiform with cranial autonomic symptoms (SUNA) and two with an undifferentiated TAC. Overall, 70 patients considered nVNS useful over a median time using nVNS of 47 (interquartile range = 18-66) months. The median time of use in patients who did not find nVNS useful was 7 (interquartile range = 4-12) months. Twenty-three patients reported an adverse event (AE), while no serious treatment-related AEs occurred. Fifty-nine patients withdrew from using the device, including 11 patients that initially reported nVNS as useful. All groups considered nVNS more useful as preventive, while cluster headache and SUNCT/SUNA patients also considered it useful as acute treatment.ConclusionsOur findings complement previous evidence of the effectiveness and tolerability of nVNS in CH in addition to other forms of TACs. Interestingly, nVNS seems to be more effective as preventive rather than as acute treatment in our cohort.