Pub Date : 2025-09-01Epub Date: 2025-09-02DOI: 10.1177/03331024251368251
Peter J Goadsby, Elena Ruiz de la Torre, Antoinette Maassen van den Brink, Pablo Irimia, Dimos D Mitsikostas, Messoud Ashina, Gisela M Terwindt, David Hurtado, Christian Lampl, Patricia Pozo-Rosich
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.
{"title":"Migraine stigma and general knowledge of migraine: A cross-sectional European survey.","authors":"Peter J Goadsby, Elena Ruiz de la Torre, Antoinette Maassen van den Brink, Pablo Irimia, Dimos D Mitsikostas, Messoud Ashina, Gisela M Terwindt, David Hurtado, Christian Lampl, Patricia Pozo-Rosich","doi":"10.1177/03331024251368251","DOIUrl":"https://doi.org/10.1177/03331024251368251","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251368251"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-09-04DOI: 10.1177/03331024251374686
Aynur Özge, Massimiliano Valeriani, Vincenzo Guidetti, Fumihiko Sakai, Derya Uludüz, Pınar Topaloğlu, Ishaq Abu-Arafeh, Amy A Gelfand, Licia Grazzi, Shuu-Jiun Wang, Kenneth J Mack, Toshiyuki Hikita, Jacques Bruijn, Serena Laura Orr, Andrew D Hershey
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.
{"title":"Transition of headache care from childhood to adulthood: Focusing needs, barriers, and models of care. A position paper of the IHS Child and Adolescent Committee.","authors":"Aynur Özge, Massimiliano Valeriani, Vincenzo Guidetti, Fumihiko Sakai, Derya Uludüz, Pınar Topaloğlu, Ishaq Abu-Arafeh, Amy A Gelfand, Licia Grazzi, Shuu-Jiun Wang, Kenneth J Mack, Toshiyuki Hikita, Jacques Bruijn, Serena Laura Orr, Andrew D Hershey","doi":"10.1177/03331024251374686","DOIUrl":"10.1177/03331024251374686","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251374686"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-09-11DOI: 10.1177/03331024251372117
Marina Romozzi, David García-Azorín, Eloisa Rubio-Beltran, Alejandro Labastida-Ramírez
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.
{"title":"Generative chatbots in headache education and research: A narrative review.","authors":"Marina Romozzi, David García-Azorín, Eloisa Rubio-Beltran, Alejandro Labastida-Ramírez","doi":"10.1177/03331024251372117","DOIUrl":"10.1177/03331024251372117","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251372117"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1177/03331024251370339
Catarina S Fernandes, Usman Ashraf, Peter J Goadsby
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.
{"title":"Neuromodulation in trigeminal autonomic cephalalgias: 11-year experience of non-invasive vagus nerve stimulation.","authors":"Catarina S Fernandes, Usman Ashraf, Peter J Goadsby","doi":"10.1177/03331024251370339","DOIUrl":"https://doi.org/10.1177/03331024251370339","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251370339"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BackgroundMany patients with medically-refractory trigeminal neuralgia (TN) fail to achieve lasting pain relief following surgery targeting the trigeminal nerve (cranial nerve five; CNV). While some studies using MRI diffusion tensor imaging (DTI) suggest that preoperative CNV microstructure may predict surgical response, the findings remain inconsistent. Furthermore, the relationship between post-surgical CNV microstructural changes and long-term pain relief is not well understood. Using a novel CNV-nerve specific DTI protocol, the present study aimed to determine whether: (1) preoperative CNV microstructure differentiates surgical responders from non-responders and (2) sustained pain relief after surgery is associated with distinct postoperative microstructural changes in CNV.MethodsWe conducted a single-centre, prospective, longitudinal study in TN patients undergoing microvascular decompression (MVD) or percutaneous rhizotomy by balloon compression (BC). Patients underwent preoperative and postoperative (one week, one month, six months and one year) high-resolution DTI scanning of CNV using a novel fluid-attenuated inversion recovery DTI protocol. Healthy controls (HC) were scanned at a single timepoint using the same protocol. CNV microstructure was inferred primarily from fractional anisotropy (FA), supplemented with other diffusion metrics. Responders were defined as patients with immediate and complete pain relief (Barrow Neurological Institute facial pain scale I or IIIa) sustained for at least two years.ResultsThirty-five TN patients (22 MVD and 13 BC) and 19 HC were studied. There was no difference in FA between HC CNV and affected ipsilateral or unaffected contralateral CNV in TN patients. However, CNV ipsilateral to the painful side of the face showed microstructural alteration in the form of reduced FA compared to the contralateral, unaffected CNV (0.45 vs. 0.49, p = 0.0017). This was largely driven by eventual surgical responders (n = 18, FA ipsilateral 0.45 vs. contralateral 0.49, p = 0.049), whereas non-responders (n = 17) showed no such difference (p = 0.15). Following surgery, responders showed early reduction in ipsilateral CNV FA by one month (0.45 vs. 0.38, p = 0.013), sustained at six months (0.38, p = 0.021) and one year (0.37, p = 0.006). The same pattern was observed for MVD and BC responders. Conversely, non-responders exhibited no significant postoperative CNV FA change. Postoperative pain-free timepoints were associated with significantly lower ipsilateral CNV FA compared to painful states or HC on average (0.39 vs. 0.45 or 0.47, p < 0.0001) and in individual patients experiencing multiple pain recurrences after repeat operations.ConclusionsLong-term pain relief after TN surgery requires the induction of specific and sustained microstructural changes in the treated CNV, irrespective of surgical modality.
背景:许多医学难治性三叉神经痛(TN)患者在针对三叉神经(颅五神经;CNV)的手术后无法实现持久的疼痛缓解。虽然一些使用MRI弥散张量成像(DTI)的研究表明术前CNV微结构可以预测手术反应,但结果仍然不一致。此外,术后CNV微结构变化与长期疼痛缓解的关系尚不清楚。本研究采用一种新的CNV神经特异性DTI方案,旨在确定:(1)术前CNV微结构是否能区分手术反应者和无反应者;(2)术后持续疼痛缓解是否与CNV术后不同的微结构变化有关。方法:我们对接受微血管减压(MVD)或经皮球囊压迫根治术(BC)的TN患者进行了一项单中心、前瞻性、纵向研究。患者术前和术后(1周、1个月、6个月和1年)采用新型液体衰减反转恢复DTI方案对CNV进行高分辨率DTI扫描。使用相同的协议在单个时间点扫描健康对照(HC)。CNV微观结构主要由分数各向异性(FA)推断,并辅以其他扩散指标。应答者被定义为立即和完全疼痛缓解(巴罗神经研究所面部疼痛量表I或IIIa)持续至少两年的患者。结果本组共35例TN患者(MVD 22例,BC 13例),HC 19例。在TN患者中,HC型CNV与受影响的同侧或未受影响的对侧CNV之间的FA无差异。然而,与对侧未受影响的CNV相比,面部疼痛侧的CNV表现为FA减少的微观结构改变(0.45 vs. 0.49, p = 0.0017)。这主要是由最终手术应答者(n = 18,同侧FA 0.45 vs对侧FA 0.49, p = 0.049)引起的,而无应答者(n = 17)没有这种差异(p = 0.15)。手术后,应答者显示同侧CNV FA早期减少1个月(0.45 vs. 0.38, p = 0.013),持续6个月(0.38,p = 0.021)和1年(0.37,p = 0.006)。在MVD和BC应答者中也观察到相同的模式。相反,无应答者术后CNV FA无明显变化。与疼痛状态或HC相比,术后无痛时间点与同侧CNV FA显著降低相关(0.39比0.45或0.47,p
{"title":"Nerve matters: Longitudinal microstructural change in the trigeminal nerve is associated with durable pain relief after surgery for trigeminal neuralgia.","authors":"Hayden J Danyluk, Abhinav Dhillon, Akshit Ayri, Christian Beaulieu, Tejas Sankar","doi":"10.1177/03331024251369827","DOIUrl":"https://doi.org/10.1177/03331024251369827","url":null,"abstract":"<p><p>BackgroundMany patients with medically-refractory trigeminal neuralgia (TN) fail to achieve lasting pain relief following surgery targeting the trigeminal nerve (cranial nerve five; CNV). While some studies using MRI diffusion tensor imaging (DTI) suggest that preoperative CNV microstructure may predict surgical response, the findings remain inconsistent. Furthermore, the relationship between post-surgical CNV microstructural changes and long-term pain relief is not well understood. Using a novel CNV-nerve specific DTI protocol, the present study aimed to determine whether: (1) preoperative CNV microstructure differentiates surgical responders from non-responders and (2) sustained pain relief after surgery is associated with distinct postoperative microstructural changes in CNV.MethodsWe conducted a single-centre, prospective, longitudinal study in TN patients undergoing microvascular decompression (MVD) or percutaneous rhizotomy by balloon compression (BC). Patients underwent preoperative and postoperative (one week, one month, six months and one year) high-resolution DTI scanning of CNV using a novel fluid-attenuated inversion recovery DTI protocol. Healthy controls (HC) were scanned at a single timepoint using the same protocol. CNV microstructure was inferred primarily from fractional anisotropy (FA), supplemented with other diffusion metrics. Responders were defined as patients with immediate and complete pain relief (Barrow Neurological Institute facial pain scale I or IIIa) sustained for at least two years.ResultsThirty-five TN patients (22 MVD and 13 BC) and 19 HC were studied. There was no difference in FA between HC CNV and affected ipsilateral or unaffected contralateral CNV in TN patients. However, CNV ipsilateral to the painful side of the face showed microstructural alteration in the form of reduced FA compared to the contralateral, unaffected CNV (0.45 vs. 0.49, <i>p</i> = 0.0017). This was largely driven by eventual surgical responders (n = 18, FA ipsilateral 0.45 vs. contralateral 0.49, <i>p</i> = 0.049), whereas non-responders (n = 17) showed no such difference (<i>p</i> = 0.15). Following surgery, responders showed early reduction in ipsilateral CNV FA by one month (0.45 vs. 0.38, <i>p</i> = 0.013), sustained at six months (0.38, <i>p</i> = 0.021) and one year (0.37, <i>p</i> = 0.006). The same pattern was observed for MVD and BC responders. Conversely, non-responders exhibited no significant postoperative CNV FA change. Postoperative pain-free timepoints were associated with significantly lower ipsilateral CNV FA compared to painful states or HC on average (0.39 vs. 0.45 or 0.47, <i>p</i> < 0.0001) and in individual patients experiencing multiple pain recurrences after repeat operations.ConclusionsLong-term pain relief after TN surgery requires the induction of specific and sustained microstructural changes in the treated CNV, irrespective of surgical modality.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251369827"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-09-13DOI: 10.1177/03331024251365908
Simone Braca, Viviana Santoro, Gabriele Sebastianelli, Christoph J Schankin, Peter J Goadsby, Francesca Puledda
Visual snow syndrome (VSS) manifests as continuous, fine-grained visual static that is often accompanied by other visual symptoms. Its frequent association with migraine, particularly migraine with aura (MwA), has prompted debate regarding a shared pathogenic substrate. To interrogate this relationship, we performed a narrative review of clinical, neuroimaging and electrophysiological studies on VSS and MwA. The clinical picture of VSS is a persistent phenomenon that does not fluctuate with the migraine cycle and shows no response to therapeutics established to be useful in migraine. Moreover, structural and functional neuroimaging in VSS consistently demonstrates selective abnormalities within primary visual, salience and attentional networks, paralleled by distinctive evidence of glutamatergic dysregulation and impaired top-down suppression in electrophysiological recordings. Collectively, the available evidence supports VSS as a discrete disorder marked by aberrant salience assignment and impaired sensory gating, with clinical features and pathophysiology that are separate from those of MwA. While features such as shared serotonergic dysregulation, involvement of comparable cortical territories and high comorbidity suggest overlap between MwA and VSS, these similarities are likely better attributed to a shared predisposition for increased cortical excitability than to a single nosological entity. Future research aiming to characterize further network abnormalities in VSS will be pivotal for guiding the development of targeted therapies.
{"title":"Visual snow vs. migraine aura: Debate summary and novel insights into the syndrome.","authors":"Simone Braca, Viviana Santoro, Gabriele Sebastianelli, Christoph J Schankin, Peter J Goadsby, Francesca Puledda","doi":"10.1177/03331024251365908","DOIUrl":"10.1177/03331024251365908","url":null,"abstract":"<p><p>Visual snow syndrome (VSS) manifests as continuous, fine-grained visual static that is often accompanied by other visual symptoms. Its frequent association with migraine, particularly migraine with aura (MwA), has prompted debate regarding a shared pathogenic substrate. To interrogate this relationship, we performed a narrative review of clinical, neuroimaging and electrophysiological studies on VSS and MwA. The clinical picture of VSS is a persistent phenomenon that does not fluctuate with the migraine cycle and shows no response to therapeutics established to be useful in migraine. Moreover, structural and functional neuroimaging in VSS consistently demonstrates selective abnormalities within primary visual, salience and attentional networks, paralleled by distinctive evidence of glutamatergic dysregulation and impaired top-down suppression in electrophysiological recordings. Collectively, the available evidence supports VSS as a discrete disorder marked by aberrant salience assignment and impaired sensory gating, with clinical features and pathophysiology that are separate from those of MwA. While features such as shared serotonergic dysregulation, involvement of comparable cortical territories and high comorbidity suggest overlap between MwA and VSS, these similarities are likely better attributed to a shared predisposition for increased cortical excitability than to a single nosological entity. Future research aiming to characterize further network abnormalities in VSS will be pivotal for guiding the development of targeted therapies.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251365908"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-09-11DOI: 10.1177/03331024251364242
Adriana Della Pietra, Adisa Kuburas, Andrew F Russo
Migraine is a complex neurological disorder involving multiple neuropeptides that modulate nociceptive and sensory pathways. The most studied peptide is calcitonin gene-related peptide (CGRP), which is a well-established migraine trigger and therapeutic target. Recently, another peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), has emerged as an alternative target for migraine therapeutics. This review compares the roles of PACAP and CGRP in preclinical mouse models of migraine. PACAP shares similarities with CGRP, and both are expressed in peripheral and central migraine-relevant regions. However, CGRP is more abundant in the trigeminal pain system, whereas PACAP is more prominent in parasympathetic ganglia that may contribute to autonomic aspects of migraine. PACAP and CGRP act on receptors that can activate overlapping but distinct intracellular signaling pathways. While both peptides elevate cAMP levels to activate protein kinase A, PACAP is more effective than CGRP at engaging an alternative cAMP pathway involving small G proteins, as well as Gq-mediated calcium pathways. Moreover, PACAP and CGRP induce similar migraine-like behaviors in mice, including cephalic and plantar mechanical allodynia, photophobia and non-evoked pain, but they do so by largely independent pathways. Notably, PACAP-mediated photophobia and mechanical allodynia symptoms are not blocked by CGRP-targeted therapies in mice. Finally, we discuss how preclinical PACAP and CGRP studies have translated to the clinic, with the exception of a PACAP type I receptor monoclonal antibody. Overall, CGRP and PACAP are likely to act by parallel and non-redundant roles in migraine pathophysiology, which suggests that a combined targeting of CGRP and PACAP may offer a more effective strategy for treating migraine.
{"title":"PACAP versus CGRP in migraine: From mouse models to clinical translation.","authors":"Adriana Della Pietra, Adisa Kuburas, Andrew F Russo","doi":"10.1177/03331024251364242","DOIUrl":"10.1177/03331024251364242","url":null,"abstract":"<p><p>Migraine is a complex neurological disorder involving multiple neuropeptides that modulate nociceptive and sensory pathways. The most studied peptide is calcitonin gene-related peptide (CGRP), which is a well-established migraine trigger and therapeutic target. Recently, another peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), has emerged as an alternative target for migraine therapeutics. This review compares the roles of PACAP and CGRP in preclinical mouse models of migraine. PACAP shares similarities with CGRP, and both are expressed in peripheral and central migraine-relevant regions. However, CGRP is more abundant in the trigeminal pain system, whereas PACAP is more prominent in parasympathetic ganglia that may contribute to autonomic aspects of migraine. PACAP and CGRP act on receptors that can activate overlapping but distinct intracellular signaling pathways. While both peptides elevate cAMP levels to activate protein kinase A, PACAP is more effective than CGRP at engaging an alternative cAMP pathway involving small G proteins, as well as Gq-mediated calcium pathways. Moreover, PACAP and CGRP induce similar migraine-like behaviors in mice, including cephalic and plantar mechanical allodynia, photophobia and non-evoked pain, but they do so by largely independent pathways. Notably, PACAP-mediated photophobia and mechanical allodynia symptoms are not blocked by CGRP-targeted therapies in mice. Finally, we discuss how preclinical PACAP and CGRP studies have translated to the clinic, with the exception of a PACAP type I receptor monoclonal antibody. Overall, CGRP and PACAP are likely to act by parallel and non-redundant roles in migraine pathophysiology, which suggests that a combined targeting of CGRP and PACAP may offer a more effective strategy for treating migraine.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251364242"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12778990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-09-18DOI: 10.1177/03331024251374310
Carl H Göbel, Ursula Müller, Hanno Witte, Katja Heinze-Kuhn, Axel Heinze, Anna Cirkel, Hartmut Göbel
AimPrimary headache disorders such as migraine and tension-type headache are highly prevalent in military populations and may severely impact operational performance and readiness. Despite this, data from many European armed forces are lacking. This study investigates headache phenotypes, diagnosis, treatment and functional impairment in active-duty personnel of a major European military organization.MethodsThis cross-sectional cohort study utilized an anonymous 33-item online questionnaire distributed across military medical centers in Germany between May and July 2023. The survey assessed demographics, headache types according to the International Classification of Headache Disorders, 3rd edition (ICHD-3), diagnostic awareness, treatment history and headache-related disability using the Migraine Disability Assessment Score (MIDAS).ResultsOf the 1189 participants, 914 (77%) completed the survey. Among them, 839 (94.9%) reported experiencing headaches in the past 12 months. Based on ICHD-3 criteria, 227 individuals (27.1%) met the complete set of criteria for migraine, while 246 (29.2%) were classified as probable migraine. Tension-type headache was reported by 222 respondents (26.5%), and cluster headache was resported by 34 (4.1%). Notably, 61.4% of participants had never received a formal diagnosis and only 38.6% had ever sought medical care for their headaches. Functional impairment was substantial: 63.8% reported losing at least one workday in the past three months due to headache. Among those with migraine, an average of 3.9 workdays per month were lost. Despite this burden, only 27.3% of individuals with migraine had ever used preventive medication.ConclusionsPrimary headache disorders are common, underdiagnosed and inadequately treated in this military population, leading to significant functional and operational impairment. Our findings underscore the urgent need for improved screening, diagnosis and evidence-based treatment strategies in uniformed health systems. The results may inform similar efforts in other military and high-demand occupational settings.
{"title":"Impact and care gaps of headache disorders in active-duty military personnel: A cross-sectional study from a European armed forces population.","authors":"Carl H Göbel, Ursula Müller, Hanno Witte, Katja Heinze-Kuhn, Axel Heinze, Anna Cirkel, Hartmut Göbel","doi":"10.1177/03331024251374310","DOIUrl":"10.1177/03331024251374310","url":null,"abstract":"<p><p>AimPrimary headache disorders such as migraine and tension-type headache are highly prevalent in military populations and may severely impact operational performance and readiness. Despite this, data from many European armed forces are lacking. This study investigates headache phenotypes, diagnosis, treatment and functional impairment in active-duty personnel of a major European military organization.MethodsThis cross-sectional cohort study utilized an anonymous 33-item online questionnaire distributed across military medical centers in Germany between May and July 2023. The survey assessed demographics, headache types according to the International Classification of Headache Disorders, 3rd edition (ICHD-3), diagnostic awareness, treatment history and headache-related disability using the Migraine Disability Assessment Score (MIDAS).ResultsOf the 1189 participants, 914 (77%) completed the survey. Among them, 839 (94.9%) reported experiencing headaches in the past 12 months. Based on ICHD-3 criteria, 227 individuals (27.1%) met the complete set of criteria for migraine, while 246 (29.2%) were classified as probable migraine. Tension-type headache was reported by 222 respondents (26.5%), and cluster headache was resported by 34 (4.1%). Notably, 61.4% of participants had never received a formal diagnosis and only 38.6% had ever sought medical care for their headaches. Functional impairment was substantial: 63.8% reported losing at least one workday in the past three months due to headache. Among those with migraine, an average of 3.9 workdays per month were lost. Despite this burden, only 27.3% of individuals with migraine had ever used preventive medication.ConclusionsPrimary headache disorders are common, underdiagnosed and inadequately treated in this military population, leading to significant functional and operational impairment. Our findings underscore the urgent need for improved screening, diagnosis and evidence-based treatment strategies in uniformed health systems. The results may inform similar efforts in other military and high-demand occupational settings.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251374310"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-09-02DOI: 10.1177/03331024251370629
Michael A Moskowitz
Cortical spreading depolarization (depression) underlies migrainous aura and is posited to cause its headache. At times, aura may start before headache, auras may start at the same time as, or shortly after headache onset, or sometimes without any headache at all. We suggest that the extent of spread and not the spread limited to eloquent cortex, is the key variable in the genesis of headache. Consistent with this notion, a first human case studied electrophysiologically showed that cortical spreading depolarization spreads extensively and silentlyWe propose a Buildup Hypothesis to explain headache generation in migraine with aura. Buildup occurs because cortical spreading depression releases noxious chemicals from cortical cells that accumulate in tissues and cerebrospinal fluid to reach levels sufficient to trigger pial afferents and cause pain. The extent of silent (or relatively silent) spread determines significant buildup. This Buildup Hypothesis helps to explain (1) typical and shorter latencies between end of aura and headache onset (approximately 0-20 minutes) and (2) why headache may not develop after aura (insufficient buildup), and also addresses temporal discrepancies such as headaches starting before an aura (i.e. subclinical spread with buildup in advance of aura). Hence, aura and headache are distinct consequences of cortical spreading depolarization.
{"title":"Rethinking migraine with aura: Why cortical spreading depolarization (depression), not aura, causes headaches.","authors":"Michael A Moskowitz","doi":"10.1177/03331024251370629","DOIUrl":"10.1177/03331024251370629","url":null,"abstract":"<p><p>Cortical spreading depolarization (depression) underlies migrainous aura and is posited to cause its headache. At times, aura may start before headache, auras may start at the same time as, or shortly after headache onset, or sometimes without any headache at all. We suggest that the extent of spread and not the spread limited to eloquent cortex, is the key variable in the genesis of headache. Consistent with this notion, a first human case studied electrophysiologically showed that cortical spreading depolarization spreads extensively and silentlyWe propose a Buildup Hypothesis to explain headache generation in migraine with aura. Buildup occurs because cortical spreading depression releases noxious chemicals from cortical cells that accumulate in tissues and cerebrospinal fluid to reach levels sufficient to trigger pial afferents and cause pain. The extent of silent (or relatively silent) spread determines significant buildup. This Buildup Hypothesis helps to explain (1) typical and shorter latencies between end of aura and headache onset (approximately 0-20 minutes) and (2) why headache may not develop after aura (insufficient buildup), and also addresses temporal discrepancies such as headaches starting before an aura (i.e. subclinical spread with buildup in advance of aura). Hence, aura and headache are distinct consequences of cortical spreading depolarization.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251370629"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-09-15DOI: 10.1177/03331024251367767
Jennifer Robblee, Fawad A Khan, Michael J Marmura, Hope L O'Brien, Lawrence D Robbins, Marielle Kabbouche Samaha, Morris Levin, Simona Sacco, Raffaele Ornello, Stephanie J Nahas, Heike Hesse, Annika Ehrlich, Adam S Sprouse-Blum, Christina Sun-Edelstein, Bronwyn Jenkins, Elizabeth K Seng, Shivang Joshi, Meredith J Barad, Mi Ji Lee, Sheena K Aurora, Mario Fernando Prieto Peres
AimDespite its frequency in tertiary headache centers, the International Classification of Headache Disorders, 3rd edition (ICHD-3) does not include refractory migraine. Multiple definitions have been proposed with a recent 2020 proposal for both refractory migraine and resistant migraine by the European Headache Federation (EHF). The aim is to reach an international consensus on the definition of refractory migraine.MethodsThis study is a Delphi consensus carried out by a group of international experts in headache medicine. Following a focus group, a panel of 20 experts and one facilitator reviewed the EHF proposed criteria to build upon their definitions. The Delphi consensus was conducted across five rounds. Questions with >70% consensus were deemed to have strong agreement, 60-70% consensus was deemed minor agreement, and <60% deemed no agreement. A final meeting was held to discuss any concerns and specific wording.ResultsThe Delphi consensus led to the development of four key categories: refractory migraine, probable refractory migraine, resistant migraine, and treatment-responsive migraine. Similar to the EHF 2020 definitions, refractory migraine requires treatment failure of all evidence-based classes, and resistant migraine requires failure of at least three classes. Probable refractory migraine criteria were designed to account for situations where treatment access barriers may prevent trials of certain medication classes (e.g. pediatrics, low to middle-income countries, lack of insurance coverage). Finally, treatment-responsive migraine criteria were developed to allow for standardization in research studies comparing refractory or resistant migraine to migraine that is treatment-responsive.ConclusionsThese four categories may aid in enrollment for studies on pathophysiology, biomarkers, and new treatment targets. Clinically, the criteria for refractory and resistant migraine will help with clinical decision-making by reinforcing the need to try evidence-based treatments and by providing guidance regarding when to try more aggressive treatment approaches. These criteria may also increase attention to this population's disease burden to help advocate for them as a specific migraine subgroup. Field testing in diverse clinical settings will be needed, but it is recommended that ICHD-3 considers inclusion of these four categories in their appendix.
{"title":"Reaching international consensus on the definition of refractory migraine using the Delphi method.","authors":"Jennifer Robblee, Fawad A Khan, Michael J Marmura, Hope L O'Brien, Lawrence D Robbins, Marielle Kabbouche Samaha, Morris Levin, Simona Sacco, Raffaele Ornello, Stephanie J Nahas, Heike Hesse, Annika Ehrlich, Adam S Sprouse-Blum, Christina Sun-Edelstein, Bronwyn Jenkins, Elizabeth K Seng, Shivang Joshi, Meredith J Barad, Mi Ji Lee, Sheena K Aurora, Mario Fernando Prieto Peres","doi":"10.1177/03331024251367767","DOIUrl":"https://doi.org/10.1177/03331024251367767","url":null,"abstract":"<p><p>AimDespite its frequency in tertiary headache centers, the International Classification of Headache Disorders, 3rd edition (ICHD-3) does not include refractory migraine. Multiple definitions have been proposed with a recent 2020 proposal for both refractory migraine and resistant migraine by the European Headache Federation (EHF). The aim is to reach an international consensus on the definition of refractory migraine.MethodsThis study is a Delphi consensus carried out by a group of international experts in headache medicine. Following a focus group, a panel of 20 experts and one facilitator reviewed the EHF proposed criteria to build upon their definitions. The Delphi consensus was conducted across five rounds. Questions with >70% consensus were deemed to have strong agreement, 60-70% consensus was deemed minor agreement, and <60% deemed no agreement. A final meeting was held to discuss any concerns and specific wording.ResultsThe Delphi consensus led to the development of four key categories: refractory migraine, probable refractory migraine, resistant migraine, and treatment-responsive migraine. Similar to the EHF 2020 definitions, refractory migraine requires treatment failure of all evidence-based classes, and resistant migraine requires failure of at least three classes. Probable refractory migraine criteria were designed to account for situations where treatment access barriers may prevent trials of certain medication classes (e.g. pediatrics, low to middle-income countries, lack of insurance coverage). Finally, treatment-responsive migraine criteria were developed to allow for standardization in research studies comparing refractory or resistant migraine to migraine that is treatment-responsive.ConclusionsThese four categories may aid in enrollment for studies on pathophysiology, biomarkers, and new treatment targets. Clinically, the criteria for refractory and resistant migraine will help with clinical decision-making by reinforcing the need to try evidence-based treatments and by providing guidance regarding when to try more aggressive treatment approaches. These criteria may also increase attention to this population's disease burden to help advocate for them as a specific migraine subgroup. Field testing in diverse clinical settings will be needed, but it is recommended that ICHD-3 considers inclusion of these four categories in their appendix.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251367767"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}