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Introduction: Headache is the most common neurological complaint at the different levels of the healthcare system, and clinical history and physical examination are essential in the diagnosis and treatment of these patients. With the objective of unifying the care given to patients with headache, the Spanish Society of Neurology’s Headache Study Group (GECSEN) has decided to establish a series of consensus recommendations to improve and guarantee adequate care in primary care, emergency services, and neurology departments. Methods: With the aim of creating a practical document, the recommendations follow the dynamics of a medical consultation: clinical history, physical examination, and scales quantifying headache impact and disability. In addition, we provide recommendations for follow-up and managing patients’ expectations of the treatment. Conclusions: With this tool, we aim to improve the care given to patients with headache in order to guarantee adequate, homogeneous care across Spain. Resumen: Introducción: La cefalea es el motivo de consulta neurológico más prevalente en los distintos niveles asistenciales, donde la anamnesis y exploración son primordiales para realizar un diagnóstico y tratamiento adecuados. Con la intención de unificar la atención de esta patología, el Grupo de Estudio de Cefalea de la Sociedad Española de Neurología (GECSEN) ha decidido elaborar unas recomendaciones consensuadas para mejorar y garantizar una adecuada asistencia en Atención Primaria, Urgencias y Neurología. Metodología: El documento es práctico, sigue el orden de la dinámica de actuación durante una consulta: anamnesis, escalas que cuantifican el impacto y la discapacidad y exploración. Además, finaliza con pautas para realizar un seguimiento adecuado y un manejo de las expectativas del paciente con el tratamiento pautado. Conclusiones: Esperamos ofrecer una herramienta que mejore la atención al paciente con cefalea para garantizar una asistencia adecuada y homogénea a nivel nacional.

Resumen: Introducción: El trastorno por estrés postraumático (TEPT) se ha postulado como un factor de cronificación de la migraña. Nuestro objetivo fue investigar la frecuencia del TEPT y los eventos vitales traumáticos (ET) en pacientes con migraña episódica (ME) y crónica (MC) y su impacto sobre parámetros clínicos, otras comorbilidades y biomarcadores de migraña. Material y métodos: Se reclutó a pacientes con ME y MC según CIC-3β en una Unidad de Cefaleas y un centro de Atención Primaria. Se utilizaron cuestionarios validados para investigar TEPT, ET, síntomas autonómicos craneales, comorbilidades (depresión, ansiedad, fatiga), discapacidad, impacto de la migraña y calidad de vida. Se determinaron los niveles séricos basales de CGRP, VIP y PACAP por ELISA. Resultados: Ciento dieciséis pacientes fueron incluidos: 35 ME y 81 MC; 19 sufrían migraña refractaria (MR). Se detectó TEPT en 23 casos (19,8%): 20 MC y 3 ME (χ2 p = 0,046; T de Fisher p = 0,073). La frecuencia de ningún ET ni el número de ET por paciente fue diferente entre MC y ME; 5/19 MR habían sufrido violación (vs. 2/97 no MR; p = 0,002). El TEPT se asoció con más síntomas autonómicos, mayor puntuación en escalas de ansiedad, depresión y fatiga, y menor calidad de vida, y no modificó los niveles de neuropéptidos. Conclusiones: Este estudio sugiere que el TEPT es frecuente en pacientes con migraña, especialmente MC, también en nuestro medio, y que particularmente el antecedente de violencia sexual es frecuente en MR. El TEPT impacta negativamente sobre la migraña, asociando más comorbilidades y peor calidad de vida, por lo que es preciso investigarlo en estos pacientes. Abstract: Introduction: Post-traumatic stress disorder (PTSD) has been proposed as a risk factor for migraine chronification. The aim of this study was to investigate the frequency of PTSD and traumatic life events (TE) in patients with episodic migraine (EM) and chronic migraine (CM) and their impact on clinical parameters, other comorbidities, and migraine biomarkers. Material and methods: Patients with EM and CM ICHD-3Beta according to the International Classification of Headache Disorders (third edition; beta version) were recruited at a headache unit and a primary care centre. We used validated questionnaires to investigate PTSD, TE, cranial autonomic symptoms, comorbidities (depression, anxiety, and fatigue), disability, migraine impact, and quality of life. Baseline serum levels of CGRP, VIP, and PACAP were determined by ELISA. Results: The study included 116 patients: 35 with EM and 81 with CM. Nineteen presented refractory migraine (RM). PTSD was detected in 23 patients (19.8%): 20 with CM and 3 with EM (chi-square: P=.046; Fisher T: P=.073). Neither the frequency of any TE nor the number of TEs per patient were different between CM and EM. A total of 5/19 patients with RM had experienced sexual violence (vs 2/97 with non-RM; P=.002). PTSD was associated with more autonomic symptoms; higher scores on anxiety, depression, and fatigue scales; and poorer quality of life; and it did not change neuropeptide levels. Conclusions: Our results suggest that PTSD is frequent in patients with migraine, and especially CM, in our setting; history of sexual violence is particularly frequent in patients with RM. PTSD has a negative impact on migraine, with higher numbers of comorbidities and poorer quality of life; therefore, further research is needed in this patient group.

Resumen: Introducción: La cefalea es muy frecuente entre la población general y un motivo habitual de consulta médica. Objetivos: Describir las características clínicas de los pacientes que acuden a urgencias por cefalea. Métodos: Estudio descriptivo con recogida prospectiva de pacientes consecutivos mayores de 15 años que acuden al Servicio de Urgencias del Hospital Universitario Marqués de Valdecilla por cefalea como motivo principal de consulta. Resultados: Se recogieron 100 pacientes. La cefalea como motivo de consulta supuso el 1,4% de las urgencias atendidas. El grupo mayoritario fue el de edades comprendidas entre los 31 y 45 años, con predominio de mujeres (61%). Se diagnosticaron 67 cefaleas primarias y 33 secundarias. El diagnóstico más frecuente fue el de migraña, con un 36% del total de cefaleas. Uno de cada 3 pacientes tenía antecedentes de cefalea y 4 de cada 5 acudieron a urgencias por decisión propia. Solo un pequeño porcentaje de los pacientes atendidos en urgencias llegaron a ingresar (12%), y 3 de cada 5 fueron derivados a atención primaria. Se realizaron pruebas complementarias al 84% de los pacientes atendidos. Se realizó un TAC craneal por cada 3 pacientes. Un 80% de los pacientes fueron correctamente diagnosticados por los médicos de urgencias. Conclusiones: La cefalea es un motivo frecuente de consulta en los servicios de urgencias, siendo más habituales las cefaleas primarias, y dentro de estas, la migraña. En nuestro medio se realiza un buen cribado y diagnóstico de las cefaleas, así como un adecuado uso de los recursos disponibles en urgencias para su diagnóstico y manejo. Abstract: Introduction: Headache is common in the general population and a frequent reason for medical consultation. Objectives: To describe the characteristics of patients attending the Emergency Department (ED) for headache. Methods: A descriptive study with prospective collection of 100 consecutive patients over 15 years old who attended our ED due to headache as the main complaint. Results: Headache accounted for 1,4% of ED visits. The most common age range is between 31 and 45 years and the majority of the patients are females (61%). We diagnosed 67 primary and 33 secondary headaches. The most frequent diagnosis was migraine, with 36% of cases. One out of 3 patients had a history of headache and 4 out of 5 consulted by their own decision. Only a small percentage of patients were admitted as inpatients (12%), and 3 out of 5 were referred to Primary Care. Complementary tests were performed on 84% of the patients. One CT scan was performed for every 3 patients. A total of 80% patients was correctly diagnosed by the ED physicians. Conclusions: Headache is a frequent complaint in the ED, where primary headaches are the most common with migraine being the most frequent reason for consultation. In our setting, there is a good screening and diagnosis of headaches, as well as an adequate use of the available resources in the ED for their diagnosis and management.

Introduction: When secondary headache is suspected and the patient is referred to the emergency department or to the outpatient neurology clinic, it is important to know which are the appropriate complementary examinations to perform and the suitable referral pathway for patients to follow.In order to establish recommendations on this matter, the Spanish Society of Neurology's Headache Study Group (GECSEN) has decided to issue a series of agreed recommendations constituting a referral protocol for patients with headache and/or craniofacial neuralgias. Development: Young neurologists with an interest and experience in headache were invited to draft a series of practical guidelines in collaboration with GECSEN's Executive Committee. For practical reasons, the document was divided into 2 articles: the first focuses on primary headaches and craniofacial neuralgias and this second article on secondary headaches and other craniofacial pain. In order for the recommendations to be helpful for daily practice, they follow a practical approach, with tables summarising referral criteria, examinations to be performed, and referral to other specialists. Conclusions: We hope to offer a guide and tools to improve decision-making regarding patients with headache, identifying complementary tests to prioritise and referral pathways to be followed, in order to avoid duplicated consultations and delayed diagnosis and treatment. Resumen: Introducción: Cuando se sospecha que estamos ante una cefalea secundaria y se deriva un paciente a Urgencias o a la consulta de Neurología es importante sabre qué exploraciones complementarias son oportunas hacer en cada caso, además de saber posteriormente cuál es el circuito adecuado que ha de seguir el paciente.Por este motivo, el Grupo de Estudio de Cefaleas de la Sociedad Española de Neurología (GECSEN) ha decidido crear unas recomendaciones consensuadas que establezcan un protocolo de derivación de pacientes con cefalea y/o neuralgias craneofaciales. Desarrollo: Se ha contactado con neurólogos jóvenes con interés y experiencia en cefalea y con la Junta Directiva del GECSEN han desarrollado este documento que, por razones prácticas, se ha dividido en 2 artículos. El primero centrado en las cefaleas primarias y neuralgias craneofaciales, y este centrado en las cefaleas secundarias y otros dolores craneofaciales. El enfoque es práctico, con tablas que resumen los criterios de derivación con exploraciones complementarias y otros especialistas a los que derivar, para que sea útil y facilite su uso en nuestra práctica asistencial diaria. Conclusiones: Esperamos ofrecer una guía y herramientas para mejorar la toma de decisiones ante un paciente con cefalea valorando exploraciones a priorizar y qué circuitos seguir para así evitar la duplicación de consultas y retrasos en el diagnóstico y en el tratamiento.

Resumen: Introducción: . Cuando se sospecha que estamos ante una cefalea secundaria y se deriva un paciente a Urgencias o a la consulta de Neurología es importante saber qué exploraciones complementarias son oportunas hacer en cada caso, además de saber posteriormente cuál es el circuito adecuado que ha de seguir el paciente.Por este motivo, el Grupo de Estudio de Cefaleas de la Sociedad Española de Neurología (GECSEN) ha decidido crear unas recomendaciones consensuadas que establezcan un protocolo de derivación de pacientes con cefalea y/o neuralgias craneofaciales. Desarrollo: Se ha contactado con neurólogos jóvenes con interés y experiencia en cefalea y con la Junta Directiva del GECSEN han desarrollado este documento que, por razones prácticas, se ha dividido en 2 artículos. El primero centrado en las cefaleas primarias y neuralgias craneofaciales, y este centrado en las cefaleas secundarias y otros dolores craneofaciales. El enfoque es práctico, con tablas que resumen los criterios de derivación con exploraciones complementarias y otros especialistas a los que derivar, para que sea útil y facilite su uso en nuestra práctica asistencial diaria. Conclusiones: Esperamos ofrecer una guía y herramientas para mejorar la toma de decisiones ante un paciente con cefalea valorando exploraciones a priorizar y que circuitos seguir para así evitarla duplicación de consultas y retrasos en el diagnóstico y en el tratamiento. Abstract: Introduction: When secondary headache is suspected and the patient is referred to the emergency department or to the outpatient neurology clinic, it is important to know which are the appropriate complementary examinations to perform and the suitable referral pathway for patients to follow.In order to establish recommendations on this matter, the Spanish Society of Neurology's Headache Study Group (GECSEN) has decided to issue a series of agreed recommendations constituting a referral protocol for patients with headache and/or craniofacial neuralgias. Development: Young neurologists with an interest and experience in headache were invited to draft a series of practical guidelines in collaboration with GECSEN's Executive Committee. For practical reasons, the document was divided into 2 articles: the first focuses on primary headaches and craniofacial neuralgias and this second article on secondary headaches and other craniofacial pain. In order for the recommendations to be helpful for daily practice, they follow a practical approach, with tables summarising referral criteria, examinations to be performed, and referral to other specialists. Conclusions: We hope to offer a guide and tools to improve decision-making regarding patients with headache, identifying complementary tests to prioritise and referral pathways to be followed, in order to avoid duplicated consultations and delayed diagnosis and treatment.

Resumen: Introducción: La migraña es un trastorno común y prevalente que contribuye considerablemente al gasto sanitario e interfiere en la calidad de vida de los pacientes. Nuestro objetivo fue explorar el nivel de estrés en el trabajo en una muestra de migrañosos y su posible asociación con la cronicidad del proceso Material y métodos: Se aplicó el test de Maslach («burnout inventory»: 22 ítems agrupados en bloques que valoran: agotamiento emocional [AE], realización personal [RP], despersonalización en el trabajo [DP]) e influencia positiva (IP) a 94 sujetos consecutivos reclutados en consultas. Las diferencias se compararon entre grupos clínicos (migraña crónica [MC] —más de 15 días/mes de cefalea/3 meses— vs. migraña episódica [ME] —< 15 días/mes—) mediante el modelo lineal general ajustado por edad y MIDAS. Resultados: La edad media fue superior en MC. Las puntuaciones medias en la escala MIDAS fueron 51 ± 4,1 en MC y 17,7 ± 15 en ME (p = 0,001). La media ajustada de AE fue en ME 24,6 ± 2,6, en MC 16,2 ± 2,6 y en controles 13,4 ± 2,3 (p = 0,03). La escala MIDAS se correlacionó inversamente con RP (p < 0,05). Discusión: Nuestros resultados señalan que el nivel de AE es mayor en ME que en MC; mientras la RP es peor cuanto mayor impacto tiene la migraña según escala MIDAS. La escala Maslach es una herramienta potencialmente útil en el estudio de las repercusiones de la migraña. Sorprendentemente, el AE es mayor en pacientes con menos crisis, lo que podría relacionarse con mecanismos de adaptación al estrés presentes en el paciente crónico. Abstract: Introduction: Migraine is a common and prevalent disease that contributes to health expenditure and interferes with quality of life. Our goal was to analyse the level of stress at work in a sample of migraine and its possible association with the chronicity of the process Material and methods: We applied the Maslach Burnout Inventory, consisting of 22 items grouped into blocks that assess emotional exhaustion (EE), personal accomplishment (PA), depersonalisation at work (DP)] and positive influence (PI), to 94 consecutive subjects recruited in the outpatient clinic. Differences were compared between clinical groups (chronic migraine [CM]: > 15 days/month with headache over a 3-month period vs episodic migraine [EM]:

Introduction: Migraine is a common and prevalent disease that contributes to health expenditure and interferes with quality of life. Our goal was to analyse the level of stress at work in a sample of migraine and its possible association with the chronicity of the process. Materials and methods: We applied the Maslach Burnout Inventory (MBI), consisting of 22 items grouped into blocks that assess emotional exhaustion (EE), personal accomplishment (PA), depersonalisation at work (DP) and positive influence (PI), to 94 consecutive subjects recruited in the outpatient clinic. Differences were compared between clinical groups (chronic migraine [CM]: >15 days/month with headache over a 3-month period vs episodic migraine [EM]:

Background: Migraine attacks have a high impact on daily activities. There is limited research on the burden of migraine on sexual functioning. Objective: To determine the prevalence of sexual dysfunction in patients with migraine and its relationship with migraine features and comorbidities. Method: This is a cross-sectional study. We included migraine patients between 18 and 60 years-old from 8 Headache Clinics in Spain. We recorded demographic data and migraine features. Patients fulfilled a survey including comorbidities, Arizona Sexual Experiences Scale, Hospital Anxiety and Depression Scale and a questionnaire about migraine impact on sexual activity. A K-nearest neighbor supervised learning algorithm was used to identify differences between migraine patients with and without sexual dysfunction. Results: We included 306 patients (85.6% women, mean age 42.3 ±11.1 years). A 41.8% of participants had sexual dysfunction. Sexual dysfunction was associated with being female (OR [95% CI]: 2.42 [1.17–5.00]; p

Abstract The aim of this study was to analyse the association between human immunodeficiency virus (HIV) related clinical and analytical parameters and the presence of subclinical atherosclerosis as well as endothelial dysfunction. This was a prospective cohort study of HIV-positive patients who underwent intima media thickness (IMT) determination and coronary artery calcium scoring to determine subclinical atherosclerosis. To detect endothelial dysfunction, the breath holding index, flow-mediated dilation and the concentration of endothelial progenitor cells (EPCs) were measured. Patients with an IMT ≥ 0.9 mm had an average of 559.3 ± 283.34 CD4/μl, and those with an IMT

Background: Current literature and a real-world study suggest that diroximel fumarate (DRF) is safer than dimethyl fumarate (DMF) in the treatment of multiple sclerosis (MS). However, no real-world study to date has significantly addressed the efficacy of this treatment., Objectives: This study aims to elucidate the safety, tolerability, and efficacy of DRF in a real-world setting, utilizing data from a Spanish national registry of patients commencing DRF therapy post-market introduction., Methods: In this multicenter, prospective observational study, data were collected from MS patients who initiated DRF treatment. The study monitored demographic and clinical characteristics, safety outcomes (including adverse events, reasons for discontinuation, and lymphocyte counts), and efficacy outcomes (radiological and clinical activity)., Results: A total of 195 MS patients across 26 neurological departments were included, predominantly female (79.5%), with a mean age of 42.17 years, and a mean duration of treatment with DRF of 6.3 months. Most patients (70.3%) reported no adverse events, while gastrointestinal issues and flushing were the most common adverse events observed. The majority of patients (84.6%) continued with DRF treatment, with tolerability issues being the primary reason for discontinuation. Efficacy analysis showed low relapse rates post-DRF initiation, with most patients exhibiting stable or improved Expanded Disability Status Scale scores and radiological assessments demonstrating minimal activity., Conclusion: This comprehensive analysis provides valuable insights into the real-world application of DRF, confirming its safety and tolerability while offering preliminary evidence of its efficacy in managing MS., Competing Interests: Declarations Funding Writing and editorial assistance was provided by Content Ed Net (Madrid, Spain) with funding from Biogen. Conflict of interest C.A. has received lecture honoraria, consultancy fees, and travel expenses from Biogen, Bristol Mayers Squibb, Merck, Novartis, Sanofi-Genzyme and Roche. A.A.T. has received fees as a speaker, consultant or travel support from Biogen, Almirall, Merck, Roche, Sanofi, Sandoz and Janssen. E.A. has no disclosures for financial affiliation, financial support nor grants moneys and has disclosure for speaker honorarium from Novartis, Merck and Biogen. JM.G.D. has received compensation as a consultant, researcher, or speaker from Biogen, Sanofi, Roche, Zenas Biopharma, Almirall, Novartis, Merck, Bristol-Myers-Squidd, and Johnson & Johnson. PM-E has received speaker and consultation fees from Allergan, Almirall, Biogen Idec, Merck, Merz, Novartis and Sanofi-Genzyme. V.G.Q has no conflict of interest related to this work. L.C.F. has received lecture honoraria, consultancy fees, clinical research funding, and travel expenses from Almirall, Amgen, AstraZeneca, Biogen, Bristol Mayers Squibb, Janssen, Merck, Neuraxpharma, Novartis, Sanofi-Genzyme, Roche. C.O.G. has received speaker and consultation fees from Alexion, Biogen Idec, BMS, Horizon, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. V.R.G. has received fees as a speaker, consultant or travel support from Almirall, Merck, Alexion, Roche and Sanofi. AB.C.R. has received honoraria as speaker/meeting moderator/courses/symposium organized by Almirall Prodesfarma S.A, Biogen Idec Inc, Bristol-Myers-Squibb, Janssen Pharmaceutical; Merck-Serono, Mylan, Novartis Pharmaceutical, Roche, Sanofi-Genzyme, Teva Pharmaceuticals; and for congress assistance from Biogen Idec Inc, Bial, Merck-Serono, Novartis Pharmaceutical, Roche, Sanofi-Genzyme, Teva Pharmaceuticals. J.R. has received speaking/consulting fees and/or travel funding from Merck, Sanofi-Genzyme, Roche, Biogen, Novartis, BMS, Jannsen and Teva. O.S. has received fees from Almirall, Biogen, Novartis, Merck, Sanofi, Alter, Bial, Teva, Neuraxfarma, Esteve, Pfizer, Roche and UCB. L.F. has no conflict of interest related to this work. F.P.P has no conflict of interest related to this work. A.A.R. has received fees as a speaker and advisor, and funding for attendance at congresses and other medical meetings, from Bayer, Biogen, Bristol, Janssen, Merck, Novartis, Roche, Sanofi and Teva. J.A.L. received consultant fees from Merck. F.I. has received speaker honoraria and travel reimbursement from Biogen, Merck, Novartis, Roche Spain, and Genzyme-Sanofi. V.C.R has no conflict of interest related to this work. AJ.C.V. has no conflict of interest related to this work. L.B. has no conflict of interest related to this work. V.G. has received speaker fees from Merck, Roche, Biogen, Novartis and Sanofi. L.A.R.A. declares to have received travel aid and financial compensation for talks from BMS and Novartis. R.G.R received payments from Biogen for participating in training conferences. AT.C.O. has received payments from Biogen for participating in training conferences for other professionals. JL.S.M. accepted travel compensation from Novartis, Merck and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer and Teva and has participated in clinical trials by Biogen, Sanofi, Merck and Roche. D.P.R. has received honoraria as a speaker, funding to attend courses and conferences, and consultancies and research grants from Merck, Biogen, Novartis, Sanofi, Teva, Roche and Almirall. F.G.M has received speaker honoraria and travel reimbursement from Biogen, Merck, Novartis, Roche Spain, and Genzyme-Sanofi. L.H.E. has received speaker and consultation fees from Biogen, Merck, Novartis, Roche and Sanofi. Ethics approval The research protocol received approval from the independent ethics committee at the Hospital Universitario de La Princesa (10 November 2022, acta CEIM 5723). Consent to participate This investigation adhered to the principles of the Helsinki Declaration and complied with the EU General Data Protection Regulation (GDPR). All personal identifiers were excluded from the findings. Consent for publication Not applicable. Data availability statement Data are available from the corresponding author upon reasonable request. Author contributions CAH and VML made substantial contributions to the conception and design of the work, interpretation of data and drafting the manuscript. All authors contributed to the acquisition of data and revised the manuscript and approved the version to be published. Code availability Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population., Methods: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected., Results: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs., Conclusions: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier B.V.)

Background: The role of beta calcitonin gene-related peptide (beta-CGRP) in gastrointestinal tract is obscure, but experimental models suggest an effect on the homeostasis of the intestinal mucosa. We measured beta-CGRP circulating levels in a large series of subjects with a recent diagnosis of inflammatory bowel disease (IBD), in order to assess the potential role of this neuropeptide in IBD pathogenesis., Methods: Morning serum beta-CGRP levels were measured by ELISA (CUSABIO, China) in 96 patients recently diagnosed of IBD and compared with those belonging from 50 matched healthy controls (HC) and 50 chronic migraine (CM) patients., Results: Beta-CGRP levels were lower in patients with IBD (3.1 ± 1.9 pg/mL; 2.9 [2.4-3.4] pg/mL) as compared to HC (4.7 ± 2.6; 4.9 [4.0-5.8] pg/mL; p < 0.001) and to CM patients (4.6 ± 2.6; 4.7 [3.3-6.2] pg/mL; p < 0.001). Beta-CGRP levels in CM were not significantly different to those of HC (p = 0.92). Regarding IBD diagnostic subtypes, beta-CGRP levels for ulcerative colitis (3.0 ± 1.9pg/mL; 2.5 [2.1-3.4] pg/mL) and Crohn's disease (3.3 ± 2.0 pg/mL; 3.2 [2.4-3.9] pg/mL) were significantly lower to those of HC (p < 0.01 and p < 0.05, respectively) and CM (p < 0.01 and p < 0.05, respectively)., Conclusions: We have found a significant reduction in serum beta-CGRP levels in patients with a recent diagnosis of all kinds of IBD as compared to two control groups without active intestinal disease, HC and CM, which may suggest a role for this neuropeptide in the pathophysiology of IBD. Our data indicate a protective role of beta-CGRP in the homeostasis of the alimentary tract., (© 2024. The Author(s).)

Objective: Human immunodeficiency virus (HIV) infected patients are at increased risk of cardiovascular disease (CVD). Multidetector computed tomography (MDCT) stratifies cardiovascular risk in asymptomatic patients with subclinical atherosclerosis. The aim of this study was to determine the ability of MCTD and clinical and laboratory parameters to assess subclinical CVD progression in HIV patients., Methods: Prospective longitudinal cohort study of patients with at least 10 years of HIV infection and 5 years of antiretroviral therapy history, low cardiovascular risk and monitored for 6 years (2015-2021). All patients underwent clinical assessment, blood analysis, carotid ultrasound, and gated MDCT in 2015 and 2021., Results: Sixty-three patients (63.5% male) with a mean age of 49.9 years (standard deviation [SD], 10.5) were included in 2015; 63 of them were followed until 2021. Comparing the results from 2015 with those from 2021, Systematic Coronary Risk Estimation-2 (SCORE2) was 2.9% (SD, 2.1) vs. 4.4% (SD,3.1); Multi-Ethnic Study of Atherosclerosis score (MESA risk) was 3.4 (SD 5.8) vs. 6.0 (SD 8.6); coronary artery calcification CAC) score >100 was 11.1% vs. 25.4% (P < 0.05); and 11% vs. 27% had carotid plaques (P = 0.03)., Conclusions: After six years of follow-up, an increase in SCORE2, carotid plaques, CAC scoring and MESA risk was observed. MDCT findings, along with other clinical and laboratory parameters, could play an important role as a marker of CVD progression in the evaluation of patients with HIV and low cardiovascular risk., (©The Author 2024. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Objective: To analyze the specificity of calcitonin gene-related peptide (CGRP) levels, we measured alpha-CGRP circulating levels in a large series of patients with a recent diagnosis of inflammatory bowel disease (IBD) who were interviewed regarding comorbid headache., Background: Several studies have found an association between migraine and IBD., Methods: In this cross-sectional study performed in an IBD clinic, morning serum alpha-CGRP levels were measured by enzyme-linked immunosorbent assay in 96 patients who were recently diagnosed with IBD and compared to those from 50 similar patients with chronic migraine (CM) and 50 healthy controls (HC)., Results: Alpha-CGRP levels were higher in patients with IBD (median [interquartile range] 56.9 [35.6-73.9] pg/mL) and patients with CM (53.0 [36.7-73.9] pg/mL) compared to HC (37.2 [30.0-51.8] pg/mL; p = 0.003; p = 0.019, respectively). Regarding IBD diagnostic subtypes, alpha-CGRP levels for ulcerative colitis (67.2 ± 49.3 pg/mL; 57.0 [35.6-73.4] pg/mL) and Crohn's disease (54.9 ± 27.5 pg/mL; 57.7 [29.1-76.1] pg/mL) were significantly higher than those of HC (p = 0.013, p = 0.040, respectively). Alpha-CGRP levels were further different in patients with IBD with migraine (70.9 [51.8-88.7] pg/mL) compared to HC (p < 0.001), patients with IBD without headache (57.5 [33.3-73.8] pg/mL; p = 0.049), and patients with IBD with tension-type headache but without migraine (41.7 [28.5-66.9] pg/mL; p = 0.004), though alpha-CGRP levels in patients with IBD without migraine (53.7 [32.9-73.5] pg/mL) remained different over HC (p = 0.028)., Conclusion: Together with CM, circulating alpha-CGRP levels are different in patients with IBD, perhaps reflecting a chronic inflammatory state. IBD is an example of how alpha-CGRP levels are not a totally specific migraine biomarker. However, alpha-CGRP levels were further increased in patients with IBD who have a history of migraine, which reinforces its role as a biomarker in migraine patients, always bearing in mind their comorbidities., (© 2024 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Background: Real-world studies have shown the sustained therapeutic effect and favourable safety profile of OnabotulinumtoxinA (BoNTA) in the long term and up to 4 years of treatment in chronic migraine (CM). This study aims to assess the safety profile and efficacy of BoNTA in CM after 5 years of treatment in a real-life setting., Methods: We performed a retrospective chart review of patients with CM in relation to BoNTA treatment for more than 5 years in 19 Spanish headache clinics. We excluded patients who discontinued treatment due to lack of efficacy or poor tolerability., Results: 489 patients were included [mean age 49, 82.8% women]. The mean age of onset of migraine was 21.8 years; patients had CM with a mean of 6.4 years (20.8% fulfilled the aura criteria). At baseline, patients reported a mean of 24.7 monthly headache days (MHDs) and 15.7 monthly migraine days (MMDs). In relation to effectiveness, the responder rate was 59.1% and the mean reduction in MMDs was 9.4 days (15.7 to 6.3 days; p  < 0.001). The MHDs were also reduced by 14.9 days (24.7 to 9.8 days; p  < 0.001). Regarding the side effects, 17.5% experienced neck pain, 17.3% headache, 8.5% eyelid ptosis, 7.5% temporal muscle atrophy and 3.2% trapezius muscle atrophy. Furthermore, after longer-term exposure exceeding 5 years, there were no serious adverse events (AE) or treatment discontinuation because of safety or tolerability issues., Conclusion: Treatment with BoNTA led to sustained reductions in migraine frequency, even after long-term exposure exceeding 5 years, with no evidence of new safety concerns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Navarro-Pérez, González-Quintanilla, Muñoz-Vendrell, Madrigal, Alpuente, Latorre, Molina, Monzón, Medrano, García-Azorín, González-Oria, Gago-Veiga, Velasco, Beltrán, Morollón, Viguera, Casas-Limón, Rodríguez-Vico, Cuadrado, Irimia, Iglesias, Guerrero-Peral, Belvís, Pozo-Rosich, Pascual and Santos-Lasaosa.)

Background: Calcitonin gene-related peptide (CGRP) is the most promising candidate to become the first migraine biomarker. However, literature shows clashing results and suggests a methodological source for such discrepancies. We aimed to investigate some of these methodological factors to evaluate the actual role of CGRP as biomarker., Methods: Previous to the experimental part, we performed a literature review of articles measuring CGRP in migraine patients. Using our 399 bio-bank sera samples, we performed a series of experiments to test the validity of different ELISA kits employed, time of sample processing, long-term storage, sampling in rest or after moderate exercise. Analysis of in-house data was performed to analyse average levels of the peptide and the effect of sex and age., Results: Literature review shows the high variability in terms of study design, determination methods, results and conclusions obtained by studies including CGRP determinations in migraine patients. CGRP measurements depends on the method and specific kit employed, also on the isoform detected, showing completely different ranges of concentrations. Alpha-CGRP and beta-CGRP had median with IQR levels of 37.5 (28.2-54.4) and 4.6 (2.4-6.4)pg/mL, respectively. CGRP content is preserved in serum within the 24 first hours when samples are stored at 4°C after clotting and immediate centrifugation. Storages at -80°C of more than 6 months result in a decrease in CGRP levels. Moderate exercise prior to blood extraction does not modulate the concentration of the peptide. Age positively correlates with beta-CGRP content and men have higher alpha-CGRP levels than women., Conclusions: We present valuable information for CGRP measurements in serum. ELISA kit suitability should be tested prior to the experiments. Alpha and beta-CGRP levels should be analysed separately as they can show different behaviours even within the same condition. Samples can be processed in a 24-h window if they have been kept in 4°C and should not be stored for more than 6 months at -80°C before assayed. Patients do not need to rest before the blood extraction unless they have performed a high-endurance exercise. For comparative studies, sex and age should be accounted for as these parameters can impact CGRP concentrations., (© 2024. The Author(s).)

Introduction: Effectiveness of candesartan in migraine prevention is supported by two randomized controlled trials. We aimed to assess the effectiveness, tolerability, and response predictors of candesartan in the preventive treatment of migraine., Methods: Observational, multicenter, prospective cohort study. The 50%, 75% and 30% responder rates, between weeks 8-12 and 20-24, were compared with the baseline. Treatment emergent adverse effects were systematically evaluated. Response predictors were estimated by multivariate regression models., Results: Eighty-six patients were included, 79.1% females, aged 39.5 (inter-quartile range [IQR] 26.3-50.3), with chronic migraine (43.0%), medication overuse headache (55.8%) and a median of two (inter-quartile range: 0.75-3) prior preventive treatments. At baseline patients had 14 (10-24) headache and 8 (5-11) migraine days per month. The 30%, 50% and 75% responder rates were 40%, 34.9% and 15.1% between weeks 8-12, and 48.8%, 36%, and 18.6% between weeks 20-24. Adverse effects were reported by 30 (34.9%) and 13 (15.1%) patients between weeks 0-12 and 12-24, leading to discontinuation in 15 (17.4%) patients. Chronic migraine, depression, headache days per month, medication overuse headache, and daily headache at baseline predicted the response between weeks 20-24., Conclusion: Candesartan effectiveness and tolerability in migraine prevention was in line with the clinical trials' efficacy. Trial registration: The study protocol is registered in ClinicalTrials.gov (NCT04138316)., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DGA received honoraria for lectures/presentations from Abbvie/Allergan, Eli Lilly, Teva, Lundbeck, and Novartis. DGA Participated in clinical trials as the principal investigator for Pfizer, BioHaven and Lundbeck. DGA is junior editor of The Journal of Headache and Pain and Neurological Sciences. DGA received honoraria from the World Health Organization as subject matter expert.ABGV received honoraria for lectures/presentations from Novartis, Lilly, Teva, Exeltis, Chiesi, Abbvie, Pfizer and Lundbeck.ÁLGP received honoraria for lectures/presentations from Abbvie/Allergan, Eli Lilly, Teva, Lundbeck, and Novartis. ALGP Participated in clinical trials as the principal investigator for Eli Lilly, Teva, Abbvie, Novartis, Amgen and Lundeck.The rest of the authors report no conflicts of interest.

Background: Some studies have suggested an association between migraine and inflammatory bowel disease. We determined migraine prevalence in a cohort of patients with inflammatory bowel disease., Methods: Patients with inflammatory bowel disease aged 18-65 years were interviewed using an ad hoc headache questionnaire. Those who admitted a history of headache in the last year answered the three questions of the ID-Migraine questionnaire. Those who answered "yes" to the three of them were classified as "definite" and those who answered "yes" to two were classified as "probable" migraine., Results: We interviewed 283 patients with inflammatory bowel disease. Of these, 176 (62.2%) had headache. Fifty-nine (20.8%; 95% CI 16.3-26.0%) met migraine criteria either definite (n = 33; 11.7%; 95% CI 8.2-16.0%) or probable (n = 26; 9.2%; 95% CI 6.1-13.2). When divided by gender, 12 men (9.6%; 95% CI 5.1-16.2%) and 47 women (29.8%; 95% CI 22.8-37.5%) met migraine criteria. The prevalence of migraine was increased in inflammatory bowel disease patients from the current cohort (20.8%) versus that reported for our general population for the same age group (12.6%; p < 0.0001). These differences remained significant in female inflammatory bowel disease patients (29.8% versus 17.2% in our general population; p < 0.0001), but not in males (9.6% in inflammatory bowel disease vs 8.0%; p = 0.30). Seventeen patients with inflammatory bowel disease (6.0%; 95% CI 3.54-9.44%) fulfilled chronic migraine criteria. There were no differences in migraine prevalence by inflammatory bowel disease subtypes., Conclusion: Migraine prevalence, including chronic migraine, seems to be increased in patients with inflammatory bowel disease. The fact that this association was stronger for women suggests an influence of sex-related factors.

OnabotulinumtoxinA is a potent inhibitor of muscle contraction that acts by preventing the release of acetylcholine at the neuromuscular junction. In pain states such as migraine, its mechanism of action is not yet fully elucidated and probably relates to the phenomena of central and peripheral sensitization within the trigeminal system. Migraine is a prevalent and disabling disorder and, especially in its variant of chronic migraine (CM), is associated with relevant symptomatic and socioeconomic burden, the objective of preventive treatment being to reduce the frequency, duration, or severity of migraine attacks. OnabotulinumtoxinA, administered by intramuscular injection, is approved for the prevention of CM and is among the most utilized preventive treatments in CM and fundamental to clinical practice. The efficacy and safety of OnabotulinumtoxinA in the treatment of CM have been verified by the PREEMPT 1 and 2 studies and confirmed by the real-world studies that followed, including the COMPEL, REPOSE, and CM PASS. OnabotulinumtoxinA not only reduces headache days but also leads to improvement in functioning and quality of life, thereby reducing migraine impact. Data about its pathophysiology, efficacy, and its place in CM treatment in the era of CGRP monoclonal antibodies are reviewed and discussed here., (Copyright © 2024 Elsevier B.V. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Breast cancer in males is a very rare entity, and survival is mainly influenced by the stage at diagnosis. The lack of early detection tools in men results in a diagnostic delay of about 5-10 years and a higher percentage of metastatic disease at diagnosis. However, the characteristics of head metastases are not well defined., Case Reports: We present 2 cases of male breast cancer with metastases affecting cranial nervous structures and we provide imaging and histologic data. Both were middle-aged patients with ductal-type, HER-2- negative, and androgen receptor-positive primary tumors., Conclusion: Although central nervous system involvement is uncommon, this entity should be considered in middle-aged males with focal neurologic symptoms. More cases would be necessary to better understand the biology of this condition in order to establish an adequate diagnosis and treatment., (© 2024 S. Karger AG, Basel.)

Objective: The objective of this study was to analyze the evolution of alpha and beta-CGRP circulating levels throughout CGRP monoclonal antibodies (mAbs) treatment in patients with chronic migraine (CM)., Methods: We recruited patients with CM beginning mAbs along with sex and age paired healthy controls (HCs). Blood was extracted before, 2 weeks (M0.5) and 3 months (M3) after the first dose of mAbs, always in free-migraine periods, and once for HCs. Alpha and beta-CGRP serum levels were measured using enzyme-linked immunosorbent assays (ELISAs) specific for each isoform., Results: Baseline alpha-CGRP levels were significantly elevated in 103 patients with CM (median = 50.3, 95% confidence interval [CI] = 40.5-57.0 pg/ml) compared to 78 HCs (median = 37.5, 95% CI = 33.9-45.0 pg/ml; 95% CI of differences = 2.85-17.08 pg/ml) and significantly decreased (n = 96) over the course of mAb treatment (M0.5: median = 40.4, 95% CI = 35.6-48.2 pg/ml; and M3: median = 40.9, 95% CI = 36.3-45.9 pg/ml). Absolute decrease of alpha-CGRP throughout the treatment positively correlated with the decrease in MMDs. Negative modulation of alpha-CGRP significantly associated with positive scores at the Patient Global Impression of Change scale and with analgesic overuse reversal. Beta-CGRP did not differ at baseline between patients with CM (median = 4.2, 95% CI = 3.0-4.8 pg/ml) and HCs (median = 4.4, 95% CI = 3.4-5.6 pg/ml; -1.09 to 0.60) nor was modulated by mAb treatment (n = 96; M0.5: median = 4.5, 95% CI = 3.5-5.2 pg/ml; and M3: median = 4.6, 95% CI = 3.7-5.2 pg/ml)., Interpretation: Treatment with mAbs, regardless of its target, is able to progressively normalize basally increased alpha-CGRP levels in CM and this effect correlates with efficacy measures, which supports a role of this neuropeptide as the first CM biomarker. ANN NEUROL 2023;94:285-294., (© 2023 American Neurological Association.)

Introduction: Headache is common in the general population and a frequent reason for medical consultation., Objectives: To describe the characteristics of patients attending the Emergency Department (ED) for headache., Methods: A descriptive study with prospective collection of 100 consecutive patients over 15 years old who attended our ED due to headache as the main complaint., Results: Headache accounted for 1.4% of ED visits. The most common age range is between 31 and 45 years and the majority of the patients are females (61%). We diagnosed 67 primary and 33 secondary headaches. The most frequent diagnosis was migraine, with 36% of cases. One out of 3 patients had a history of headache and 4 out of 5 consulted by their own decision. Only a small percentage of patients were admitted as inpatients (12%), and 3 out of 5 were referred to Primary Care. Complementary tests were performed on 84% of the patients. One CT scan was performed for every 3 patients. A total of 80% patients was correctly diagnosed by the ED physicians., Conclusions: Headache is a frequent complaint in the ED, where primary headaches are the most common with migraine being the most frequent reason for consultation. In our setting, there is a good screening and diagnosis of headaches, as well as an adequate use of the available resources in the ED for their diagnosis and management., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Post-traumatic stress disorder (PTSD) has been proposed as a risk factor for chronification of migraine. The aim of this study was to investigate the frequency of PTSD and traumatic life events (TE) in patients with episodic (EM) and chronic migraine (CM) and their impact on clinical parameters, other comorbidities, and migraine biomarkers., Material and Methods: Patients with EM and CM according to the International Classification of Headache Disorders (third edition; beta version) were recruited at a headache unit and a primary care centre. We used questionnaires validated for research on PTSD, TEs, cranial autonomic symptoms, comorbidities (depression, anxiety, and fatigue), disability, migraine impact, and quality of life. Baseline serum levels of CGRP, VIP, and PACAP were determined by ELISA., Results: The study included 116 patients: 35 with EM and 81 with CM. Nineteen presented refractory migraine. PTSD was detected in 23 patients (19.8%): 20 with CM and 3 with EM (chi-square: P = .046; Fisher T: P = .073). No significant differences were identified between the EM and CM groups for frequency of any TE nor the number of TEs per patient. A total of 5/19 patients with refractory migraine had experienced sexual violence (vs 2/97 with non-refractory migraine; P = .002). PTSD was associated with more autonomic symptoms; higher scores on anxiety, depression, and fatigue scales; and poorer quality of life; it did not change neuropeptide levels., Conclusions: Our results suggest that PTSD is frequent in patients with migraine, and especially CM, in our setting; history of sexual violence is particularly frequent in patients with refractory migraine. PTSD has a negative impact on migraine, with higher numbers of comorbidities and poorer quality of life; therefore, further research is needed in this patient group., Competing Interests: Declaration of competing interest The authors of this study have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Introduction: The role of the central and peripheral nervous system in the generation of migraine is not well understood. Our aim was to determine whether peripheral trigeminal nerve stimuli, such as nasopharyngeal swabs, could trigger migraine attacks., Subjects and Methods: A survey was sent to 658 doctors, nurses and medical students, asking about the presence of headache suggestive of migraine after carrying out a SARS-CoV-2 swab test, their previous history of migraine, and demographic and headache-related characteristics. Those who tested positive or had associated clinical signs and symptoms of COVID were excluded., Results: A total of 377 people were recruited, 309 of whom were included in the sample. Forty-seven (15.2%) reported headache suggestive of migraine after the swab test and 42 (89.4%) of them had a previous history of migraine. The risk of developing migraine was higher in the subgroup of patients with a history of headache suggestive of migraine - odds ratio: 22.6 (95% confidence interval: 8.597-59.397); p < 0.001. No differences were found between the main characteristics of attacks suggestive of migraine before and after the swab test, except for a lower percentage of associated aura afterwards (42.8% vs. 26.1%; p = 0.016). Individuals with previous attacks suggestive of migraine with a frequency of more than two episodes per month had a higher risk of developing a headache suggestive of migraine after the test - odds ratio = 2.353 (95% confidence interval: 1.077-5.145); p = 0.03., Conclusions: Nasopharyngeal swabbing may trigger migraine attacks, with a greater likelihood in individuals with a higher frequency of previous migraines. This would confirm the idea that peripheral stimuli on the trigeminal nerve can trigger migraine attacks in individuals with migraine, according to their degree of trigeminovascular sensitisation.

Background: Headache is among the most frequent symptoms of acute COVID-19 infection. Its mechanisms remain obscure, but due to its migraine-like characteristics, the activation of the trigeminal system could account for its underlying pathophysiology., Methods: Our aim was to compare the serum levels of CGRP, as a theoretical marker of trigemino-vascular activation, in 25 COVID-19 inpatients with lung involvement experiencing headache, against 15 COVID-19 inpatients without headache and with those of 25 matched healthy controls with no headache history., Results: Morning serum alpha-CGRP levels, as measured by ELISA (Abbexa, UK), were increased in COVID-19 patients with headache (55.2±34.3 pg/mL) vs. controls (33.9±14.0 pg/mL) (p < 0.01). Alpha-CGRP levels in COVID-19 patients without headache were also significantly increased (43.3 ± 12.8 pg/mL; p = 0.05) versus healthy controls, but were numerically lower (-28.2%; p = 0.36) as compared to COVID-19 patients with headache., Conclusion: CGRP levels are increased in COVID-19 patients experiencing headache in the acute phase of this disease, which could explain why headache frequently occurs in COVID-19 and strongly supports a role for trigeminal activation in the pathophysiology of headache in this viral infection., (© 2023. The Author(s).)