InterMiG: international differences in the therapeutic approach to migraine patients in specialized headache centers.

BACKGROUND: There is currently a wide therapeutic arsenal for migraine patients, without a single first-line preventive drug and we choose the different available alternatives taking into account comorbidities, national guidelines, previous treatments and personal experiences. Our objective was to evaluate the differences in the use of migraine treatments between neurologists from different countries. METHODS: This is a multi-centre observational study carried out by neurologists from specialized headache units in seven countries, retrospective with consecutive inclusion of all patients presenting with a migraine diagnosis, over a period of three months. RESULTS: A total of 734 patients were recruited but only 600 were considered in the analysis in order to homogenize the patient cohorts from countries: 200 Spain (ES), 100 Italy (IT), 85 Russia (RUS), 80 Germany (DE), 60 Portugal (PT), 45 Poland (PL) and 30 Australia (AU). 85.4 % of patients were women with a mean age of 42.6 ± 11.8 years. Considering previous and current preventive treatment, the order of use was: antidepressants (69.3 %), antiepileptic drugs (54.7 %), beta-blockers and antihypertensive drugs (49.7 %), OnabotulinumtoxinA (44.0 %) and others (36.2 %). Statistically significant differences were found between all pharmacological classes: antidepressants were commonly used in all countries, with the exception of Poland (AU: 76.7 %, IT: 71.0 %, DE: 60.0 %, PL: 31.1 %, PT: 71.7 %, RUS: 70.6 %, ES: 78.5 %; p < 0.0001); antiepileptic drugs were more frequently prescribed in Portugal, Australia and Spain (AU: 73.3 %, IT: 40.0 %, DE: 37.5 %, PL: 48.9 %, PT: 85.0 %, RUS: 29.4 % and ES: 69.0 %; p < 0.0001); beta-blockers and antihypertensive drugs were frequently used in all countries except Italy (AU: 60.0 %, IT: 14.0 %, DE: 53.8 %, PL: 48.9 %, PT: 68.3 %, RUS: 49.4 % and ES: 59.0 %; p < 0.0001); BTX-A were predominately used in Spain, Italy and Australia (AU:56.7 %, IT:58.0 %, DE:20.0 %, PL: 42.2 %, PT: 26.7 %, RUS: 24.7 % and ES: 58.5 %; p < 0.0001) and others were most frequently used in Poland (AU: 0.0 %, IT: 19.0 %, DE: 42.5 %, PL: 95.6 %, PT: 31.7 %, RUS: 3.5 % and ES: 49.5 %; p < 0.0001). If only patients without comorbidities are considered (200/600), statistically differences between countries persist in all preventive treatments. CONCLUSIONS: There is heterogeneity in the choice of preventive treatment between different countries. Prospective comparative studies of the different oral and subcutaneous alternatives would help to create a global therapeutic algorithm that would guarantee the best option for our patients.

Evaluation of the concomitant use of oral preventive treatments and onabotulinumtoxinA in chronic migraine: the PREVENBOX study.

BACKGROUND AND PURPOSE: OnabotulinumtoxinA is an effective preventive treatment for chronic migraine (CM). In CM, in addition to a reduction in headache frequency, a decreased reliance on oral prophylactics is also indicative of treatment effectiveness. This study aimed to quantify the change in the use of oral prophylactics after treatment with onabotulinumtoxinA in patients with CM. METHODS: This was a retrospective, multicentric, cross-sectional study. Patients with CM (International Classification of Headache Disorders-3beta) that had been treated with onabotulinumtoxinA were enrolled consecutively. We collected parameters related to each patient's pre-treatment situation, as well as their current situation, focusing on frequency and intensity of migraine, number of oral prophylactics and the respective cycle of onabotulinumtoxinA. Univariate and logistic regression analyses were performed. RESULTS: We included 542 patients, 90.0% of whom were taking oral preventive treatments. During treatment with onabotulinumtoxinA, 47.8% withdrew at least one prophylactic and 41.6% stopped using oral prophylactics altogether. Factors associated with a reduction or cessation of oral prophylactics were >50% improvement in frequency and intensity, remission to episodic migraine, use of topiramate as an initial treatment, increased number of infiltrations and shorter chronification period (P < 0.05). The multivariate analysis showed that a chronification period <20 months, more than five cycles of onabotulinumtoxinA, >50% improvement in pain intensity and topiramate as an initial treatment were predictors of a reduction in oral prophylactics (area under the curve, 70.3%; P < 0.001). CONCLUSIONS: Our study demonstrated the efficacy and safety of onabotulinumtoxinA. This treatment reduced the use of oral prophylactics. Withdrawal of oral prophylactics was most likely to occur after five cycles of treatment.

Psychosocial repercussion of migraine: is it a stigmatized disease?

INTRODUCTION: Stigma manifests both in prejudices and rejection from society towards patients who suffer from a specific pathology, and by patient's internalization of this discrimination, with the consequent repercussions on their state of mind and quality of life. The aim of the study was to quantify the stigma associated with migraine and analyze whether it is related to the clinical-demographic characteristics of the patients, as well as the possible impact on their daily lives. MATERIALS AND METHODS: The stigma scale for chronic illness (SSCI) and other questionnaires were administered to 56 patients with episodic migraine (EM), 18 with chronic migraine (CM), and 21 with epilepsy, as a control group. RESULTS: The mean SSCI score was higher (51.6 ± 15.0) in the CM group than in the EM (45.0 ± 13.5) and epilepsy (47.6 ± 15.5) groups, without reaching statistical significance. In addition, the score was higher in patients who were unemployed, divorced, and in those who had migraine with aura. A statistically significant correlation was found between the SSCI score and the impact of migraine on daily life, the presence of stress, anxiety and depression, and low self-esteem. CONCLUSIONS: There is a stigma around migraine in our society, which seems to be more prevalent in patients with certain socio-demographic characteristics, and that is related to stress, mood alterations, and low self-esteem. Trying to reduce stigma could contribute to improve the control of migraine and reduce the impact of the disease at a socio-economic level.

Real world preventative drug management of migraine among Spanish neurologists.

BACKGROUND: Many different preventatives have showed efficacy in the treatment of migraine. National guidelines differ in their recommendations and patients' characteristics are usually taken into account in their selection. In Spain, real life use of preventive therapies seems to be heterogeneous. We aimed to evaluate differences in clinical practice and adherence to national guidelines among Spanish neurologists. METHODS: Observational descriptive study. A survey was conducted among neurologists ascribed to the Spanish Society of Neurology. Participants were differentiated in accordance with their dedication to headache disorders. We analysed socio-demographic parameters and evaluated 43 questions considering migraine management as well as therapeutic choices regarding migraine sub-types and finally, neurologists' personal perception. RESULTS: One hundred fifty-five neurologists participated from 17 different regions, 43.4% of them female and 53.3% under 40 years of age. 34.9% confirmed headache disorders as their main interest. The first choice for preventive therapy in chronic migraine among participants was topiramate (57%) followed by amytriptiline (17.9%) and beta-blockers (14.6%). However in episodic migraine, the preferred options were beta-blockers (47.7%), topiramate (21.5%) and amytriptiline (13.4%). Regarding perceived efficacy, topiramate was considered the best option in chronic migraine (42.7%) followed by onabotulinumtoxinA (25.5%) and amitryptiline (22.4%). Where episodic migraine was concerned, surveyed neurologists perceived topiramate (43.7%) and beta-blockers (30.3%) as the best options. When we evaluated the duration of treatment use with a view to adequate therapeutic response, 43.5% of neurologists preferred 3 months duration and 39.5% were in favour of 6 months duration in episodic migraine. However, considering the preferred duration of treatment use in chronic migraine, 20.4% recommended 3 months, 42.1% preferred 6 months and 12.5% and 22.4% opted for 9 and 12 months respectively. When considering onabotulinumtoxinA therapy, the number of prior therapeutic failures was zero in 7.2% of neurologists, one in 5.9%, two in 44.1%, three in 30.9% and four or more in 11.9%. Following an initial treatment failure with onabotulinumtoxinA, 49% of subjects decided against a second treatment. The number of OnabotA procedures before considering it as ineffective was two in 18.9% of neurologists, three in 70.8% and four in 10.4%. CONCLUSIONS: The initial management of migraine among Spanish Neurologists is in line with most guidelines, where first choice preventative drugs are concerned. The Management of episodic migraine differed from chronic migraine, both in terms of neurologist preference and in their perceived efficacy.

CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA.

BACKGROUND: Some variables have been proposed as predictors of efficacy of OnabotulinumtoxinA in chronic migraine patients, but data available are inconclusive. We aimed to analyse the influence of single nucleotide polymorphisms in the response to OnabotulinumtoxinA. METHODS: We included 156 female patients treated with OnabotulinumtoxinA accordingly to PREEMPT paradigm in three headache units. OnabotulinumtoxinA was offered to patients that had not responded to topiramate and at least one other preventative. Age at first procedure was 43.7 ± 11.8 years (16-74). Patients with a reduction of at least 50% in the number of migraine days after two OnabotulinumtoxinA procedures were considered as responders. We analysed 25 polymorphisms selected for their relevance regarding migraine pathophysiology and their association with migraine according to previously published genome-wide association studies. Genotyping was performed using KASP probes and a LightCycler-480 (Roche-Diagnostics). Allelic, genotypic frequencies and dominance/recesivity hypothesis of the allelic variants were compared between responders and non-responders by Fisher's exact test. RESULTS: Response to treatment with OnabotulinumtoxinA was achieved in 120 patients (76,9%). Two polymorphisms showed differences: CALCA rs3781719, where allele C represents 26.9% in responders and 40.9% in non-responders (p = 0.007, OR = 3.11 (1.33-7.26)); and TRPV1 rs222749, where allele A represents 4.17% in responders and 12.5% in non-responders (p = 0.013, OR = 3.29 (1.28-8.43)). No significant differences in rest of polymorphisms or clinical or demographic variables were found. CONCLUSIONS: Polymorphic variations of CALCA and TRPV1 genes might play a role as prognostic markers of efficacy of OnabotulinumtoxinA in chronic migraine female patients in our population.

Specificity of electroclinical features in the diagnosis of ring chromosome 20.

BACKGROUND: Ring chromosome 20 (R20) syndrome is a chromosomal disorder characterized mainly by drug-resistant frontal lobe seizures, recurrent nonconvulsive status epilepticus (NCSE), and typical EEG features. The aim of this study was to investigate if this triad is common and specific to all patients with R20. METHODS: In this cross-sectional study (from 2000 to 2011), we selected patients who fulfilled at least two out of three criteria: drug-resistant frontal lobe seizures, recurrent NCSE, and characteristic electroencephalography (EEG) features. In all patients, diagnosis was based on karyotype analysis of at least 100 metaphases. RESULTS: We identified 36 patients who met at least two of the selected criteria: six patients (16.7%) with R20 and 30 (83.3%) without R20 (non-R20). All patients with R20 met all three criteria. Eleven (36.7%) patients without R20, however, also displayed the full triad. In 19 patients without R20 (63.3%), one of the three clinical features was missing: frontal lobe seizures were not resistant to antiepileptic drugs (AED) in four (13.3%), recurrent NCSE was missing in six (20%), and nine (30%) patients did not have typical EEG features. Based on this data, specificity was 63.3%, positive predictive value was 35.3%, and sensitivity and negative predictive values were 100%. Additionally, a review of all publications describing the R20 phenotype revealed that 81.98% of patients with R20 display the full electroclinical triad. CONCLUSIONS: In our study, all patients with R20 displayed the three electroclinical characteristics. This is in line with previous reports (presenting high sensitivity and negative predictive value). However, these features can also be observed in other epilepsies and are not specific to R20. Our findings suggest that in the presence of the full triad of symptoms, karyotype analysis focused on chromosome 20 should be conducted.

Diagnosis and treatment of disorders of intracranial pressure: consensus statement of the Spanish Society of Neurology's Headache Study Group.

Primary intracranial pressure disorders include idiopathic intracranial hypertension and spontaneous intracranial hypotension. Remarkable advances have been made in the diagnosis and treatment of these 2entities in recent years. Therefore, the Spanish Society of Neurology's Headache Study Group (GECSEN) deemed it necessary to prepare this consensus statement, including diagnostic and therapeutic algorithms to facilitate and improve the management of these disorders in clinical practice. This document was created by a committee of experts belonging to GECSEN, and is based on a systematic review of the literature, incorporating the experience of the participants, and establishes practical recommendations with levels of evidence and grades of recommendation.

The MIGREX study: Prevalence and risk factors of sexual dysfunction among migraine patients.

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<0.001), being older than 46.5 years (4.04 [2.48-6.59]; p<0.001), having chronic migraine (2.31 [1.41-3.77]; p=0.001), using preventive medication (2.45 [1.35-4.45]; p=0.004), analgesic overusing (3.51 [2.03-6.07]; p<0.001), menopause (4.18 [2.43-7.17]; p<0.001) and anxiety (2.90 [1.80-4.67]; p<0.001) and depression (6.14 [3.18-11.83]; p<0.001). However, only female gender, age, menopause and depression were the statistically significant variables selected in the model to classify migraine patients with or without sexual dysfunction (Accuracy [95% CI]: 0.75 (0.62-0.85), Kappa: 0.48, p=0.005). CONCLUSIONS: Sexual dysfunction is frequent in migraine patients visited in a headache clinic. However, migraine characteristics or use of preventive medication are not directly associated with sexual dysfunction. Instead, risk factors for sexual dysfunction were female gender, higher age, menopause and depression.

Evaluation of the burden of migraine on the partner's lifestyle.

BACKGROUND: Despite the number of research studies regarding the individual burden of migraine, few studies have examined its impact on the patients' partners. We aim to assess migraine effects on the patients' partners on sentimental relationship, children relationship, friendship, and work, as well as the caregiver burden, anxiety and/or depression. METHODS: A cross-sectional observational study was conducted through an online survey of partners of patients with migraine followed-up in 5 Headache Units. Questions about the 4 areas of interest and 2 scales (Hospital Anxiety and Depression Scale and Zarit scale) were included. Scores were compared against the population prevalence. RESULTS: One hundred and fifty-five answers were analysed. Among the patient's partners 135/155 (87.1%) were men, with a mean age of 45.6 ± 10.1 years. Migraine's main effects on partners were observed in the sentimental relationship and items concerning children and friendships, with a minor impact at work. Partners showed a moderate burden (12/155 = 7.7% [4.1%-13.1%]), and a higher moderate-severe anxiety rate (23/155 = 14.8% [9.6%-21.4%]), and similar depression rate (5/155 = 3.2% [1.1%-7.3%]) compared to the National Health Survey. CONCLUSIONS: The burden of migraine impacts the partners' personal relationship, childcare, friendship and work. Moreover, certain migraine partners showed a moderate burden according to Zarit scale and higher anxiety levels than the Spanish population.

Headache: pregnancy and breastfeeding. Recommendations of the Spanish Society of Neurology's Headache Study Group.

INTRODUCTION: Headache is one of the most common neurological complaints, and is most frequent during reproductive age. As a result, we are routinely faced with pregnant or breastfeeding women with this symptom in clinical practice. It is important to know which pharmacological choices are the safest, which should not be used, and when we should suspect secondary headache. To this end, the Spanish Society of Neurology's Headache Study Group has prepared a series of consensus recommendations on the diagnostic and therapeutic algorithms that should be followed during pregnancy and breastfeeding. DEVELOPMENT: This guide was prepared by a group of young neurologists with special interest and experience in headache, in collaboration with the Group's Executive Committee. Recommendations focus on which drugs should be used for the most frequent primary headaches, both during the acute phase and for prevention. The second part addresses when secondary headache should be suspected and which diagnostic tests should be performed in the event of possible secondary headache during pregnancy and breastfeeding. CONCLUSIONS: We hope this guide will be practical and useful in daily clinical practice and that it will help update and improve understanding of headache management during pregnancy and breastfeeding, enabling physicians to more confidently treat these patients.

Headache: what to ask, how to examine, and what scales to use. Recommendations of the Spanish society of neurology's headache study group.

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.

Calcitonin gene-related peptide in migraine: from pathophysiology to treatment.

INTRODUCTION: It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. DEVELOPMENT: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. CONCLUSIONS: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.

The premonitory phase: A crucial stage in migraine. / Fase premonitoria, una etapa clave en la migraña.

INTRODUCTION: The premonitory phase comprises a wide range of symptoms that precede the onset of pain in a migraine episode by up to 48hours. Premonitory symptoms are often not recognised by patients but do have a significant impact on their quality of life. As these symptoms represent the first stage of a migraine attack, they are crucial in improving our understanding of the key points of the origin of migraine. DEVELOPMENT: This paper uses a question-answer format to review the main clinical studies analysing premonitory symptoms, their predictive capacity, the relationship between these symptoms and the biology of migraine, and the role of neuroimaging in the premonitory phase. Finally, we discuss the relevance of these symptoms as potential therapeutic targets in the future. CONCLUSIONS: This study of the premonitory phase has demonstrated that the hypothalamus plays an essential role in the origin of migraine attacks. We should consider the search for new targets in acute migraine treatment in order to act before the onset of the pain. This would imply a radical change in the lives of patients with migraine.

Persistent headache after COVID-19: Pathophysioloy, clinic and treatment.

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. The acute infection is characterised not only by respiratory symptoms, but also by multiple systemic manifestations, including neurological symptoms. Among these, headache is a frequent complaint. As the pandemic progresses and the population of patients recovering from COVID-19 grows, it is becoming apparent that the headache present in the acute stage of the infection may persist for an indeterminate period, becoming a major problem for the patient and potentially leading to disability. In this review we describe the pathophysiological and clinical aspects of persistent headache after COVID-19 based on the information currently available in the literature and the authors' clinical experience.

El SARS-CoV-2 (Síndrome Respiratorio Agudo Grave ­ Coronavirus 2) es el virus responsable de la pandemia por la Enfermedad por el Coronavirus de 2019 (COVID-19). La fase aguda de la enfermedad se caracteriza no sólo por síntomas respiratorios, sino que el cuadro clínico puede estar acompañado de múltiples síntomas sistémicos, incluyendo los neurológicos. Entre ellos, la cefalea es una queja frecuente. A medida que avanza la pandemia y crece la población de pacientes que se recuperan del COVID-19, se está observando que la cefalea presente en la fase aguda de la infección puede persistir durante un periodo de tiempo indeterminado, convirtiéndose un problema capital para el paciente y llegando a condicionar discapacidad. En esta revisión proporcionamos información acerca de los aspectos fisiopatológicos y clínicos de la cefalea persistente tras el COVID-19 en base a la información disponible en la literatura actual y la experiencia clínica de los autores.

Safety of anti-CGRP monoclonal antibodies in patients with migraine during the COVID-19 pandemic: Present and future implications.

BACKGROUND AND OBJECTIVE: CGRP, a neuropeptide involved in migraine pathophysiology, is also known to play a role in the respiratory system and in immunological conditions such as sepsis. We analyzed the impact of the use of CGRP antagonists in patients with migraine during the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus. METHODS: This is a multicentre cross-sectional study. From May to November 2020, through a national survey distributed by the Spanish Society of Neurology, we collected data about the presence of COVID-19 symptoms including headache and their characteristics and severity in patients with migraine treated with anti-CGRP monoclonal antibodies (mAb), and compared them with patients with migraine not receiving this treatment. We also conducted a subanalysis of patients with COVID-19 symptoms. RESULTS: We recruited 300 patients with migraine: 51.7% (155/300) were taking anti-CGRP mAbs; 87.3% were women (262/300). Mean age (standard deviation) was 47.1 years (11.6). Forty-one patients (13.7%) met diagnostic criteria for COVID-19, with no statistically significant difference between patients with and without anti-CGRP mAb treatment (16.1% vs 11.0%, respectively; P=.320). Of the patients with COVID-19, 48.8% (20/41) visited the emergency department and 12.2% (5/41) were hospitalised. Likewise, no clinical differences were found between the groups of patients with and without anti-CGRP mAb treatment. CONCLUSION: Anti-CGRP mAbs may be safe in clinical practice, presenting no association with increased risk of COVID-19.

The MIGREX study: Prevalence and risk factors of sexual dysfunction among migraine patients.

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<0.001), being older than 46.5 years (4.04 [2.48-6.59]; p<0.001), having chronic migraine (2.31 [1.41-3.77]; p=0.001), using preventive medication (2.45 [1.35-4.45]; p=0.004), analgesic overusing (3.51 [2.03-6.07]; p<0.001), menopause (4.18 [2.43-7.17]; p<0.001) and anxiety (2.90 [1.80-4.67]; p<0.001) and depression (6.14 [3.18-11.83]; p<0.001). However, only female gender, age, menopause and depression were the statistically significant variables selected in the model to classify migraine patients with or without sexual dysfunction (Accuracy [95% CI]: 0.75 (0.62-0.85), Kappa: 0.48, p=0.005). CONCLUSIONS: Sexual dysfunction is frequent in migraine patients visited in a headache clinic. However, migraine characteristics or use of preventive medication are not directly associated with sexual dysfunction. Instead, risk factors for sexual dysfunction were female gender, higher age, menopause and depression.

Safety of anti-CGRP monoclonal antibodies in patients with migraine during the COVID-19 pandemic: Present and future implications.

BACKGROUND AND OBJECTIVE: CGRP, a neuropeptide involved in migraine pathophysiology, is also known to play a role in the respiratory system and in immunological conditions such as sepsis. We analyzed the impact of the use of CGRP antagonists in patients with migraine during the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus. METHODS: This is a multicentre cross-sectional study. From May to November 2020, through a national survey distributed by the Spanish Society of Neurology, we collected data about the presence of COVID-19 symptoms including headache and their characteristics and severity in patients with migraine treated with anti-CGRP monoclonal antibodies (mAb), and compared them with patients with migraine not receiving this treatment. We also conducted a subanalysis of patients with COVID-19 symptoms. RESULTS: We recruited 300 patients with migraine: 51.7% (155/300) were taking anti-CGRP mAbs; 87.3% were women (262/300). Mean age (standard deviation) was 47.1 years (11.6). Forty-one patients (13.7%) met diagnostic criteria for COVID-19, with no statistically significant difference between patients with and without anti-CGRP mAb treatment (16.1% vs 11.0%, respectively; P=.320). Of the patients with COVID-19, 48.8% (20/41) visited the emergency department and 12.2% (5/41) were hospitalised. Likewise, no clinical differences were found between the groups of patients with and without anti-CGRP mAb treatment. CONCLUSION: Anti-CGRP mAbs may be safe in clinical practice, presenting no association with increased risk of COVID-19.

How and when to refer patients diagnosed with secondary headache and other craniofacial pain in the Emergency Department and Primary Care: Recommendations of the Spanish Society of Neurology's Headache Study Group. / Cómo y cuándo derivar un paciente con cefalea secundaria y otros tipos de dolores craneofaciales desde Urgencias y Atención Primaria: recomendaciones del Grupo de Estudio de Cefaleas de la Sociedad Española de Neurología.

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.

How and when to refer patients diagnosed with primary headache and craniofacial neuralgia in the Emergency department or Primary Care: Recommendations of the Spanish Society of Neurology's Headache Study Group. / Cómo y cuándo derivar un paciente con cefalea primaria y neuralgia craneofacial desde Urgencias y Atención Primaria: recomendaciones del Grupo de Estudio de Cefalea de la Sociedad Española de Neurología.

INTRODUCTION: When a patient is diagnosed with primary headache or craniofacial neuralgia in the emergency department or in primary care, and is referred to a neurologist due to the complexity of the case, it is useful to know whether additional examination should be sought and the priority (urgent, preferential or normal) with which the patient should be seen. This will avoid unnecessary delays in patients with disabling headache and where organic causes are suspected. In order to issue recommendations on this matter, the Spanish Society of Neurology's Headache Study Group has decided to create a series of agreed recommendations constituting a referral protocol for patients with headache and/or craniofacial neuralgia. DEVELOPMENT: Young neurologists with an interest and experience in headache were invited to draft a series of practical guidelines in collaboration with Spanish Society of Neurology's Headache Study Group Executive Committee. For practical reasons, the document was divided into 2 articles: this first article focuses on primary headaches and craniofacial neuralgias and the second on secondary headaches. 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.

Evidence of and experience with the use of onabotulinumtoxinA in trigeminal neuralgia and primary headaches other than chronic migraine. / Evidencia y experiencia del uso de onabotulinumtoxinA en neuralgia del trigémino y cefaleas primarias distintas de la migraña crónica.

INTRODUCTION: In the field of headaches, onabotulinumtoxinA (onabotA) is well established as a treatment for chronic migraine (CM). In recent years, it has been used increasingly to treat other primary headaches (high-frequency episodic migraine, trigeminal-autonomic cephalalgias, nummular headache) and trigeminal neuralgia. As this treatment will progressively be incorporated in the management of these patients, we consider it necessary to reflect, with a fundamentally practical approach, on the possible indications of onabotA, beyond CM, as well as its administration protocol, which will differ according to the type of headache and/or neuralgia. DEVELOPMENT: This consensus document was drafted based on a thorough review and analysis of the existing literature and our own clinical experience. The aim of the document is to serve as guidelines for professionals administering onabotA treatment. The first part will address onabotA's mechanism of action, and reasons for its use in other types of headache, from a physiopathological and clinical perspective. In the second part, we will review the available evidence and studies published in recent years. We will add an "expert recommendation" based on our own clinical experience, showing the best patient profile for this treatment and the most adequate dose and administration protocol. CONCLUSION: Treatment with onabotA should always be individualised and considered in selected patients who have not responded to conventional therapy.