Eptinezumab for the preventive treatment of episodic and chronic migraine: a narrative review.

Eptinezumab, a monoclonal antibody that targets calcitonin gene-related peptide (CGRP), was recently approved in Europe for the prophylactic treatment of migraine in adults who have at least four migraine days a month. Eptinezumab is administered by intravenous infusion every 12 weeks. During recent months, a considerable amount of evidence from eptinezumab trials has been published. The aim of this review is to describe the existing evidence on the tolerability, safety and efficacy of eptinezumab in patients with migraine. Data from randomized (PROMISE-1, PROMISE-2, RELIEF and DELIVER) and open-label (PREVAIL) phase 3 clinical trials have demonstrated the favorable effect of eptinezumab in migraine symptoms from first day of treatment. These studies showed that eptinezumab results in an overall reduction in mean monthly migraine days (MMDs), increases in the ≥50% and ≥ 75% migraine responder rates (MRRs) and improvements in patient-reported outcome measures in both patients with episodic migraine (EM) and with chronic migraine (CM), including patients who failed previous preventive treatments. The RELIEF trial also showed that eptinezumab, within 2 h of administration, reduced headache pain, migraine-associated symptoms and acute medication use when administered during a migraine attack. Eptinezumab benefits manifested as early as day 1 after dosing and with the subsequent doses lasted up to at least 2 years. Treatment-emergent adverse events reported by ≥2% of patients included upper respiratory tract infection and fatigue. Current evidence demonstrates that eptinezumab has a potent, fast-acting, sustained migraine preventive effect in patients with EM and CM. Eptinezumab has also shown to be well tolerated, supporting its use in the treatment of patients with migraine and inclusion in the current migraine therapeutic options.

RE-START: Exploring the effectiveness of anti-calcitonin gene-related peptide resumption after discontinuation in migraine.

BACKGROUND AND PURPOSE: According to the latest European guidelines, discontinuation of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP MAb) may be considered after 12-18 months of treatment. However, some patients may worsen after discontinuation. In this study, we assessed the response following treatment resumption. METHODS: This was a prospective study conducted in 14 Headache Units in Spain. We included patients with response to anti-CGRP MAb with clinical worsening after withdrawal and resumption of treatment. Numbers of monthly migraine days (MMD) and monthly headache days (MHD) were obtained at four time points: before starting anti-CGRP MAb (T-baseline); last month of first treatment period (T-suspension); month of restart due to worsening (T-worsening); and 3 months after resumption (T-reintroduction). The response rate to resumption was calculated. Possible differences among periods were analysed according to MMD and MHD. RESULTS: A total of 360 patients, 82% women, with a median (interquartile range [IQR]) age at migraine onset of 18 (12) years. The median (IQR) MHD at T-baseline was 20 (13) and MMD was 5 (6); at T-suspension, the median (IQR) MHD was 5 (6) and MMD was 4 (5); at T-worsening, the median (IQR) MHD was 16 (13) and MMD was 12 (6); and at T-reintroduction, the median (IQR) MHD was 8 (8) and MHD was 5 (5). In the second period of treatment, a 50% response rate was achieved by 57.4% of patients in MHD and 65.8% in MMD. Multivariate models showed significant differences in MHD between the third month after reintroduction and last month before suspension of first treatment period (p < 0.001). CONCLUSION: The results suggest that anti-CGRP MAb therapy is effective after reintroduction. However, 3 months after resumption, one third of the sample reached the same improvement as after the first treatment period.

Recomendaciones de consenso para el tratamiento de la prevención de la migraña / Consensus recommendations for the treatment of migraine prevention

Objetivo los objetivos son conocer la opinión de neurólogos y farmacéuticos hospitalarios sobre aquellos aspectos aún en el debate respecto al papel de los anticuerpos monoclonales anti-CGRP en el tratamiento preventivo de la migraña. Identificar aquellas controversias aún existentes. Proponer recomendaciones consensuadas de mejora asistencial. Y promover el acceso de los clínicos y los pacientes a estos nuevos tratamientos en la prevención de la migraña con fármacos biológicos, a fin de mejorar la atención y seguimiento del paciente. Métodos se identificaron y valoraron recomendaciones para la utilización de fármacos biológicos en la prevención de la migraña a través de la metodología de consenso Delphi, proponiendo 88 aseveraciones agrupadas en 3 temas: un módulo de clínica que trata sobre el manejo de los tratamientos biológicos en la migraña, un módulo de pacientes que trata sobre las estrategias de educación al paciente y mejora de la adhesión y un módulo de coordinación que incluye las aseveraciones relacionadas con las estrategias para mejorar el trabajo conjunto entre los 2 colectivos. Se empleó la escala ordinal de Likert de 9 puntos para puntuar dichas recomendaciones y, posteriormente, los datos se analizaron estadísticamente a través de diferentes métricas. Resultados tras las 2 rondas de consulta, se alcanzó consenso en el acuerdo en 71 aseveraciones (80,7%) y consenso en el desacuerdo en una de ellas (1,1%), quedando como indeterminadas 16 aseveraciones (18,2%) de las 88 debatidas. Conclusiones el alto grado de consenso indica que la opinión de neurólogos y farmacéuticos hospitalarios sobre el papel de los anticuerpos monoclonales anti-CGRP en el tratamiento de la migraña es muy similar y permite identificar aquellas controversias aún existentes, para mejorar la atención y seguimiento del paciente con migraña. (AU)

Objective The objectives are to know the opinion of neurologists and hospital pharmacists on those aspects still under debate regarding the role of anti-CGRP monoclonal antibodies in the preventive treatment of migraine. To identify those controversies that still exist. To propose agreed recommendations for improvement of care. And to promote access of clinicians and patients to these new treatments in the prevention of migraine with biological drugs, in order to improve patient care and follow-up. Methodology Recommendations for the use of biological drugs in the prevention of migraine were identified and evaluated through the Delphi consensus methodology, proposing 88 statements grouped into three themes: a clinical module that deals with the management of biological treatments in migraine; a patient module that discusses patient education and adherence improvement strategies; and a coordination module that includes statements related to strategies to improve joint work between the two groups. The 9-point Likert ordinal scale was used to score these recommendations and, subsequently, the data was statistically analyzed through different metrics. Results After both rounds of voting, consensus was reached in agreement on 71 of the 88 statements (80.7%), leaving one statement (1.1%) with consensus in disagreement and 16 remaining as indeterminate (18.2%). Conclusions The high degree of consensus indicates that the opinion of neurologists and hospital pharmacists on the role of anti-CGRP monoclonal antibodies in the treatment of migraine is very similar and allows identifying those controversies that still exist, to improve the care and follow-up of patients with migraine. (AU)

Prophylactic treatment can modify vascular risk biomarkers in high-frequency episodic and chronic migraine patients: a pilot study.

To evaluate whether preventive treatment can modify endothelial and oxidative biomarkers of vascular disease risk in patients with high-frequency episodic and chronic migraine. In this observational, prospective pilot study, 88 prophylactic treatment-naïve patients with episodic and chronic migraine and 56 healthy sex/age matched controls underwent ultrasonography exams and blood tests at baseline, and again in the migraine patients after 3 months' treatment with metoprolol or topiramate. Biomarkers for endothelial function and oxidative stress were analyzed. At baseline, patients with migraine in the low-frequency episodic group had differences exclusively in nitrates 17.6 versus 27.33 µM; p = 0.046 compared to the controls. However, when comparing the group comprised of patients with high-frequency episodic migraine and chronic migraine versus controls, statistically significant differences appeared in hsCRP 2.68 versus 1.64 mg/dL; p = 0.049, vWF antigen (133% vs. 110%; p = 0.020, vWF activity (111% vs. 90%; p = 0.010) and isoprostane levels (181 vs. 238 µM; p = 0.05). Only in the chronic migraine subgroup did we found statistically significant differences in CIMT (0.60 vs. 0.54 mm; p = 0.042) which were significantly greater than in the controls. After treatment, patients who respond to preventive treatment exhibited significantly higher levels of nitrates (24.2-13.8 µM; p = 0.022) and nitrites (10.4-3.43 µM; p = 0.002) compared than non-responders. Moreover, biomarker levels improved in treatment-responsive patients with migraine; hsCRP levels decreased from 2.54 to 1.69 mg/dL (p < 0.05), vWF activity levels decreased from 124 to 103 IU/dL (p = 0.003) and prothrombin activity decreased from 1.01 to 0.93 (p = 0.01). These differences were also observed in the high-frequency and chronic migraine subgroup and reach statistical significance in the case of hsCRP, which decreased from 2.12 to 0.83 mg/dL (p = 0.048). Patients with migraines have differences in biomarker levels compared to controls, suggesting endothelial and oxidative dysfunction. The greatest differences in biomarker levels compared to controls are observed in migraine patients in the high-frequency and chronic migraine subgroups. Based on our results, preventive treatment is capable of modifying markers of endothelial dysfunction and oxidative stress in migraine patients, even in cases of chronic and high-frequency migraine.

Evaluation of the ICHD-3 diagnostic criteria for cardiac cephalalgia and new proposal.

BACKGROUND: The current International Classification of Headache Disorders, 3rd edition (ICHD-3) diagnostic criteria for cardiac cephalalgia were established according to previous case reports and the opinion of experts. We aimed to assess the ICHD-3 diagnostic criteria for cardiac cephalalgia. METHODS: We conducted a series of cases study and evaluated these criteria in 54 patients with cardiac cephalalgia. Next, we assessed whether the ICHD-3 diagnostic criteria B, C and D for migraine without aura were fulfilled by these patients. RESULTS: ICHD-3 criteria A, B, C1, C2 and D for cardiac cephalalgia were met by 100% of patients, whereas criterion C3 was fulfilled by 81.5%. The least frequently fulfilled sub-criterion was C3b (accompanied by nausea) (18.5%). Moreover, we found that ICHD-3 criteria B, C and D for migraine without aura were met by a low proportion of patients: 11.1%, 46.3% and 25.9%, respectively, and no patient fulfilled the three criteria simultaneously. CONCLUSION: Based on our results, we propose revised diagnostic criteria for cardiac cephalalgia. We suggest removing criterion C3 and C4. We also suggest removing the word "migraine-like" from its description.

[Translated article] Consensus recommendations on the preventive treatment of migraine.

OBJECTIVE: The objectives are to know the opinion of neurologists and hospital pharmacists on those aspects still under debate regarding the role of anti-Calcitonin Gene-related Peptide monoclonal antibodies in the preventive treatment of migraine. To identify those controversies that still exist. To propose agreed recommendations for improvement of care. And to promote access of clinicians and patients to these new treatments in the prevention of migraine with biological drugs, in order to improve patient care and follow-up. METHODOLOGY: Recommendations for the use of biological drugs in the prevention of migraine were identified and evaluated through the Delphi consensus methodology, proposing 88 statements grouped into 3 themes: a clinical module that deals with the management of biological treatments in migraine; a patient module that discusses patient education and adherence improvement strategies; and a coordination module that includes statements related to strategies to improve joint work between the two groups. The 9-point Likert ordinal scale was used to score these recommendations and, subsequently, the data was statistically analysed through different metrics. RESULTS: After both rounds of voting, consensus was reached in agreement on 71 of the 88 statements (80.7%), leaving 1 statement (1.1%) with consensus in disagreement and 16 remaining as indeterminate (18.2%). CONCLUSIONS: The high degree of consensus indicates that the opinion of neurologists and hospital pharmacists on the role of anti-Calcitonin Gene-related Peptide monoclonal antibodies in the preventive treatment of migraine is very similar and allows identifying those controversies that still exist, to improve the care and follow-up of patients with migraine.

Early Wearing-Off Effect of OnabotulinumtoxinA in Chronic Migraine: A Prospective Real-Life Study.

OBJECTIVE: Chronic migraine (CM) is a significant public health problem that affects 2.2% of the global population. Onabotulinumtoxin A (OnabotA) is a safe and effective prophylactic treatment for patients with CM. The standard injection interval for OnabotA is 12 weeks. Nevertheless, some patients experience a wearing-off effect (WOE) in the weeks preceding the next scheduled cycle. The objectives of this study are to determine the prevalence of early WOE, to analyze variables that could be clinical predictors and to specify which interval is the most appropriate to define the existence of this phenomenon. METHODS: This is a prospective single-center study of consecutive adult patients with CM who, after failing previous prophylactic therapies, started OnabotA treatment following the PREEMPT protocol between June and December of 2021. RESULTS: A total of 59 patients (93.2% female, age 44 ± 12 years) were included. A total of 37 patients (64.9%) fulfilled medication overuse criteria. Of the total patients, 40.6% reported WOE and this was more frequent after the first cycle (35.6%). Depression and anxiety disorder was a statistically significant clinical predictor of WOE (OR 3.4; CI 95% 1.22-10.84; p = 0.028). A better cut-off point to consider WOE seems to be at 10 weeks. CONCLUSIONS: Early WOE is common in patients on OnabotA treatment for CM. Individualizing the standard 12-week injection, using total doses of 195 U, and managing psychiatric comorbidities with pharmacological and non-pharmacological strategies may improve treatment outcomes and reduce OnabotA WOE.

Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients.

BACKGROUND: Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. METHODS: In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. RESULTS: A total of 162 patients were included, median age 68 years (range 65-87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.1 ± 7.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days ≥ 30%, ≥ 50%, ≥ 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). CONCLUSIONS: Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice.

Consensus recommendations for the treatment of migraine prevention. / Recomendaciones de consenso para el tratamiento de la prevención de la migraña.

OBJECTIVE: The objectives are to know the opinion of neurologists and hospital pharmacists on those aspects still under debate regarding the role of anti-CGRP monoclonal antibodies in the preventive treatment of migraine. To identify those controversies that still exist. To propose agreed recommendations for improvement of care. And to promote access of clinicians and patients to these new treatments in the prevention of migraine with biological drugs, in order to improve patient care and follow-up. METHODOLOGY: Recommendations for the use of biological drugs in the prevention of migraine were identified and evaluated through the Delphi consensus methodology, proposing 88 statements grouped into three themes: a clinical module that deals with the management of biological treatments in migraine; a patient module that discusses patient education and adherence improvement strategies; and a coordination module that includes statements related to strategies to improve joint work between the two groups. The 9-point Likert ordinal scale was used to score these recommendations and, subsequently, the data was statistically analyzed through different metrics. RESULTS: After both rounds of voting, consensus was reached in agreement on 71 of the 88 statements (80.7%), leaving one statement (1.1%) with consensus in disagreement and 16 remaining as indeterminate (18.2%). CONCLUSIONS: The high degree of consensus indicates that the opinion of neurologists and hospital pharmacists on the role of anti-CGRP monoclonal antibodies in the treatment of migraine is very similar and allows identifying those controversies that still exist, to improve the care and follow-up of patients with migraine.

Circadian rhythm of blood pressure in patients with drug-resistant mesial temporal lobe epilepsy.

OBJECTIVE: To determine whether patients with drug-resistant mesial temporal lobe epilepsy present with an alteration in the autonomic circadian regulation of blood pressure. METHODS: A prospective case‒control study was designed, with a case group comprising patients with drug-resistant mesial temporal lobe epilepsy and a control group comprising healthy volunteers. Twenty-four-hour outpatient blood pressure monitoring was performed to assess the existence of a normal (dipping) or altered (non-dipping) circadian pattern. In addition, analytical and ultrasound parameters (carotid intima-media thickness) of vascular risk and sleep quality were evaluated. RESULTS: Twenty-four subjects were recruited in each study group, amongst whom no demographic differences or history of vascular risk were observed. A higher percentage of participants with a non-dipping pattern was observed in the group of patients with epilepsy (62.5% vs. 12.5, p = 0.001). In the case group, significant differences were also observed in carotid intima-media thickness, with a greater probability of presenting with pathological values (p = 0.022). CONCLUSION: The results suggest a disorder of the central autonomic control of blood pressure in patients with drug-resistant mesial temporal lobe epilepsy, with a greater probability of developing an alteration of the circadian rhythm of blood pressure. This dysfunction may be a factor involved in the increased cardiovascular risk in this population.

Prevalence, clinical characteristics and associated factors of cardiac cephalalgia: A prospective study.

BACKGROUND: The prevalence of cardiac cephalalgia is unknown and there is limited information about its clinical features. We aimed to assess the prevalence of cardiac cephalalgia, its clinical characteristics and associated factors. METHODS: We conducted a prospective study of patients with suspected acute coronary syndrome admitted to the Cardiology Service at Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain, over a one-year period. We interviewed patients within the first 24 hours of admission using a standardized case-report form to assess the presence of headache in relation to the acute coronary syndrome and its characteristics. RESULTS: We included 438 patients, 381 with confirmed myocardial ischemia. Prevalence of cardiac cephalalgia was 14.2% (n = 54). The most common features were frontal location, pressing quality and moderate intensity. Pain referred to the jaws (aOR 2.61; 95% CI 1.33-5.12; p = 0.005), palpitations (aOR 3.65; 95% CI 1.57-8.50; p = 0.003) and circumflex coronary artery as the culprit artery for the myocardial ischemia (aOR 3.8; 95% CI 1.07-13.74; p = 0.021) were related to cardiac whereas history of hypertension was inversely associated (aOR 0.37: 95% CI 0.18-0.74; p = 0.005). CONCLUSION: The prevalence of cardiac cephalalgia was 14.2%. Our study provides valuable information about cardiac cephalalgia characteristics that suggest revision of current diagnostic criteria.

Adaptation and Validation of the Spanish Version of Decisional Conflict Scale in People with Migraine in Spain.

Purpose: We aimed to validate the Spanish version of the Decisional Conflict Scale (DCS) and analyze its psychometric properties in people with migraine. Patients and Methods: The DCS validation comprised two phases. First, a translation and cross-cultural adaptation following the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Good Practices: 1-preparation, 2-independent forward translation, 3-reconciliation, 4-back-translation, 5-harmonization, 6-clinical review, and 7-content validation in a group of migraine patients. Second, the analysis of the psychometric properties. The reliability or internal consistency of the DCS scale and subscales was assessed using Cronbach's α value. The item-subscale correlation was also evaluated. A floor and ceiling effects for DCS score was considered when at least 15% of respondents obtained DCS >90 (ceiling) or <10 (floor). The construct validity was studied through the correlation between the DCS subscales and by the correlation between the DCS and other questionnaires (Decision Self-Efficacy Scale [DSES] and 9-item Shared Decision-Making [SDM-Q-9]). Spearman's coefficients were estimated for the correlations. Results: The cross-cultural adaptation was conducted on 17 patients who completed the questionnaire in a mean of 2.4 ±1.1 minutes. Generally, more than 75% of them considered that DCS items were adequate, easy to understand, and relevant. The psychometric properties were evaluated in a sample of n=128 patients. Accordingly, the internal consistency of DCS was high, with a Cronbach's α of 0.97 for the scale and between 0.87 to 0.96 for subscales. Also, a slight floor effect was observed, with 24.2% of patients having DCS scores <10. The correlation between subscales exceeded Spearman's coefficient of 0.7. Whereas the correlation between the DCS and the other questionnaires was generally moderate (Spearman's coefficient >0.4). Conclusion: The Spanish version (Spain) of the DCS has very acceptable psychometric properties (reliability and construct validity) and good potential for assessing decisional conflicts among migraine patients.

Cardiac cephalalgia: a narrative review and ICHD-3 criteria evaluation.

BACKGROUND: Cardiac cephalalgia is an unusual condition that occurs during an episode of myocardial ischemia. Information about cardiac cephalalgia is scarce and its characteristics and physiopathology remain unclear. Our aim is to provide a narrative review of clinical characteristics and physiopathology of cardiac cephalalgia and to evaluate the current diagnostic criteria.  METHODS: A search through PubMed was undertaken for studies on cardiac cephalalgia published until 20th September 2022. We summarized the literature and provide a comprehensive review of the headache characteristics and possible mechanisms. We also evaluated current International Classification of Headache Disorders third edition diagnostic criteria based on prior reported cases.  RESULTS: In total, 88 cases were found. Headache characteristics were variable. Occipital location and throbbing pain were the most frequently reported. Headache was accompanied in most cases by cardiac symptoms. Criterion B was fulfilled by 98% of cases, criterion C1 by 72%, and criteria C2a and C2b by 37 and 93.2%, respectively. Regarding headache features described in diagnostic criterion C3, 'moderate to severe intensity', 'accompanied by nausea', 'not accompanied by photophobia or phonophobia' and 'aggravated by exertion', were reported in 75, 31, 55 and 55% of cases, respectively. CONCLUSION: Cardiac cephalalgia characteristics are variable and the headache features described in the diagnostic criterion C3 might not be adequate. Given that cardiac cephalalgia can be the manifestation of a life-threatening condition it is important to increase the knowledge about this entity.

Theory of mind: a new perspective on cluster headache-a cross-sectional study.

INTRODUCTION: Theory of mind (ToM) is the ability to attribute mental states of self and others, such as beliefs (cognitive ToM) and feelings (affective ToM). Based on the role of the hypothalamus in pain and social cognition, our aim is to determine whether ToM is impaired in patients with cluster headache (CH). METHODS: Cross-sectional study in which 31 episodic cluster headache (ECH) patients outside the bout and 20 matched controls carried out social cognition and executive function tasks. Patients were recruited from an outpatient Headache Unit. RESULTS: Patients performed worse than healthy controls at cognitive ToM (t = 4.2, p < 0.001) task but not at affective ToM. Executive function was also impaired (t = 4.8, p < 0.001) and higher scores at anxiety and depression questionnaires (t = - 2.9, p = 0.006; t = - 3.6, p = 0.001) were reported. There was no correlation between ToM scores and executive function, anxiety and depression symptoms, or disease duration and severity. DISCUSSION: Our results suggest that ECH patients can perceive other people's or selves' feelings (affective ToM) but have more difficulties than healthy subjects at recognizing beliefs (cognitive ToM).

Evaluation of the Impact of the COVID-19 Lockdown in the Clinical Course of Migraine.

OBJECTIVE: Previous studies have demonstrated that emotional stress, changes in lifestyle habits and infections can worsen the clinical course of migraine. We hypothesize that changes in habits and medical care during coronavirus disease 2019 (COVID-19) lockdown might have worsened the clinical course of migraine. DESIGN: Retrospective survey study collecting online responses from migraine patients followed-up by neurologists at three tertiary hospitals between June and July 2020. METHODS: We used a web-based survey that included demographic data, clinical variables related with any headache (frequency) and migraine (subjective worsening, frequency, and intensity), lockdown, and symptoms of post-traumatic stress. RESULTS: The response rate of the survey was 239/324 (73.8%). The final analysis included 222 subjects. Among them, 201/222 (90.5%) were women, aged 42.5 ± 12.0 (mean±SD). Subjective improvement of migraine during lockdown was reported in 31/222 participants (14.0%), while worsening in 105/222 (47.3%) and was associated with changes in migraine triggers such as stress related to going outdoors and intake of specific foods or drinks. Intensity of attacks increased in 67/222 patients (30.2%), and it was associated with the subjective worsening, female sex, recent insomnia, and use of acute medication during a headache. An increase in monthly days with any headache was observed in 105/222 patients (47.3%) and was related to symptoms of post-traumatic stress, older age and living with five or more people. CONCLUSIONS: Approximately half the migraine patients reported worsening of their usual pain during the lockdown. Worse clinical course in migraine patients was related to changes in triggers and the emotional impact of the lockdown.

Effects of the onabotulinumtoxinA follow-up delay in migraine course during the COVID-19 lockdown.

BACKGROUND: Face-to-face procedures have been postponed during COVID-19 pandemic. We aim to evaluate the impact of onabotulinumtoxinA follow-up delay in migraine during COVID-19 pandemic. METHODS: Subjective worsening, intensity of migraine attacks, and frequency of headache and migraine were retrospectively compared between patients with unmodified and interrupted onabotulinumtoxinA follow-up in Headache Units. RESULTS: We included 67 patients with chronic migraine or high-frequency episodic migraine under onabotulinumtoxinA treatment, 65 (97.0%) female, 44.5 ± 12.1 years old. Treatment administration was voluntarily delayed in 14 (20.9%) patients and nine (13.4%) were unable to continue follow-up. Patients with uninterrupted follow-up during lockdown presented 7.6 and 8.1 less monthly days with headache (adjusted p = 0.017) and migraine attacks (adjusted p = 0.009) compared to patients whose follow-up was interrupted, respectively. CONCLUSION: Involuntary delay of onabotulinumtoxinA follow-up in patients with migraine due to COVID-19 pandemic was associated with a higher frequency of headache and migraine attacks. Safe administration of onabotulinumtoxinA during lockdown should be promoted.

Acute migraine management in the emergency department: experience from a large Spanish tertiary hospital.

To assess the characteristics of the management of patients with migraine who present to the emergency department (ED) with a migraine attack. Retrospective, observational study analyzing demographic, clinical, diagnostic and therapeutic characteristics of patients with migraine diagnosis presenting to ED for a migraine attack between 2016 and 2019. We reviewed the clinical records of 847 cases. 82.2% were women with mean age of 34.9 years. 87.2% had episodic migraine and 12.2% chronic migraine. 62.3% (528/847) had taken analgesics before visiting the ED [non-steroidal-anti-inflammatory drugs (NSAIDs) (300/528; 56.9%) and triptans (261/528; 49.5%)]. 25.4% (215/847) received blood testing and 6.4% (55/847) received cranial CT. Medication was administered in 77.2% cases (654/847). The median time-to-treatment was 70 min (IQR 42-120). NSAIDs (81%, 530/654), antiemetics (43.1%, 282/654) and metamizole (39% 255/654) were the most used. Triptans were administered in 7 cases (1.1%) and opioids in 84 (12.8%). At discharge, preventive treatment was prescribed or modified in 8.2% of cases (69/839) and triptans were prescribed in 129 cases (15.3%). 70.5% (592/839) were instructed to follow-up with their primary care provider (PCP), 21.5% (181/839) with a general neurologist and 7.9% (66/839) with a headache specialist. The majority of migraine patients were not receiving the recommended acute migraine-specific medication, both in the outpatient and in the ED setting, being especially remarkable the rare use of triptans in the ED. Furthermore, we found an elevated use of urgent complementary tests, mainly blood tests.

Cognitive performance in patients with episodic cluster headache outside and inside the active cluster.

BACKGROUND: Previous studies have shown worse cognitive performance in cluster headache (CH) patients compared to healthy controls; however, little is known about cognitive performance in episodic CH (ECH) patients outside and inside the active cluster (AC). OBJECTIVE: Our aim is to compare cognitive function in ECH patients outside and inside the AC. METHODS: In this cross-sectional, observational study, four neuropsychological tests (Trail Making Test [TMT], Stroop Test [ST], verbal fluency [VF], and Symbol Digit Modalities Test [SDT]) were completed by 21 ECH patients at two different points in time: outside and inside the AC. We also assessed self-reported sleep quality and the presence of anxiety or depressive symptoms. Scores were compared. RESULTS: There was not any difference between the scores of the neuropsychological tests performed outside and inside the AC (TMT-A: 23 vs. 23.5; p = 0.984; TMT-B: 96.5 vs. 85.9; p = 0.104; ST word reading: 101.0 vs. 101.2; p = 0.938; ST color naming: 73.0 vs. 73.4; p = 0.858; ST color word: 44.0 vs. 46.0; p = 0.498; SDMT: 44.0 vs. 44.6; p = 0.961; VF phonemic: 29.5 vs. 30.2; p = 0.714; VF semantic: 20 vs. 21; p = 0.489). We found a worsening in the sleep quality component of the Pittsburgh Sleep Quality Index median scores in patients outside the AC (2 vs. 1; p = 0.046). CONCLUSIONS: Our findings suggest that patients with ECH have a similar cognitive performance outside and during the AC.

Cutaneous Allodynia in Migraine: A Narrative Review.

OBJECTIVE: In the present work, we conduct a narrative review of the most relevant literature on cutaneous allodynia (CA) in migraine. BACKGROUND: CA is regarded as the perception of pain in response to non-noxious skin stimulation. The number of research studies relating to CA and migraine has increased strikingly over the last few decades. Therefore, the clinician treating migraine patients must recognize this common symptom and have up-to-date knowledge of its importance from the pathophysiological, diagnostic, prognostic and therapeutic point of view. METHODS: We performed a comprehensive narrative review to analyze existing literature regarding CA in migraine, with a special focus on epidemiology, pathophysiology, assessment methods, risk for chronification, diagnosis and management. PubMed and the Cochrane databases were used for the literature search. RESULTS: The prevalence of CA in patients with migraine is approximately 60%. The mechanisms underlying CA in migraine are not completely clarified but include a sensitization phenomenon at different levels of the trigemino-talamo-cortical nociceptive pathway and dysfunction of brainstem and cortical areas that modulate thalamocortical inputs. The gold standard for the assessment of CA is quantitative sensory testing (QST), but the validated Allodynia 12-item questionnaire is preferred in clinical setting. The presence of CA is associated with an increased risk of migraine chronification and has therapeutic implications. CONCLUSIONS: CA is a marker of central sensitization in patients with migraine that has been associated with an increased risk of chronification and may influence therapeutic decisions.

Cost of fremanezumab, erenumab, galcanezumab and onabotulinumtoxinA associated adverse events, for migraine prophylaxis in Spain.

Objective: To compare the cost of adverse events (AEs) associated with preventive treatment of migraine with fremanezumab, versus erenumab, galcanezumab, and onabotulinumtoxinA.Methods: A probabilistic modeling analysis was performed, using second-order Monte Carlo simulations, with 1,000 simulations, in patients with at least 4 days of migraine per month, from the perspective of the National Health System and a time horizon of 12 weeks. The frequency of AEs described in the clinical trials was analyzed with 12 weeks of treatment. Unit costs (€) of management of AEs were obtained from public health prices, expert panels, and published Spanish studies.Results: Fremanezumab would generate average savings of -€469 (95% CI -€303; -€674) versus erenumab, -€268 (95% CI -€171; -€391) versus galcanezumab, -€1,100 (95% CI -€704; -€1,608) or -€1,295 (95% CI -€835; -€1,893) versus onabotulinumtoxinA using real-life or clinical trial data, respectively.Conclusions: The different safety profile of treatment with fremanezumab, compared to erenumab, galcanezumab, and onabotulinumtoxinA, would generate savings in health-care resources in all the scenarios considered.