RESUMO
BACKGROUND AND PURPOSE: The aim was to evaluate the effect of anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies on depressive symptoms in subjects with migraine and to determine whether depressive symptoms predict treatment response. METHODS: Patients with migraine treated with erenumab and fremanezumab at the Leiden Headache Centre completed daily E-headache diaries. A control group was included. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Center for Epidemiological Studies Depression Scale (CES-D) questionnaires at baseline (T0) and after 3 months (T1). First, the effect of treatment on the reduction in HADS-D and CES-D scores was assessed, with reduction in depression scores as the dependent variable and reduction in monthly migraine days (MMD) and treatment with anti-CGRP medication as independent variables. Second, depression as a predictor of treatment response was investigated, using the absolute reduction in MMD as a dependent variable and age, gender, MMD, active depression, impact, stress and locus of control scores as independent variables. RESULTS: In total, n = 108 patients were treated with erenumab, n = 90 with fremanezumab and n = 68 were without active treatment. Treatment with anti-CGRP medication was positively associated with a reduction in the HADS-D (ß = 1.65, p = 0.01) compared to control, independent of MMD reduction. However, the same effect was not found for the CES-D (ß = 2.15, p = 0.21). Active depression predicted poorer response to erenumab (p = 0.02) but not to fremanezumab (p = 0.09). CONCLUSION: Anti-CGRP (ligand or receptor) monoclonals lead to improvement of depressive symptoms in individuals with migraine, independent of migraine reduction. Depression may predict treatment response to erenumab but not to fremanezumab.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Humanos , Peptídeo Relacionado com Gene de Calcitonina/uso terapêutico , Ligantes , Depressão/tratamento farmacológico , Transtornos de Enxaqueca/tratamento farmacológico , CefaleiaRESUMO
Background: Telemedicine offers a promising solution to enhance the delivery and personalization of headache care. Integrating electronic (e-)tools enables the objective monitoring of migraine. Objectives: This study aims to demonstrate the relevance of e-tools for personalized headache care, assess patient and caregiver compliance and satisfaction, and present their use in enhancing care. Methods: Firstly, a systematic review was performed to validate the diagnostic accuracy of e-diaries for diagnosing migraine. Secondly, we collected e-diary data prospectively from diagnosed adult migraine patients at the Leiden Headache Center. Finally, questionnaires were sent to evaluate satisfaction of patients and health care providers with the Leiden e-headache diary and video consultations. Results: In the systematic review, the Leiden Headache Center's e-diary was the only validated tool. Patients (n = 1,009) were followed for a median of 181 days (interquartile range [IQR] 84-240). Compliance was 96.4% (IQR 85.2 - 99.1%), with 10.8% of days missing. Factors positively associated with compliance were older age (p < 0.001), female sex (p < 0.001), higher e-diary grade (p < 0.001), and clinical use (p = 0.04). The e-diary received a median score of 8/10 and was well-liked by patients (n = 535) and providers (n = 23). Video consultations were a good alternative for physical visits according to 76.9% of patients and 84.6% of providers. Conclusion: Validated e-headache diaries and video consultations in telemedicine enhance headache care accessibility, providing convenient care at preferred times and locations.
RESUMO
BACKGROUND: This longitudinal cohort study aimed to investigate changes in migraine-related outcomes following COVID-19 infection and vaccination. METHODS: We identified 547 clinically diagnosed migraine patients from the Leiden Headache Center who kept a headache E-diary during the COVID-19 pandemic (February 2020 to August 2022). We sent a questionnaire to register their COVID-19 infection and/or vaccination dates. After applying inclusion criteria, n = 59 participants could be included in the infection analysis and n = 147 could be included in the vaccination analysis. Primary outcome was the change in monthly migraine days (MMD) between 1 month prior and 1 month post COVID-19 infection or vaccination. Secondary outcome variables were change in monthly headache days (MHD) and monthly acute medication days (MAMD). RESULTS: Vaccination against COVID-19 was associated with an increase in MMD (1.06; 95% confidence interval [CI] = 0.57-1.55; p < 0.001), MHD (1.52; 95% CI = 0.91-2.14; p < 0.001) and MAMD (0.72; 95% CI = 0.33-1.12; p < 0.001) in the first month post-vaccination. COVID-19 infection solely increased the number of MAMD (1.11; 95% CI = 0.10-1.62; p < 0.027), but no statistically significant differences in MMD or MHD were observed. CONCLUSIONS: Our findings imply that vaccination against COVID-19 is associated with an increase in migraine, indicating a possible role of inflammatory mediators in migraine pathophysiology.
Assuntos
COVID-19 , Transtornos de Enxaqueca , Humanos , Estudos Longitudinais , Pandemias , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos de Coortes , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/prevenção & controle , Cefaleia , VacinaçãoRESUMO
BACKGROUND: There is a need for standardization of the definition of a migraine day for clinical and research purposes. METHODS: We prospectively compared different definitions of a migraine day with E-diary data of n = 1494 patients with migraine. We used a baseline definition based on migraine characteristics with a duration of ≥4 hours OR triptan intake (independently from its effect) OR (visual) aura lasting 5-60 minutes. RESULTS: Of all migraine days defined by triptan intake only, 66.2% had a duration <4 hours. Adjusting the headache duration criterion to ≥30 minutes led to a decrease in days defined by triptan intake only and resulted in a 5.4% increase in total migraine days (equals 0.45 migraine day increase in monthly migraine days). These additional migraine days had a median duration of 2.5 hours. CONCLUSION: We propose to define a migraine day as follows: 1) (a) headache duration ≥30 minutes; (b) matching ≥2 of four characteristics: unilateral, pulsating, moderate to severe pain, aggravation by or causing avoidance of routine physical activity; and (c) during headache ≥1 of the following: nausea and/or vomiting, photophobia and phonophobia or 2) (visual) aura duration 5-60 minutes or 3) a day with headache for which acute migraine-specific medication is used irrespective of its effect.
Assuntos
Epilepsia , Transtornos de Enxaqueca , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Cefaleia , Náusea , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêutico , Triptaminas/uso terapêuticoRESUMO
BACKGROUND AND PURPOSE: Anti-calcitonin gene-related peptide (CGRP) (receptor) antibodies effectively reduce overall migraine attack frequency, but whether there are differences in effect between perimenstrual and nonperimenstrual migraine days has not been investigated. METHODS: We performed a single-arm study among women with migraine. Participants were followed with electronic E-diaries during one (pretreatment) baseline month and 6 months of treatment with either erenumab or fremanezumab. Differences in treatment effect on perimenstrual and nonperimenstrual migraine days were assessed using a mixed effects logistic regression model, with migraine day as dependent variable; treatment, menstrual window, and an interaction term (treatment × menstrual window) as fixed effects; and patient as a random effect. RESULTS: There was no interaction between the menstrual window and treatment effect, indicating that the reduction in migraine days under treatment was similar during the menstrual window and the remainder of the menstrual cycle (odds ratio for treatment = 0.44, 95% confidence interval = 0.38-0.51). CONCLUSIONS: Our findings support prophylactic use of anti-CGRP (receptor) antibodies for women with menstrual migraine, as this leads to consistent reductions in number of migraine days during the entire menstrual cycle.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Humanos , Feminino , Ciclo Menstrual , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controleRESUMO
OBJECTIVE: In this prospective cohort study, characteristics of perimenstrual and non-perimenstrual migraine attacks in women were compared with migraine attacks in men. BACKGROUND: Women report longer migraine attacks and more accompanying symptoms than men in cross-sectional questionnaire studies, but this has not been confirmed in longitudinal studies. Supposed differences could result from different characteristics specific to perimenstrual migraine attacks, or of attacks in women in general. METHODS: This cohort study was performed among patients with migraine who were treated at the Leiden Headache Clinic. We assessed differences in migraine attack characteristics between men and women who were prospectively followed by a previously validated electronic headache diary. The primary outcome was "attack" duration. Differences between perimenstrual (Days -2 to +3 of the menstrual cycle) and non-perimenstrual attacks in women versus attacks in men were corrected for age, chronic migraine, and medication overuse headache. RESULTS: A total of 1347 women and 284 men were included, reflecting the preponderance of women in migraine prevalence. Crude median (first and third quartile [Q1-Q3]) attack duration in men was 32.1 [17.7-53.6] h, compared to 36.7 [21.9-62.4] h for non-perimenstrual migraine attacks and 44.4 [17.9-79.0] h for perimenstrual migraine attacks in women. After correction for confounding, perimenstrual migraine attacks were 1.62 (95% confidence interval [CI] 1.47-1.79; p < 0.001) and non-perimenstrual 1.15 (95% CI 1.05-1.25; p = 0.003) times longer compared to migraine attacks in men. The mean relapse percentage in men was 9.2%, compared to 12.6% for non-perimenstrual migraine attacks, and 15.7% for perimenstrual migraine attacks. Relapse risk was greater for perimenstrual (odds ratio [OR] 2.39, 95% CI 1.93-2.95; p < 0.001), but not for non-perimenstrual (OR 1.18, 95% CI 0.97-1.45; p = 0.060) attacks. Migraine attacks in women were more often accompanied by photophobia, phonophobia, and nausea, but less often aura. CONCLUSION: Compared to attacks in men, both perimenstrual and non-perimenstrual migraine attacks are of longer duration and are more often accompanied by associated symptoms. A sex-specific approach to migraine treatment and research is needed.
Assuntos
Transtornos de Enxaqueca , Caracteres Sexuais , Humanos , Feminino , Masculino , Estudos de Coortes , Estudos Prospectivos , Estudos Transversais , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/tratamento farmacológico , Estudos Longitudinais , CefaleiaRESUMO
BACKGROUND: Currently, there is no evidence-based hormonal treatment for migraine in women. Several small studies suggest a beneficial effect of combined oral contraceptives, but no large randomized controlled trial has been performed. As proof of efficacy is lacking and usage may be accompanied by potentially severe side effects, there is a great need for clarity on this topic. METHODS: Women with menstrual migraine (n = 180) are randomly assigned (1:1) to ethinylestradiol/levonorgestrel 30/150 µg or vitamin E 400 IU. Participants start with a baseline period of 4 weeks, which is followed by a 12-week treatment period. During the study period, a E-headache diary will be used, which is time-locked and includes an automated algorithm differentiating headache and migraine days. RESULTS: The primary outcome will be change in monthly migraine days (MMD) from baseline (weeks - 4 to 0) to the last 4 weeks of treatment (weeks 9 to 12). Secondary outcomes will be change in monthly headache days (MHD) and 50% responder rates of MMD and MHD. CONCLUSIONS: The WHAT! trial aims to investigate effectivity and safety of continuous combined oral contraceptive treatment for menstrual migraine. Immediate implementation of results in clinical practice is possible. TRIAL REGISTRATION: Clinical trials.gov NCT04007874 . Registered 28 June 2019.
Assuntos
Anticoncepcionais Orais Combinados , Transtornos de Enxaqueca , Humanos , Feminino , Anticoncepcionais Orais Combinados/efeitos adversos , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/tratamento farmacológico , Cefaleia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Background: Anti-CGRP-(receptor-)monoclonal antibodies (anti-CGRP(R)-mAbs) represent a novel class of drugs for migraine treatment, but their long-term cerebrovascular and cardiovascular (CV) safety warrants further examination. Methods: In this observational cohort study we assessed the CV safety for erenumab and fremanezumab in a real-world setting during a follow-up period of at least 1 year. Patients with hypertension or CV history were excluded. We conducted ECGs and collected clinical data at treatment initiation and thereafter every 3 months, including liver and kidney function, lipid-, electrolyte-and glucose levels. Results: Among patients receiving erenumab (n = 101) or fremanezumab (n = 92), 3.1% (6/193) developed abnormal ECGs or CV adverse events. Of these, three (1.6%) experienced moderate to severe CV adverse events (cerebellar stroke, spontaneous coronary artery dissection, and pericarditis) and discontinued treatment. The remaining three (1.6%) developed non-threatening ECG abnormalities without physical complaints. No significant changes were observed in liver and kidney function, lipid-, electrolyte-, or glucose levels. Discussion: We observed CV events in 1.6% of patients with 1.5-year follow-up of anti-CGRP(R)-mAbs treatment. We advise awareness regarding CV events in patients with migraine undergoing CGRP-targeted treatment, not as a confirmation of increased risk but as a proactive measure to address potential multifactorial influences.
RESUMO
BACKGROUND AND OBJECTIVES: Anti-calcitonin gene-related peptide (CGRP) (receptor) antibodies are approved as preventive treatment for migraine. Recent concerns have been raised after a retrospective analysis of postmarketing case reports of elevated blood pressure (BP) associated with erenumab. In this prospective follow-up study, we aimed to assess the safety regarding BP in a real-world setting. METHODS: All people with migraine who were treated with erenumab and fremanezumab at the Leiden Headache Center between January 2019 and January 2021 were included. BP measurements were collected from baseline (T0) until 12 months of follow-up, with a 3-month interval (T1-T4). Mixed linear models were fitted with time as a fixed effect and the patient as a random effect. RESULTS: Both systolic and diastolic BP were increased at all time points T1-T4 compared with T0 (p < 0.001). The maximum estimated increase in the mean systolic BP was 5.2 mm Hg (95% CI 3.1-7.5). The maximum estimated increase in the mean diastolic BP was 3.5 mm Hg (95% CI 2.0-4.9). In the erenumab group (n = 109), both systolic and diastolic BP were increased at all time points compared with T0 (all p < 0.001). For fremanezumab (n = 87), systolic but not diastolic BP was increased compared with T0 at T1 (p = 0.006) and T2 (p = 0.004). Four patients (3.7%) with normal BP at T0 required antihypertensive treatment after erenumab was started. DISCUSSION: The mean systolic and diastolic BP increased after anti-CGRP (receptor) antibodies were started. The majority of patients remained within the normal BP limits, but some patients required antihypertensive treatment. Physicians should be aware that people with migraine may be at risk of developing hypertension when treated with anti-CGRP (receptor) antibodies, and this should be added to (inter)national treatment guidelines. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that anti-CGRP (receptor) antibodies increase BP when used to treat patients with migraine.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Humanos , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Seguimentos , Estudos Retrospectivos , Pressão Sanguínea , Estudos Prospectivos , Anti-Hipertensivos/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológicoRESUMO
BACKGROUND AND OBJECTIVES: Endogenous and exogenous female sex hormones are considered important contributors to migraine pathophysiology. Previous studies have cautiously suggested that perimenstrual migraine attacks have a longer duration and are associated with higher disability compared to nonperimenstrual attacks, but they showed conflicting results on acute therapy efficacy, pain intensity, and associated symptoms. We compared perimenstrual and nonperimenstrual migraine attack characteristics and assessed premenstrual syndrome (PMS) in women with migraine. METHODS: Women with migraine were invited to complete a headache e-diary. Characteristics of perimenstrual attacks and nonperimenstrual attacks were compared. The primary outcome was attack duration. Secondary outcomes were headache intensity, accompanying symptoms, acute medication intake, and pain coping. Mixed effects models were used to account for multiple attacks within patients. PMS was assessed in patients without hormonal contraceptives. Subgroup analyses were performed for women with menstrually related migraine (MRM) and nonmenstrually related migraine (non-MRM) and women with a natural menstrual cycle and women using hormonal contraceptives. RESULTS: A representative group of 500 participants completed the e-diary for at least 1 month. Perimenstrual migraine attacks (n = 998) compared with nonperimenstrual attacks (n = 4097) were associated with longer duration (20.0 vs 16.1 hours, 95% confidence interval 0.2-0.4), higher recurrence risk (odds ratio [OR] 2.4 [2.0-2.9]), increased triptan intake (OR 1.2 [1.1-1.4]), higher headache intensity (OR 1.4 [1.2-1.7]), less pain coping (mean difference -0.2 [-0.3 to -0.1]), more pronounced photophobia (OR 1.3 [1.2-1.4]) and phonophobia (OR 1.2 [1.1-1.4]), and less aura (OR 0.8 [0.6-1.0]). In total, 396/500 women completed the diary for ≥3 consecutive menstrual cycles, of whom 56% (221/396) fulfilled MRM criteria. Differences in attack characteristics became more pronounced when focusing on women with MRM and women using hormonal contraceptives. Prevalence of PMS was not different for women with MRM compared to non-MRM (11% vs 15%). DISCUSSION: The longer duration of perimenstrual migraine attacks in women (with MRM) is associated with higher recurrence risk and increased triptan use. This may increase the risk of medication overuse and emphasizes the need to develop female-specific prophylactic treatment.
Assuntos
Prontuários Médicos , Menstruação , Transtornos de Enxaqueca , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/etiologia , Prevalência , Triptaminas/uso terapêuticoRESUMO
BACKGROUND: Epicardial adipose tissue located close to the atrial wall can change the electric conduction of the left atrium, potentially leading to atrial fibrillation (AF). The aim of this study was to assess whether an increased atrial adipose tissue mass posterior to the left atrium is related to AF independent of demographical and cardiovascular risk factors. METHODS AND RESULTS: Two hundred patients with AF and 200 patients without AF who underwent computed tomographic angiography were included. The posterior left atrial adipose tissue mass was quantified on computed tomographic angiography images as tissue with Hounsfield Units between -195 and -45. The adipose tissue mass was significantly larger in patients with AF compared with patients with sinus rhythm: 10.6±5.5 versus 4.7±3.5 g, P<0.001. In a multiple variable model (including age, body mass index, sex, coronary artery calcium score, diabetes mellitus, hypertension, hypercholesterolemia, family history of coronary artery disease, and known coronary artery disease), each gram increase of posterior left atrial adipose tissue was associated with 1.32 odds ratio of having AF (95% confidence interval, 1.22-1.43; P<0.001). Furthermore, the addition of the adipose tissue mass to the multiple variable analysis significantly increased the discriminatory ability to predict AF: increase in the area under the receiver operating characteristic, 0.88 (95% confidence interval, 0.84-0.91) versus 0.81 (0.76-0.85), P<0.001. CONCLUSIONS: Posterior left atrial adipose tissue mass is significantly larger in patients with AF versus without AF. An increase in adipose tissue was independently associated with AF and provided incremental value over well-known predictors of AF. These findings add to the hypothesis that the posterior left atrial adipose tissue mass contributes to structural and electric remodeling leading to AF.