Introduction:ICHD-3 integrates neuralgias affecting trigeminal terminal branches within broader trigeminal pain categories rather than defining them as distinct entities. In this context, their frequency and clinical characteristics remain poorly characterized. We aimed to describe their frequency and clinical characteristics in a headache unit registry. Methods:We conducted a retrospective, descriptive cohort study based on a prospective registry initiated in January 2008 at a headache unit. Patients diagnosed between January 2008 and January 2023 who fulfilled ICHD-2 criteria for nasociliary (code 13.5), supraorbital (13.6), or other terminal branch neuralgias (13.7) were included. Demographic and clinical data were collected and analyzed. Results:Among 8728 patients evaluated during the study period, 108 (1.2%) met inclusion criteria; 71 (65.7%) were women. Mean age at symptom onset was 47.4 ± 18.7 years (range 6-89), and mean time from onset to diagnosis was 34.4 ± 68.5 months (range 1-420). The most frequent neuralgias were supraorbital (39.8%) and auriculotemporal (25.9%), followed by supratrochlear (8.3%), infraorbital (7.4%), lacrimal (7.4%), mental (5.6%), nasociliary (4.6%), and infratrochlear (0.9%). Conclusion:Trigeminal terminal branch neuralgias represent a small but consistent clinical presentation defined by topographic distribution and sensory features. Recognition of these features supports anatomically guided evaluation and peripheral interventions.

OBJECTIVES:The aim of this study was to describe the long-term effectiveness and treatment persistence of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (MAbs) in migraine and to identify baseline factors associated with 2-year treatment continuation. METHODS:A prospective observational multicenter registry-based study of anti-CGRP MAbs was conducted. We analyzed changes in monthly headache days (MHDs) at 24 months (M24) compared with baseline in those who reached M24 (ON-group). We analyzed patterns of response at 4 time points (6, 12, 18, and 24 months). We defined sustained response (SR) as a ≥50% reduction in MHDs at ≥3 of 4 time points. We compared baseline characteristics of the ON-group with those of the discontinuation group because of lack of effectiveness (OFF-group). RESULTS:A total of 1,340 individuals reached M24 (ON-group: median age 48.0 [41.0-55.0] years; 81.7% female). The median MHD at baseline was 20.0 (13.0-28.0) days. At M24, 60.4% of patients demonstrated ≥50% reduction in MHDs (809/1,340). The proportion of participants achieving SR at M24 was 53.8% (142/264). When compared with the ON-group (n = 1,340), the OFF-group (n = 1,057) showed statistically significant higher baseline MHDs (ON: 20.0 [13.0-28.0] vs OFF: 25.0 [16.0-28.0]) and a greater proportion of patients with aura (ON: 16.2% vs OFF: 22.9%), depression (ON: 22.8% vs OFF: 37.9%), and obesity (ON: 7.2% vs OFF: 19.1%) (p < 0.001). DISCUSSION:Sustained reductions in MHDs to anti-CGRP treatment at 2 years was observed. Delayed treatment onset, migraine with aura, depression, and obesity may negatively affect treatment persistence. CLASSIFICATION OF EVIDENCE:This study provides Class IV evidence that, in patients with migraine, treatment with anti-CGRP MAbs is associated with sustained reductions in MHDs over a 24-month period.

Introducción Establecer si determinados rasgos de personalidad podrían predecir la respuesta a los anticuerpos monoclonales (AcM) frente al péptido relacionado con el gen de la calcitonina (CGRP) en pacientes con migraña. Método Estudio observacional con diseño de cohortes prospectiva. Pacientes con migraña crónica (MC) o episódica de alta frecuencia (MEAF) tratados de acuerdo con los criterios nacionales de reembolso con AcM frente al CGRP en una unidad de cefaleas de un hospital terciario. Se recabaron variables clínicas y demográficas. Se consideró respuesta la reducción de al menos un 50% en el número de días al mes de cefalea a los 3meses de tratamiento. Se administró el test de Salamanca para evaluar los rasgos de personalidad. Resultados Se incluyeron 104 pacientes, 88 (84,6%) mujeres con 46,5±10,3 años en el momento del inicio del tratamiento. En 88 (84,6%), diagnóstico de MC. Tratamiento con galcanezumab y fremanezumab (52 casos cada fármaco). Respuesta en 75 pacientes (72,1%). En el grupo de pacientes respondedores se observó menor edad al inicio del tratamiento (44,1±10,6 vs 49,7±9,1, p= 0,006), menor latencia en años inicio migraña-tratamiento (22,4±12,2 vs 28,2±14,4, p=0,029) y menor latencia en meses inicio MC o MEAF-tratamiento (90,4±51,9 vs 118,5±61,2, p=0,013). Los rasgos de personalidad más presentes en la muestra fueron: histriónico (64,4%), anancástico (52,9%) y ansioso (50%). Predijo la ausencia de respuesta al tratamiento la presencia del rasgo inestabilidad emocional subtipo límite (OR: 0,24 [0,09-0,64]). Conclusiones Los rasgos de personalidad, junto a otras variables clínicas y demográficas, pueden ser factores predictores de respuesta al tratamiento con AcM frente al CGRP.

Introducción La residencia es una etapa fundamental para adquirir competencias clínicas y científicas necesarias en neurología. Aunque la cefalea es una enfermedad prevalente e incapacitante, no siempre recibe la atención formativa adecuada. En 2015, una encuesta reveló carencias importantes en la formación de los residentes de neurología en cefaleas en España. El objetivo de este estudio es analizar la situación actual (2025) y compararla con los datos previos, integrando también la perspectiva de los tutores. Material y métodos Estudio observacional transversal basado en una encuesta online anónima dirigida a residentes y tutores de neurología en España. Se recogieron datos sobre rotaciones, técnicas, percepción de calidad formativa e implicación en investigación. Se compararon los resultados actuales con los obtenidos en 2015, y entre tutores y residentes. Resultados Participaron 109 residentes y 54 tutores. Un 88% de residentes había rotado en cefaleas vs. 48% en 2015. Un 44% dominaba técnicas como toxina botulínica o bloqueos vs. 36%. Solo el 47% de los residentes considera adecuada su formación vs. 83% de los tutores. Un 21% había participado en investigación en cefaleas, pero los tutores estimaban un 62%. El 89% de tutores apoyan la obligatoriedad de la rotación. Conclusiones Aunque se han logrado avances en la última década, la formación en cefaleas sigue siendo percibida como insuficiente por muchos residentes. Se propone incorporar una rotación específica obligatoria, reforzar el aprendizaje técnico y fomentar la investigación tutelada.

AimAtogepant is a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist approved for migraine prevention. This study primarily evaluated its effectiveness and safety in real-world clinical practice, focusing on patients with treatment-resistant migraine, defined according to the European Headache Federation (EHF) criteria as failure of at least three classes of preventive medications, including onabotulinumtoxinA or anti-CGRP monoclonal antibodies (mAbs).MethodsThis prospective multicentre study was conducted across 15 tertiary Headache Units in Spain. Demographic and clinical data, prior preventives, monthly headache days (MHD), monthly migraine days (MMD), and adverse events (AEs) were systematically collected at baseline, 3 months (primary endpoint), and/or 6 months (secondary endpoint).ResultsA total of 513 patients were enrolled (mean age 48 years; 88% women). The 3-month analysis included 455 patients, with median MHD decreasing from 21 (IQR 15-30) to 14 (IQR 6-30) and MMD from 14 (IQR 10-20) to 8 (IQR 3-15) (both p < 0.0001). A ≥ 50% reduction was achieved by 34% (MHD) and 29% (MMD), with ≥75% responses in 16% and 13%. Adverse events were mostly mild, mainly constipation (30%) and nausea (18%), and the 3-month discontinuation rate was 11.8%. Responders had shorter migraine chronicity, less analgesic overuse, and fewer prior preventive failures. Although prior inadequate response to anti-CGRP mAbs reduced the likelihood of improvement, it did not prevent meaningful benefit. At analysis, 151 patients had reached the 6-month visit, showing further improvement (MHD 10 [IQR 5-20]; MMD 6 [IQR 4-12]) and fewer adverse events.ConclusionsAtogepant showed robust real-world effectiveness and good tolerability in a large, treatment-resistant migraine cohort, with clinically meaningful improvement at 3 months and incremental benefit in the subgroup evaluated at 6 months. Lower migraine chronicity and fewer prior preventive failures were associated with better outcomes, supporting the earlier introduction of anti-CGRP therapies in clinical practice.Trial RegistrationClinical Trials.gov NCT06241313.

BackgroundThe International Headache Society has proposed new treatment goals for migraine prevention in real world, as a way to set higher standards of care. This study provides the first assessment of the proportion of individuals achieving them after 6 months of migraine-specific treatment with anti-CGRP monoclonal antibodies (MAbs).MethodsThis was a prospective, real-world, European multicenter study, including adults with migraine treated with anti-CGRP MAbs (EUREkA cohort). We assessed the proportions of individuals in each treatment goal category-migraine freedom (no monthly migraine days [MMD]); optimal control (< 4 MMD), modest control (4-6 MMD); insufficient control (>6 MMD)-after 6 months of treatment. We also assessed the proportion of individuals with ≥50% reduction in MMD in the insufficient control group.ResultsOf the 5818 individuals in the EUREkA cohort, 4963 had 6 months data. Of these, 82.3% (4086/4963) were females and the median age was 48.0 [40.0-55.0] years. At baseline, the median monthly headache days [MHD] and MMD were 20.0 [13.3-28.0] and 15.0 [10.0-20.0], respectively. All participants were classified as having insufficient headache control (>6 MMD) at baseline. At month 6, 6.9% (342/4963) had migraine freedom, 22.9% (1137/4963) optimal control, 24.6% (1223/4963) modest control and 45.6% (2261/4963) insufficient control. In the insufficient control group, 27.1% (613/2261) had ≥50% reduction in MMD.ConclusionsHigh standards of care, defined as optimal disease control or even migraine freedom, are achieved in real-world settings with anti-CGRP MAbs in approximately 30% of individuals with a high migraine burden. These findings highlight the need to expand global access to these treatments. Future studies should explore whether initiating migraine-specific preventive treatments earlier could further reduce residual migraine days in responders, enabling a larger proportion of patients to achieve optimal disease control.

OBJECTIVE:This study aimed to evaluate demographic characteristics, treatment effectiveness, and safety outcomes in patients with migraine undergoing anti-calcitonin gene-related peptide (CGRP) treatments regarding the presence of autoimmune diseases. BACKGROUND:CGRP has an important role in migraine pathophysiology through neuronal modulation in the trigeminovascular nociceptive system and activation of neuro-inflammatory cascades. We hypothesized that autoimmune diseases may influence treatment response and safety profiles in patients with migraine treated with anti-CGRP treatments. METHODS:This was a retrospective multicenter, age- and sex-matched cohort study in headache units/headache clinics in Spain and United Kingdom between May 2024 and May 2025 including patients treated with CGRP monoclonal antibodies from prospectively collected cohorts. Patients were assessed for demographics, migraine-related characteristics, treatment effectiveness (monthly migraine days [MMD] and/or monthly headache days [MHD]), and safety outcomes. The main outcome was the effectiveness measured by ≥50% response rate in MMD between the two groups. Secondary outcomes included other effectiveness measurements regarding the number of MMD and MHD and treatment emerging adverse events. RESULTS:A total of 388 patients with migraine under anti-CGRP treatments (194 with autoimmune diseases and 194 age- and sex-matched controls without autoimmune diseases) were included. The proportion of patients achieving a ≥50% response rate in MMD was higher in patients without autoimmune diseases at 6 (69% vs. 53%; p = 0.006) and 9 months (74% vs. 52%; p = 0.006). Treatment emerging adverse events were comparable between the two groups (35% vs. 38%; p = 0.575). Patients with autoimmune disease had a significantly lower likelihood of achieving a ≥50% response in MMD compared with those without autoimmune disease (adjusted odds ratio, 0.61; 95% confidence interval, 0.44-0.85; p = 0.006), independent of comorbid depression and medication overuse. CONCLUSIONS:Our study shows that anti-CGRP treatments are effective and safe for patients with migraine regardless the presence of autoimmune diseases, although an increased treatment response in patient without autoimmune disorders compared to patients with autoimmune disorders was observed. These findings highlight the need for early intervention, tailored strategies, and vigilant monitoring in patients with migraine and autoimmune disorders. Further research should explore immunomodulatory approaches to enhance outcomes.

INTRODUCTION:Residency is a key stage for acquiring the clinical and research competencies required in neurology. Although headache disorders are highly prevalent and disabling, they do not always receive adequate attention during training. In 2015, a national survey revealed major gaps in headache training among neurology residents in Spain. This study aims to assess the current situation (2025) and compare it with previous data, while incorporating the perspective of residency tutors. MATERIAL AND METHODS:We conducted a cross-sectional, observational study based on an anonymous online survey distributed to neurology residents and tutors across Spain. The survey collected data on rotations, technical procedures, perceived quality of training, and research involvement. Current results were compared with those from 2015, as well as between residents and tutors. RESULTS:A total of 109 residents and 54 tutors participated. Eighty-eight percent of residents had rotated through a headache unit vs 48% in 2015. Forty-four percent reported being proficient in techniques such as botulinum toxin injections or nerve blocks vs 36%. Only 47% of residents considered their headache training adequate, compared to 83% of tutors. While 21% of residents had participated in headache-related research, tutors estimated this at 62%. Eighty-nine percent of tutors supported making headache rotations mandatory. CONCLUSIONS:Although progress has been made over the past decade, headache training is still perceived as insufficient by many residents. We recommend implementing a mandatory rotation in headache, reinforcing hands-on training in technical procedures, and promoting structured research mentorship.

BACKGROUND:Chronic migraine is a debilitating disorder characterized by central sensitization and impaired habituation. Although OnabotulinumtoxinA (OnabotA) is an established preventive treatment, its precise mechanism of action and predictors of therapeutic response remain elusive. In this prospective cohort study, we integrated clinical parameters with algometric assessments, a recognized tool for evaluating peripheral sensitization, to develop machine learning-based predictive models to forecast migraine treatment response and effectiveness. METHODS:Seventy-six patients underwent comprehensive clinical evaluations and pressure pain threshold measurements. Key clinical and algometric variables were identified using a feature selection algorithm and incorporated into linear regression models for continuous outcomes (reductions in migraine days, headache days, symptomatic medication use, and triptan use) and an ordinal logistic regression model for categorical treatment response considering percentage of decrease in headache days [3 classes: low (<50%), moderate (50%-75%), and high (>75%) responders]. RESULTS:The linear regression models yielded significant correlations, exemplified by a reduction in migraine days (ρ = 0.762, RMSE = 5.70) and symptomatic medication days (ρ = 0.503, RMSE = 7.84). Similarly, the ordinal logistic regression model achieved an overall accuracy of 56.6% to predict treatment effectiveness (κ = 0.334 for 3 classes), as well as 71.1%, 64.5%, and 77.6% accuracies to predict high, moderate, and low OnabotA response. Notably, incorporating algometric data significantly enhanced predictive performance compared to models based solely on clinical variables. CONCLUSIONS:These findings support the potential of combined clinical and algometric evaluation as a practical biomarker for optimizing OnabotA therapy in chronic migraine, warranting further validation in larger, multicenter studies.

Atogepant is approved for migraine prevention and has shown strong efficacy in clinical trials. However, its effectiveness following failure of anti-CGRP monoclonal antibodies (MAbs) has not been evaluated in large real-world populations. This multicenter observational study conducted across Spanish headache units included adults with migraine who initiated atogepant after failure of ≥ 1 anti-CGRP MAb and had ≥ 3 months of follow-up. Baseline demographic and clinical variables were collected prospectively, with follow-up assessments at months 3 and 6. The primary outcome was the proportion of patients achieving a ≥ 50

BACKGROUND:Patients with migraine aged ≥65 years old are underrepresented in clinical trials. This study compares effectiveness, excellent response, and tolerability of galcanezumab in patients ≥65 years and those younger than 65 years, specifically assessing age as a predictor of response. METHODS:This real-life, multicenter cohort study included patients with chronic or high-frequency episodic migraine who did not respond to more than or equal to three preventive drugs, treated with galcanezumab, and followed for 12 months from 12 Spanish hospitals, between November 2019 and January 2022. Effectiveness was defined as ≥50% reduction in monthly headache days (MHD), and excellent response as ≥75% reduction at 6 months. Tolerability was based on the percentage of patients discontinuing due to adverse events. RESULTS:We included 1055 patients (934 patients <65 years, 121 patients ≥65 years). Older patients had higher baseline MHD [25 (interquartile range [IQR] 15-30) vs. 20 (14-30), p = 0.045], but lower HIT-6 scores [67 (IQR 63-72) vs. 69 (66-73), p < 0.001]. Effectiveness was similar across age groups at 3 (57.0% vs. 48.8%, p = 0.090), 6 (57.0% vs. 51.8%, p = 0.281), and 12 months (52.1% vs. 51.4%, p = 0.889). However, excellent response was more frequent in the ≥65 years group at 3 months (32.2% vs. 23.1%, p = 0.028) and 6 months (33.9% vs. 23.5%, p = 0.012), with a non-significant difference at 12 months (33.1% vs. 25.4%, p = 0.071). Tolerability was comparable within age groups (5.8% discontinuation due to adverse effects in patients ≥65 years vs. 6.7% in patients <65 years; p = 0.837). Age was independently associated with effectiveness (adjusted odds ratio [aOR]: 1.02; 95% confidence interval [CI]: 1.004-1.03) and excellent response (aOR: 1.02; 95% CI: 1.01-1.04). A statistically significant association was found in the logistic regression model for excellent response when age was dichotomized at 65 years, with increasing age linked to a higher likelihood of an excellent treatment response (aOR: 1.79; 95% CI: 1.13-2.82, p = 0.012). CONCLUSIONS:Galcanezumab is as effective and well-tolerated in patients aged ≥65 years as in younger patients but older patients showed a higher rate of excellent response. Age is associated with a better response to galcanezumab.

Preclinical evidence supports the immunoregulatory role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology. The increasing use of anti-CGRP therapies in patients with migraine and other comorbidities raises the question whether the potential use of anti-CGRP monoclonal antibodies (CGRP-mAbs) therapies in combination with other immunological therapies is effective and safe. This multicenter study included patients with migraine receiving CGRP-mAbs combined with immunosuppressive and immunomodulatory treatments. Clinical and demographic data, treatment history, laboratory markers and treatment-emergent adverse events (TEAEs) were analyzed. Effectiveness outcomes included the change in monthly migraine days (MMD) and monthly headache days (MHD) at 3, 6, 9 and 12 months, alongside the > 50

Abstract Background The relationship between physical activity (PA) and migraine is insufficiently understood. Studies have not analysed levels of PA or Time Sitting (TS) during preventive treatment, nor the role these might play in the response to preventive treatment. Methods An observational, longitudinal prospective study in a headache clinic was conducted. All consecutive chronic migraine patients initiating fremanezumab were invited to participate and were followed for three visits. The International Physical Activity Questionnaire (IPAQ) - long version was used. Results Seventy-six patients with a median of 46 years old, 84.2% female were enrolled. One month after fremanezumab administration, there was a significant increase of most PA variables and a significant decrease in TS levels compared with baseline; headache days and walking, TS and migraine days showed a moderate correlation. Three months after initiation, all PA variables statistically increased and TS levels statistically decreased, and variables such as headache/migraine days showed a moderate correlation with all PA variables analysed. In the multivariate analysis, higher levels of walking at baseline were independently associated with response to fremanezumab (ORa: 1.194; CI: 1.018–1.401, p = 0.029). Conclusion Patients who spent more time walking before starting treatment, were more likely to have a response to fremanezumab. PA and TS levels changed since the first month and correlated with clinical variables.

BackgroundReal-world studies have shown the sustained therapeutic effect and favourable safety profile of OnabotulinumtoxinA (BoNTA) in the long term and up to 4 years of treatment in chronic migraine (CM). This study aims to assess the safety profile and efficacy of BoNTA in CM after 5 years of treatment in a real-life setting.MethodsWe performed a retrospective chart review of patients with CM in relation to BoNTA treatment for more than 5 years in 19 Spanish headache clinics. We excluded patients who discontinued treatment due to lack of efficacy or poor tolerability.Results489 patients were included [mean age 49, 82.8% women]. The mean age of onset of migraine was 21.8 years; patients had CM with a mean of 6.4 years (20.8% fulfilled the aura criteria). At baseline, patients reported a mean of 24.7 monthly headache days (MHDs) and 15.7 monthly migraine days (MMDs). In relation to effectiveness, the responder rate was 59.1% and the mean reduction in MMDs was 9.4 days (15.7 to 6.3 days; p < 0.001). The MHDs were also reduced by 14.9 days (24.7 to 9.8 days; p < 0.001). Regarding the side effects, 17.5% experienced neck pain, 17.3% headache, 8.5% eyelid ptosis, 7.5% temporal muscle atrophy and 3.2% trapezius muscle atrophy. Furthermore, after longer-term exposure exceeding 5 years, there were no serious adverse events (AE) or treatment discontinuation because of safety or tolerability issues.ConclusionTreatment with BoNTA led to sustained reductions in migraine frequency, even after long-term exposure exceeding 5 years, with no evidence of new safety concerns.

BACKGROUND AND PURPOSE:Anti-calcitonin gene-related peptide (CGRP) therapies are recent preventive therapies approved for both episodic and chronic migraine. One of the measures of effectiveness is the withdrawal of other preventive treatments. The objective of this study is to quantify the impact of anti-CGRP drugs in concomitant preventive treatment in patients with migraine. METHODS:This was an observational, retrospective, multicenter cohort study with patients from nine national headache units. Patients with migraine undergoing treatment for at least 6 months with anti-CGRP antibodies, who were initially associated with some preventive treatment (oral and/or onabotulinumtoxinA) were included. Demographic and clinical variables were collected, as well as variables related to headache. Differences according to withdrawal or nonwithdrawal were evaluated. RESULTS:A total of 408 patients were included, 86.52% women, 48.79 (SD = 1.46) years old. Preventive treatment was withdrawn in 43.87% (179/408), 20.83% partially and 23.04% totally. In 27.45% (112/408), it was maintained exclusively due to comorbidity and in 28.6% (117/408) due to partial efficacy. The most frequent time of withdrawal was between 3 and 5 months after the start of treatment. The baseline characteristics associated with nonwithdrawal were comorbidities: insomnia, hypertension and obesity, chronic migraine, and medication overuse. In the multivariate analysis, the absence of high blood pressure, a greater number of preventive treatments at the start, and a lower number of migraine days/month after anti-CGRP treatment were independently associated with withdrawal of the treatment (p < 0.05). CONCLUSIONS:Anti-CGRP antibodies allow the withdrawal of associated preventive treatment in a significant percentage of patients, which supports its effectiveness in real-life conditions.