Álvaro Sierra-Mencía

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. 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. 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%). 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.

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. image

Background: Headache is a common symptom during acute viral infections, and its pathophysiology has been linked with the immune response to the virus. Headache is one of the most frequent symptoms of coronavirus disease 2019 (COVID-19), and it has been associated with a more efficient immune response and a better prognosis. The aim of this article is to evaluate whether vaccination could modify the clinical phenotype and the probability of developing persistent headache after acute COVID-19. Methods: A case–control study comparing the duration of the headache and the clinical phenotype between fully vaccinated individuals and non-vaccinated controls was conducted. Each case was matched with two controls that were paired by age, sex, and prior history of headache. Patients were evaluated by a physician that administered a structured questionnaire and were followed up for at least three months. Results: The sample included 103 cases and 206 controls, with a median age of 42 (inter-quartile range (IQR) 33–51); 68% were female; and 26% had a prior history of headache. Headache had a shorter duration for vaccinated patients (4 (IQR 2–8) vs. 8 (IQR 4–16.5) days, p < 0.001). Vaccinated patients had a higher frequency of holocranial topography, pressing quality, phonophobia, and cranial autonomic symptoms. Conclusions: Our results suggest that full vaccination modifies the clinical phenotype of COVID-19 onset-associated headache and might lead to a shorter duration. These findings could represent an additional benefit of COVID-19 vaccines, which could extend to the post-COVID-19 phase and decrease the probability of a persistent disabling symptom such as headache.

Introduction: Alcohol-induced headaches are one of the most prevalent types of headaches. The International Classification of Headache Disorders defined them as throbbing and bilateral, and their phenotype combines characteristics of migraines and headaches secondary to low cerebrospinal fluid pressure. We aimed to evaluate the factors associated with the presence of a headache as a hangover symptom. Methods: This was a prospective cohort study, including 32 healthy individuals who voluntarily consumed alcohol and completed self-administered questionnaires during three separate alcohol consumption and hangover episodes. Results: A headache was a hangover symptom in 55/96 (57.3%) episodes. The phenotype was predominantly holocranial (94.5%), frontal (98.2%), and pressing (67.2%), with a median intensity of 6 (IQR 4–8). Headaches worsened with physical activity (100%) and had orthostatic changes (89.1%). A prior history of headaches was associated with headache occurrence (odds ratio: 3.480; 95% confidence interval (CI): 1.084 to 11.177), and headache precipitation by standing up was associated with a shorter duration (hazard ratio: 0.257; 95% CI: 0.073 to 0.901). Conclusions: Delayed alcohol-induced headaches had a migraine-like phenotype. An orthostatic pattern suggestive of a low cerebrospinal fluid pressure was associated with a shorter duration of the headache.

Background: 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. Methods: 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% response rate. Moreover, autoimmune disease progression was also evaluated. We explored differences between patients with and without autoimmune disease activation. Results: Among 89 patients, there were 80 (90%) females with a mean age of 50 years (SD: 11), who had a high prevalence of psychiatric comorbidities (anxiety 44%, depression 49%) and medication overuse (68%). Patients receiving immunological treatments experienced significant reductions in MMD and MHD, with MMD decreasing from 16 (SD: 7) at baseline to 9 (SD: 8) at 6 months, and MHD dropping from 23 (SD: 8) to 17 (SD: 11). A 50% response in MMD was achieved by 46% at 6 months. TEAEs were reported in 28%, most commonly constipation (16%) and dizziness (9%). Conclusions: CGRP-mAbs therapies combined with immunological treatments appear effective and safe in patients with autoimmune diseases. Larger prospective studies are necessary to confirm these findings and optimize management strategies.

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 (OR_a: 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.

To describe the need and effectiveness of acute and preventive medications in a series of 100 consecutive patients referred due to COVID-19-related headaches. Patients were aged 48.0 (standard deviation (SD): 12.4), 84% were female, and 56% had a prior history of headache. The most common headache phenotype was holocranial (63%), frontal (48%), pressing (75%), of moderate intensity (7 out of 10), and accompanied by photophobia (58%). Acute medication was required by 93%, with paracetamol (46%) being the most frequently used drug, followed by ibuprofen (44%). The drugs with the highest proportion of a 2 h pain-freedom response were dexketoprofen (58.8%), triptans (57.7%), and ibuprofen (54.3%). Preventive treatment was required by 75% of patients. The most frequently used drugs were amitriptyline (66%), anesthetic blockades (18%), and onabotulinumtoxinA (11%). The drugs with the highest 50% responder rate were amitriptyline (45.5%), mirtazapine (50%), and anesthetic blockades (38.9%). The highest 75% responder rate was experienced following onabotulinumtoxinA (18.2%). In conclusion, most patients required acute medication, with triptans and non-steroidal anti-inflammatory drugs achieving the best responses. Three-quarters of patients required preventive medication. The most frequently used drug was amitriptyline, which obtained the best results. In some treatment-resistant patients, anesthetic blockades and onabotulinumtoxinA were also beneficial.

Background and purpose: Influenza is a common cause of acute respiratory infection, with headache being one of the symptoms included in the European Commission case definition. The prevalence of headache as a symptom of influenza remains unknown. We aimed to describe the incidence and prevalence of headache in patients with influenza.Methods: All consecutive patients who met the definition criteria of influenza‐like illness during the influenza seasons 2010–2011 through 2021–2022 were included. The seasonal cumulative incidence of influenza per 1000 patients at risk and the prevalence of headache as an influenza symptom were calculated, including the 95% confidence intervals (CIs). Subgroup analyses were done based on patients' sex, age group, microbiological confirmation, vaccination status, and influenza type/subtype/lineage.Results: During the study period, 8171 patients were eligible. The incidence of headache in the context of influenza varied between 0.24 cases per 1000 patients (season 2020–2021) and 21.69 cases per 1000 patients (season 2017–2018). The prevalence of headache was 66.1% (95% CI = 65.1%–67.1%), varying between 49.6% (season 2021–2022) and 80.1% (season 2010–2011). The prevalence of headache was higher in women (67.9% vs. 65.7%, p = 0.03) and higher in patients between 15 and 65 years old. Headache was more prevalent in patients infected with B subtypes than A subtypes (68.7% vs. 56.9%, p < 0.001). There were no notable differences regarding vaccination status or microbiological confirmation of the infection.Conclusions: Headache is a common symptom in patients with influenza, with a prevalence higher than that observed in other viral infections.

Headache is a common symptom of influenza infection; however, its causes and consequences remain uncertain. In this manuscript, we analyzed which demographic and clinical factors were associated with the presence of headache during the course of influenza infection and whether patients with headache had a different prognosis, evaluated by need of hospitalization, sick leave or school absenteeism. The influence study (NCT05704335) was an observational study that analyzed data routinely collected from the Health Sentinel Network between 2010 and 2020. During the study period, 7832 cases were considered, among which, 5275 (67.4%) reported headache. The presence of headache was independently associated with myalgia (2.753; 95%CI: 2.456–3.087, P < 0.001), asthenia (OR: 1.958; 95%CI: 1.732–2.214, P < 0.001), shivering (OR: 1.925; 95%CI: 1.718–2.156, P < 0.001), nasopharyngeal erythema (OR: 1.505; 95%CI: 1.293–1.753, P < 0.001), fever (OR: 1.469; 95%CI: 1.159–1.861; P = 0.001), sudden onset of symptoms (OR: 1.380; 95%CI: 1.120–1.702, p = 0.004), female sex (OR: 1.134; 95%CI: 1.023–1.257, P = 0.018), and gastrointestinal symptoms (OR: 1.169; 95%CI: 1.039–1.315; P = 0.01). Patients with headache had a sex and age adjusted lower odds of being referred to the hospital (OR: 0.463; 95%CI: 0.264–0.812, P = 0.007) and a higher odd of having a sick leave and/or school absenteeism (absenteeism (OR: 1.342; 95%CI: 1.190–1.514, P < 0.001). In conclusion, the presence of headache seems associated with symptoms caused by the innate immune response. These findings support a headache pathophysiology linked with the innate immune response. Due to the potential negative consequences and its treatable nature, clinicians should systematically evaluate it and, whenever necessary, treat it too.