Primary Headache Research Articles (Page 1)

Background: Headache is a frequent symptom in children, which often leads to the execution of neuroradiological examinations and to finding of incidentalomas. In fact, headache is often attributed to primary headache, neurological disorder common in the developmental age. Recent widespread access to neuroradiological examinations has led to a consequent increase in the number of incidental brain lesions in children with headache. Methods: We conducted a retrospective study including 28 patients under 18 years with primary headache and incidental findings of suspected low-grade lesion at brain MRI. Data were collected on age, sex, headache characteristics. Neurological and fundus oculi evaluation were normal. All patients were treated conservatively with neuroimaging surveillance of suspected low-grade lesion. All lesions detected were defined as hyperintense in T2/FLAIR sequences, negative DWI, no increase, surrounding edema and mass effect. The lesions were divided into supratentorial (thalamic) and infratentorial (cerebellar). The first follow-up MRI was performed after 6 months and follow-ups were carried out every 12 to 18 months. Results: Patients included 13 females (46%) and 15 males (54%): 67.8% presented migraine without aura, 25% tensive headache, 14.3% migraine with aura, 7% both tensive headache and migraine without aura. Average frequency of attacks was 2.9 attack/month. Regarding intensity of attacks: 32% presented slight attack, 57% moderate and 11% had severe attacks. Average follow-up period was 43.7 months. In following period: 7% was stable at 84 months, 17.8% at 72 months, 21.5% at 60 months, 46.5% at 48 months, 64.3% at 36 months, 96.5% at 24 months. 96.5% of the patients showed radiological stability during the whole follow-up period. No significant radiological changes were found during follow-up in 27 of 28 patients. Conclusion: With the increasing detail of imaging techniques and their execution, there has been an increase in number of incidentally brain lesions in children with primary headache, leading to a management dilemma for pediatric neurologists. The incidentally low-grade lesions are not related to headache. This study reports data on long-term clinical and radiological follow-up period in patients with primary headache and occasional low-grade lesion findings during headache assessment, showing the stability over time and safety of conservative management.

Background: Primary headaches are common in pediatric age and can significantly impact children's quality of life especially when they have a high frequency. Best practices in headache management involve a multidisciplinary approach combining pharmacological and non-pharmacological strategies. Among the latter, psychological interventions targeting cognitive, behavioral, and emotional factors have shown efficacy in reducing migraine-related pain, distress, and disability. Mindfulness is a recent behavioral approach that offers an effective option for adolescents with headache, helping reduce pain and disability by increasing awareness and teaching techniques alternative to medications. Methods: This is a prospective study involving patients aged 11–18 years, referred to four juvenile headache centers and meeting defined inclusion and exclusion criteria. Selected patients participated in eight weekly online 1-hour sessions of guided mindfulness-based meditation combined with education on healthy lifestyle habits to prevent or reduce the impact of headache. Follow-up assessments are scheduled at 3, 6 and 12 months, including clinical evaluations and standardized questionnaires completed by both patients and parents. Results: Twenty-eight adolescents with frequent primary headaches (migraine or tension-type headache) were enrolled. The intervention demonstrated good feasibility with high participation and adherence rates to the weekly sessions. Only 3 participants have dropped out, with an overall adherence rate of 89.3%. No significant side effects were reported; in one case, dropout was due to increased anxiety. In preliminary analysis, patients reported a subjective impression of global improvement. We expect positive changes in standardized tests at 3, 6 and 12-months follow up. Conclusion: This study investigated a well-tolerated, promising and feasible behavioral intervention for adolescents with high-frequency primary headaches. Our preliminary results showed high compliance and favorable disease progression in our population, demonstrating that mindfulness (made online in small groups) is a valuable and safe approach in adjunct to preventive drugs.

Background: The role of alcoholic drinks as a migraine trigger has been repeatedly debated and reviewed. A notable discrepancy has been highlighted regarding the frequency and triggering role of the various types of primary headache. Many factors may affect the reliability of survey data, including the headache classification by the International Headache Society (IHS) and the type of studies (generally retrospective). The objective of this update was to evaluate whether recent studies concerning the controversial relationship between alcoholic drinks (AD) and headache had brought confirmation or innovation. Methods: Prospective studies concerning the triggering role of AD, vasodilation as a possible mechanism, alcohol consumption, the effect of alcohol infusion, and the role of alcohol-induced analgesia were evaluated and discussed. Results and Conclusion: This update reports many recent prospective studies confirming the limited role of AD as a triggering factor. Furthermore, the lower consumption of AD in migraine patients is once again and definitively highlighted by recent studies, and it is discussed whether this is due to reverse causality. Since many substances have been tested to provoke migraine and correlate with cerebrovascular dilatation, it is once again underlined why ethanol, a natural trigger with vasodilating properties, has not been tested until now in migraine patients. Some studies show that ethanol infusion does not provoke headache within 5 to 8 hours, but only a delayed hangover headache in some subjects. Finally, since alcohol analgesia is used as self-medication and moderate alcohol consumption may be associated with a decreased likelihood of developing chronic pain, it is debated why this does not happen in migraineurs.

Chronic migraine (CM) is a common primary headache occurring on 15 or more days per month and for more than three months. It presents a considerable therapeutic challenge. Botulinum toxin (BoNT) has emerged as a promising treatment for CM, particularly in patients unresponsive to standard pharmacological therapy or experiencing adverse effects. Its therapeutic benefit is based on blocking the release of nociceptive neuropeptides modulating pain pathways. Clinical efficacy and safety of BoNT have been demonstrated in multiple randomized controlled CM trials showing a significant reduction of headache frequency. This review provides an overview of efficacy and safety of BoNT for CM.

Risk of depression and suicide in adults with pre-existing primary headaches.

Primary headaches as the reason for consultation in Primary Care: a prospective study.

Migraine and tension-type headache in multiple sclerosis: A two-year, prospective, longitudinal, controlled study.

Mediation analysis of anxiety and depression between alexithymia and frequency of headache attacks and impact on suicidal ideation in primary headache.

What do I need to know about headaches if I am a Primary Care doctor?

Neuroimaging and Diagnostic Workup for Headache.

Clinical History and Examination of Headaches.

Migraine.

Dipyrone induces sex-dependent latent sensitization in a preclinical model of medication overuse headache.

A Comprehensive Review of Trigeminal Autonomic Cephalalgias.

Medication Overuse Headache.

AimHeadache is one of the most frequent somatic complaints in psychiatric practice and is often attributed to underlying mental disorders. However, primary headache disorders—particularly migraine and tension‐type headache (TTH)—commonly coexist with psychiatric conditions. Evidence from psychiatric outpatient settings remains limited.MethodsWe conducted a retrospective chart review of all psychiatric outpatients who visited our 600‐bed regional general hospital between April 1, 2023, and March 31, 2024. Among 2525 patients, we identified 360 individuals with headache‐related insurance diagnoses and extracted data on headache labels, treating departments, and prescribed medications. For calcitonin gene–related peptide (CGRP)‐targeted monoclonal antibodies, we extended the observation period to March 31, 2025, to describe an exploratory case series including additional prescriptions.ResultsOf 2525 psychiatric outpatients, 360 (14.3%) carried a headache‐related insurance diagnosis. The most frequent labels were “headache” (203/360, 56.4%), migraine (92/360, 25.6%), and TTH (46/360, 12.8%); cluster headache and medication‐overuse headache (MOH) were each recorded in 1/360 (0.3%). Headache care was most often delivered within psychiatry (153/360, 42.5%), followed by neurology (42/360, 11.7%), neurosurgery (40/360, 11.1%), general internal medicine (28/360, 7.8%), and rheumatology/collagen‐vascular disease (15/360, 4.2%). Commonly documented agents included nonsteroidal anti‐inflammatory drug (NSAIDs) (40/360, 11.1%), acetaminophen (38/360, 10.6%), triptans (23/360, 6.4%), Japanese Kampo formulas (16/360, 4.4%), and CGRP monoclonal antibodies (6/360, 1.7%). At the agent level, acetaminophen (n = 38), loxoprofen (n = 33), zolmitriptan (n = 14), goreisan (n = 8), sumatriptan (n = 6), kakkonto (n = 6), diclofenac (n = 4), valproic acid (n = 4), and naratriptan (n = 3) were among the most frequently listed. In the exploratory CGRP analysis (total seven patients through March 31, 2025), six were women; the mean age was 48.4 ± 9.2 years. Psychiatric comorbidities were heterogeneous, including eating disorder, bipolar disorder, post‐traumatic stress disorder, dysthymia with social anxiety disorder, schizophrenia, autism spectrum disorder, and neurotic depression. All cases experienced headache improvement; two required switching to another CGRP agent for recurrent attacks yet maintained benefit. One patient temporarily discontinued due to a rash before resuming a different CGRP agent. In contrast, medium‐term changes in mood/anxiety were limited.ConclusionIn a psychiatric outpatient cohort, primary headaches were common and frequently managed within psychiatry. CGRP‐targeted therapy yielded headache relief even under psychiatric comorbidity, while psychiatric symptoms did not uniformly improve, underscoring the need for parallel mental‐health interventions alongside headache‐specific care. Strengthening cross‐specialty pathways and early headache evaluation within psychiatry are warranted.

The role of Epstein-Barr virus (EBV) in multiple sclerosis (MS) pathogenesis is supported by the increased MS risk after infectious mononucleosis. This study aimed to evaluate EBV infection in our pediatric-onset MS (POMS) cohort. MS patients with disease onset < 18years of age seen at Bambino Gesù Children's Hospital were included. We searched for anti-EBV nuclear antigen (EBNA) Immunoglobulin G (IgG) and anti-viral capsid antigen (VCA) IgG and IgM. For comparison, we analyzed the EBV infection seroprevalence in an age- and sex-matched control cohorts of immunologically-healthy children and subjects with non-neurological autoimmune diseases. Fifty-seven POMS were included; all had a previous EBV infection. The controls' cohort included one-hundred and sixty-two patients with a median age of 12years (range 6-17), encompassing two subgroups: non-autoimmune (i.e. primary headaches) and autoimmune controls, namely inflammatory bowel disease and juvenile idiopathic arthritis. In the control group, ninety-six (59%) were EBV seropositive. EBV seropositivity was significantly higher in POMS than in the controls' cohort (OR = 79.2, 95% C.I. 4.8-1305), and compared to autoimmune and non-autoimmune controls separately (p < 0.0001). In our POMS cohort, EBV seropositivity was 100%, higher than previously reported. Our results support a disease-specific role of EBV in the MS development compared to other pediatric autoimmune disorders, consistent with evidence reported in adult-onset MS.

Migraine, a primary headache disorder, is the third disabling disease of neurological disorders worldwide. The pathological mechanism underlying migraine remains poorly understood. Lipid metabolism may be related to migraine pathophysiology. We aimed to investigate the causal relationship between plasma lipids and migraine or its subtypes, including migraine with aura (MA) and migraine without aura (MO), and explore whether the circulating cytokines serve as mediators in the pathway from plasma lipids to migraine. A two-step Mendelian randomization (MR) approach was used to assess the mediating effect. The summary genetic data for 179 lipid species were obtained from were derived from a genome-wide association studies (GWAS) summary dataset encompassing 7,174 individuals. The summary genetic data for 91 circulating cytokines were obtained from genome-wide pQTL mapping data. The summary genetic data of GWAS related to migraine and its subtypes were derived from the FinnGen Release 10 database. The MR Analysis methods included the inversevariance- weighted (IVW), MR-Egger, and weighted median. The risk of migraine was reduced mediated by CD5 with phosphatidylinositol (18:1_18:2), sphingomyelin (d34:1), and sphingomyelin (d38:1). The risk of migraine and MA was reduced mediated by CD6 with sphingomyelin (d40:1) and sphingomyelin (d42:2). The risk of migraine and MA was increased mediated by CD6 with phosphatidylethanolamine (O- 16:1_18:2). CD5 and CD6 were found to be related to migraine. CD5 and CD6 may affect migraine by immunological dysregulation-induced neuroinflammation. Six plasma lipids are associated with two cytokines, indicating that lipid metabolism participates in neuroinflammation, and T cells may be part of it. Plasma levels of lipids were associated with the risk of migraine. The circulating cytokines may serve as mediators in the pathway from plasma lipids to migraine. CD5 and CD6 appeared to mediate the causal relationship between plasma lipids and migraine or MA, including four kinds of sphingomyelin, one phosphatidylinositol, and one phosphatidylethanolamine.

Introduction: Primary headache is a neurological disorder not caused by structural abnormalities or other medical conditions. It affects people globally and can occur across different ages, genders, and socioeconomic backgrounds. Objective: This study aims to describe the demographic and clinical profile of patients diagnosed with primary headache at the Tanjung Priok Health Center during January–December 2023. Method: A descriptive cross-sectional approach was used. Data were collected through a total sampling technique based on patient medical records. A total of 125 patients met the inclusion criteria. Result and Discussion: The most prevalent diagnosis was tension-type headache, accounting for 74.4% of cases. Most patients were female (61.6%) and aged between 31 and 60 years (51.2%). Housewives represented the largest occupational group (52.8%). Medication was the most frequently used treatment (90.4%). These findings suggest that hormonal, lifestyle, and psychosocial factors may contribute to the higher prevalence among adult women. Conclusion: Tension-type headache was the dominant form of primary headache. Most cases occurred in women aged 31–60 years, predominantly housewives, with medication being the main therapeutic option.

The aim of this case series is to describe a clinical phenotype of midfacial pain and suggest its potential as a candidate for future iterations of headache and facial pain classifications. Patients with facial pain that is located in the middle part of the face often consult otorhinolaryngologic, neurologic, or pain specialists. In the past, a diagnosis of midfacial pain was suggested if other causes were excluded. This case series is based on a retrospective analysis of patients consulted in two headache and facial pain centers. The patients were selected if the pain was located in the zygomatic, infraorbital, or nasal region, and rhinosinusitis and other primary or secondary facial pain syndromes were excluded during a comprehensive diagnostic process. Twelve patients in the 18-74 years age group (median, 40.5 years; interquartile range [IQR], 18.3; 4 of 12 [33%] patients were women), from two tertiary headache and facial pain centers in Warsaw and Hamburg were included in the case series based on consultations conducted between January 1, 2024, and December 31, 2024. Patients reported 20-30 (median, 30; IQR, 2.8; mean = 28.1; standard deviation, 3.2) monthly facial pain days of mostly moderate intensity (range from 1 to 9; median, 5; IQR, 2.125; mean = 5.2; SD, 1.9) on Numeric Rating Scale. Pain was described as dull, pressing, or tension-like and was bilateral in 10 of 12 (83%) patients. Seven of 12 (58%) patients described pain occurring simultaneously in regions innervated by the first (nasal region) and second branch (infraorbital) of the trigeminal nerve. This study provides preliminary evidence for a distinct phenotype of idiopathic midfacial pain that is not caused by rhinosinusitis, stomatognathic disorders, or facial manifestations of primary headaches. Our data call for prospective studies on this type of idiopathic facial pain for future International Classification of Headache Disorders and International Classification of Orofacial Pain editions.