Background: Diagnosing headache disorders poses significant challenges, particularly in primary and secondary levels of care (PSLC), potentially leading to misdiagnosis and underdiagnosis. This study evaluates diagnostic agreement for migraine, tension-type headache (TTH), and cluster headache (CH) between PSLC and tertiary care (TLC) and assesses adherence to the International Classification of Headache Disorders 3rd edition (ICHD-3) guidelines. Methods: A retrospective, cross-sectional analysis was conducted at Charité - Universitätsmedizin Berlin’s tertiary headache center. The patients’ self-reported diagnoses from the PSLC were compared with those in TLC and with ICHD-3 criteria. Cohen’s kappa (κ) and R² were used to assess diagnostic agreement. Results: Among 1,468 patients (43.4 ± 14.4 years; 74.5% women), 69.5% reported a diagnosis in PSLC, and 99.5% were diagnosed at their first TLC visit. Overall agreement between PSLC and TLC was 80% (κ = 0.55; R²=30%). Agreement between the PSLC and ICHD-3 was 77% for migraine, 82% for TTH, and 96% for CH (κ = 0.65; R²=41%). TLC diagnoses aligned with ICHD-3 in over 90%. Conclusion: Our findings indicate a significant degree of diagnostic agreement across different levels of care according to the ICHD-3 guidelines. However, there remains insufficient reliability in clinical diagnostics, highlighting the need for continued efforts to improve the early recognition and diagnostic accuracy and consistency of primary headaches to optimize patient care and treatment outcomes in Germany.

Chronic migraine (CM) affects approximately 2% of the general population and is defined by the persistence of migraine symptoms for at least 15 days per month for at least 3 months. CM is often refractory to common drug treatments and is associated with a significant burden in functions of daily life during ictal phases, productivity loss, and direct costs. Modulation of pain is considered pivotal to reduce its impact and to improve the quality of life among patients with CM. In recent years, neuromodulation in CM has received growing attention; however, there remains no consensus regarding the effectiveness and safety of these procedures. Previous invasive methods such as occipital nerve neurolysis and interruption of the trigeminal dorsal root are not indicated due to high rates of relapsing pain and frequent procedural complications. Although emerging neuromodulation methods, both noninvasive, such as vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS), remote electrical neuromodulation (REM), and invasive, such as deep brain stimulation (DBS), occipital nerve stimulation (ONS), and high-frequency 10-Hz spinal cord stimulation (HF-10 SNS) have demonstrated promising outcomes in early clinical trials, their use has yet to be integrated into routine clinical practice. In this review, study evidence and strength of recommendations are assessed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Other conditions such as therapeutic risk/benefit, direct and indirect costs, use of resources, and patient/clinician preferences are also evaluated.

Migraine significantly impairs quality of life, reduces workplace productivity, and imposes a substantial socio-economic burden. The severity of migraine correlates with its impact on quality of life and healthcare costs, emphasizing the need for adequate management. In the past, primary care services often faced issues of inadequate treatment. This study evaluates differences in pharmacological recommendations for acute and preventive migraine treatments across primary, secondary, and tertiary care settings. This cross-sectional study involves patients with confirmed migraine (with or without aura) visiting the tertiary headache center at Charité Berlin between 12/2015 and 01/2023 for the first time. Data on headache characteristics and prior treatments for acute and prophylactic treatments at primary/secondary and recommendations from tertiary level of care were retrieved from medical letters written after first consultation. Among 1,047 migraine patients (42 years, 84% women), 99% had received treatment for acute migraine attacks by primary/secondary care facilities, and 96% were using it at their first consultation, with 63% advised to use a triptan. The average number of triptans tested prior to referral was 1 ± 0.99. Prophylactic treatment was prescribed to 52% of patients by primary/secondary care facilities, with an average of 1.2 ± 1.6 prior prophylactic attempts per patient, and 44% were actively using it at the time of consultation. More than two thirds of patients with over four monthly migraine days were not using prophylactic treatment at referral. Tricyclic antidepressants, beta-blocker and, anticonvulsants were prescribed significantly more often in primary/secondary care settings while Onabotulinumtoxin-A and Calcitonin Gene-Related Peptide(-receptor) antibodies were more commonly initiated in tertiary care. Treatment recommendations from primary/secondary settings were revised in 77% of patients following consultation at the tertiary headache clinic. Compared to previous studies, the overall prescription of acute and prophylactic therapies in primary and secondary care facilities has improved. Further progress is needed in expanding the range of triptans and prophylactic treatments tested before referring patients to specialized centers. However, given the selected study population, the findings may not be fully applicable to all patients treated in primary/secondary care, especially those already receiving adequate care without being referred to specialized settings.

Discontinuation of treatment with monoclonal antibodies (mAb) targeting the Calcitonin Gene-Related Peptide (CGRP) pathway leads to an increase in migraine frequency. We aimed to assess changes in free and total CGRP plasma concentrations after the discontinuation of CGRP(-receptor) mAbs. This prospective analysis included 59 patients with migraine (n = 25 erenumab, n = 25 galcanezumab, n = 9 fremanezumab) who discontinued mAbs after ≥8 months of treatment. Patients were visited at the time of the last mAb injection (V1) and 16 weeks later (V2). For control, 30 migraine patients without preventive drug therapy were included. We measured free CGRP plasma concentrations in the erenumab and fremanezumab group and total CGRP concentrations in the galcanezumab group. Free CGRP plasma concentrations did not change after treatment discontinuation [erenumab: V1 31.2 pg/mL (IQR 25.8–45.6), V2 30.3 pg/mL (IQR 22.9–47.6), p = 0.65; fremanezumab V1 29.4 pg/mL (IQR 16.4–61.9), V2 34.4 (19.2–62.0), p = 0.86]. Controls had similar CGRP values of 32.6 pg/mL (IQR 21.3–44.6). Total CGRP concentrations in the galcanezumab group were 5439.3 pg/mL (2412.7–6338.1) at V1, and decreased to 1853.2 pg/mL (1136.5–3297.0) at V2 (p < 0.001). Cessation of treatment with CGRP(-R) mAbs did not have an impact on the free-circulating CGRP concentrations. Total CGRP decreased significantly after three months of treatment discontinuation.

Hormonal contraception (HC) can influence the migraine burden and should be considered in the comprehensive management of women with migraine. In this study, we aim to investigate the influence of migraine and migraine aura on the prescribing behavior of combined oral contraception (COC) and progestogen monotherapy (PM) in gynecological outpatient care. From October 2021 to March 2022, we performed an observational, cross-sectional study using a self-administered online-based survey. The questionnaire was distributed by mail and e-mail among 11,834 practicing gynecologists in Germany using the publicly available contact information. A total of 851 gynecologists responded to the questionnaire, of whom 12% never prescribe COC in the presence of migraine. Further 75% prescribe COC depending on the presence of limiting factors such as cardiovascular risk factors and comorbidities. When deciding to start PM, migraine appears to be less relevant, as 82% prescribe PM without restrictions. In the presence of aura, 90% of gynecologists do not prescribe COC at all, while PM is prescribed in 53% without restrictions. Almost all gynecologists reported to be actively involved in migraine therapy by having already initiated (80%), discontinued (96%), or changed (99%) HC due to migraine. Our results reveal that participating gynecologists actively consider migraine and migraine aura before and while prescribing HC. Gynecologists appear cautious in prescribing HC in patients with migraine aura.