Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world.

BACKGROUND: Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months. METHODS: European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as ≥50% and ≥75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response. RESULTS: Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models. CONCLUSIONS: This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success.

[Trigeminal neuralgia: drug therapy : The new German guideline]. / Medikamentöse Therapie der Trigeminusneuralgie : Die neue Leitlinie.

Trigeminal neuralgia is characterized by severe, lightning-like attacks of pain, which are mandatory for the diagnosis. The pain typically occurs on one side and is often triggered by simply touching the face, chewing or talking. In acute exacerbations, this can also hinder food and fluid intake, resulting in a life-threatening clinical picture. A distinction is made between classical, secondary and idiopathic trigeminal neuralgia. For the diagnosis of trigeminal neuralgia, the medical history and imaging procedures are key for classification. The only active substances approved for the treatment of trigeminal neuralgia in Germany are carbamazepine and phenytoin, which is why off-label drugs often need to be used if there is no or insufficient effect or inacceptable side effects. Cooperation between research and clinical practice to improve the care of affected patients is therefore essential.

[Migraine and psychosomatic comorbidity]. / Migräne und psychosomatische Komorbiditäten.

As a common neurological disorder (10-15% of the population), migraine is associated with numerous comorbidities, particularly other pain syndromes, mental illnesses and functional disorders. These 'psychosomatic' comorbidities increase with migraine severity. Severely affected, comorbid patients also often have a poorer response to specific migraine therapy. Interestingly, migraine and the comorbidities mentioned have a number of common aetiological or facilitating factors, e.g. genetic factors, and show a higher incidence in women and in people with previous traumatic experiences, as well as (in the case of pain syndromes) signs of central sensitization. Another common feature is the association with current or chronic stress. We propose an extended diathesis-stress model that takes into account interrelated but individually different vulnerabilities and, depending on the stress experience, can depict both the occurrence of individual disorders (e.g. an isolated migraine) and the joint occurrence of migraine with other pain syndromes and other psychosomatic comorbidities. In summary, psychosomatic comorbidities should always be kept in mind in migraine therapy and, if necessary, treated early and multimodally.

Longitudinal changes in human supraspinal processing after RIII-feedback training to improve descending pain inhibition.

The human body has the ability to influence its sensation of pain by modifying the transfer of nociceptive information at the spinal level. This modulation, known as descending pain inhibition, is known to originate supraspinally and can be activated by a variety of ways including positive mental imagery. However, its exact mechanisms remain unknown. We investigated, using a longitudinal fMRI design, the brain activity leading up and in response to painful electrical stimulation when applying positive mental imagery before and after undergoing a previously established RIII-feedback paradigm. Time course analysis of the time preceding painful stimulation shows increased haemodynamic activity during the application of the strategy in the PFC, ACC, insula, thalamus, and hypothalamus. Time course analysis of the reaction to painful stimulation shows decreased reaction post-training in brainstem and thalamus, as well as the insula and dorsolateral PFC. Our work suggests that feedback training increases activity in areas involved in pain inhibition, while simultaneously decreasing the reaction to painful stimuli in brain areas related to pain processing, which points to an activation of decreased spinal nociception. We further suggest that the insula and the thalamus may play a more important role in pain modulation than previously assumed.

Effects of Transcranial Direct Current Stimulation (t-DCS) of the Cerebellum on Pain Perception and Endogenous Pain Modulation: a Randomized, Monocentric, Double-Blind, Sham-Controlled Crossover Study.

Accumulating evidence demonstrates a role of the cerebellum in nociception. Some studies suggest that this is mediated via endogenous pain modulation. Here, we used t-DCS to test the effects of modulation of cerebellar function on nociception and endogenous pain modulation. Anodal, cathodal, and sham cerebellar t-DCS were investigated in a cross-over design in 21 healthy subjects. The nociceptive flexor (RIII) reflex, conditioning pain modulation (CPM), and offset analgesia (OA) paradigms were used to assess endogenous pain modulation. Somatosensory evoked potentials (SEPs) and pain ratings were used to assess supraspinal nociception and pain perception, respectively. No significant t-DCS effects were detected when including all t-DCS types and time points (baseline, 0, 30, 60 min post t-DCS) in the analysis. Exploratory analysis revealed an increased RIII reflex size immediately after cathodal t-DCS (compared to sham, P = 0.046, η2p = 0.184), in parallel with a trend for a decrease in electrical pain thresholds (P = 0.094, η2p = 0.134), and increased N120 SEP amplitudes 30 min after cathodal compared to anodal t-DCS (P = 0.007, η2p = 0.374). OA was increased after anodal compared to sham stimulation (P = 0.023, η2p = 0.232). Exploratory results suggested that cathodal (inhibitory) cerebellar t-DCS increased pain perception and reduced endogenous pain inhibition while anodal (excitatory) t-DCS increased endogenous pain inhibition. Results are principally compatible with activation of endogenous pain inhibition by cerebellar excitation. However, maybe due to limited t-DCS skull penetration, effects were small and unlikely to be clinically significant.

What do patients' efficacy and tolerability ratings of acute migraine medication tell us? Cross-sectional data from the DMKG Headache Registry.

BACKGROUND: Most migraine patients need an effective acute medication. Real-world data can provide important information on the performance of acute migraine medication in clinical practice. METHODS: We used data from the German Migraine and Headache Society Headache Registry, where patients rate efficacy and tolerability of and satisfaction with each of their acute headache medications. RESULTS: A total of 1756 adult migraine patients (females: 85%, age: 39.5 ± 12.8 years, headache days per month: 13.5 ± 8.1) were included. Of these, 93% used acute medication, most frequently triptans (59.3%) and/or non-opioid analgesics (56.4%), and 58.5% rated efficacy as good or very good. This was more frequent for triptans (75.4%) than for non-opioid analgesics (43.6%, p < 0.001). Among non-opioid analgesics, naproxen was rated most effective (61.9% very good or good, p < 0.001 compared to ibuprofen, acetylsalicylic acid and paracetamol). Patient-rated efficacy significantly declined with higher headache frequencies (p < 0.001), and this effect remained significant after omitting patients overusing acute medication. CONCLUSION: In the present population recruited at specialized headache centers, patients rated triptans as more effective than non-opioid analgesics, naproxen as more effective than ibuprofen, and acute medication efficacy decreased with increasing headache frequency.Trial registration: The German Migraine and Headache Society Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081).

[Headache associated with COVID-19 vaccination: how to classify?] / COVID-19-Impfung-assoziierte anhaltende Kopfschmerzen: Wie einordnen?

INTRODUCTION: In the setting of acute COVID-19 infection, headache occurs in 10-60% of patients and may last for days and, in a smaller proportion of patients, weeks (about 10%). However, it is less recognized that headache may also occur after vaccination with a short latency and may persist for a longer period in a still unclear number of patients. METHODS: Retrospective description of headache and course in a case series of 32 outpatients with headache that changed or recurred after COVID-19 vaccination. RESULTS: The majority of patients experienced an exacerbation of migraine headache; rare headache syndromes such as intracranial hypertension or thunderclap headache occurred in 2 patients. Headache manifested in more than 50% of patients within the first 48 h after vaccination. Over 50% of patients who received a triptan improved. CONCLUSION: The pathophysiological relationship between vaccination and persistent headache is not yet clearly understood. The short latency, partial efficacy of cortisone, and initial findings showing an increase of various inflammatory markers during the course of headache in COVID infection suggest a possible involvement of the innate immune system and here the inflammasome. Furthermore, the response to triptan in a proportion of patients also indicates activation of the trigeminovascular system.

[Consensus statement of the migraine and headache societies (DMKG, ÖKSG, and SKG) on the duration of pharmacological migraine prophylaxis]. / Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe.

Migraine is the most common neurological disorder and can be associated with a high degree of disability. In addition to non-pharmacological approaches to reduce migraine frequency, pharmacological migraine preventatives are available. Evidence-based guidelines from the German Migraine and Headache Society (DMKG), and German Society for Neurology (DGN), Austrian Headache Society (ÖKSG), and Swiss Headache Society (SKG) are available for indication and application. For therapy-relevant questions such as the duration of a pharmacological migraine prevention, no conclusions can be drawn from currently available study data. The aim of this review is to present a therapy consensus statement that integrates the current data situation and, where data are lacking, expert opinions. The resulting current recommendations on the duration of therapy for pharmacological migraine prophylaxis are shown here.

[Consensus statement of the migraine and headache societies (DMKG, ÖKSG, and SKG) on the duration of pharmacological migraine prophylaxis]. / Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe.

Migraine is the most common neurological disorder and can be associated with a high degree of disability. In addition to non-pharmacological approaches to reduce migraine frequency, pharmacological migraine preventatives are available. Evidence-based guidelines from the German Migraine and Headache Society (DMKG), and German Society for Neurology (DGN), Austrian Headache Society (ÖKSG), and Swiss Headache Society (SKG) are available for indication and application. For therapy-relevant questions such as the duration of a pharmacological migraine prevention, no conclusions can be drawn from currently available study data. The aim of this review is to present a therapy consensus statement that integrates the current data situation and, where data are lacking, expert opinions. The resulting current recommendations on the duration of therapy for pharmacological migraine prophylaxis are shown here.

Effects of Introvision, a self-regulation method with a mindfulness-based perception technique in migraine prevention: a monocentric randomized waiting-list controlled study (IntroMig Study).

BACKGROUND: Migraine is a brain disorder with recurrent headache attacks and altered sensory processing. Introvision is a self-regulation method based on mindfulness-like perception techniques, developed at the University of Hamburg. Here, we examined the effect of Introvision in migraine prevention. METHODS: Migraineurs with at least five headache days per month were block-randomized to the experimental group (EG) or waiting list group (WL), the latter starting Introvision training six weeks after the EG. Participants learned Introvision in six weekly on-site group sessions with video-conference support followed by three individual video-conference sessions. Headache diaries and questionnaires were obtained before Introvision training and three months after the last individual Introvision session. RESULTS: Fifty-one patients completed the study. The primary outcome, headache days of the EG after Introvision training compared to those of the WL before the training, showed no significant effect (10.6 ± 7.7, n = 22; vs. 10.9 ± 6.3, n = 29, p = 0.63; Mann-Whitney-U-Test). The secondary outcome, comparing pooled EG and WL data before and after Introvision training, revealed a significant reduction of headache days (from 11.7 ± 6.5 to 9.8 ± 7.0; p = 0.003; Wilcoxon-paired-Test) as well as of acute medication intake and Headache-Impact-Test 6 (HIT-6) scores and increased self-efficacy as quantified by increased FKMS-scores (FKMS: german short form of the Headache Management Self-Efficacy Scale (HMSE)). CONCLUSION: Although the study did not reach its primary endpoint, several secondary outcome parameters in the pooled (non-controlled) pre-post analysis showed an improvement with a decrease in monthly headache days by 1.9 days/ month. A larger randomized controlled trial has to corroborate these preliminary findings. TRIAL REGISTRATION: NCT03507400, Registration date 09.03.2018.

Headache impact and socioeconomic status: findings from a study of the German Migraine and Headache Society (DMKG).

BACKGOUND: Headache disorders are not only among the most prevalent, they are also among the most disabling disorders worldwide. This paper investigates the association between headache impact on daily life and the socioeconomic status (SES) of headache sufferers. METHODS: Data stem from a random general population sample in Germany. Respondents who reported having headache for at least a year and were aged ≥ 18 years were included in the study. A standardized questionnaire addressing headache and headache treatment was filled in during the face-to-face survey. The impact of headache on daily life was measured using the German version of the Headache Impact Test (HIT-6). RESULTS: Higher headache impact was found in low and medium SES compared to high SES. After adjustment for sociodemographics, headache-related factors (analgesic use, headache duration, headache frequency, migraine diagnosis), depressive symptoms, physical inactivity and obesity, an increased odds ratio of having higher headache impact in low SES compared to high SES was found: OR = 1.83, 95% CI [1.43, 2.23], p = .014. When the interactions "SES*obesity", "SES*depressive symptoms", and "SES*physical inactivity" were added, the results showed a significant interaction effect of "SES*obesity". Obese persons with low SES were 3.64 times more likely to have higher headache impact than non-obese persons with low SES. No significant differences between obese and non-obese persons were found in the medium and high SES groups. CONCLUSIONS: SES is an important factor that should not be neglected in headache awareness campaigns and headache treatment. Longitudinal studies are needed in the future to investigate whether lifestyle interventions, such as weight reduction, can help to reduce headache impact in people in lower SES.

Health equity, care access and quality in headache - part 2.

BACKGROUND: Headache disorders are a global public health concern affecting diverse populations. This review examines headache service organizations in low-, middle-, and high-income countries. It addresses global challenges in pharmacological headache treatment, with a focus on safety, tolerability, reproductive and child health, and outlines disparities in accessing innovative treatments worldwide. MAIN BODY: Organized headache services are essential due to the wide prevalence and varying severity of headache disorders. The tiered headache service model is globally recognized, although its implementation varies based on financial and workforce considerations. Headache burden affects well-being, causing disability, economic challenges, and work limitations, irrespective of location or income. All nations still require improved diagnosis and treatment, and the majority of countries face obstacles including limited access, awareness, economic barriers, and inadequate health policies. Provided adequate internet availability, telemedicine could help improve health equity by expanding access to headache care, since it can offer patients access to services without lengthy waiting times or extensive travel and can provide healthcare unavailable in underserved areas due to staff shortages. Numerous health disparities restrict global access to many headache medications, especially impacting individuals historically excluded from randomized controlled trials, such as those with cardiovascular and cerebrovascular conditions, as well as pregnant women. Furthermore, despite advancements in researching migraine treatments for young patients, the options for treatment remain limited. Access to headache treatment relies on factors like medication availability, approval, financial coverage, and healthcare provider expertise. Inadequate public awareness leads to neglect by policymakers and undertreatment by patients and healthcare providers. Global access discrepancies are exacerbated by the introduction of novel disease-specific medications, particularly impacting Asian, African, and Latin American nations excluded from clinical trials. While North America and Europe experience broad availability of migraine treatments, the majority of countries worldwide lack access to these therapies. CONCLUSIONS: Healthcare disparities, treatment access, and medication availability are concerning issues in headache medicine. Variations in national healthcare systems impact headache management, and costly innovative drugs are widening these gaps. Healthcare practitioners and experts should acknowledge these challenges and work towards minimizing access barriers for equitable global headache care in the future.

Triptan non-response in specialized headache care: cross-sectional data from the DMKG Headache Registry.

BACKGROUND: Triptans are effective for many migraine patients, but some do not experience adequate efficacy and tolerability. The European Headache Federation (EHF) has proposed that patients with lack of efficacy and/or tolerability of ≥ 2 triptans ('triptan resistance') could be considered eligible for treatment with the novel medications from the ditan and gepant groups. There is little data on the frequency of 'triptan resistance'. METHODS: We used patient self-report data from the German Migraine and Headache Society (DMKG) Headache Registry to assess triptan response and triptan efficacy and/or tolerability failure. RESULTS: A total of 2284 adult migraine patients (females: 85.4%, age: 39.4 ± 12.8 years) were included. 42.5% (n = 970) had failed ≥ 1 triptan, 13.1% (n = 300) had failed ≥ 2 triptans (meeting the EHF definition of 'triptan resistance'), and 3.9% (n = 88) had failed ≥ 3 triptans. Compared to triptan responders (current use, no failure, n = 597), triptan non-responders had significantly more severe migraine (higher frequency (p < 0.001), intensity (p < 0.05), and disability (p < 0.001)), that further increased with the level of triptan failure. Responders rates were highest for nasal and oral zolmitriptan, oral eletriptan and subcutaneous sumatriptan. CONCLUSION: In the present setting (specialized headache care in Germany), 13.1% of the patients had failed ≥ 2 triptans. Triptan failure was associated with increased migraine severity and disability, emphasizing the importance of establishing an effective and tolerable acute migraine medication. Acute treatment optimization might include switching to one of the triptans with the highest responder rates and/or to a different acute medication class. TRIAL REGISTRATION: The DMKG Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081).

Headache characteristics and postoperative course in Chiari I malformation.

BACKGROUND: Chiari I malformation typically presents with cough headache. However, migraine-like or tension-type-like headaches may also occur. There are limited publications on Chiari I malformation-associated headache semiologies and the effect of foramen magnum decompression on different headache types. METHODS: A retrospective analysis complemented by structured phone interviews was performed on 65 patients with Chiari I malformation, treated at our hospital between 2010 and 2021. Headache semiology (according to ICHD-3), frequency, intensity, and radiological characteristics were evaluated pre- and postoperatively. RESULTS: We included 65 patients. 38 patients were female and 27 male. Mean age was 43.9 ± 15.7 years. Headache was predominant in 41 patients (63.0%). Twenty-one patients had cough headache and 20 had atypical headache (12 migrainous, eight tension-type headache-like). Thirty-five patients with headache underwent surgery. Frequency, intensity, and analgesic use was significantly reduced in cough headache (p < 0.001). Atypical headaches improved less (p = 0.004 to 0.176). Exploratory analysis suggested that larger preoperative tonsillar descent correlated with larger postoperative headache intensity relief (p = 0.025). CONCLUSION: Decompression was effective in Chiari I malformation-related cough headache. Atypical headache responded less well, and the causal relation with Chiari I malformation remains uncertain. For atypical headache, decompression should only be considered after failed appropriate preventive therapy and within an interdisciplinary approach involving a neurologist.

Effect of antibody switch in non-responders to a CGRP receptor antibody treatment in migraine: A multi-center retrospective cohort study.

BACKGROUND: Switching between antibody classes might be a treatment option in migraine patients who have not responded to one class of a CGRP-(receptor) monoclonal antibody (mAb), but there are no efficacy data so far. In this real-world analysis, we assessed the treatment response to a CGRP-mAb in patients that have previously failed the CGRP-receptor-mAb erenumab. METHODS: We analyzed retrospective headache diary data of 78 patients with migraine who switched between CGRP-mAbs classes at four German headache centers either due to lack of efficacy or intolerable side effects. Among these, we identified 25 patients who did not respond to erenumab after three treatment cycles (defined as <30% reduction of monthly headache days) and had complete headache documentation at least one month before and during both treatments. We assessed the ≥30% responder rate at month three after switching from erenumab to a CGRP-mAb (galcanezumab or fremanezumab) (primary endpoint). Secondary endpoints included ≥50% responder rate, monthly headache days, and monthly days with acute medication use. In an exploratory subgroup analysis patients were stratified for daily and non-daily headache. RESULTS: The switch from erenumab to a CGRP-mAb led to a ≥30% response in one-third (32%) of the patients after three treatment cycles. A ≥50% response was achieved in 12% of the patients. Monthly headache days were reduced in month three compared to baseline (20.8 ± 7.1 to 17.8 ± 9.1; p = 0.009). Stratified analysis revealed that no patient with daily headache (n = 9) responded to the treatment switch, while a 30% response was achieved by 50% of patients with non-daily headache (n = 16). CONCLUSION: Our findings demonstrate that a relevant proportion of erenumab non-responders might benefit from a treatment switch to a CGRP-mAb. Switching seems to be a promising treatment option especially in migraine patients with non-daily headache.

Psychological factors associated with headache frequency, intensity, and headache-related disability in migraine patients.

BACKGROUND: Several psychological cofactors of migraine have been identified, but relationships to different headache parameters (e.g., headache frequency vs. headache-related disability) are only incompletely understood. METHODS: We cross-sectionally assessed 279 migraine patients at their first presentation at our tertiary headache center. We obtained headache and acute medication frequency, pain intensity, the Migraine Disability Assessment Scale (MIDAS), and the Pain Disability Index (PDI) as headache-related outcomes as well as scores of the Hospital Anxiety and Depression Scale (HADS), the Pain Catastrophizing Scale (PCS), Pain-Related Control Scale (PRCS), and Avoidance Endurance Questionnaire (AEQ) as psychological factors. RESULTS: Linear regression models revealed the highest associations of the psychological factors with the PDI (adjusted R2 = 0.296, p < 0.001, independent predictors: PCS, AEQ social avoidance, depression) followed by the MIDAS (adjusted R2 = 0.137, p < 0.001, predictors: depression, AEQ social avoidance) and headache frequency (adjusted R2 = 0.083, p < 0.001, predictors: depression, AEQ humor/distraction). Principal component analysis corroborated that psychological factors were preferentially associated with the PDI, while the MIDAS loaded together with headache frequency. CONCLUSION: Our results suggest that psychological factors are more strongly associated with the subjective degree of headache-related disability measured by the PDI than with the days with disability (MIDAS) or the more objective parameter of headache frequency. This once again highlights the need for comprehensive assessment of migraine patients with different headache parameters and the need for considering psychological treatment, especially in patients with high disability.

Cluster Headache Impact Questionnaire (CHIQ) - a short measure of cluster headache related disability.

BACKGROUND: Cluster headache (CH) is a severe, highly disabling primary headache disorder. However, there is little research on CH-related disability, and most of it is based on non CH-specific questionnaires. The aim of this study was to develop a short, CH-specific disability questionnaire. METHODS: The 8-item Cluster Headache Impact Questionnaire (CHIQ) was developed based on a literature review and patient and expert interviews. The questionnaire was tested in 254 CH patients (171 males; 47.5 ± 11.4 years; 111 chronic CH, 85 active episodic CH, 52 episodic CH in remission) from our tertiary headache center or from a German support group. RESULTS: Reliability and validity of the CHIQ was evaluated in active episodic and chronic CH patients (n = 196). Internal consistency (Cronbach's α = 0.88) and test-retest reliability (ICC 0.91, n = 41) were good. Factor analysis identified a single factor. Convergent validity was shown by significant correlations with the Headache Impact Test (HIT-6, r = 0.58, p < 0.001), subscales of the depression, anxiety and stress scales (DASS, r = 0.46-0.62; p < 0.001) and with CH attack frequency (r = 0.41; p < 0.001). CHIQ scores significantly differentiated between chronic CH (25.8 ± 6.5), active episodic CH (23.3 ± 6.9) and episodic CH patients in remission (13.6 ± 11.9, p < 0.05 for all 3 comparisons). CONCLUSIONS: The CHIQ is a short, reliable, valid, and easy to administer measure of CH-related disability, which makes it a useful tool for clinical use and research.

The headache registry of the German Migraine and Headache Society (DMKG): baseline data of the first 1,351 patients.

BACKGROUND: Although good treatment options exist for many headache disorders, not all patients benefit and disability continues to be large. To design strategies for improving headache care, real-world data observing standard care is necessary. Therefore, the German Migraine and Headache Society (DMKG) has established the DMKG Headache Registry. Here we present methods and baseline data. METHODS: Accredited German headache centers (clinic-based or private practice) can offer participation to their patients. Patients provide headache history, current headache load (including a mobile headache diary), medication and comorbidities and answer validated questionnaires, prior to their physician appointment. Physicians use these data as the base of their history taking, and add, change or confirm some central information. Before the next visit, patients are asked to update their data. Patients will continuously be included over the next years. RESULTS: The present analysis is based on the first 1,351 patients (1110 females, 39.6 ± 12.9 years) with a completed first visit. Most participants had a migraine diagnosis. Participants had 14.4 ± 8.5 headache days and 7.7 ± 6.1 acute medication days per month and 63.9% had a migraine disability assessment (MIDAS) grade 4 (severe disability). 93.6% used at least one acute headache medication, most frequently a triptan (60.0%) or non-opioid analgesic (58.3%). 45.0% used at least one headache preventive medication, most frequently an antidepressant (11.4%, mostly amitriptyline 8.4%) or a CGRP(receptor) antibody (9.8%). Most common causes for discontinuation of preventive medication were lack of effect (54.2%) and side effects (43.3%). CONCLUSION: The DMKG Headache Registry allows to continuously monitor headache care at German headache centers in both a cross-sectional and a longitudinal approach. TRIAL REGISTRATION: The DMKG Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081 ).

Long COVID headache.

Headache is among the most frequent symptoms persisting or newly developing after coronavirus disease 2019 (COVID-19) as part of the so-called long COVID syndrome. The knowledge on long COVID headache is still limited, however growing evidence is defining the features of this novel condition, in particular regarding clinical characteristics, some pathophysiological mechanisms and first treatment recommendations. Long COVID headache can present in the form of worsening of a preexisting primary headache, or, more specifically, in the form of a new (intermittent or daily) headache starting during the acute infection or after a delay. It often presents together with other long COVID symptoms, most frequently with hyposmia. It can manifest with a migrainous or, more frequently, with a tension-type-like phenotype. Persistent activation of the immune system and trigeminovascular activation are thought to play a role. As there are virtually no treatment studies, treatment currently is largely guided by the existing guidelines for primary headaches with the corresponding phenotype. The present report, a collaborative work of the international group of the Junior Editorial Board of The Journal of Headache and Pain aims to summarize the most recent evidence about long COVID headache and suggests approaches to the diagnosis and treatment of this disorder.

Baseline tear fluid CGRP is elevated in active cluster headache patients as long as they have not taken attack abortive medication.

BACKGROUND: Calcitonin gene-related peptide plays a key role in cluster headache pathophysiology. It is released from the trigeminal nerve, which also innervates the eye. In this study, we tested if tear fluid calcitonin gene-related peptide measurement detects elevated calcitonin gene-related peptide levels in cluster headache patients compared to controls. METHODS: Calcitonin gene-related peptide concentration in tear fluid and plasma of 16 active episodic and 11 chronic cluster headache patients (all outside acute attacks) and 60 controls were assessed using ELISA. RESULTS: Cluster headache patients without use of attack abortive medication in the last 48 h showed significantly elevated tear fluid calcitonin gene-related peptide levels (1.78 ± 1.57 ng/ml, n = 17) compared to healthy controls (0.79 ± 0.74 ng/ml, p = 0.003) and compared to cluster headache patients who had used attack abortive medication in the last 48 h (0.84 ± 1.40 ng/ml, n = 10, p = 0.022). High calcitonin gene-related peptide levels in cluster headache patients were independent of the occurrence of a cluster headache attack in the last 48 hours (no attack: 1.95 ± 1.65 ng/ml, n = 8; attack: 1.63 ± 1.59 ng/ml, n = 9, p = 0.82) as long as no acute medication was used. No significant difference in tear fluid calcitonin gene-related peptide levels between episodic (1.48 ± 1.34 ng/ml) and chronic cluster headache patients (2.21 ± 1.88 ng/ml, p = 0.364) was detected. In contrast to these results in tear fluid, there were no significant group differences in plasma calcitonin gene-related peptide levels. CONCLUSION: This study shows that active cluster headache patients have increased calcitonin gene-related peptide levels in tear fluid compared to healthy subjects, which are reduced to control levels after intake of attack abortive medication. Calcitonin gene-related peptide measurement in tear fluid is non-invasive, and has the advantage of allowing direct access to calcitonin gene-related peptide released from the trigeminal nerve.