Disability in cluster headache is more than attack frequency - results from and validation of the English version of the Cluster Headache Impact Questionnaire (CHIQ).

BACKGROUND: Cluster headache (CH) is associated with high disability. The Cluster Headache Impact Questionnaire (CHIQ) is a short, disease-specific disability questionnaire first developed and validated in German. Here, we validated the English version of this questionnaire. METHODS: The CHIQ was assessed together with nonspecific headache-related disability questionnaires in CH patients from a tertiary headache center and an American self-help group. RESULTS: 155 active episodic and chronic CH patients were included. The CHIQ showed good internal consistency (Cronbach's α = 0.91) and test-retest reliability (ICC = 0.93, n = 44). Factor analysis identified a single factor. Convergent validity was shown by significant correlations with the Headache Impact Test™ (HIT-6™, ρ = 0.72, p < 0.001), the Hospital Anxiety and Depression Scale (HADS depression: ρ = 0.53, HADS anxiety: ρ = 0.61, both p < 0.001), the Perceived Stress Scale (PSS-10, ρ = 0.61, p < 0.001) and with CH attack frequency (ρ = 0.29, p < 0.001). Chronic CH patients showed the highest CHIQ scores (25.4 ± 7.9, n = 76), followed by active episodic CH and episodic CH patients in remission (active eCH: 22.2 ± 8.7, n = 79; eCH in remission: 14.1 ± 13.1, n = 127; p < 0.001). Furthermore, the CHIQ was graded into 5 levels from "no to low impact" to "extreme impact" based on the patients' perception. Higher CHIQ grading was associated with higher attack and acute medication frequency, HIT-6™, HADS and PSS scores. CONCLUSION: The English version of the CHIQ is a reliable, valid, and disease-specific patient-reported outcome measure to assess the impact of headaches on CH patients.

Pain Sensitivity Questionnaire: Cross-cultural adaptation and validation of the Greek version.

INTRODUCTION: The Pain Sensitivity Questionnaire (PSQ) was developed to assess general pain sensitivity. OBJECTIVE: This study aimed to validate the Greek version of PSQ. METHODS: The questionnaire was translated into Greek (PSQ-GR) and piloted in a small sample of patients with chronic pain (n = 35). A total of 146 chronic pain patients and healthy volunteers completed the PSQ-GR, the Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS) and Central Sensitization Inventory (CSI). To evaluate the test-retest reliability, 36 volunteers completed the PSQ-GR twice over 7 ± 2 days. RESULTS: Internal consistency was excellent (Cronbach's alpha 0.90-0.96) for PSQ-total, PSQ-minor, and PSQ-moderate. The Intraclass Correlation Coefficient was estimated at 0.90-0.96 for PSQ-total, PSQ-minor and PSQ-moderate and the SEM was 0.59-0.90 for PSQ-total, PSQ-minor and PSQ-moderate approximately. The smallest detectable change was 0.48 for PSQ-total, 0.47 for PSQ-minor and 0.44 for PSQ-moderate. Positive and significant correlations were observed between PSQ-GR and HADS (r = 0.38, p < 0.01), PCS (r = 0.41, p < 0.01) and CSI (r = 0.30, p < 0.01). Statistically significant differences in PSQ-GR scores were identified between the healthy volunteers and the chronic pain patients. CONCLUSION: The PSQ-GR is a reliable and valid tool that can assess pain sensitivity in healthy individuals and chronic musculoskeletal pain patients.

Minimal important difference of the Migraine Disability Assessment (MIDAS): Longitudinal data from the DMKG Headache Registry.

BACKGROUND: The Migraine Disability Assessment (MIDAS) is widely used. However, there are limited data on how much a reduction in the MIDAS score indicates a change that matters to the patient. METHODS: Data from the DMKG (i.e. German Migraine and Headache Society) Headache Registry were used to determine the minimal important difference (MID) of the MIDAS, using the Patient Global Impression of Change (PGIC) as anchor and applying average change and receiver operating characteristic curve methods. RESULTS: In total, 1218 adult migraine patients (85.6% female, 40.2 ± 12.8 years, baseline MIDAS 44.2 ± 47.4, follow-up MIDAS 36.5 ± 45.3) were included. For patients with baseline MIDAS >20 (MIDAS grade IV, n = 757), different methods using PGIC "somewhat improved" as anchor yielded percent change MIDs of the MIDAS between -29.4% and -33.2%. For baseline MIDAS between 6 and 20 (grades II and III, n = 334), using PGIC "much improved" as anchor, difference change MIDs were between -3.5 and -4.5 points. CONCLUSIONS: Based on the above results, we estimated the MID of the MIDAS at -30% for patients with a baseline MIDAS >20, and at -4 points for those with a baseline MIDAS of 6-20, for a tertiary headache care population. TRIAL REGISTRATION: The DMKG Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081).

[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.

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.

Translation, cross-cultural adaptation, and measurement properties of the Arabic version of the pain sensitivity questionnaire.

Background: The Pain Sensitivity Questionnaire (PSQ) is a reliable and valid self-reported tool for the assessment of pain sensitivity in clinical practice. The PSQ has been translated, validated, and cross-culturally adapted into multiple languages. However, a validated Arabic version of the PSQ is not available. Thus, this study aims to translate, validate, and cross-culturally adapt the English version of the PSQ into the Arabic language. Methods and materials: The English version of the PSQ was translated and culturally adapted into Arabic following international guidelines. The psychometric properties of the final version of the PSQ-Arabic (PSQ-A) were tested among 119 patients with different persistent musculoskeletal (MSK) pain. Findings: The Cronbach's α for the PSQ-A-total, PSQ-A-moderate, and PSQ-C-minor were 0.81, 0.79, and 0.76, respectively. The means for the PSQ-A-total, PSQ-A-moderate, and PSQ-C-minor scores were 5.07 (±1.28), 5.64 (±2.07), and 4.50 (±0.50). The test-retest reliability measured with the interclass correlation coefficient for 68 subjects was 0.80 for the PSQ-A-total, 0.74 for the PSQ-A-moderate, and 0.77 for the PSQ-A-minor. The PSQ-A-total and the PSQ-A-minor showed positive significant correlations with pain catastrophizing scale (PCS) (r = 0.15, 0.17); P ≤ 0.05), respectively. The PSQ-A-total, PSQ-A-moderate, and PSQ-A-minor showed positive significant correlations with the Brief Pain Inventory (BPI)-pain scores (r = 0.47, 0.43, 0.45; P ≤ 0.01), respectively and with the BPI-pain interference scores (r = 0.37, 0.33, 0.34; P ≤ 0.01), respectively. Conclusions: This study shows that the PSQ-A is a reliable and valid tool to assess individuals with pain sensitivity in Arabic populations. Further studies are recommended to examine the concurrent validity of the PSQ-A against experimental pain sensitivity measures.

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.

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 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.

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).

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 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.

[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.

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.