Cluster Headache Research Articles

German language adaptation of the Cluster Headache Quality of Life Scale (CH-QoL)

BackgroundCluster headache (CH) can lead to high disability and reduced quality of life (QoL). QoL should be assessed as an important outcome both in research and in clinical care. The 28-item Cluster Headache Quality of Life Scale (CH-QoL) is a valid self-report questionnaire to assess disease-specific QoL. A German version is lacking. This study aims to develop a German-language version and to determine its psychometric properties.MethodsThe CH-QoL was translated into German by two headache experts and blindly back-translated by two professional translators. Additionally, the CH-QoL was tested for comprehensibility by nine persons with CH. In this multi-stage process, linguistic discrepancies were repeatedly discussed in an expert panel and appropriate modifications were conducted to optimize the translation. A cross-sectional online survey, comprising the CH-QoL and further self-report questionnaires such as the Cluster Headache Scales (CHS), yielded a sample of N = 106 persons with CH (53.8% female, M = 45.5 [SD = 11.8] years, 48.1% episodic CH, 51.9% chronic CH, 79.2% currently having recurring CH attacks).ResultsExploratory factor analysis revealed two clearly interpretable factors (“restriction of activities of daily living”, and “impact on mood and interpersonal relationships”), which is in discrepancy to the four factors of the original English version. The model fit was good, with χ2(323) = 590.74, p < .001, RMSEA = 0.088, SRMR = 0.053, TLI = 0.857. Reliability was very good (McDonald’s omega ω = 0.97, Subscale/Factor 1: ω = 0.96, Subscale/Factor 2: ω = 0.92). Correlational analyses (correlations with related questionnaires as well as with clinical parameters) confirmed convergent validity.ConclusionsSince the German version of the CH-QoL has very good psychometric properties, it is suitable for the assessment of disease-specific QoL in people with CH in German-speaking countries.Trial registrationThis study is registered with the German Clinical Trials Register (DRKS-ID: DRKS00028475, registration date 03 March 2022).

Cephalgic syndrome in patients with acromegaly

The aim of this review is to summarize the data available in the literature on the causes of headache in patients with acromegaly, as well as on the effect of various methods of acromegaly treatment on headache. Publications were searched in the PubMed database using the keywords «Headache in patients with acromegaly», «Headache in patients with pituitary adenomas», «Tension-type headache», «Migraine». Headache in patients with pituitary adenomas secreting somatotropic hormone (STH) is not uncommon: according to various authors, cephalgic syndrome occurs in 30-70% of patients with acromegaly and can worsen their quality of life, along with other factors, up to disability. By the nature of development, headache with acromegaly is classified into primary (migraine, tension headache, trigeminal autonomic cephalgia, for example, SUNCT syndrome and cluster headaches), and can also be caused by various causes directly related to the tumor. All this requires differential diagnosis. The factors causing headaches in somatotropinomas have not yet been well studied and require further research. These include the mass effect of the tumor, hormonal hypersecretion, pathology of the temporomandibular joint, sodium and fluid retention in the body, psychological factors, etc. The authors evaluated the effect on headache of various methods of acromegaly treatment: transnasal transsphenoidal adenomectomy, radiation therapy and drug therapy with somatostatin analogues, dopamine agonists and growth hormone receptor antagonist. However, even when normal levels of STH and insulin-like growth factor 1 (IGF-1) are reached, cephalgic syndrome may persist, therefore patients should be warned about this in advance and referred to a cephalgologist to select adequate headache therapy.

Current and Novel Therapies for Cluster Headache: A Narrative Review.

Cluster headache (CH) is an excruciating and debilitating primary headache disorder. The prevalence is up to 1.3%, and the typical onset is around age 30. Often misdiagnosed as migraine, particularly in children, the diagnosis rate of CH has been increasing among women. CH is characterized by intense unilateral pain and autonomic symptoms, significantly impacting patients' quality of life, mental health, and productivity.Genetic associations suggest a familial risk for developing CH, with lifestyle factors also potentially playing a role. The pathophysiology involves alterations in both central and peripheral nervous system, with the hypothalamus, trigeminocervical complex, and neuropeptides such as calcitonin gene-related peptide (CGRP) being implicated.Nonpharmacological treatments focus on patient education and lifestyle modifications, while pharmacological treatments include acute therapies such as oxygen and subcutaneous or nasal sumatriptan, as well as preventive therapies like verapamil, lithium, and CGRP monoclonal antibodies. Transitional options include oral corticosteroids and greater occipital nerve injections. Emerging interventional procedures offer new avenues for managing refractory cases. Noninvasive vagal nerve stimulation and occipital nerve stimulation show promise for both acute and preventive treatment. Careful consideration of safety profiles is crucial in specific populations such as pregnant patients and children.Current treatments still leave patients highly burdened by limited efficacy and side effects. Future research continues to explore novel pharmacological targets, interventional procedures, and the potential role of psychedelics in CH management. Comprehensive, multifaceted treatment strategies are essential to improve the daily functioning and quality of life for individuals with CH.

The relation of cluster headache to alexithymia, depression, and anxiety.

The pathophysiology of cluster headaches (CHs) involves the trigeminovascular system, the parasympathetic nervous system, and the hypothalamus. Because of the affected hypothalamus, there may be limbic system involvement in CH. To investigate the relationship between depression, anxiety, and alexithymia in CH, to demonstrate that the limbic system is affected. A total of 18 patients with CHs who were outside of cluster period and 18 healthy controls were included. Participants were administered the Beck depression inventory (BDI), Beck anxiety inventory (BAI), and Toronto alexithymia scale-20 (TAS-20). Patients with CHs had significantly higher rates of alexithymia (p = 0.003) and depression (p = 0.014) than controls. There was no significant difference in anxiety levels (p = 0.297) between groups. It was shown that, in addition to previously identified psychiatric disorders, alexithymia can accompany CHs in patients.

Headaches in SLE patients: a cross-sectional analysis of clinical, immunological, and Radiological Correlations.

Systemic Lupus Erythematosus (SLE) is a multifaceted autoimmune disorder characterized by diverse clinical manifestations, including a significant prevalence of headaches. This cross-sectional study aimed to thoroughly explore the relationship between SLE and headaches by analysing their prevalence, types, and associated clinical, immunological, and radiological factors. A comparative analysis was conducted on 179 SLE patients, who were categorized into two groups: those with headaches and those without. Data collection encompassed demographic details, disease activity levels, neurological assessments, immunological profiles, and brain imaging results. Headaches were diagnosed and classified following the International Classification of Headache Disorders (ICHD-3). Disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Statistical analyses were performed to identify significant associations and correlations. Headaches were observed in 55% of the SLE patients, predominantly presenting as tension-type headaches (65%) and migraines (27%). Notably, no patients met the criteria for a lupus-specific headache. The Headache Group exhibited significantly higher disease activity (SLEDAI scores). Tension-type and migraine headaches were particularly associated with increased muco-cutaneous manifestations. The presence of antiphospholipid (aPL) antibodies was significantly linked to migraines and cluster headaches. While neurological disorders such as ischemic stroke and venous sinus thrombosis were more prevalent in the Headache Group, these findings were not statistically significant. Brain MRI abnormalities were detected in 9.4% of patients with headaches, including venous sinus thrombosis (2.3%), ischemic stroke (5.8%), and white matter hyperintensities (1.1%). This study underscore es the complex relationship between SLE and headaches, suggesting that headaches may serve as an indicator of heightened SLE disease activity. Immunological factors, particularly aPL antibodies, show a strong association with specific headache types. MRI abnormalities further emphasize the intricate neurobiological aspects in SLE patients experiencing headaches. Continued research is essential to better understand biomarkers, genetic factors, and effective treatment strategies for managing headaches in SLE patients.

Neurological and Systemic Pitfalls in the Diagnosis of Cluster Headaches: A Case-Based Review.

To describe different pitfalls in the diagnosis of primary cluster headaches (CHs) with the guidance of seven case vignettes. The question of whether primary CHs and migraines are totally different entities has been long debated. Autonomic features can be detected in as many as 60% of migraine patients. Although some genetic similarities have been found, CACNA1A mutations have not been detected among CH patients with hemimotor aura in contrast to hemiplegic migraine. Recently, functional MRI studies have shown that the left thalamic network was the most discriminative MRI feature in distinguishing migraine from CH patients. Compared to migraine, CH patients showed decreased functional interaction between the left thalamus and cortical areas mediating interception and sensory integration. However, clinically the most significant feature had been the restlessness and agitation seen during headache attacks patients with CHs. This feature is also important in distinguishing cluster patients from other patients having other trigeminal autonomic cephalalgias except for a subset of patients with hemicrania continua. CH is an important member of the group of headache disorders characterized by their association with one or more autonomic features in the trigeminal nerve distribution and termed Trigeminal Autonomic Cephalalgias (TACs). Although CH is a relatively rare condition, judged by the distress it generally causes to the affected individual, early diagnosis and institution of appropriate therapy seem mandatory. Correct diagnosis of CHs needs avoidance of pitfalls. Such pitfalls generally include differentiation from migraine, differentiation from other side locked headache disorders, from other trigeminal autonomic cephalalgias (TACs), and lastly, recognition of rare presentations of cluster-like manifestations with hemiplegic aura and simulating trigeminal and glossopharyngeal neuralgias. Differentiation between primary and symptomatic CHs related to sellar pathologies and systemic medical conditions is of equal importance. In the present review such issues are discussed with the assistance of seven case vignettes.

Characteristics of men and women with medically diagnosed cluster headache in a national integrated healthcare system: A Veterans Health Administration cohort study.

Describe the epidemiology of cluster headache (CH) using Veterans Health Administration (VHA) Electronic Health Record (EHR) data. Epidemiologic studies of CH at the population level are difficult because it has a prevalence of ~0.1%. Hospital system-wide studies are an attractive alternative as they have large numbers of patients and broader populations than headache or neurology clinic-based studies. The VHA is an ideal hospital-based system in which to study CH because it is nationwide, predominantly male, has a strong focus on mood disorders and suicidality, and has accessible individual medical records. Here, we report the first headache study based on an ongoing longitudinal cohort of patients with CH using VHA EHR data. The VHA EHR data were accessed from Fiscal Year 2008 to 2019. Patients with CH consisted of all patients with at least one outpatient visit containing a CH diagnosis code from the International Classification of Diseases (ICD)-9 or -10. We extracted data on demographic features, incidence, and prevalence, as well as pain and psychiatric comorbidities. Of the 1,524,960 distinct patients who presented for headache treatment in the VHA between Fiscal Year 2008-2019, 24,131 had at least one visit with a CH diagnosis. The 1-year period prevalence of a CH diagnosis in the VHA ranges from 0.08% to 0.10% for women and 0.10% to 0.18% for men. A larger proportion of women versus men received a diagnosis of unspecified CH (59.6% [1412/2368] vs. 53.6% [11,663/21,763], p < 0.001). Most patients with CH had both comorbid headache and non-headache pain diagnoses. Headache not-otherwise-specified was the most common comorbid headache disorder at 70.0% (16,885/24,131) and was more common in women (76.1%, 1801/2368) compared to men (69.3%, 15,084/21,763). Other common comorbidities included migraine, depression, tobacco use, and obstructive sleep apnea. Rates of suicidal ideation or attempt were almost 50% higher in women (5-year proportion 9.4%, 222/2368) with CH compared to men (6.6%, 1433/21,763). To our knowledge this is the largest hospital system study of CH to date and reinforces several previous studies. Pain, mental health, and sleep disorders comorbidities are particularly prevalent in this group and were often more common in women compared to men with CH. Future work should examine gender and race stratified prevalence estimates within the VHA and other healthcare systems.

Sex and gender differences in the epidemiology, clinical features, and pathophysiology of trigeminal autonomic cephalalgias

Emerging evidence suggests that primary headaches, classified as trigeminal autonomic cephalalgias (TACs), may exhibit sex and gender differences in clinical features, mechanisms, and treatment responses. While epidemiological and clinical gender-specific differences have been widely reported for cluster headache, limited evidence is available for other TACs. In this narrative review, we have analyzed the existing data on the influence of sex and gender on cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks, and hemicrania continua. Given the role of calcitonin gene-related peptide (CGRP) in migraine and cluster headache, sex and gender differences in the levels and function of CGRP in preclinical models and patients are reported. Future studies are warranted to elucidate the role of sex and gender in the complex interplay of genetic and neurochemical factors in TACs.

Pre-cluster symptoms in a Taiwanese cohort of cluster headache: symptom profiles and clinical predictions

BackgroundPre-cluster symptoms (PCSs) are symptoms preceding cluster bouts and might have implications for the treatment of cluster headache (CH). This study investigated the prevalence of PCSs, and their utility in predicting upcoming bouts as well as the associations with therapeutic efficacy.MethodsWe prospectively collected data from patients with CH. Each patient received a structured interview and completed questionnaire surveys during CH bouts. In sub-study 1, we cross-sectionally analyzed the prevalence, symptomatology, and predictability of upcoming bouts. Overall, 34 PCSs, divided into seven categories, were queried, including head and neck pain, cranial autonomic symptoms, restlessness, fatigue or mood changes, sleep alterations, constitutional symptoms, and generalized pain. In sub-study 2, we recorded the weekly frequency of CH attacks after the initiation of verapamil concurrently with a 14-day transitional therapy based on the patients’ headache diary. A responder to verapamil was defined as a patient who have a reduction from baseline of at least 50% in the weekly frequency of CH attacks 4 weeks after the initiation of verapamil.ResultsA total of 168 CH patients (women/men: 39/129) completed the study. In sub-study 1, we found 149 (88.7%) experienced PCSs, with a median of 24 (IQR 18 to 72) hours before the bouts. Up to 57.7% of patients with PCS reported that they could predict upcoming bouts. Among the seven categories of PCSs, head and neck pain was the most common (81.0%) and was associated with a higher predictability of upcoming bouts (odds ratio [OR] = 4.0; 95% confidence interval [CI] 1.7–9.6). In sub-study 2, we found two categories of PCSs were associated with the response to verapamil: sleep alteration (OR = 2.5 [95% CI = 1.3–4.8], p = 0.004) and ≥ 1 cranial autonomic symptoms (OR = 2.7 [95% CI = 1.4–5.1], p = 0.003).ConclusionPCSs were very common in CH and could be used to predict upcoming bouts. Different symptom categories of PCSs may have different clinical implications.

Solubility determination and thermodynamic modelling of verapamil hydrochloride in methanol-water binary solvent systems from 293.15 K to 323.15 K

Verapamil Hydrochloride is a key calcium channel blocker used to treat cardiovascular disorders and prevent cluster headaches by inhibiting calcium influx, thus improving cardiovascular health. The solubility of Verapamil Hydrochloride (VH) in methanol + water binary solvent systems were studied using a gravimetric method at temperatures from 293.15 K to 323.15 K under atmospheric pressure. The solubility increased with temperature and methanol content, with the highest mole fraction solubility at a 0.90 methanol mole fraction and the lowest at 0.10. Various models, including Apelblat, Van't Hoff, modified Jouyban–Acree, and CNIBS/R-K, were used to calculate theoretical solubility, with RAD and RMSD assessing the model accuracy. Thermodynamic analysis indicated that VH dissolution is endothermic and entropy-driven. This data is valuable for optimizing VH purification and crystallization processes in the pharmaceutical industry.

ANODYNE study: A double-blind randomized trial of greater occipital nerve block of methylprednisolone and lignocaine versus placebo as a transitional preventive treatment for episodic cluster headache.

There is inadequate evidence of the efficacy of greater occipital nerve block (GONB) for the preventive treatment of cluster headaches. We assessed the efficacy and tolerability of GONB injections as a transitional preventive treatment for episodic cluster headaches (ECH). This randomized, double-blind, placebo-controlled, parallel-group trial conducted at GB Pant Institute of Postgraduate Medical Education and Research, New Delhi, India, included ECH patients diagnosed by ICHD-3 criteria, aged 18-65, with one or more attacks per 24 h for seven days before randomization (baseline). ECH patients were either not on preventive medications or on stable doses for at least three months. ECH patients were randomized to receive active GONB (2 ml methylprednisolone (80 mg) and 2 ml lignocaine (2%)) and placebo (4 ml saline injections). Before giving GONB, lignocaine jelly was applied topically to mask the effect of numbness following the GONB. The primary efficacy endpoint was the mean change in weekly attack frequency from baseline to Week 4. Efficacy analyses were performed in a modified intention-to-treat population that included all patients who received at least one injection of GONB and had a follow-up for one week following GONB. The safety analysis included treatment-emergent adverse effects (TEAE) in all patients who received at least one dose of investigational product. The trial was registered with the Clinical Trials Registry of India (CTRI/2021/21/038397). Forty ECH patients were randomized between December 2021 and January 2023. Thirty-nine patients (19 in the active and 20 in the placebo groups) were available for efficacy analysis. The change in weekly attack frequency from baseline to Week 4 was -11.1 (95% CI: -8.5 to -4.4) for the active group compared to -7.7 (95% CI: -11.8 to -9.8) for placebo (mean difference -3.4 (95% CI: -5.2 to -1.7, p < 0.001). We noted TEAE in 18 (90%) of 20 patients who received the active drug and in 18 (90%) of 20 patients who received a placebo (p = 0.38). The common TEAE were local site bleeding and pain, which were mild and transient. No serious adverse events were reported. This study found that GONB with methylprednisolone and lignocaine significantly reduced the weekly attack frequency from baseline to Week 1 through Week 4 in ECH patients compared to a placebo. GONB was well tolerated.

Four Decades of OccipitalNerveStimulation for Headache Disorders: A Systematic Review.

Chronic headaches are a significant source of disability worldwide. Despite the development of conventional strategies, a subset of patients remain refractory and/or experience side effects following these treatments. Hence, occipital nerve stimulation (ONS) should be considered as an alternative strategy for intractable chronic headaches. This review aims toprovidea comprehensive overview of the effectiveness, safety, mechanisms and practical application ofONSfor the treatment of headache disorders. Overall response rate of ONS is 35.7-100%, 17-100%, and 63-100% in patients with cluster headache, chronic migraine and occipital neuralgia respectively. Regarding the long-term effectivity in all groups, 41.6-88.0% of patients remain responders after ≥ 18.3months. The most frequently reported adverse events include lead migration/fracture (13%) and local pain (7.3%). Based on our results, ONS can be considered a safe and effective treatment for chronic intractable headache disorders. To support more widespread application of ONS, additional research with larger sample sizes should be conducted.

ID: 316629 In-Silico Methodology to Produce Innovative Designs for a Cranial Nerve Stimulator to Treat Cluster Headache

ID: 316629 In-Silico Methodology to Produce Innovative Designs for a Cranial Nerve Stimulator to Treat Cluster Headache

Quality by Design Approach to Nasal Mucoadhesive Microspheres: Enhanced Sumatriptan Succinate Delivery through Formulation and Characterization.

The primary therapeutic indications for sumatriptan succinate (STS) include the treatment of migraine and cluster headaches. To enhance mucoadhesion, sodium carboxymethyl cellulose (SCMC) and hydroxyl propyl methyl cellulose (HPMC K15M) were used in this study to develop nasal mucoadhesive microspheres of STS. A central composite design, facilitated by Design Expert software, was employed to assess the impact of polymer concentrations on mucoadhesion, involving nine different formulations. The study’s findings indicated that the microspheres were uniformly sized and spherical and that the polymers were compatible with STS. The optimal formulation, consisting of 220.711 mg of SCMC and 150 mg of HPMC K15M, demonstrated the highest level of mucoadhesion. This combination effectively regulated the discharge of STS from the mucoadhesive microspheres and significantly improved their mucoadhesive properties. These results suggest that the strategic use of SCMC and HPMC K15M can enhance the performance of nasal mucoadhesive microspheres, ensuring a controlled release of STS and improved adhesion to mucosal surfaces. This has the potential to optimize the therapeutic efficacy of STS in treating migraine and cluster headaches.

Low-dose psilocybin in short-lasting unilateral neuralgiform headache attacks: results from an open-label phase Ib ascending dose study.

Short-lasting unilateral neuralgiform headache attacks (SUNHA) are trigeminal autonomic cephalalgiasthat feature intense and recurrent paroxysms of pain and autonomic symptoms. Many patients are left with debilitating symptoms despite best-available treatment. Psychedelics, such as the serotonin 2A partial agonist psilocybin, have shown promise in related disorders such as migraine and cluster headache. In this open-label phase Ib ascending dose study, we aimed to assess the effects of low-dose oral psilocybin with psychological support in six to 12 patients with chronic SUNHA. Study objectives were to determine effects on cognition, as well as safety, tolerability, and effects on headache severity and frequency. Oral psilocybin in ascending doses of 5, 7.5, and 10 mg (one dose per session; three dosing sessions in total) were administered. Cognition was assessed via the Cambridge Neuropsychological Tests Automated Battery. Headache attacks were assessed via headache diaries and the six-item Headache Impact Test (HIT-6). Subjective dose intensity was assessed via the five-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). The study was terminated early due to recruitment difficulties; four patients were enrolled, three of whom were study completers. Post hoc, we undertook a thematic analysis of the applicable free-text clinical trial notes from the dosing and subsequent visits (n = 22). An inductive method was employed to establish emergent themes. No significant adverse events were recorded. We were unable to collect data as planned on cognitive function during the acute experience due to high ratings of subjective dose intensity (mean 5D-ASC scores 37.8-45.7). The impact of the headaches remained severe throughout the duration of the trial (HIT-6 mean scores 64.3-65.7). There were limited effects on headache duration and severity based on the diaries; however, mean daily attack frequency decreased by >50% in two participants at final follow-up (22.9 to 11.0 and 56.4 to 28.0, respectively). Completing participants and their clinicians recorded "much" (two participants) or "minimal" improvements (one participant) at final follow-up via the Clinical Global Impression rating scale. Thematic analysis indicated that psychological insights were key features of participants' experience; these insights included re-configured relationships to their headache pain. The study met with recruitment difficulties and cognition could not be assessed during the acute experience due to subjective dose intensity, likely mediated in part by expectancy effects. The clinical results provide no conclusive evidence for the use of psilocybin in SUNHA. We suggest that accounting for psychological factors in chronic SUNHA may be an important facet of treatment.

Smoking and cluster headache presentation and responsiveness to treatment

BackgroundThough an association between cluster headache (CH) and smoking has been postulated, data from the Middle East region is scarce.Aim of workTo study the relationship between smoking and CH clinical characteristics and responsiveness to therapy in Egypt.MethodologyThis was a prospective cohort hospital-based study conducted on patients with episodic and chronic CH in a tertiary headache clinic in Egypt during the period between 2019 and 2023. Patients were consecutively recruited at the time of their presentation and were followed up for two weeks after initiation of prophylactic treatment and steroids (as transitional therapy).ResultsOf 172 patients with CH recruited, 144 (83.7%) were smokers. Twenty-eight patients (16.3%) had chronic CH. The mean age was 42.08 ± 10.93 (20–66) years, and 131 (76.2%) were males. Smokers had a significantly higher median number of cluster bouts in the past five years (3.0 (IQR2.0–4.0) versus 2.0 (IQR 1.0–2.0)) and worse HIT-6 scores [51.0 (44.0–59.75) versus 41.0 (38.0–41.75)] than non-smokers (p < 0.001). The number of cluster bouts in the past five years was positively correlated with the smoking index (r = 0.249 (p = 0.006) and the smoking duration (in years) (r = 0.392 (p < 0.001)). HIT-6 scores were significantly correlated with the age at smoking onset (r=-0.190, = 0.023), smoking index (r = 0.519, p < 0.001), smoking duration (r = 0.611, p < 0.001), and number of cigarettes consumed per day (r = 0.392, p < 0.001).ConclusionSmoking is significantly correlated with the daily frequency of CH attacks, the frequency of CH bouts in the past five years, and the HIT-6 scores among our cohort.

The impact of fear of attacks on pain-related disability in cluster headache: Insights from the fear avoidance model.

This study utilized the theoretical framework of the "fear avoidance model" (FAM) and investigated the role of fear of attack in pain-related disability. To this end, a measurement specific to cluster headache (CH) was used to investigate whether fear of attacks, alongside attack frequency, is a significant predictor of pain-related disability in CH. Cluster headache substantially impacts daily functioning, yet empirical research exploring specific contributing factors is limited. A cross-sectional online survey was undertaken in patients with CH, gathering sociodemographic, clinical data, and responses on the Cluster Headache Scale and the Depression, Anxiety and Stress Scale. Analysis of data from 640 patients (chronic CH: 287/640 [44.8%]; female: 264/640 [41.3%]; male: 373/640 [58.3%]; gender diverse: three of 640 [0.5%]; age range: 18-86 years; mean [standard deviation] Cluster Headache Scales subscale disability score: 36.9 [9.8]; out of 869 respondents) revealed that both attack frequency and fear of attacks significantly predicted pain-related disability (p < 0.001, percentage of variance explained: R2 = 0.24). More variance was explained by fear of attacks (R2 = 0.22) than by attack frequency (R2 = 0.02). This relationship remained significant even when controlling for depression and anxiety, which were also identified as independent predictors of pain-related disability (p < 0.001, R2 = 0.44). This study emphasizes the relevance of psychological factors in CH-related disability. Fear of attacks was found to be an independent predictor, while attack frequency was of minor relevance. Empirical investigation of the FAM in CH could improve the understanding of the mechanisms underlying disability and contribute to the development of CH-specific interventions.

Causal relationship between primary headache mediated by circulating cytokines and cerebral cortex structure: a mediation Mendelian randomization study.

Inflammation may be related to structural changes in the cerebral cortex. We aimed to explore whether cytokines mediate the link between these changes and primary headache. The summary statistics of genome-wide association study (GWAS) related to migraine and its subtypes, cluster headache were derived from the FinnGen Release 10 database, and tension-type headache data was from the GWAS Catalog. Ninety-one cytokines were obtained from genome-wide pQTL mapping data. GWAS data on cortical surface area (SA) and thickness (TH) came from the ENIGMA Consortium. The methods of Mendelian randomization (MR) analysis included the inverse-variance-weighted (IVW), MR-Egger, and weighted median. Migraine reduces the SA of paracentral[β = -1.3645, OR = 0.2555, 95%CI (0.0660, 0.9898)] by fibroblast growth factor-23(FGF-23), with an intermediate ratio (IR) of 38.13%. Migraine may reduce the TH of superior parietal[β = -0.0029, OR = 0.9971, 95%CI (0.9943, 0.9999)] by interleukin (IL)-15RA, with an absolute IR of 11.11%. Migraine without aura may reduce the TH of rostral anterior cingulate[β = -0.0005, OR = 0.9995, 95%CI (0.9991, 0.9999)] by IL-18R1, with an IR of 11.63%. FGF23 and IL-15RA are associated with reduced SA or TH in migraine, while IL-18R1 is associated with increased TH in migraine without aura.

Circannual worsening in cluster headache correlates with daylight change.

Plain Language SummaryCluster headache attacks typically occur with circadian rhythmicity and seasonal variability.In this article, we show that circannual rhythmicity of cluster headache attacks with its peak occurrence in spring and autumn could be explained by the rapidity in daylight alterations over the photoperiod, which is not constant but maximal at the time of equinoxes in spring. The peak of cluster attack occurrence at the equinoxes in spring and autumn coincides with greater leaps in day length, leading to interfere with synchronization of endogenous pacemaker systems. Interactions with the serotonergic system, also following circannual fluctuations are discussed.

Radiosurgery for Facial Pain: A Narrative Review.

The surgical treatment of pain has been an integral part of neurosurgery since the early 20th century when Harvey Cushing pioneered ganglionectomy for trigeminal neuralgia. Over the ensuing years, as anatomic and physiologic knowledge of pain systems grew, new techniques aimed at new targets were developed for various pain conditions. Our objective was to provide an informative and up-to-date summary of radiosurgery for chronic facial pain, emphasizing trigeminal neuralgia and discussing the advantages and challenges of this modality. A PubMed search with keywords ("trigeminal neuralgia" or "cluster headache" or "glossopharyngeal neuralgia") and ("radiosurgery") and ("systematic review" or "review") was conducted. Relevant publications in English published from January 2000 to May 2022 were screened manually for their title, abstract, and even full text to determine their relevance. References from the searched articles were also searched as other supplementary articles. We excluded original articles and personal series from the analysis and only considered systematic reviews to maintain the transparency in the record. A total of 19 studies for trigeminal neuralgia (n > 100), 52 cases of cluster headache, and 42 cases of glossopharyngeal neuralgia were found. Radiosurgery remains the safest among various treatment options with equitable pain control with other percutaneous procedures. MVD remains the gold standard for long-term pain control. There is no difference in efficacy or tolerance between patients treated with gamma knife, linear accelerator, or CyberKnife. The minimum recommended prescription dose was 70 Gy (level of evidence II), and the maximum dose was 90 Gy (level of evidence III) in a single fraction. Radiosurgery provides 5-year pain control in 50% of patients without medication (85% of patients with/without medication) with an average latency period of 1-3 months. Approximately 8-15% of patients will experience a recurrence of pain after an average period of 1 year. Prospective pain relief will be about 60% at 3 years, 40% at 7 years, and 37% in 10 years. The main complication was facial hypoesthesia occurring in 25-50% of patients within 6 months-3 years and disabling in 10% of cases. Cluster headache and glossopharyngeal neuralgia are emerging conditions for treatment with GKRS, although long-term efficacy remains to be studied. Having searched PubMed and other databases and summarized the application of radiosurgery for facial pain, we concluded that radiosurgery is undoubtedly a promising tool for chronic facial pain, but further studies are needed to realize its long-term efficiency and advanced applications of the same.