Headache最新文献

Objectives/background: This study was undertaken to assess the therapeutic efficacy of galcanezumab in preclinical models of migraine and cluster headache and to determine potential shared trigeminovascular mechanisms of action. Galcanezumab is a humanized monoclonal antibody that binds to the neuropeptide calcitonin gene-related peptide, preventing its biological activity. It has been approved as a preventive treatment for both episodic and chronic migraine and episodic cluster headache, the most common trigeminal autonomic cephalalgia.

Methods: Trigeminovascular and trigeminal-autonomic reflex activation was evoked via electrical stimulation of the dura mater or superior salivatory nucleus (SSN), respectively. Evoked responses were recorded in the spinal trigeminal nucleus along with ongoing spontaneous neuronal and cutaneous noxious-evoked and non-noxious-evoked neuronal activity. Rats received either galcanezumab or human control IgG, and responses were compared between groups.

Results: Galcanezumab robustly reduced spontaneous (maximum decrease in dural-evoked: 73% [±3.5] at 4 h 30 min [p = 0.002]; in SSN-evoked: 67% [±10.7] at 4 h [p = 0.01]) and cutaneous non-noxious-evoked (maximum decrease in dural-evoked: 50% [±5.7], p = 0.004; in SSN-evoked: 47% [±10.5], p = 0.005, at the last recording time point) neuronal activation in the trigeminocervical complex, highlighting a general inhibition of trigeminal sensory processing. Furthermore, it significantly inhibited cutaneous noxious-evoked (maximum decrease in dural-evoked: 38% [±5.2], p = 0.005; in SSN-evoked: 34% [±7.6], p = 0.005, at the last recording time point), durovascular-evoked (maximum decrease 48% [±6] at the last recording time point, p = 0.001), and SSN-evoked responses (maximum decrease: 32% [±2.6] at 4 h, p < 0.001), demonstrating a clear reduction of trigeminal nociception, independent of the mode of activation. Galcanezumab did not have any effect on the mean arterial blood pressure.

Conclusion: Galcanezumab likely acts via a shared trigeminovascular mechanism to dampen noxious and nonnoxious sensory stimuli in preclinical models of migraine and trigeminal autonomic cephalalgias. This further supports the clinical efficacy of galcanezumab for migraine and cluster headache, while demonstrating general inhibition that may be of relevance to other facial pain conditions.

Background: Venous sinus stenting is an effective treatment for idiopathic intracranial hypertension (IIH) with venous sinus stenosis (VSS), which can reduce intracranial pressure (ICP) and alleviate symptoms. The present study aimed to investigate the associations between baseline characteristics and 6-month post-stenting ICP (hereinafter referred to as ICP6M).

Methods: Data from a prospective cohort of patients with IIH + VSS who received venous sinus stenting and a 6-month follow-up at a tertiary medical institution in China between January 2017 and June 2023 were analyzed. Demographic features, clinical manifestations, VSS characteristics and pre-stenting transstenotic gradients were collected. At the 6-month follow-up, improvements in symptoms and signs, and the ICP were evaluated. Independent factors associated with ICP6M were identified.

Results: A total of 104 patients (median age 35.0 years, 83.7% female) were included in the study. After adjustment for sex, disease duration, pre-stenting transstenotic gradient, Frisen Grade of both eyes, symptoms of visual disturbance, sinus dominance, and stenosis side, patients with extrinsic stenosis (β = 32.88, 95% confidence interval [CI] 14.16-51.60) had greater ICP6M values. Age (β = -0.98, 95% CI -1.88 to -0.08) was negatively associated with ICP6M, whereas body mass index (BMI, β = 3.88, 95% CI 1.95-5.81) and pre-stenting ICP (β = 0.35, 95% CI 0.12-0.57) were positively associated with ICP6M.

Conclusion: This study demonstrated that stenosis type, age, BMI, and pre-stenting ICP are independent predictors of ICP6M in stented patients with IIH + VSS. Close monitoring should be directed towards patients with extrinsic stenosis, younger age, higher BMI, and higher pre-stenting ICP, as these patients may have higher post-stenting ICP and subsequently poorer outcomes.

Objective: To assess the prevalence of primary headache associated with sexual activity (PHS) among adults seeking medical help for a headache in clinic-based settings.

Background: Primary headache associated with sexual activity is a benign primary headache disorder currently recognized as one of indomethacin-responsive and exercise-related cephalalgias. The epidemiology of PHS among adult patients assessed for headache in the tertiary headache centers is yet to be established.

Methods: PubMed/MEDLINE, Embase, and ScienceDirect databases were thoroughly searched for observational studies published since January 1, 1988, to November 11, 2024, that reported the relative frequency of PHS among adult patients evaluated for a headache in a clinic-based setting. The additional search of CINAHL (EBSCO) was performed on January 28, 2025, to see whether any relevant articles could have been omitted during the initial search process. The Meta-Analyses of Observational Studies in Epidemiology Guidelines were strictly followed by the study's design. Risk of bias was assessed using Joanna Briggs Institute Checklist for Studies Reporting Prevalence Data. The study's protocol was pre-registered on PROSPERO (ID: CRD42024611082).

Results: Of the original 854 records, 10 research articles (40,702 total individuals, 129 patients with PHS) satisfied all eligibility requirements. The majority of the studies showed a low risk of bias. The prevalence of PHS among adult patients evaluated for a headache in a tertiary care setting was 0.37% (95% confidence interval [CI], 0.17-0.81; 95% prediction interval [PI], 0.02%-6.20%; Luis Furuya-Kanamori index = 0.58) with substantial heterogeneity noted across the studies (I² = 91.66%). Interestingly, unlike in other primary headache disorders, males have been diagnosed with PHS considerably more often than females (0.28% [95% CI, 0.12-0.63; 95% PI, 0.02%-4.10%] vs. 0.18% [95% CI, 0.09-0.37; 95% PI, 0.02%-1.65%]). Moreover, sex-specific subgroup analysis revealed that PHS was more common among males (1.54%; 95% CI, 0.26-8.57), in comparison to female-specific subgroup (0.61%; 95% CI, 0.22-1.71). The pooled mean age of onset of PHS was 37.35 years (95% CI, 35.35-39.35; 95% PI, 34.01-40.69).

Conclusions: Our results showed that PHS is a rare headache disorder among adults evaluated for a headache in a clinic-based setting. Furthermore, PHS is more frequent among males and is diagnosed predominantly in males, typically in their mid-30s.

Objective: The objectives of this study were to compare the efficacy, including dose response, and safety of rimegepant, an orally administered small-molecule calcitonin gene-related peptide receptor antagonist, with placebo for the acute treatment of migraine in Japan.

Background: There is a substantial unmet need for the acute treatment of migraine in Japan due to undesirable attributes of existing acute treatments.

Methods: In this Phase 2/3, double-blind, randomized trial, adults with a ≥1-year history of migraine were recruited to 50 study centers in Japan. Participants were randomly assigned to receive rimegepant 25 mg, rimegepant 75 mg, or placebo and instructed to treat a single migraine attack of moderate or severe pain intensity. The randomization was stratified by preventive migraine medication use (yes or no). The primary endpoint was the proportion of participants with pain freedom at 2 h post-dose. Formal hypothesis testing was conducted for rimegepant 75 mg versus placebo. Safety was assessed based on adverse events (AEs).

Results: The study was conducted from August 9, 2022, through January 19, 2024. A total of 706 treated participants were evaluable for efficacy (rimegepant 25 mg, n = 238; rimegepant 75 mg, n = 238; placebo, n = 230) and safety (rimegepant 25 mg, n = 239; rimegepant 75 mg, n = 238; placebo, n = 229). Response rates for pain freedom at 2 h post-dose were 21.0% (rimegepant 25 mg), 32.4% (rimegepant 75 mg), and 13.0% (placebo): percentage difference rimegepant 75 mg versus placebo was 19.4% (95% confidence interval 12.0-26.8%, p < 0.001). On-treatment AEs were reported by 7.1% (rimegepant 25 mg), 9.2% (rimegepant 75 mg), and 6.6% (placebo) of treated participants; all were mild or moderate in intensity and most were not considered related to the study drug.

Conclusion: Rimegepant 75 mg demonstrated efficacy superior to placebo for the acute treatment of migraine, with a favorable safety profile, in participants in Japan. A dose-response relationship was observed for rimegepant (NCT05399459).

Plain language summary: This randomized trial was designed to test the effectiveness and safety of rimegepant for the acute treatment of migraine among adults in Japan. Results indicated that rimegepant was more effective than placebo, and the 75 mg dose was observed to be more effective than the 25 mg dose. These results are similar to previous findings from clinical studies in other countries, and suggest that rimegepant can help patients with migraine in Japan.

Objectives/background: Migraine is common among women, particularly during their reproductive years. There is limited research on the use of antimigraine medication before and during pregnancy. This study was undertaken to describe the use of antimigraine medication 3 months before pregnancy and in the first trimester among women with migraine and to evaluate maternal characteristics associated with continued use in the first trimester.

Methods: In this cross-sectional study, we used patient-reported data from the Copenhagen Pregnancy Cohort from October 2013 to May 2019 and included all women with migraine before pregnancy. The use of antimigraine medication before pregnancy and during the first trimester was assessed descriptively.

Results: Among women with migraine (N = 1586), 1241 of 1586 (78.2%) reported use of any antimigraine medication before pregnancy, and 347 of 1586 (21.8%) in the first trimester. Before pregnancy, paracetamol was the most used medication (793/1586, 50.0%), followed by ibuprofen (417/1586, 26.3%) and sumatriptan (191/1586, 12.0%). In the first trimester, paracetamol remained the most common medication (271/1586, 17.1%), followed by sumatriptan (49/1586, 3.1%), whereas the use of ibuprofen declined to 11 of 1586 (0.7%). A total of 278 of 1586 (17.5%) reported frequent use (daily or 1-2 times/week) of antimigraine medication before pregnancy, but only 79 of 1586 (5.0%) in the first trimester. Having a short length of education of 1-2 years, other chronic somatic diseases, or mental illness were, after adjustment for maternal age and parity, associated with frequent use of antimigraine medication in the first trimester compared to women with higher education, without other chronic somatic diseases, or without mental illness, respectively (adjusted odds ratio [aOR] = 3.09, 95% confidence interval [CI] = 1.93-4.95; aOR = 1.92, 95% CI = 1.14-3.23; and aOR = 2.14, 95% CI = 1.05-4.38).

Conclusion: Most women with migraine used antimigraine medication before pregnancy, whereas usage decreased markedly in the first trimester. Only a few women had frequent use in the first trimester. Women with a short length of education of 1-2 years, additional chronic somatic diseases, or mental illness were more likely to report use of antimigraine medication. By offering an overview of patient-reported use of antimigraine medication before and during early pregnancy in a hospital-based setting, this study contributes to existing knowledge in the field and provides valuable insights for clinicians working with pregnant women affected by migraine.

Objectives/background: This study was undertaken to test the ability of a widely used enzyme-linked immunosorbent assay (ELISA) kit to detect calcitonin gene-related peptide (CGRP) isoforms to better understand currently published clinical data. There is significant interest in measuring CGRP as a biomarker in headache and migraine research, with ELISAs being the preferred detection method. ELISAs use antibodies that have been raised against an antigen to allow selective quantification of an analyte in a sample. Understanding the specificity of these antibodies is crucial to interpreting results. One commercially available kit (Cusabio CSB-E08210h, Kit A) is purported to specifically detect β-CGRP (one of the two CGRP isoforms) over α-CGRP and has been used to investigate the potential for CGRP to be used as a biomarker for migraine. We investigated the ability of this kit to detect multiple isoforms of CGRP to better interpret published clinical results. We used a second ELISA kit (Bertin Bioreagent, A05481, Kit B) that is nonselective for the different CGRP isoforms as a control to ensure the CGRP we used could be detected in ELISAs.

Methods: We performed ELISAs according to the manufacturer's instructions, testing concentrations within the advertised range of each kit. At least three independent experiments were conducted for each kit.

Results: Kit B was able to detect both human and mouse α-CGRP and β-CGRP with a high degree of reproducibility. In contrast, Kit A did not detect bioactive forms of human α-CGRP or β-CGRP, nor mouse α-CGRP or β-CGRP.

Conclusion: Kit A may not be reliable for future studies, as it does not appear to detect mature bioactive CGRP. Importantly, conclusions from previous studies that used this kit may need to be reevaluated, as it is not clear what analyte the kit has detected. Our findings also highlight the importance of understanding research tools to ensure accurate interpretation of results.