Headache最新文献

Objectives/background: To determine whether the volume of specific subcortical structures differ between people with migraine and healthy controls, and whether these volumes vary across distinct migraine subtypes and phases. Subcortical structures, including regions involved in pain processing and sensory integration, play a key role in migraine pathophysiology, yet studies on volumetric differences have shown conflicting results. This study uses a large cohort and robust imaging methods to clarify whether subcortical volumes differ in migraine.

Methods: In this cross-sectional study at the Danish Headache Center in Denmark, conducted between January 2020 and December 2023, adult participants with migraine and age- and sex-matched healthy controls underwent a single magnetic resonance imaging session at 3T. T1-weigthed scans were acquired to measure the volumes of subcortical structures using automated segmentation techniques. The structures analyzed included the thalamus, putamen, caudate nucleus, pallidum, nucleus accumbens, amygdala, and hippocampus.

Results: Imaging data from 295 participants and 154 healthy controls were included in the final analyses. No significant differences were observed between participants with migraine and healthy controls in thalamic volume (migraine: 7243 ± 923 mm³ vs. healthy controls: 7350 ± 782 mm³; p = 0.774) or hippocampal volume (migraine: 4204 ± 398 mm³ vs. healthy controls: 4307 ± 446 mm³; p = 0.337). No differences were observed in any other subcortical structure. Likewise, different subgroup analyses revealed no volumetric differences in episodic versus chronic migraine, migraine with aura versus without aura, ictal versus headache free, or between each migraine subgroup and healthy controls (all p > 0.05 after multiple comparison correction).

Conclusion: In this large cross-sectional study, we found no evidence of subcortical volume differences between adults with migraine and healthy controls. Furthermore, no differences were found across migraine subtypes or phases. These findings indicate that subcortical volumetric measures are not suitable as imaging biomarkers of migraine. Future research should explore functional and metabolic alterations in subcortical structures to better understand the neurobiologic underpinnings of migraine.

Objectives/background: This study aimed to systematically review the literature and summarize, as well as quantitatively pool when feasible, longitudinal evidence regarding psychosocial predictors of headache chronification.

Methods: A comprehensive search was conducted in PubMed/MEDLINE, CINAHL, and PsycInfo. The Domain-Determinants-Outcome framework was used to design the search strategy, and studies were screened according to the Patients Intervention Comparator Outcome Timing Setting framework. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was performed, and the certainty of evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation approach.

Results: The initial search, including two additional studies identified through hand-searching, yielded 1509 studies after removal of duplicates, of which eight met the inclusion criteria. Seven studies focused on depression as a predictor of migraine chronification and one on depression as a predictor of tension-type headache (TTH) chronification. One study examined anxiety and another studied stress as predictors of both migraine and TTH chronification. Five studies were included in the meta-analysis for depression as predictor; the pooled unadjusted risk ratio was 2.26 (95% confidence interval = 1.69-3.02), the adjusted risk ratio was 1.53 (95% confidence interval = 1.47-1.58), and Grades of Recommendation, Assessment, Development, and Evaluation assessment indicated that depression is a significant predictor of migraine chronification, with a moderate certainty of evidence. For anxiety and stress, the certainty of evidence was rated as moderate. Due to limited data, no firm conclusions could be drawn for other psychosocial factors or for predictors of TTH chronification.

Conclusion: There is moderate certainty of evidence supporting depression as a predictor of migraine chronification. For anxiety and stress in relation to migraine and TTH, the certainty of evidence is moderate.

Objectives: To evaluate the associations between the Life's Essential 8 (LE8) factors proposed by the American Heart Association and migraine disorders in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Background: There is limited information about the relationship of cardiovascular/cerebrovascular risk factors with migraine types, severity, and sex-specific differences.

Methods: The LE8 factors and migraine types (no migraine, migraine without aura [MWO], and migraine with aura [MWA]) and severity were cross-sectionally evaluated based on information from wave 2 (2012-2014) of the ELSA-Brasil. The LE8 factors' metrics were computed following the American Heart Association's scoring system. Migraine diagnoses were based on the ICHD-3 criteria. Sociodemographic- and preventive medication use-adjusted odds ratios (aORs) with a 95% confidence interval (CIs) are reported for the associations between LE8 factors adherence levels (low [reference], moderate, and high) and migraine type, severity (defined as attack frequency ≥ 15 days/month [reference: <15 days/month]), and sex.

Results: Of 4312 participants (mean age: 55.1 years, SD ± 8.9; 54.3% [2342/4312] female), MWO and MWA were identified in 19.3% (835/4312) and 10.6% (460/4312) of participants, respectively. Low, moderate, and high adherence to the LE8 total factors were identified in 11.8% (511/4312), 74.0% (3189/4312), and 14.2% (615/4312) of participants, respectively. Overall, compared to no migraine, high adherence to the LE8 total score was associated with a lower occurrence of MWA [aOR: 0.36 (95% CI: 0.23, 0.55)], MWO [aOR: 0.56 (95% CI: 0.40, 0.78)], and severity [aOR: 0.46 (95% CI: 0.26, 0.82)]. Among females, high adherence to physical activity, sleep health, body mass index, blood lipids, and blood pressure was associated with a lower prevalence of MWA, whereas physical activity and nicotine exposure were associated with a lower prevalence of MWO. Among males, high adherence to nicotine exposure was associated with increased odds of MWO, whereas high adherence to diet and blood lipids was associated with higher and lower odds of frequent headache attacks, respectively.

Conclusion: In the ELSA-Brasil study, high adherence to the LE8 total score was associated with lower occurrence of migraine disorders and severity, with type-, severity-, and sex-specific associations. The cross-sectional design precludes causal inferences, and further investigations are warranted to evaluate the clinical utility of the LE8 framework for reducing migraine burden, particularly in females.

Objective/background: This study was undertaken to assess participants' impression of use and satisfaction with STS101 in a long-term, open-label safety study. The ASCEND study assessed the safety and tolerability of STS101, an investigational drug-device combination of 5.2 mg dihydroergotamine in a single-use nasal delivery device for the acute treatment of migraine with/without aura, across 12 months.

Methods: ASCEND (NCT04406649) was an open-label, single-arm, prospective interventional study in adults (18-65 years) with history of migraine from September 2020 to January 2023. Participants could self-administer STS101 for ≤2 doses within 24 h to treat a single migraine attack and ≤12 doses/month. Data on patient global impression, ease-of-use impression, patient likelihood of use, and comparison of study medication with previously used migraine medication were collected at 3-, 6-, and 12-month timepoints. Participants' ratings were assessed using a 5-point Likert scale. Exploratory efficacy parameters (freedom from pain and most bothersome symptom) were recorded in participants' electronic diaries.

Results: Overall, the majority of participants had favorable impressions of STS101, which were consistent across the assessments at 3-, 6-, and 12-month timepoints. STS101 was considered easy or very easy to use by 92.3%, 92.9%, and 91.2% of participants at months 3, 6, and 12, respectively. After 3, 6, and 12 months of use, 78.9%, 80.5%, and 73.7% of participants indicated they were likely or very likely to use STS101 if it was available. When asked at the 3-, 6-, and 12-month assessments to compare STS101 to their usual migraine medication, 63.9%, 74.1%, and 70.1% of participants agreed or strongly agreed that STS101 helped them return to normal faster than their usual medication. A total of 64.9%, 66.1%, and 69.3% of participants agreed or strongly agreed that STS101 worked faster and 67.0%, 73.7%, and 72.5% of participants agreed or strongly agreed that STS101 worked more consistently than their usual medication. Treatment with STS101 showed freedom from headache pain at 2, 4, 24, and 48 h postdose in 33.3%, 61.3%, 86.2%, and 91.1% of participants, respectively. Similar trends were seen in freedom from most bothersome symptom as reported by 53.3%, 78.0%, 91.9%, and 93.7% of participants at 2, 4, 24, and 48 h postdose, respectively.

Conclusion: Participant impression data through 12 months suggest that STS101 was generally perceived as favorable by participants on multiple attributes. Most considered STS101 easy to use and indicated they would be likely to use the product if it were available. Exploratory efficacy evaluations indicated beneficial effects.

Background: Headache disorders, particularly migraine and tension-type headache, are significant contributors to disability worldwide, with a rising burden over recent decades. This burden varies across regions, sexes, and age groups.

Methods: We used data from the Global Burden of Disease Study 2021 study to examine the incidence, prevalence, and disability-adjusted life years (DALYs) of headache disorders across 204 countries and territories.

Results: Between 1990 and 2021, the global burden of headache disorders increased significantly, with incidence rising from 533.8 million (95% uncertainty intervals [UI]: 472.5-591.4) to 809.2 million (95% UI: 717.8-896.0), prevalence from 1.79 billion (95% UI: 1.65-1.94) to 2.81 billion (95% UI: 2.60-3.03), and disability-adjusted life years from 30.3 million (95% UI: 5.96-64.8) to 48.0 million (95% UI: 9.80-100.7). Females consistently bore a 1.6-fold higher DALY burden than males, particularly in the 15-49 years age group. Middle sociodemographic index regions, especially in Latin America, saw the most substantial increases in both all-age rates and age-standardized rates. Projections to 2050 indicate further growth, with incidence reaching 1.08 billion, prevalence 3.84 billion, and DALYs 631.7 million.

Conclusions: The global burden of headache disorders is rising, with notable variations across regions, sexes, and age groups. Sex differences, with higher rates in females, remain consistent, although the burden in males is increasing rapidly. Effective management strategies are urgently needed, including improved healthcare services, increased awareness, and targeted interventions to enhance patients' quality of life and the efficiency of global healthcare systems.

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.