Headache最新文献

Objective: To explore the relationships among anxiety, depression, and headache-related disability in a pediatric clinic-based retrospective cross-sectional study.

Background: Anxiety and depression are commonly considered comorbidities of headache disorders and are frequently seen in children and adolescents. These conditions can contribute to disability and may have a cumulative impact. In this study, we tested whether self-reported anxiety and/or depression in youth were associated with headache-related disability.

Methods: This was a retrospective cross-sectional study of children ages 6-17 years old who completed a headache intake questionnaire at the time of a new outpatient neurology visit. Those who reported on behavioral health symptoms, involvement of a behavioral health provider (i.e., yes/no), and the PedMIDAS (a validated metric of headache-related disability) were included. The relationship between anxiety and/or depression and headache-related disability was examined.

Results: Of the 12,660 questionnaires queried, 9118 met criteria for inclusion. Respondents were 64.0% female and had a median age of 13.5 years (interquartile range [IQR] 10.3, 15.7). Compared to patients without self-reported anxiety/depression, patients with anxiety and depression reported higher headache-related disability (M = 17.0, [IQR 6.0, 41.0]) even after accounting for covariates (estimated difference = 6.0, 95% confidence interval [CI: 4.4-7.5]). For participants with anxiety and/or depression, having a behavioral health provider was associated with greater headache-related disability (estimated difference = 7.0; 95% CI 4.6-9.3).

Conclusions: Patients with self-reported anxiety and/or depression reported higher headache-related disability. Having a behavioral health provider was associated with greater headache-related disability, indicating the complexity and high level of need for this population. Further research is needed to understand the directionality of these results; however, patients with headache as well as depression and or anxiety are a vulnerable group who may benefit from an integrated care model.

Background: Understanding the neural mechanisms underlying migraine and other primary headache disorders is critical for the development of long-term cures. Magnetoencephalography (MEG), an imaging modality that measures neuronal currents and cortical excitability with high temporal and superior spatial resolution, has been increasingly used in neurological research. Initial MEG studies showed promise in directly recording cortical spreading depression-a cortical correlate of migraine with aura. However, lately MEG technology has highly evolved with greater potential to reveal underlying pathophysiology of migraine and primary headache disorders, and aid in the identification of biomarkers.

Objective: To systematically review the use of MEG in migraine and other primary headache disorders and summarize findings.

Methods: We conducted a systematic search and selection of MEG studies in migraine and primary headache disorders from inception until June 8, 2023, in Medline, Embase, Cochrane, and Scopus databases. Peer-reviewed English articles reporting the use of MEG for clinical or research purposes in migraine and primary headache disorders were selected.

Results: We found 560 articles and included 38 in this review after screening. Twelve studies investigated resting-state, while others investigated a sensory modality using an evoked or event-related paradigm with a total of 35 cohort and 3 case studies. Thirty-two studies focused exclusively on migraine, while the rest reported other primary headache disorders.

Conclusion: The findings show an evolution of MEG from a 7- to a 306-channel system and analysis evolving from sensor-level evoked responses to more advanced source-level connectivity measures. A relatively few MEG studies portrayed migraine and primary headache disorders as a sensory abnormality, especially of the visual system. We found heterogeneity in the datasets, data reporting standards (due to constantly evolving MEG technology and analysis methods), and patient characteristics. Studies were inadequately powered and there was no evidence of blinding procedures to avoid selection bias in case-control studies, which could have led to false-positive findings. More studies are needed to investigate the affective-cognitive aspects that exacerbate pain and disability in migraine and primary headache disorders.

Background: While headache disorders are linked to low physical activity levels, the impact of depression on this relationship is unclear.

Objective: To assess how single and comorbid diagnoses of migraine and tension-type headache (TTH) interact with depression and leisure-time physical activity (LTPA) levels in The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Methods: In this cross-sectional analysis based on the ELSA-Brasil baseline data, the relationship of migraine, TTH (both assessed with the International Classification of Headache Disorders, Second Edition), and depression (assessed with the Clinical Interview Schedule-Revised) with LTPA levels (International Physical Activity Questionnaire) was investigated by employing linear regression models. Models were adjusted for sociodemographic, lifestyle, and clinical covariates, and interaction terms were created to examine additive effects of comorbid conditions.

Results: Among 14,088 participants, 54.4% (7668/14,088) were female, prevalence rates were: TTH = 39.6% (5573/14,088), migraine = 27.0% (3806/14,088), depression = 0.7% (94/14,088), depression + TTH = 1.1% (148/14,088), and depression + migraine = 2.5% (356/14,088). The mean (standard deviation) LTPA levels across the groups were: no headache + no depression = 148.7 (183.0) min/week, TTH = 133.5 (170.1) min/week, migraine = 110.3 (154.8) min/week, depression = 76.5 (146.3) min/week, depression + TTH = 84.5 (127.7) min/week, and depression + migraine = 64.3 (123.2) min/week. Negative associations were found for depression (β = -55.1, 95% confidence interval [CI] -93.6 to -17.0; p = 0.005), migraine (β = -24.7, 95% CI -33.2 to -15.4; p < 0.001), and TTH (β = -15.5, 95% CI -23.1 to -7.6; p < 0.001) with LTPA. No interaction effect was observed for depression + TTH (β = 36.0, 95% CI -12.6 to 84.6; p = 0.147) and depression + migraine (β = 31.7, 95% CI -11.3 to 74.7; p = 0.149), indicating no additive effect of comorbid conditions on LTPA levels. After adjusting for headache attack frequency, only depression + migraine remained negatively associated with LTPA (β = -38.7, 95% CI -71.6 to -5.8; p = 0.021).

Conclusions: Headache disorders and depression were independently and inversely associated with LTPA, with the strongest effects seen in depression alone or comorbid with migraine.

Background: Observational studies have reported inconsistent relationships between migraine and the risk of intracranial aneurysm and subarachnoid hemorrhage (SAH).

Objective: To determine whether genetic liability to migraine is associated with risk of intracranial aneurysm and aneurysmal SAH.

Methods: This study was designed as a two-sample Mendelian randomization (MR) analysis. Genetic associations with migraine were obtained from a large-scale meta-analysis of five population and clinic-based genome-wide association studies of migraine (102,084 cases and 771,257 controls of European ancestry). Genetic associations with intracranial aneurysm and SAH were obtained from a meta-analysis of 22 population-based genome-wide association studies (7495 cases and 71,934 controls of European ancestry). Findings were corroborated by sensitivity analyses and replicated in an independent sample of combined cases of intracranial aneurysm and SAH (3529 cases and 234,948 controls of Asian ancestry from the Biobank Japan and China Kadoorie Biobanks). In secondary analyses, we investigated the outcomes of extracranial aneurysm in the FinnGen and UK Biobank cohorts (up to 7466 combined cases of thoracic and abdominal aortic aneurysm).

Results: Genetic liability to migraine was associated with increased risk of the combined outcome of unruptured intracranial aneurysm and SAH (odds ratio [OR] of outcome per doubling in migraine liability 1.19, 95% confidence interval [CI] 1.06-1.35; p = 0.005). This finding was replicated in an independent sample (OR 1.15, 95% CI 1.02-1.30; p = 0.027), and there were similar associations across the component outcomes of unruptured intracranial aneurysm (OR 1.20, 95% CI 1.01-1.42; p = 0.035) and SAH (OR 1.18, 95% 1.04-1.33; p = 0.008). These findings were consistent in sensitivity analyses robust to violations of the MR assumptions. In reverse MR analyses, genetic liability to intracranial aneurysm was not associated with migraine (OR 1.03, 95% CI 0.99-1.07; p = 0.141). In a secondary analysis, there were similar associations of genetic liability to migraine with all forms of aortic aneurysm (OR for combined thoracic and aortic aneurysm 1.18, 95% CI 1.10-1.27; p = 8.49 × 10^-6).

Conclusion: Genetic liability to migraine was associated with increased risk of intracranial and extracranial aneurysms, supporting a causal relationship between liability to migraine and these traits. Further work is needed to identify the biological mechanisms and clinical relevance of these findings.

Objective: The potential for drug-drug interaction of multiple-dose intranasal zavegepant on the single-dose oral contraceptive ethinyl estradiol and levonorgestrel (EE-LNG) was evaluated.

Background: Zavegepant (as a nasal spray) is a calcitonin gene-related peptide receptor antagonist approved in the United States for treatment of acute migraine in adults.

Methods: This single-center, Phase 1, open-label, fixed-sequence study included healthy, nonsmoking females (18-45 years old). In treatment Period 1, a single oral dose of EE-LNG 0.02-0.10 mg was administered on Day 1. In treatment Period 2, intranasal zavegepant (20 mg daily; 10 mg per nostril separated by 1 h) was administered on Days 1-5; 1 oral dose of EE-LNG 0.02-0.10 mg was administered immediately after first 10 mg intranasal zavegepant dose on Day 2. Blood samples for EE-LNG concentrations were collected on Day 1, treatment Period 1, and Day 2, treatment Period 2, and zavegepant concentrations on Day 2, treatment Period 2. Noncompartmental pharmacokinetic parameters included maximum observed concentration (C_max), area under the concentration-time curve (AUC) from Time 0 to last non-zero concentration (AUC_0-t), and AUC from Time 0 to infinity (AUC_0-inf). The safety and pharmacokinetic sample sizes were 26 and 23, respectively.

Results: Statistical comparisons of pharmacokinetic exposure parameters after co-administration of zavegepant and EE-LNG versus EE-LNG alone showed small, but statistically insignificant, changes in either EE or LNG exposure. EE comparison ratios (90% confidence intervals [CIs]) were 109.9% (105.3%, 114.8%) for AUC_0-inf and 110.2% (104.6%, 116.1%) for C_max. LNG comparison ratios (90% CIs) were 107.0% (100.2%, 114.3%) for AUC_0-inf and 108.8% (99.9%, 118.4%) for C_max. Frequently reported treatment-emergent adverse events included dysgeusia (n = 25, 96%), throat irritation (n = 11, 42%), headache (n = 10, 39%), nasal discomfort (n = 7, 27%), pharyngeal paresthesia (n = 5, 19%), and nausea (n = 4, 15%).

Conclusion: Co-administration of zavegepant nasal spray with a single dose of an oral contraceptive resulted in no clinically meaningful changes (<12% increase) in EE-LNG exposure.

Objective: To explore the efficacy and safety of 5% lidocaine-medicated plaster (LMP) in patients with trigeminal neuralgia (TN).

Background: TN is an excruciatingly painful type of neuropathic facial pain. Anti-epileptics are the first-line treatment for TN; however, these oral drugs alone sometimes fail to achieve satisfactory analgesic effects. Two retrospective studies have shown that LMP can be an effective and safe treatment option for some patients with TN. No other high-quality clinical studies have explored the effect and safety of LMP in patients with TN.

Methods: The PATCH trial is an enriched enrollment with randomized withdrawal, double-blind, vehicle-controlled, parallel-group trial performed at five study centers. Eligible patients with TN received LMP during a 3-week initial open-label phase. Patients who met the response criteria entered the double-blind treatment phase and were randomly assigned for treatment with either LMP (LMP group) or vehicle patches (control group) at a 1:1 ratio. Patients who met the criteria for treatment failure were withdrawn from the double-blind treatment phase, and treatment was continued in the remaining patients for up to 28 days. The primary outcome was the number of treatment failures. The secondary endpoints were the time to loss of therapeutic response (LTR) in the double-blind phase and the weekly mean pain severity in both the open-label phase and the double-blind phase of the study.

Results: The first patient was enrolled in this study on May 1, 2021, and the enrollment of the last patient was completed on August 26, 2022. A total of 307 patients were initially screened, 226 (74.0%) of whom entered the open-label phase. Of the 226 respondents, 124 (55.0%) were randomized to the double-blind phase. In the double-blind phase, 62 patients were assigned to the LMP group, and 62 were assigned to the control group. For the primary endpoint, 16 (26.0%) patients with LMP and 36 (58.0%) patients with vehicle patches met the treatment failure criteria during the double-blind phase (relative risk, 0.48; 95% confidence interval [CI], 0.31 to 0.75; p < 0.001). The survival curve of the LTR showed that the LTR of LMP was significantly longer than that of the vehicle patches (hazard ratio, 0.275; 95% CI, 0.15 to 0.50; log-rank p < 0.001). LMP also significantly reduced the weekly mean pain severity in the double-blind phase of the study (p = 0.007).

Conclusions: LMP produced partial relief of pain symptoms in some patients with TN. For responders, LMP may be used as an add-on therapy in a multidrug treatment protocol.