Cephalalgia最新文献

Background/AimPersistent idiopathic facial pain (PIFP) is a rare condition with a lifetime prevalence of approximately 0.03%. It is characterized by persistent daily facial pain without identifiable cause and presents diagnostic and therapeutic challenges due to unknown pathophysiology, symptom overlap with other painful disorders, and limited evidence-based treatments. The aim of this Delphi study was to establish international consensus-derived guidelines for the management of patients with PIFP.MethodsA three-round Delphi study was conducted with 16 international pain experts, each with ≥10 years of clinical experience in pain management and extensive peer-reviewed publications. The first round involved open-ended questions, and the qualitative data were analyzed using systematic text condensation, resulting in a quantitative questionnaire with 42 statements. Subsequent rounds employed Likert-scale responses to these statements. Consensus was defined as ≥80% agreement or disagreement. In addition, if 11-12 (68-75 percent) out of the 16 experts agreed or disagreed, consensus was not reached, but a majority was considered to have a particular opinion.ResultsConsensus was reached in 35 out of the 42 statements (83%), emphasizing multidisciplinary collaboration and avoidance of invasive procedures in the treatment of PIFP. In an additional three statements (7%) a majority of the experts agreed with each other. In four statements (10%), no consensus or majority was reached. Pharmacological treatments, including tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids, may be considered; however, opioids should generally be avoided in the treatment of PIFP. Patient education and behavioral therapies are important interventions, and the most important measure of therapeutic success is improved quality of lifeConclusionThe present Delphi study has established internationally derived consensus guidelines and recommendations for the evaluation and comprehensive management of patients with PIFP. This is a first step in gathering knowledge for future evidence-based guidelines and more specific treatment recommendations. These international expert consensus guidelines recommend a multi- or interdisciplinary approach in managing PIFP, avoiding invasive interventions and prioritizing patient-centered outcomes.

BackgroundChronic migraine (CM) is highly disabling, and many patients fail to respond to monotherapy with approved preventive treatments. OnabotulinumtoxinA (BoNTA) and atogepant act on distinct but complementary targets within the trigeminovascular system and may exert additive or synergistic effects when used together. Real-world data on their combination remain scarce.MethodsWe prospectively analyzed adult patients with CM who had received at least three prior BoNTA cycles and initiated atogepant 60 mg/day for a minimum of 24 weeks as add on to BoNTA. Co-primary outcomes were changes in monthly migraine days (MMDs) and ≥50% response rate at 24 weeks. Secondary outcomes included disability, medication use, tolerability and subgroup comparisons by prior monoclonal antibodies exposure.ResultsAmong 101 patients, 82 completed 24 weeks of co-treatment. Mean MMDs decreased by 6.5 days (p < 0.001) and 45.1% of patients achieved a ≥50% reduction. Acute medication days decreased by 6.0 (p < 0.001) and Headache Impact Test-6 scores improved significantly (mean change: -4.0; p < 0.001). Patient's Global Impression of Change scores indicated moderate-to-great improvement. Anti-calcitonin gene-related peptide naïve patients experienced larger reductions in MMDs (-7.75 vs. -5.87) and disability scores compared to non-naïve patients. Multivariable analysis identified only baseline acute medication use as predictor of response. Adverse events were mild and consistent with known safety profiles for both drugs separately; no novel safety concerns emerged.ConclusionsThe addition of atogepant to BoNTA might be effective and well tolerated in real-world setting, including CM patients previously exposed to multiple preventives. Prospective controlled trials and health-economic evaluations are warranted to validate these observations and inform future clinical guidelines.

BackgroundIt is becoming increasingly evident that the vasculature is implicated in migraine pathophysiology. Calcitonin gene-related peptide (CGRP) acts as one of the key migraine mediators through various mechanisms that includes endothelium-mediated cerebral vessel vasodilation. Endothelial cells express mechanosensitive Piezo1 channels and have been suggested to play a role in migraine pathophysiology. However, the crosstalk between these two migraine-related signalling pathways remains unclear.MethodsWe measured intracellular calcium (Ca²⁺) in human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs), after exposure to Yoda1, a specific Piezo1 channel agonist, with and without CGRP. In addition, we investigated the effects of CGRP and Yoda1 on cellular remodelling by staining for focal adhesion (FA) protein paxillin using immunocytochemistry.ResultsOur data suggest that a one-hour sensitization of hiPSC-ECs with CGRP followed by application of Yoda1 leads to a higher intracellular Ca²⁺ level compared to when Yoda1 and CGRP are acutely applied separately or combined, suggesting at least indirect crosstalk between the two signalling pathways in the vascular system. CGRP receptor antagonist BIBN4096 significantly reduced the intracellular Ca²⁺ level under this sensitization protocol, confirming effective CGRP pathway blockade. The results also show that a one-hour sensitization of CGRP and Piezo1 activation affects cellular remodelling as evidenced by an increased number and area size of paxillin FA points per cell in hiPSC-ECs.ConclusionsWe have generated a human cell assay based on iPSC-derived endothelial cells and provided some evidence for crosstalk between mechanosensitive Piezo1 channels and CGRP in our hiPSC-EC system, which shows the potential for in vitro modelling of vascular implications relevant to migraine.

BackgroundMany guidelines list migraine with aura (MwA) as a contraindication to estrogen-containing combined hormonal contraceptives (CHCs) due to vascular risks. However, current evidence is based on small sample studies with potential influence by confounding factors. Additionally, few studies have examined the vascular risk associated with modern CHCs with lower dose estrogen, particularly in relation to aura status. The present study aims to investigate the vascular risk of modern CHCs in women with migraine with and without aura.MethodsWe used a de-identified electronic medical record database with 120 million patients across multiple health systems in the United States of America. We included female patients aged 18-45 years who received a migraine diagnosis code, had at least three office visits within three years, and were prescribed at least one migraine-specific medication within 6 months following the first outpatient visit. All data after 2010 were included. Patients with prior cardiovascular events were excluded. Our composite endpoint consisted of acute ischemic stroke, acute myocardial infarction, deep vein thrombosis/pulmonary embolism and intravenous thrombolytic administration. We stratified our analysis according to CHC exposure and aura status and compared the incidence of the endpoint with high-dimensional propensity score-matching between CHC users and non-users in (i) the overall cohort, (ii) MwA and (iii) migraine without aura (MwoA); between MwA and MwoA in (iv) patients prescribed CHCs; and in (v) those without CHC prescriptions.ResultsWe included 5535 patients who received CHC prescriptions and 21,520 who did not. 114 (2.06%) of CHC users and 547 (2.54%) of CHC non-users had at least one vascular event. With propensity score-matched comparison, the composite endpoint did not significantly differ between CHC and non-CHC in the overall migraine group, those with MwA and the MwoA group. In those prescribed CHC, MwA and MwoA did not differ in all the outcomes. For CHC non-users, MwA was associated with a higher incidence of acute ischemic stroke (hazard ratio = 2.45; 95% confidence interval = 1.58-3.78; p < 0.001; n = 6201 in each group) and the composite endpoint (hazard ratio = 1.34; 95% confidence interval = 1.08-1.67; p = 0.008).ConclusionsOur real-world study showed that exposure to modern CHC was not associated with a significant increase in vascular risk in women aged 18-45 years with migraine, MwA or MwoA who have no prior cardiovascular events. However, in those who never received CHC, MwA was associated with higher vascular risks compared to MwoA. While limitations exist using large scale electronic medical record databases for analysis, our results suggest that carefully designed prospective studies should be conducted to reassess the vascular risk associated with CHC use in women with migraine, especially MwA.

BackgroundGreater occipital nerve block (GONB) has become an established treatment for migraine. Though numerous systematic reviews and randomised control trials (RCTs) are cited as supporting evidence, the quality and consistency of this data remains unclear.MethodsAn umbrella review of systematic reviews investigating GONB for migraine was conducted. Additionally, an independent systematic review and meta-analysis of relevant RCTs was performed in accordance with PRISMA guidelines. Both evaluated MEDLINE ('PubMed'), Embase, and CENTRAL databases.ResultsNine relevant systematic reviews were identified; all had significant limitations and/or contained methodological errors. The reviews had been cited 256 times. None were eligible for statistical analysis.Sixteen RCTs (930 patients) and seven RCTs (401 patients) were included for qualitative and quantitative analyses respectively. Studies were heterogeneous in their methodologies. No serious adverse effects were identified. With moderate certainty, local anaesthetic (LA) GONB reduces headache severity in acute migraine attacks at 30 min (-2.08; p < 0.001). With low certainty, weekly bilateral LA GONB injections reduce headache severity (-1.33; p < 0.001) and monthly headache days (-4.46; p < 0.001) at one month for chronic migraine. Sustained benefits of GONB remain unclear. Data was insufficient to analyse the efficacy of steroid GONB, LA-steroid GONB, nor unilateral GONB for chronic migraine, and GONB - of any type - for episodic migraine.ConclusionsThere is limited RCT evidence supporting GONB for the treatment of migraine. Existing systematic reviews should be interpreted with caution. RCTs with homogeneous methodologies are required to evaluate GONB in the management of disability in migraine.Trial RegistrationPROSPERO registration ID: CRD42024595492.

BackgroundEvoked potentials are widely used to investigate sensory and nociceptive processing abnormalities in migraine. However, electrophysiological distinctions between migraine subtypes remain insufficiently characterized in the literature. The aim was to systematically review and summarize neurophysiological abnormalities in evoked potential studies (visual, auditory, brainstem, somatosensory and laser) in migraine patients, with a particular focus on latency, amplitude, habituation and clinical correlations across subtypes and healthy controls.MethodsFollowing PRISMA guidelines, we searched PubMed, EMBASE and Web of Science for studies, terms included "Migraine Disorders," "Migraine," "Vestibular Diseases" and "Evoked Potentials", which were published from 2000 to 2024 were included. Risk of bias was assessed using a modified Newcastle-Ottawa Scale.ResultsIn total, 813 studies were screened, resulting in 55 studies meeting the inclusion criteria. Patients with migraine with aura demonstrated higher amplitudes and asymmetry of visual evoked potentials compared to those with migraine without aura. Habituation deficits were particularly evident across all types of evoked potentials. A few studies compared chronic and episodic migraine, reporting higher brainstem and somatosensory evoked potential amplitudes in chronic migraine.ConclusionsMigraine patients have a consistent habituation deficit on all evoked potential parameters. Migraine with aura and chronic migraine may have higher cortical excitability. Further research with larger sample sizes, standardized methodologies and an accurate comparison of migraine phases will enlighten our understanding of the migraine subtypes.Trial RegistrationPROSPERO ID: CRD42024502803.

AimThe diagnostic criteria for chronic migraine, which are based on the total number of monthly headache days, are the subject of ongoing debate. The present study aimed to investigate and compare the burden of disease and quality of life between high-frequency episodic migraine and chronic migraine, using data from the large population-based PopHEAD study.MethodsPopHEAD is a population-based cross-sectional study in the Norwegian county of Vestfold and Telemark performed in 2023. Among 28,753 randomly selected adults (aged 18-70 years) invited to complete an electronic questionnaire, 8265 (28.7%) participants responded. The questionnaire was a modified version of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation questionnaire, and migraine was classified using a diagnostic algorithm that has been validated by telephone interview in this population. High-frequency episodic migraine was classified according to newly proposed criteria, and chronic migraine according to International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria. Using linear regression for continuous variables and logistic regression for binary outcomes, we compared the disease burden and quality of life between participants classified with high-frequency episodic migraine and those with chronic migraine. The analysis was conducted in two steps: a primary analysis adjusted for age and sex, as well as a second analysis with an additional adjustment for monthly migraine days.ResultsOf the 8265 responders, 225 had high-frequency episodic migraine and 349 had chronic migraine. Compared to the high-frequency episodic migraine group, the chronic migraine group had more monthly migraine days (17.9 vs. 9.7, p < 0.001) and headache days (20.8 vs. 9.9, p < 0.001). The chronic migraine group also used more acute medication (p < 0.001). In analyses adjusted for age and sex, participants with chronic migraine reported greater disease burden across almost all measures, including work and social impairment, and had a lower quality of life (p < 0.01). With additional adjustment for monthly migraine days, no significant differences in disease burden were found between the two groups, except from days missed from household work (p = 0.03).ConclusionsThe higher disease burden observed in chronic migraine compared to high-frequency episodic migraine was fully explained by the higher number of monthly migraine days in the chronic migraine group. Our findings support previous suggestions to simplify the ICHD-3 criteria for chronic migraine by basing it solely on the number of monthly migraine days.