Cephalalgia最新文献

Observational studies have linked migraine to a wide range of risk factors and diseases, although the causality of these associations is uncertain. Mendelian randomization (MR) is an analytic paradigm that exploits germline genetic variants as natural experiments, providing a framework for causal inference from observational data. In this narrative review, we summarize the core principles and assumptions of MR and highlight methodological considerations unique to its application to migraine research. We review key MR findings across several domains of migraine research, noting areas of consistent evidence, as well as conflicting results. We then discuss limitations of MR in the context of migraine research, emphasizing that MR is not a panacea for causal inference. We conclude by underscoring the need for interdisciplinary collaboration between methodologists and domain experts to prioritize patient-relevant questions, refine analytic approaches and translate genetic insights into more effective therapies.

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.

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.