Cephalalgia最新文献

BackgroundMigraine is a highly prevalent neurological disorder with many treatment options, both pharmacological and non-pharmacological. Artificial intelligence (AI) has great potential to optimize treatment selection strategies for individual patients. This review provides an overview of AI models and the techniques used to predict migraine treatment outcomes.MethodsWe conducted a literature search in PubMed and examined studies that reported employing AI models to predict migraine preventive and acute treatment outcomes. We also explored incorporating AI/machine learning to enhance personalized migraine treatment strategies, including forecasting migraine attacks. Additionally, we summarized future research directions, including incorporating multimodality data, using AI frameworks for the discovery of novel treatment targets, and advancing the field with innovative AI techniques such as digital twins, conversational AI and virtual AI agents.ResultsStudies have employed ML and deep learning on a combination of clinical features and imaging data to predict acute or preventive migraine treatment outcomes with reported success. Continued model optimization, validation, and prospective assessment of the clinical utility of deploying ML models in real-world settings are crucial.ConclusionsWhile AI has demonstrated success in predicting migraine treatment responses, future research incorporating novel AI techniques and diverse data sources could pave the way to advance personalized migraine treatment.

Migraine is a common neurological disorder that predominantly affects women during their reproductive years, presenting unique challenges in the context of pregnancy, breastfeeding, and pregnancy planning. In the present review, we intend to summarize those challenges and propose possible solutions. Women with migraine, particularly those with aura, face an increased risk of pregnancy-related complications, including preeclampsia, stroke, and preterm birth, highlighting the need for careful monitoring throughout gestation. When migraine persists during pregnancy, management should prioritize non-pharmacological approaches, with a strong emphasis on lifestyle modifications and behavioral therapies. In some settings, non-invasive neuromodulation may also be a reasonable option. However, disabling migraine should not be left untreated and may require pharmacological management. Pharmacological treatments should be chosen primarily based on safety considerations, as many migraine medications are not suitable for use during pregnancy. Given the limited safety data available for several treatments, shared decision-making between patients and healthcare providers is essential. During breastfeeding, medication selection should focus on minimizing infant exposure while ensuring effective migraine control for the mother. In women of childbearing potential, caution is needed when prescribing certain migraine treatments, as unplanned pregnancies can occur. Special considerations should also be given to those requiring preventive treatment while planning pregnancy. Given the complexities of migraine management in this population, an individualized approach is crucial to balancing maternal well-being with fetal and infant safety.

AimThis study aimed to evaluate the efficacy and tolerability of rimegepant for the prevention of episodic migraine in participants with a documented history of inadequate response to 2-4 categories of traditional oral preventive medication (OPM).MethodsThis multinational phase 4 trial consisted of an untreated 28-day observational phase (OP) and a 12-week double-blind treatment (DBT) phase. Participants with 4-14 monthly migraine days (MMDs), <15 monthly headache days (<7 non-migraine) and documented previous inadequate response to 2-4 traditional OPM categories were enrolled. Participants were randomized to rimegepant 75 mg orally disintegrating tablet (ODT) or placebo every other day (EOD). The primary endpoint was mean change from the OP in MMDs through the 12-week DBT phase. Key secondary endpoints were tested hierarchically to control type I errors. Tolerance and safety were assessed throughout the DBT phase.ResultsIn total, 328 participants received rimegepant and 324 received placebo. The most common OPM categories with prior inadequate response were anticonvulsants (61%), beta-blockers (56%) and amitriptyline (51%). The mean ± SD number of MMDs in the OP was 8.4 ± 2.4 and 8.3 ± 2.3, respectively, in the rimegepant (n = 324) and placebo (n = 319) groups. Across the DBT phase, participants who received rimegepant had a significantly larger mean change from the OP in MMDs than those who received placebo (-2.1 vs. -0.5 days; difference = -1.6 days; 95% confidence interval (CI) = -2.1 to -1.2; p < 0.0001). All key secondary endpoints favored rimegepant: (i) percentage of participants with ≥50% reduction from the OP in MMDs with moderate or severe pain intensity across the DBT phase (difference: 20.1%; 95% CI = 13.7 to 26.5; p < 0.0001); (ii) mean change from the OP in MMDs in the first month of the DBT phase (difference: -1.7 days; 95% CI = -2.3 to -1.2; p < 0.0001); (iii) mean change from the OP in MMDs in the last month of the DBT phase (difference: -1.4 days; 95% CI = -2.1 to -0.8; p < 0.0001); (iv) mean change from baseline in Migraine-Specific Quality-of-Life Questionnaire v2.1 Restrictive Role Function domain score at week 12 of the DBT phase (difference: 6.6 points; 95% CI = 3.6 to 9.5; p < 0.0001); and (v) mean change from baseline in Migraine Interictal Burden Scale score at week 12 of the DBT phase (difference: -0.9 points; 95% CI = -1.4 to -0.4; p = 0.0006). Rimegepant was well tolerated with a safety profile not notably different from placebo.ConclusionsRimegepant 75 mg ODT EOD is efficacious and well tolerated for the prevention of episodic migraine in participants with a documented history of inadequate response to 2-4 categories of traditional OPM.Trial RegistrationClinicalTrials.gov, NCT05518123 (https://clinicaltrials.gov/study/NCT05518123).

BackgroundCalcitonin gene-related peptide (CGRP) has a causative role in migraine pathogenesis but its effects on trigeminal afferents are still unclear. Corticosteroids represent a very useful tool in headache therapy with an unknown mechanism of action. Despite the widespread effects of corticosteroids on gene transcription, whether they regulate CGRP expression within the trigeminovascular system remains to be investigated.MethodsThe effects of dexamethasone on expression of CGRP and its receptor subunits receptor activity-modifying protein (RAMP1) and calcitonin receptor-like receptor (CLR) have been evaluated in rat thyroid parafollicular CA77 and human neuroblastoma SHSY-5Y cell cultures, as well as in isolated human peripheral blood mononuclear cells. The effects of dexamethasone on the rat and human CGRP promoter were also evaluated. In vivo, rats and mice were treated with betamethasone (320 µg/kg for 10 days) to investigate whether the drug altered the expression of CGRP, RAMP1 and CLR in the trigeminal ganglion (TG). We also evaluated the effect of betamethasone on CGRP mRNA stability and release from the mouse TG, as well as on mouse spontaneous or nitroglycerin-induced cephalic allodynia.ResultsWe report that dexamethasone triggered transcriptional activation of the rat and human CGRP gene, also increasing transcript levels of RAMP1 but not of CLR in cultured cells. These effects were paralleled in the TG of rats and mice challenged with betamethasone, with mice also showing increased expression levels of CLR. Of note, although a 13-fold increase of the CGRP releasable pool occurred in the TG of betamethasone-treated mice, the animals were not sensitized to cephalic allodynia.ConclusionsIn keeping with the emerging immunosuppressing effects of CGRP, corticosteroids increase its expression in rat and human cell lines, as well as in rodent TG. Evidence that a substantial increase of releasable CGRP in the TG does not reduce orofacial pain thresholds suggests that basal release of endogenous CGRP differs from its exogenous administration in terms of trigeminal afferent sensitization.

BackgroundThis study investigates the therapeutic potential of a combined dose of cannabidiol (CBD) and tetrahydrocannabinol (THC) at a 100:1 ratio (100 mg/kg CBD and 1 mg/kg THC) in mitigating central calcitonin gene-related peptide (CGRP)-induced migraine symptoms in a mouse model.MethodsThe 100:1 ratio of CBD to THC was administered intraperitoneally, 60 minutes prior to starting all the assays, followed by intracerebroventricular CGRP administration, 30 minutes later, with behavior assays conducted 30 minutes after CGRP injection. To determine whether pretreatment of CBD:THC could counteract CGRP-induced light aversion, we utilized the light/dark assay, which also recorded motility behavior. To investigate whether CBD:THC pretreatment could alleviate CGRP-induced spontaneous pain, we used the automated squint assay.ResultsOur findings show that pretreatment with 100:1 CBD:THC rescued light aversion caused by centrally administered CGRP in CD1 mice. Additionally, CBD:THC pretreatment rescued the increased resting time in darkness, decreased transitions between light and dark zones, and partially rescued the decreased rearing behavior induced by centrally administered CGRP. Moreover, an open field assay confirmed that centrally administered CGRP did not induce anxiety in a light independent assay. Finally, our findings from the automated squint assay indicate that pretreatment with 100:1 CBD:THC partially rescued centrally administered CGRP-induced spontaneous pain.ConclusionsCollectively, these results demonstrate that a combination of CBD and THC can alleviate light aversion and pain symptoms induced by a centrally-acting migraine trigger.

BackgroundThe diagnosis, treatment and monitoring of patients with idiopathic intracranial hypertension (IIH) are highly complex processes that require interdisciplinary collaboration with respect to neurology, ophthalmology, neuroradiology, neurosurgery and endocrinology. Accordingly, there is a consensus among international guidelines that the management of these aspects of care should be the responsibility of specialized centers that are equipped with appropriate facilities. The objective of the Austrian Network for Idiopathic Intracranial Hypertension (AN4IH) is to establish a national network of excellence and to provide comprehensive recommendations for the structure and operation of specialized IIH centers (AN4IH centers), including an integrated, interdisciplinary diagnostic and treatment pathway.MethodsThis consensus was developed by an interdisciplinary panel of experts convened by Austrian neurologists, (neuro)ophthalmologists, neuroradiologists, neurosurgeons and endocrinologists. The process adhered to a formal consensus methodology.ResultsThe AN4IH consensus provides a comprehensive, integrated, interdisciplinary framework addressing care infrastructure, urgency stratification, diagnostics, treatment and monitoring, as well as considerations related to family planning and pregnancy in patients with IIH. The AN4IH consensus is explicitly intended as a supplement and extension to existing international guidelines.ConclusionsThe management of IIH necessitates a structured, interdisciplinary approach to optimize patient outcomes. Through formal consensus methodology, the AN4IH provides expert - and where available evidence - based recommendations for specialized care centers, emphasizing standardized diagnostic pathways, urgency stratification and tailored treatment protocols. By fostering collaboration and institutionalizing best practices, the AN4IH model represents a significant advancement in delivering comprehensive, patient-centered care for this complex neurological disorder and encourages participants to create a secure, quality-controlled shared database for the collection of all clinical and paraclinical data, alongside the establishment of a biobank for the storage of biosamples.

BackgroundA subset of individuals with migraine are unsuitable for triptans due to intolerance, lack of efficacy, or contraindications. This phase 4 study assessed the efficacy and tolerability of a single 75-mg dose of rimegepant orally disintegrating tablet (ODT) for acute treatment of migraine in adults with documented triptan unsuitability.MethodsParticipants (aged ≥18 years with 4-14 migraine days per month) with documented history of (A) intolerance and/or lack of efficacy to ≥2 triptans or (B) contraindication to triptans were randomized (1:1) to rimegepant 75 mg ODT or placebo to treat a single migraine attack of moderate or severe pain intensity. Randomization was stratified by history of clinically relevant cardiovascular disease. The primary endpoint was the percentage of participants with migraine pain relief (no or mild pain) at 2 h post dose. Key secondary endpoints, tested using a hierarchal approach to control type 1 error, included the percentage of participants with migraine pain freedom at 2 h, rescue medication use within 24 h, return to normal function at 2 h, sustained return to normal function from 2-24 h and from 2-48 h, sustained migraine pain relief from 2-24 h and from 2-48 h, sustained migraine pain freedom from 2-24 h and from 2-48 h, and most bothersome symptom freedom at 2 h. Safety was assessed via adverse events (AEs) and laboratory tests.ResultsOverall, 585 participants (89.1% were female, mean age was 42.9 years) received study medication (rimegepant, n = 295; placebo, n = 290). Participants analyzed for efficacy (rimegepant, n = 286; placebo, n = 284) had documented failure to ≥2 triptans with ≥1 reason due to prior intolerance (30.5%) and/or ≥1 reason due to lack of efficacy (84.9%); 9.1% had a contraindication. Rimegepant demonstrated superiority over placebo for the primary endpoint of migraine pain relief at 2 h (55.9% vs 32.7%; difference [95% CI]: 23.2% [15.3-31.1%]; p < 0.0001) and all 10 alpha-protected key secondary endpoints including pain freedom at 2 h (all p ≤ 0.0005). AE rates were similar across treatments (12.5% vs 12.1%), with no severe AEs, serious AEs, or clinically significant laboratory test abnormalities reported in the rimegepant group.ConclusionsA single 75-mg dose of rimegepant ODT was efficacious and well tolerated for acute treatment of migraine in adults unsuitable for triptans. This first prospective trial of a gepant in this population supports calcitonin gene-related peptide antagonism as a valuable option when triptans are unsuitable.Trial RegistrationClinicaltrials.gov NCT05509400.

BackgroundAlthough guidelines for clinical trials have proposed a definition for a migraine day, randomised clinical trials tend to vary in their definition used.MethodsDefinitions of a migraine day in phase III trials with monoclonal antibodies and small molecules targeting the calcitonin gene-related peptide pathway for the preventive treatment of migraine were compared.ResultsTwelve different definitions were found across 23 trials. Variation in headache duration, the inclusion or exclusion of probable migraine and the inclusion or exclusion of a treated migraine attack with a specific or non-specific drug were most subject to debate. No single criterium or set of criteria was common to all definitions used. The most common single criterium used was a minimal headache duration of at least 30 minutes where only two clinical trials allowed for a headache with a shorter duration to be included.ConclusionThere is a pressing need for a standardised accepted definition of a migraine day both from a clinical and research perspective.