Cephalalgia最新文献

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.

BackgroundSecond and third generation gepants have been recently approved for migraine therapy. They represent the first drugs that are able to work as both preventatives and symptomatics of the migraine attack. Their ability to counteract calcitonin gene-related peptide signaling has been convincingly shown, but where they act to exert the therapeutic effects remains unsolved. Although the low brain/plasma ratio suggests peripheral antimigraine activity of gepants, recent preclinical and clinical lines of evidence hint that these compounds may also act centrally.MethodsBy means of mass spectrometry analysis, we have measured the biodistribution of atogepant and rimegepant in plasma, dura mater, trigeminal ganglion (TG), parietal brain cortex and hypothalamus of mice. The biodistribution of oxazepam has been also determined as that of a prototypical brain permeant drug. Animals received interspecies (human-to-mouse) converted doses. Drugs were administered orally, as single or repeated (seven days) dosing. Atogepant was also administered as a single oral or intranasal dose matching (mg/kg) that adopted in migraine patients.ResultsUpon administration of interspecies converted oral doses, we found that atogepant reached similar C_max in plasma and TG after three hours, that then rapidly decreased at six and 12 hours. Of note, atogepant contents in the parietal brain cortex linearly increased up to six hours (reaching a brain/plasma concentration ratio of 5.6) and substantially decreased at 12 hours. Tissue contents of rimegepant were lower than those of atogepant, although the drug reached in the brain C_max analogues to those found in the TG. Three hours after dosing, we also found the highest accumulation of atogepant and rimegepant in the dura, with substantial accumulation even in the hypothalamus where drug contents equaled those present in the TG. Of note, when atogepant was administered orally or intranasally at a dose corresponding to that adopted in patients, it also reached brain contents comparable to those found in the TG. However, a preferred delivery of atogepant to the TG was obtained with the intranasal route. At variance with oxazepam, the two gepants did not accumulate in the TG or parietal brain cortex upon a seven day oral treatment.ConclusionsThe data obtained in the present study indicate substantial and transient permeation of the mouse brain by gepants.

BackgroundThis narrative review establishes the current state of the art of machine learning approaches for prediction of migraine attacks. Related concepts are highlighted including the identification of triggers or premonitory symptoms and methods for evaluating prediction models. Existing efforts at machine learning prediction of individual migraine headaches and attacks are reviewed in detail. Challenges in this task are discussed.ResultsA variety of input data and modeling approaches have been used. It is consistently found that individualized models provide better results compared to a generalized model and achievable performance varies considerably between individuals. Patient needs should be assessed to discover what a valuable prediction looks like. The field should develop common standards for evaluating migraine prediction algorithms.Conclusions/InterpretationsWhile the problem is far from solved there is great potential and reason to believe that feasible solutions that improve the quality of life of those with migraine are within our grasp.

BackgroundMenstrually-related migraine (MRM) is a subtype of migraine associated with the ovarian cycle that imposes a significant burden on female patients. Although MRM and non-menstrual migraine (NMM) differ in clinical presentation and treatment response, their distinct neural mechanisms remain unclear. Emerging evidence suggests that alterations in intrinsic functional connectivity (FC) within and between large-scale brain networks may underlie the phenotypic heterogeneity of migraine subtypes. This study investigated FC alterations between patients with MRM and NMM, explored their correlations with clinical characteristics, and assessed the preliminary utility of FC in subtype differentiation.MethodsResting-state functional magnetic resonance imaging (MRI) with independent component analysis was used to examine whole-brain FC in 50 patients with MRM, 50 with NMM and 50 age-balanced healthy controls (HC). We analyzed within- and between-network connectivity across major resting-state networks, including the frontoparietal, default mode, salience and dorsal attention networks, and applied logistic regression to test whether FC values could classify migraine subtypes. Correlation analyses were further performed between FC measures and clinical indices, including disease duration, headache frequency, visual analog scale scores and Headache Impact Test (HIT-6) scores.ResultsBoth MRM and NMM groups showed weaker within-network connectivity compared to HCs, primarily in the right frontoparietal, default mode and salience networks. Compared with NMM, the MRM group exhibited significantly stronger connectivity in the left frontoparietal network and weaker between-network connectivity between the dorsal attention and default mode networks. In the women with migraine, FC within the dorsal attention network (DAN) was negatively correlated with disease duration (r = -0.200, p = 0.046) and HIT-6 score (r = -0.183, p = 0.049). Furthermore, FC between the DAN and auditory network was inversely associated with disease duration (r = -0.225, p = 0.025). The logistic regression model achieved an area under the receiver operating characteristic curve of 0.73 (sensitivity = 0.70; specificity = 0.64) in distinguishing MRM from NMM.ConclusionsOur findings reveal both shared and distinct alterations in large-scale brain networks in MRM and NMM, potentially explaining differences in clinical presentation and treatment response. This enhanced understanding of migraine pathophysiology supports the development of subtype-specific diagnostic tools and targeted therapies and underscores the value of resting-state fMRI as a non-invasive tool for migraine phenotyping and personalized care.Registration NumberChiCTR2200065586.

AimTo evaluate the effect of treatment onset-time on the effectiveness of remote electrical neuromodulation (REN) for acute treatment of migraine.MethodsA real-world evidence study on migraine patients who treated with REN . REN treatments initiated within one hour of migraine attack onset (headache or aura) were classified as "early"; those initiated after one hour were classified as "late". Treatments with baseline and two-hour reports were termed "evaluable" and analyzed.ResultsAmong 55,261 patients (37.9 ± 18.5 years, 83.4% female) who conducted 586,981 treatments, 56.5% were administered early. Effectiveness was calculated from "evaluable" treatments, varying between 6413 and 35,581 treatments depending on the outcome. Early treatments yielded higher responder-rates than late (p < 0.001, significant following Bonferroni correction for multiple comparisons) for pain relief (65.1% vs. 46.6%; Δ = 18.5%), pain freedom (28.8% vs. 14.5%; Δ = 14.3%), functional disability relief (58.1% vs. 49.3%; Δ = 8.8%), functional disability freedom (35.4% vs. 20.9%; Δ = 14.5%), and freedom from photophobia (26.9% vs. 19.0%; Δ = 7.9%), phonophobia (34.0% vs. 25.9%; Δ = 8.1%) and nausea/vomiting (51.5% vs. 38.7%; Δ = 12.8%). Similarly, patients consistently treating early with REN (in 50% or more of their treatments) experienced higher efficacy (p < 0.001). Similar effects were seen in youths.ConclusionsEarly acute treatment with REN enhanced patient outcomes by up to two-fold compared to late treatment onset. Educating providers and patients to "treat as early as possible" boosts clinical and patient-centered results.