Cephalalgia最新文献

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.

BackgroundMigraine is a complex disabling neurological disease characterized by recurrent headache attacks lasting 4-72 h with moderate to severe intensity and other accompanying symptoms. While chronic migraine (CM) and episodic migraine (EM) are primarily differentiated by the frequency of headache and migraine days, underlying clinical and functional differences have been described. OnabotulinumtoxinA (onabotA) has been approved as a preventive treatment for CM with controlled clinical and real-world evidence suggesting potential benefits for treatment of EM. Given the lack of randomized controlled trial data, PRECLUDE, a prospective phase 3 trial was designed to evaluate the efficacy and safety of onabotA for the preventive treatment of EM.MethodsThe PRECLUDE trial was a phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group trial with an open-label onabotA 195 U extension phase. In total, 775 patients aged 18-65 years with a history of migraine attacks were randomized (1:1:1) to receive placebo, onabotA 155 U, or onabotA 195 U. Patients recorded daily headache data and medication use via an electronic diary (eDiary) during a four-week screening phase, 24-week double-blind phase, followed by a 24-week open-label extension phase. The primary endpoint was the change in the frequency of monthly migraine days from baseline across months 5 and 6.ResultsAll treatment groups showed a reduction in the frequency of monthly migraine days from baseline; however, neither the onabotA 155 U group nor the 195 U group demonstrated a statistically significant improvement compared to the placebo group (p >0 .05). Similarly, secondary endpoints, including changes in monthly headache days, 50% responder rates and monthly acute medication use days, did not reach statistical significance. Adverse events in this trial were consistent with previous findings for onabotA in CM and were generally mild to moderate in severity.ConclusionsThe PRECLUDE trial demonstrated that onabotA was well tolerated but did not show significant efficacy compared to placebo for the endpoint reducing migraine days from baseline in patients with EM as defined by the trial protocol. While onabotA is effective for CM, these findings highlight the need for further research to better understand the pathophysiological differences between EM and CM and to understand whether there is a potential subset of EM patients which respond to onabotA.

BackgroundWhile the association between migraine, neck pain, and cervical musculoskeletal dysfunctions is well established in adults, such a relationship remains unclear in the pediatric population. This gap limits our understanding of early pathophysiological mechanisms and hinders the development of targeted interventions.ObjectiveTo assess self-reported neck pain, pressure pain threshold (PPT), global cervical range of motion (ROM), and upper cervical mobility in children and adolescents with and without migraine.MethodsA cross-sectional study was conducted with 102 participants in total (51 with migraine - MG - and 51 controls - CG), aged six to 16 years. Neck pain characteristics (presence, frequency, intensity, and duration) were recorded. Cervical ROM was measured in flexion, extension, lateral flexion, and rotation. Upper cervical mobility was evaluated using the Flexion Rotation Test (FRT), and PPT was bilaterally assessed in the sternocleidomastoid, levator scapulae, suboccipital, upper trapezius, and anterior scalene muscles. Comparisons between groups were made using Student's t-test, Mann-Whitney U test, or Chi-square test, with a significance level set at 5%.ResultsCompared to the control group, the MG showed a higher prevalence of neck pain (39.2% vs. 5.9%; p < 0.001) and longer average duration (19 ± 8.6 vs. 8 ± 3.4 h; p = 0.046). Reduced lateral flexion (p < 0.001) and reduced upper cervical mobility (p < 0.001) were observed in the MG. Additionally, all evaluated muscles exhibited significantly lower PPT values in the MG (p < 0.001) than controls, indicating increased pain sensitivity.ConclusionSimilar to adults, children and adolescents with migraine demonstrate cervical musculoskeletal impairments, including neck pain, reduced cervical mobility-especially in lateral flexion and upper cervical rotation-and heightened sensitivity in craniocervical muscles. These findings support the routine inclusion of cervical musculoskeletal assessments in the clinical management of pediatric migraine.