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Some observed problems of the evidence presented for zolmitriptan nasal spray in the "Evidence-Based Recommendations of Pharmacological Treatment of Migraine Attacks". 在“偏头痛发作药物治疗的循证建议”中提出的唑米曲坦鼻喷雾剂的证据中存在一些观察到的问题。
IF 4.6 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-11-01 Epub Date: 2025-11-06 DOI: 10.1177/03331024251393937
Peer Tfelt-Hansen, Anders Hougaard
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引用次数: 0
Biodistribution of atogepant and rimegepant in mouse peripheral and central structures of relevance to migraine pathogenesis. 与偏头痛发病相关的小鼠外周和中枢结构中同孕激素和孕激素的生物分布。
IF 4.6 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-11-01 Epub Date: 2025-11-28 DOI: 10.1177/03331024251378713
Alessandra Pistolesi, Francesco De Cesaris, Daniela Buonvicino, Alberto Chiarugi

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 Cmax 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 Cmax 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.

研究背景:第二代和第三代偏头痛患者最近被批准用于偏头痛治疗。它们是第一批既能预防偏头痛又能治疗偏头痛症状的药物。它们对抗降钙素基因相关肽信号的能力已得到令人信服的证明,但它们如何发挥治疗效果仍未得到解决。虽然低脑/血浆比值表明患者的外周抗偏头痛活性,但最近的临床前和临床证据提示这些化合物也可能起中枢作用。方法采用质谱分析方法,测定了同孕剂和巨孕剂在小鼠血浆、硬脑膜、三叉神经节、顶叶大脑皮层和下丘脑中的生物分布。恶西泮的生物分布也被确定为一种典型的脑渗透药物。动物接受跨物种(人-鼠)转换剂量。药物口服,单次或重复(7天)给药。在偏头痛患者中,atgepant也被采用单次口服或鼻内剂量匹配(mg/kg)给药。结果经跨种转换剂量口服后,3 h后同聚物在血浆和TG中的Cmax值相近,6 h和12 h后迅速下降。值得注意的是,大脑顶叶皮层中的促凝剂含量在6小时内呈线性增加(达到脑/血浆浓度比5.6),在12小时时大幅下降。尽管该药物在脑组织中达到的Cmax类似于在TG中发现的Cmax,但rimegepant的组织含量低于atogepant。给药3小时后,我们还发现硬脑膜中聚集了最多的同聚剂和巨聚剂,甚至在下丘脑也有大量的聚集,那里的药物含量与TG中的含量相当。值得注意的是,当以与患者相应的剂量口服或鼻内给药时,它也达到了与TG相当的脑含量。然而,通过鼻内途径获得了对TG的首选递送。与恶西泮不同的是,口服7天后,这两种药物没有在TG或顶叶脑皮质中积累。结论本研究的数据表明,基因对小鼠大脑有大量和短暂的渗透。
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引用次数: 0
The promise of machine learning in predicting migraine attacks. 机器学习预测偏头痛发作的前景。
IF 4.6 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-11-01 Epub Date: 2025-11-03 DOI: 10.1177/03331024251391207
Gina Dumkrieger

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.

这篇叙述性综述建立了预测偏头痛发作的机器学习方法的当前状态。相关概念被强调,包括识别触发或前兆症状和评估预测模型的方法。详细回顾了机器学习预测个体偏头痛和发作的现有努力。讨论了这一任务中的挑战。结果采用了多种输入数据和建模方法。人们一致发现,与广义模型相比,个性化模型提供了更好的结果,并且个体之间的可实现性能差异很大。应该评估病人的需求,以发现有价值的预测是什么样的。该领域应该制定评估偏头痛预测算法的通用标准。结论/解释虽然这个问题还远未解决,但有很大的潜力和理由相信,改善偏头痛患者生活质量的可行解决方案就在我们掌握之中。
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引用次数: 0
IHC 2025 late-breaking abstracts. IHC 2025最新摘要。
IF 4.6 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-11-01 Epub Date: 2025-11-12 DOI: 10.1177/03331024251387884
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引用次数: 0
Divergent functional connectivity patterns in menstrually-related and non-menstrual migraine: A large-scale resting-state fMRI study. 月经相关和非月经偏头痛的不同功能连接模式:一项大规模静息状态fMRI研究。
IF 4.6 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-11-01 Epub Date: 2025-11-18 DOI: 10.1177/03331024251396102
Yusha Tang, Hua Li, Bosi Dong, Leihao Sha, Ruiqi Yang, Lei Chen

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.

月经相关性偏头痛(MRM)是一种与卵巢周期相关的偏头痛亚型,对女性患者造成了很大的负担。尽管MRM和非经期偏头痛(NMM)在临床表现和治疗反应上有所不同,但其独特的神经机制尚不清楚。新出现的证据表明,大规模脑网络内部和之间的内在功能连接(FC)的改变可能是偏头痛亚型表型异质性的基础。本研究调查了MRM和NMM患者之间FC的改变,探讨了它们与临床特征的相关性,并评估了FC在亚型分化中的初步应用。方法静息状态功能磁共振成像(MRI)结合独立成分分析,对50例MRM患者、50例NMM患者和50例年龄平衡健康对照(HC)的全脑FC进行检测。我们分析了主要静息状态网络(包括额顶叶、默认模式、显著性和背侧注意网络)的网络内部和网络之间的连通性,并应用逻辑回归测试FC值是否可以分类偏头痛亚型。进一步进行FC测量与临床指标的相关性分析,包括疾病持续时间、头痛频率、视觉模拟量表评分和头痛影响测试(HIT-6)评分。结果与hc相比,MRM组和NMM组均表现出较弱的网络内连通性,主要是在右侧额顶叶、默认模式和显著性网络。与NMM相比,MRM组左侧额顶叶网络的连通性显著增强,背侧注意网络与默认模式网络的网络间连通性较弱。在女性偏头痛患者中,背侧注意网络(DAN)内的FC与病程(r = -0.200, p = 0.046)和HIT-6评分(r = -0.183, p = 0.049)呈负相关。此外,DAN和听觉网络之间的FC与疾病持续时间呈负相关(r = -0.225, p = 0.025)。logistic回归模型在区分MRM和NMM时,受试者工作特征曲线下面积为0.73(灵敏度= 0.70,特异性= 0.64)。结论我们的研究结果揭示了MRM和NMM中大尺度脑网络的共同和不同的改变,这可能解释了临床表现和治疗反应的差异。这种对偏头痛病理生理学的深入了解支持了亚型特异性诊断工具和靶向治疗的发展,并强调了静息状态fMRI作为偏头痛表型和个性化护理的非侵入性工具的价值。登记NumberChiCTR2200065586。
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引用次数: 0
The effect of treatment onset time on acute efficacy in migraine patients treating with remote electrical neuromodulation (REN). 治疗起始时间对远程神经电调节治疗偏头痛急性疗效的影响。
IF 4.6 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-10-01 Epub Date: 2025-10-09 DOI: 10.1177/03331024251370696
Jessica Ailani, Istvan Tomaschek, Alit Stark-Inbar, Sharon Shmuely, Alon Ironi, Daniel Noam Lax

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.

目的探讨治疗起始时间对远程神经电调节(REN)治疗急性偏头痛疗效的影响。方法对经REN治疗的偏头痛患者进行实证研究。在偏头痛发作(头痛或先兆)一小时内开始REN治疗被归类为“早期”;在一小时后开始的人被归类为“迟到”。基线治疗和两小时报告被称为“可评估的”并进行分析。结果55,261例患者(37.9±18.5岁,女性占83.4%)接受586,981次治疗,其中56.5%为早期治疗。有效性是从“可评估的”治疗中计算出来的,根据结果在6413到35,581种治疗之间变化。早期治疗的应答率高于晚期(p < 0.05)
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引用次数: 0
Abstracts from the 22nd International Headache Congress, 11-13 September 2025, São Paulo, Brazil. 第22届国际头痛大会,2025年9月11-13日,巴西圣保罗。
IF 4.6 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-10-01 Epub Date: 2025-10-16 DOI: 10.1177/03331024251366059
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引用次数: 0
OnabotulinumtoxinA for the preventive treatment of episodic migraine: Results from the phase 3, multicenter randomized, double-blind, placebo-controlled phase of the PRECLUDE trial. OnabotulinumtoxinA用于预防治疗发作性偏头痛:来自多中心、随机、双盲、安慰剂对照试验的3期结果。
IF 4.6 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-10-01 Epub Date: 2025-10-15 DOI: 10.1177/03331024251370769
Patricia Pozo-Rosich, Andrew M Blumenfeld, Richard B Lipton, Ronald E DeGryse, Beibei Li, Aubrey M Adams, Thu Nguyen, Lynn James, Mitchell F Brin

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.

背景:偏头痛是一种复杂的致残性神经系统疾病,其特征是反复发作的头痛,持续4-72小时,强度中等至重度,并伴有其他症状。虽然慢性偏头痛(CM)和发作性偏头痛(EM)主要通过头痛频率和偏头痛天数来区分,但已经描述了潜在的临床和功能差异。onabotuinumtoxina (onabotA)已被批准作为CM的预防性治疗药物,有对照临床和实际证据表明onabotA治疗EM的潜在益处。鉴于缺乏随机对照试验数据,我们设计了一项前瞻性3期试验,旨在评估onabotA预防EM的有效性和安全性。开放标签onabotA 195u扩展期的平行组试验。共有775名年龄在18-65岁、有偏头痛发作史的患者被随机(1:1:1)分为安慰剂组、onabotA 155u组和onabotA 195u组。在为期四周的筛选阶段、24周的双盲阶段和24周的开放标签扩展阶段,患者通过电子日记(eDiary)记录每日头痛数据和药物使用情况。主要终点是第5个月和第6个月每月偏头痛天数频率的变化。结果:所有治疗组均显示每月偏头痛天数较基线减少;然而,与安慰剂组相比,onabotA 155u组和195u组均未显示出统计学上显著的改善(p < 0.05)。同样,次要终点,包括每月头痛天数、50%应答率和每月急性用药天数的变化,也没有达到统计学意义。该试验中的不良事件与先前在CM中onabotA的发现一致,严重程度一般为轻度至中度。结论:preude试验表明,onabotA耐受性良好,但与安慰剂相比,在试验方案定义的EM患者中,从基线减少偏头痛天数的终点没有显示出显著的疗效。虽然onabotA对CM有效,但这些发现强调需要进一步研究,以更好地了解EM和CM之间的病理生理差异,并了解是否存在对onabotA有反应的EM患者的潜在亚群。
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引用次数: 0
Cervical musculoskeletal dysfunctions in pediatric migraine: A cross-sectional study. 儿童偏头痛的颈椎肌肉骨骼功能障碍:一项横断面研究。
IF 4.6 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-10-01 Epub Date: 2025-10-17 DOI: 10.1177/03331024251387033
Nathiely Viana da Silva, Débora Bevilaqua-Grossi, Juliana Pradela, Fabiola Dach, Carina Ferreira Pinheiro-Araujo

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.

虽然偏头痛、颈部疼痛和颈椎肌肉骨骼功能障碍之间的关联在成人中已经确立,但在儿科人群中这种关系尚不清楚。这一差距限制了我们对早期病理生理机制的理解,并阻碍了有针对性干预措施的发展。目的评估儿童和青少年偏头痛患者自我报告的颈部疼痛、压痛阈值(PPT)、整体颈椎活动度(ROM)和上颈椎活动度。方法对102名参与者进行了一项横断面研究(51名偏头痛患者- MG -和51名对照组- CG),年龄6至16岁。记录颈部疼痛特征(存在、频率、强度和持续时间)。在屈曲、伸展、侧屈和旋转时测量颈椎ROM。使用屈曲旋转试验(FRT)评估上颈椎活动度,并评估双侧胸锁乳突肌、肩胛提肌、枕下肌、上斜方肌和前斜角肌的PPT。组间比较采用学生t检验、Mann-Whitney U检验或卡方检验,显著性水平设为5%。结果与对照组相比,MG组颈痛发生率较高(39.2% vs. 5.9%
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引用次数: 0
Complementary, but not equivalent: Clarifying the role of RWE and RCT in migraine research. 互补但不等同:阐明RWE和RCT在偏头痛研究中的作用。
IF 4.6 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-10-01 Epub Date: 2025-10-09 DOI: 10.1177/03331024251381333
Mario F P Peres, Hsiangkuo Yuan, Cristina Tassorelli
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引用次数: 0
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Cephalalgia
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