Headache最新文献

{"title":"Re-evaluation of the dinosaur tail sign: Analysis of spinal magnetic resonance imaging signs in patients with chronic post-dural-puncture headache.","authors":"Charlotte Zander, Horst Urbach, Katharina Wolf, Amir El Rahal, Florian Volz, Christian Fung, Laura Krismer, Hansjörg Mast, Jürgen Beck, Niklas Lützen","doi":"10.1111/head.70210","DOIUrl":"https://doi.org/10.1111/head.70210","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to assess magnetic resonance imaging (MRI) findings of the lumbar spine in patients with chronic post-dural-puncture headache.</p><p><strong>Background: </strong>Post-dural-puncture headache is a common complication after dural puncture usually resolving within 14 days. However, a chronic course (>14 days persistence) is increasingly being recognized and may lead to tremendous symptom burden. While current research shows that MRI of the head is mostly unremarkable in chronic post-dural-puncture headache, lumbar imaging signs have not yet been systematically studied.</p><p><strong>Methods: </strong>This is a retrospective, single-center diagnostic case-control study. We identified all patients between 09/2022 and 12/2024 at the University Hospital Freiburg, Germany, with chronic post-dural-puncture headache (defined as persisting symptoms for >14 days post puncture or after ≥1 epidural blood patch), and recruited 30 healthy controls between 10/2024 and 07/2025 without prior history of intentional or unintentional lumbar puncture, all undergoing 3D high-resolution heavily T2-weighted lumbar MRI (at 0.63 mm spatial resolution). The \"dinosaur tail sign\" (interspinous arched T2w-hyperintensities) was assessed as originally published, recording numbers of involved spinal levels, while its appearance was subjectively graded as subtle, moderate, or prominent. Moreover, presence of arachnoid blebs and lumbar extradural fluid were recorded. Evaluation was independent and blinded; discrepancies were resolved by consensus. In a subgroup of patients with T1-weighted contrast-enhanced lumbar spine imaging (51/54), suspicious enhancement, which potentially may be attributable to the puncture, was analyzed, while none of the controls received contrast enhanced spinal MRI.</p><p><strong>Results: </strong>The final cohort resulted in 54 patients with chronic post-dural-puncture headache with 44 females (81%) and a mean age of 38.2 years (SD ±9.8). The dinosaur tail sign was present in 27/54 patients (50%) and 21/30 controls (70%), with a numerically higher frequency in controls (70% vs. 50%, odds ratio [OR] 2.31, 95% confidence interval [CI] 0.83-6.84, p = 0.107, p-adjusted = 0.240). The sign appeared at a median of two levels in both groups (interquartile range [IQR] 2.0-4.0 for patients vs. 1.0-3.0 for controls). Visual impression of the sign was graded subtle in 15 patients vs. 15 controls, moderate in nine vs. six, and prominent in three (two of three with extradural fluid) vs. none (p = 0.321, p-adjusted = 0.432 for all groups). Lumbar extradural fluid was observed in 4/54 patients (7%), arachnoid blebs in 10/54 patients (19%; 9% definite, 9% suspicious), with one patient presenting with two suspected blebs. Neither extradural fluid nor arachnoid blebs were found in any controls. Overall, noticeable contrast enhancement in the lumbar spine was found in 17/51 patients (33%).</p><p><strong>Conclusion: </strong>The","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In reply to: \"Spontaneous intracranial hypotension and autonomic dysfunction association highlights POTS as a central nervous system disorder\".","authors":"Woo-Seok Ha, Da Eun Jung, Sojung Yoon, Joonho Kim, Min Kyung Chu","doi":"10.1111/head.70223","DOIUrl":"https://doi.org/10.1111/head.70223","url":null,"abstract":"","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orofacial pain disorder or trigeminal autonomic cephalalgia? Insights into pathophysiology and implications in medicine and dentistry.","authors":"Marcela Romero-Reyes, Simon Akerman","doi":"10.1111/head.70219","DOIUrl":"https://doi.org/10.1111/head.70219","url":null,"abstract":"<p><strong>Objective: </strong>This narrative review highlights the importance of orofacial pain considerations in the differential diagnosis of trigeminal autonomic cephalalgias (TACs)/trigeminal autonomic orofacial pains (TAOPs). In addition, we provide novel insights into the pathophysiology of the presentation of TACs in the maxillary (V2) and mandibular (V3) trigeminal distributions (TAOPs).</p><p><strong>Background: </strong>TACs are lifelong disorders characterized by severe unilateral head pain accompanied by cranial autonomic phenomena. However, the head pain experienced may refer to the face, be present solely in the orofacial region as TAOPs, or even be experienced as a toothache. These presentations, involving V2/V3, may resemble disorders of diverse etiology and pathophysiology that may share some similarities with TACs, confusing the patient while relating symptoms, and creating a diagnostic dilemma for the clinician potentially leading to misdiagnosis. Moreover, TACs pathophysiology has not been discussed in relation to V2/V3 presentations (TAOPs).</p><p><strong>Methods: </strong>A literature search was performed on PubMed/Scopus to find relevant literature about TACs and TAOPs, and case reports of orofacial presentations. Deep reanalysis of several of our published articles on preclinical models of TACs was conducted to assess potential of V2-V3 components.</p><p><strong>Results: </strong>TACs orofacial presentations are not as common but if present can lead to misdiagnosis with significant consequences. Patients presenting TACs involving the midface as TAOPs experience an important delay for a correct diagnosis including multiple and diverse health provider visits, with a risk of having well-intended but misguided procedures. Differential diagnosis considerations need to include dental/odontogenic causes, sinusitis, temporomandibular disorders, Eagle syndrome, trigeminal neuralgia, and migraine (orofacial migraine, neurovascular orofacial pain). A reanalysis of preclinical data provides novel insights into this orofacial involvement. In two TAC-specific preclinical neuronal populations, recording either trigeminal or superior salivatory nucleus neurons, it was observed that ~20% and 37.5% of neurons, respectively, had cutaneous receptive fields that included or were exclusively within the V2-V3 trigeminal division. Whereas the numbers are not large, these demonstrate that even in rodent models in neuronal populations that could be considered TAC-like, they can extend to, or exclusively involve, the facial region, similar to TAOPs.</p><p><strong>Conclusion: </strong>The potential presence of TACs in the orofacial region can be observed from preclinical models to the clinical setting. The International Classification of Headache Disorders (ICHD) needs to recognize this additional localization, as well as the intraoral one, including dental structures. Education about TACs/TAOPs in the medical and dental setting is vital. Evidence h","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between sleep duration and migraine frequency, disability, and perceived stress in the Headache Assessment via a Digital Platform in United States (HeAD-US) study.","authors":"Angeliki Vgontzas, Kristina M Fanning, Ryan C Bostic, Alexandre Urani, François Cadiou, Richard B Lipton, Ali Ezzati","doi":"10.1111/head.70215","DOIUrl":"10.1111/head.70215","url":null,"abstract":"<p><strong>Objective: </strong>To examine the association between self-reported sleep duration and migraine frequency and disability.</p><p><strong>Background: </strong>Adults with migraine have similar average nightly sleep duration compared to those without migraine, but the clinical impact of short or long sleep duration on migraine burden is less well defined.</p><p><strong>Methods: </strong>We conducted a cross-sectional analysis from the Headache Assessment via a Digital Platform in the United States (HeAD-US) Study, a survey of adult users of the Migraine Buddy App completed between September and November 2023. Participants reported average nightly sleep duration and headache features, and completed the Perceived Stress Scale-4, the Migraine Disability Assessment Test, and the Patient Health Questionnaire-4 for anxiety and depression. Sleep duration was categorized as short (≤6 h), normal (7-9 h), and long (≥10 h). Migraine diagnosis adhered to the International Classification of Headache Disorders-3.</p><p><strong>Results: </strong>The 6267 participants had a mean age of 41.5 ± 13.1 years, were 91.7% female, and had a mean sleep duration of 6.92 h (SD 1.32, range 2-15). Compared to normal sleep duration, short sleep was associated with 10.9% higher expected number monthly headache days (adjusted incidence risk ratio [aIRR] = 1.11, 95% confidence interval [CI]: 1.05-1.17) and 13.6% higher expected MIDAS scores (aIRR = 1.14, 95% CI: 1.08-1.20). Long sleep was associated with 27.1% higher expected number of monthly headache days (aIRR = 1.27, 95% CI: 1.07-1.51) and 66.0% higher expected MIDAS scores (aIRR = 1.66, 95% CI: 1.41-1.96). Perceived stress statistically accounted for approximately 48% of the observed association between short sleep duration and monthly headache days (MHD) and 30% of the observed association between long sleep duration and MHD.</p><p><strong>Conclusions: </strong>Unhealthy sleep duration, particularly long sleep, is associated with greater migraine burden, characterized by increased headache frequency and disability. Perceived stress statistically accounted for part, but not all, of the observed associations between nonoptimal sleep duration and migraine burden.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel targets in headache: A narrative review.","authors":"Adriana Della Pietra, Peter J Goadsby, Carolina Oldoni, Stephen Silberstein, Fred Cohen, Simon Akerman","doi":"10.1111/head.70202","DOIUrl":"10.1111/head.70202","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives/background: &lt;/strong&gt;This narrative review summarizes novel applications for the use of calcitonin gene-related peptide (CGRP)-targeted therapies that go beyond migraine, the latest updates with respect to targeting pituitary adenylate cyclase-activating peptide (PACAP) as therapeutic in migraine, as well as exploring other more recently discovered targets that are undergoing preclinical through advanced clinical development, for the prevention and treatment of headache disorders. Headache disorders affect over one billion individuals worldwide and represent a major public health burden. Although CGRP-targeted therapies have transformed migraine care, a substantial proportion of patients do not achieve adequate relief or remain untreated. Therefore, there is the need to identify and validate novel mechanistic targets across the full spectrum of headache disorders.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This narrative review reports preclinical and clinical evidence for emerging therapeutic targets in headache, with a focus on those presented at the 2025 Scottsdale meeting of the American Headache Society, during the Advanced Science session. Literature searches were performed on specific topic areas using PubMed/Scopus to find relevant peer-reviewed literature, as well as studies in ongoing clinical trial registries.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In addition to their established efficacy in migraine, CGRP-targeted therapies are increasingly being explored across other headache disorders, reflecting their broader relevance to headache pathophysiology. Beyond CGRP, several promising targets have emerged. PACAP has been identified as a CGRP-independent headache mediator, supported by robust preclinical data and two phase 2 trials demonstrating preventive efficacy with a PACAP monoclonal antibody in migraine. The endocannabinoid system shows antinociceptive potential, particularly through multitarget modulation of cannabinoid receptors and endocannabinoid-degrading enzymes. Several therapeutic targets in earlier stages of development are also gaining attention. Among these, prolactin signaling and orexin-2 receptor pathways represent sex-specific mechanisms, demonstrating female-specific and male-specific relevance in headache-related nociception, respectively. Additionally, protease-activated receptor-2 is implicated in dural-trigeminovascular nociceptive sensitization and advancing through early clinical development. Finally, modulation of reactive nitroxidative species with peroxynitrite has emerged as an early-stage strategy given its role in trigeminovascular sensitization and central pain maintenance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Altogether, these emerging targets expand the therapeutic landscape for headache disorders beyond CGRP and support a shift toward alternative, sex-informed, and potentially combinatorial approaches for headache prevention and treatment, with the potential to benefit the untreated portion of patie","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution and target engagement of peripherally administered fremanezumab in the cerebrospinal fluid of healthy volunteers.","authors":"Jacki Rorabaugh, Edward Hellriegel, Juline Bryson, Ryan Tiver, Hang Zeng, Xiaofeng Lu, Steve Barash, Giulia Ghibellini, Olga Szilagyi, Ignacio Echenique, Andrew H Ahn, Peter J Goadsby, Laura Rabinovich-Guilatt","doi":"10.1111/head.70227","DOIUrl":"https://doi.org/10.1111/head.70227","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives/background: &lt;/strong&gt;Our objective was to describe the distribution of fremanezumab to the cerebrospinal fluid (CSF) in healthy volunteers, and investigate its engagement and stabilization of its target, calcitonin gene-related peptide (CGRP). Fremanezumab is a CGRP-targeting monoclonal antibody approved for migraine prevention. Although the efficacy of peripherally administered monoclonal antibodies targeting CGRP, such as fremanezumab, has been established for the modulation of migraine, the extent of their distribution and target engagement within the central nervous system remains largely uncharacterized.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This open-label, nonrandomized, parallel-group, no-treatment control, pharmacokinetics clinical trial was conducted between February 16, 2023, and April 1, 2023, in the United States. Healthy volunteers were assigned to one of five groups: Group 1 had no drug intervention, and Groups 2-5 received 900 mg fremanezumab intravenously. Blood and CSF samples were collected in Group 1 (n=6; baseline for blood and CSF control) and at 1 day (Group 2; n=5), 3 days (Group 3; n=5), 15 days (Group 4; n=5), and 30 days (Group 5; n=5) postinfusion. Additional blood sampling occurred in select groups at 15 min postinfusion and at predetermined time points up to 31 days postinfusion. Plasma and CSF samples were analyzed for fremanezumab and total CGRP using in-house immunoassays and high-performance liquid chromatography tandem-mass spectrometry.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Mean (SD) plasma fremanezumab concentration peaked at the end of the 1-h intravenous infusion (333599.2 ng/mL [54658.6]) and decreased over the subsequent 31 days postinfusion (60482.3 ng/mL [10473.9]). CSF fremanezumab was detected at the earliest measured time point of 1 day postinfusion (mean [SD]=134.2 ng/mL [38.8]), increased at 15 days (243.6 ng/mL [189.4]), and remained sustained 30 days postinfusion (219.3 ng/mL [77.3]). Mean (SD) CSF-to-plasma concentration ratios increased over time, from 0.06% (0.02%) at 1 day to 0.36% (0.14%) at 30 days postinfusion. In plasma, sustained target engagement was demonstrated through the rapid rise of total CGRP, peaking at 15 days (mean [SD]=359.1 pg/mL [90.0]), and was sustained to 31 days postinfusion (260.5 pg/mL [43.0]). In the CSF, total CGRP was below detection limits for the control (Group 1) but was quantifiable at 1 day and sustained to 30 days postinfusion, with mean (SD) values ranging from 1.8-3.3 pg/mL (0.4-2.2). No severe or treatment-related adverse events were reported, and no participant withdrew due to an adverse event.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The present findings suggest the rapid distribution of fremanezumab into the central nervous system after peripheral administration, and the persistent retention of fremanezumab and target engagement of CGRP in the CSF. Further studies are required to determine whether entry into the CSF and target engagement play a role ","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-administered medication devices' environmental waste consequences.","authors":"Sophia Wenzel, Richard Wenzel, Bradley Torphy, Jessica Ailani","doi":"10.1111/head.70214","DOIUrl":"https://doi.org/10.1111/head.70214","url":null,"abstract":"","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of head and neck pain and obstructive sleep apnea in women with macromastia: A cross-sectional analysis.","authors":"Kristyn Spera Pocock, Joseph Rigdon, Liza Smirnoff, Chris Mills, Lisa R David, Rebecca Erwin Wells, Richard B Lipton, Leon S Moskatel","doi":"10.1111/head.70226","DOIUrl":"https://doi.org/10.1111/head.70226","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives/background: &lt;/strong&gt;Symptomatic macromastia, or breast hypertrophy, is associated with musculoskeletal and neurological symptoms, including headache and neck pain. Though insurers list headache as an indication for breast reduction surgery, its relationship to specific headache phenotypes, neck pain disorders, and sleep-related disorders remains poorly understood. Our objectives were to evaluate the potential relationship between macromastia and chronic migraine, neck pain, cervical radiculopathy, occipital neuralgia, and obstructive sleep apnea (OSA), and to assess factors that influence the likelihood of treatment with reduction mammoplasty in an academic neurology practice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a retrospective cross-sectional study of women with and without macromastia by reviewing the charts of women with and without diagnosed macromastia (using the International Classification of Diseases, Tenth Revision code N62, hypertrophy of the breast) treated at an academic neurology practice from January 1, 2017, to December 31, 2024. Groups were matched on age, race-ethnicity, and body mass index (BMI) using propensity matching. In both groups, we analyzed diagnostic codes for chronic migraine, neck pain, cervical radiculopathy, occipital neuralgia, and OSA. The primary outcome was the prevalence of queried craniocervical pain disorders (e.g., chronic migraine, neck pain, occipital neuralgia, and cervical radiculopathy) in women with macromastia versus controls. For our secondary outcome, we examined the prevalence of OSA and rates of reduction mammoplasty in women with macromastia by type of craniocervical diagnostic code.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We identified 347 women with macromastia and 340 matched controls. Postmatch differences remained for mean BMI (28.0 [SD = 6.7] vs. 26.5 [SD = 6.5] kg/m&lt;sup&gt;2&lt;/sup&gt;, standardized mean difference = 0.194), depression (48.4% vs. 29.7%, p &lt; 0.001), and anxiety (57.3% vs. 32.9%, p &lt; 0.001). After adjusting for BMI, demographics, and comorbid mood disorders, women with macromastia had significantly higher adjusted prevalence ratios (aPRs) for chronic migraine (aPR = 1.40; 95% CI = 1.16-1.68, p = 0.003), neck pain (aPR = 2.04; 95% CI = 1.65-2.53, p = 0.003), cervical radiculopathy (aPR = 2.38; 95% CI = 1.39-4.06, p = 0.026), and OSA (aPR = 1.54; 95% CI = 1.23-1.95, p = 0.003), but not occipital neuralgia (aPR = 1.54; 95% CI = 0.98-2.39, p = 0.054), compared to controls. Among women with macromastia, only those with neck pain were more likely to undergo reduction mammoplasty.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In our retrospective, cross-sectional study, compared to women without macromastia, women with macromastia had a higher prevalence of chronic migraine, neck pain, cervical radiculopathy, and OSA. Women with macromastia and neck pain were more likely to have breast reduction surgery compared to women with macromastia without neck pain. Prospective, longit","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early improvements in function with atogepant as assessed by the Activity Impairment in Migraine-Diary: Post hoc analyses of three randomized, phase 3 clinical trials of atogepant for the preventive treatment of migraine.","authors":"Richard B Lipton, Pranav Gandhi, Andreas R Gantenbein, Brett Dabruzzo, Karen Carr, Jonathan Stokes, Molly Duan, Rashmi B Halker Singh, Hsiangkuo Yuan, Dawn C Buse","doi":"10.1111/head.70188","DOIUrl":"https://doi.org/10.1111/head.70188","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Evaluate early functional improvements with the preventive migraine treatment atogepant using Activity Impairment in Migraine-Diary (AIM-D) individual and activity limitation items, and complete improvement in AIM-D Performance of Daily Activities (PDA) and Physical Impairment (PI) domain scores assessed weekly during the first 4 weeks of three phase 3 trials.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Patient-reported functional outcomes are critical for assessing response to preventive migraine treatments, yet analyses of treatment effects on function at early timepoints are limited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Post hoc analyses assessed AIM-D data in three multicenter, placebo-controlled, double-blind, parallel-group, 12-week, randomized clinical trials in participants who received once-daily atogepant 60 mg or placebo: ADVANCE (episodic migraine [EM], 4-14 monthly migraine days [MMDs]; United States trial, December 14, 2018-June 19, 2020), ELEVATE (EM with prior failure to two to four classes of oral preventive migraine treatments; international trial, March 5, 2021-August 4, 2022), and PROGRESS (chronic migraine [CM]; ≥15 monthly headache days, including ≥8 MMDs; international trial, March 11, 2019-January 20, 2022). A separate activity limitation item was included in the daily eDiary to assess limitation of activity over the past 24 h. The percent change from baseline in each AIM-D item score and the activity limitation item score, and the proportions of participants achieving complete improvement (i.e., scores of zero) in AIM-D PDA or PI domain scores, were evaluated at weeks 1 through 4. A mixed model for repeated measures analysis compared least squares mean change from baseline in individual AIM-D items and activity limitation. A generalized linear mixed model compared the relative odds of achieving complete improvement.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In ADVANCE, ELEVATE, and PROGRESS, participants treated with atogepant versus placebo generally had a greater reduction in the individual AIM-D item scores at weeks 1 (ADVANCE, p: &lt;0.001-0.14; ELEVATE, all items p: &lt;0.001; PROGRESS, p: &lt;0.001-0.003), 2 (ADVANCE, p: &lt;0.001-0.018; ELEVATE, p: &lt;0.001-0.002; PROGRESS, p: 0.006-0.192), 3 (ADVANCE, p: &lt;0.001-0.001; ELEVATE, p: &lt;0.001-0.003; PROGRESS, p: 0.004-0.460), and 4 (ADVANCE, p: &lt;0.001-0.028; ELEVATE, p: &lt;0.001-0.050; PROGRESS, p: &lt;0.001-0.067). At weeks 1 through 4, participants in ADVANCE and ELEVATE showed greater improvements in the activity limitation item scores with atogepant versus placebo (all p ≤ 0.001). There were higher odds of achieving complete improvement in the PDA and PI domain scores at weeks 1-4 with atogepant versus placebo across all trials (odds ratios: ADVANCE, 1.614-3.089; ELEVATE, 2.298-5.363; PROGRESS, 2.106-7.617).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;For preventive migraine treatment, atogepant once daily versus placebo was associated with early improvements in AIM-D individual and ac","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous intracranial hypotension and autonomic dysfunction association highlights postural orthostatic tachycardia syndrome as a central nervous system disorder.","authors":"Svetlana Blitshteyn","doi":"10.1111/head.70216","DOIUrl":"https://doi.org/10.1111/head.70216","url":null,"abstract":"","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}