Headache最新文献

{"title":"The influence of renal impairment on the pharmacokinetics of rimegepant: Results of a phase 1, open-label, single-dose, parallel-group study.","authors":"Rajinder Bhardwaj, Beth Morris, Richard Bertz, Kyle Matschke, Robert Croop, Jing Liu","doi":"10.1111/head.15041","DOIUrl":"10.1111/head.15041","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to investigate the pharmacokinetics of rimegepant in participants with mild, moderate, or severe renal impairment compared to healthy adults with normal renal function.</p><p><strong>Background: </strong>Rimegepant is a calcitonin gene-related peptide receptor antagonist approved in the United States for treatment of acute and preventive treatment of migraine.</p><p><strong>Methods: </strong>In this Phase 1, open-label, four-group, pharmacokinetic study, 36 participants were grouped by degree of renal impairment according to estimated glomerular filtration rate (eGFR): normal; mild (60-89 mL/min/1.73 m²); moderate (30-59 mL/min/1.73 m²); and severe (<30 mL/min/1.73 m²). Participants received a single 75-mg oral rimegepant tablet to determine total and unbound plasma rimegepant concentrations using both matched and pooled control analysis. The study enrollment period began on October 17, 2017, and concluded on March 27, 2018.</p><p><strong>Results: </strong>For mild, moderate, and severe renal impairment groups, respectively, compared with matched control groups, total geometric least-square mean ratios (90% confidence intervals) were 1.06 (0.75-1.52), 1.40 (0.97-2.02), and 1.04 (0.70-1.57) for area under the concentration-time curve from time zero to infinity (AUC_0-inf) and 1.20 (0.75-1.92), 0.76 (0.42-1.37), and 0.90 (0.50-1.62) for maximum observed concentration (C_max). Geometric mean ratios of unbound AUC_0-inf were 1.22 (0.82-1.82), 1.84 (1.30-2.61), and 2.57 (1.86-3.56) in the mild, moderate, and severe renal impairment groups, respectively, using the pooled control group analysis. Relationships for eGFR versus total plasma concentrations and pharmacokinetic parameters showed no significant trends; however, there was a statistically significant (p < 0.05) relationship showing greater unbound rimegepant AUC_0-inf and C_max in participants with lower eGFR.</p><p><strong>Conclusions: </strong>Among participants with mild, moderate, or severe renal impairment, a ≤40% increase in total rimegepant exposure was observed following single-dose 75-mg administration. Unbound rimegepant AUC_0-inf exposure increased 1.8- and 2.6-fold in participants with moderate and severe renal impairment, respectively. The pharmacokinetic results from this study and safety data from other clinical studies were used to support rimegepant dosing recommendations in patients with renal impairment. Rimegepant has not been studied in patients with end-stage renal disease or in patients on dialysis and should be avoided in those populations.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":"1381-1393"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144951631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world barriers to health care utilization among people living with migraine: Insights from the All of Us Research Program.","authors":"Idris Demirsoy, Richard B Lipton, Ali Ezzati","doi":"10.1111/head.15007","DOIUrl":"10.1111/head.15007","url":null,"abstract":"<p><strong>Objectives/background: </strong>This study was undertaken to compare health care utilization barriers between participants with medically diagnosed migraine and matched controls without diagnosed migraine. Migraine imposes a significant burden on individuals and on health care systems worldwide. The role of sociodemographic factors and comorbidities in shaping health care utilization for migraine remains insufficiently understood, necessitating further investigation.</p><p><strong>Methods: </strong>The All of Us Research Program is a large-scale, prospective cohort study funded by the National Institutes of Health. It collects extensive demographic, lifestyle, and health information through self-reports and electronic health records. This analysis uses the Controlled Tier Dataset V7, covering participant data from May 2018 to May 2024. Participants with migraine were identified based on self-reported data from the survey and confirmation of a medical migraine diagnosis through electronic health records using Systematized Nomenclature of Medicine (SNOMED) codes. Additionally, migraine-free controls were propensity-matched to the migraine cases on age, sex, race, and income.</p><p><strong>Results: </strong>We identified 8346 migraine cases and an equal number of controls. Each group had an average age of 53.3 years and was 87% female. Despite matching for demographic variables and income, people with migraine had significantly more financial, social, and access barriers than those without migraine. There were higher rates of financial difficulties (46.8% vs. 40.3%, p < 0.001) and more transportation issues (9.9% vs. 5.8%, p < 0.001). They also reported more frequent doctor visits within the past 6 months (93.6% vs. 88.9%, p < 0.001) and a greater number of total doctor visits annually compared to those free of diagnosed migraine (31.1% vs. 17.4%, p < 0.001).</p><p><strong>Conclusion: </strong>This study highlights the significant financial, social, and access barriers faced by participants with migraine, alongside higher health care utilization, compared to those without diagnosed migraine despite matching for demographic variables and income. These findings underscore the substantial burden of migraine and emphasize the urgent need for targeted interventions to enhance health care accessibility and reduce the burden on affected individuals. These data do not capture the burden of undiagnosed migraine due to the method of case ascertainment.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":"1344-1354"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Na⁺, K⁺-ATPase by cardiotonic steroids: Participation in the sodium theory for migraine.","authors":"Roger Gregory Biringer","doi":"10.1111/head.14980","DOIUrl":"10.1111/head.14980","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The sodium theory for migraine proposes that excessive sodium pumping into the cerebrospinal fluid (CSF) leads to sodium infiltration into the neural tissue, which can lead to activation and central sensitization of trigeminovascular neurons, predisposing individuals to migraine. Dysregulation of the Na&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;-ATPase pump in the choroid plexus is likely to be the primary cause of elevated sodium in the CSF. The identity of intrinsic regulatory molecules that are inhibitors for this pump and their involvement in migraine have been the subject of numerous studies; however, data detailing the involvement of only a few of these regulatory molecules in migraine pathology are published. The regulation mechanisms and the path for these regulators are currently unknown.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This review aims to present data supporting the sodium theory for migraine and explore potential mechanisms for brain sodium dysregulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;PubMed, Google Scholar, and UniProtKB/Swiss-Prot were searched for articles and corroborating information through March 2024. Search items for PubMed and Google Scholar included headache, migraine, Na&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;-ATPase, cardiotonic steroids, ouabain, digoxin, bufalin, marinobufagenin, telocinobufagin, organic anion transporters, and ATP-binding cassette transporters. The Human Protein Atlas was used to obtain receptor and transporter expression levels.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Clinical and preclinical studies reveal that dysregulation of Na&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;-ATPase in the choroid plexus results in excess CSF sodium that enhances central sensitization, predisposing individuals to migraine. Preclinical work also shows that the exogenous, plant-derived cardiotonic steroid ouabain can prevent and alleviate migraine by inhibiting Na&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;-ATPase. Four additional exogenous cardiotonic steroids are also known to inhibit Na&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;-ATPase in vitro, and all five have similar, if not identical, structures to molecules found in human tissues. The documented, evaluated, and potential mechanisms for the involvement of these endogenous cardiotonic steroids in regulating CSF sodium in humans and how these molecules reach the Na&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;-ATPase are presented.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Thus far, only endogenous ouabain is known to regulate CSF sodium levels by regulating Na&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;-ATPase in the choroid plexus epithelium. Four other endogenous regulators similar or identical in structure to digoxin, bufalin, marinobufagenin, and telocinobufagin also have the potential to regulate CSF sodium levels in this manner, but this has yet to be proven. The source for these endogenous regulators is most likely the hypothalamus through paracrine signaling to the choroid plexus; however, endocrine signaling from the hypothalamus or adrenal tissue ","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":"1477-1491"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325311","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":"Graphical abstracts.","authors":"Carolina Guillot, Arathi S Nandyala","doi":"10.1111/head.15018","DOIUrl":"10.1111/head.15018","url":null,"abstract":"","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":"1267"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144617145","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":"Plain Language Summary Publication: Perceived discrimination and migraine-specific quality of life: A cross-sectional survey study in a Black/African American sample.","authors":"Mara Getz, Larry Charleston, Cynthia E Armand, Allison W Willis, Elizabeth Seng","doi":"10.1111/head.15028","DOIUrl":"10.1111/head.15028","url":null,"abstract":"","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":"1500-1501"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803968","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":"Correction to \"Smartphone-delivered progressive muscle relaxation for the treatment of migraine in primary care: A randomized controlled trial\".","authors":"","doi":"10.1111/head.14939","DOIUrl":"10.1111/head.14939","url":null,"abstract":"","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":"1502"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144951520","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":"Lessons from the coronavirus disease 2019 pandemic: Investigating the bidirectional relationship between coronavirus disease 2019 and migraine based on the MECH-HK cohort study.","authors":"Jingbo Liang, Lin Yang, Qingling Yang, Yan Zhang, Qi Sun, Jing Qin, Alice Yuen Loke, Harry Haoxiang Wang, Yao Jie Xie","doi":"10.1111/head.15040","DOIUrl":"10.1111/head.15040","url":null,"abstract":"<p><strong>Background: </strong>Although the coronavirus disease 2019 (COVID-19) pandemic has ended, its impact on patients with migraine has revealed critical gaps in understanding how migraine interacts with respiratory infections. Exploring this bidirectional relationship is essential for improving migraine management and protecting vulnerable populations during future outbreaks.</p><p><strong>Objectives: </strong>To examine (1) the impact of migraine on COVID-19 manifestations and the risk of post-acute sequelae of COVID-19 (PASC), and (2) the effect of COVID-19 infection on migraine features.</p><p><strong>Methods: </strong>We conducted a longitudinal study, with both prospective and retrospective data collection, nested within the Migraine Exposures and Cardiovascular Health in Hong Kong Chinese Women (MECH-HK) cohort. Two cohort-wide assessments were conducted at baseline (2019-2020) and follow-up (2021-2023). Monthly migraine features, including attack frequency, duration, and intensity, were prospectively tracked using migraine diaries. COVID-19-related outcomes, including symptom burden, self-perceived severity, time-to-test negativity, and PASC, were retrospectively self-reported during follow-up. To examine the bidirectional relationship, Substudy 1 used regression models to evaluate how baseline migraine status influenced infection-related outcomes among participants who contracted COVID-19 between baseline and follow-up. Substudy 2 used mixed-effects models to compare longitudinal changes in migraine features between the infection and noninfection groups.</p><p><strong>Results: </strong>In Substudy 1 (n = 1085; mean age: 54.3 ± 9.4 years), women with migraine (n = 122) reported significantly greater COVID-19 symptom burden compared to participants without migraine (mild: adjusted rate ratio [aRR], 1.30; 95% confidence interval [CI], 1.16-1.47; moderate/severe: aRR, 1.44; 95% CI, 1.03-2.01), higher self-perceived severity (adjusted odds ratio [aOR], 1.45; 95% CI, 1.01-2.09), and an elevated risk of PASC (aOR, 1.87; 95% CI, 1.23-2.82), which may suggest heightened vulnerability in this population. In Substudy 2, participants who contracted COVID-19 (n = 73) exhibited a 35% increase in the geometric mean of monthly migraine attack frequency during the first 3 months postinfection (adjusted geometric mean ratio [aGMR], 1.35; 95% CI, 1.10-1.65), whereas no such increase was observed in the noninfection group (n = 128) during the corresponding period. No significant changes in attack duration or intensity were observed in either group.</p><p><strong>Conclusions: </strong>Migraine and COVID-19 exhibit a bidirectional relationship. Women with migraine experienced more severe COVID-19 manifestations and greater PASC risk, whereas infection was associated with increased migraine attack frequency. These findings emphasize the need for tailored migraine management strategies, particularly in the context of future viral outbreaks.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":"1279-1293"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144951626","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":"Beyond \"other\": Exploring representation of minoritized individuals in headache research.","authors":"Nan Cheng, Rashmi B Halker Singh","doi":"10.1111/head.15013","DOIUrl":"https://doi.org/10.1111/head.15013","url":null,"abstract":"","PeriodicalId":12844,"journal":{"name":"Headache","volume":"65 8","pages":"1460-1461"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124520","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":"Underdiagnosis and impact of menstrual migraine in real-world clinical practice: A real-world survey.","authors":"Gisela Terwindt, Jessica Ailani, Jessica Cirillo, Lucy Abraham, Aaron Jenkins, Phillip Saccone, Karin Hygge Blakeman, Feng Dai, James Jackson, Sophie Barlow, William Whitton, Lucy Hancock, Boryana Galabova","doi":"10.1111/head.14996","DOIUrl":"10.1111/head.14996","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This cross-sectional study aimed to evaluate the frequency of menstrual migraine (MM) reporting in clinical practice and to compare the clinical burden, treatment patterns, and patient satisfaction between those with and without MM.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;People with MM experience more severe, disabling, and prolonged attacks than people with non-MM. Research indicates that approximately two thirds of females with migraine may experience MM; however, the prevalence of MM is often underreported and there is a lack of awareness regarding the condition.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study analyzed secondary data from the Adelphi Real World Migraine Disease Specific Programme™, a cross-sectional survey with retrospective data collection conducted across France, Germany, Italy, Spain, the United Kingdom, and the United States from May 2022 to February 2024. Physicians completed an attitudinal survey, and provided data for consecutively consulting patients with migraine, containing questions on demographics, clinical characteristics, treatment history (including reasons for treatment choice, treatment satisfaction, and adherence), and symptomatic burden. Patients voluntarily completed a questionnaire on their current symptom burden, migraine pain severity, treatment satisfaction, and other patient-reported outcomes. Outcomes between patients with and without a physician-confirmed diagnosis of MM were compared using statistical and comparative tests. Patients were eligible for inclusion if they were female, aged 18-55 years, and had menstrual periods.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Overall, 627 physicians reported data on 3215 patients who met the inclusion criteria, with 1037 (32.3%) having a physician-confirmed diagnosis of MM. The patient questionnaire was completed by 931 patients, of whom 340 (36.5%) had a physician-confirmed diagnosis of MM. While physicians estimated on average that 38.5% of their patients experienced MM, 32.3% of patients had a physician-confirmed diagnosis of MM, as reported from the individual patient record forms. Additionally, 14.0% of patients without a physician-confirmed diagnosis of MM self-reported menstruation as a trigger for their migraine. Clinically, there were few differences observed between patient groups, except for higher migraine attack severity in patients with MM (p &lt; 0.001). Patients with and without MM were prescribed a similar number of acute treatments (mean [standard deviation, SD]: both 1.1 [0.7]), but patients with physician-confirmed MM were prescribed fewer preventive treatments (mean [SD]: 0.5 [0.6] vs. 0.6 [0.6], p &lt; 0.001). Lower physician-reported satisfaction with acute (21.6% vs. 29.4%, p = 0.024) and preventative treatment (22.0% vs. 34.8%, p = 0.010) was observed in patients with MM compared to those without MM. Patients with MM also reported less satisfaction with their acute treatment than those without MM (19.4% vs. 27.8%, p = 0.013).&lt;/p","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":"1413-1427"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal fluid and serum biomarkers in idiopathic intracranial hypertension: A systematic review.","authors":"Marina Romozzi, Fabio Zeoli, Renata Martinelli, Federico Tosto, Antonio Funcis, Giuseppe Garignano, Sabrina Chiloiro, Lucia Di Nardo, Catello Vollono, Alessandro Olivi, Paolo Calabresi, Francesco Signorelli","doi":"10.1111/head.15023","DOIUrl":"10.1111/head.15023","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to systematically review the literature on soluble biomarkers in adults with idiopathic intracranial hypertension (IIH).</p><p><strong>Background: </strong>Idiopathic intracranial hypertension is a multifactorial disorder marked by elevated intracranial pressure without a clear cause. Although it primarily affects overweight women of reproductive age, its pathogenesis remains incompletely understood. Symptoms include headache and visual disturbances due to papilledema. Increasing attention has focused on soluble biomarkers in serum and to understand disease mechanisms and aid diagnosis and management.</p><p><strong>Methods: </strong>This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in PROSPERO (CRD420250630653). The systematic literature search was conducted across PubMed, Web of Science, and Scopus for studies published in English between January 1995 and December 2024. Articles investigating cerebrospinal fluid (CSF) and/or blood biomarkers in adult patients with IIH were included. Multiple reviewers independently conducted screening, data extraction, and quality assessment. The risk of bias was evaluated using the ROBINS-I tool.</p><p><strong>Results: </strong>A total of 38 studies on serum/plasma, urine, and CSF biomarkers met the inclusion criteria. The identified biomarkers were categorized into five main groups: (1) metabolic/endocrine, (2) systemic and neurogenic inflammation, (3) neurodegeneration, (4) neural antibodies and CSF dynamics, and (5) miscellaneous. Consistently elevated leptin levels were reported across studies, alongside evidence of cortisol dysregulation, altered androgen profiles, and insulin resistance. Inflammatory markers were frequently elevated, indicating a state of low-grade systemic inflammation; however, findings regarding specific inflammatory markers were variable and lacked consistency. Two studies evaluated calcitonin gene-related peptide (CGRP) in plasma, finding elevated levels in IIH, especially in those with migraine-like headache. Neuronal markers like neurofilament light chain (NfL) were increased and correlated with disease severity. Emerging candidates included microRNAs, metabolites identified through metabolomic approaches, and novel proteins discovered via proteomic analyses.</p><p><strong>Conclusions: </strong>IIH appears to involve interplay of inflammatory, metabolic, and neurodegenerative processes. Although androgen dysregulation, leptin, and NfL show the most consistent association, substantial heterogeneity in study methods and populations limits generalizability. CGRP may emerge as a promising biomarker reflecting the predominant clinical symptom-headache-potentially guiding future therapeutic strategies.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":"1462-1476"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}