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Introduction: Cognitive symptoms are reported commonly throughout all phases of a migraine; however, there is a paucity of objective cognitive profiling. Previous studies have been limited by practice effect, and variable populations., Methods: Participants completed 1 month of daily testing with a computerised cognitive battery involving a simple reaction (SRT), choice reaction (CRT) and a working memory test (WM). Results were correlated with their diary to identify interictal scores, and scores during each phase of a migraine, and non-migraine headache days., Results: A total of 16 patients with episodic migraine participated. During the headache phase of a migraine, responses to SRT, CRT and WM tasks were significantly slower and less accurate than interictally. During the postdrome, WM task performance was slower and less accurate. Non-migraine headache days were not associated with significant change., Conclusion: The headache and postdromal phase of a migraine day was associated with objective evidence of cognitive dysfunction in patients with episodic migraine., (© 2024. The Author(s).)

Background and Methods: In this narrative review, we introduce key artificial intelligence (AI) and machine learning (ML) concepts, aimed at headache clinicians and researchers. Thereafter, we thoroughly review the use of AI in headache, based on a comprehensive literature search across PubMed, Embase and IEEExplore. Finally, we discuss limitations, as well as ethical and political perspectives., Results: We identified six main research topics. First, natural language processing can be used to effectively extract and systematize unstructured headache research data, such as from electronic health records. Second, the most common application of ML is for classification of headache disorders, typically based on clinical record data, or neuroimaging data, with accuracies ranging from around 60% to well over 90%. Third, ML is used for prediction of headache disease trajectories. Fourth, ML shows promise in forecasting of headaches using self-reported data such as triggers and premonitory symptoms, data from wearable sensors and external data. Fifth and sixth, ML can be used for prediction of treatment responses and inference of treatment effects, respectively, aiming to optimize and individualize headache management., Conclusions: The potential uses of AI and ML in headache are broad, but, at present, many studies suffer from poor reporting and lack out-of-sample evaluation, and most models are not validated in a clinical setting., Competing Interests: Declaration of conflicting interestsAnker Stubberud has received lecture honoraria from TEVA. AS holds a patent related to Cerebri developed by Nordic Brain Tech AS, an app intervention that includes headache forecasting. In addition, AS may benefit financially from a license agreement between Nordic Brain Tech AS and NTNU. Helge Langseth reports no conflicts of interest. Parashkev Nachev is funded by Wellcome and the NIHR BRC Biomedical Research Centre. He has shareholdings in two university spin-outs, Sonalis and Hologen. Manjit S. Matharu is chair of the medical advisory board of the CSF Leak Association; has served on advisory boards for AbbVie, Eli Lilly, Kriya, Lundbeck, Pfizer, Salvia and TEVA; has received payment for educational presentations from AbbVie, Eli Lilly, Lundbeck, Pfizer and TEVA; has received grants from Abbott, Medtronic and Ehlers Danlos Society; and has a patent on system and method for diagnosing and treating headaches (WO2018051103A1, issued). Erling Tronvik has received personal fees for lectures/advisory boards: Novartis, Eli Lilly, Abbvie, TEVA, Roche, Lundbeck, Pfizer, Biogen. Consultant for and owner of stocks and IP in Man & Science. Stocks and IP in Nordic Brain Tech (includes headache forecasting) and Keimon Medical. Non-personal research grants from several sources, including EU, Norwegian Research Council, Dam foundation, KlinBeForsk. Commissioned research (non-personal): Lundbeck, Eli-Lilly.

Background: A novel technique for injection of OnabotulinumtoxinA (BTA) towards the sphenopalatine ganglion (SPG) has shown promise in refractory chronic migraine (CM) and chronic cluster headache (CCH). Open label safety and efficacy data are presented here., Methods: Patients with refractory CM or CCH who had received at least one injection and completed headache diaries were included. Efficacy was defined as ≥50% reduction in moderate-to-severe headache days for CM, or ≥50% reduction in attack frequency for CCH, at weeks five to eight., Results: Over 261 injections, there were 123 adverse events (AE), of which one was serious. Most (93%) AEs were mild and all were transient. The 50% response to one injection was 81% for CM and 69% for CCH. The response gradually reduced over subsequent months for CM but stayed between 55% and 67% for CCH. Repeated injections were beneficial., Conclusions: Injections resulted in improvement for both groups and was maintained with repeated injections. Repeat injection after three months may be beneficial in CM. Adverse events were not uncommon, but universally transient, presumably as a result of the mechanism of action of BTA. Repeated BTA injection towards the SPG could be an effective treatment for refractory CM and CCH. Larger, randomised, placebo-controlled trials are required., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SH and KAJ have no conflicts of interest. LS receives research funding from The Wellington Hospital, London, UK. IA has stocks in Keimon Medical. TWM has been an honorary lecturer for Roche, TEVA Norway AS and Lundbeck AS and is a programme committee member for Lilly. He is a shareholder in Vilje Bionics AS and Keimon Medical AS. MSM serves on the advisory board for AbbVie, Abbott, Eli Lilly, Kriya, Lundbeck, Pfizer, Salvia and TEVA and has received payment for the development of educational presentations from AbbVie, Eli Lilly, Lunbeck and TEVA. He has received research grants from Abbott, Ehler's Danlos Society and Medtronic. He holds a patent (WO2018051103A1) on System and method for diagnosing and treating headaches. He is the chair of the medical advisory board of the CSF Leak Association. ET has Intellectual Property Rights for the MultiGuide device that is used in this paper and which is licensed to Man & Science. He is a consultant for and owner of stocks in Man & Science. He has received personal fees for lectures/ advisory boards from Novartis, Eli Lilly, Abbvie, TEVA, Roche, Lundbeck, Pfizer and Biogen, and has stocks and IP in Nordic Brain Tech. He also has stocks in Keimon Medical. He has received non-personal research funding from several sources, including EU, Norwegian Research Council, Dam foundation, KlinBeForsk. Commissioned research (non-personal): Lundbeck, Pfizer. DB may benefit financially from a commercialization of a proposed treatment targeting the SPG and the intervention device used to perform the treatment through intellectual properties rights and has consulted for Man & Science within the past 12 months.

Background: Few studies of migraine have evaluated migraine disability across multiple countries using the same methodology., Methods: This cross-sectional, web-based survey was conducted in 2021-2022 in Canada, France, Germany, Japan, UK and USA. Respondents with migraine were identified based on modified International Classification of Headache Disorders, 3rd edition, criteria. Headache features (Migraine Symptom Severity Score (MSSS, range: 0-21), presence of allodynia (Allodynia Symptom Checklist, ASC-12)) and migraine burden (Patient Health Questionnaire-4 (PHQ-4), Migraine-Specific Quality of Life questionnaire version 2.1 (MSQ v2.1), Work Productivity and Activity Impairment (WPAI) questionnaire) were evaluated., Results: Among 14,492 respondents with migraine across countries, the mean ± SD MSSS was 15.4 ± 3.2 and 48.5% (7026/14,492) of respondents had allodynia based on ASC-12. Of all respondents living with migraine, 35.5% (5146/14,492) reported moderate to severe anxiety and/or depression symptoms. Mean ± SD MSQ v2.1 Role Function-Restrictive, Role Function-Preventive and Emotional Function domain scores were 60.7 ± 22.9, 71.5 ± 23.0 and 65.1 ± 27.2, respectively. The WPAI mean ± SD percentages of respondents who missed work or worked impaired as a result of migraine were 6.8 ± 18.1% and 41.0 ± 30.1%, respectively., Conclusions: For every country surveyed, migraine was associated with high levels of symptom severity, with allodynia and with substantial burden., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Zaza Katsarava, MD, has been a speaker and/or consultant for, and/or received research support from Allergan, Amgen/Novartis, Eli Lilly, Merck and Teva. Dawn C. Buse, PhD, has received grant support and honoraria from AbbVie, Amgen, Biohaven, Collegium, Eli Lilly, Lundbeck, Teva and Theranica and for work on the editorial board of Current Pain and Headache Reports and is the national principal investigator in the United States for the CaMEO-I Study. Elizabeth Leroux, MD, has received speaker fees and consulting fees from Allergan, Eli Lilly and Teva Neuroscience; consulting fees from Aralez Pharmaceuticals, McKesson Canada and Medscape; speaking fees, consulting fees and reimbursement for travel from Novartis; and reimbursement for travel from IHS-GPAC. Michel Lanteri-Minet, MD, reports personal fees for advisory boards, speaker panels, or investigation studies from Allergan, Amgen, Astellas, ATI, BMS, Boehringer, Boston Scientific, CoLucid, Convergence, GlaxoSmithKline, Grunenthal, IPSEN, Lilly, Lundbeck, Medtronic, Menarini, MSD, Novartis, Orion Pharma, Pfizer, Reckitt Benckiser, Saint-Jude, Salvia BioElectronics, Sanofi-Aventis, Teva, UCB, UPSA and Zambon. Fumihiko Sakai, MD, is a consultant, speaker or scientific advisor for Amgen, Eisai, Eli Lilly, Otsuka and Teva, and the national principal investigator in Japan for the CaMEO-I Study. Manjit Matharu, MD, serves on the advisory board for Abbott, AbbVie, Eli Lilly, Lundbeck, Medtronic, Pfizer, Salvia and Teva; has received payment for the development of educational presentations from AbbVie, electroCore, Eli Lilly, Novartis and Teva; and is the national principal investigator in the United Kingdom for the CaMEO-I Study. Aubrey Manack Adams, PhD, and Karen Carr, PhD, are employees of AbbVie and may hold AbbVie stock. Kristina M. Fanning, PhD, is managing director of MIST Research, which has received research funding from AbbVie, Allay Lamp, NYC Langone Health, Juva Health and GlaxoSmithKline via grants to the National Headache Foundation. Richard B. Lipton, MD, receives research support from the Marx Foundation, the National Headache Foundation, the National Institutes of Health and the US Food and Drug Administration. He serves as a consultant or advisory board member for or has received honoraria or research support from AbbVie/Allergan, Amgen, Biohaven, Dr Reddy's Laboratories (Promius), electroCore, Eli Lilly, GlaxoSmithKline, Lundbeck, Merck, Novartis, Teva, Vector and Vedanta Research; receives royalties from Informa and Wolff's Headache, 8th edition (Oxford University Press, 2009); holds stock/options in Axon, Biohaven, CoolTech and Manistee; and is the overall principal investigator for the CaMEO-I Study.

Background: Chronic headache disorders are disabling. The CHESS trial studied the effects of a short non-pharmacological intervention of education with self-management support for people affected by migraine and/or tension type headache for at least 15 days per month for at least three months. There were no statistically significant effects on the Headache Impact Test-6 (HIT-6) at 12-months. However, we observed improvement in pain self-efficacy questionnaire (PSEQ) and short-term HIT-6. We explored the impact of the CHESS intervention on PSEQ, and subsequently, on the HIT-6 and chronic headache quality of life questionnaire (CH-QLQ) at four, eighth and 12 months., Methods: We included all 736 participants from the CHESS trial. We used simple linear regression models to explore the change of HIT-6 and CH-QLQ with treatment and PSEQ at baseline (predictor analysis), and the interaction between treatment and baseline PSEQ (moderator analysis). We considered the change of PSEQ from baseline to four months as a mediator in the mediation analysis., Results: Baseline PSEQ neither predicted nor moderated outcomes. The prediction effect on change of HIT-6 from baseline to 12 months was 0.01 (95% CI, -0.03 to 0.04) and the interaction (moderation) effect was -0.07 (95% CI, -0.15 to 0.002). However, the change of PSEQ from baseline to 4-month mediated the HIT-6 (baseline to 8-, and 12-month) and all components of CH-QLQ (baseline to 8-, and 12-month). The CHESS intervention improved the mediated variable, PSEQ, by 2.34 (95% CI, 0.484 to 4.187) units and this corresponds to an increase of 0.21 (95% CI, 0.03 to 0.45) units in HIT-6 at 12-months. The largest mediated effect was observed on the CH-QLQ Emotional Function, an increase of 1.12 (95% CI, 0.22 to 2.20)., Conclusions: PSEQ was not an effective predictor of outcome. However, change of short-term PSEQ mediated all outcomes, albeit minimally. Future behavioural therapy for chronic headache may need to consider how to achieve larger, and more sustained increases level of self-efficacy than that achieved within the CHESS trial., Trial Registration: ISRCTN79708100., (© 2024. The Author(s).)

Background: We aimed to develop the first machine learning models to predict citation counts and the translational impact, defined as inclusion in guidelines or policy documents, of headache research, and assess which factors are most predictive., Methods: Bibliometric data and the titles, abstracts, and keywords from 8600 publications in three headache-oriented journals from their inception to 31 December 2017 were used. A series of machine learning models were implemented to predict three classes of 5-year citation count intervals (0-5, 6-14 and, >14 citations); and the translational impact of a publication. Models were evaluated out-of-sample with area under the receiver operating characteristics curve (AUC)., Results: The top performing gradient boosting model predicted correct citation count class with an out-of-sample AUC of 0.81. Bibliometric data such as page count, number of references, first and last author citation counts and h-index were among the most important predictors. Prediction of translational impact worked optimally when including both bibliometric data and information from the title, abstract and keywords, reaching an out-of-sample AUC of 0.71 for the top performing random forest model., Conclusion: Citation counts are best predicted by bibliometric data, while models incorporating both bibliometric data and publication content identifies the translational impact of headache research., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Nurses work at headache centres throughout Europe, and their care for migraine patients is acknowledged. However, the specific roles and tasks of nursing vary, and a unified understanding is lacking, posing challenges to knowledge sharing and research., Objectives: Using an e-Delphi study method, the objective is to obtain healthcare professional headache experts' opinions on nursing-specific roles and tasks and combine this into consensus statements for nurse recommendations for migraine treatment., Methods: A three-round questionnaire study was conducted with nurses and neurologists from 18 specialised headache centres in 10 countries. In round 1, statements were compiled from a systematic examination of existing literature and expert opinions. In rounds 2 and 3, the experts rated the importance of statements (from round 1) on a 5-point Likert scale. Statements were analysed using a content analysis method, and the consensus of pre-defined statements was evaluated with gradually increased predetermined criteria using descriptive statistics., Results: Twenty-one experts, representing all 10 countries, participated. The predetermined consensus of ≥70% agreement was reached for 42 out of the initial 63 statements. These statements formed the final recommendations within two themes: "The nurses' roles and tasks in the clinical setting" and "The nurses' roles and tasks in educating patients and colleagues." The consensus level of statements was strong, with 40% receiving unanimous agreement (100%) and 97% achieving relatively high agreement (>80%)., Conclusion: Nursing plays a vital role with diverse tasks in migraine care. This study offers practical recommendations and a framework for nurses, equipping them with a clinical tool to enhance care and promote a coordinated approach to migraine treatment., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.V.R. has received honoraria from Lundbeck and Eli Lilly for Advisory Boards and written compendium; R.H.J. has received honoraria for lectures and patient leaflets from MSD, Berlin-Chemie Menarini, ATI, and Pfizer and participated in medical advisory boards for ATI and Electrocore and conducted clinical trials for Eli-Lilly and ATI; A.G. has received honoraria for lectures or consulting from AbbVie, Almirall, Biogen, BioMed, Curatis, EliLilly, Lundbeck, Neurolite, Novartis, TEVA/Mepha; S.L. received fees for attending advisory meetings, presentations and preparing presentation materials from AbbVie, TEVA, Eli Lilly, Tillots Pharma, Salvia and Novartis; M.S.M. is chair of the medical advisory board of the CSF Leak Association, serves on the advisory board for Abbott, AbbVie, Eli Lilly, Salvia, Lundbeck, Pfizer and TEVA, has received payment for the development of educational presentations from AbbVie, Eli Lilly, Lundbeck, TEVA and Pfizer; S.B.M. has received travel grants from Lundbeck, TEVA, AbbVie and for Advisory board for AbbVie, Lundbeck, Novartis, TEVA; M.H. received funding for travel and/or speaker honoraria from TEVA, Lundbeck and compensation for advisory service or producing educational material from TEVA, Lundbeck and Novartis; All other authors have declared no conflict of interests.

Background: We aimed to create a multidisciplinary consensus clinical guideline for best practice in the diagnosis, investigation and management of spontaneous intracranial hypotension (SIH) due to cerebrospinal fluid leak based on current evidence and consensus from a multidisciplinary specialist interest group (SIG)., Methods: A 29-member SIG was established, with members from neurology, neuroradiology, anaesthetics, neurosurgery and patient representatives. The scope and purpose of the guideline were agreed by the SIG by consensus. The SIG then developed guideline statements for a series of question topics using a modified Delphi process. This process was supported by a systematic literature review, surveys of patients and healthcare professionals and review by several international experts on SIH., Results: SIH and its differential diagnoses should be considered in any patient presenting with orthostatic headache. First-line imaging should be MRI of the brain with contrast and the whole spine. First-line treatment is non-targeted epidural blood patch (EBP), which should be performed as early as possible. We provide criteria for performing myelography depending on the spine MRI result and response to EBP, and we outline principles of treatments. Recommendations for conservative management, symptomatic treatment of headache and management of complications of SIH are also provided., Conclusions: This multidisciplinary consensus clinical guideline has the potential to increase awareness of SIH among healthcare professionals, produce greater consistency in care, improve diagnostic accuracy, promote effective investigations and treatments and reduce disability attributable to SIH., Competing Interests: Competing interests: JA: remuneration for consultancy advice and education provision from Allergan/AbbVie and TEVA. HA-L: lectures and education paid by International Medical Press, Sanofi and Eisai. LCJ: lecture fees received from Radiopaedia. SC: research fellowship sponsored by Abbott. LD'A: supported by an NIHR Academic Clinical Fellowship and was the recipient of a research fellowship sponsored by B Braun. BD: remuneration for consultancy advice and education provision from TEVA, Allergan and Lilly. PJD: shareholding in BMS, Regeneron and Ionis Pharma. SE: owns the North Midlands Neurosciences. VI: reports speaker fees and honoraria from Theravance Biopharma and Jensen, outside of the present work; supported by the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre. SL: received fees for attending advisory meetings, presentations and preparing presentation materials from Allergan, TEVA, Eli Lilly and Novartis. MSM: chair of the medical advisory board of the CSF Leak Association, serves on the advisory board for Abbott, Allergan, Novartis, Eli Lilly, Medtronic, Autonomic Technologies and TEVA, and has received payment for the development of educational presentations from Allergan, electroCore, Eli Lilly, Novartis and TEVA. CJ, SM, JP, RS, TT: members of CSF Leak Association. S-JW: received honoraria as a moderator from AbbVie, Pfizer, Eli Lilly and Biogen, and has been the PI in trials sponsored by AbbVie, Novartis and Lundbeck. He has received research grants from the Taiwan Minister of Technology and Science (MOST), Brain Research Center, National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan, Taipei Veterans General Hospital, Taiwan Headache Society and Taiwan branches of Eli Lilly and Novartis., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Chronic Migraine Epidemiology and Outcomes-International study provides insight into people with migraine in multiple countries., Methods: This cross-sectional, observational, web-based cohort study was conducted in Canada, France, Germany, Japan, United Kingdom, and United States. An initial Screening Module survey solicited general healthcare information from a representative sample and identified participants with migraine based on modified International Classification of Headache Disorders-3 criteria; those with migraine completed a detailed survey based on validated migraine-specific assessments., Results: Among 90,613 people who correctly completed the screening surveys, 76,121 respondents did not meet the criteria for migraine, while 14,492 did. Among respondents with migraine, mean age ranged from 40 to 42 years. The median number of monthly headache days ranged from 2.33 to 3.33 across countries, while the proportion of respondents with moderate-to-severe disability (measured by Migraine Disability Assessment) ranged from 30% (Japan) to 52% (Germany). The proportion of respondents with ≥15 monthly headache days ranged from 5.4% (France) to 9.5% (Japan). Fewer than half of respondents with migraine in each country reported having received a migraine diagnosis., Conclusion: These results demonstrated high rates of migraine-related disability and underdiagnosis of migraine across six countries. This study will characterize country-level burden, treatment patterns, and geographical differences in care.

Background: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAb) are an effective treatment of migraine however may have possible off-target effects. Pre-clinical studies implicate CGRP in several aspects of bone turnover and homeostasis. The clinical effect of CGRP mAb on bone turnover is not known, however., Methods: Between June 2021 and July 2022, a multi-centre prospective cohort study was undertaken with eligible patients undergoing paired testing of the validated bone turnover markers procollagen type I N-terminal propeptide (P1NP) and serum C-terminal telopeptide of type I collagen (CTX) prior to and at least three months following administration of a CGRP mAb., Results: A total of 45 patients with a mean age of 41.8 (SD 11.9) were included in the final analysis, all of whom received a ligand-targeting CGRP mAb. Administration of a CGRP mAb was associated with a statistically significant increase in P1NP from 44.5 microg/L to 51.5 microg/L (p = 0.004), but no significant change in CTX., Conclusion: In otherwise homeostatic conditions, short-term administration of a CGRP mAb is associated with increased P1NP, a bone formation marker but not with increased CTX, a bone resorption marker. Further study is required to validate these findings over longer time periods, in a larger cohort, and in pre-existing states of increased calcium stress and bone-turnover.

Objective: To perform a systematic review and meta-analysis of the epidemiology, precipitants, phenotype, comorbidities, pathophysiology, treatment, and prognosis of primary new daily persistent headache., Methods: We searched PubMed/Medline, EMBASE, Cochrane, and clinicaltrials.gov until 31 December 2022. We included original research studies with any design with at least five participants with new daily persistent headache. We assessed risk of bias using National Institutes of Health Quality Assessment Tools. We used random-effects meta-analysis where suitable to calculate pooled estimates of proportions. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis compliant study is registered with PROSPERO (registration number CRD42022383561)., Results: Forty-six studies met inclusion criteria, predominantly case series, including 2155 patients. In 67% (95% CI 57-77) of cases new daily persistent headache has a chronic migraine phenotype, however new daily persistent headache has been found to be less likely than chronic migraine to be associated with a family history of headache, have fewer associated migrainous symptoms, be less vulnerable to medication overuse, and respond less well to injectable and neuromodulatory treatments., Conclusions: New daily persistent headache is a well described, recognisable disorder, which requires further research into its pathophysiology and treatment. There is a lack of high-quality evidence and, until this exists, we recommend continuing to consider new daily persistent headache a distinct disorder.

Introduction: Triggers, premonitory symptoms and physiological changes occur in the preictal migraine phase and may be used in models for forecasting attacks. Machine learning is a promising option for such predictive analytics. The objective of this study was to explore the utility of machine learning to forecast migraine attacks based on preictal headache diary entries and simple physiological measurements., Methods: In a prospective development and usability study 18 patients with migraine completed 388 headache diary entries and self-administered app-based biofeedback sessions wirelessly measuring heart rate, peripheral skin temperature and muscle tension. Several standard machine learning architectures were constructed to forecast headache the subsequent day. Models were scored with area under the receiver operating characteristics curve., Results: Two-hundred-and-ninety-five days were included in the predictive modelling. The top performing model, based on random forest classification, achieved an area under the receiver operating characteristics curve of 0.62 in a hold-out partition of the dataset., Discussion: In this study we demonstrate the utility of using mobile health apps and wearables combined with machine learning to forecast headache. We argue that high-dimensional modelling may greatly improve forecasting and discuss important considerations for future design of forecasting models using machine learning and mobile health data.

Background and Objectives: Chronic headache disorders are a major cause of pain and disability. Education and supportive self-management approaches could reduce the burden of headache disability. We tested the effectiveness of a group educational and supportive self-management program for people living with chronic headaches., Methods: This was a pragmatic randomized controlled trial. Participants were aged 18 years or older with chronic migraine or chronic tension-type headache, with or without medication overuse headache. We primarily recruited from general practices. Participants were assigned to either a 2-day group education and self-management program, a one-to-one nurse interview, and telephone support or to usual care plus relaxation material. The primary outcome was headache related-quality of life using the Headache Impact Test (HIT)-6 at 12 months. The primary analysis used intention-to-treat principles for participants with migraine and both baseline and 12-month HIT-6 data., Results: Between April 2017 and March 2019, we randomized 736 participants. Because only 9 participants just had tension-type headache, our main analyses were on the 727 participants with migraine. Of them, 376 were allocated to the self-management intervention and 351 to usual care. Data from 586 (81%) participants were analyzed for primary outcome. There was no between-group difference in HIT-6 (adjusted mean difference = -0.3, 95% CI -1.23 to 0.67) or headache days (0.9, 95% CI -0.29 to 2.05) at 12 months. The Chronic Headache Education and Self-management Study intervention generated incremental adjusted costs of £268 (95% CI, £176-£377) (USD383 [95% CI USD252-USD539]) and incremental adjusted quality-adjusted life years (QALYs) of 0.031 (95% CI -0.005 to 0.063). The incremental cost-effectiveness ratio was £8,617 (USD12,322) per QALY gained., Discussion: These findings conclusively show a lack of benefit for quality of life or monthly headache days from a brief group education and supportive self-management program for people living with chronic migraine or chronic tension-type headache with episodic migraine., Trial Registration Information: Registered on the International Standard Randomized Controlled Trial Number registry, ISRCTN79708100 16th December 2015 doi.org/10.1186/ISRCTN79708100. The first enrollment was April 24, 2017., Classification of Evidence: This study provides Class III evidence that a brief group education and self-management program does not increase the probability of improvement in headache-related quality of life in people with chronic migraine., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Shunted patients often complain of headaches after flights. The effect of air travel on shunt systems is unknown. We describe the case of a patient with longstanding hydrocephalus, who suffered flight-induced clinical deterioration and shunt overdrainage in two independent occasions. The patient, clinically stable for 1.5 and 5 years before each episode, reported severe headaches starting during the descent stages of the air travel. On both occasions, brain MRI imaging demonstrated pronounced ventricular size reduction. This case suggests that flight-induced shunt overdrainage can occur and should be suspected in patients with prolonged headaches and/or clinical deterioration triggered by air travel.

In 1995, a committee of the International Headache Society developed and published the first edition of the Guidelines for Controlled Trials of Drugs in Cluster Headache. These have not been revised. With the emergence of new medications, neuromodulation devices and trial designs, an updated version of the International Headache Society Guidelines for Controlled Clinical Trials in Cluster Headache is warranted. Given the scarcity of evidence-based data for cluster headache therapies, the update is largely consensus-based, but takes into account lessons learned from recent trials and demands by patients. It is intended to apply to both drug and neuromodulation treatments, with specific proposals for the latter when needed. The primary objective is to propose a template for designing high quality, state-of-the-art, controlled clinical trials of acute and preventive treatments in episodic and chronic cluster headache. The recommendations should not be regarded as dogma and alternative solutions to particular methodological problems should be explored in the future and scientifically validated.

Objective: To assess the prevalence and burden of autonomic symptoms in migraine, and determine the relationship with migraine frequency., Background: Autonomic symptoms in migraine have been theorized to occur in the setting of inter-ictal sympathetic hypoactivity and hyper-sensitivity. There is limited data prospectively assessing cranial and extra-cranial autonomic symptoms with a validated instrument, or longitudinal data on the relationship between migraine disease activity and autonomic symptoms., Methods: Patients attending a single tertiary academic center were recruited into a prospective cohort study between September 2020 and June 2022. In addition to standard clinical care, they completed several surveys including the Composite Autonomic Symptom Scale (COMPASS-31) questionnaire, a validated survey of autonomic symptoms., Results: A total of 43 patients (66.7% female, median age 42, IQR 17) were included in the final analysis. There was a baseline 20 monthly headache days (MHD) (IQR 21.7), and 65.1% of the population had chronic migraine by ICHD-3 criteria. A significantly elevated weighted COMPASS-31 score was reported in 60.5% of respondents (mean 30.3, SD 13.3) at baseline. After 12 months treatment, significant improvements were reported in migraine frequency (median MHD 20-8.7) and disability (median Migraine Disability Assessment Score 67-48), but not in autonomic symptoms (mean score 30.3, SD 11.2)., Conclusion: Autonomic symptoms were frequently reported in patients with migraine. However, they did not correlate with headache frequency or reversion to episodic frequency. Further study is required to elucidate specific approaches and treatments for autonomic symptoms, and further evaluate the underlying pathophysiological mechanisms., Competing Interests: Author JR has received funding from the Pharmaceutical Society of Australia and the Limbic supported by unrestricted educational grants from Viatris and Novartis respectively. Author EF has been supported by grants from the NHMRC Medical Postgraduate Research Scholarship APP1150482, The Royal Australasian College of Physicians Research Entry Scholarship, AVANT Doctors In Training Scholarship, and Monash University Bridging Postdoctoral Fellowship, and her institution has also received research grants from Brain Foundation, the Australian Epilepsy Research Fund, the Viertel Foundation, and Lundbeck, outside the submitted work. Author MM serves on the advisory board for Allergan, Novartis, Eli Lilly, Autonomic Technologies Inc., and TEVA and has received payment for the development of educational presentations from Allergan, electroCore, Eli Lilly, Novartis and TEVA. Author EH has served on advisory boards for SanofiGenzyme, Novartis, Teva, Eli Lilly, Allergan, Lundbeck, been involved in clinical trials sponsored by Novartis, Teva, Xalud, Cerecin, and has received payment for educational presentations from Allergan, Teva, Eli Lilly and Novartis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ray, Cheema, Foster, Gunasekera, Mehta, Corcoran, Matharu and Hutton.)

Background: Headache is a common presentation of postural tachycardia syndrome, yet robust prevalence data is lacking., Objectives: To undertake a systematic review and meta-analysis to estimate the prevalence of headache disorders in postural tachycardia syndrome, and to explore the potential shared pathophysiological mechanisms that underpin these conditions as well as treatment options., Methods: Three databases were searched for publications evaluating prevalence of migraine (primary outcome) and general and orthostatic headache (secondary outcomes) in patients with postural tachycardia syndrome. Two independent reviewers selected studies and extracted data. A random-effects meta-analysis calculated the pooled prevalence of migraine in postural tachycardia syndrome. A narrative literature review explored the pathophysiology and treatment options for concurrent headache disorders and postural tachycardia syndrome., Results: Twenty-three articles met inclusion criteria. Estimated pooled prevalence of migraine in postural tachycardia syndrome was 36.8% (95% CI 2.9-70.7%). Various shared pathophysiological pathways for these conditions, as well as proposed treatment strategies, were identified. Limitations : Heterogeneity of study design, populations, and methodology for identifying headache disorders and postural tachycardia syndrome limited the generalisability of results., Conclusions: Migraine is a commonly reported comorbidity in POTS, however the true prevalence cannot be determined from the current literature. Further studies are required to assess this comorbidity and investigate the underlying mechanisms, as well as identify effective treatment strategies.

Introduction: The use of lidocaine (lignocaine) and ketamine infusion in the inpatient treatment of patients with headache disorders is supported by small case series. We undertook a retrospective cohort study in order to assess the efficacy, duration and safety of lidocaine and ketamine infusions., Methods: Patients admitted between 01/01/2018 and 31/07/2021 were identified by ICD code and electronic prescription. Efficacy of infusion was determined by reduction in visual analog score (VAS), and patient demographics were collected from review of the hospital electronic medical record., Results: Through the study period, 83 infusions (50 lidocaine, 33 ketamine) were initiated for a headache disorder (77 migraine, three NDPH, two SUNCT, one cluster headache). In migraine, lidocaine infusion achieved a ≥50% reduction in pain in 51.1% over a mean 6.2 days (SD 2.4). Ketamine infusion was associated with a ≥50% reduction in pain in 34.4% over a mean 5.1 days (SD 1.5). Side effects were observed in 32 and 42.4% respectively. Infusion for medication overuse headache (MOH) led to successful withdrawal of analgesia in 61.1% of lidocaine, and 41.7% of ketamine infusions., Conclusion: Lidocaine and ketamine infusions are an efficacious inpatient treatment for headache disorders, however associated with prolonged length-of-stay and possible side-effects., Competing Interests: JR has received payment for educational presentations from Viatris. RS has served on advisory boards for Novartis, Teva, Eli Lilly, Allergan, Lundbeck and has received payment for educational presentations from Allergan, Teva, Eli Lilly and Novartis. MM serves on the advisory board for Allergan, Novartis, Eli Lilly, Autonomic Technologies Inc. and TEVA and has received payment for the development of educational presentations from Allergan, electroCore, Eli Lilly, Novartis and TEVA. EH has served on advisory boards for Sanofi-Genzyme, Novartis, Teva, Eli Lilly, Allergan, Lundbeck, been involved in clinical trials sponsored by Novartis, Teva, Xalud, Cerecin, and has received payment for educational presentations from Allergan, Teva, Eli Lilly and Novartis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ray, Cheng, Tsan, Hussain, Stark, Matharu and Hutton.)

Objective: A better understanding of the effect of position on intracranial pressure (ICP) and compliance is important for the development of treatment strategies that can restore normal cerebrospinal fluid (CSF) dynamics. There is limited knowledge on the effect of position on intracranial compliance. In this cross-sectional study the authors tested the association of pulse amplitude (PA) with position and the day/night cycle. Additionally, they describe the postural ICP and PA changes of patients with "normal" ICP dynamics., Methods: This single-center retrospective study included patients with suspected and/or confirmed CSF dynamics abnormalities who had been examined with elective 24-hour ICP monitoring between October 2017 and September 2019. Patients had been enrolled in a short exercise battery including four positions: supine, lumbar puncture position in the left lateral decubitus position, sitting, and standing. Each position was maintained for 2 minutes, and mean ICP and PA were calculated for each position. The 24-hour day and night median ICP and PA data were also collected. Linear regression models were used to test the correlation of PA with position and day/night cycle. All linear regressions were corrected for confounders. The postural ICP monitoring results of patients without obvious ICP dynamics abnormality were summarized., Results: One hundred one patients (24 males and 77 females) with a mean age of 39 ± 13years (mean ± standard deviation) were included in the study. The adjusted linear regression models demonstrated a significant association of ICP with position and day/night cycle, with upright (sitting and standing) and day ICP values lower than supine and night ICP values. The adjusted linear regression model was also significant for the association of PA with position and day/night cycle, with upright and day PA values higher than supine and night PA results. These associations were confirmed for patients with and without shunts. Patients without clear ICP dynamics abnormality had tighter control of their postural ICP changes than the other patients; however, the difference among groups was not statistically significant., Conclusions: This is the largest study investigating the effect of postural changes on intracranial compliance. The results of this study suggest that PA, as well as ICP, is significantly associated with posture, increasing in upright positions compared to that while supine. Further studies will be needed to investigate the mechanism behind this association.

Background: Calcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response., Cases: We present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy., Conclusion: This case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward., (© 2021. The Author(s).)

Background: Chronic migraine (CM) and episodic migraine (EM) are associated with substantial headache-related disability, poor quality of life and global societal burden. In this subgroup analysis from the CONQUER study, we report efficacy outcomes from a pre-specified analysis of galcanezumab versus placebo in patients with CM or EM and 3-4 prior preventive medication category failures due to inadequate efficacy (after at least 2 months at maximum tolerated dose), or safety or tolerability reasons. The patient population is of particular interest due to evidence of decreased quality of life and increased economic burden among patients with migraine that is inadequately managed and is of interest to decision-makers globally., Methods: Key outcomes included overall mean change from baseline in monthly migraine headache days and proportions of patients achieving ≥30% (CM), ≥50%, and ≥ 75% reduction (response rates) in monthly migraine headache days across Months 1-3. Patient functioning and disability were evaluated at Month 3., Results: Of the 462 randomized patients, 186 (40.3%) had a history of 3-4 preventive category failures. Galcanezumab versus placebo resulted in significantly (P ≤ .001) larger overall mean reduction in monthly migraine headache days (total: - 5.49 versus - 1.03; CM: - 6.70 versus - 1.56; EM: - 3.64 versus - 0.65). Similarly, the ≥50% response rate was significantly (P ≤ .001) higher with galcanezumab versus placebo (total: 41.0 versus 12.7; CM: 41.5 versus 8.4; EM: 41.1 versus 16.5). In the CM group, the ≥30% response rate was significantly higher in the galcanezumab group than the placebo group (CM, 57.5 versus 19.8, P ≤ .0001) as was the ≥75% response rate (13.3 versus 2.6, P ≤ .05). Galcanezumab also resulted in significant (P < .0001) improvements in patient functioning and reductions in disability., Conclusions: Galcanezumab was effective in a difficult-to-treat population of patients with CM or EM who had failed 3-4 prior preventive medication categories., Trial Registration: CONQUER. Clinicaltrials.gov identifier: NCT03559257 ., (© 2021. The Author(s).)

Objective: To evaluate the utility of brain MRI and ophthalmic biomarkers for the prediction of intracranial hypertension, we have studied the association between 6 biomarkers and 24-hour intracranial pressure (ICP) monitoring results in 45 patients., Methods: This single-center observational study includes patients who underwent 24-hour ICP monitoring, brain MRI (within 3 months), and ophthalmic assessment (during ICP monitoring). Six biomarkers were investigated: pituitary gland shape, vertical tortuosity of the optic nerve, distension of the optic nerve sheath, optic disc protrusion (MRI), papilledema (slit lamp biomicroscopy), and spontaneous venous pulsations (SVP, infrared video recordings)., Results: Forty-five patients (mean age 39 ± 14 years, 38 women) met the inclusion criteria. All 6 biomarkers had a significant association with 24-hour ICP. Concave pituitary gland was observed with moderately elevated median ICP. Protrusion of the optic disc (MRI), papilledema, and absence of SVP were associated with the highest median ICP values. Twenty patients had raised ICP (median 24-hour ICP >5.96 mm Hg, cutoff obtained through Youden index calculation). Patients with all normal biomarkers had normal median ICP in 94% (standard error 6%) of the cases. All patients with ≥3 abnormal biomarkers had intracranial hypertension. The combination of at least 1 abnormal biomarker in MRI and ophthalmic assessments was highly suggestive of intracranial hypertension (area under the curve 0.94, 95% confidence interval 0.93-0.94) CONCLUSIONS: Brain MRI and ophthalmic biomarkers can noninvasively guide the management of patients with suspected CSF dynamics abnormalities. Patients with multiple abnormal biomarkers (≥3) or a combination of abnormal MRI and ophthalmic biomarkers are likely to have intracranial hypertension and should be managed promptly., (© 2021 American Academy of Neurology.)

Importance: Spontaneous intracranial hypotension (SIH) is a highly disabling but often misdiagnosed disorder. The best management options for patients with SIH are still uncertain., Objective: To provide an objective summary of the available evidence on the clinical presentation, investigations findings, and treatment outcomes for SIH., Data Sources: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline-compliant systematic review and meta-analysis of the literature on SIH. Three databases were searched from inception to April 30, 2020: PubMed/MEDLINE, Embase, and Cochrane. The following search terms were used in each database: spontaneous intracranial hypotension, low CSF syndrome, low CSF pressure syndrome, low CSF volume syndrome, intracranial hypotension, low CSF pressure, low CSF volume, CSF hypovolemia, CSF hypovolaemia, spontaneous spinal CSF leak, spinal CSF leak, and CSF leak syndrome., Study Selection: Original studies in English language reporting 10 or more patients with SIH were selected by consensus., Data Extraction and Synthesis: Data on clinical presentation, investigations findings, and treatment outcomes were collected and summarized by multiple observers. Random-effect meta-analyses were used to calculate pooled estimates of means and proportions., Main Outcomes and Measures: The predetermined main outcomes were the pooled estimate proportions of symptoms of SIH, imaging findings (brain and spinal imaging), and treatment outcomes (conservative, epidural blood patches, and surgical)., Results: Of 6878 articles, 144 met the selection criteria and reported on average 53 patients with SIH each (range, 10-568 patients). The most common symptoms were orthostatic headache (92% [95% CI, 87%-96%]), nausea (54% [95% CI, 46%-62%]), and neck pain/stiffness (43% [95% CI, 32%-53%]). Brain magnetic resonance imaging was the most sensitive investigation, with diffuse pachymeningeal enhancement identified in 73% (95% CI, 67%-80%) of patients. Brain magnetic resonance imaging findings were normal in 19% (95% CI, 13%-24%) of patients. Spinal neuroimaging identified extradural cerebrospinal fluid in 48% to 76% of patients. Digital subtraction myelography and magnetic resonance myelography with intrathecal gadolinium had high sensitivity in identifying the exact leak site. Lumbar puncture opening pressures were low, normal (60-200 mm H2O), and high in 67% (95% CI, 54%-80%), 32% (95% CI, 20%-44%), and 3% (95% CI, 1%-6%), respectively. Conservative treatment was effective in 28% (95% CI, 18%-37%) of patients and a single epidural blood patch was successful in 64% (95% CI, 56%-72%). Large epidural blood patches (>20 mL) had better success rates than small epidural blood patches (77% [95% CI, 63%-91%] and 66% [95% CI, 55%-77%], respectively)., Conclusions and Relevance: Spontaneous intracranial hypotension should not be excluded on the basis of a nonorthostatic headache, normal neuroimaging findings, or normal lumbar puncture opening pressure. Despite the heterogeneous nature of the studies available in the literature and the lack of controlled interventional studies, this systematic review offers a comprehensive and objective summary of the evidence on SIH that could be useful in guiding clinical practice and future research.

Introduction: The management of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) remains challenging in view of the paucity of data and evidence-based treatment recommendations are missing., Methods: In this single-centre, non-randomised, prospective open-label study, we evaluated and compared the efficacy of oral and parenteral treatments for SUNCT and SUNA in a real-world setting. Additionally, single-arm meta-analyses of the available reports of SUNCT and SUNA treatments were conducted., Results: The study cohort comprised 161 patients. Most patients responded to lamotrigine (56%), followed by oxcarbazepine (46%), duloxetine (30%), carbamazepine (26%), topiramate (25%), pregabalin and gabapentin (10%). Mexiletine and lacosamide were effective in a meaningful proportion of patients but poorly tolerated. Intravenous lidocaine given for 7-10 days led to improvement in 90% of patients, whereas only 27% of patients responded to a greater occipital nerve block. No statistically significant differences in responders were observed between SUNCT and SUNA. In the meta-analysis of the pooled data, topiramate was found to be significantly more effective in SUNCT than SUNA patients. However, a higher proportion of SUNA than SUNCT was considered refractory to medications at the time of the topiramate trial, possibly explaining this isolated difference., Conclusions: We propose a treatment algorithm for SUNCT and SUNA for clinical practice. The response to sodium channel blockers indicates a therapeutic overlap with trigeminal neuralgia, suggesting that sodium channels dysfunction may be a key pathophysiological hallmark in these disorders. Furthermore, the therapeutic similarities between SUNCT and SUNA further support the hypothesis that these conditions are variants of the same disorder., Competing Interests: Competing interests: GL has received speaker honoraria, funding for travel and has received honoraria for participation in advisory boards sponsored by Allergan, Novartis, Eli Lilly and TEVA. He has received speaker honoraria, funding for travel from electroCore, Nevro Corp. and Autonomic Technologies. AS is cofounder of Nordic Brain Tech, a company developing a non-pharmacological biofeedback treatment for migraine and holds a pending patent application relating to the company’s product. KR has nothing to declare. SL has received payment for attending advisory meetings and development of presentation from Allergan Novartis, Eli Lilly and TEVA. ET: is a cofounder and shareholder of Nordic Brain Tech AS and Palion Medical AS. He serves on advisory board for Eli Lilly and Novartis and TEVA. He has received speaker honoraria from Eli Lilly, Novartis, Allergan and TEVA. MSM serves on the advisory board for Abbott, Allergan, Eli Lilly, Medtronic, Novartis, TEVA; has received payment for the development of educational presentations from Allergan, electroCore, Eli Lilly, Medtronic, Novartis, and TEVA; and, has received research grants from Abbott, electroCore and Medtronic., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The hydrodynamics of cerebrospinal fluid shunts have been described in vitro; however, knowledge on the response of intracranial pressure (ICP) to valve settings adjustments in vivo is limited. This study describes the effect of adjusting the shunt valve setting on ICP in a cohort of patients with complex symptom management., Method: Single-centre retrospective observational study. Patients who underwent ICP-guided valve setting adjustments during 24-h continuous ICP monitoring, between 2014 and 2019, were included. Patients with suspected shunt malfunction were excluded. Median night ICP before and after the valve adjustments were compared (Δ night ICP). The responses of ICP to valve adjustment were divided into 3 different groups as follows: expected, paradoxical and no response. The frequency of the paradoxical response and its potential predicting factors were investigated., Results: Fifty-one patients (37 females, 14 males, mean age 38 years) receiving 94 valve setting adjustments met the study inclusion criteria. Patients' underlying conditions were most commonly hydrocephalus (47%) or idiopathic intracranial hypertension (43%). The response of ICP to valve setting adjustments was classified as 'expected' in 54 cases (57%), 'paradoxical' in 17 cases (18%) and 'no effect' (Δ night ICP < 1 mmHg) in 23 cases (24%). There was a significant correlation between the Δ night ICP and the magnitude of valve setting change in both the investigated valves (Miethke ProGAV, p = 0.01 and Medtronic Strata, p = 0.02)., Conclusions: Paradoxical ICP changes can occur after shunt valve setting adjustments. This observation should be taken into account when performing ICP-guided valve adjustments and is highly relevant for the future development of "smart" shunt systems.

Objectives: To define the characteristics of post-traumatic headache with cluster headache phenotype (PTH-CH) and to compare these characteristics with primary CH., Methods: A retrospective study was conducted of patients seen between 2007 and 2017 in a headache centre and diagnosed with PTH-CH that developed within 7 days of head trauma. A control cohort included 553 patients with primary CH without any history of trauma who attended the headache clinic during the same period. Data including demographics, attack characteristics and response to treatments were recorded., Results: Twenty-six patients with PTH-CH were identified. Multivariate analysis revealed significant associations between PTH-CH and family history of CH (OR 3.32, 95% CI 1.31 to 8.63), chronic form (OR 3.29, 95% CI 1.70 to 6.49), parietal (OR 14.82, 95% CI 6.32 to 37.39) or temporal (OR 2.04, 95% CI 1.10 to 3.84) location of pain, and presence of prominent cranial autonomic features during attacks (miosis OR 11.24, 95% CI 3.21 to 41.34; eyelid oedema OR 5.79, 95% CI 2.57 to 13.82; rhinorrhoea OR 2.65, 95% CI 1.26 to 5.86; facial sweating OR 2.53, 95% CI 1.33 to 4.93). Patients with PTH-CH were at a higher risk of being intractable to acute (OR 12.34, 95% CI 2.51 to 64.73) and preventive (OR 16.98, 95% CI 6.88 to 45.52) treatments and of suffering from associated chronic migraine (OR 10.35, 95% CI 3.96 to 28.82)., Conclusion: This largest series of PTH-CH defines it as a unique entity with specific evolutive profile. Patients with PTH-CH are more likely to suffer from the chronic variant, have marked autonomic features, be intractable to treatment and have associated chronic migraine compared with primary CH., Competing Interests: Competing interests: MSM serves on the advisory board for Allergan, St Jude Medical, Medtronic and Eli Lilly, and has received payment for the development of educational presentations from Allergan, St Jude Medical, Medtronic and electroCore., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: A convenient and reliable method for noninvasive intracranial pressure assessments is desirable to reduce the need for invasive procedures (eg, intracranial pressure monitoring and lumbar punctures) and allow clinicians to identify and treat patients with intracranial hypertension in a timely manner., Objective: To determine whether infrared video assessment of spontaneous retinal venous pulsation is associated with intracranial pressure and is a valid tool to indicate the presence or absence of raised intracranial pressure in patients without papilledema., Design, Setting, and Participants: A single-center prospective study was conducted at a tertiary referral center between January 2017 and May 2018. Patients consecutively admitted for clinically indicated elective 24-hour invasive intracranial pressure monitoring had ophthalmic review including infrared video recording of their spontaneous venous pulsation. Two neuro-ophthalmologists, who were masked to the intracranial pressure monitoring results, independently graded the spontaneous venous pulsation (grade 0 to 3). Analysis began in June 2018., Main Outcomes and Measures: The association between simultaneously recorded intracranial pressure and spontaneous venous pulsation (binary variable: present/absent) assessed through retinal infrared video recordings was evaluated using a multiple linear regression model., Results: Of 105 patients, the mean (SD) age was 39 (14) years, and 79 (75%) were women. The mean (SD) simultaneous intracranial pressure was 1 (5) mm Hg for 91 patients (86.7%) with spontaneous venous pulsations and 13 (14) mm Hg for 14 patients (13.3%) without spontaneous venous pulsations. A multiple linear regression model adjusted for 7 potential confounders confirmed a statistically significant association between intracranial pressure and spontaneous venous pulsation (β = -9.1; 95% CI, -13.7 to -4.6; P < .001; adjusted R2 = 0.42)., Conclusions and Relevance: The absence of spontaneous venous pulsation on retinal infrared video recordings is significantly associated with higher levels of intracranial pressure and should raise the suspicion of intracranial hypertension.