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Background: Headache disorders are among the most common and disabling medical conditions worldwide, have a great societal impact and are a common reason to seek medical care. Headache disorders are often misdiagnosed and undertreated, and the number of headache fellowship-trained physicians cannot meet patient demand. Educational initiatives for non-headache-specialist clinicians may be an avenue to increase clinician competency and patient access to appropriate management., Objective: To undertake a scoping review of the educational initiatives in headache medicine for medical students, trainees, general practitioners/primary care physicians, and neurologists., Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping reviews, an author (M.D.), with the help of a medical librarian, conducted a search of the Embase, Ovid Medline, and PsychInfo databases for articles related to medical educational initiatives on headache medicine in medical students, residents, and physicians over the last 20 years., Results: A total of 17 articles met the inclusion criteria for this scoping review. Six articles were identified for medical students, seven for general practitioners/primary care physicians, one for emergency medicine residents, two for neurology residents, and one for neurologists. Certain educational initiatives were headache-focused while others had headaches as one of the educational topics. Educational content was delivered and assessed via diverse and innovative means, such as flipped classroom, simulation, theatrical performance, repeated quizzing and study, and a formalized headache elective., Conclusion: Education initiatives in headache medicine are important to improve competency and patient access to appropriate management of various headache disorders. Future research should focus on using innovative and evidence-based methods of content delivery, knowledge, and procedural assessment, and evaluating changes in practice behaviors., (© 2023 American Headache Society.)

Objectives: We evaluated interventions to facilitate recovery in children, adolescents and adults with a sport-related concussion (SRC)., Design: Systematic review including risk of bias (modified Scottish Intercollegiate Guidelines Network tool)., Data Sources: MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase, APA PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL Plus with Full Text, SPORTDiscus and Scopus searched until March 2022., Study Eligibility Criteria: (1) Original research including randomised controlled trials (RCTs), quasi-experimental designs, cohort, comparative effectiveness studies; (2) focus on SRC; (3) English; (4) peer-reviewed and (5) evaluated treatment., Results: 6533 studies were screened, 154 full texts reviewed and 13 met inclusion (10 RCTs, 1 quasi-experimental and 2 cohort studies; 1 high-quality study, 7 acceptable and 5 at high risk of bias). Interventions, comparisons, timing and outcomes varied, precluding meta-analysis. For adolescents and adults with dizziness, neck pain and/or headaches >10 days following concussion, individualised cervicovestibular rehabilitation may decrease time to return to sport compared with rest followed by gradual exertion (HR 3.91 (95% CI 1.34 to 11.34)) and when compared with a subtherapeutic intervention (HR 2.91 (95% CI 1.01 to 8.43)). For adolescents with vestibular symptoms/impairments, vestibular rehabilitation may decrease time to medical clearance (vestibular rehab group 50.2 days (95% CI 39.9 to 60.4) compared with control 58.4 (95% CI 41.7 to 75.3) days). For adolescents with persisting symptoms >30 days, active rehabilitation and collaborative care may decrease symptoms., Conclusions: Cervicovestibular rehabilitation is recommended for adolescents and adults with dizziness, neck pain and/or headaches for >10 days. Vestibular rehabilitation (for adolescents with dizziness/vestibular impairments >5 days) and active rehabilitation and/or collaborative care (for adolescents with persisting symptoms >30 days) may be of benefit., Competing Interests: Competing interests: VA Financial: Australian National Health and Medical Research Council and Medical Research Future fund: research grants. Royalties: Pearson Publishing (Test of Everyday Attention) Collaboration: Australian Football League (Partnership agreement to fund research—funds go to my institute) Boards: Editorship: Journal of Neuropsychology, Neuropsychology, Journal of Clinical & Experimental Neuropsychology. GAD is a member of the Scientific Committee of the 6th International Consensus Conference on Concussion in Sport; an honorary member of the AFL Concussion Scientific Committee; Section Editor, Sport and Rehabilitation, NEUROSURGERY; and has attended meetings organised by sporting organisations including the NFL, NRL, IIHF, IOC and FIFA; however, has not received any payment, research funding or other monies from these groups other than for travel costs. CTD Pharmaceutical:-2021 pharmaceutical funded invited expert panelist (Teva) for CGRP monoclonal antibody treatment in chronic migraine-2022 pharmaceutical funded grant for growth hormone deficiency following concussion Grants/Research Support: Canadian Department of National Defense, HBI, CIHR, Tri-council funding New Frontiers, Alberta Provincial government, Foundations for PMR Patents: urine metabolites diagnosis of concussion. NF International independent FIFA Concussion Advisory Group GOTS Concussion Committee Innovation and Technology Panel, UK Department for Digital, Culture, Media and SportInternational Consensus Group on Concussion in Sports (CISG), NINDSCDE Sports Concussion CDE Subacute Subgroup (National Institute of Health) IFAB Concussion Expert Group Member: Swiss Neurology Society, Swiss Society for Clinical Neurophysiology, European Neuro-Ophthalmology Society, Concussion in Sport Group (CISG) Editorial Board Member: Journal of Concussion, Journal of Science and Medicine in Football. IG has paid employment relationships with McGill University and the McGill University Health CenterI have received grants in the last 3 years from: Canadian Institutes of Health Research, Fonds de recherche du Québec—Santé, Research Institute of the McGill University Health Center, McGill University, Institut National du Sport du QuébecI have no conflicts of interest with regards to the material being presented or discussed at the conference. KMG has received grant funding from NFL for the NFL LONG study. He also serves on the NCAA Scientific Advisory Board in an unpaid capacity. KAH has nothing to disclose. SAH is co-founder and senior advisor, The Sports Institute at UW Medicine (unpaid), Centers for Disease Control and Prevention and National Center for Injury Prevention and Control Board Pediatric Mild Traumatic Brain Injury Guideline Workgroup (unpaid), Concussion in Sport Group (Travel support), NCAA Concussion Safety Advisory Group (unpaid), Team Physician, Seattle Mariners; Former Team Physician, Seattle Seahawks; occasional payment for expert travel testimony, support for professional meetings. Mr CJ has nothing to declare. MM is a sport and exercise medicine physician working in private consulting practice and is the Chief Medical Officer at the Australian Football League. Shareholder of Olympic Park Sports Medicine Centre in Melbourne. Ex-senior physician at the Hawthorn Football Club (AFL) Ex-Chief Executive Officer of the AFL Doctors Association. Research grants received from the Australian Football League, outside the submitted work.Travel support received from the Australian Football League, FIFA and the International Olympic Committee to attend and present at international conferences. Member of the Scientific Committee for the 6th International Consensus Conference on Concussion in Sport. Honorary member of the International Concussion in Sport Group. Honorary member of the Australian Rugby Union Concussion Advisory Group.Independent Concussion Consultant for World Rugby. CLM reports no financial COI Volunteer positions: Concussion team physician, Shipley School Board of Trustees, American College of Sports Medicine Board of Directors, American Medical Society for Sports Medicine Board of Directors, Pediatric Research in Sports Medicine Executive Committee, Council on Sports Medicine and Fitness, American Academy of Pediatrics Advisory Board, Untold Foundation, Pink Concussions, Headway Foundation Editorial Board, Journal of Adolescent Health, Frontiers in Neuroergonomics, Exercise, Sport and Movement. JP is Editor BJSM (honorarium), Member of World Rugby Concussion Advisory Group (unpaid), Independent Concussion Consultant for World Rugby (fee per consultation), Medical consultant to South African Rugby (unpaid), Co-chair of the Scientific Committee, 6th International Conference on Concussion in Sport (unpaid), Board member of the Concussion in Sport Group (unpaid), Scientific Board member, EyeGuideTM (unpaid). JKR-M has current or past research funding from the Centers for Disease Control and Prevention; Department of Defense—USA Medical Research Acquisition Activity, National Collegiate Athletic Association-Department of Defense Mind Matters Challenge; National Athletic Trainers’ Association Foundation; National Football League; and National Operating Committee on Standards for Athletic Equipment. She has consulted for Allied Health Education (paid) and received speaker honorarium and travel reimbursements for talks given. She is on the editorial boards (all unpaid) for Journal of Athletic Training, Journal of Sport Rehabilitation and Frontiers in Sports and Active Living. Previously she served on the editorial board for the International Journal of Athletic Training and Therapy (paid). She served previously (unpaid) on USA Football’s Football Development Council and is currently on USA Football’s Girls Football Council. She is also a member of several committees or the National Athletic Trainers’ Association and the North Carolina High School Athletic Association’s Sports Medicine Advisory Committee. PER has nothing to declare. KJS has received grant funding from the Canadian Institutes of Health Research, National Football League Scientific Advisory Board, International Olympic Committee Medical and Scientific Research Fund, World Rugby, Mitacs Accelerate, University of Calgary) with funds paid to her institution and not to her personally. She is an Associate Editor of BJSM (unpaid) and has received travel and accommodation support for meetings where she has presented. She is coordinating the writing of the systematic reviews that will inform the 6th International Consensus on Concussion in Sport, for which she has received an educational grant to assist with the administrative costs associated with the writing of the reviews. She is a member of the AFL Concussion Scientific Committee (unpaid position) and Brain Canada (unpaid positions). She works as a physiotherapy consultant and treats athletes of all levels of sport from grass roots to professional. NDS: Employee salary from the University of British Columbia, Research grants from the Canadian Institutes of Health Research, Canada Foundation for Innovation, WorkSafeBC and the US Department of Defense (no salary contributions), Research salary support from the Michael Smith Foundation for Health Research, Editorial board member for Neuropsychology and the Journal of Head Trauma Rehabilitation (unpaid), Chair of the American Congress of Rehabilitation Medicine Mild TBI Task Force (unpaid), Member of the Scientific Advisory Committee, Brain Injury Canada (unpaid), Clinical neuropsychological consulting fees from the National Hockey League, Major League Soccer, and NDS Inc (<10% of total income). KOY: is editor-in-chief of the journal Neuropsychology and receives an editorial stipend from the American Psychological Association. He is an unpaid consulting editor for the journals Archives of Clinical Neuropsychology and Journal of Head Trauma Rehabilitation. He is an unpaid member of the Scientific Advisory Committee for Brain Injury Canada. He is the chair of the Canadian Concussion Network, which is funded by a grant from Canadian Institutes of Health Research (CIHR) to his institution; He is the principal applicant on the grant but receives no income from it. He is a principal investigator on another grant from CIHR from which he derives no income. He is a coinvestigator on research grants from CIHR, the US National Institutes of Health (NIH), Brain Canada Foundation and National Football League Scientific Advisory Board; He derives income only from the grant from NIH. He serves as a member of a CIHR grant review panel for which he receive a small honorarium. He receives book royalties from Guilford Press and Cambridge University Press. He has received travel support and honorarium for presentations to multiple organisations. He has served or serves on the following committees/boards for which I receives honorarium: 1. Independent Data Monitoring Committee (IDMC), Care for Post-Concussive Symptoms Effectiveness (CARE4PCS-2) Trial, National Institute for Child Health and Human Development 2. Observational Study Monitoring Board (OSMB), Approaches and Decisions in Acute Pediatric TBI (ADAPT) Trial, National Institute of Neurological Disorders and Stroke National Research Advisory Council, National Pediatric Rehabilitation Resource Center, Center for Pediatric Rehabilitation: Growing Research, Education, and Sharing Science (C-PROGRESS), Virginia Tech University., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract Background Idiopathic intracranial hypertension (IIH) is a neurological disorder characterized by increased intracranial pressure. Whilst lumbar puncture (LP) is necessary for the diagnosis of IIH, its therapeutic effect remains unclear. Our aim was to evaluate the therapeutic effect of a single LP in people with IIH (pwIIH). Methods In this prospective observational study, we analysed short-term neurological and ophthalmological outcomes in pwIIH before, one (D1) and seven days (D7) after the LP. The primary outcome was the change in papilledema degree from baseline. Secondary outcomes included visual outcomes, morphological changes in optical coherence tomography (peripapillary retinal nerve fibre layer [pRNFL] thickness and ganglion cell layer [GCL] volume) and transbulbar sonography (arachnoid optic nerve sheath diameter [AONSD]), and headache outcomes (peak and median headache severity and burden related to headache). Results We included 30 pwIIH (mean age 32.8 years [SD 8.4], 93.3% female, median cerebrospinal fluid [CSF] opening pressure 33.0 cmCSF [IQR 26.9–35.3], median body mass index (BMI) 34.8 kg/m2 [IQR 30.9–40.9]). The median papilledema grading at baseline was 2 (Friedman DI (1999) Pseudotumor cerebri. Neurosurg Clin N Am 10(4):609–621 viii); (Mollan SP, Aguiar M, Evison F, Frew E, Sinclair AJ (2019) The expanding burden of idiopathic intracranial hypertension. Eye Lond Engl 33(3):478–485); (Ab D, Gt L, Nj V, Sl G, Ml M, Nj N et al. (2007) Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol [Internet]. Apr [cited 2024 Jun 2];143(4). https://pubmed.ncbi.nlm.nih.gov/17386271/ ) and was significantly reduced at D7 (2 [1–2], p = 0.011). Median pRNFL thickness had decreased significantly at D7 (-9 μm [-62.5, -1.3], p = 0.035), with pRNFL thickness at baseline being associated with the pRNFL change (F(1,11) = 18.79, p = 0.001). Mean AONSD had decreased significantly at both D1 (-0.74 mm [0.14], p

Introduction: Posterior reversible encephalopathy syndrome (PRES) is a disorder of subcortical vasogenic edema causing reversible neurologic dysfunction which includes headache, altered sensorium, seizures, and visual disturbances. It is a relatively rare disease with a myriad of nonspecific symptoms with similar presentations to that seen in other diseases such as stroke and cortical venous thrombosis. Hence, accurate diagnosis is needed for early detection to guide the management of such patients. This is a single-center retrospective study from June 2022 to May 2024 to identify the demographic profile, etiologies, imaging features, and prognosis of patients diagnosed with PRES. Materials and Methods: Diagnosis of PRES was made on the basis of clinical history, neurological examination, and magnetic resonance imaging brain after ruling out other possible differential diagnoses. The patients who satisfied Fugate et al. criteria were included in the study. The data were collected from the hospital database. Patients with alternate diagnoses were excluded from the study. Results: There were 22 patients diagnosed with PRES. There were 20 (91%) females among the cohort. Eighteen (82%) patients had headache. Fourteen (64%) patients had seizures all of which were generalized tonic–clonic seizures. All had positive imaging findings with 2 patients having leptomeningeal enhancement in the presence of normal cerebrospinal fluid findings. Blood pressure (BP) was normal in 5 (22%) patients. Most of the patients were postpartum without a prior history of hypertension or preeclampsia. Conclusion: PRES is a reversible entity with the imaging findings primarily involving the posterior part of the brain. It can also involve anterior circulation and spinal cord. Normotensive PRES is possible and should not be overlooked if the patient has all features of PRES but has normal BP. It has a female predilection with the most vulnerable state being immediate postpartum. Although recurrence is possible, PRES does not require long-term medications. Complicated PRES presents with SAH and intracranial hemorrhage.

Introduction: Neurological disorders in pregnancy pose a major diagnostic challenge as they are a significant contributor to mortality and morbidity in pregnancy. Neurological complications may manifest at any time during pregnancy or puerperium even after what seemed to be a normal pregnancy. A thorough understanding of the patterns of these diseases is essential for prediction and early identification. Aim: To study the aetiology, clinical profile, morbidity and mortality patterns of acute neurological emergencies in postpartum women. Materials and Methods: This hospital- based descriptive study was conducted in the Department of Obstetrics and Gynaecology at Government Vellore Medical College and Hospital, Vellore, Tamil Nadu, India between February 2021 and August 2022. A total of 76 postnatal mothers who met the inclusion criteria were selected using consecutive sampling. Details pertaining to personal, demographic, antenatal risk factors, labour/delivery and postnatal events were recorded using a pretested semi-structured questionnaire. The data were entered into Microsoft Excel and analysed using Statistical Package for the Social Sciences (SPSS) 21.0, with the data expressed as frequency and proportion. Results: Among the 76 women included in the study, more than half were multiparous women 42 (55%) and the majority were young adults aged

Abstract Objective To assess rates of traversing barriers to care to access optimal clinical outcomes in people with migraine internationally. Background People in need of medical care for migraine should consult a health care professional knowledgeable in migraine management, obtain an accurate diagnosis, and receive an individualized treatment plan, which includes scientific society guideline-recommended treatments where appropriate. Methods The Chronic Migraine Epidemiology and Outcomes-International (CaMEO-I) Study was a cross-sectional, web-based survey conducted from July 2021 through March 2022 in Canada, France, Germany, Japan, the United Kingdom, and the United States (US). Respondents who met modified International Classification of Headache Disorders, 3rd edition, criteria for migraine and had Migraine Disability Assessment Scale (MIDAS) scores of ≥ 6 (i.e., mild, moderate, or severe disability) were deemed to need medical care and were included in this analysis. Minimally effective treatment required that participants were currently consulting a health care professional for headache (barrier 1), reported an accurate diagnosis (barrier 2), and reported use of minimally appropriate pharmacologic treatment (barrier 3; based on American Headache Society 2021 Consensus Statement recommendations). Proportions of respondents who successfully traversed each barrier were calculated, and chi-square tests were used to assess overall difference among countries. Results Among 14,492 respondents with migraine, 8,330 had MIDAS scores of ≥ 6, were deemed in need of medical care, and were included in this analysis. Current headache consultation was reported by 35.1% (2926/8330) of respondents. Compared with the US, consultation rates and diagnosis rates were statistically significantly lower in all other countries except France where they were statistically significantly higher. Total appropriate treatment rates were also statistically significantly lower in all other countries compared with the US except France, which did not differ from the US. All 3 barriers were traversed by only 11.5% (955/8330) of respondents, with differences among countries (P

Abstract Background We have previously shown headache to be highly prevalent in Cameroon. Here we present the attributed burden. We also perform a headache-care needs assessment. Methods This was a cross-sectional survey among adults (18–65 years) in the general population. Multistage cluster-sampling in four regions (Centre, Littoral, West and Adamawa), home to almost half the country’s population, generated a representative sample. We used the standardised methodology of the Global Campaign against Headache, including the HARDSHIP questionnaire, with diagnostic questions based on ICHD-3 and enquiries into symptom burden, impaired participation (lost productivity and disengagement from social activity), quality of life (QoL) using WHOQoL-8, and willingness to pay (WTP) for effective care. We defined headache care “need” in terms of likelihood of benefit, counting all those with probable medication-overuse headache (pMOH) or other headache on ≥ 15 days/month (H15 +), with migraine on ≥ 3 days/month, or with migraine or tension-type headache (TTH) and meeting either of two criteria: a) proportion of time in ictal state (pTIS) > 3.3% and intensity ≥ 2 (moderate-to-severe); or b) ≥ 3 lost days from paid and/or household work in the preceding 3 months. Results Among 3,100 participants, mean frequency of any headache was 6.7 days/month, mean duration 13.0 h and mean intensity 2.3 (moderate). Mean pTIS was 9.8%, which (with prevalence factored in) diluted to 6.1–7.4% of all time in the population. Most time was spent with H15 + (5.3% of all time), followed by TTH (1.0%) and migraine (0.8%). For all headache, mean lost days/3 months were 3.4 from paid work, 3.0 from household work and 0.6 from social/leisure activities, diluting to 2.5, 2.2 and 0.6 days/3 months in the population. QoL (no headache: 27.9/40) was adversely impacted by pMOH (25.0) and other H15 + (26.0) but not by migraine (28.0) or TTH (28.0). WTP (maximally XAF 4,462.40 [USD 7.65] per month) was not significantly different between headache types. An estimated 37.0% of adult Cameroonians need headache care. Conclusion Headache disorders in Cameroon are not only prevalent but also associated with high attributed burden, with heavily impaired participation. Headache-care needs are very high, but so are the economic costs of not providing care.

Abstract Physical activity can worsen migraine, leading to reduced activity levels in adults with chronic migraine. This study investigated the change in average steps per day, as a surrogate marker of physical activity, in adults with chronic migraine successfully treated with monoclonal antibodies against calcitonin gene-related peptide or its receptor. Data were obtained from adults with chronic migraine, who were classified as responders to preventive treatment with monoclonal antibodies. The primary endpoint was the difference in a mean number of steps per day between the 3 months prior to treatment initiation and the first 3 months after treatment initiation. The secondary endpoint was the correlation between the change in steps per day and the change in monthly migraine days. Twenty-two (20 females) participants with a median age of 48.5 years were enrolled. The median number of steps per day increased from 4421 at baseline to 5241 after treatment (P = 0.039). We found a positive correlation between the increase in steps per day and the treatment response (P = 0.013). In conclusion, an increase in physical activity, based on steps per day, positively correlated with treatment response to monoclonal antibodies. Automatically registered daily step count data might be used to monitor physical activity as a response to preventive treatment in adults with chronic migraine.

Abstract Purpose The prevalence of migraine headache is higher in women. Low barometric pressure is a factor in headache triggering, but sex-related differences have not been identified. The purpose of this study was to examine sex-related differences in headache triggered by low barometric pressure. Methods Study subjects aged 20–49 years were randomly selected from a research company’s (Macromill, Inc.) web panel. Those with chronic migraine or tension-type headache invited to complete a web-based self-administered questionnaire. Logistic regression analysis was performed with the objective variable as the Headache Impact Test-6 (HIT-6) high scores (56 or more) or headache triggered by low barometric pressure. Results Participants were 332 women and 337 men in the headache population. HIT-6 high scores were associated with age at headache occurrence 20 years or younger (OR: odds ratio 1.85, 95% CI: confidence interval 1.15–2.99, p = 0.012) and headache triggered by low barometric pressure (OR 2.11, 95%CI 1.51–2.94, p

Abstract Background Cluster headache is characterized by activation of the trigeminovascular pathway with subsequent pain signalling in the meningeal vessels, and inflammation has been suggested to play a role in the pathophysiology. To further investigate inflammation in cluster headache, inflammatory markers were analysed in patients with cluster headache and controls. Methods We performed a case–control study, collecting cerebrospinal fluid and serum samples from healthy controls, cluster headache patients in remission, active bout, and during an attack to cover the dynamic range of the cluster headache phenotype. Inflammatory markers were quantified using Target 48 OLINK cytokine panels. Results Altered levels of several cytokines were found in patients with cluster headache compared to controls. CCL8, CCL13, CCL11, CXCL10, CXCL11, HGF, MMP1, TNFSF10 and TNFSF12 levels in cerebrospinal fluid were comparable in active bout and remission, though significantly higher than in controls. In serum samples, CCL11 and CXCL11 displayed decreased levels in patients. Only one cytokine, IL-13 was differentially expressed in serum during attacks. Conclusion and interpretation Our data shows signs of possible neuroinflammation occurring in biological samples from cluster headache patients. Increased cerebrospinal fluid cytokine levels are detectable in active bout and during remission, indicating neuroinflammation could be considered a marker for cluster headache and is unrelated to the different phases of the disorder.

Abstract Background Neurogenic meningeal inflammation is regarded as a key driver of migraine headache. Multiple evidence show importance of inflammatory processes in the dura mater for pain generation but contribution of the leptomeninges is less clear. We assessed effects of cortical spreading depolarization (CSD), the pathophysiological mechanism of migraine aura, on expression of inflammatory mediators in the leptomeninges. Methods A single CSD event was produced by a focal unilateral microdamage of the cortex in freely behaving rats. Three hours later intact cortical leptomeninges and parenchyma of ipsi-lesional (invaded by CSD) and sham-treated contra-lesional (unaffected by CSD) hemispheres were collected and mRNA levels of genes associated with inflammation (Il1b, Tnf, Ccl2; Cx3cl1, Zc3h12a) and endocannabinoid CB2 receptors (Cnr2) were measured using qPCR. Results Three hours after a single unilateral CSD, most inflammatory factors changed their expression levels in the leptomeninges, mainly on the side of CSD. The meninges overlying affected cortex increased mRNA expression of all proinflammatory cytokines (Il1b, Tnf, Ccl2) and anti-inflammatory factors Zc3h12a and Cx3cl1. Upregulation of proinflammatory cytokines was found in both meninges and parenchyma while anti-inflammatory markers increased only meningeal expression. Conclusion A single CSD is sufficient to produce pronounced leptomeningeal inflammation that lasts for at least three hours and involves mostly meninges overlying the cortex affected by CSD. The prolonged post-CSD inflammation of the leptomeninges can contribute to mechanisms of headache generation following aura phase of migraine attack.

Abstract Background Pulmonary arteriovenous malformations are a relatively uncommon medical condition, affecting roughly 1 in every 2500 individuals. Of those suffering from pulmonary arteriovenous malformations, 80% have an underlying genetic condition: hereditary hemorrhagic telangiectasia. Case presentation We present the case of a 20-year-old Pakistani male with a history of persistent slower-onset frontal headaches that increased in severity within the course of the day. His hemoglobin was 18 g/dl, indicating polycythemia, for which he had undergone seven venesections in a month previously. His physical examination was unremarkable. His computed tomography scan depicted multiple dilated tortuous vessels with branching linear opacities in the right lower lobe of the lungs. The multiple feeding arteries were supplied by the right main pulmonary artery, and the large draining veins led to the right inferior pulmonary vein. This was identified as a diffuse pulmonary arteriovenous malformation. He was recommended for a right pulmonary artery angiogram. It showed multiple tortuous vessels with a nidus and large draining veins—features of a diffuse arteriovenous malformation in the right lower lobe of the lung consistent with the computed tomography scan. Embolization of two of these vessels feeding the arteriovenous malformation was conducted, using Amplatzer Vascular plug 2, whereas multiple pushable coils (five coils) were used for embolizing the third feeding vessel. This achieved 70–80% successful embolization of right pulmonary AVM; however, some residual flow was still seen in the arteriovenous malformation given the complexity of the lesion. Immediately after, his oxygen saturation improved from 78% to 96%. Conclusion Diffuse pulmonary arteriovenous malformations, as seen in this patient, are rare, accounting for less than 5% of total pulmonary arteriovenous malformations diagnosed. The patient presented with a complaint of progressive frontal headaches, which can be attributed to low oxygen saturation or the presence of a cerebral arteriovenous malformation. There was no history of hereditary hemorrhagic telangiectasia in the patient’s family. Furthermore, although most patients with hereditary hemorrhagic telangiectasia and hence pulmonary arteriovenous malformation have complaints of iron-deficiency anemia, our patient in contrast was suffering from polycythemia. This can be explained as a compensatory mechanism in hypoxemic conditions. Moreover, the patient had no complaint of hemoptysis or epistaxis, giving a varied presentation in comparison with a typical pulmonary arteriovenous malformation.

Abstract Background India is a large and populous country where reliable data on headache disorders are relatively scarce. This study in northern India (Delhi and National Capital Territory Region [NCR], including surrounding districts in the States of Haryana, Uttar Pradesh and Rajasthan) continues the series of population-based studies within the Global Campaign against Headache and follows an earlier study, using the same protocol and questionnaire, in the southern State of Karnataka. Methods This cross-sectional study used the Global Campaign’s established methodology. Biologically unrelated Indian nationals aged 18–65 years were included through multistage random sampling in both urban and rural areas of NCR. Interviews at unannounced household visits followed the structured Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire in its original English version or in the validated Hindi version. Demographic enquiry was followed by a neutral headache screening question and diagnostic questions based on the International Classification of Headache Disorders edition 3 (ICHD-3), which focused on each respondent’s most bothersome headache. Questions about headache yesterday (HY) enabled estimation of 1-day prevalence. A diagnostic algorithm first identified participants reporting headache on ≥ 15 days/month (H15+), diagnosing probable medication-overuse headache (pMOH) in those also reporting acute medication use on ≥ 15 days/month, and “other H15+” in those not. To all others, the algorithm applied ICHD-3 criteria in the order definite migraine, definite tension-type headache (TTH), probable migraine, probable TTH. Definite and probable diagnoses were combined. Results Adjusted for age, gender and habitation, 1-year prevalences were 26.3% for migraine, 34.1% for TTH, 3.0% for pMOH and 4.5% for other H15+. Female preponderance was seen in all headache types except TTH: migraine 35.7% vs. 15.1% (aOR = 3.3; p

Abstract Background Our recent studies have shown headache disorders to be very common in the central and western sub-Saharan countries of Benin and Cameroon. Here we report headache in nearby Mali, a strife-torn country that differs topographically, culturally, politically and economically. The purposes were to estimate headache-attributed burden and need for headache care. Methods We used cluster-random sampling in seven of Mali’s eleven regions to obtain a nationally representative sample. During unannounced household visits by trained interviewers, one randomly selected adult member (18–65 years) from each household was interviewed using the structured HARDSHIP questionnaire, with enquiries into headache in the last year and, additionally, headache yesterday (HY). Headache on ≥ 15 days/month (H15+) was diagnosed as probable medication-overuse headache (pMOH) when associated with acute medication use on ≥ 15 days/month, and as “other H15+” when not. Episodic headache (on

Abstract Introduction The development of several experimental migraine provocation models has significantly contributed to an understanding of the signaling mechanisms of migraine. The early history of this development and a view to the future are presented as viewed by the inventor of the models. Methods Extensive knowledge of the literature was supplemented by scrutiny of reference lists. Results Early studies used methodologies that were not blinded. They suggested that histamine and nitroglycerin (Glyceryl trinitrate, GTN) could induce headache and perhaps migraine. The development of a double blind, placebo-controlled model, and the use of explicit diagnostic criteria for induced migraine was a major step forward. GTN, donor of nitric oxide (NO), induced headache in people with- and without migraine as well as delayed migraine attacks in those with migraine. Calcitonin gene-related peptide (CGRP) did the same, supporting the development of CGRP antagonists now widely used in patients. Likewise, pituitary adenylate cyclase activating peptide (PACAP) provoked headache and migraine. Recently a PACAP antibody has shown anti migraine activity in a phase 2 trial. Increase of second messengers activated by NO, CGRP and PACAP effectively induced migraine. The experimental models have also been used in other types of headaches and have been combined with imaging and biochemical studies. They have also been used for drug testing and in genetic studies. Conclusion Conclusion. Human migraine provocation models have informed about signaling mechanisms of migraine leading to new drugs and drug targets. Future use of these models in imaging-, biochemistry- and genetic studies as well as in the further study of animal models is promising.

Abstract Background New onset or worsening of a headache disorder substantially contributes to the disease burden of post-COVID-19. Its management poses a suitable means to enhance patients’ participation in professional, social, and personal activities. Unfortunately, the pathophysiology of post-COVID-19 headaches is poorly understood. This study aims to investigate the role of (neuro-) inflammatory mechanisms in order to guide the development of anti-inflammatory treatment strategies. Methods We included patients from the interdisciplinary post-COVID-19 Rehabilitation Study (PoCoRe, n = 184 patients) run at a tertiary care university hospital, comprising patients with PCR-confirmed SARS-CoV-2 infection ≥ 6 weeks prior to their initial consultation. Patients reporting any headache since their infection were considered for this study (n = 93). These were interviewed and classified according to the International Classification of Headache Disorders, Third Edition (ICHD-3) by headache specialists. Patient sera were additionally analysed for levels of VILIP-1, MCP-1 (CCL2), sTREM-2, BDNF, TGF-ß1, VEGF, IL-6, sTREM-1, ß-NGF, IL-18, TNF-alpha, sRAGE, and CX3CL1 (Fractalkine). Markers of inflammation were compared between four groups of patients (none, unchanged, worsened, or new headache disorder). Results Patients reported experiencing more severe headaches (n = 17), new onset headaches (n = 46), unchanged headaches (n = 18), and surprisingly, some patients denied having any headaches (n = 12) despite self-reports. Serum levels of CX3CL1 were increased in the worsened (2145 [811–4866] pg/ml) and new onset (1668 [0-7357] pg/ml) headache group as compared to patients with no (1129 [0-5379] pg/ml) or unchanged (1478 [346–4332] pg/ml) headaches. Other markers also differed between groups, but most significantly between patients with worsened (TGF-ß1: 60 [0-310] pg/ml, VEGF: 328 [86–842] pg/ml, ß-NGF: 6 [3–38] pg/ml) as compared to unchanged headaches (TGF-ß1: 29 [0–77] pg/ml, VEGF: 183 [72–380] pg/ml, ß-NGF: 3 [2–89] pg/ml). The results did not differ between headache phenotypes. Discussion This study provides evidence that worsened or new headaches following COVID-19 are associated with pro-(neuro-)inflammatory profiles. This supports the use of anti-inflammatory treatment options in this population, especially in the subacute phase.

Abstract Background Idiopathic intracranial hypertension (IIH) is a debilitating condition characterized by increased intracranial pressure often presenting with chronic migraine-like headache. Calcitonin gene-related peptide (CGRP) plays an important pathophysiological role in primary headaches such as migraine, whilst its role in IIH has not yet been established. Methods This longitudinal exploratory study included patients with IIH, episodic migraine (EM) in a headache-free interval and healthy controls (HC). Blood samples were collected from a cubital vein and plasma CGRP (pCGRP) levels were measured by standardized ELISA. Results A total of 26 patients with IIH (mean age 33.2 years [SD 9.2], 88.5% female, median BMI 34.8 kg/m2 [IQR 30.0–41.4]), 30 patients with EM (mean age 27.6 years [7.5], 66.7% female) and 57 HC (mean age 25.3 years [5.2], 56.1% female) were included. pCGRP levels displayed a wide variation in IIH as well as in EM and HC on a group-level. Within IIH, those with migraine-like headache had significantly higher pCGRP levels than those with non-migraine-like headache (F(2,524) = 84.79; p

Abstract Background Pain, an evolutionarily conserved warning system, lets us recognize threats and motivates us to adapt to those threats. Headache pain from migraine affects approximately 15% of the global population. However, the identity of any putative threat that migraine or headache warns us to avoid is unknown because migraine pathogenesis is poorly understood. Here, we show that a stress-induced increase in pituitary adenylate cyclase-activating polypeptide-38 (PACAP38), known as an initiator of allosteric load inducing unbalanced homeostasis, causes headache-like behaviour in male mice via mas-related G protein-coupled receptor B2 (MrgprB2) in mast cells. Methods The repetitive stress model and dural injection of PACAP38 were performed to induce headache behaviours. We assessed headache behaviours using the facial von Frey test and the grimace scale in wild-type and MrgprB2-deficient mice. We further examined the activities of trigeminal ganglion neurons using in vivo Pirt-GCaMP Ca2+ imaging of intact trigeminal ganglion (TG). Results Repetitive stress and dural injection of PACAP38 induced MrgprB2-dependent headache behaviours. Blood levels of PACAP38 were increased after repetitive stress. PACAP38/MrgprB2-induced mast cell degranulation sensitizes the trigeminovascular system in dura mater. Moreover, using in vivo intact TG Pirt-GCaMP Ca2+ imaging, we show that stress or/and elevation of PACAP38 sensitized the TG neurons via MrgprB2. MrgprB2-deficient mice showed no sensitization of TG neurons or mast cell activation. We found that repetitive stress and dural injection of PACAP38 induced headache behaviour through TNF-a and TRPV1 pathways. Conclusions Our findings highlight the PACAP38-MrgprB2 pathway as a new target for the treatment of stress-related migraine headache. Furthermore, our results pertaining to stress interoception via the MrgprB2/PACAP38 axis suggests that migraine headache warns us of stress-induced homeostatic imbalance.

Abstract Background Cross-sectional and longitudinal studies have been conducted to investigate the association between migraine and any headache and white matter hyperintensities (WMH). However, studies are inconsistent regarding the strength of the association and its clinical significance. The aim of our study was to investigate the association between headache and its subtypes (migraine with aura (MigA+), migraine without aura (MigA-), non-migraine headache (nonMigHA)) and WMH and its course in the population-based 1000BRAINS study using state-of-the-art imaging techniques and migraine classification according to modified international classification of headache disorders. Methods Data from 1062 participants (45% women, 60.9 ± 13.0 years) with ever or never headache (neverHA) and complete quantitative (WMH volume) and qualitative (Fazekas classification) WMH data at first imaging and after 3.7 ± 0.7 years (393 participants) were analyzed. The sex-specific association between headache and its subtypes and WMH volume and its change was evaluated by linear regression, between headache and its subtypes and Fazekas score high vs. low (2–3 vs. 0–1) by log-binomial regression, adjusted for confounders. Results The lifetime prevalence of headache was 77.5% (10.5% MigA+, 26.9% MigA-, 40.1% nonMigHA). The median WMH volume was 4005 (IQR: 2454–6880) mm3 in women and 4812 (2842–8445) mm3 in men. Women with any headaches (all headache types combined) had a 1.23 [1.04; 1.45]-fold higher WMH volume than women who reported never having had a headache. There was no indication of higher Fazekas grading or more WMH progression in women with migraine or any headaches. Men with migraine or any headaches did not have more WMH or WMH progression compared to men without migraine or men who never had headache. Conclusions Our study demonstrated no increased occurrence or progression of WMH in participants with mgiraine. But, our results provide some evidence of greater WMH volume in women with headache of any type including migraine. The underlying pathomechanisms and the reasons why this was not shown in men are unclear and require further research.

Abstract Background There are no robust population-based Australian data on prevalence and attributed burden of migraine and medication-overuse headache (MOH) data. In this pilot cross-sectional study, we aimed to capture the participation rate, preferred response method, and acceptability of self-report questionnaires to inform the conduct of a future nationwide migraine/MOH epidemiological study. Methods We developed a self-report questionnaire, available in hard-copy and online, including modules from the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, the Eq. 5D (quality of life), and enquiry into treatment gaps. Study invitations were mailed to 20,000 randomly selected households across Australia’s two most populous states. The household member who most recently had a birthday and was aged ≥ 18 years was invited to participate, and could do so by returning a hard-copy questionnaire via reply-paid mail, or by entering responses directly into an online platform. Results The participation rate was 5.0% (N = 1,000). Participants’ median age was 60 years (IQR 44–71 years), and 64.7% (n = 647) were female. Significantly more responses were received from areas with relatively older populations and middle-level socioeconomic status. Hard copy was the more commonly chosen response method (n = 736). Females and younger respondents were significantly more likely to respond online than via hard-copy. Conclusions This pilot study indicates that alternative methodology is needed to achieve satisfactory engagement in a future nationwide migraine/MOH epidemiological study, for example through inclusion of migraine screening questions in well-resourced, interview-based national health surveys that are conducted regularly by government agencies. Meanwhile, additional future research directions include defining and addressing treatment gaps to improve migraine awareness, and minimise under-diagnosis and under-treatment.

Abstract Background Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. Methods This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). Results A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173–2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082–1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307–2.439, p

Abstract Background The objective of this study was to investigate the trends and prescribing patterns of antimigraine medicines in China. Methods The prescription data of outpatients diagnosed with migraine between 2018 and 2022 were extracted from the Hospital Prescription Analysis Cooperative Project of China. The demographic characteristics of migraine patients, prescription trends, and corresponding expenditures on antimigraine medicines were analyzed. We also investigated prescribing patterns of combination therapy and medicine overuse. Results A total of 32,246 outpatients who were diagnosed with migraine at 103 hospitals were included in this study. There were no significant trend changes in total outpatient visits, migraine prescriptions, or corresponding expenditures during the study period. Of the patients who were prescribed therapeutic medicines, 70.23% received analgesics, and 26.41% received migraine-specific agents. Nonsteroidal anti-inflammatory drugs (NSAIDs; 28.03%), caffeine-containing agents (22.15%), and opioids (16.00%) were the most commonly prescribed analgesics, with corresponding cost proportions of 11.35%, 4.08%, and 19.61%, respectively. Oral triptans (26.12%) were the most commonly prescribed migraine-specific agents and accounted for 62.21% of the total therapeutic expenditures. The proportion of patients receiving analgesic prescriptions increased from 65.25% in 2018 to 75.68% in 2022, and the proportion of patients receiving concomitant triptans decreased from 29.54% in 2018 to 21.55% in 2022 (both P

Abstract Background Phosphodiesterase 3 (PDE-3) inhibition have been implicated in the neurobiologic underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to ascertain whether PDE-3 inhibition can elicit migraine-like headache in persons with PPTH. Methods We tested cilostazol, which inhibits PDE-3, in a randomized, double-blind, placebo-controlled, two-way crossover study involving persons with PPTH attributed to mild traumatic brain injury. The randomized participants were allocated to receive oral administration of either 200-mg cilostazol or placebo (calcium tablet) on two separate experiment days. The primary end point was the incidence of migraine-like headache during a 12-hour observation window post-ingestion. The secondary endpoint was the area under the curve (AUC) for reported headache intensity scores during the same observation window. Results Twenty-one persons underwent randomization and completed both experiment days. The mean participants’ age was 41.4 years, and most (n = 17) were females. During the 12-hour observation window, 14 (67%) of 21 participants developed migraine-like headache post-cilostazol, in contrast to three (14%) participants after placebo (P =.003). The headache intensity scores were higher post-cilostazol than after placebo (P

Abstract Background Patients with migraine often have poor sleep quality between and during migraine attacks. Furthermore, extensive research has identified photophobia as the most common and most bothersome symptom in individuals with migraine, second only to headache. Seeking the comfort of darkness is a common strategy for managing pain during an attack and preventing its recurrence between episodes. Given the well-established effects of daily light exposure on circadian activity rhythms and sleep quality, this study aimed to investigate the relationship between photophobia symptoms and sleep quality in a cohort of patients with migraine. Methods A cross-sectional observational study was conducted using existing data extracted from the American Registry for Migraine Research (ARMR). Participants with a migraine diagnosis who had completed the baseline questionnaires (Photosensitivity Assessment Questionnaire (PAQ), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-2 (PHQ-2)), and selected questions of the ARMR Sleep questionnaire were included. Models were created to describe the relationship of photophobia and photophilia with various sleep facets, including sleep quality (SQ), sleep disturbance (SDis), sleep onset latency (SOL), sleep-related impairments (SRI), and insomnia. Each model was controlled for age, sex, headache frequency, anxiety, and depression. Results A total of 852 patients meeting the inclusion criteria were included in the analysis (mean age (SD) = 49.8 (13.9), 86.6% (n = 738) female). Those with photophobia exhibited significantly poorer sleep quality compared to patients without photophobia (p

Abstract Background The series of population-based studies conducted by the Global Campaign against Headache has, so far, included Pakistan and Saudi Arabia from the Eastern Mediterranean Region. The Maghreb countries of North Africa, also part of this Region, are geographically apart and culturally very different from these countries. Here we report a study in Morocco. Methods We applied the standardised methodology of Global Campaign studies, with cluster-randomized sampling in regions of Morocco selected to be representative of its diversities. In three of these regions, in accordance with this methodology, we made unannounced visits to randomly selected households and, from each, interviewed one randomly selected adult member (aged 18–65 years) using the HARDSHIP structured questionnaire translated into Moroccan Arabic and French. In a fourth region (Fès), because permission for such sampling was not given by the administrative authority, people were randomly stopped in streets and markets and, when willing, interviewed using the same questionnaire. This was a major protocol violation. Results We included 3,474 participants, 1,074 (41.7%) from Agadir, 1,079 (41.9%) from Marrakech, 422 (16.4%) from Tétouan and 899 from Fès. In a second protocol violation, interviewers failed to record the non-participating proportion. In the main analysis, excluding Fès, observed 1-year prevalence of any headache was 80.1% among females, 68.2% among males. Observed 1-day prevalence (headache yesterday) was 17.8%. After adjustment for age and gender, migraine prevalence was 30.8% (higher among females [aOR = 1.6]) and TTH prevalence 32.1% (lower among females [aOR = 0.8]). Headache on ≥ 15 days/month (H15+) was very common (10.5%), and in more than half of cases (5.9%) associated with acute medication overuse (on ≥ 15 days/month) and accordingly diagnosed as probable medication-overuse headache (pMOH). Both pMOH (aOR = 2.6) and other H15+ (aOR = 1.9) were more common among females. In the Fès sample, adjusted prevalences were similar, numerically but not significantly higher except for other H15+. Conclusions While the 1-year prevalence of headache among adults in Morocco is similar to that of many other countries, migraine on the evidence here is at the upper end of the global range, but not outside it. H15 + and pMOH are very prevalent, contributing to the high one-day prevalence of headache.

Abstract Background The Global Campaign against Headache is conducting a series of population-based studies to fill the large geographical gaps in knowledge of headache prevalence and attributable burden. One major region not until now included is South America. Here we present a study from Peru, a country of 32.4 million inhabitants located at the west coast of South America, notable for its high Andes mountains. Methods The study was conducted in accordance with the standardized methodology used by the Global Campaign. It was a cross-sectional survey using cluster randomised sampling in five regions to derive a nationally representative sample, visiting households unannounced, and interviewing one randomly selected adult member (aged 18–65 years) of each using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire translated into South American Spanish. The neutral screening question (“Have you had headache in the last year?”) was followed by diagnostic questions based on ICHD-3 and demographic enquiry. Results The study included 2,149 participants from 2,385 eligible households (participating proportion 90.1%): 1,065 males and 1,084 females, mean age 42.0 ± 13.7 years. The observed 1-year prevalence of all headache was 64.6% [95% CI: 62.5–66.6], with age-, gender- and habitation-adjusted prevalences of 22.8% [21.0-24.6] for migraine (definite + probable), 38.9% [36.8–41.0] for tension-type headache (TTH: also definite + probable), 1.2% [0.8–1.8] for probable medication-overuse headache (pMOH) and 2.7% [2.1–3.5] for other headache on ≥ 15 days/month (H15+). One-day prevalence of headache (reported headache yesterday) was 12.1%. Migraine was almost twice as prevalent among females (28.2%) as males (16.4%; aOR = 2.1; p 3,500 versus

Abstract Background The Global Burden of Disease (GBD) study is increasingly well informed with regard to headache disorders, but sub-Saharan Africa (SSA) remains one of the large regions of the world with limited data directly derived from population-based studies. The Global Campaign against Headache has conducted three studies in this region: Ethiopia in the east, Zambia in the south and Cameroon in Central SSA. Here we report a similar study in Benin, the first from West SSA. Methods We used the same methods and questionnaire, applying cluster-randomized sampling in three regions of the country, randomly selecting households in each region, visiting these unannounced and randomly selecting one adult member (aged 18–65 years) of each household. The HARDSHIP structured questionnaire, translated into Central African French, was administered face-to-face by trained interviewers. Demographic enquiry was followed by diagnostic questions based on ICHD-3 criteria. Results From 2,550 households with eligible members, we recruited 2,400 participants (participating proportion 94.1%). Headache ever was reported by almost all (95.2%), this being the lifetime prevalence. Headache in the last year was reported by 74.9%. Age-, gender- and habitation-adjusted estimates of 1-year prevalence were 72.9% for all headache, 21.2% for migraine (including definite and probable), 43.1% for TTH (also including definite and probable), 4.5% for probable medication-overuse (pMOH) and 3.1% for other headache on ≥ 15 days/month. One-day (point) prevalence of headache was 14.8% according to reported headache on the day preceding interview. Conclusions Overall, these findings are evidence that headache disorders are very common in Benin, a low-income country. The prevalence of pMOH, well above the estimated global mean of 1–2%, is evidence that poverty is not a bar to medication overuse. The findings are very much the same as those in a similar study in its near neighbour, Cameroon. With regard to migraine, they are reasonably in accord with two of three earlier studies in selected Beninese populations, which did not take account of probable migraine. This study adds to the hitherto limited knowledge of headache in SSA.

Abstract Background To date, migraine is diagnosed exclusively based on clinical criteria, but fluid biomarkers are desirable to gain insight into pathophysiological processes and inform clinical management. We investigated the state-dependent profile of fluid biomarkers for neuroaxonal damage and microglial activation as two potentially relevant aspects in human migraine pathophysiology. Methods This exploratory study included serum and cerebrospinal fluid (CSF) samples of patients with migraine during the headache phase (ictally) (n = 23), between attacks (interictally) (n = 16), and age/sex-matched controls (n = 19). Total Tau (t-Tau) protein, glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and neurofilament light chain (NfL) were measured with the Neurology 4-plex kit on a Single Molecule Array SR-X Analyzer (Simoa® SR-X, Quanterix Corp., Lexington, MA). Markers of microglial activation, C-X3-C motif chemokine ligand 1 (CX3CL1) and soluble triggering receptor expressed on myeloid cells 2 (sTREM2), were assessed using an immunoassay. Results Concentrations of CX3CL1 but not sTREM2 were significantly increased both ictally and interictally in CSF but not in serum in comparison to the control cohort (p = 0.039). ROC curve analysis provided an AUC of 0.699 (95% CI 0.563 to 0.813, p = 0.007). T-Tau in serum but not in CSF was significantly increased in samples from patients taken during the headache phase, but not interictally (effect size: η2 = 0.121, p = 0.038). ROC analysis of t-Tau protein in serum between ictal and interictal collected samples provided an AUC of 0.729 (95% CI 0.558 to 0.861, p = 0.006). The other determined biomarkers for axonal damage were not significantly different between the cohorts in either serum or CSF. Discussion CX3CL1 in CSF is a novel potential fluid biomarker of migraine that is unrelated to the headache status. Serum t-Tau is linked to the headache phase but not interictal migraine. These data need to be confirmed in a larger hypothesis-driven prospective study.

Background: Bow Hunter syndrome (BHS) is a rare, but important cause of posterior circulation stroke. It is also known as Rotational vertebral artery syndrome and is caused by transient dynamic vertebro-basilar insufficiency on movement of the neck in the presence of certain soft tissue or bone anomalies in the cranio-vertebral region. Case presentation: We present a case of Bow hunter syndrome in an 18-year-old adult male who presented with vomiting, occipital headache and loss of balance, with findings of posterior circulation stroke on imaging. Medical causes of young stroke, including vasculitis and clotting disorders were ruled out, following which a diagnostic conventional angiography and CT angiography was performed. The cause of vascular compromise in our case was the presence of vertebral anomalies, in particular, the presence of a partial ponticulus posticus with formation of an incomplete arcuate foramen. He was treated with cervical spine immobilisation and C1–C2 fixation. In addition, our patient had a single posterior inferior cerebellar artery (PICA) on the side of the dynamic insufficiency, which lead to bilateral cerebellar infarcts. Our case is unique because it demonstrates a combination of osseous and vascular developmental anomalies resulting in posterior circulation stroke. Conclusions: Though uncommon, BHS should be considered in the list of differentials in otherwise unexplained cases of posterior circulation stroke. Conventional angiography with dynamic manoeuvres is the modality of choice for documenting the rotational vertebral artery occlusion. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Addressing secondary headaches in SARS-CoV-2 infection is crucial for effective management and care optimization. This review aims to synthesize data on headache characteristics and the impact of pre-existing headache conditions on these symptoms in SARS-CoV-2 infection. CONTENTS: A systematic search was conducted across multiple databases, including PubMed/Medline, Cochrane Collaboration, Web of Science, Scopus, LILACS, Embase, Open Grey, and Google Scholar, to identify studies on headache characteristics associated with SARS-CoV-2. The search focused on headache symptoms, characteristics, onset, duration, and response to treatment during and post-infection. Twenty-three studies met the inclusion criteria. Approximately 42.1% of individuals with SARS-CoV-2 reported headaches, resembling tension-type headaches and migraines. These headaches often manifested within the first three days of infection and could persist for up to four months. The data suggest that trigeminovascular activation and pro-inflammatory mediators play a significant role in headache pathogenesis, with pre-existing headache conditions exacerbating the symptoms. The importance of effective pain management strategies must be emphasized. CONCLUSION: Headache is a prevalent symptom among SARS-CoV-2 infected individuals, with significant implications for patient care. The findings emphasize the importance of recognizing headache characteristics in SARS-CoV-2 management and suggest that tailored clinical approaches are essential for effective symptom relief.

Cryptococcal meningitis is a rare disease caused by Cryptococcus neoformans or Cryptococcus gatii as the fungal pathogen in humans. The disease is highly prevalent in people living with human immunodeficiency virus (HIV) and is the major cause of mortality in an immunocompromised individual. This life-threatening disease does not often occur with specific signs and symptoms. We reported a case of an early adulthood HIV-infected patient with a mild headache and low-grade fever. There was no altered mental status or other significant specific manifestations. Blood examination, chest radiography, and computed tomography scan revealed no significant results. C. neoformans were isolated from a culture of the cerebrospinal fluid specimen as the conventional gold standard examination for cryptococcal meningitis. A positive result was confirmed in the India ink staining preparation. The patient was treated with fluconazole monotherapy for the induction and consolidation phase and showed a positive disease progression during observations.

Abstract We investigated the relationship between dietary phytochemical index (DPI) and migraine headaches in Iranian patients, analyzing both clinical and psychological traits. A cross-sectional study was conducted using non-obese adults aged 20–50 years who were diagnosed with migraine. The study used a validated 168-item food frequency questionnaire to assess the usual dietary intake of participants. The DPI was calculated using the following formula: [daily energy derived from phytochemical-rich foods (in kJ)/total daily energy intake (in kJ)] × 100. Clinical outcomes of migraine including frequency, duration, and severity of headaches, as well as migraine-related disability were obtained using relevant questionnaires. Moreover, the mental health profile of patients including depression, anxiety, and stress, as well as serum levels of nitric oxide (NO) were measured. A Poisson regression was used for headache frequency. Linear regression analyzed migraine-related outcomes including duration, severity, migraine-related disability, and serum NO levels. In addition, psychological traits were analyzed via logistic regression. A total of 262 individuals (85.5% females) with a mean age of 36.1 years were included in the analysis. The frequency of migraine attacks was lower in patients in the last DPI tertile compared to those in the first DPI tertile both in the crude [incidence rate ratio (IRR) = 0.70, 95% confidence interval (CI) 0.63, 0.78, Ptrend

Abstract Background Knowledge of the prevalence and attributable burden of headache disorders in India is sparse, with only two recent population-based studies from South and East India. These produced conflicting results. A study in North India is needed. We report the methodology of such a study using, and validating, a Hindi translation of the Headache-Attributed Restriction, Disability, Social Handicap, and Impaired Participation (HARDSHIP) questionnaire developed by Lifting The Burden (LTB). Almost half of the Indian population speak Hindi or one of its dialects. Methods The study adopted LTB’s standardized protocol for population-based studies in a cross-sectional survey using multistage random sampling conducted in urban Delhi and a surrounding rural area. Trained interviewers visited households unannounced, randomly selected one adult member from each and applied the Hindi version of HARDSHIP in face-to-face interviews. The most bothersome headache reported by participants was classified algorithmically into headache on ≥ 15 days/month (H15 +), migraine (including definite and probable) or tension-type headache (including definite and probable). These diagnoses were mutually exclusive. All participants diagnosed with H15 + and a 10% subsample of all others were additionally assessed by headache specialists and classified as above. We estimated the sensitivity and specificity of HARDSHIP diagnoses by comparison with the specialists’ diagnoses. Results From 3,040 eligible households, 2,066 participants were interviewed. The participating proportions were 98.3% in rural areas but 52.9% in urban Delhi. In the validation subsample of 291 participants (149 rural, 142 urban), 61 did not report any headache (seven of those assessed by HARDSHIP, eight by headache specialists and 46 by both) [kappa = 0.83; 95% CI: 0.74-0.91]. In the remaining 230 participants who reported headache in the preceding year, sensitivity, specificity and kappa with (95% CI) were 0.73 (0.65-0.79), 0.80 (0.67-0.90) and 0.43 (0.34-0.58) for migraine; 0.71 (0.56-0.83), 0.80 (0.730.85) and 0.43 (0.37-0.62) for TTH and 0.75 (0.47-0.94), 0.93 (0.89-0.96) and 0.46 (0.34-0.58) for H15 + respectively. Conclusion This study validates the Hindi version of HARDSHIP, finding its performance similar to those of other versions. It can be used to conduct population surveys in other Hindi-speaking regions of India.

Abstract Background Knowledge of headache prevalence, and the burdens attributable to headache disorders, remains incomplete in sub-Saharan Africa (SSA): reliable studies have been conducted only in Zambia (southern SSA) and Ethiopia (eastern SSA). As part of the Global Campaign against Headache, we investigated the prevalence of headache in Cameroon, in Central SSA. Methods We used the same methodology as the studies in Zambia and Ethiopia, employing cluster-randomized sampling in four regions of Cameroon, selected to reflect the country’s geographic, ethnic and cultural diversities. We visited, unannounced, randomly selected households in each region, and randomly selected one adult member (aged 18–65 years) of each. Trained interviewers administered the Headache-Attributed Restriction, Disability and Impaired Participation (HARDSHIP) structured questionnaire, developed by an international expert consensus group and translated into Central African French. Demographic enquiry was followed by diagnostic questions based on ICHD-3 criteria. Results Headache was a near-universal experience in Cameroon (lifetime prevalence: 94.8%). Observed 1-year prevalence of headache was 77.1%. Age- and gender-adjusted estimates were 76.4% (95% confidence interval: 74.9–77.9) for any headache, 17.9% (16.6–19.3) for migraine (definite + probable), 44.4% (42.6–46.2) for tension-type headache (TTH; also definite + probable), 6.5% (5.7–7.4) for probable medication-overuse headache (pMOH) and 6.6% (5.8–7.6) for other headache on ≥ 15 days/month (H15 +). One-day prevalence (“headache yesterday”) was 15.3%. Gender differentials were as expected (more migraine and pMOH among females, and rather more TTH among males). pMOH increased in prevalence until age 55 years, then declined somewhat. Migraine and TTH were both associated with urban dwelling, pMOH, in contrast, with rural dwelling. Conclusions Headache disorders are prevalent in Cameroon. As in Zambia and Ethiopia, estimates for both migraine and TTH exceed global mean estimates. Attributable burden is yet to be reported, but these findings must lead to further research, and measures to develop and implement headache services in Cameroon, with appropriate management and preventative strategies.

Abstract The lesser occipital nerve (LON) has one of the most variations among occipital nerves. We aimed to investigate morphological and morphometric features of LON. A total of 24 cadavers, 14 males (58%) and 10 females (42%), were dissected bilaterally. LON was classified into 3 types. The number of branches and the perpendicular distances of the point where LON emerged from the posterior border of sternocleidomastoid muscle to vertical and transverse lines passing through external occipital protuberance were determined. The shortest distance between LON and great auricular nerve (GAN), and linear distance of LON to its branching point were measured. The most common variant was Type 1 (30 sides, 62.5%), followed by Type 2 (12 sides, 25%) and Type 3 (6 sides, 12.5%), respectively. In males, Type 1 (22 sides, 78.6%) was the most common, while Type 1 (8 sides, 40%) and Type 2 (8 sides, 40%) were equally common and the most common in females. On 48 sides, 2–9 branches of LON were observed. The perpendicular distance of said point to vertical and transverse lines was meanly 63.69 ± 11.28 mm and 78.83 ± 17.21 mm, respectively. The shortest distance between LON and GAN was meanly 16.62 ± 10.59 mm. The linear distance of LON to its branching point was meanly 31.24 ± 15.95 mm. The findings reported in this paper may help clinicians in estimating the location of the nerve and/or its branches for block or decompression surgery as well as preservation of LON during related procedures.

Abstract Background The upper cervical dorsal root ganglia (DRG) are important for the transmission of sensory information associated with the back of the head and neck, contributing to head pain. Calcitonin receptor (CTR)-based receptors, such as the amylin 1 (AMY1) receptor, and ligands, calcitonin gene-related peptide (CGRP) and amylin, have been linked to migraine and pain. However, the contribution of this system to nociception involving the cervical DRG is unclear. Therefore, this study aimed to determine the relative distribution of the CTR, CGRP, and amylin in upper cervical DRG. Methods CTR, CGRP, and amylin immunofluorescence was examined relative to neural markers in C1/2 DRG from male and female mice, rats, and human cases. Immunofluorescence was supported by RNA-fluorescence in situ hybridization examining amylin mRNA distribution in rat DRG. Results Amylin immunofluorescence was observed in neuronal soma and fibres. Amylin mRNA (Iapp) was also detected. Amylin and CGRP co-expression was observed in 19% (mouse), 17% (rat), and 36% (human) of DRG neurons in distinct vesicle-like neuronal puncta from one another. CTR immunoreactivity was present in DRG neurons, and both peptides produced receptor signalling in primary DRG cell cultures. CTR-positive neurons frequently co-expressed amylin and/or CGRP (66% rat; 84% human), with some sex differences. Conclusions Amylin and CGRP could both be local peptide agonists for CTR-based receptors in upper cervical DRG, potentially acting through autocrine and/or paracrine signalling mechanisms to modulate neuron function. Amylin and its receptors could represent novel pain targets.

Abstract Glymphatic system is an emerging pathway of removing metabolic waste products and toxic solutes from the brain tissue. It is made of a network of perivascular spaces, filled in cerebrospinal and interstitial fluid, encompassing penetrating and pial vessels and communicating with the subarachnoid space. It is separated from vessels by the blood brain barrier and from brain tissue by the endfeet of the astrocytes rich in aquaporin 4, a membrane protein which controls the water flow along the perivascular space. Animal models and magnetic resonance (MR) studies allowed to characterize the glymphatic system function and determine how its impairment could lead to numerous neurological disorders (e.g. Alzheimer’s disease, stroke, sleep disturbances, migraine, idiopathic normal pressure hydrocephalus). This review aims to summarize the role of the glymphatic system in the pathophysiology of migraine in order to provide new ways of approaching to this disease and to its therapy.

Migraine is one of the most prevalent and disabling neurological conditions, presenting episodes of throbbing headache that limit activities of daily living. Several factors may influence migraine frequency, such as lifestyle or alcohol consumption. Among the most recognised ones, sleep plays a biunivocal role, since poor sleep quality may worsen migraine frequency, and a high migraine frequency may affect sleep quality. In this paper, the authors evaluate the relationship between migraine and insomnia by exploring a cohort of patients affected by episodic or chronic migraine. To do so, a phone interview was performed, asking patients about their migraine frequency and mean pain intensity, in addition to the questions of the Insomnia Severity Index. The last one explores several symptoms impairing sleep that focus on insomnia. Patients complaining of insomnia showed an increased migraine frequency, and a weak but significant correlation was found between headache days per month and insomnia scores. Such results were particularly evident in patients affected by chronic migraine. Such results suggest how insomnia, in the presented data, seems to be associated with migraine frequency but not with pain intensity.

Abstract Background About one-third of persons with migraine experience transient neurologic symptoms, referred to as aura. Despite its widespread prevalence, comprehensive clinical descriptions of migraine with aura remain sparse. Therefore, we aimed to provide an in-depth phenotypic analysis of aura symptoms and characteristics in a cross-sectional study of a large sample of adults diagnosed with migraine with aura. Methods Data were extracted from the baseline characteristics of participants in the Registry for Migraine (REFORM) study – a single-center, prospective, longitudinal cohort study. Participants were adults diagnosed with migraine aura, reporting ≥ 4 monthly migraine days in the preceding 3 months. Trained personnel conducted in-person semi-structured interviews, capturing details on the nature, duration, localization, and progression of individual aura symptoms. Results Of the 227 enrolled participants with migraine with aura, the mean age was 41.1 years, with a predominant female representation (n = 205 [90.3%]). Visual aura was present in 215 (94.7%) participants, somatosensory aura in 81 (35.7%), and speech and/or language aura in 31 (13.7%). A single type of aura was observed in 148 (65.2%) participants, whilst 79 (34.8%) reported multiple aura types. Most participants (n = 220 [96.9%]) described their aura symptoms as positive or gradually spreading. Headache in relation to aura was noted by 218 (96.0%) participants, with 177 (80.8%) stating that the onset of aura symptoms preceded the onset of headache. Conclusions This study offers a detailed clinical depiction of persons with migraine with aura, who were predominantly enrolled from a tertiary care unit. The findings highlight potential gaps in the available literature on migraine with aura and should bolster clinicians’ acumen in diagnosing migraine with aura in clinical settings.

Background & Aims: Headache has been a common problem for humans since ancient times. The aim of this study was to investigate the prevalence of ear, nose, and throat diseases in patients with headache. Materials & Methods: In this descriptive cross-sectional study, we reviewed medical records of 100 patients presenting with headache to the ENT clinic of Imam Khomeini Hospital in Urmia, Iran, between 2019 and 2021. The type of headache (primary or secondary) was diagnosed based on medical history, clinical examinations, and paraclinical examinations (CT scan) and completion of a checklist for each patient. Chi-square and independent t-tests were used to analyze data. The p value < 0.05 was considered significant. Results: Of 100 patients, 58 (58%) had primary headaches with a mean age of 1.72 ± 4.77 years, and 42 (42%) had secondary headaches with a mean age of 5.57 ± 1.43 years (p < 0.01). There was a significant difference in the type of headache and location of pain in patients except for the back of the head and the top of the head (p < 0.05). Of the 58 patients with primary headaches, 26 (44.8%), and of the 42 patients with secondary headaches, 10 (23.8%) woke up from sleep due to headache (p < 0.03). Of the 58 patients with primary headaches, 38 (65.5%), and of the 42 patients with secondary headaches, 12 (28.6%) had their headache worsened by light and noise (p < 0.001). Conclusion: Of all patients, 42% had secondary headaches, which most commonly had symptoms of sinus pain. These patients were treated by an otolaryngologist. Patients with non-sinus headaches were referred to a neurologist.