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1.
Neurosurg Rev ; 47(1): 253, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38829433

PURPOSE: The study intends to clarify the optimal endoscopic endonasal surgical strategy for symptomatic Rathke's cleft cysts (RCCs). METHODS: We retrospectively analyzed patients with RCCs that underwent EEA surgery. The strategy for surgical and reconstruction method selection was presented. Patients were split into groups of fenestration open or closed. Pre- and postoperative symptoms, imaging, ophthalmologic, and endocrinologic exams were reviewed. The incidence of complications and the recurrence rates were determined. RESULTS: The 75 individuals were all received primary operations. The fenestration closed group contained 32 cases, while the fenestration open group contained 43 cases. The median follow-up period was 39 months. The three primary complaints were headache (n = 51, 68.00%), vision impairment (n = 45, 60.00%), and pituitary dysfunction (n = 16, 21.33%). Of the 51 patients with preoperative headaches, 48 (94.12%) reported improvement in their symptoms following surgery. Twenty-three out of 45 patients (51.11%) experienced an improvement in visual impairment. Pituitary dysfunction was found improved in 14 out of 16 individuals (87.50%). There was no discernible difference in the rate of symptom alleviation between both groups. There were three patients (3/75, 4.00%) had cyst reaccumulation. One of them (1/75, 1.33%), which needed reoperation, was healed using pterional approach. In term of complications, cerebral infections occurred in two patients (2/75, 2.67%). Both of them recovered after antibiotic treatment. No postoperative cerebrospinal fluid rhinorrhea occurred. One patient (1/75, 1.33%) in the open group experienced epistaxis. There was no persistent hypopituitarism or diabetes insipidus (DI). Analysis of headache related factors showed that the presence of wax like nodules was related to it. CONCLUSION: RCC was successfully treated with endoscopic endonasal surgery with few problems when the fenestration was kept as open as feasible. Preoperative identification of T2WI hypointense nodules may be a potential reference factor for surgical indication.


Central Nervous System Cysts , Humans , Male , Central Nervous System Cysts/surgery , Central Nervous System Cysts/complications , Female , Adult , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult , Adolescent , Neuroendoscopy/methods , Aged , Postoperative Complications/epidemiology , Pituitary Neoplasms/surgery , Headache/etiology , Neurosurgical Procedures/methods
2.
Brain Behav ; 14(6): e3583, 2024 Jun.
Article En | MEDLINE | ID: mdl-38841826

OBJECTIVE: To investigate the prevalence of neuroimaging in patients with primary headaches and the clinician-based rationale for requesting neuroimaging in China. DATA SOURCES AND STUDY SETTING: This study included patients with primary headaches admitted to hospitals and clinicians in China. We identified whether neuroimaging was requested and the types of neuroimaging conducted. STUDY DESIGN: This was a cross-sectional study, and convenience sampling was used to recruit patients with primary headaches. Clinicians were interviewed using a combination of personal in-depth and topic-selection group interviews to explore why doctors requested neuroimaging. DATA COLLECTION: We searched for the diagnosis of primary headache in the outpatient and inpatient systems according to the International Classification of Diseases-10 code of patients admitted to six hospitals in three provincial capitals by 2022.We selected three public and three private hospitals with neurology specialties that treated a corresponding number of patients. PRINCIPLE FINDINGS: Among the 2263 patients recruited for this study, 1942 (89.75%) underwent neuroimaging. Of the patients, 1157 (51.13%) underwent magnetic resonance imaging (MRI), 246 (10.87%) underwent both head computed tomography (CT) and MRI, and 628 (27.75%) underwent CT. Fifteen of the 16 interviewed clinicians did not issue a neuroimaging request for patients with primary headaches. Furthermore, we found that doctors issued a neuroimaging request for patients with primary headaches mostly, to exclude the risk of misdiagnosis, reduce uncertainty, avoid medical disputes, meet patients' medical needs, and complete hospital assessment indicators. CONCLUSIONS: For primary headaches, the probability of clinicians requesting neuroimaging was higher in China than in other countries. There is considerable room for improvement in determining appropriate strategies to reduce the use of low-value care for doctors and patients.


Magnetic Resonance Imaging , Neuroimaging , Humans , China , Cross-Sectional Studies , Neuroimaging/methods , Neuroimaging/statistics & numerical data , Male , Adult , Female , Middle Aged , Headache Disorders, Primary/diagnostic imaging , Tomography, X-Ray Computed/statistics & numerical data , Young Adult , Headache/diagnostic imaging , Adolescent
4.
BMC Public Health ; 24(1): 1511, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38840082

BACKGROUND: Many Ebola virus disease (EVD) survivors have reported somatic and neuropsychological symptoms after discharge from the Ebola Treatment Unit (ETU). Since the 2014-2016 Ebola epidemic in West Africa, various studies have investigated and identified these symptoms. Evidence on somatic symptoms is widely available in the literature, however, there is no concise overview of the prevalence across different time intervals. METHODS: This meta-analysis was conducted following the (PRISMA) guidelines. A database search was conducted to identify original studies that reported the prevalence of symptoms. The primary outcome measure was the prevalence rate of several somatic symptoms. Results were pooled, and prevalence rates were assessed over time, to elucidate any particular trends. RESULTS: We included 23 studies (5,714 participants). The pooled prevalence was: arthralgia 50% (95% CI: 41%-59%); headache 44% (95% CI: 36%-52%); myalgia 32% (95% CI: 26%-38%); abdominal pain 27% (95% CI: 15%-39%); fatigue 25% (95% CI: 19%-31%); numbness of feet 16% (95% CI: 14%-18%); numbness of hands 12% (95% CI: 10%-14%) and hearing loss 9% (95% CI: 5%-12%). Prevalence across different time intervals revealed significant patterns. All the symptoms persisted for more than 2 years after discharge except for abdominal pain. CONCLUSION: The pooled prevalence rates of somatic symptoms are notably high. Arthralgia and headache are the most prevalent of the symptoms, with hearing loss and numbness in hands and feet being the least. We found that arthralgia, myalgia, and abdominal pain decreased over time. However, headache, fatigue, numbness of hands and feet, and hearing loss increased over time.


Hemorrhagic Fever, Ebola , Survivors , Humans , Hemorrhagic Fever, Ebola/epidemiology , Prevalence , Survivors/statistics & numerical data , Survivors/psychology , Medically Unexplained Symptoms , Arthralgia/epidemiology , Headache/epidemiology , Africa, Western/epidemiology , Fatigue/epidemiology , Africa/epidemiology
5.
J Headache Pain ; 25(1): 72, 2024 May 07.
Article En | MEDLINE | ID: mdl-38714978

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 < 0.001) as independent risk factors for the occurrence of headaches. There were 443 AVMs with headache symptoms. After propensity score matching, the microsurgery group (OR 7.27, 95% CI 2.82-18.7 p < 0.001), stereotactic radiosurgery group(OR 9.46, 95% CI 2.26-39.6, p = 0.002), and multimodality treatment group (OR 8.34 95% CI 2.87-24.3, p < 0.001) demonstrate significant headache relief compared to the conservative group. However, there was no significant difference between the embolization group (OR 2.24 95% CI 0.88-5.69, p = 0.091) and the conservative group. CONCLUSIONS: This study identified potential risk factors for headaches in AVMs and found that microsurgery, stereotactic radiosurgery, and multimodal therapy had significant benefits in headache relief compared to conservative treatment. These findings provide important guidance for clinicians when developing treatment options that can help improve overall treatment outcomes and quality of life for patients.


Headache , Intracranial Arteriovenous Malformations , Humans , Female , Intracranial Arteriovenous Malformations/complications , Intracranial Arteriovenous Malformations/therapy , Male , Headache/etiology , Headache/therapy , Adult , Retrospective Studies , Risk Factors , Middle Aged , Young Adult , Conservative Treatment/methods , Treatment Outcome , Embolization, Therapeutic/methods , Adolescent
6.
Prim Care ; 51(2): 179-193, 2024 Jun.
Article En | MEDLINE | ID: mdl-38692769

Headache is consistently one of the most common complaints reported by patients in the medical setting worldwide. Headache can be a symptom of another condition or illness, secondary to the disruption of homeostasis, or can be a primary disorder with inherent variability and patterns. Headache disorders, whether primary or secondary, can cause significant disability and loss of quality of life for those affected. As such, it is important for primary care providers to feel confident evaluating and treating patients with headache, especially given the limited access to Headache Medicine subspecialists.


Headache , Primary Health Care , Humans , Headache/diagnosis , Headache/therapy , Diagnosis, Differential , Headache Disorders/diagnosis , Headache Disorders/therapy
7.
WMJ ; 123(2): 138-140, 2024 May.
Article En | MEDLINE | ID: mdl-38718245

The constellation of fevers accompanied by headache and vomiting is a red flag for clinicians that appropriately triggers evaluation for meningitis and other life-threatening diagnoses. When symptoms persist even after these conditions are ruled out, patient care becomes more challenging. We present the case of a 6-year-old male with a history of autism spectrum disorder who presented with 6 months of headaches and associated vomiting and intermittent fevers with negative infectious workup despite cerebrospinal fluid pleocytosis. Serial neuroimaging and laboratory evaluation ultimately led to a diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) presenting as aseptic meningitis. The clinical and radiographic findings of MOGAD are widely variable and overlap with several other inflammatory conditions, which makes diagnosis challenging. This case highlights the importance of recognizing this rare MOGAD presentation as an infectious meningitis mimic.


Myelin-Oligodendrocyte Glycoprotein , Humans , Male , Diagnosis, Differential , Child , Myelin-Oligodendrocyte Glycoprotein/immunology , Headache Disorders/etiology , Headache Disorders/diagnosis , Meningitis, Aseptic/diagnosis , Meningitis/diagnosis , Headache/etiology
8.
BMJ Open ; 14(5): e074596, 2024 May 31.
Article En | MEDLINE | ID: mdl-38821571

OBJECTIVES: During the COVID-19 pandemic, healthcare workers (HCWs) are at a serious risk of contracting this virus. Therefore, they should use personal protective equipment (PPE) to protect themselves. Long-term use of these devices has led to many side effects, including headaches. This study investigated the prevalence of headaches related to using PPE in HCWs during the COVID-19 pandemic. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, PubMed, Scopus and Web of Science databases were searched from December 2019 to February 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: All cross-sectional studies that investigated the prevalence of headache complications caused by PPE were included. DATA EXTRACTION AND SYNTHESIS: Two researchers reviewed the articles separately and independently. The Appraisal Tool for Cross-Sectional Studies was used to address study design quality and the risk of bias in cross-sectional studies. The heterogeneity of the studies was checked with the I2 statistic, and due to the high heterogeneity, the random effects model was used for synthesis. Data were analysed using Comprehensive Meta-Analysis software V.3.3.70. RESULTS: Out of 3218 articles retrieved for all side effects, 40 were eligible for this meta-analysis. The prevalence of headaches related to the use of PPE in these 40 studies, with a sample size of 19 229 people, was 43.8% (95% CI 43.1% to 44.6%, I2=98.6%, p<0.001). Based on the meta-regression results, no significant relationship was observed between the prevalence of headaches and variables such as year of publication, study location, sample size and quality of studies. CONCLUSION: Headache is one of the common side effects of PPE, which can interfere with HCWs' performance. It is suggested that manufacturers improve the quality of their equipment while healthcare managers should equip and train staff adequately to minimise side effects, ensuring health and enhanced service delivery. PROSPERO REGISTRATION NUMBER: CRD42021264874.


COVID-19 , Headache , Health Personnel , Personal Protective Equipment , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Personal Protective Equipment/adverse effects , Headache/epidemiology , Headache/etiology , Prevalence , SARS-CoV-2 , Pandemics , Occupational Diseases/epidemiology , Occupational Diseases/prevention & control , Occupational Diseases/etiology
9.
Clin Neuropharmacol ; 47(3): 87-96, 2024.
Article En | MEDLINE | ID: mdl-38743602

OBJECTIVES: Clinical manifestations of vitamin B12 deficiency are varied and may result in missed or delayed diagnosis. This investigation explores the diverse clinical manifestations and demographic characteristics of vitamin B12 deficiency in neurology outpatients, aiming to enhance timely diagnosis and outcomes. METHODS: The severity of vitamin B12 deficiency was classified as absolute (≤150 pg/mL) or borderline deficiency (150-300 pg/mL). We conducted a retrospective analysis of 165 outpatients with vitamin B12 deficiency at the department of neurology between May 2020 and May 2021. RESULT: Absolute vitamin B12 deficiency was found in 23.0% of the patients. The most common age range was 50-60 years, the most common cause was vegetarianism, and the most common symptom was headache. Epileptiform symptoms were more likely to occur in younger patients (<20 years old) with vitamin B12 deficiency, whereas psychiatric symptoms were more likely to occur in older patients (>70 years old). Vegetarians, salivation, and nonmegaloblastic anemia were more obvious in patients with absolute vitamin B12 deficiency, whereas headaches often showed borderline B12 deficiency. CONCLUSIONS: The clinical characteristics of vitamin B12 deficiency are complex and nonspecific. The diagnosis should be based on multiple factors.


Outpatients , Vitamin B 12 Deficiency , Humans , Vitamin B 12 Deficiency/complications , Vitamin B 12 Deficiency/diagnosis , Vitamin B 12 Deficiency/epidemiology , Retrospective Studies , Middle Aged , Male , Female , Aged , Adult , Young Adult , Adolescent , Headache/diagnosis , Aged, 80 and over , Neurology
10.
J Headache Pain ; 25(1): 78, 2024 May 15.
Article En | MEDLINE | ID: mdl-38745272

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.


Disease Progression , Magnetic Resonance Imaging , Migraine Disorders , White Matter , Humans , Female , Male , White Matter/diagnostic imaging , White Matter/pathology , Middle Aged , Migraine Disorders/diagnostic imaging , Migraine Disorders/epidemiology , Migraine Disorders/pathology , Headache/epidemiology , Headache/diagnostic imaging , Cross-Sectional Studies , Aged , Longitudinal Studies , Adult , Sex Factors
11.
Clin Ter ; 175(3): 154-162, 2024.
Article En | MEDLINE | ID: mdl-38767072

Background: Rising global concerns about COVID-19 recently gained more research attention due to the ease of person-to-person transmission, various symptoms after healing, and the shortage of effective antiviral therapy. The study aims to analyze post-COVID conditions and clinical manifestations of cardiovascular lesions in patients recovering from COVID-19 infection. Methods: A practical examination of post-COVID conditions manifestation was conducted in a prospective cohort study, involving 250 patients diagnosed with COVID-19 between June 1, 2021, and August 31, 2021. The study specifically focused on analyzing the cardiovascular effects of COVID-19, utilizing data from a subgroup of 200 patients previously discharged from the hospital with elevated troponin levels. The cardiovascular variables assessed included tachycardia, ischemia, heart attack, myocarditis, hypertension, blood clots, and heart failure. Results: It has been observed that among surviving patients, the following symptoms persisted: anosmia/ageusia (59%), severe dyspnea (36.7%), palpitations and complaints related to the cardiovascular sys-tem (15.8%), headaches (13.2%), arthralgia (11.7%), myalgia (9.8%), and hair problems (≥5%). By the 60th day, a reduction in symptoms by 5-10% was noted, and by the 90th day, a decrease in activity by 25-35% was observed. Patients aged 40-60 years exhibited the highest percentage of cardiovascular diseases (75%). Conclusions: Consequently, the SARS-CoV-2 virus underscores the critical importance of cardiological attention in patient care. Cardiac screening results in individuals with COVID-19 reveal a significant prevalence of serious heart problems, affecting over half of the patients. This emphasizes the necessity for heightened vigilance and specialized cardiac care when managing patients with COVID-19.


COVID-19 , Cardiovascular Diseases , Humans , COVID-19/complications , Male , Middle Aged , Female , Prospective Studies , Adult , Cardiovascular Diseases/etiology , Cardiovascular Diseases/epidemiology , Aged , Post-Acute COVID-19 Syndrome , Anosmia/etiology , Myalgia/etiology , Arthralgia/etiology , Headache/etiology , Dyspnea/etiology
14.
BMC Musculoskelet Disord ; 25(1): 347, 2024 May 02.
Article En | MEDLINE | ID: mdl-38693507

BACKGROUND: Benign Joint Hypermobility Syndrome (BJHS) is a most common hereditary connective tissue disorders in children and adolescents. This study aimed to investigate the prevalence and subtypes of headache in children with BJHS. METHODS: This observational-analytical study was conducted in a case-control setting on school children aged 7 to 16 years in 2021-2023 in Isfahan, Iran. Students were examined for BJHS using Beighton criteria by a pediatric rheumatologist. Headache disorder was diagnosed according to the Child Headache-Attributed Restriction, Disability, and Social Handicap and Impaired Participation (HARDSHIP) questionnaires for child and adolescent and International Classification of Headache Disorders (ICHD-III). RESULTS: A total of 4,832 student (mean age 10.3 ± 3.1 years), 798 patients with BJHS and 912 healthy children were evaluated. The probability of headache in children aged 7-11 with hypermobility was 3.7 times lower than in children aged 12-16 with hypermobility (P = 0.001). The occurrence of headache in children with BJHS was more than the control group (P = 0.001), and the probability of headache in children with BJHS was 3.7 times higher than in healthy children (P = 0.001). Migraine was the most common headache type reported of total cases. The probability of migraine in children with BJHS was 4.5 times higher than healthy children ( P = 0.001). CONCLUSION: This study showed a significant correlation between BJHS and headache (especially migraine) in children and adolescents.


Headache , Joint Instability , Joint Instability/congenital , Humans , Adolescent , Child , Male , Female , Case-Control Studies , Iran/epidemiology , Joint Instability/epidemiology , Joint Instability/diagnosis , Joint Instability/complications , Prevalence , Headache/epidemiology , Headache/diagnosis , Ehlers-Danlos Syndrome/epidemiology , Ehlers-Danlos Syndrome/diagnosis , Ehlers-Danlos Syndrome/complications
17.
Environ Int ; 188: 108776, 2024 Jun.
Article En | MEDLINE | ID: mdl-38810494

OBJECTIVE: Headache is one of the most prevalent and disabling health conditions globally. We prospectively explored the urban exposome in relation to weekly occurrence of headache episodes using data from the Dutch population-based Occupational and Environmental Health Cohort Study (AMIGO). MATERIAL AND METHODS: Participants (N = 7,339) completed baseline and follow-up questionnaires in 2011 and 2015, reporting headache frequency. Information on the urban exposome covered 80 exposures across 10 domains, such as air pollution, electromagnetic fields, and lifestyle and socio-demographic characteristics. We first identified all relevant exposures using the Boruta algorithm and then, for each exposure separately, we estimated the average treatment effect (ATE) and related standard error (SE) by training causal forests adjusted for age, depression diagnosis, painkiller use, general health indicator, sleep disturbance index and weekly occurrence of headache episodes at baseline. RESULTS: Occurrence of weekly headache was 12.5 % at baseline and 11.1 % at follow-up. Boruta selected five air pollutants (NO2, NOX, PM10, silicon in PM10, iron in PM2.5) and one urban temperature measure (heat island effect) as factors contributing to the occurrence of weekly headache episodes at follow-up. The estimated causal effect of each exposure on weekly headache indicated positive associations. NO2 showed the largest effect (ATE = 0.007 per interquartile range (IQR) increase; SE = 0.004), followed by PM10 (ATE = 0.006 per IQR increase; SE = 0.004), heat island effect (ATE = 0.006 per one-degree Celsius increase; SE = 0.007), NOx (ATE = 0.004 per IQR increase; SE = 0.004), iron in PM2.5 (ATE = 0.003 per IQR increase; SE = 0.004), and silicon in PM10 (ATE = 0.003 per IQR increase; SE = 0.004). CONCLUSION: Our results suggested that exposure to air pollution and heat island effects contributed to the reporting of weekly headache episodes in the study population.


Air Pollutants , Air Pollution , Environmental Exposure , Exposome , Headache , Humans , Headache/epidemiology , Headache/chemically induced , Male , Female , Netherlands/epidemiology , Middle Aged , Prospective Studies , Adult , Environmental Exposure/statistics & numerical data , Air Pollutants/analysis , Air Pollution/statistics & numerical data , Air Pollution/adverse effects , Environmental Health , Cohort Studies , Surveys and Questionnaires , Particulate Matter/analysis , Urban Population/statistics & numerical data
18.
Cephalalgia ; 44(5): 3331024241251488, 2024 May.
Article En | MEDLINE | ID: mdl-38690640

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.


Bibliometrics , Biomedical Research , Headache , Machine Learning , Translational Science, Biomedical , Biomedical Research/statistics & numerical data , Translational Science, Biomedical/statistics & numerical data , Practice Guidelines as Topic , Periodicals as Topic , ROC Curve , Area Under Curve , Authorship , Random Forest , Humans , Datasets as Topic
19.
Commun Biol ; 7(1): 646, 2024 May 27.
Article En | MEDLINE | ID: mdl-38802570

Headache disorders are the most common disorders of the nervous system. The lifetime prevalence of headache disorders show that some individuals never experience headache. The etiology of complete freedom from headache is not known. To assess genetic variants associated with complete freedom from headache, we performed a genome-wide association study of individuals who have never experienced a headache. We included 63,992 individuals (2,998 individuals with complete freedom from headache and 60,994 controls) from the Danish Blood Donor Study Genomic Cohort. Participants were included in two rounds, from 2015 to 2018 and in 2020. We discovered a genome-wide significant association, with the lead variant rs7904615[G] in ADARB2 (EAF = 27%, OR = 1.20 [1.13-1.27], p = 3.92 × 10-9). The genomic locus was replicated in a non-overlapping cohort of 13,032 individuals (539 individuals with complete freedom from headache and 12,493 controls) from the Danish Blood Donor Study Genomic Cohort (p < 0.05, two-sided). Participants for the replication were included from 2015 to 2020. In conclusion, we show that complete freedom from headache has a genetic component, and we suggest that ADARB2 is involved in complete freedom from headache. The genomic locus was specific for complete freedom from headache and was not associated with any primary headache disorders.


Blood Donors , Genome-Wide Association Study , Adult , Female , Humans , Male , Middle Aged , Cohort Studies , Denmark/epidemiology , Genetic Loci , Genetic Predisposition to Disease , Headache/genetics , Polymorphism, Single Nucleotide , RNA-Binding Proteins/genetics
20.
J Headache Pain ; 25(1): 87, 2024 May 28.
Article En | MEDLINE | ID: mdl-38802819

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.


Mast Cells , Pituitary Adenylate Cyclase-Activating Polypeptide , Stress, Psychological , Animals , Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism , Mast Cells/metabolism , Male , Mice , Stress, Psychological/complications , Stress, Psychological/metabolism , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , Trigeminal Ganglion/metabolism , Headache/etiology , Headache/metabolism , Headache/physiopathology , Mice, Knockout , Mice, Inbred C57BL , Disease Models, Animal
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