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Abstract Background Female sex is a known risk factor of brain disorders with raised intracranial pressure (ICP) and sex hormones have been suggested to alter cerebrospinal fluid (CSF) dynamics, thus impairing ICP regulation in CSF disorders such as idiopathic intracranial hypertension (IIH). The choroid plexus (CP) is the tissue producing CSF and it has been hypothesized that altered hormonal composition could affect the activity of transporters involved in CSF secretion, thus affecting ICP. Therefore, we aimed to investigate if expression of various transporters involved in CSF secretion at CP were different between males and females and between females in different estrous cycle states. Steroid levels in serum was also investigated. Methods Female and male rats were used to determine sex-differences in the genes encoding for the transporters Aqp1 and 4, NKCC1, NBCe2, NCBE; carbonic anhydrase enzymes II and III (CA), subunits of the Na+/K+-ATPase including Atp1a1, Atp1b1 and Fxyd1 at CP. The estrous cycle stage metestrus (MET) and estrous (ES) were determined before euthanasia. Serum and CP were collected and subjected to RT-qPCR analysis and western blots. Serum was used to measure steroid levels using liquid chromatography tandem mass spectrometry (LC–MS/MS). Results Significant differences in gene expression and steroid levels between males and ES females were found, while no differences were found between male and MET females. During ES, expression of Aqp1 was lower (p

Abstract Background The kaolin induced obstructive hydrocephalus (OHC) model is well known for its ability to increase intracranial pressure (ICP) in experimental animals. Papilledema (PE) which is a predominant hallmark of elevated ICP in the clinic has not yet been studied in this model using high-resolution digital fundus microscopy. Further, the long-term effect on ICP and optic nerve head changes have not been fully demonstrated. In this study we aimed to monitor epidural ICP after induction of OHC and to examine changes in the optic disc. In addition, we validated epidural ICP to intraventricular ICP in this disease model. Method Thirteen male Sprague-Dawley rats received an injection into the cisterna magna containing either kaolin-Ringer’s lactate suspension (n = 8) or an equal amount of Ringer’s lactate solution (n = 5). Epidural ICP was recorded post-operatively, and then continuously overnight and followed up after 1 week. The final epidural ICP value after 1 week was confirmed with simultaneous ventricular ICP measurement. Optic disc photos (ODP) were obtained preoperatively at baseline and after one week and were assessed for papilledema. Results All animals injected with kaolin developed OHC and had significant higher epidural ICP (15.49 ± 2.47 mmHg) compared to control animals (5.81 ± 1.33 mmHg) on day 1 (p

Abstract The Global Campaign against Headache, as a collaborative activity with the World Health Organization (WHO), was formally launched in Copenhagen in March 2004. In the month it turns 18, we review its activities and achievements, from initial determination of its strategic objectives, through partnerships and project management, knowledge acquisition and awareness generation, to evidence-based proposals for change justified by cost-effectiveness analysis.

IntroductionMigraine is a highly prevalent and disabling neurological disease. Excessive use of acute medications can lead to medication-overuse headache (MOH), occurring when a patient experiences an increasing number of headache and migraine days, despite taking greater amounts of acute medication. To treat MOH, a preventive migraine treatment and/or withdrawal of the overused medication(s) are advised. Brief Educational Intervention (BEI) has been shown to be an effective tool with promising results for MOH. Here, we report the design of a clinical trial that aims to evaluate the efficacy of eptinezumab, an anti-calcitonin gene-related peptide preventive migraine treatment, as an add-on to BEI for treatment of MOH in those with chronic migraine.Methods and analysisRESOLUTION will be a phase 4, multi-national, randomized, double-blind, placebo-controlled study. This study will enroll approximately 570 participants with dual diagnoses of chronic migraine and MOH. Eligible patients will be randomly allocated to one of two treatment groups, BEI and eptinezumab (100 mg; n = 285) or BEI and placebo (n = 285), in a 1:1 ratio. The primary endpoint is the change from baseline in monthly migraine days over weeks 1–4. Secondary and exploratory endpoints will assess monthly migraine days over weeks 1–12, MOH remission, transition from chronic to episodic migraine, health-related quality of life, work productivity, and the safety and tolerability of eptinezumab in this patient population.Ethics and disseminationThis study will be conducted in accordance with good clinical practice. All patients will be fully informed about the study, including the risks and benefits of participation, and all participants will provide informed consent for participation in the trial and dissemination of results.

Abstract Headache and facial pain are among the most common, disabling and costly diseases in Europe, which demands for high quality health care on all levels within the health system. The role of the Danish Headache Society is to educate and advocate for the needs of patients with headache and facial pain. Therefore, the Danish Headache Society has launched a third version of the guideline for the diagnosis, organization and treatment of the most common types of headaches and facial pain in Denmark. The second edition was published in Danish in 2010 and has been a great success, but as new knowledge and treatments have emerged it was timely to revise the guideline. The recommendations for the primary headaches and facial pain are largely in accordance with the European guidelines produced by the European Academy of Neurology. The guideline should be used a practical tool for use in daily clinical practice for primary care physicians, neurologists with a common interest in headache, as well as other health-care professionals treating headache patients. The guideline first describes how to examine and diagnose the headache patient and how headache treatment is organized in Denmark. This description is followed by sections on the characteristics, diagnosis and treatment of each of the most common primary and secondary headache disorders and trigeminal neuralgia. The guideline includes many tables to facilitate a quick overview. Finally, the particular challenges regarding migraine and female hormones as well as headache in children are addressed.

Abstract Background Elevated intracranial pressure (ICP) is observed in association with a range of brain disorders. There is limited insight into the regulatory mechanisms of ICP under physiological conditions, and consequently also under pathological conditions. Thereby, to understand the mechanisms underlying ICP dynamics, precise, valid and long-term ICP recordings are of importance in the preclinical setting. Herein, we used a novel telemetric system for ICP recordings which allowed for long-term recordings in freely-moving rats. The aim was to investigate ICP dynamics under different physiological states and investigate how factors such as surgery/recovery, body position, light–dark, co-housing, weight and anesthesia may influence ICP and its waveforms. Methods A telemetric device was implanted epidurally in rats and signals were recorded continuously for up to 50 days (n = 14). Recording was divided into three experimental periods: a surgical recovery period (RP), a physiological period (PP) and an experimental period (EP). Histology was performed to study the morphology of implanted rats and non-implanted rats (n = 17). Results For the first time, we can demonstrate continuous ICP recordings in freely-moving and co-housed rats for up to 50 days with a high degree of stability. The mean ICP in the recording periods were; RP: 3.2 ± 0.6 mmHg, PP: 5.0 ± 0.6 mmHg and EP: 4.7 ± 0.6 mmHg. In the RP, the ICP was significantly lower compared to the PP (P = 0.0034). Significant light–dark difference in ICP with 21% increase in respiratory slow-wave amplitude was observed in the co-housed animals but not in single-housed animals. The ICP signal was raised during the dark period relative to the light (Δ0.3 ± 0.07 mmHg, P = 0.0043). Administration of anesthesia gave a short-term increase in ICP followed by a significant decrease in ICP. No signs of tissue damage or inflammation were found in the implanted brains. Conclusions ICP dynamics were influenced by several factors such as, use of anesthesia, light–dark difference and housing conditions. Our study demonstrates the importance of performing ICP physiological measurements in freely-moving animals. This has significant implications for moving the preclinical research field forward in order to properly study ICP physiology during disease development and to explore drug targets for alleviating increased ICP.

Abstract Background Factors associated with development of medication-overuse headache (MOH) in migraine patients are not fully understood, but with respect to prevention, the ability to predict the onset of MOH is clinically important. The aims were to examine if personality characteristics, disability and physical activity level are associated with the onset of MOH in a group of migraine patients and explore to which extend these factors combined can predict the onset of MOH. Methods The study was a single-center prospective observational study of migraine patients. At inclusion, all patients completed questionnaires evaluating 1) personality (NEO Five-Factor Inventory), 2) disability (Migraine Disability Assessment), and 3) physical activity level (Physical Activity Scale 2.1). Diagnostic codes from patients’ electronic health records confirmed if they had developed MOH during the study period of 20 months. Analyses of associations were performed and to identify which of the variables predict onset MOH, a multivariable least absolute shrinkage and selection operator (LASSO) logistic regression model was fitted to predict presence or absence of MOH. Results Out of 131 participants, 12 % (n=16) developed MOH. Migraine disability score (OR=1.02, 95 % CI: 1.00 to 1.04), intensity of headache (OR=1.49, 95 % CI: 1.03 to 2.15) and headache frequency (OR=1.02, 95 % CI: 1.00 to 1.04) were associated with the onset of MOH adjusting for age and gender. To identify which of the variables predict onset MOH, we used a LASSO regression model, and evaluating the predictive performance of the LASSO-mode (containing the predictors MIDAS score, MIDAS-intensity and –frequency, neuroticism score, time with moderate physical activity, educational level, hours of sleep daily and number of contacts to the headache clinic) in terms of area under the curve (AUC) was weak (apparent AUC=0.62, 95% CI: 0.41-0.82). Conclusion Disability, headache intensity and frequency were associated with the onset of MOH whereas personality and the level of physical activity were not. The multivariable LASSO model based on personality, disability and physical activity is applicable despite moderate study size, however it can be considered as a weak classifier for discriminating between absence and presence of MOH.

The aim of the current study was to compare lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and quality of life (QoL) in poststroke and healthy men. Thirty poststroke men with stroke-related LUTS, and as controls, 96 healthy men participated in this controlled, cross-sectional study. Participants filled in the Danish Prostate Symptom Score (DAN-PSS-1) Questionnaire, the International Index of Erectile Function (IIEF-5), the 36-Item Short Form (SF-36), the Nocturia Quality-of-Life (N-QoL) Questionnaire. In the age group ≤55 years, comparing poststroke men with healthy controls both with LUTS, the results indicated DAN-PSS-1, total score median 13 (4-17) versus 3 (2-6), p = .05; IIEF-5 25 (14-25) versus 24 (23-25), p = .06; SF-12, total score 499 (360-679) versus 695 (644-734), p = .02; and N-QoL 98 (70-100) versus 96 (90-100), p = .65. In the age group >55 years, comparing poststroke men with healthy controls both with LUTS, the results indicated DAN-PSS-1, total score 13 (8-24) versus 5 (2-7), p < .01; IIEF-5 13 (5-20) versus 25 (24-25), p < .01; SF-36, total score 585 (456-718) versus 742 (687-772), p < .01; and N-QoL, total score 81 (66-95) versus 98 (80-100), p < .01. The results demonstrated that in age group above, but not below 55 years, poststroke men with LUTS had significantly higher frequency of severe and bothersome LUTS and ED than the healthy controls with LUTS, while QoL and N-QoL were significantly lower in comparison. It is recommended to identify and assess older poststroke men for LUTS, ED, and QoL.

Abstract Background Idiopathic Intracranial Hypertension (IIH) is characterized by an elevation of intracranial pressure (ICP no identifiable cause. The aetiology remains largely unknown, however observations made in a number of recent clinical studies are increasing the understanding of the disease and now provide the basis for evidence-based treatment strategies. Methods The Embase, CDSR, CENTRAL, DARE and MEDLINE databases were searched up to 1st June 2018. We analyzed randomized controlled trials and systematic reviews that investigate IIH. Results Diagnostic uncertainty, headache morbidity and visual loss are among the highest concerns of clinicians and patients in this disease area. Research in this field is infrequent due to the rarity of the disease and the lack of understanding of the underlying pathology. Conclusions This European Headache Federation consensus paper provides evidence-based recommendations and practical advice on the investigation and management of IIH.

INTRODUCTION:Idiopathic intracranial hypertension (IIH) is a disorder of increased intracranial fluid pressure (ICP) of unknown etiology. This study aims to investigate osmolality of cerebrospinal fluid (CSF) from patients with IIH. METHODS:We prospectively collected CSF from individuals referred on suspicion of IIH from 2011-2013. Subjects included as patients fulfilled Friedman and Jacobson's diagnostic criteria for IIH. Individuals in whom intracranial hypertension was refuted were included as controls. Lumbar puncture with ICP measurement was performed at inclusion and repeated for patients after three months of treatment. Osmolality was measured with a Vapor Pressure Osmometer. RESULTS:We collected 90 CSF samples from 38 newly diagnosed patients and 28 controls. At baseline 27 IIH-samples and at 3 months follow-up 35 IIH-samples were collected from patients. We found no significant differences in osmolality between 1) patients at baseline and controls (p = 0. 86), 2) patients at baseline and after 3 months treatment (p = 0.97), and 3) patients with normalized pressure after 3 months and their baseline values (p = 0.79). Osmolality in individuals with normal ICP from 6-25 cmH2O (n = 41) did not differ significantly from patients with moderately elevated ICP from 26-45 cmH2O (n = 21) (p = 0.86) and patients with high ICP from 46-70 cmH2O (n = 4) (p = 0.32), respectively. There was no correlation between osmolality and ICP, BMI, age and body height, respectively. Mean CSF osmolality was 270 mmol/kg (± 1 SE, 95% confidence interval 267-272) for both patients and controls. CONCLUSIONS:CSF osmolality was normal in patients with IIH, and there was no relation to treatment, ICP, BMI, age and body height. Mean CSF osmolality was 270 mmol/kg and constitutes a reference for future studies. Changes in CSF osmolality are not responsible for development of IIH. Other underlying pathophysiological mechanisms must be searched.