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  • 1
    Online Resource
    Online Resource
    Wiley ; 2023
    In:  Headache: The Journal of Head and Face Pain Vol. 63, No. 9 ( 2023-10), p. 1220-1231
    In: Headache: The Journal of Head and Face Pain, Wiley, Vol. 63, No. 9 ( 2023-10), p. 1220-1231
    Abstract: Caffeine, a non‐selective adenosine receptor (AR) antagonist, is the most consumed psychostimulant in the world. Caffeine has been suggested to regulate cerebrospinal fluid secretion and is known both to alleviate and to trigger headache; however, its effect on the regulation of intracranial pressure (ICP) is not known. Therefore, we aimed to investigate the effects of caffeine on ICP and nociceptive responses. Methods Female Sprague–Dawley rats were implanted with a novel telemetric device for continuous ICP recordings, which allowed for continuous recordings in freely moving rats. A single dose of caffeine (30 or 120 mg/kg intraperitoneally) was given. In a second group (non‐implanted), the acute effects of 30 mg/kg caffeine on periorbital threshold using Von Frey testing and spontaneous behavior were utilized using an automated behavioral registration platform (Laboratory, Animal, Behavior, Observation, Registration and Analysis System) in a randomized cross‐over study. Quantitative polymerase chain reaction and immunofluorescence were used to localize ARs in the choroid plexus. Results A single dose of 30 mg/kg caffeine lowered the ICP by 35% at 165 min after administration (saline: 0.16 ± 0.9 vs caffeine: −1.18 ± 0.9 ΔmmHg, p  = 0.0098) and lasted up to 12 h. Administration of 120 mg/kg caffeine showed a faster onset of decrease in ICP within 15 min by 50% ( p  = 0.0018) and lasted up to 12 h. The periorbital pain thresholds were higher after 1 h (saline: 224.6 ± 15.1 vs caffeine: 289.5 ± 8.7 g, p  = 0.005) and lasted up to 5 h. Caffeine‐treated rats had increased locomotor activity, speed, and changed grooming behavior. Expression of AR 1 was found in the choroid plexus. Conclusions This study demonstrates that caffeine has a lowering effect on ICP as an acute treatment. Interestingly, caffeine acutely caused an increased response in cephalic thresholds supporting hypoalgesic effects. Future studies investigating the beneficial effects of caffeine for elevated ICP are warranted.
    Type of Medium: Online Resource
    ISSN: 0017-8748 , 1526-4610
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 2
    In: BMC Neuroscience, Springer Science and Business Media LLC, Vol. 24, No. 1 ( 2023-11-09)
    Abstract: 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  〈  0.01) and NKCC1 was higher in females compared to males. CAII was lower while CAIII was higher in ES females (p  〈  0.0001). Gene expression of Atp1a1 was lower in ES compared to male (p = 0.0008). Several of these choroidal genes were also significantly different in MET compared to females in ES. Differences in gene expression during the estrus cycle were correlated to serum level of steroid hormones. Protein expression of AQP1 (p = 0.008) and CAII (p = 0.035) was reduced in ES females compared to males. Conclusions This study demonstrates for the first time that expression at CP is sex-dependent and markedly affected by the estrous cycle in female rats. Further, expression was related to hormone levels in serum. This opens a completely new avenue for steroid regulation of the expression of CSF transporters and the close link to the understanding of CSF disorders such as IIH.
    Type of Medium: Online Resource
    ISSN: 1471-2202
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 3
    In: Cephalalgia, SAGE Publications, Vol. 33, No. 15 ( 2013-11), p. 1238-1247
    Abstract: About 10% of cluster headache patients have the chronic form. At least 10% of this chronic group is intractable to or cannot tolerate medical treatment. Open pilot studies suggest that occipital nerve stimulation (ONS) might offer effective prevention in these patients. Controlled neuromodulation studies in treatments inducing paraesthesias have a general problem in blinding. We have introduced a new design in pain neuromodulation by which we think we can overcome this problem. Methods/design We propose a prospective, randomised, double-blind, parallel-group international clinical study in medically intractable, chronic cluster headache patients of high- versus low-amplitude ONS. Primary outcome measure is the mean number of attacks over the last four weeks. After a study period of six months there is an open extension phase of six months. Alongside the randomised trial an economic evaluation study is performed. Discussion The ICON study will show if ONS is an effective preventive therapy for patients suffering medically intractable chronic cluster headache and if there is a difference between high- and low-amplitude stimulation. The innovative design of the study will, for the first time, assess efficacy of ONS in a blinded way.
    Type of Medium: Online Resource
    ISSN: 0333-1024 , 1468-2982
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2013
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  • 4
    In: Headache: The Journal of Head and Face Pain, Wiley, Vol. 60, No. 8 ( 2020-09), p. 1569-1580
    Abstract: Neuronal‐specific enolase (NSE) and protein S100B have gained considerable interest as the markers of CNS injury, glial cell activation, and/or blood‐brain barrier (BBB) disruption. No studies have investigated NSE and S100B in cluster headache (CH), but these biomarkers could contribute to the understanding of CH. Methods Patients with episodic CH in bout (eCHa), in remission (eCHr), and chronic CH (cCH) were included in this randomized, double‐blind, placebo‐controlled, 2‐way cross‐over provocation study carried out at the Danish Headache Center. The primary endpoints included (1) differences of NSE and S100B in between groups (eCHa, eCHr, and cCH) at baseline; (2) differences over time in plasma concentrations of NSE and S100B between patient developing an attack and those who did not; (3) differences in plasma concentrations over time of NSE and S100B between active day and placebo day. Baseline findings were compared to the historical data on migraine patients and healthy controls and presented with means ± SD. Results Nine eCHa, 9 eCHr, and 13 cCH patients completed the study and blood samples from 11 CGRP‐induced CH attacks were obtained. There were no differences in NSE levels between CH groups at baseline, but CH patients in active disease phase had higher levels compared with 32 migraine patients (9.1 ± 2.2 µg/L vs 6.0 ± 2.2 µg/L, P   〈  .0001) and 6 healthy controls (9.1 ± 2.2 µg/L vs 7.3 ± 2.0 µg/L, P  = .007). CGRP‐infusion caused no NSE changes and, but a slight, non‐significant, increase in NSE was seen in patients who reported a CGRP‐induced CH attack (2.39 µg/L, 95% Cl [−0.26, 3.85], P  = .061). At baseline S100B levels in eCHa patients were higher compared to cCH patients (0.06 ± 0.02 µg/L vs 0.04 ± 0.02 µg/L, P  = .018). Infusion of CGRP and CGRP‐induced attacks did not change S100B levels. Apart from induced CH‐attacks no other adverse events were noted. Conclusions At baseline eCHa patients had higher S100B plasma levels than cCH patients and there was a slight, however not significant, NSE increase in response to CGRP‐induced CH attack. Our findings suggest a possible role of an ictal activation of glial cells in CH pathophysiology, but further studies are warranted.
    Type of Medium: Online Resource
    ISSN: 0017-8748 , 1526-4610
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 410130-3
    detail.hit.zdb_id: 2020316-0
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  • 5
    In: JAMA Neurology, American Medical Association (AMA), Vol. 75, No. 10 ( 2018-10-01), p. 1187-
    Type of Medium: Online Resource
    ISSN: 2168-6149
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2018
    detail.hit.zdb_id: 2702023-X
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  • 6
    In: Annals of Neurology, Wiley, Vol. 94, No. 4 ( 2023-10), p. 713-726
    Abstract: The objective of this study was to aggregate data for the first genomewide association study meta‐analysis of cluster headache, to identify genetic risk variants, and gain biological insights. Methods A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse‐variance genomewide association meta‐analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans‐ancestry meta‐analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome‐wide association, fine‐mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses. Results The estimated single nucleotide polymorphism (SNP)‐based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta‐analysis, and one additional locus in the trans‐ethnic meta‐analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk‐taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine. Interpretation This first genomewide association study meta‐analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor. ANN NEUROL 2023;94:713–726
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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    detail.hit.zdb_id: 2037912-2
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  • 7
    In: Headache: The Journal of Head and Face Pain, Wiley, Vol. 62, No. 1 ( 2022-01), p. 26-35
    Abstract: To investigate the safety and efficacy of intranasal ketamine for the treatment of a single cluster headache (CH) attack. Background Acute treatment options for patients with CH who have an insufficient response to oxygen and triptans are limited. Intranasal ketamine has anecdotally been successful in treating a CH attack. Methods We conducted an open‐label pilot study enrolling 23 patients with chronic CH ( International Classification of Headache Disorders , 3rd edition), and of these, 20 patients treated a single CH attack with intranasal ketamine. Under in‐hospital observation, patients received 15 mg of intranasal ketamine every 6 min a maximum of five times. The primary endpoint was a 50% reduction in pain intensity within 15 min after initiating treatment. Results The primary endpoint was not met; 15 min after the first ketamine administration, the mean reduction in pain intensity was 1.1 (95% confidence interval [CI]: −0.6 to 2.7, p  = 0.188) on the numeric rating scale (NRS), equivalent to a 15% reduction in pain intensity. However, 30 min after the first application, the pain intensity was reduced by 59% on an 11‐point NRS (mean difference: 4.3, 95% CI: 2.4–6.2, p   〈  0.001, N  = 16) and 11 out of 16 (69%) scored 4 or below on the NRS. Four patients received rescue medication 15 min after the first ketamine application and were therefore excluded from the analysis at 30 min. Half of the patients preferred ketamine to oxygen and/or sumatriptan injection. No serious adverse events were identified during the trial. Conclusion Intranasal ketamine may be an effective acute treatment for CH at 30 min but should be tested in a larger controlled design. Patients and physicians should be conscious of the abuse potential of ketamine.
    Type of Medium: Online Resource
    ISSN: 0017-8748 , 1526-4610
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 410130-3
    detail.hit.zdb_id: 2020316-0
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  • 8
    Online Resource
    Online Resource
    Wiley ; 2022
    In:  Headache: The Journal of Head and Face Pain Vol. 62, No. 3 ( 2022-03), p. 396-397
    In: Headache: The Journal of Head and Face Pain, Wiley, Vol. 62, No. 3 ( 2022-03), p. 396-397
    Type of Medium: Online Resource
    ISSN: 0017-8748 , 1526-4610
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 410130-3
    detail.hit.zdb_id: 2020316-0
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  • 9
    In: Headache: The Journal of Head and Face Pain, Wiley, Vol. 64, No. 1 ( 2024-01), p. 55-67
    Abstract: To evaluate the feasibility and prophylactic effect of psilocybin as well as its effects on hypothalamic functional connectivity (FC) in patients with chronic cluster headache (CCH). Background CCH is an excruciating and difficult‐to‐treat disorder with incompletely understood pathophysiology, although hypothalamic dysfunction has been implicated. Psilocybin may have beneficial prophylactic effects, but clinical evidence is limited. Methods In this small open‐label clinical trial, 10 patients with CCH were included and maintained headache diaries for 10 weeks. Patients received three doses of peroral psilocybin (0.14 mg/kg) on the first day of weeks five, six, and seven. The first 4 weeks served as baseline and the last 4 weeks as follow‐up. Hypothalamic FC was determined using functional magnetic resonance imaging the day before the first psilocybin dose and 1 week after the last dose. Results The treatment was well tolerated. Attack frequency was reduced by mean (standard deviation) 31% (31) from baseline to follow‐up ( p FWER  = 0.008). One patient experienced 21 weeks of complete remission. Changes in hypothalamic–diencephalic FC correlated negatively with a percent change in attack frequency ( p FWER  = 0.03, R  = −0.81), implicating this neural pathway in treatment response. Conclusion Our results indicate that psilocybin may have prophylactic potential and implicates the hypothalamus in possible treatment response. Further clinical studies are warranted.
    Type of Medium: Online Resource
    ISSN: 0017-8748 , 1526-4610
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2024
    detail.hit.zdb_id: 410130-3
    detail.hit.zdb_id: 2020316-0
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  • 10
    In: Obstetrical & Gynecological Survey, Ovid Technologies (Wolters Kluwer Health), Vol. 77, No. 3 ( 2022-3), p. 133-134
    Abstract: (Abstracted from Nat Rev Endocrinol 2021;17:757–766) Paracetamol, otherwise known as acetaminophen, is the active ingredient in over 600 prescription and nonprescription analgesic and antipyretic medications. Worldwide and in the United States, more than 50% and 65% of pregnant women use acetaminophen, respectively.
    Type of Medium: Online Resource
    ISSN: 1533-9866 , 0029-7828
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 391345-4
    detail.hit.zdb_id: 2043471-6
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