The Journal of Headache and Pain最新文献

{"title":"Amplitude of low-frequency fluctuation after a single-trigger pain in patients with classical trigeminal neuralgia.","authors":"Xiuhong Ge,&nbsp;Luoyu Wang,&nbsp;Lei Pan,&nbsp;Haiqi Ye,&nbsp;Xiaofen Zhu,&nbsp;Sandra Fan,&nbsp;Qi Feng,&nbsp;Wenhua Yu,&nbsp;Zhongxiang Ding","doi":"10.1186/s10194-022-01488-8","DOIUrl":"https://doi.org/10.1186/s10194-022-01488-8","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore the central mechanism of classical trigeminal neuralgia (CTN) by analyzing the static amplitude of low-frequency fluctuation (sALFF) and dynamic amplitude of low-frequency fluctuation (dALFF) in patients with CTN before and after a single-trigger pain.</p><p><strong>Methods: </strong>This study included 48 patients (37 women and 11 men, age 55.65 ± 11.41 years) with CTN. All participants underwent 3D-T1WI and three times resting-state functional magnetic resonance imaging. The images were taken before stimulating the trigger zone (baseline), within 5 s after stimulating the trigger zone (triggering-5 s), and in the 30th minute after stimulating the trigger zone (triggering-30 min). The differences between the three measurements were analyzed using a repeated-measures analysis of variance.</p><p><strong>Results: </strong>The sALFF values of the bilateral middle occipital gyrus and right cuneus gradually increased, and the values of the left posterior cingulum gyrus and bilateral superior frontal gyrus gradually decreased in triggering-5 s and triggering-30 min. The values of the right middle temporal gyrus and right thalamus decreased in triggering-5 s and subsequently increased in triggering-30 min. The sALFF values of the left superior temporal gyrus increased in triggering-5 s and then decreased in triggering-30 min. The dALFF values of the right fusiform gyrus, bilateral lingual gyrus, left middle temporal gyrus, and right cuneus gyrus gradually increased in both triggering-5 s and triggering-30 min.</p><p><strong>Conclusions: </strong>The sALFF and dALFF values changed differently in multiple brain regions in triggering-5 s and triggering-30 min of CTN patients after a single trigger of pain, and dALFF is complementary to sALFF. The results might help explore the therapeutic targets for relieving pain and improving the quality of life of patients with CTN.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"117"},"PeriodicalIF":7.4,"publicationDate":"2022-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9461270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33451071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Applying a biopsychosocial model to migraine: rationale and clinical implications.","authors":"Chiara Rosignoli,&nbsp;Rafaele Ornello,&nbsp;Agnese Onofri,&nbsp;Valeria Caponnetto,&nbsp;Licia Grazzi,&nbsp;Alberto Raggi,&nbsp;Matilde Leonardi,&nbsp;Simona Sacco","doi":"10.1186/s10194-022-01487-9","DOIUrl":"https://doi.org/10.1186/s10194-022-01487-9","url":null,"abstract":"","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"116"},"PeriodicalIF":7.4,"publicationDate":"2022-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9450348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33447959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantity changes in acute headache medication use among patients with chronic migraine treated with eptinezumab: subanalysis of the PROMISE-2 study.","authors":"Robert P Cowan,&nbsp;Michael J Marmura,&nbsp;Hans-Christoph Diener,&nbsp;Amaal J Starling,&nbsp;Jack Schim,&nbsp;Joe Hirman,&nbsp;Thomas Brevig,&nbsp;Roger Cady","doi":"10.1186/s10194-022-01482-0","DOIUrl":"https://doi.org/10.1186/s10194-022-01482-0","url":null,"abstract":"<p><strong>Background: </strong>Patients with chronic migraine (CM) treated with eptinezumab in the PROMISE-2 trial achieved greater reductions in migraine and headache frequency, impact, and acute headache medication (AHM) use than did patients who received placebo. This post hoc analysis examines relationships between headache frequency reductions and changes in AHM use in patients in PROMISE-2.</p><p><strong>Methods: </strong>PROMISE-2 was a double-blind, placebo-controlled trial conducted in adults with CM. Patients were randomized to eptinezumab 100 mg, 300 mg, or placebo, administered intravenously once every 12 weeks for up to two doses. Patients recorded headache/AHM information daily and for each event in an electronic diary; data from all days with daily reports were included. Shifts in headache frequency and AHM use were assessed in the three populations: total CM population, patients with CM and medication-overuse headache (MOH), and patients with CM and MOH who were ≥ 50% responders during treatment (response over weeks 1-24).</p><p><strong>Results: </strong>A total of 1072 adults with CM received treatment (eptinezumab, n = 706; placebo, n = 366). Mean baseline headache frequency was 20.5 days; mean baseline AHM days was 13.4; 431 patients had MOH, of which 225 (52.2%) experienced ≥50% response over weeks 1-24. Relative to baseline, the proportion of days with both headache and AHM use decreased 25.1% (eptinezumab) versus 17.0% (placebo) in the total population (N = 1072), 29.2% versus 18.4% in the MOH subpopulation (n = 431), and 38.3% versus 31.5% in the CM with MOH population with ≥50% response subgroup (n = 225) during weeks 1-24. The proportion of days with headache and triptan use decreased 9.1% (eptinezumab) versus 5.8% (placebo), 11.8% versus 7.2%, and 14.5% versus 12.6%, respectively. Reductions in other AHM types were smaller.</p><p><strong>Conclusions: </strong>In this post hoc analysis, eptinezumab use in patients with CM was associated with greater decreases in days with headache with AHM overall and with triptans in particular. The magnitude of effect was greater in the subgroup of CM patients with MOH and ≥ 50% response.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT02974153 . Eptinezumab reduces headache frequency and acute medication use in patients with chronic migraine.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"115"},"PeriodicalIF":7.4,"publicationDate":"2022-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9446734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40354735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in utilization and costs of migraine medications, 2017-2020.","authors":"Jennifer L Nguyen,&nbsp;Kiraat Munshi,&nbsp;Samuel K Peasah,&nbsp;Elizabeth C S Swart,&nbsp;Monal Kohli,&nbsp;Rochelle Henderson,&nbsp;Chester B Good","doi":"10.1186/s10194-022-01476-y","DOIUrl":"https://doi.org/10.1186/s10194-022-01476-y","url":null,"abstract":"<p><strong>Objective: </strong>This study examines changes in utilization and costs trends associated with migraine medications.</p><p><strong>Background: </strong>Migraine attacks are a burden to many patients. There are many pharmacotherapy options available with newer migraine drug classes entering the market in the past decade. Little is known about the use, associated costs, and the impact of the newer agents.</p><p><strong>Methods: </strong>This retrospective, cross-sectional study examined 2017-2020 administrative claims from a large national pharmacy benefits manager. Patients aged ≥ 18 years enrolled in commercial, Medicare, Medicaid, or health insurance exchange insurance plans who filled ≥ 2 prescription claims for triptans, ergotamines, isometheptenes, gepants, ditans, and CGRP mABs were included. A two-sample t-test was conducted to estimate whether differences in mean utilization and costs between 2017 and 2020 were statistically significant for migraine drug classes, except for CGRP mABs, which were estimated between 2018 and 2020.</p><p><strong>Results: </strong>The sample ranged from 161,369 (2017) to 240,330 (2020) patients. 84.5% (n = 203,110; 2020) of patients were women. The number of 30-day adjusted prescription fills for prophylaxis remained stable over the four-year period, except for CGRP mABs, which increased from 0.5% (n = 0.007; 2018) to 5.3% (n = 0.075; 2020). Antiepileptics, antidepressants and beta blockers were the most common prophylaxes, while triptans, non-steroidal anti-inflammatory drugs/non-narcotic analgesics and opioids were the most common treatments utilized. CGRP mABs were the most expensive, while utilization of triptans were the highest. CGRP mABs had the largest increase in utilization (177.5%) and costs (166.3%) PPPM in 2020 ($291.17) compared to 2018 ($109.35), the year they were first available (p < 0.001). Between 2018 and 2020, costs increased overall and for commercial and Medicare enrollees, but remained unchanged for Medicaid and HIX members.</p><p><strong>Conclusion: </strong>Our study demonstrates a shift in migraine medication utilization from 2017-2020, where increased use of CGRP mABs had a significant contribution to increased costs. These increased pharmacy costs must be weighed against the improved tolerability of these agents likely resulting in other healthcare and indirect cost savings.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"111"},"PeriodicalIF":7.4,"publicationDate":"2022-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33441358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioral and psychological factors in individuals with migraine without psychiatric comorbidities.","authors":"Francesca Pistoia,&nbsp;Federico Salfi,&nbsp;Gennaro Saporito,&nbsp;Raffaele Ornello,&nbsp;Ilaria Frattale,&nbsp;Giulia D'Aurizio,&nbsp;Daniela Tempesta,&nbsp;Michele Ferrara,&nbsp;Simona Sacco","doi":"10.1186/s10194-022-01485-x","DOIUrl":"https://doi.org/10.1186/s10194-022-01485-x","url":null,"abstract":"<p><strong>Background: </strong>It is well known that the course of migraine is influenced by comorbidities and that individual psychological characteristics may impact on the disease. Proper identification of psychological factors that are relevant to migraine is important to improve non-pharmacological management. This study aimed at investigating the relationship between psychological factors and migraine in subjects free of psychiatric comorbidities.</p><p><strong>Methods: </strong>A sample of women with episodic (EM) and chronic migraine (CM) without history of psychiatric comorbidities were included in this cross-sectional study. The study also included female healthy controls (HC) without migraine or other primary headaches. We evaluated sleep, anxiety, depression, intolerance of uncertainty, decision making style and tendence to pain catastrophizing by validated self-report questionnaires or scales. Comparisons among groups were performed using ANOVA and Bonferroni post-hoc tests. Statistical significance was set at p < 0.05.</p><p><strong>Results: </strong>A total of 65 women with EM (mean age ± SD, 43.9 ± 7.2), 65 women with CM (47.7 ± 8.5), and 65 HC (43.5 ± 9.0) were evaluated. In sleep domains, CM patients reported poorer overall sleep quality, more severe sleep disturbances, greater sleep medication use, higher daytime dysfunction, and more severe insomnia symptoms than HC. EM group showed better sleep quality, lower sleep disturbances and sleep medication use than CM. On the other hand, the analysis highlighted more severe daytime dysfunction and insomnia symptoms in EM patients compared to HC. In anxiety and mood domains, CM showed greater trait anxiety and a higher level of general anxiety sensitivity than HC. Specifically, CM participants were more afraid of somatic and cognitive anxiety symptoms than HC. No difference in depression severity emerged. Finally, CM reported a higher pain catastrophizing tendency, more severe feeling of helplessness, and more substantial ruminative thinking than EM and HC, whilst EM participants reported higher scores in the three above-mentioned dimensions than HC. The three groups showed similar decision-making styles, intolerance of uncertainty, and strategies for coping with uncertainty.</p><p><strong>Conclusions: </strong>Even in individuals without psychiatric comorbidities, specific behavioral and psychological factors are associated with migraine, especially in its chronic form. Proper identification of those factors is important to improve management of migraine through non-pharmacological strategies.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"110"},"PeriodicalIF":7.4,"publicationDate":"2022-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40645175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional improvement in children and adolescents with primary headache after an interdisciplinary multimodal therapy program: the DreKiP study.","authors":"Hanna Sobe,&nbsp;Matthias Richter,&nbsp;Reinhard Berner,&nbsp;Maja von der Hagen,&nbsp;Antje Hähner,&nbsp;Ingo Röder,&nbsp;Thea Koch,&nbsp;Rainer Sabatowski,&nbsp;Anna Klimova,&nbsp;Gudrun Gossrau","doi":"10.1186/s10194-022-01481-1","DOIUrl":"https://doi.org/10.1186/s10194-022-01481-1","url":null,"abstract":"<p><strong>Background: </strong>More than 2/3 of children and adolescents in Germany regularly suffer from headaches. Headache-related limitations in everyday life, school drop-out and educational impairment are common. Structured therapy programs for young headache patients are widely missing.</p><p><strong>Methods: </strong>One hundred eleven patients with frequent migraine and/or tension type headache were treated in a 15 hour group program in afternoons, parallel with school, parents received 7 hours of therapy. At the beginning of the program (T0), 6 (T1) and 12 months (T2) after completion, data on headache related disability (PedMidas), headache frequency, intensity, and pediatric pain disability score (PPDI) were prospectively collected to investigate the effects of the therapy.</p><p><strong>Results: </strong>Seventy-five patients (9-19 years, median = 14; 66.7% female) and their parents provided patient reported outcome measures showing at T1 (65 patients) and T2 (47 patients) reduced headache frequency (last 3 months headache days median T0: 30 days; T1: 18 days, reduction of median 12 days since T0; T2: 13 days, reduction of median 17 days since T0). Linear mixed models revealed significant reduction (T0/T1 p = 0,002; T0/T2 p = 0,001). Reduced headache disability has been reported at T1 and T2 (PedMidas median T0 = 30, T1 = 15, T2 = 7; p < 0,001, p < 0,001 respectively). Follow up data of a subgroup of patients 24 months after the treatment point to sustainable effects.</p><p><strong>Conclusions: </strong>The interdisciplinary multimodal headache therapy program DreKiP reduces headache frequency and headache related disability significantly 6-12 months following its completion.</p><p><strong>Trial registration: </strong>DRKS00027523, retrospectively registered.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"109"},"PeriodicalIF":7.4,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40443113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased risk of all-cause, Alzheimer's, and vascular dementia in adults with migraine in Korea: a population-based cohort study.","authors":"Kyungduk Hurh,&nbsp;Sung Hoon Jeong,&nbsp;Seung Hoon Kim,&nbsp;Suk-Yong Jang,&nbsp;Eun-Cheol Park,&nbsp;Sung-In Jang","doi":"10.1186/s10194-022-01484-y","DOIUrl":"https://doi.org/10.1186/s10194-022-01484-y","url":null,"abstract":"<p><strong>Background: </strong>Studies investigating the association between migraine and dementia have reported inconsistent findings. This study aimed to evaluate whether patients with migraine have an increased risk of dementia compared to individuals without migraine.</p><p><strong>Methods: </strong>We obtained data from the 2002-2019 Korean National Health Insurance Health Screening Cohort. Non-migraine controls were selected using a 1:1 risk-set matching with a time-dependent propensity score. The main outcome was the development of all-cause dementia, and the secondary outcome was the development of each cause of dementia (Alzheimer's, vascular, mixed or other specified, and unspecified dementia). The incidence rate of dementia was calculated using Poisson regression, and the association between migraine and dementia was evaluated using Cox proportional hazards regression.</p><p><strong>Results: </strong>Among 88,390 participants, 66.1% were female, and the mean baseline age was 55.3 ± 9.4 years. During the study period, dementia cases were identified in 4,800 of the 44,195 patients with migraine and 3,757 of the 44,915 matched controls. The incidence rate of dementia was 139.6 (95% confidence interval [CI], 135.7-143.5) and 107.7 (95% CI, 104.3-111.1) cases per 10,000 person-years in patients with migraine and matched controls, respectively. Patients with migraine had a 1.30 (hazard ratio [HR], 1.30; 95% CI, 1.25-1.35), 1.29 (HR, 1.29; 95% CI, 1.23-1.35), 1.35 (HR, 1.35; 95% CI, 1.19-1.54), 1.36 (HR, 1.36; 95% CI, 1.00-1.83), and 1.30 (HR, 1.30; 95% CI, 1.17-1.45) times higher risk of developing all-cause dementia, Alzheimer's dementia, vascular dementia, mixed or other specified dementias, and unspecified dementia than their matched controls, respectively.</p><p><strong>Conclusion: </strong>Our results suggest that migraine is associated with an increased risk of subsequent dementia. Further research is warranted to confirm these findings and to reveal the underlying mechanisms.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"108"},"PeriodicalIF":7.4,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40439498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insular functional connectivity in migraine with aura.","authors":"Cédric Gollion,&nbsp;Fleur Lerebours,&nbsp;Federico Nemmi,&nbsp;Germain Arribarat,&nbsp;Fabrice Bonneville,&nbsp;Vincent Larrue,&nbsp;Patrice Péran","doi":"10.1186/s10194-022-01473-1","DOIUrl":"https://doi.org/10.1186/s10194-022-01473-1","url":null,"abstract":"<p><strong>Introduction: </strong>Insula plays an integrating role in sensory, affective, emotional, cognitive and autonomic functions in migraine, especially in migraine with aura (MA). Insula is functionally divided into 3 subregions, the dorsoanterior, the ventroanterior and the posterior insula respectively related to cognition, emotion, and somatosensory functions. This study aimed at investigating functional connectivity of insula subregions in MA.</p><p><strong>Methods: </strong>Twenty-one interictal patients with MA were compared to 18 healthy controls (HC) and 12 interictal patients with migraine without aura (MO) and were scanned with functional MRI during the resting state. Functional coupling of the insula was comprehensively tested with 12 seeds located in the right and left, dorsal, middle, ventral, anterior and posterior insula, by using a seed-to-voxel analysis.</p><p><strong>Results: </strong>Seed-to-voxel analysis revealed, in MA, a strong functional coupling of the right and left antero-dorsal insula with clusters located in the upper cerebellum. The overlap of these cerebellar clusters corresponded to the vermis VI. These functional couplings were not correlated to duration of MA, frequency of MA attacks nor time since last MA attack, and were not found in MO.</p><p><strong>Discussion: </strong>The anterior insula and superior cerebellum, including vermis VI, are components of the central Autonomic Nervous System (ANS) network. As these regions are involved in the control of cardiovascular parasympathetic tone, we hypothesize that this connectivity may reflect the cardiovascular features of MA.</p><p><strong>Conclusion: </strong>The anterior dorsal insula is connected with vermis VI in MA patients in the resting state. This connectivity may reflect the cardiovascular features of MA.</p><p><strong>Trial registration: </strong>NCT02708797.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"106"},"PeriodicalIF":7.4,"publicationDate":"2022-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40708124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical spreading depression can be triggered by sensory stimulation in primed wild type mouse brain: a mechanistic insight to migraine aura generation.","authors":"Sahin Hanalioglu,&nbsp;Aslihan Taskiran-Sag,&nbsp;Hulya Karatas,&nbsp;Buket Donmez-Demir,&nbsp;Sinem Yilmaz-Ozcan,&nbsp;Emine Eren-Kocak,&nbsp;Yasemin Gursoy-Ozdemir,&nbsp;Turgay Dalkara","doi":"10.1186/s10194-022-01474-0","DOIUrl":"https://doi.org/10.1186/s10194-022-01474-0","url":null,"abstract":"<p><strong>Background: </strong>Unlike the spontaneously appearing aura in migraineurs, experimentally, cortical spreading depression (CSD), the neurophysiological correlate of aura is induced by non-physiological stimuli. Consequently, neural mechanisms involved in spontaneous CSD generation, which may provide insight into how migraine starts in an otherwise healthy brain, remain largely unclear. We hypothesized that CSD can be physiologically induced by sensory stimulation in primed mouse brain.</p><p><strong>Methods: </strong>Cortex was made susceptible to CSD with partial inhibition of Na⁺/K⁺-ATPase by epidural application of a low concentration of Na⁺/K⁺-ATPase blocker ouabain, allowing longer than 30-min intervals between CSDs or by knocking-down α2 subunit of Na⁺/K⁺-ATPase, which is crucial for K⁺ and glutamate re-uptake, with shRNA. Stimulation-triggered CSDs and extracellular K⁺ changes were monitored in vivo electrophysiologically and a K⁺-sensitive fluoroprobe (IPG-4), respectively.</p><p><strong>Results: </strong>After priming with ouabain, photic stimulation significantly increased the CSD incidence compared with non-stimulated animals (44.0 vs. 4.9%, p < 0.001). Whisker stimulation also significantly increased the CSD incidence, albeit less effectively (14.9 vs. 2.4%, p = 0.02). Knocking-down Na⁺/K⁺-ATPase (50% decrease in mRNA) lowered the CSD threshold in all mice tested with KCl but triggered CSDs in 14.3% and 16.7% of mice with photic and whisker stimulation, respectively. Confirming Na⁺/K⁺-ATPase hypofunction, extracellular K⁺ significantly rose during sensory stimulation after ouabain or shRNA treatment unlike controls. In line with the higher CSD susceptibility observed, K⁺ rise was more prominent after ouabain. To gain insight to preventive mechanisms reducing the probability of stimulus-evoked CSDs, we applied an A1-receptor antagonist (DPCPX) to the occipital cortex, because adenosine formed during stimulation from ATP can reduce CSD susceptibility. DPCPX induced spontaneous CSDs but only small-DC shifts along with suppression of EEG spikes during photic stimulation, suggesting that the inhibition co-activated with sensory stimulation could limit CSD ignition when K⁺ uptake was not sufficiently suppressed as with ouabain.</p><p><strong>Conclusions: </strong>Normal brain is well protected against CSD generation. For CSD to be ignited under physiological conditions, priming and predisposing factors are required as seen in migraine patients. Intense sensory stimulation has potential to trigger CSD when co-existing conditions bring extracellular K⁺ and glutamate concentrations over CSD-ignition threshold and stimulation-evoked inhibitory mechanisms are overcome.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"107"},"PeriodicalIF":7.4,"publicationDate":"2022-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9392331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40640139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent headache after first-ever ischemic stroke: clinical characteristics and factors associated with its development.","authors":"Elena R Lebedeva,&nbsp;Anton V Ushenin,&nbsp;Natalia M Gurary,&nbsp;Denis V Gilev,&nbsp;Nadezda V Kislyak,&nbsp;Jes Olesen","doi":"10.1186/s10194-022-01479-9","DOIUrl":"https://doi.org/10.1186/s10194-022-01479-9","url":null,"abstract":"<p><strong>Background: </strong>It is poorly described how often headache attributed to stroke continues for more than 3 months, i.e. fulfils the criteria for persistent headache attributed to ischemic stroke. Our aims were: 1) to determine the incidence of persistent headache attributed to past first-ever ischemic stroke (International headache society categories 6.1.1.2); 2) to describe their characteristics and acute treatment; 3) to analyse the prevalence of medication overuse headache in patients with persistent headache after stroke; 4) to evaluate factors associated with the development of persistent headache after stroke.</p><p><strong>Methods: </strong>The study population consisted of 550 patients (mean age 63.1, 54% males) with first-ever ischemic stroke, among them 529 patients were followed up at least three months after stroke. Standardized semi-structured interview forms were used to evaluate these headaches during professional face-to-face interviews at stroke onset and telephone interviews at 3 months.</p><p><strong>Results: </strong>At three months, 61 patients (30 women and 31 men, the mean age 60.0) of 529 (11.5%) follow-up patients had a headache after stroke: 34 had a new type of headache, 21 had a headache with altered characteristics and 6 patients had a headache without any changes. Therefore 55 (10.4%) patients had a persistent headache attributed to ischemic stroke. Their clinical features included: less severity of accompanying symptoms, slowly decreasing frequency and development of medication overuse headache in one-third of the patients. The following factors were associated with these headaches: lack of sleep (29.1%, p = 0.009; OR 2.3; 95% CI 1.2-4.3), infarct in cerebellum (18.2%, p = 0.003; OR 3.0; 95% CI 1.4-6.6), stroke of undetermined etiology (50.9%, p = 0.003; OR 2.3; 95% CI 1.3-4.1), less than 8 points by NIHSS score (90.9%, p = 0.007; OR 3.4; 95% CI 1.4-8.6) and low prevalence of large-artery atherosclerosis (12.7%, p = 0.006; OR 0.3; 95% CI 0.2-0.80).</p><p><strong>Conclusion: </strong>Persistent headache attributed to ischemic stroke is not rare and frequently leads to medication overuse. The problem is often neglected because of other serious consequences of stroke but actually, it has a considerable impact on quality of life. It should be a focus of interest in the follow-up of stroke patients.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"103"},"PeriodicalIF":7.4,"publicationDate":"2022-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9382765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40621151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}