Cephalalgia : an international journal of headache最新文献

{"title":"Migraine therapeutics differentially modulate the CGRP pathway.","authors":"Minoti Bhakta,&nbsp;Trang Vuong,&nbsp;Tetsuya Taura,&nbsp;David S Wilson,&nbsp;Jennifer R Stratton,&nbsp;Kimberly D Mackenzie","doi":"10.1177/0333102420983282","DOIUrl":"https://doi.org/10.1177/0333102420983282","url":null,"abstract":"<p><strong>Background: </strong>The clinical efficacy of migraine therapeutic agents directed towards the calcitonin-gene related peptide (CGRP) pathway has confirmed the key role of this axis in migraine pathogenesis. Three antibodies against CGRP - fremanezumab, galcanezumab and eptinezumab - and one antibody against the CGRP receptor, erenumab, are clinically approved therapeutics for the prevention of migraine. In addition, two small molecule CGRP receptor antagonists, ubrogepant and rimegepant, are approved for acute migraine treatment. Targeting either the CGRP ligand or receptor is efficacious for migraine treatment; however, a comparison of the mechanism of action of these therapeutic agents is lacking in the literature.</p><p><strong>Methods: </strong>To gain insights into the potential differences between these CGRP pathway therapeutics, we compared the effect of a CGRP ligand antibody (fremanezumab), a CGRP receptor antibody (erenumab) and a CGRP receptor small molecule antagonist (telcagepant) using a combination of binding, functional and imaging assays.</p><p><strong>Results: </strong>Erenumab and telcagepant antagonized CGRP, adrenomedullin and intermedin cAMP signaling at the canonical human CGRP receptor. In contrast, fremanezumab only antagonized CGRP-induced cAMP signaling at the human CGRP receptor. In addition, erenumab, but not fremanezumab, bound and internalized at the canonical human CGRP receptor. Interestingly, erenumab also bound and internalized at the human AMY₁ receptor, a CGRP receptor family member. Both erenumab and telcagepant antagonized amylin-induced cAMP signaling at the AMY₁ receptor while fremanezumab did not affect amylin responses.</p><p><strong>Conclusion: </strong>The therapeutic effect of agents targeting the CGRP ligand versus receptor for migraine prevention (antibodies) or acute treatment (gepants) may involve distinct mechanisms of action. These findings suggest that differing mechanisms could affect efficacy, safety, and/or tolerability in migraine patients.</p>","PeriodicalId":195255,"journal":{"name":"Cephalalgia : an international journal of headache","volume":" ","pages":"499-514"},"PeriodicalIF":4.9,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0333102420983282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25401335","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":"Responses of spinal trigeminal neurons to noxious stimulation of paranasal cavities - a rat model of rhinosinusitis headache.","authors":"Michael Koch,&nbsp;Julika Sertel-Nakajima,&nbsp;Karl Messlinger","doi":"10.1177/0333102420970467","DOIUrl":"https://doi.org/10.1177/0333102420970467","url":null,"abstract":"<p><strong>Background: </strong>The pathophysiology of headaches associated with rhinosinusitis is poorly known. Since the generation of headaches is thought to be linked to the activation of intracranial afferents, we used an animal model to characterise spinal trigeminal neurons with nociceptive input from the dura mater and paranasal sinuses.</p><p><strong>Methods: </strong>In isoflurane anaesthetised rats, extracellular recordings were made from neurons in the spinal trigeminal nucleus with afferent input from the exposed frontal dura mater. Dural and facial receptive fields were mapped and the paranasal cavities below the thinned nasal bone were stimulated by sequential application of synthetic interstitial fluid, 40 mM potassium chloride, 100 µM bradykinin, 1% ethanol (vehicle) and 100 µm capsaicin.</p><p><strong>Results: </strong>Twenty-five neurons with input from the frontal dura mater and responses to chemical stimulation of the paranasal cavities were identified. Some of these neurons had additional receptive fields in the parietal dura, most of them in the face. The administration of synthetic interstitial fluid, potassium chloride and ethanol was not followed by significant changes in activity, but bradykinin provoked a cluster of action potentials in 20 and capsaicin in 23 neurons.</p><p><strong>Conclusion: </strong>Specific spinal trigeminal neurons with afferent input from the cranial dura mater respond to stimulation of paranasal cavities with noxious agents like bradykinin and capsaicin. This pattern of activation may be due to convergent input of trigeminal afferents that innervate dura mater and nasal cavities and project to spinal trigeminal neurons, which could explain the genesis of headaches due to disorders of paranasal sinuses.</p>","PeriodicalId":195255,"journal":{"name":"Cephalalgia : an international journal of headache","volume":" ","pages":"535-545"},"PeriodicalIF":4.9,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0333102420970467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38612978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"It is time to consider even chronic migraine as a real chronic disease.","authors":"Marta Altieri,&nbsp;Mariangela Fratino,&nbsp;Ilaria Maestrini,&nbsp;Marta Puma,&nbsp;Vittorio Di Piero","doi":"10.1177/0333102420953108","DOIUrl":"https://doi.org/10.1177/0333102420953108","url":null,"abstract":"To the Editor: Due to the recent coronavirus disease 2019 (COVID-19) pandemic infection, on 10 March 2020 Italy entered the lockdown and non-essential adult elective medical and surgical procedures were stopped. According to these restrictions, clinical activities at our tertiary headache center in Rome were stopped until 4 May. Starting from June, the outpatient clinic reopened for urgent visits, and our local Health Authority rescheduled the visits cancelled during the lockdown. They settled priority criteria based on the risk attributed to each pathology, ranging from high to minimal risk. On the basis of this six-point scale of risk attribution, headache appears to be at “minimal risk” and therefore visits are rescheduled to a much later date, practically months after what was previously planned (1). In order to investigate the impact of COVID-19 and lockdown on chronic migraine patients (2), we developed a 36-item self-report questionnaire divided into five domains. Each item was scored on a Likert scale ranging from 0–4: Never, 0; rarely, 1; sometimes, 2; often, 3; almost always, 4. In the first domain, we evaluated any concerns about migraine and drug therapy in relation to COVID-19 pandemia (score 0–28); in the second, about family and personal caregiving (score 0–16); in the third, about working activity (score 0–16); in the fourth, both general (4 G; score 0–32) and disease-related (4 DR; score 0–32) emotions during the lockdown; in the fifth, future expectations concerning health status, social life and working activity (score 0–20). We evaluated both a total score (0–144) and the impact on patients of each domain (none, mild and high impact), using cut-off values (see Table 1). A hundred questionnaires were emailed to the most recent consecutive chronic migraine patients visited at our headache center. Sixty-five patients replied (48 F, age 46.1 12.8 years, education 14 4 years) from 15 March to 4 May. Among them, 33 were married and lived with an average of two people per family. All patients were taking prophylactic therapy.","PeriodicalId":195255,"journal":{"name":"Cephalalgia : an international journal of headache","volume":" ","pages":"631-633"},"PeriodicalIF":4.9,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0333102420953108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38302995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health technology assessment for the acute and preventive treatment of migraine: A position statement of the International Headache Society.","authors":"Hans Christoph Diener,&nbsp;Messoud Ashina,&nbsp;Isabelle Durand-Zaleski,&nbsp;Tobias Kurth,&nbsp;Michel Lantéri-Minet,&nbsp;Richard B Lipton,&nbsp;Daniel A Ollendorf,&nbsp;Patricia Pozo-Rosich,&nbsp;Cristina Tassorelli,&nbsp;Gisela Terwindt","doi":"10.1177/0333102421989247","DOIUrl":"https://doi.org/10.1177/0333102421989247","url":null,"abstract":"<p><p>The Clinical Trials Subcommittee of the International Headache Society presents the first Health Technology Assessment for the Acute Treatment of Migraine Attacks and Prevention of Migraine. Health technology assessments are systematic evaluations of the properties, effects, and consequences of healthcare technologies; this position statement is designed to inform decision makers about access to and reimbursement for medications and devices for the acute and preventive treatment of migraine. This position statement extends beyond the already available guidelines on randomized controlled trials for migraine to incorporate real-world evidence and a synthetic approach for considering multiple data sources and modelling methods when assessing the value of migraine treatments.</p>","PeriodicalId":195255,"journal":{"name":"Cephalalgia : an international journal of headache","volume":" ","pages":"279-293"},"PeriodicalIF":4.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0333102421989247","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38840611","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":"Polypharmacy and comorbidities during pregnancy in a cohort of women with migraine.","authors":"Mollie E Wood,&nbsp;Rebecca C Burch,&nbsp;Sonia Hernandez-Diaz","doi":"10.1177/0333102420975394","DOIUrl":"https://doi.org/10.1177/0333102420975394","url":null,"abstract":"<p><strong>Objective: </strong>To describe longitudinal patterns of medication use throughout pregnancy in women with migraine.</p><p><strong>Methods: </strong>We used the IBM MarketScan healthcare claims database in the US to create a cohort of pregnancies enrolled between 2011-2015 resulting in live or stillbirth. Migraine headache was identified based on ICD-9-CM diagnosis codes or procedure codes recorded in clinical encounters. Outcomes were patterns of prescriptions filled for medications that may be used to prevent migraine (antiepileptics, antihypertensives, antidepressants) or treat acute episodes (opioids, triptans, acetaminophen) and of other comorbid conditions (hypertension, psychiatric diagnoses, epilepsy). We used group-based multi-trajectory models to cluster women into similar longitudinal patterns of prescription fills.</p><p><strong>Results: </strong>Of 859,501 pregnancies, 8168 had migraine. Within migraineurs, before pregnancy, the most commonly filled prescription was for a triptan (43.2%), followed by opioids (26.7%), acetaminophen (26.2%), antidepressants (24.9%), antiepileptics (18.6%) and antihypertensives (12.3%). Antiepileptics, antidepressants, and triptans were frequently discontinued early in pregnancy with few new users, while antihypertensives were discontinued by some users, but continued or initiated by a minority of users late in pregnancy. Opioids and acetaminophen were used intermittently throughout pregnancy. Comorbidities included hypertension (10.8%), epilepsy (4.7%), depression (14.0%), and anxiety (15.6%). Polypharmacy involving both preventive and acute medications was most common before pregnancy (31.4%) and declined in first trimester (14.7%). In all, 25.9% of women filled prescriptions for two or more acute medications before pregnancy.</p><p><strong>Conclusions: </strong>Medication use patterns during pregnancy for women with migraine are complex. Patterns of polypharmacy and comorbidity during pregnancy highlight an under-studied area relevant for maternal and child health outcomes.</p>","PeriodicalId":195255,"journal":{"name":"Cephalalgia : an international journal of headache","volume":" ","pages":"392-403"},"PeriodicalIF":4.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0333102420975394","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38672712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atrial fibrillation and migraine with aura in young adults with ischemic stroke.","authors":"Cédric Gollion,&nbsp;Julie Gazagnes,&nbsp;Vincent Fabry,&nbsp;Marianne Barbieux-Guillot,&nbsp;Fleur Lerebours,&nbsp;Vincent Larrue","doi":"10.1177/0333102420970880","DOIUrl":"https://doi.org/10.1177/0333102420970880","url":null,"abstract":"<p><strong>Background: </strong>Migraine is associated with an increased risk of ischemic stroke. The associations are stronger in migraine with aura than in migraine without aura, in women than in men, and in younger subjects. However, the mechanisms by which migraine might increase the risk of ischemic stroke are debated.</p><p><strong>Methods: </strong>We analysed the associations between migraine without aura and migraine with aura and the causes of ischemic stroke in patients aged 18-54 years treated consecutively in a university hospital stroke center.</p><p><strong>Results: </strong>A total of 339 patients (mean/SD age 43.8/8.8 years, 62.83% male) were included. Migraine with aura was diagnosed in 58 patients, and migraine without aura in 54 patients. Patients with migraine with aura were younger and had fewer traditional cardiovascular risk factors than patients with no migraine. Migraine with aura was strongly associated with atrial fibrillation (odds ratio, 5.08; 95% confidence interval, 1.24-21.92; <i>p</i> = 0.011) and negatively associated with atherosclerosis (odds ratio, 0.29; 95% confidence interval, 0.05-0.97; <i>p</i> = 0.033) and small vessel disease (odds ratio, 0.13; 95% confidence interval, 0.00-0.87; <i>p</i> = 0.022). No other cause of stroke was significantly associated with migraine. The most common cause of stroke was atherosclerosis in no-migraine patients, dissection in migraine without aura patients and patent foramen ovale in migraine with aura patients. Atrial fibrillation was, together with dissection, the second leading cause of stroke in migraine with aura patients, accounting for 10.34% of cases in this subgroup.</p><p><strong>Conclusion: </strong>We showed that atrial fibrillation was a common cause of ischemic stroke in young adults with migraine with aura.</p>","PeriodicalId":195255,"journal":{"name":"Cephalalgia : an international journal of headache","volume":" ","pages":"375-382"},"PeriodicalIF":4.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0333102420970880","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38612658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel, injury-free rodent model of vulnerability for assessment of acute and preventive therapies reveals temporal contributions of CGRP-receptor activation in migraine-like pain.","authors":"Caroline M Kopruszinski,&nbsp;Edita Navratilova,&nbsp;Juliana Swiokla,&nbsp;David W Dodick,&nbsp;Iain P Chessell,&nbsp;Frank Porreca","doi":"10.1177/0333102420959794","DOIUrl":"https://doi.org/10.1177/0333102420959794","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;Development and characterization of a novel injury-free preclinical model of migraine-like pain allowing mechanistic assessment of both acute and preventive treatments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A \"two-hit\" hyperalgesic priming strategy was used to induce vulnerability to a normally subthreshold challenge with umbellulone, a transient receptor potential ankyrin 1 (TRPA1) activator, in uninjured female and male C57BL/6 mice. Priming (i.e. the first hit) was induced by three consecutive daily episodes of restraint stress; repeated umbellulone was also evaluated for potential priming effects. Sixteen days after the first restraint stress, mice received inhalational umbellulone (i.e. the second hit) to elicit migraine-like pain. Medications currently used for acute or preventive migraine therapy including propranolol (a beta blocker) and sumatriptan (5HT1&lt;sub&gt;B/D&lt;/sub&gt; agonist), as well as olcegepant, an experimental calcitonin gene related peptide (CGRP) receptor antagonist and nor-Binaltorphimine (nor-BNI), an experimental long-acting kappa opioid receptor (KOR) antagonist, were investigated for their efficacy to block priming and prevent or reverse umbellulone-induced allodynia in primed animals. To assess migraine-like pain, cutaneous allodynia was determined by responses to periorbital or hindpaw probing with von Frey filaments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Repeated restraint stress, but not umbellulone exposure, produced transient cutaneous allodynia that resolved within 16 d. Restraint stress produced long-lasting priming that persisted beyond 16 d, as demonstrated by reinstatement of cutaneous allodynia following inhalational umbellulone challenge. Pretreatment with propranolol or nor-BNI prior to restraint stress prevented both transient cutaneous allodynia and priming, demonstrated by a lack of umbellulone-induced cutaneous allodynia. Following establishment of restraint stress priming, olcegepant, but not propranolol or nor-BNI, prevented umbellulone-induced cutaneous allodynia. When administered 1 h after umbellulone, sumatriptan, but not olcegepant, reversed umbellulone-induced cutaneous allodynia in restraint stress-primed rats.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;We have developed a novel injury-free model with translational relevance that can be used to study mechanisms relevant to migraine-like pain and to evaluate novel acute or preventive treatments. Restraint stress priming induced a state of vulnerability to a subthreshold stimulus that has been referred to as \"latent sensitization\". The development of latent sensitization could be prevented by blockade of stress pathways with propranolol or with a kappa opioid receptor antagonist. Following establishment of latent sensitization, subthreshold stimulation with umbellulone reinstated cutaneous allodynia, likely from activation of meningeal TRPA1-expressing nociceptors. Accordingly, in restraint stress-primed animals, sumatriptan reversed umbellulone","PeriodicalId":195255,"journal":{"name":"Cephalalgia : an international journal of headache","volume":" ","pages":"305-317"},"PeriodicalIF":4.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0333102420959794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38426675","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":"Muscle endurance training of the neck triggers migraine attacks.","authors":"Gabriela F Carvalho,&nbsp;Kerstin Luedtke,&nbsp;Tibor M Szikszay,&nbsp;Debora Bevilaqua-Grossi,&nbsp;Arne May","doi":"10.1177/0333102420970184","DOIUrl":"https://doi.org/10.1177/0333102420970184","url":null,"abstract":"<p><strong>Background: </strong>Most migraine patients report neck pain as part of their migraine symptomatology, but it is unknown whether triggering neck pain would induce migraine attacks. Our aim was to assess the occurrence of headache and/or neck pain after an endurance test of the neck muscles among migraineurs and controls.</p><p><strong>Methods: </strong>Sixty-five patients with migraine and 32 headache-free participants underwent a manual examination of the cervical spine by an assessor blinded towards the diagnosis and were sub-classified according to the appearance or absence of neck pain. Subsequently, the endurance of the neck flexors and extensors was tested three times, in a random order. The maximum sustained duration was recorded and the test was terminated when the subject was unable to maintain the position or reported pain. On the day after the assessment, participants were asked to report the potential occurrence of headache or neck symptoms.</p><p><strong>Results: </strong>None of the controls reported headache after assessment, while migraine-like headache was reported by 42% of the patients with migraine (<i>p</i> < 0.001) after 15.8 h (SD: 10.0). Neck pain was more prevalent in migraineurs compared to controls (45% vs. 16%, <i>p</i> = 0.006). When considering the neck pain subtype, there were no differences among the three profiles regarding neck pain but participants with referred pain to the head reported a migraine attack more often (45%, <i>p</i> = 0.03).</p><p><strong>Conclusion: </strong>Patients with migraine are more likely to report neck pain and migraine attacks following a neck muscle endurance test. Participants with neck pain referred to the head during manual examination had a greater prevalence of migraine attacks than those without or with only local pain.</p>","PeriodicalId":195255,"journal":{"name":"Cephalalgia : an international journal of headache","volume":" ","pages":"383-391"},"PeriodicalIF":4.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0333102420970184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38612656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient loss of interhemispheric functional connectivity following unilateral cortical spreading depression in awake rats.","authors":"Lyudmila V Vinogradova,&nbsp;Elena M Suleymanova,&nbsp;Tatiana M Medvedeva","doi":"10.1177/0333102420970172","DOIUrl":"https://doi.org/10.1177/0333102420970172","url":null,"abstract":"<p><strong>Objective: </strong>Growing evidence shows a critical role of network disturbances in the pathogenesis of migraine. Unilateral pattern of neurological symptoms of aura suggests disruption of interhemispheric interactions during the early phase of a migraine attack. Using local field potentials data from the visual and motor cortices, this study explored effects of unilateral cortical spreading depression, the likely pathophysiological mechanism of migraine aura, on interhemispheric functional connectivity in freely behaving rats.</p><p><strong>Methods: </strong>Temporal evolution of the functional connectivity was evaluated using mutual information and phase synchronization measures applied to local field potentials recordings obtained in homotopic points of the motor and visual cortices of the two hemispheres in freely behaving rats after induction of a single unilateral cortical spreading depression in the somatosensory S1 cortex and sham cortical stimulation.</p><p><strong>Results: </strong>Cortical spreading depression was followed by a dramatic broadband loss of interhemispheric functional connectivity in the visual and motor regions of the cortex. The hemispheric disconnection started after the end of the depolarization phase of cortical spreading depression, progressed gradually, and terminated by 5 min after initiation of cortical spreading depression. The network impairment had region- and frequency-specific characteristics and was more pronounced in the visual cortex than in the motor cortex. The period of impaired neural synchrony coincided with post-cortical spreading depression electrographic aberrant activation of the ipsilateral cortex and abnormal behavior.</p><p><strong>Conclusion: </strong>The study provides the first evidence that unilateral cortical spreading depression induces a reversible loss of functional hemispheric connectivity in the cortex of awake animals. Given a critical role of long-distance cortical synchronization in sensory processing and sensorimotor integration, the post-cortical spreading depression breakdown of functional connectivity may contribute to neuropathological mechanisms of aura generation.</p>","PeriodicalId":195255,"journal":{"name":"Cephalalgia : an international journal of headache","volume":" ","pages":"353-365"},"PeriodicalIF":4.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0333102420970172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38675605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medication overuse in a subgroup analysis of phase 3 placebo-controlled studies of galcanezumab in the prevention of episodic and chronic migraine.","authors":"David W Dodick,&nbsp;Erin G Doty,&nbsp;Sheena K Aurora,&nbsp;Dustin D Ruff,&nbsp;Virginia L Stauffer,&nbsp;Jakub Jedynak,&nbsp;Yan Dong,&nbsp;Eric M Pearlman","doi":"10.1177/0333102420966658","DOIUrl":"https://doi.org/10.1177/0333102420966658","url":null,"abstract":"<p><strong>Introduction: </strong>Acute medication overuse is prevalent in patients with migraine.</p><p><strong>Methods: </strong>In three phase 3, double-blind, randomized, placebo-controlled studies, patients with episodic migraine (EVOLVE-1 and EVOLVE-2) or chronic migraine (REGAIN) were randomized 2:1:1 to monthly subcutaneous injections of placebo or galcanezumab 120 or 240 mg for 3 or 6 months. This subgroup analysis evaluated mean changes in the number of monthly migraine headache days in each treatment among patients with versus without baseline acute medication overuse via mixing modelling with repeated measures.</p><p><strong>Results: </strong>The percentages of patients with baseline medication overuse in placebo, galcanezumab 120-mg and 240-mg groups, respectively, were 19.4%, 17.3%, and 19.3% for EVOLVE-1/-2 (pooled; <i>post hoc</i>), and 63.4%, 64.3%, and 64.1% for REGAIN (<i>a priori</i>). Both galcanezumab doses demonstrated significant improvement compared with placebo for overall least squares mean change in monthly migraine headache days in patients with baseline medication overuse in both the episodic and chronic migraine studies (<i>p</i> ≤ 0.001). Furthermore, both galcanezumab doses reduced average monthly medication overuse rates compared to placebo (<i>p</i> < 0.001) in both patient populations with medication overuse at baseline.</p><p><strong>Conclusions: </strong>Galcanezumab appears to be effective for the preventive treatment of episodic and chronic migraine in patients who overuse acute medications.<b>Trial registration:</b> ClinicalTrials.gov Identifiers: NCT02614183, NCT02614196, and NCT02614261.</p>","PeriodicalId":195255,"journal":{"name":"Cephalalgia : an international journal of headache","volume":" ","pages":"340-352"},"PeriodicalIF":4.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0333102420966658","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38657678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}