Subjects -> MEDICAL SCIENCES (Total: 8810 journals)
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INTERNAL MEDICINE (180 journals)                     

Showing 1 - 180 of 180 Journals sorted alphabetically
Abdomen     Open Access  
ACP Hospitalist     Full-text available via subscription   (Followers: 9)
ACP Internist     Full-text available via subscription   (Followers: 10)
ACP Journal Club     Full-text available via subscription   (Followers: 11)
Acta Clinica Belgica     Hybrid Journal   (Followers: 1)
Acute and Critical Care     Open Access   (Followers: 11)
Acute Medicine     Full-text available via subscription   (Followers: 9)
Advances in Hepatology     Open Access   (Followers: 4)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
African Journal of Primary Health Care & Family Medicine     Open Access   (Followers: 6)
African Journal of Thoracic and Critical Care Medicine     Open Access  
American Family Physician     Full-text available via subscription   (Followers: 38)
American Journal of Hypertension     Hybrid Journal   (Followers: 31)
Anales de Medicina Interna     Open Access   (Followers: 1)
Anatomy & Physiology : Current Research     Open Access   (Followers: 9)
Angiology     Hybrid Journal   (Followers: 5)
Annals of Colorectal Research     Open Access   (Followers: 1)
Annals of Internal Medicine     Full-text available via subscription   (Followers: 392)
AORN Journal     Hybrid Journal   (Followers: 27)
Apollo Medicine     Open Access  
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archivos de Medicina Interna     Open Access   (Followers: 1)
Asia Oceania Journal of Nuclear Medicine & Biology     Open Access   (Followers: 4)
Asian Pacific Journal of Tropical Disease     Full-text available via subscription   (Followers: 3)
Australasian Physical & Engineering Sciences in Medicine     Hybrid Journal   (Followers: 1)
BMI Journal : Bariátrica & Metabólica Iberoamericana     Open Access   (Followers: 1)
BMJ Open Diabetes Research & Care     Open Access   (Followers: 35)
BMJ Quality & Safety     Hybrid Journal   (Followers: 69)
Bone & Joint Journal     Hybrid Journal   (Followers: 138)
Brain Communications     Open Access   (Followers: 4)
Brain Science Advances     Open Access  
Canadian Journal of General Internal Medicine     Open Access   (Followers: 2)
Cardiovascular Medicine in General Practice     Full-text available via subscription   (Followers: 7)
Case Reports in Internal Medicine     Open Access   (Followers: 1)
Cell Death & Disease     Open Access   (Followers: 3)
Cellular and Molecular Gastroenterology and Hepatology     Open Access   (Followers: 3)
Cephalalgia     Hybrid Journal   (Followers: 8)
Cephalalgia Reports     Open Access   (Followers: 4)
Chronic Diseases and Injuries in Canada     Free   (Followers: 1)
Clinical Ethics     Hybrid Journal   (Followers: 13)
Clinical Liver Disease     Open Access   (Followers: 5)
Clinical Nutrition     Hybrid Journal   (Followers: 98)
Clinical Thyroidology     Full-text available via subscription   (Followers: 1)
CNE Pflegemanagement     Hybrid Journal  
Communication Law and Policy     Hybrid Journal   (Followers: 5)
Current Diabetes Reports     Hybrid Journal   (Followers: 30)
Current Hepatology Reports     Hybrid Journal  
Current Research: Integrative Medicine     Open Access  
CVIR Endovascular     Open Access   (Followers: 1)
Der Internist     Hybrid Journal   (Followers: 12)
Diabetes     Full-text available via subscription   (Followers: 603)
Diabetes Care     Full-text available via subscription   (Followers: 578)
Diabetes Internacional     Open Access  
Diabetes Spectrum     Full-text available via subscription   (Followers: 17)
Diagnosis     Hybrid Journal   (Followers: 1)
Egyptian Journal of Bronchology     Open Access  
Egyptian Journal of Internal Medicine     Open Access   (Followers: 1)
Egyptian Journal of Neurosurgery     Open Access  
Egyptian Liver Journal     Open Access   (Followers: 2)
Egyptian Spine Journal     Open Access  
EMC - Aparato Locomotor     Hybrid Journal  
Endovascular Neuroradiology / Ендоваскулярна нейрорентгенохірургія     Open Access   (Followers: 1)
eNeuro     Open Access   (Followers: 3)
Ergonomics     Hybrid Journal   (Followers: 24)
European Journal of Inflammation     Open Access   (Followers: 2)
European Journal of Internal Medicine     Full-text available via subscription   (Followers: 10)
European Journal of Translational Myology     Open Access  
European Radiology Experimental     Open Access   (Followers: 2)
Head and Neck Tumors     Open Access   (Followers: 1)
Health Sociology Review     Hybrid Journal   (Followers: 14)
HemaSphere     Open Access   (Followers: 2)
Hepatology Communications     Open Access  
Hepatoma Research     Open Access   (Followers: 3)
Human Physiology     Hybrid Journal   (Followers: 5)
ImmunoHorizons     Open Access  
Immunological Medicine     Open Access  
Infectious Diseases: Research and Treatment     Open Access   (Followers: 5)
Inflammation and Regeneration     Open Access   (Followers: 2)
Inflammatory Intestinal Diseases     Open Access  
Innere Medizin up2date     Hybrid Journal   (Followers: 1)
Internal and Emergency Medicine     Hybrid Journal   (Followers: 5)
Internal Medicine Journal     Hybrid Journal   (Followers: 9)
International Journal of Abdominal Wall and Hernia Surgery     Open Access   (Followers: 1)
International Journal of Anatomy and Research     Open Access   (Followers: 2)
International Journal of Angiology     Hybrid Journal  
International Journal of Artificial Organs     Hybrid Journal   (Followers: 3)
International Journal of Hyperthermia     Open Access  
International Journal of Internal Medicine     Open Access   (Followers: 3)
International Journal of Noncommunicable Diseases     Open Access  
International Journal of Psychiatry in Clinical Practice     Hybrid Journal   (Followers: 6)
Iranian Journal of Neurosurgery     Open Access   (Followers: 1)
Italian Journal of Anatomy and Embryology     Open Access   (Followers: 1)
JAC-Antimicrobial Resistance     Open Access   (Followers: 4)
JAMA Internal Medicine     Full-text available via subscription   (Followers: 364)
JCSM Clinical Reports     Open Access   (Followers: 3)
JHEP Reports     Open Access  
JIMD Reports     Open Access  
JMV - Journal de Médecine Vasculaire     Hybrid Journal   (Followers: 1)
Joint Commission Journal on Quality and Patient Safety     Hybrid Journal   (Followers: 41)
JOP. Journal of the Pancreas     Open Access   (Followers: 2)
Journal of Basic & Clinical Physiology & Pharmacology     Hybrid Journal   (Followers: 1)
Journal of Bone Oncology     Open Access   (Followers: 1)
Journal of Cancer & Allied Specialties     Open Access  
Journal of Clinical and Experimental Hepatology     Full-text available via subscription   (Followers: 3)
Journal of Clinical Movement Disorders     Open Access   (Followers: 3)
Journal of Community Hospital Internal Medicine Perspectives     Open Access  
Journal of Cutaneous Immunology and Allergy     Open Access  
Journal of Developmental Origins of Health and Disease     Hybrid Journal   (Followers: 2)
Journal of Endoluminal Endourology     Open Access  
Journal of Gastroenterology and Hepatology Research     Open Access   (Followers: 4)
Journal of General Internal Medicine     Hybrid Journal   (Followers: 23)
Journal of Hypertension     Hybrid Journal   (Followers: 14)
Journal of Infectious Diseases     Hybrid Journal   (Followers: 48)
Journal of Interdisciplinary Medicine     Open Access  
Journal of Internal Medicine     Hybrid Journal   (Followers: 11)
Journal of Liver : Disease & Transplantation     Hybrid Journal   (Followers: 7)
Journal of Medical Internet Research     Open Access   (Followers: 24)
Journal of Movement Disorders     Open Access   (Followers: 2)
Journal of Pain and Symptom Management     Hybrid Journal   (Followers: 46)
Journal of Pancreatic Cancer     Open Access  
Journal of Renal and Hepatic Disorders     Open Access  
Journal of Solid Tumors     Open Access   (Followers: 1)
Journal of Sports Medicine and Allied Health Sciences : Official Journal of the Ohio Athletic Trainers Association     Open Access   (Followers: 1)
Journal of the American Board of Family Medicine     Open Access   (Followers: 11)
Journal of the European Mosquito Control Association     Open Access  
Journal of Translational Internal Medicine     Open Access  
Jurnal Vektor Penyakit     Open Access  
La Revue de Medecine Interne     Full-text available via subscription   (Followers: 3)
Lege artis - Das Magazin zur ärztlichen Weiterbildung     Hybrid Journal   (Followers: 1)
Liver Cancer International     Open Access  
Liver Research     Open Access  
Molecular Diagnosis & Therapy     Hybrid Journal   (Followers: 3)
Molecular Therapy - Oncolytics     Open Access  
Multiple Sclerosis and Demyelinating Disorders     Open Access   (Followers: 7)
MYOPAIN. A journal of myofascial pain and fibromyalgia     Hybrid Journal   (Followers: 18)
Neuro-Oncology Advances     Open Access   (Followers: 1)
Neurobiology of Pain     Open Access   (Followers: 2)
Neurointervention     Open Access   (Followers: 6)
Neuromuscular Diseases     Open Access  
Nigerian Journal of Gastroenterology and Hepatology     Full-text available via subscription  
OA Alcohol     Open Access   (Followers: 5)
Oncological Coloproctology     Open Access  
Open Journal of Internal Medicine     Open Access  
Pleura and Peritoneum     Open Access  
Pneumo News     Full-text available via subscription  
Polish Archives of Internal Medicine     Full-text available via subscription   (Followers: 2)
Preventing Chronic Disease     Free   (Followers: 2)
Progress in Transplantation     Hybrid Journal   (Followers: 1)
Prostate International     Open Access   (Followers: 2)
Psychiatry and Clinical Psychopharmacology     Open Access   (Followers: 1)
Pulmonary Therapy     Open Access   (Followers: 2)
Quality of Life Research     Hybrid Journal   (Followers: 20)
Research and Practice in Thrombosis and Haemostasis     Open Access  
Revista Chilena de Fonoaudiología     Open Access   (Followers: 1)
Revista de la Sociedad Peruana de Medicina Interna     Open Access   (Followers: 4)
Revista del Instituto de Medicina Tropical     Open Access  
Revista Hispanoamericana de Hernia     Open Access   (Followers: 1)
Revista Médica Internacional sobre el Síndrome de Down     Full-text available via subscription   (Followers: 1)
Revista Virtual de la Sociedad Paraguaya de Medicina Interna     Open Access   (Followers: 1)
Romanian Journal of Diabetes Nutrition and Metabolic Diseases     Open Access   (Followers: 1)
Romanian Journal of Internal Medicine     Open Access  
Russian Journal of Child Neurology     Open Access   (Followers: 1)
Scandinavian Journal of Primary Health Care     Open Access   (Followers: 8)
Schlaf     Hybrid Journal  
Schmerzmedizin     Hybrid Journal  
Scientific Journal of the Foot & Ankle     Open Access   (Followers: 1)
SciMedicine Journal     Open Access   (Followers: 3)
SEMERGEN - Medicina de Familia     Full-text available via subscription   (Followers: 1)
The Journal of Critical Care Medicine     Open Access   (Followers: 9)
Therapeutic Advances in Chronic Disease     Open Access   (Followers: 8)
Therapeutic Advances in Musculoskeletal Disease     Hybrid Journal   (Followers: 6)
Thieme Case Report     Hybrid Journal   (Followers: 1)
Tijdschrift voor Urologie     Hybrid Journal  
Tissue Barriers     Hybrid Journal   (Followers: 1)
Transactions of the Royal Society of Tropical Medicine and Hygiene     Hybrid Journal   (Followers: 3)
Transgender Health     Open Access   (Followers: 3)
Trends in Anaesthesia and Critical Care     Full-text available via subscription   (Followers: 23)
US Cardiology Review     Open Access  
Vascular and Endovascular Review     Open Access   (Followers: 1)
Ожирение и метаболизм     Open Access  


Similar Journals
Journal Cover
Journal Prestige (SJR): 1.581
Citation Impact (citeScore): 3
Number of Followers: 8  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0333-1024 - ISSN (Online) 1468-2982
Published by Sage Publications Homepage  [1151 journals]
  • Migraine therapeutics differentially modulate the CGRP pathway
    • Authors: Minoti Bhakta, Trang Vuong, Tetsuya Taura, David S Wilson, Jennifer R Stratton, Kimberly D Mackenzie
      Pages: 499 - 514
      Abstract: Cephalalgia, Volume 41, Issue 5, Page 499-514, April 2021.
      BackgroundThe 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.MethodsTo 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.ResultsErenumab 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.ConclusionThe 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.
      Citation: Cephalalgia
      PubDate: 2021-02-25T05:15:26Z
      DOI: 10.1177/0333102420983282
      Issue No: Vol. 41, No. 5 (2021)
  • Use of medicinal plants for headache, and their potential implication in
           medication-overuse headache: Evidence from a population-based study in
    • Authors: Elise Øien Sørnes, Ajay Risal, Kedar Manandhar, Hallie Thomas, Timothy J Steiner, Mattias Linde
      Pages: 561 - 581
      Abstract: Cephalalgia, Volume 41, Issue 5, Page 561-581, April 2021.
      BackgroundIn Nepal, traditional treatment using medicinal plants is popular. Whereas medication-overuse headache is, by definition, caused by excessive use of acute headache medication, we hypothesized that medicinal plants, being pharmacologically active, were as likely a cause.MethodsWe used data from a cross-sectional, nationwide population-based study, which enquired into headache and use of medicinal plants and allopathic medications. We searched the literature for pharmacodynamic actions of the medicinal plants.ResultsOf 2100 participants, 1794 (85.4%) reported headache in the preceding year; 161 (7.7%) reported headache on ≥15 days/month, of whom 28 (17.4%) had used medicinal plants and 117 (72.7%) allopathic medication(s). Of 46 with probable medication-overuse headache, 87.0% (40/46) were using allopathic medication(s) and 13.0% (6/46) medicinal plants, a ratio of 6.7:1, higher than the overall ratio among those with headache of 4.9:1 (912/185). Of 60 plant species identified, 49 were pharmacodynamically active on the central nervous system, with various effects of likely relevance in medication-overuse headache causation. ConclusionsMPs are potentially a cause of medication-overuse headache, and not to be seen as innocent in this regard. Numbers presumptively affected in Nepal are low but not negligible. This pioneering project provides a starting point for further research to provide needed guidance on use of medicinal plants for headache.
      Citation: Cephalalgia
      PubDate: 2021-01-13T04:43:47Z
      DOI: 10.1177/0333102420970904
      Issue No: Vol. 41, No. 5 (2021)
  • Board Walk – April 2021
    • Authors: Messoud Ashina, Zaza Katsarava
      Pages: 634 - 636
      Abstract: Cephalalgia, Volume 41, Issue 5, Page 634-636, April 2021.

      Citation: Cephalalgia
      PubDate: 2021-04-14T12:03:42Z
      DOI: 10.1177/03331024211001298
      Issue No: Vol. 41, No. 5 (2021)
  • The Secondary Headaches
    • Authors: Anish Bahra, Randolph W Evans
      Pages: 427 - 430
      Abstract: Cephalalgia, Volume 41, Issue 4, Page 427-430, April 2021.

      Citation: Cephalalgia
      PubDate: 2021-03-17T05:35:20Z
      DOI: 10.1177/0333102421999996
      Issue No: Vol. 41, No. 4 (2021)
  • Diagnosis and treatment of idiopathic intracranial hypertension
    • Authors: Naz Raoof, Jan Hoffmann
      Pages: 472 - 478
      Abstract: Cephalalgia, Volume 41, Issue 4, Page 472-478, April 2021.
      ObjectiveTo review and discuss the clinical presentation and treatment of idiopathic intracranial hypertension.DiscussionVisual alterations and headache are the two main symptoms of idiopathic intracranial hypertension, although additional features including cranial nerve palsies, cognitive deficits, olfactory deficits and tinnitus are not uncommon. The headache associated with idiopathic intracranial hypertension frequently has a migrainous phenotype. The underlying cause of the disorder has not yet been elucidated. Several hypotheses have been postulated but none of them can explain the full clinical picture. Therapeutic options remain limited, focusing mainly on reduction in body weight and the reduction of CSF production with carbonic anhydrase inhibitors.ConclusionThe accurate diagnosis of idiopathic intracranial hypertension is essential as visual deterioration due to papilledema may be irreversible. Given its phenotypic similarity and frequent overlap with chronic migraine it is essential to consider idiopathic intracranial hypertension in the diagnostic workup of chronic headache; in particular, when considering its increasing prevalence. Understanding in detail the pathophysiological mechanisms behind the associated headache would also allow study of current and future therapeutic options in a structured way.
      Citation: Cephalalgia
      PubDate: 2021-02-26T05:12:45Z
      DOI: 10.1177/0333102421997093
      Issue No: Vol. 41, No. 4 (2021)
  • Headache secondary to cerebrovascular disease
    • Authors: John F Rothrock, Hans-Christoph Diener
      Pages: 479 - 492
      Abstract: Cephalalgia, Volume 41, Issue 4, Page 479-492, April 2021.
      ObjectivesTo discuss headache secondary to cerebrovascular disease.BackgroundHeadache is an important symptom in cerebrovascular diseases. In some conditions, headache is the leading symptom. Migraine is associated with an increased risk of stroke.MethodsThe authors undertook a literature search for the terms “headache” and “cerebrovascular diseases”.ResultsWe report studies on headache in subarachnoidal hemorrhage, intracerebral hemorrhage, ischemic stroke, TIA, basilar artery thrombosis, cervical artery dissection, cerebellar stroke, arteritis and cerebral sinus venous thrombosis. In addition, we discuss migraine and stroke and thunderclap headache.ConclusionsHeadache is a leading symptom in many cerebrovascular diseases. Headache in combination with focal neurological deficits requires immediate diagnosis and treatment.
      Citation: Cephalalgia
      PubDate: 2021-03-19T04:53:02Z
      DOI: 10.1177/0333102421999045
      Issue No: Vol. 41, No. 4 (2021)
  • Erenumab prevents the occurrence of migraine attacks and not just migraine
           days: Post-hoc analyses of a phase III study
    • Authors: Hans-Christoph Diener, Messoud Ashina, Shannon Ritter, Gabriel Paiva Da Silva Lima, Soeren Rasmussen, Ronald Zielman, Peer Tfelt-Hansen
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundThis post-hoc analysis was conducted to evaluate the effect of erenumab on monthly migraine days, monthly migraine attacks, and attack duration in patients with episodic migraine to investigate whether erenumab actually prevents the occurrence of migraine attacks and/or shortens them.MethodsWe conducted a post-hoc analysis of the data from the STRIVE study, in 955 patients with episodic migraine. Relative changes from baseline to mean over months 4, 5 and 6 of the double-blind treatment phase in monthly migraine days, monthly migraine attacks and mean migraine attack duration were assessed.ResultsErenumab reduced monthly migraine days and monthly migraine attacks compared with placebo in a similar way. Erenumab had only a minor impact on shortening the duration of migraine attacks.ConclusionThese post-hoc analyses demonstrate that the decrease in monthly migraine days by erenumab is mainly driven by a reduction in the frequency of monthly migraine attacks and to a much lesser extent by shortening the duration of migraine attacks.Trial registration: This study is registered at (NCT02456740)
      Citation: Cephalalgia
      PubDate: 2021-05-03T05:54:49Z
      DOI: 10.1177/03331024211010308
  • Paroxysmal localized Hyperhidrosis, a case-report: When excessive sweating
           occurs in combination with severe headaches
    • Authors: Marleen H van Coevorden, Mariëtte WCJ Schoofs, Jeroen Venhovens
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundParoxysmal localized hyperhidrosis is a rare disorder of the central autonomic nervous system. No association between paroxysmal hyperhidrosis and severe headache has been previously described in literature.Case description: A 65-year-old woman with idiopathic paroxysmal localized hyperhidrosis combined with severe holocranial headache attacks is described in this case report. Extensive diagnostic testing by means of laboratory examinations, 24-hour urinalyses, chest X-ray, abdominal ultrasound and computed tomography scans, and brain and spinal cord magnetic resonance imaging could not identify an underlying disorder. A diagnosis of idiopathic paroxysmal localized hyperhidrosis was made, and the patient was successfully treated with clonidine 0.075 mg three times a day, without any side effects.ConclusionParoxysmal localized hyperhidrosis is a rare central autonomic nervous system disorder that can occur in combination with severe headache. Both the headache and paroxysmal hyperhidrosis complaints were treated effectively with clonidine in the patient described in this case-report.
      Citation: Cephalalgia
      PubDate: 2021-05-03T05:12:54Z
      DOI: 10.1177/03331024211006843
  • Clinical, oculographic, and vestibular test characteristics of vestibular
    • Authors: Allison S Young, Benjamin Nham, Andrew P Bradshaw, Zeljka Calic, Jacob M Pogson, Mario D’Souza, G Michael Halmagyi, Miriam S Welgampola
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundWe characterise the history, vestibular tests, ictal and interictal nystagmus in vestibular migraine.MethodWe present our observations on 101 adult-patients presenting to an outpatient facility with recurrent spontaneous and/or positional vertigo whose final diagnosis was vestibular migraine (n = 27) or probable vestibular migraine (n = 74). Ictal and interictal video-oculography, caloric and video head impulse tests, vestibular-evoked myogenic potentials and audiometry were performed.ResultsCommon presenting symptoms were headache (81.2%), spinning vertigo (72.3%), Mal de Débarquement (58.4%), and motion sensitivity (30.7%). With fixation denied, ictal and interictal spontaneous nystagmus was observed in 71.3 and 14.9%, and purely positional nystagmus in 25.8 and 55.4%. Spontaneous ictal nystagmus was horizontal in 49.5%, and vertical in 21.8%. Ictal spontaneous and positional nystagmus velocities were 5.3 ± 9.0°/s (range 0.0–57.4), and 10.4 ± 5.8°/s (0.0–99.9). Interictal spontaneous and positional nystagmus velocities were
      Citation: Cephalalgia
      PubDate: 2021-05-03T05:12:52Z
      DOI: 10.1177/03331024211006042
  • The first prevalence study of primary headaches in adults in a
           post-conflict area of Serbia
    • Authors: Nenad Milošević, Jasna Zidverc Trajković, Milija Mijajlović, Jovana Milošević, Ana Podgorac, Zdravko Vitošević, Tatjana Novaković, Tatjana Pekmezović
      Abstract: Cephalalgia, Ahead of Print.
      AimThe aim of the present study was to establish annual prevalence of primary headaches, migraine, and tension-type headache among adults in a post-conflict area of Serbia.MethodsThe data for this cross-sectional study was obtained via face-to-face interviews using questionnaires specifically designed for this purpose, in line with the available guidelines. The study sample included adults aged 18–65 years whose native language is Serbian with residence in six predominantly Serbian communities in Kosovo and Metohija. Relevant diagnoses were established according to the diagnostic criteria of the International Classification of Headache Disorders, 3rd edition.ResultsThe study included 1062 adults. Analyses indicated 47.7% prevalence of primary headaches. The 1-year prevalence of migraine (with aura and without aura) and tension-type headache was established at 15.2% (3.3% and 11.9%), and 32.2%, respectively. One-year prevalence of chronic headache was calculated at 3.5%, while the prevalence of medication overuse headache was slightly lower at 2.9%. Primary headaches were more prevalent among women, participants residing south of the river Ibar, married or cohabiting individuals, as well as among interviewees (persons) who reported feeling unsafe in Kosovo and Metohija. This is the first study of the prevalence of primary headache disorders in Serbia. The obtained data is comparable to the data available for other countries, especially those in the Balkan region.
      Citation: Cephalalgia
      PubDate: 2021-05-03T05:12:51Z
      DOI: 10.1177/03331024211006043
  • Determinants of pain interference and headache impact in patients who have
           chronic migraine with medication overuse: Results from the MOTS trial
    • Authors: Todd J Schwedt, Soma Sahai-Srivastava, Natalia Murinova, Marius Birlea, Zubair Ahmed, Kathleen Digre, Kristina Lopez, William Mullally, Maike Tiede Blaya, Karly Pippitt, Fred Michael Cutrer, Justin DeLange, Howard Schecht, Paul Rizzoli, Judy Lane, John Wald, Melissa M Cortez, Vincent T Martin, Nicole M Spare, Joseph G Hentz, Teri Robert, David W Dodick
      Abstract: Cephalalgia, Ahead of Print.
      Objective“Pain interference” and “headache impact” refer to negative consequences that pain and headache have on one’s life. This study investigated determinants of these negative impacts in a large patient cohort who have chronic migraine with medication overuse.MethodsSix hundred and eleven adults were enrolled from 34 headache, neurology, and primary care clinics. Negative consequences of chronic migraine with medication overuse were determined using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 6b questionnaire and the Headache Impact Test 6. Relationships between PROMIS-6b and Headache Impact Test 6 scores with demographics, headache characteristics, medication use, anxiety symptoms, and depression symptoms were assessed with linear regression. Elastic Net regression was used to develop a multiple regression model.ResultsPROMIS-6b T-Scores averaged 65.2 (SD 5.4) and Headache Impact Test 6 scores averaged 65.0 (SD 5.3), indicating severe negative consequences of chronic migraine with medication overuse. Chronic migraine with medication overuse interfered with enjoyment of life, concentration, daily activities, doing tasks away from home, and socializing. Depression symptom severity had the strongest relationship with pain interference and headache impact. Moderate-to-severe headache frequency, headache intensity, and anxiety symptoms were also associated with pain interference and headache impact.ConclusionsChronic migraine with medication overuse is associated with substantial negative consequences, the extent of which is most strongly related to depression symptoms.
      Citation: Cephalalgia
      PubDate: 2021-05-03T05:12:49Z
      DOI: 10.1177/03331024211006903
  • E-diary use in clinical headache practice: A prospective observational
    • Authors: Daphne S van Casteren, Iris E Verhagen, Irene de Boer, Simone de Vries Lentsch, Rolf Fronczek, Erik W van Zwet, Antoinette MaassenVanDenBrink, Gisela M Terwindt
      Abstract: Cephalalgia, Ahead of Print.
      AimTo determine whether our E-diary can be used to diagnose migraine and provide more reliable migraine-related frequency numbers compared to patients’ self-reported estimates.MethodsWe introduced a self-developed E-diary including automated algorithms differentiating headache and migraine days, indicating whether a patient has migraine. Reliability of the E-diary diagnosis in combination with two previously validated E-questionnaires was compared to a physician’s diagnosis as gold standard in headache patients referred to the Leiden Headache Clinic (n = 596). In a subset of patients with migraine (n = 484), self-estimated migraine-related frequencies were compared to diary-based results.ResultsThe first migraine screening approach including an E-headache questionnaire, and the E-diary revealed a sensitivity of 98% and specificity of 17%. In the second approach, an E-migraine questionnaire was added, resulting in a sensitivity of 79% and specificity of 69%. Mean self-estimated monthly migraine days, non-migrainous headache days and days with acute medication use were different from E-diary-based results (absolute mean difference ± standard deviation respectively 4.7 ± 5.0, 6.2 ± 6.6 and 4.3 ± 4.8).ConclusionThe E-diary including algorithms differentiating headache and migraine days showed usefulness in diagnosing migraine. The use emphasised the need for E-diaries to obtain reliable information, as patients do not reliably recall numbers of migraine days and acute medication intake. Adding E-diaries will be helpful in future headache telemedicine.
      Citation: Cephalalgia
      PubDate: 2021-05-03T05:12:47Z
      DOI: 10.1177/03331024211010306
  • Letter to the editor regarding “Safety profile of erenumab, galcanezumab
           and fremanezumab in pregnancy and lactation: Analysis of the WHO
           pharmacovigilance database”
    • Authors: Yoel Kessler, Xiaoping Ning, Joshua M Cohen
      Abstract: Cephalalgia, Ahead of Print.

      Citation: Cephalalgia
      PubDate: 2021-05-03T05:12:46Z
      DOI: 10.1177/03331024211006827
  • Reply to the Letter to the Editor by Kessler Y et al. regarding the
           manuscript “Safety profile of erenumab, galcanezumab and fremanezumab in
           pregnancy and lactation: Analysis of the WHO pharmacovigilance
    • Authors: Roberta Noseda, Francesca Bedussi, Claudio Gobbi, Chiara Zecca, Alessandro Ceschi
      Abstract: Cephalalgia, Ahead of Print.

      Citation: Cephalalgia
      PubDate: 2021-05-03T05:12:46Z
      DOI: 10.1177/03331024211006849
  • Distinguishing persistent post-traumatic headache from migraine:
           Classification based on clinical symptoms and brain structural MRI data
    • Authors: Catherine D Chong, Visar Berisha, Katherine Ross, Mazher Kahn, Gina Dumkrieger, Todd J Schwedt
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundPersistent post-traumatic headache most commonly has symptoms that overlap those of migraine. In some cases, it can be clinically difficult to differentiate persistent post-traumatic headache with a migraine phenotype from migraine. The objective of this study was to develop a classification model based on questionnaire data and structural neuroimaging data that distinguishes individuals with migraine from those with persistent post-traumatic headache.MethodsQuestionnaires assessing headache characteristics, sensory hypersensitivities, cognitive functioning, and mood, as well as T1-weighted magnetic resonance imaging and diffusion tensor data from 34 patients with migraine and 48 patients with persistent post-traumatic headache attributed to mild traumatic brain injury were included for analysis. The majority of patients with persistent post-traumatic headache had a migraine/probable migraine phenotype (77%). A machine-learning leave-one-out cross-validation algorithm determined the average accuracy for distinguishing individual migraine patients from individual patients with persistent post-traumatic headache.ResultsBased on questionnaire data alone, the average classification accuracy for determining whether an individual person had migraine or persistent post-traumatic headache was 71.9%. Adding imaging data features to the model improved the classification accuracy to 78%, including an average accuracy of 97.1% for identifying individual migraine patients and an average accuracy of 64.6% for identifying individual patients with persistent post-traumatic headache. The most important clinical features that contributed to the classification accuracy included questions related to anxiety and decision making. Cortical brain features and fibertract data from the following regions or tracts most contributed to the classification accuracy: Bilateral superior temporal, inferior parietal and posterior cingulate; right lateral occipital, uncinate, and superior longitudinal fasciculus. A post-hoc analysis showed that compared to incorrectly classified persistent post-traumatic headache patients, those who were correctly classified as having persistent post-traumatic headache had more severe physical, autonomic, anxiety and depression symptoms, were more likely to have post-traumatic stress disorder, and were more likely to have had mild traumatic brain injury attributed to blasts.DiscussionA classification model that included a combination of questionnaire data and structural imaging parameters classified individual patients as having migraine versus persistent post-traumatic headache with good accuracy. The most important clinical measures that contributed to the classification accuracy included questions on mood. Regional brain structures and fibertracts that play roles in pain processing and pain integration were important brain features that contributed to the classification accuracy. The lower classification accuracy for patients with persistent post-traumatic headache compared to migraine may be related to greater heterogeneity of patients in the persistent post-traumatic headache cohort regarding their traumatic brain injury mechanisms, and physical, emotional, and cognitive symptoms.
      Citation: Cephalalgia
      PubDate: 2021-04-30T04:56:43Z
      DOI: 10.1177/0333102421991819
  • Photophobia and allodynia in persistent post-traumatic headache are
           associated with higher disease burden
    • Authors: Melissa M Cortez, Leah Millsap, Natalie A Rea, Christopher Sciarretta, KC Brennan
      Abstract: Cephalalgia, Ahead of Print.
      ObjectiveTo assess photophobia and allodynia in subjects with post-traumatic headache and examine how these sensory hypersensitivities associate with clinical measures of disease burden.BackgroundPost-traumatic headache is the most frequent and disabling long-term consequence of mild traumatic brain injury. There is evidence of sensory dysfunction in acute post-traumatic headache, and it is known from other headache conditions that sensory amplifications correlate with more severe disease. However, systematic studies in post-traumatic headache are surprisingly scarce.MethodsWe tested light and tactile sensitivity, along with measures of disease burden, in 30 persistent post-traumatic headache subjects and 35 controls.ResultsIn all, 79% of post-traumatic headache subjects exhibited sensory hypersensitivity based on psychophysical assessment. Of those exhibiting hypersensitivity, 54% exhibited both light and tactile sensitivity. Finally, sensory thresholds were correlated across modalities, as well as with headache attack frequency.ConclusionsIn this study, post-traumatic headache subjects with both light and tactile sensitivity had significantly higher headache frequencies and lower sensitivity thresholds to both modalities, compared to those with single or no sensory hypersensitivity. This pattern suggests that hypersensitivity across multiple modalities may be functionally synergistic, reflect a higher disease burden, and may serve as candidate markers of disease.
      Citation: Cephalalgia
      PubDate: 2021-04-29T04:49:39Z
      DOI: 10.1177/03331024211010304
  • Safety and efficacy of ubrogepant in participants with major
           cardiovascular risk factors in two single-attack phase 3 randomized
           trials: ACHIEVE I and II
    • Authors: Susan Hutchinson, Stephen D Silberstein, Andrew M Blumenfeld, Richard B Lipton, Kaifeng Lu, Sung Yun Yu, Lawrence Severt
      Abstract: Cephalalgia, Ahead of Print.
      ObjectiveTo examine the safety and efficacy of ubrogepant for acute treatment of migraine across cardiovascular (CV) disease risk categories.MethodsACHIEVE I and II were multicenter, double-blind, single-attack, phase 3 trials in adults with migraine, with or without aura. Participants were randomized 1:1:1 to placebo or ubrogepant (50 or 100 mg in ACHIEVE I; 25 or 50 mg in ACHIEVE II), to treat one migraine attack of moderate or severe headache pain intensity. This post-hoc analysis pooled data from ubrogepant 50 mg and placebo groups from the ACHIEVE trials to examine the safety and efficacy of ubrogepant by baseline cardiovascular disease risk factors. Using a cardiovascular risk assessment algorithm, participants were categorized as having no cardiovascular risk, low cardiovascular risk or moderate-high cardiovascular risk at baseline. Treatment-emergent adverse events were documented 48 h and 30 days after taking the trial medication. Co-primary efficacy outcomes were 2-h pain freedom and 2-h absence of most bothersome migraine-associated symptom.ResultsOverall, 3358 participants were randomized in the ACHIEVE trials (n = 2901 safety population; n = 2682 modified intent-to-treat population). In the safety population, 11% of participants were categorized as moderate-high (n = 311), 32% low (n = 920), and 58% no cardiovascular risk factors (n = 1670). The proportion of ubrogepant participants reporting a treatment-emergent adverse event was comparable across risk categories and similar to placebo. The treatment effects of ubrogepant versus placebo were consistent across cardiovascular risk categories for all efficacy outcomes.ConclusionThe safety and efficacy of ubrogepant for the acute treatment of a single migraine attack did not differ by the presence of major cardiovascular risk factors. No evidence of increased treatment-emergent adverse events or cardiac system organ class adverse events with ≥2 major cardiovascular risk factors and no safety concerns were identified.Trial Registration: ACHIEVE I number, NCT02828020; ACHIEVE II number, NCT02867709
      Citation: Cephalalgia
      PubDate: 2021-04-20T05:22:28Z
      DOI: 10.1177/03331024211000311
  • Time lost due to an attack – a novel patient-reported outcome measure
           for acute migraine treatments
    • Authors: Heiko Pohl, Silvia Benemei, David Garcia-Azorin, Joanna Dixon, Elizabeth Huzzey, Michel D Ferrari
      Abstract: Cephalalgia, Ahead of Print.
      ObjectiveWe propose a new outcome measure to assess the efficacy of migraine treatments translating the approach of the Global Burden of Disease studies from a societal to an individual level: Instead of calculating “years lived with disability”, we suggest estimating “time lost due to an attack”.MethodsTime lost due to an attack is calculated by multiplying the duration and the degree of impaired functioning during an attack.ResultsTime lost due to an attack, different from other outcome measures, does not just focus on the short-term analgesic effects of treatments, but rather on the improvement of all migraine symptoms and restoration of functioning, also considering therapy-related impairment. Importantly, time lost due to an attack measures the entire time patients are not functioning normally, from onset to complete resolution.ConclusionsTime lost due to an attack represents a new paradigm to assess migraine burden in single patients for a patient-centered evaluation of both acute and prophylactic treatments.
      Citation: Cephalalgia
      PubDate: 2021-04-20T05:22:26Z
      DOI: 10.1177/03331024211006048
  • Premonitory symptoms in migraine from China: A multi-clinic study of 4821
    • Authors: Xiaolin Wang, Ziming Yin, Yajun Lian, Yanmei Xu, Yajie Li, Jiale Liu, Qun Gu, Fanhong Yan, Zhaoli Ge, Yu Lian, Dongmei Hu, Sufen Chen, Rongfei Wang, Xiaoyan Chen, Jing Liu, Mingjie Zhang, Ye Ran, Ping Zhou, Jingyi Ma, Xudong Lv, Zhao Dong, Shengyuan Yu
      Abstract: Cephalalgia, Ahead of Print.
      ObjectiveTo observe the prevalence and characteristics of premonitory symptoms in Chinese migraineurs and explore their associations with migraine-related factors.MethodMigraineurs who visited a tertiary headache clinic and one of nine neurology clinics between May 2014 and November 2019 were studied.ResultAmong the 4821 patients meeting the migraine criteria (International Classification of Headache Disorders, 3rd edition), 1038 (21.5%) patients experienced at least one premonitory symptom. The most common premonitory symptoms were neck stiffness, dizziness, yawning and drowsiness. The logistic regression analysis demonstrated that aura, photophobia, aggravation by routine physical activity, triggers, family history, depression, coffee consumption and physical exercise were associated with an increased probability of experiencing premonitory symptoms (p ≤ 0.001). The premonitory symptoms of migraine with and without aura differ in prevalence and most common symptoms. The cluster analysis revealed pairwise clustering of the following premonitory symptoms: Photophobia/phonophobia, concentration change/dysesthesia, loquacity/overactivity, yawning/drowsiness, fatigue/dizziness, and mood change/irritability. The correlation analysis of triggers and premonitory symptoms revealed that temperature change, environment change, sleep disorder, activity and stress were related to multiple premonitory symptoms, and that food, light, menstruation, alcohol and odor were related to special premonitory symptoms (p ≤ 0.001).ConclusionThe prevalence of premonitory symptoms among migraineurs in China is 21.5%. Some factors influence the probability of experiencing premonitory symptoms. Paired premonitory symptoms in the clustering analysis may share similar origins. Certain triggers associated with multiple premonitory symptoms may induce brain dysfunction; however, other triggers that overlap with corresponding special premonitory symptoms may be premonitory symptoms or a form of premonitory symptom.
      Citation: Cephalalgia
      PubDate: 2021-02-26T05:12:43Z
      DOI: 10.1177/0333102421997850
  • Trans-nasal high-flow dehumidified air in acute migraine headaches: A
           randomized controlled trial
    • Authors: Rushil Shah, Fabrizio Assis, Bharat Narasimhan, Vahe Khachadourian, Shijie Zhou, Harikrishna Tandri, Nauman Tariq
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundIntranasal high flow of dehumidified (dry) air results in evaporative cooling of nasal passages. In this randomized clinical trial, we investigated the effect of dry gas induced nasal cooling on migraine headaches.MethodsIn this single-blind study, acute migraineurs were randomized to either nasal high-flow dry oxygen, dry air, humidified oxygen or humidified air (control) at 15 L/min for 15 min. All gases were delivered at 37°C. Severity of headache and other migraine associated symptoms (International Classification for Headache Disorders, 3rd edition criteria) were recorded before and after therapy. The primary endpoint was change in pain scores, while changes in nausea, photosensitivity and sound sensitivity scores served as secondary endpoints. A linear regression model was employed to estimate the impact of individual treatment components and their individual interactions.ResultsFifty-one patients (48 ± 15 years of age, 82% women) were enrolled. When compared to the control arm (humidified air), all therapeutic arms showed a significantly greater reduction in pain scores (primary endpoint) at 2 h of therapy with dry oxygen (−1.6 [95% CI −2.3, −0.9]), dry air (−1.7 [95% CI −2.6, −0.7)]), and humidified oxygen (−2.3 [95% CI −3.5, −1.1]). A significantly greater reduction in 2-h photosensitivity scores was also noted in all therapeutic arms (−1.8 [95% CI −3.2, −0.4], dry oxygen; −1.7 [95% CI −2.9, −0.4], dry air; (−2.1 [95% CI −3.6, −0.6], humidified oxygen) as compared to controls. The presence of oxygen and dryness were independently associated with significant reductions in pain and photosensitivity scores. No adverse events were reported.ConclusionTrans-nasal high-flow dry gas therapy may have a role in reducing migraine associated pain.Clinical Trial registration: NCT04129567
      Citation: Cephalalgia
      PubDate: 2021-02-26T05:12:41Z
      DOI: 10.1177/0333102421997766
  • CGRP monoclonal antibody prevents the loss of diffuse noxious inhibitory
           controls (DNIC) in a mouse model of post-traumatic headache
    • Authors: Caroline M Kopruszinski, Joelle M Turnes, Juliana Swiokla, Troy J Weinstein, Todd J Schwedt, David W Dodick, Trent Anderson, Edita Navratilova, Frank Porreca
      Abstract: Cephalalgia, Ahead of Print.
      AimDetermine the role of calcitonin-gene related peptide in promoting post-traumatic headache and dysregulation of central pain modulation induced by mild traumatic brain injury in mice.MethodsMild traumatic brain injury was induced in lightly anesthetized male C57BL/6J mice by a weight drop onto a closed and unfixed skull, which allowed free head rotation after the impact. We first determined possible alterations in the diffuse noxious inhibitory controls, a measure of net descending pain inhibition called conditioned pain modulation in humans at day 2 following mild traumatic brain injury. Diffuse noxious inhibitory control was assessed as the latency to a thermally induced tail-flick that served as the test stimulus in the presence of right forepaw capsaicin injection that provided the conditioning stimulus. Post-traumatic headache-like behaviors were assessed by the development of cutaneous allodynia in the periorbital and hindpaw regions after mild traumatic brain injury. We then determined if intraperitoneal fremanezumab, an anti-calcitonin-gene related peptide monoclonal antibody or vehicle administered 2 h after sham or mild traumatic brain injury induction could alter cutaneous allodynia or diffuse noxious inhibitory control responses on day 2 post mild traumatic brain injury.ResultsIn naïve and sham mice, capsaicin injection into the forepaw elevated the latency to tail-flick, reflecting the antinociceptive diffuse noxious inhibitory control response. Periorbital and hindpaw cutaneous allodynia, as well as a loss of diffuse noxious inhibitory control, was observed in mice 2 days after mild traumatic brain injury. Systemic treatment with fremanezumab blocked mild traumatic brain injury-induced cutaneous allodynia and prevented the loss of diffuse noxious inhibitory controls in mice subjected to a mild traumatic brain injury.InterpretationSequestration of calcitonin-gene related peptide in the initial stages following mild traumatic brain injury blocked the acute allodynia that may reflect mild traumatic brain injury-related post-traumatic headache and, additionally, prevented the loss of net descending inhibition within central pain modulation pathways. As loss of conditioned pain modulation has been linked to multiple persistent pain conditions, dysregulation of descending modulatory pathways may contribute to the persistence of post-traumatic headache. Additionally, evaluation of the conditioned pain modulation/diffuse noxious inhibitory controls response may serve as a biomarker of vulnerability for chronic/persistent pain. These findings suggest that early anti-calcitonin-gene related peptide intervention has the potential to be effective both for the treatment of mild traumatic brain injury-induced post-traumatic headache, as well as inhibiting mechanisms that may promote post-traumatic headache persistence.
      Citation: Cephalalgia
      PubDate: 2021-02-21T03:53:37Z
      DOI: 10.1177/0333102420981688
  • Comprehensive clinical phenotyping of nitroglycerin infusion induced
           cluster headache attacks
    • Authors: Diana Y Wei, Peter J Goadsby
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundNitroglycerin administration allows the study of cluster headache attacks in their entirety in a standardised way.MethodsA single-blind, placebo-controlled, cross-over study using weight-calculated intravenous nitroglycerin administration at 0.5 µg/kg/min over 20 minutes to study cluster headache attacks, including accompanying non-headache symptoms and cranial autonomic symptoms.ResultsThirty-three subjects with cluster headache were included in the study; 24 completed all three study visits. Nitroglycerin-induced attacks developed in 26 out of 33 subjects (79%) receiving unblinded nitroglycerin infusion, and in 19 out of 25 subjects (76%) receiving single-blinded nitroglycerin infusion, compared with one out of 24 subjects (4%) receiving single-blinded placebo infusion. Episodic cluster headache subjects had a shorter latency period to a nitroglycerin-induced attack compared to the chronic cluster headache (CCH) subjects (U = 15, z = −2.399, p = 0.016). Sixteen of nineteen episodic cluster headache (mean, 84%; 95% confidence interval, 66–100%) and 11 of 14 chronic cluster headache subjects developed a nitroglycerin-induced attack (79%, 54–100%) following the unblinded nitroglycerin infusion. Following the single-blinded nitroglycerin infusion, eight out of 13 episodic cluster headache (62%, 31–92%) and 11 out of 12 chronic cluster headache (92%, 73–100%) subjects developed nitroglycerin-induced attacks. Nitroglycerin induced non-headache symptoms in the majority of subjects receiving it: 91% in the open unblinded nitroglycerin visit and 84% in the single-blinded nitroglycerin visits, compared with 33% in the single-blinded placebo visit. Cranial autonomic symptoms were induced by nitroglycerin infusion, 94% in the open unblinded nitroglycerin visit and 84% in the single-blinded nitroglycerin visit, compared with 17% in the single-blinded placebo visit.ConclusionIntravenous weight-adjusted nitroglycerin administration in both episodic cluster headache in bout and chronic cluster headache is effective and reliable in inducing cluster headache attacks, cranial autonomic symptoms and non-headache symptoms.
      Citation: Cephalalgia
      PubDate: 2021-02-21T03:53:37Z
      DOI: 10.1177/0333102421989617
  • Two hundred and forty-eight cases of visual snow: A review of potential
           inciting events and contributing comorbidities
    • Authors: Dev G Mehta, Ivan Garza, Carrie E Robertson
      Abstract: Cephalalgia, Ahead of Print.
      ObjectiveTo review characteristics and outcomes of all cases of visual snow seen at our institution, with attention to possible triggering events or comorbidities.MethodsThis is a retrospective case series of patients seen at our tertiary care center from January 1994 to January 2020. Charts were reviewed if they contained the term “visual snow”.ResultsOf the 449 charts reviewed, 248 patients described seeing visual snow in part or all of their vision. Thirty-eight reported transient visual snow as their typical migraine aura. Of the remaining 210 patients, 89 were reported to have either an inciting event or contributing comorbidity for their visual snow symptoms, including: Post-concussion (n = 15), dramatic change in migraine or aura (n = 14), post-infection (n = 13), hallucinogen persisting perception disorder (n = 10), ocular abnormalities (n = 7), idiopathic intracranial hypertension (n = 4), neoplastic (n = 1), and posterior cortical atrophy (n = 1). Some patients had partial improvement with benzodiazepines (n = 6), lamotrigine (n = 5), topiramate (n = 3) and acetazolamide (n = 3). Presenting characteristics were similar, but patients with visual snow attributed to an inciting event or contributing comorbidity were more likely to have some improvement in their symptoms by last follow-up compared to spontaneous visual snow (p 
      Citation: Cephalalgia
      PubDate: 2021-02-21T03:53:36Z
      DOI: 10.1177/0333102421996355
  • Patients with episodic migraine show increased T2 values of the trapezius
           muscles – an investigation by quantitative high-resolution magnetic
           resonance imaging
    • Authors: Nico Sollmann, Paul Schandelmaier, Dominik Weidlich, Corinna Börner, Giada Urban, Magdalena Lang, Claus Zimmer, Dimitrios C Karampinos, Mirjam N Landgraf, Florian Heinen, Thomas Baum, Michaela V Bonfert
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundNeck pain is frequent in patients with migraine. Likewise, evidence for inflammatory processes in the trapezius muscles is accumulating. However, non-invasive and objectively assessable correlates are missing in vivo.MethodsTwenty-one subjects with episodic migraine (mean age: 24.6 ± 3.1 years, 18 females) and 22 controls (mean age: 23.0 ± 2.2 years, 17 females) without any history of headache prospectively underwent physical examination and quantitative magnetic resonance imaging of the trapezius muscles. A T2‐prepared turbo spin-echo sequence was acquired for manual segmentation of the trapezius muscles and extraction of mean T2 values.ResultsThere were no statistically significant differences regarding age, sex, body mass index, or number of myofascial trigger points (mTrPs) between groups. All patients with migraine presented with mTrPs in the trapezius muscles. T2 of the entire trapezius muscles was significantly higher in the migraine group when compared to controls (31.1 ± 0.8 ms vs. 30.1 ± 1.1 ms; p = 0.002).ConclusionsElevated T2 values of the trapezius muscles may indicate subtle inflammatory processes within musculature among patients with migraine because T2 increase is likely to stem from edematous changes. Future work may validate this finding in larger cohorts, but muscle T2 might have potential to develop into a viable in vivo biomarker for muscular affection in migraine.
      Citation: Cephalalgia
      PubDate: 2021-02-21T03:53:35Z
      DOI: 10.1177/0333102421996374
  • The burden of migraine on acute and emergency services in a London
           teaching hospital
    • Authors: Jessica Southwell, Shazia K Afridi
      Abstract: Cephalalgia, Ahead of Print.
      ObjectiveThere is a lack of data on the burden of primary headache disorders such as migraine on emergency services. Existing data relies on a coding of “headache”, which encompasses both primary and secondary headache of all causes; for example, subarachnoid haemorrhage. Guy’s and St Thomas’ NHS Trust in London is one of the UK’s busiest emergency departments with 150,000 attendances per year. Our aim was to assess the healthcare resource utilisation of primary headaches, in particular migraine, in acute medical services.MethodsWe conducted an audit of all adult presentations to the emergency department of Guy’s and St Thomas’ Hospitals which were coded as “headache” over the first 6 months of 2018. We reviewed the initial diagnosis at presentation and also at discharge, investigations and outcome.ResultsOf 78,273 attendances to the emergency department, there were 976 presentations to the emergency department with “headache” as their primary complaint. “Migraine” was the most frequent of all diagnoses, accounting for 30% of all headache presentations and 25% of headache admissions. We calculated the cost of admitting and investigating migraine as £131,250 over the 6-month period.ConclusionEmergency admissions for migraine represent an avoidable cost and burden for both the hospital and the migraineur. This data informs us about the need to develop better care pathways for migraine in the community and to improve headache education for physicians and patients.
      Citation: Cephalalgia
      PubDate: 2021-02-19T05:53:25Z
      DOI: 10.1177/0333102420981734
  • Effect of single dose Erenumab on cortical responses evoked by cutaneous
           a-delta fibers: A pilot study in migraine patients
    • Authors: Marina de Tommaso, Marianna Delussi, Eleonora Gentile, Katia Ricci, Silvia Giovanna Quitadamo, Giuseppe Libro
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundErenumab is a monoclonal antibody against calcitonin gene-related peptide receptors, which showed efficacy in migraine attack prevention. The aims of the present pilot study were to i) evaluate the effect of single dose of Erenumab 70 mg on laser evoked potentials from trigeminal and brachial stimulation in a cohort of migraine patients; ii) correlate the neurophysiological changes with clinical outcome after 3 months’ treatment.MethodsLaser evoked potentials were recorded by 61 electroencephalogram channels before (T0), 1 h (T1) and 7 days after (T2) Erenumab 70 mg injection, stimulating the left and right forehead and the right hand. Laser evoked potential control 1 h after the injection served as placebo session.ResultsSeventeen migraine patients were evaluated. The N1 and N2 component obtained from the right and left trigeminal stimulation diminished in amplitude at T2, compared to T0 and T1 conditions. N2 habituation reduction slightly recovered at T2. Laser evoked potential changes did not correlate with clinical improvement after 3 months of Erenumab treatment.ConclusionsA single dose of Erenumab has a mild inhibitory effect on cortical responses evoked from trigeminal cutaneous a-delta fibers. Though this phenomenon was not predictive of the clinical outcome, it confirms a wide representation of calcitonin gene-related peptide receptors on trigeminal afferents.
      Citation: Cephalalgia
      PubDate: 2021-02-17T05:37:14Z
      DOI: 10.1177/0333102421996345
  • Twenty-five years of triptans – a nationwide population study
    • Authors: Olafur B Davidsson, Isa A Olofsson, Lisette JA Kogelman, Michael Asger Andersen, Klaus Rostgaard, Henrik Hjalgrim, Jes Olesen, Thomas Folkmann Hansen
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundThe efficacy of triptans as the main acute treatment strategy for migraine headache at the population-wide level needs to be understood to inform clinical decision-making. We summarise key trends in triptan use using more than 25 years of Danish nationwide data.MethodsWe conducted a nationwide register-based cohort study based on all Danish residents with access to public healthcare between 1 January 1994 and 31 October 2019 and summarise informative trends of all purchases of triptans in Denmark in the same period. Complete purchase records of Sumatriptan, Naratriptan, Zolmitriptan, Rizatriptan, Almotriptan, Eletriptan, and Frovatriptan were used.FindingsOver a 25-year period, triptan use increased from 345 to 945 defined daily doses (DDD) per 1000 inhabitants per year and the yearly prevalence of triptan use increased from 5.17 to 14.57 per 1000 inhabitants. Between 2014 and 2019, 12.3% of the Danish migraine population purchased a triptan. Following their initial purchase, 43% of patients had not repurchased triptans within 5 years. At most, 10% of patients indicating triptan discontinuation tried more than one triptan. The prevalence of triptan overuse, defined as having purchased at least 20 DDDs of triptans per month for 3 consecutive months, increased in parallel with the prevalence of triptan use, prevalent in 56 of every 1000 triptan users every year between 2014 and 2019. InterpretationIn a cohort with access to free clinical consultations and low medication costs, we observed low rates of triptan adherence, likely due to disappointing efficacy and/or unpleasant side effects rather than economic considerations. Triptan success continues to be hindered by poor implementation of clinical guidelines and high rates of treatment discontinuance.
      Citation: Cephalalgia
      PubDate: 2021-02-15T04:35:42Z
      DOI: 10.1177/0333102421991809
  • Early treatment with sumatriptan prevents PACAP38-induced migraine: A
           randomised clinical trial
    • Authors: Nita Katarina Frifelt Wienholtz, Casper Emil Christensen, Ditte Georgina Zhang, Hande Coskun, Hashmat Ghanizada, Mohammad Al-Mahdi Al-Karagholi, Jens Hannibal, Alexander Egeberg, Jacob P Thyssen, Messoud Ashina
      Abstract: Cephalalgia, Ahead of Print.
      ObjectiveTo determine whether early treatment with sumatriptan can prevent PACAP38-induced migraine attacks.MethodsA total of 37 patients with migraine without aura were enrolled between July 2018 to December 2019. All patients received an intravenous infusion of 10 picomole/kg/min of PACAP38 over 20 min followed by an intravenous infusion of 4 mg sumatriptan or placebo over 10 min on two study days in a randomised, double-blind, placebo-controlled, crossover study.ResultsOf 37 patients enrolled, 26 (70.3%) completed the study and were included in analyses. Of the 26 patients, four (15%) developed a PACAP38-induced migraine attack on sumatriptan and 11 patients (42%) on placebo (p = 0.016). There were no differences in area under the curve for headache intensity between sumatriptan (mean AUC 532) and placebo (mean AUC 779) (p = 0.35). Sumatriptan significantly constricted the PACAP38-dilated superficial temporal artery immediately after infusion (T30) compared with infusion of placebo (p 
      Citation: Cephalalgia
      PubDate: 2021-02-11T05:05:27Z
      DOI: 10.1177/0333102420975395
  • Anti-CGRP monoclonal antibodies for migraine prevention: A systematic
           review and likelihood to help or harm analysis
    • Authors: Konstantina Drellia, Lili Kokoti, Christina I Deligianni, Dimitrios Papadopoulos, Dimos D Mitsikostas
      Abstract: Cephalalgia, Ahead of Print.
      Introduction and objectiveMonoclonal antibodies targeting the calcitonin gene-related peptide pathway (anti-CGRP mAbs) have shown promising efficacy in randomised clinical trials for the prevention of episodic and chronic migraine, but no head-to-head comparisons with established treatments are available. We aimed to examine absolute differences in benefit-risk ratios between anti-CGRP mAbs, topiramate and propranolol for the prevention of episodic migraine and between anti-CGRP mAbs, topiramate and onabotulinumtoxinA for the prevention of chronic migraine using a likelihood to help versus harm analysis.MethodsThe number of patients needed to be treated for a patient to achieve ≥ 50% reduction in migraine days (NNTB50%) was used as an effect size metric of efficacy. The number of patients needed to be treated for a patient to experience an adverse event that led to treatment discontinuation (NNTHD-AE) was used as a measure of risk. Likelihood to help versus harm values – which are the ratios of NNTH:NNTB – were calculated using data from phase 3 randomised clinical trials.ResultsAll agents tested were more likely to be beneficial than harmful (likelihood to help versus harm > 1) with the exception of topiramate at 200 mg per day for the prevention of episodic migraine. Anti-CGRP mAbs in all tested doses had higher LHH values than propranolol or topiramate for episodic migraine and onabotulinumtoxinA or topiramate for chronic migraine prevention. Fremanezumab had the highest LHH ratio in episodic migraine and galcanezumab in chronic migraine.ConclusionThis analysis showed that anti-CGRP mAbs exhibit a more favourable benefit-risk ratio than established treatments for episodic and chronic migraine. Head-to-head studies are needed to confirm these results.
      Citation: Cephalalgia
      PubDate: 2021-02-11T05:05:25Z
      DOI: 10.1177/0333102421989601
  • Combination of acupuncture and medical training therapy on tension type
           headache: Results of a randomised controlled pilot study
    • Authors: Joerg Schiller, Matthias Karst, Tim Kellner, Wen Zheng, Daniel Niederer, Lutz Vogt, Isabelle Eckhardt, Florian Beissner, Christoph Korallus, Christian Sturm, Christoph Egen, Christoph Gutenbrunner, Matthias Georg Fink
      Abstract: Cephalalgia, Ahead of Print.
      ObjectivesThe aim of this study was to compare the effects of acupuncture and medical training therapy alone and in combination with those of usual care on the pain sensation of patients with frequent episodic and chronic tension-type headache.DesignThis was a prospective single-centre randomised controlled trial with four balanced treatment arms. The allocation was carried out by pre-generated randomisation lists in the ratio 1:1:1:1 with different permutation block sizes.SettingThe study was undertaken in the outpatient clinic of Rehabilitation Medicine of the Hannover Medical School.Participants and interventions: Ninety-six adult patients with tension-type headache were included and randomised into usual care (n = 24), acupuncture (n = 24), medical training (n = 24), and combination of acupuncture and medical training (n = 24). One patient was excluded from analysis because of withdrawing her/his consent, leaving 95 patients for intention to treat analysis. Each therapy arm consisted of 6 weeks of treatment with 12 interventions. Follow-up was at 3 and 6 months.Main outcome measuresPain intensity (average, maximum and minimum), frequency of headache, responder rate (50% frequency reduction), duration of headache and use of headache medication.Clinical results: The combination of acupuncture and medical training therapy significantly reduced mean pain intensity compared to usual care (mean = −38%, standard deviation = 25%, p = 0.012). Comparable reductions were observed for maximal pain intensity (−25%, standard deviation = 20%, 0.014) and for minimal pain intensity (−35%, standard deviation = 31%, 0.03). In contrast, neither acupuncture nor medical training therapy differed significantly from usual care. No between-group differences were found in headache frequency, mean duration of headache episodes, and pain medication intake. At 3 months, the majority of all patients showed a reduction of at least 50% in headache frequency. At 6 months, significantly higher responder rates were found in all intervention groups compared to usual care.ConclusionsIn contrast to monotherapy, only the combination of acupuncture and medical training therapy was significantly superior in reduction of pain intensity compared to usual care.Trial registration: Registered on 11 February 2019. German Clinical Trials Register, DRKS00016723.
      Citation: Cephalalgia
      PubDate: 2021-02-10T04:41:38Z
      DOI: 10.1177/0333102421989620
  • Effect of comorbid migraine on propranolol efficacy for painful TMD in a
           randomized controlled trial
    • Authors: Inna E Tchivileva, Richard Ohrbach, Roger B Fillingim, Pei Feng Lim, Massimiliano Di Giosia, Margarete Ribeiro-Dasilva, John H Campbell, Holly Hadgraft, Janet Willis, Samuel J Arbes, Gary D Slade
      Abstract: Cephalalgia, Ahead of Print.
      IntroductionThe migraine-preventive drug propranolol is efficacious in reducing pain from temporomandibular disorder, suggesting potential modifying or mediating effects of comorbid migraine.MethodsIn this randomized controlled trial, myofascial temporomandibular disorder patients were treated with propranolol or placebo for 9 weeks. The primary endpoint was change in a facial pain index derived from daily symptom diaries. Linear and logistic regression models tested for a migraine × treatment-group interaction in reducing facial pain index. Counterfactual models explored changes in headache impact and heart rate as mediators of propranolol's efficacy.ResultsPropranolol's efficacy in reducing facial pain index was greater among the 104 migraineurs than the 95 non-migraineurs: For example, for the binary ≥ 30% reduction in facial pain index, odds ratios were 3.3 (95% confidence limits: 1.4, 8.1) versus 1.3 (0.5, 3.2), respectively, although the interaction was statistically non-significant (p = 0.139). Cumulative response curves confirmed greater efficacy for migraineurs than non-migraineurs (differences in area under the curve 26% and 6%, respectively; p = 0.081). While 9% of the treatment effect was mediated by reduced headache impact, 46% was mediated by reduced heart rate.ConclusionsPropranolol was more efficacious in reducing temporomandibular disorder pain among migraineurs than non-migraineurs, with more of the effect mediated by reduced heart rate than by reduced headache impact.Study identification and registrationSOPPRANO; NCT02437383;
      Citation: Cephalalgia
      PubDate: 2021-02-09T06:18:57Z
      DOI: 10.1177/0333102421989268
  • The prevalence of migraine in Argentina: A reappraisal
    • Authors: Marco Lisicki, María L Figuerola, Lucas Bonamico, Daniel Lew, María T Goicochea
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundArgentina has one of the largest territories in the world, which spreads over a lengthy latitudinal span. Its population is mainly composed of a mixture of South American natives and the descendants of numerous waves of European immigrants. Results from a previous study suggested that the prevalence of migraine in Argentina is the lowest in the region. Here we aimed to reassess the prevalence of migraine in Argentina applying a more sensitive and specific screening tool.MethodsWe conducted a random computer assisted telephonic interview (n= 2500) using the Migraine Screen Questionnaire to evaluate the prevalence of migraine and some of its features among Argentinian adults.ResultsThe overall prevalence of migraine was 9.5% (14% in females and 5% in males). Estimated migraine prevalence rates ranged between 6.3% and 12% across different regions. The approximated prevalence of high frequency and chronic migraine were 1.9% and 1.5% of the total population respectively. Consumption of analgesics on 10 or more days per month was reported by 18% of migraine sufferers (≈1.7% of the population).ConclusionsThe prevalence of migraine in Argentina is higher than previously reported. Prevalence rates vary extensively across the territory. Specifically evaluating the determinants of these variations might be a promising avenue of research.
      Citation: Cephalalgia
      PubDate: 2021-02-02T04:29:09Z
      DOI: 10.1177/0333102421989262
  • TRESK background potassium channel modifies the TRPV1-mediated nociceptor
           excitability in sensory neurons
    • Authors: Miklós Lengyel, Dominika Hajdu, Alice Dobolyi, Judit Rosta, Gábor Czirják, Mária Dux, Péter Enyedi
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundTWIK-related spinal cord potassium channel (TRESK) background potassium channels have a key role in controlling resting membrane potential and excitability of sensory neurons. A frameshift mutation leading to complete loss of TRESK function has been identified in members of a family suffering from migraine with aura. In the present study, we examined the role of TRESK channels on nociceptor function in mice.MethodsCalcium imaging was used to investigate the role of TRESK channels in the modulation of the response evoked by transient receptor potential vanilloid 1 (TRPV1) receptor stimulation in dorsal root ganglion neurons. Release of calcitonin gene-related peptide from trigeminal afferents and changes in meningeal blood flow were also measured. Experiments were performed on wild-type and TRESK knockout animals.ResultsInhibition of TRESK increased the TRPV1-mediated calcium signal in dorsal root ganglion neurons and potentiated capsaicin-induced increases in calcitonin gene-related peptide release and meningeal blood flow. Activation of TRESK decreased the capsaicin sensitivity of sensory neurons, leading to an attenuation of capsaicin-induced increase in meningeal blood flow. In TRESK knockout animals, TRPV1-mediated nociceptive reactions were unaffected by pretreatment with TRESK modulators.ConclusionsPharmacological manipulation of TRESK channels influences the TRPV1-mediated functions of nociceptors. Altered TRESK function might contribute to trigeminal nociceptor sensitization in migraine patients.
      Citation: Cephalalgia
      PubDate: 2021-02-02T04:29:08Z
      DOI: 10.1177/0333102421989261
  • A population-based survey for disabling headaches in Greece: Prevalence,
           burden and treatment preferences
    • Authors: Theodoros S Constantinidis, Chryssa Arvaniti, Nikolaos Fakas, Jobst Rudolf, Evangelos Kouremenos, Ermioni Giannouli, Dimos D Mitsikostas
      Abstract: Cephalalgia, Ahead of Print.
      ObjectiveTo estimate the prevalence, burden and current treatment of disabling primary headaches in a large sample of the Greek population aged 18–70 years old.MethodsThis is an observational descriptive study, with cross-sectional design performed by quantitative computer-assisted telephone interviews, using a validated 37-item questionnaire for headaches. The prevalence, burden, and current treatment of primary headaches (ICHD-3) were recorded along with participants’ treatment preferences.ResultsOut of 10,008 interviewed participants, 1197 (12.0%) reported headaches affecting performance. The annual prevalence of migraine was 8.1% (95% confidence interval, 7.6–8.7, corresponding to 0.6 million Greeks), of chronic migraine 1.0% (95% confidence interval, 0.8–1.2, corresponding to 0.1 million), and of tension-type headache 3.8% (95% confidence interval, 3.4–4.2, corresponding to 0.3 million). The participants with headaches reported 0.5 headache-induced lost workdays per month (corresponding to 5.8 million lost workdays annually) and reductions in performance on 2.8 workdays per month (corresponding to 30.9 million workdays annually). In all, 43.4% of headache participants felt bad/ashamed because of headaches and 21.9% sought professional treatment, most often from a private neurologist. 83.8% of headache participants had never taken pharmacological prophylaxis, and only 5.5% were currently under preventative treatment. For both prophylactic and acute treatment, headache participants prefer oral medication to injection or stimulation devices.ConclusionMore than 10% of the Greek adult population up to 70 years old experience disabling headaches, causing a dramatic work loss. More than 80% of these have never taken pharmacological prophylaxis. Thus, enriching the quality of life of people with headaches relies crucially on expanding awareness about headaches and their treatment.
      Citation: Cephalalgia
      PubDate: 2021-02-02T04:29:05Z
      DOI: 10.1177/0333102421989630
  • Prevalence of pre-cluster symptoms in episodic cluster headache: Is it
           possible to predict an upcoming bout'
    • Authors: Adam Sebastian Pedersen, Agneta Snoer, Mads Barloese, Anja Petersen, Rigmor Højland Jensen
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundEarly symptoms prior to a cluster headache bout have been reported to occur days or weeks before the actual beginning of the cluster headache bouts. This study aimed to describe the prevalence of pre-cluster (premonitory) symptoms and examine the predictability of an upcoming cluster headache bout.Methods100 patients with episodic cluster headache were included in this retrospective cross-sectional study. All patients underwent a semi-structured interview including 25 questions concerning pre-cluster symptoms.ResultsPre-cluster symptoms were reported by 86% of patients with a mean of 6.8 days (interquartile range 3–14) preceding the bout. An ability to predict an upcoming bout was reported by 57% with a mean 4.6 days (interquartile range 2–7) before the bout. Occurrence of shadow attacks was associated with increased predictability (odds ratio: 3.06, confidence interval: 1.19–7.88, p-value = 0.020). In remission periods, 58% of patients reported mild cluster headache symptoms and 53% reported occurrence of single shadow attacks.ConclusionsThe majority of episodic cluster headache patients experienced pre-cluster symptoms, and more than half could predict an upcoming bout, suggesting the significant potential of early intervention. Furthermore, the experience of mild cluster headache symptoms and infrequent shadow attacks in remission periods is common and suggest an underlying pathophysiology extending beyond the cluster headache bouts.
      Citation: Cephalalgia
      PubDate: 2021-01-21T04:30:38Z
      DOI: 10.1177/0333102421989255
  • Occipital ischaemic stroke after visual snow phenomenon – a case
    • Authors: Teresa Catarci
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundPersistent migraine with aura and neuroimaging examinations revealing ischaemia in the contralateral cortex may be associated with migrainous infarction. Despite being a neurological symptom that is distinct from migraine with aura, the visual snow phenomenon may also be associated with cerebral ischaemia. Here we describe a patient who reported short-lasting daily symptoms of visual snow that affected his entire visual field before becoming continuous and left-sided following acute occipital brain ischaemia. Case reportIn February 2017, a 74-year-old retired male was referred to our headache outpatient clinic with a diagnosis of recent right occipital cerebral ischaemia and migraine with aura. The patient reported visual snow symptoms that had changed from being bilateral and temporary to left-sided and permanent one day upon awakening; after being admitted to hospital a few hours later, he discovered he had had a stroke. He said he had never had any symptoms of migraine with aura. The visual snow phenomenon disappeared completely after about 1 year.ConclusionsIn our patient, a temporary daily visual snow phenomenon reversed to a persistent one. This phenomenon occurred in the part of his visual field that had been affected by the ischaemic occipital stroke, as typically happens in migrainous infarction. We hypothesise that the occipital lesion disrupted the inhibitory circuits, leading to a quadrantopic persistent visual snow. Since the mechanism may be the same as that observed in migrainous infarction, though with a different pathophysiology, it is possible to speculate that the aura in this case is the result, as opposed to the cause, of stroke in most patients.
      Citation: Cephalalgia
      PubDate: 2021-01-13T04:43:50Z
      DOI: 10.1177/0333102420985444
  • Safety profile of erenumab, galcanezumab and fremanezumab in pregnancy and
           lactation: Analysis of the WHO pharmacovigilance database
    • Authors: Roberta Noseda, Francesca Bedussi, Claudio Gobbi, Chiara Zecca, Alessandro Ceschi
      Abstract: Cephalalgia, Ahead of Print.
      ObjectiveTo assess the safety profile of erenumab, galcanezumab and fremanezumab in pregnancy and lactation.MethodsSafety reports of suspected adverse drug reactions were retrieved from VigiBase as of 31 December 2019, for a case-by-case assessment and disproportionality analysis using the reporting odds ratio (ROR).ResultsThere were 94 safety reports: 50 (53.2%) on erenumab, 31 (33.0%) on galcanezumab, and 13 (13.8%) on fremanezumab. In five (5.3%) safety reports, drug exposure occurred prior to pregnancy, in 85 (90.4%) during pregnancy, in one (1.1%) during lactation, in one (1.1%) via paternal exposure, and in two (2.1%) the exposure time was unknown. Out of 94 safety reports, 51 (54.3%) consisted only of drug exposure, while 43 (45.7%) additionally reported 47 adverse drug reactions including maternal toxicities (n = 18), poor breastfeeding (n = 1), spontaneous abortion (n = 23), preterm birth/prematurity (n = 3), and birth defects (n = 2). There was no signal of disproportionate reporting for spontaneous abortion compared to the full database (reporting odds ratio 1.46, 95% confidence interval 0.97–2.20). When triptans were used as a comparator group, a signal of disproportionate reporting for spontaneous abortion was detected in association with erenumab, galcanezumab, and fremanezumab (reporting odds ratio 1.86, 95% confidence interval 1.12–3.13), which was not statistically significant after excluding confounded safety reports (reporting odds ratio 1.21, 95% confidence interval 0.67–2.21).ConclusionsNo specific maternal toxicities, patterns of major birth defects, or increased reporting of spontaneous abortion were found. However, because of the relatively limited number of adverse drug reactions reported and the lack of long-term safety data, continuous surveillance is required in pregnant and lactating women exposed to these drugs.
      Citation: Cephalalgia
      PubDate: 2021-01-13T04:43:49Z
      DOI: 10.1177/0333102420983292
  • Effect of lockdown during COVID-19 on migraine: A longitudinal cohort
    • Authors: Iris E Verhagen, Daphne S van Casteren, Simone de Vries Lentsch, Gisela M Terwindt
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundThe objective of this study was to assess whether migraine-related outcomes changed during intelligent lockdown when compared with the prior period.MethodsThis was a cohort study evaluating the first month of intelligent lockdown in the Netherlands (12 March to 8 April 2020) compared with one baseline month (13 February to 11 March 2020). We identified 870 migraine patients treated at the Leiden Headache Center with headache e-diaries during the period of interest. Adherence to the e-diary had to be ≥80%, yielding 592 enrolled patients.ResultsIntelligent lockdown led to a decrease in monthly migraine days (−0.48; 95% CI: −0.78 to −0.18, p = 0.002) and acute medication days (−0.48; 95% CI: −0.76 to −0.20, p 
      Citation: Cephalalgia
      PubDate: 2021-01-12T04:19:29Z
      DOI: 10.1177/0333102420981739
  • The migraine postdrome: Spontaneous and triggered phenotypes
    • Authors: Nazia Karsan, Abigail Peréz-Rodríguez, Karthik Nagaraj, Pyari R Bose, Peter J Goadsby
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundNon-painful symptoms in migraine following headache resolution can last up to days. Studying the postdrome is important to appreciate the morbidity associated with migraine.MethodsFifty-three subjects (n = 53) with migraine were studied in an experimental setting, collecting historical phenotypic information on the postdrome in their spontaneous attacks, and also associated with nitroglycerin-triggered attacks, while being observed prospectively. In a separate headache clinic-based cohort of migraineurs (n = 42), who were age and sex-matched to the experimental group, the same phenotypic data were extracted from their clinic records. Spontaneous and nitroglycerin-triggered attack phenotypes, and experimental and clinical cohort phenotypes were compared using agreement analysis.ResultsIn the experimental group, 100% had a postdrome with their triggered attack, while 98% reported a postdrome in their spontaneous attacks. In the clinical group, 79% had reported a postdrome. In the experimental group, there was good agreement between spontaneous and nitroglycerin-triggered tiredness, hunger, mood change, sensory sensitivities and vertigo and with similarity in premonitory and postdrome phenotypes experienced in the same individual.ConclusionsThe migraine postdrome is common and symptomatically similar to the premonitory phase. The nitroglycerin model and migraine abortive agents can be used to study the postdrome experimentally. Systematic questioning of symptoms, as well as collateral histories from direct observers of migraine attacks, are likely to enhance symptomatic capture of the migraine postdrome, and aid understanding of attack mediation, abortion and neurobiology.
      Citation: Cephalalgia
      PubDate: 2021-01-11T04:41:30Z
      DOI: 10.1177/0333102420975401
  • Management of thunderclap headache in the emergency room: A retrospective
           cohort study
    • Authors: David García-Azorín, Nuria González-García, Jaime Abelaira-Freire, Alberto Marcos-Dolado, Ángel Luis Guerrero, Francisco Javier Martín-Sanchez, Jesús Porta-Etessam
      Abstract: Cephalalgia, Ahead of Print.
      IntroductionThe evaluation of red flags is crucial for the accurate the diagnosis of headache disorders, especially for thunderclap headache. We analysed if secondary headache disorders were adequately ruled out in patients that presented to the emergency room with thunderclap headache.MethodsIn this retrospective cohort study, we screened all patients that visited the emergency room for headache, including those that described thunderclap headache. We measured the frequency with which secondary causes were not adequately ruled out. We analysed the order of the exams, the final diagnosis, and the time elapsed between arrival, initial request for imaging, and the completion of the imaging.ResultsWe screened 2132 patients, and 42 (1.9%) fulfilled eligibility criteria. Mean age was 43.1 ± 17.1 years, and 57% of patients were female. For 22 (52.4%) patients, the work-up was incomplete. Vascular study was missing in 16 (38.1%) patients, cerebrospinal fluid evaluation in nine (21.4%), and magnetic resonance imaging in seven (16.7%), with multiple assessments missing in six (14.3%). There were ten different combinations in which the exams were performed, with the most frequent being the second exam’s cerebral spinal fluid evaluation in 18 (52.9%) and the computed tomography angiogram in 10 (29.4%). A secondary cause of thunderclap headache was found in 16 (38.1%) patients, and four (9.5%) had a primary headache diagnosis after an adequate and complete study.ConclusionsThunderclap onset was described in one of every 50 patients that visited the emergency room for headache. More than half of these patients were not adequately managed. More than a third of thunderclap headache patients had a secondary cause.
      Citation: Cephalalgia
      PubDate: 2021-01-08T04:49:46Z
      DOI: 10.1177/0333102420981721
  • Is pituitary MRI screening necessary in cluster headache'
    • Authors: Lou Grangeon, Emer O’Connor, Daisuke Danno, Thanh Mai Pham Ngoc, Sanjay Cheema, Erling Tronvik, Indran Davagnanam, Manjit Matharu
      Abstract: Cephalalgia, Ahead of Print.
      ObjectiveTo determine the prevalence and clinical predictors of pituitary adenomas in cluster headache patients, in order to determine the necessity of performing dedicated pituitary magnetic resonance imaging in patients with cluster headache.MethodsA retrospective study was conducted of all consecutive patients diagnosed with cluster headache and with available brain magnetic resonance imaging between 2007 and 2017 in a tertiary headache center. Data including demographics, attack characteristics, response to treatments, results of neuroimaging, and routine pituitary function tests were recorded.ResultsSeven hundred and eighteen cluster headache patients attended the headache clinic; 643 underwent a standard magnetic resonance imaging scan, of whom 376 also underwent dedicated pituitary magnetic resonance imaging. Pituitary adenomas occurred in 17 of 376 patients (4.52%). Non-functioning microadenomas (n = 14) were the most common abnormality reported. Two patients, one of whom lacked the symptoms of pituitary disease, required treatment for their pituitary lesion. No clinical predictors of those adenomas were identified after multivariate analysis using random forests. Systematic pituitary magnetic resonance imaging scanning did not benefit even a single patient in the entire cohort.ConclusionThe prevalence of pituitary adenomas in cluster headache is similar to that reported in the general population, thereby precluding an over-representation of pituitary lesions in cluster headache. We conclude that the diagnostic assessment of cluster headache patients should not include specific pituitary screening. Only patients with standard brain magnetic resonance imaging findings or symptoms suggestive of a pituitary disorder require brain magnetic resonance imaging with dedicated pituitary views.
      Citation: Cephalalgia
      PubDate: 2021-01-07T05:58:37Z
      DOI: 10.1177/0333102420983303
  • Prevalence and characteristics of Alice in Wonderland Syndrome in adult
           migraineurs: Perspectives from a tertiary referral headache unit
    • Authors: Giulio Mastria, Valentina Mancini, Marco Di Cesare, Marta Puma, Michele Alessiani, Barbara Petolicchio, Alessandro Viganò, Vittorio Di Piero
      Pages: 515 - 524
      Abstract: Cephalalgia, Volume 41, Issue 5, Page 515-524, April 2021.
      BackgroundMigraine affects how the brain processes sensory information at multiple levels. The aberrant integration of visual and somatosensory stimuli is thought to underlie Alice in Wonderland Syndrome, a disorder often reported as being associated with migraine. However, there is still a lack of knowledge about the epidemiology of this syndrome in migraineurs and the association between Alice in Wonderland Syndrome episodes and migraine attacks. Therefore, we conducted a prospective cohort study to systematically evaluate the prevalence and the clinical features of Alice in Wonderland Syndrome in a large sample of patients with migraine.MethodsAll the patients attending for the first time a tertiary-level headache clinic were consecutively screened for Alice in Wonderland Syndrome symptoms by means of an ad hoc questionnaire and detailed clinical interview, over a period of 1.5 years. Patients experiencing Alice in Wonderland Syndrome symptoms were contacted for a follow-up after 8–12 months.ResultsTwo hundred and ten patients were recruited: 40 patients (19%) reported lifetime occurrence of Alice in Wonderland Syndrome, 90% of whom (38/40) had migraine with aura. Thirty-one patients experienced episodes of Alice in Wonderland Syndrome within 1 h from the start of migraine headache. Patients reported either visual or visual and somatosensory symptoms (i.e. somatosensory symptoms never presented alone). We collected the follow-up details of 30 patients with Alice in Wonderland Syndrome, 18 of whom had been prescribed a preventive treatment for migraine. After 8–12 months, 5 of the treated patients reported a decrease, while 13 reported no episodes of Alice in Wonderland Syndrome.ConclusionAlice in Wonderland Syndrome prevalence in migraineurs was found to be higher than expected. Alice in Wonderland Syndrome was mostly associated with migraine with aura and tended to occur close to the migraine attack, suggesting the existence of a common pathophysiological mechanism. Patients treated with migraine preventive treatments had a higher chance of decreasing or even resolving Alice in Wonderland Syndrome episodes.
      Citation: Cephalalgia
      PubDate: 2020-11-10T06:57:02Z
      DOI: 10.1177/0333102420968245
      Issue No: Vol. 41, No. 5 (2020)
  • Real-life treatment of cluster headache in a tertiary headache center –
           results from the Danish Cluster Headache Survey
    • Authors: Anja Sofie Petersen, Nunu Lund, Rigmor Højland Jensen, Mads Barloese
      Pages: 525 - 534
      Abstract: Cephalalgia, Volume 41, Issue 5, Page 525-534, April 2021.
      BackgroundPharmacological treatment of cluster headache constitutes the core of clinical management, but evidence is sparse. We aimed to generate insight in the existing treatment and identify associations between clinical features and treatment response.MethodsPatients aged 18–65 diagnosed with cluster headache according to the ICHD-2 completed a questionnaire followed by a structured interview. Multiple logistic regression was used to identify associations.ResultsThe population consisted of 400 patients with an episodic: chronic ratio of 1.7:1. Episodic patients were more likely to respond to triptans (odds ratio = 1.77, confidence interval: 1.08–2.91, p = 0.023) and oxygen (odds ratio = 1.64, confidence interval: 1.05–2.57, p = 0.031) than chronic. Oxygen response was less likely if pain intensity was very severe (odds ratio = 0.53, confidence interval: 0.33–2.57, p = 0.006) and the risk of a poor response increased with disease duration (odds ratio = 0.79, confidence interval: 0.65–0.96, p = 0.016). Among current users of sumatriptan injection and oxygen, the proportion achieving 100% relief was higher with sumatriptan injection (p > 0.001) than with oxygen. No associations were identified regarding verapamil. Only 57% of current users of preventive medication responded at a 50% level.ConclusionEpisodic cluster headache is more responsive to acute therapy than chronic. Further, sumatriptan injection was more effective than oxygen and the responder-rate was limited with verapamil. More effective acute and preventive therapies are needed for cluster headache patients.
      Citation: Cephalalgia
      PubDate: 2020-11-18T05:22:58Z
      DOI: 10.1177/0333102420970455
      Issue No: Vol. 41, No. 5 (2020)
  • Responses of spinal trigeminal neurons to noxious stimulation of paranasal
           cavities – a rat model of rhinosinusitis headache
    • Authors: Michael Koch, Julika Sertel-Nakajima, Karl Messlinger
      Pages: 535 - 545
      Abstract: Cephalalgia, Volume 41, Issue 5, Page 535-545, April 2021.
      BackgroundThe 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.MethodsIn 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.ResultsTwenty-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.ConclusionSpecific 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.
      Citation: Cephalalgia
      PubDate: 2020-11-18T05:28:40Z
      DOI: 10.1177/0333102420970467
      Issue No: Vol. 41, No. 5 (2020)
  • Time course of efficacy of ubrogepant for the acute treatment of migraine:
           Clinical implications
    • Authors: Peter J Goadsby, Andrew M Blumenfeld, Richard B Lipton, David W Dodick, Kavita Kalidas, Aubrey M Adams, Abhijeet Jakate, Chengcheng Liu, Armin Szegedi, Joel M Trugman
      Pages: 546 - 560
      Abstract: Cephalalgia, Volume 41, Issue 5, Page 546-560, April 2021.
      BackgroundThe full utility of an acute treatment requires examination of the entire time course of effect during a migraine attack. Here the time course of effect of ubrogepant is evaluated.MethodsACHIEVE-I and -II were double-blind, single-attack, Phase 3 trials. Adults with migraine were randomised 1:1:1 to placebo or ubrogepant (50mg or 100mg, ACHIEVE-I; 25 mg or 50 mg, ACHIEVE-II). Pain freedom, absence of most bothersome symptom, and pain relief were assessed at various timepoints. Samples were collected for pharmacokinetic analysis. Data were pooled for this post-hoc analysis.ResultsParticipants’ (n = 912 placebo, n = 887 ubrogepant 50 mg, pooled analysis population) mean age was 41 years, with a majority female and white. Pain relief separated from placebo by 1 h (43% versus 37% [OR, 95% CI: 1.30, 1.0–1.59]), absence of most bothersome symptom by 1.5 h (28% versus 22% [1.42, 1.14–1.77]), and pain freedom by 2 h (20% vs. 13% [1.72, 1.33–2.22]). Efficacy was sustained from 2–24 h (pain relief: 1.71, 1.1–2.6; pain freedom: 1.71, 1.3–2.3) and remained separated at 48 h (pain relief: 1.7, 1.1–2.6; pain freedom: 1.31, 1.0–1.7). Pharmacokinetic analysis demonstrated maximum plasma concentrations were achieved at 1 h, with pharmacologically active concentrations reached within 11 min and remaining above the EC90 for nearly 12 h.ConclusionsEvaluation of the time course of effect of ubrogepant showed pain relief as the most sensitive and earliest measure of clinical effect, followed by absence of most bothersome symptom, and pain freedom. Efficacy was demonstrated out to 48 h, providing evidence of the long-lasting effect of ubrogepant. This evaluation supports the role of examining the entire time course of effect to understand fully the utility of an acute treatment for migraine.Trial registration: ACHIEVE I (, NCT02828020) and ACHIEVE II (, NCT02867709)
      Citation: Cephalalgia
      PubDate: 2020-11-26T12:03:21Z
      DOI: 10.1177/0333102420970523
      Issue No: Vol. 41, No. 5 (2020)
  • Headache complexity (number of symptom features) differentiates
           post-traumatic from non-traumatic headaches
    • Authors: Ann I Scher, James S McGinley, RJ Wirth, Richard B Lipton, Heidi Terrio, Lisa A Brenner, Wesley R Cole, Karen Schwab
      Pages: 582 - 592
      Abstract: Cephalalgia, Volume 41, Issue 5, Page 582-592, April 2021.
      BackgroundPost-traumatic headaches are a common sequela of mild traumatic brain injury (concussion). It is unclear whether or how these headaches differ phenotypically from primary headaches.ObjectiveDetermine whether there is an overarching unobserved latent trait that drives the expression of observed features of post-traumatic headache and other headaches.MethodsData from this post-hoc analysis come from the Warrior Strong Cohort Study conducted from 2010 through 2015. Approximately 25,000 soldiers were screened for concussion history at routine post-deployment health assessments. A random sample was invited to participate, enrolling 1567. Twelve observed headache phenotypic features were used to measure “headache complexity”, the latent trait of clinical interest, using single factor confirmatory factor analysis. We compared headache complexity between groups and determined whether headache complexity predicted accessing medical care for headache.ResultsOf 1094 soldiers with headaches, 198 were classified as having post-traumatic headache. These headaches were compared to those in the other soldiers (647 without concussion history and 249 with concussion history). Soldiers with post-traumatic headache had greater endorsement of all 12 headache features compared to the soldiers with non-concussive headaches. The confirmatory factor analysis showed good model fit (χ2 (51) = 95.59, p = 0.0002, RMSEA = 0.03, comparative fit index = 0.99, and Tucker-Lewis index = 0.99), providing empirical support for the headache complexity construct. Soldier groups differed in their mean headache complexity level (p 
      Citation: Cephalalgia
      PubDate: 2020-11-27T08:40:21Z
      DOI: 10.1177/0333102420974352
      Issue No: Vol. 41, No. 5 (2020)
  • Neurovascular contact plays no role in trigeminal neuralgia secondary to
           multiple sclerosis
    • Authors: Navid Noory, Emil Andonov Smilkov, Jette Lautrup Frederiksen, Tone Bruvik Heinskou, Anne Sofie Schott Andersen, Lars Bendtsen, Stine Maarbjerg
      Pages: 593 - 603
      Abstract: Cephalalgia, Volume 41, Issue 5, Page 593-603, April 2021.
      IntroductionA demyelinating plaque and neurovascular contact with morphological changes have both been suggested to contribute to the etiology of trigeminal neuralgia secondary to multiple sclerosis (TN-MS). The aim of this study was to confirm or refute whether neurovascular contact with morphological changes is involved in the etiology of TN-MS.MethodsWe prospectively enrolled consecutive TN-MS patients from the Danish Headache Center. Clinical characteristics were collected systematically. MRI scans were done using a 3.0 Tesla imager and were evaluated by the same experienced blinded neuroradiologist.ResultsSixty-three patients were included. Fifty-four patients were included in the MRI analysis. There was a low prevalence of neurovascular contact with morphological changes on both the symptomatic side (6 (14%)) and the asymptomatic side (4 (9%)), p = 0.157. Demyelinating brainstem plaques along the trigeminal afferents were more prevalent on the symptomatic side compared to the asymptomatic side (31 (58%) vs. 12 (22%), p 
      Citation: Cephalalgia
      PubDate: 2020-11-28T05:16:27Z
      DOI: 10.1177/0333102420974356
      Issue No: Vol. 41, No. 5 (2020)
  • Interictal amylin levels in chronic migraine patients: A case-control
    • Authors: Pablo Irimia, Iván Martínez-Valbuena, Ane Mínguez-Olaondo, Clara Domínguez-Vivero, Juan-Antonio Sánchez-Arias, Eduardo Martínez-Vila, María-Rosario Luquin, Rogelio Leira
      Pages: 604 - 612
      Abstract: Cephalalgia, Volume 41, Issue 5, Page 604-612, April 2021.
      BackgroundRecently, amylin and its receptors were found in different structures involved in migraine pathophysiology. Here, we evaluate interictal concentrations of amylin and calcitonin gene-related peptide in peripheral blood as biomarkers for chronic migraine.MethodsWe prospectively recruited patients with episodic migraine, chronic migraine and healthy controls. Interictal amylin and calcitonin gene-related peptide levels were assessed in blood samples using enzyme linked immunosorbent assay.ResultsWe assessed plasma samples from 58 patients with episodic migraine (mean age 37.71 ± 10.47, 87.9% female), 191 with chronic migraine (mean age 46.03 ± 11.93, 95% female), and on 68 healthy controls (mean age 43.58 ± 11.08 years, 86% female). Body mass index was 25.94 ± 4.53 kg/m2 for migraine patients and 25.13 ± 4.92 kg/m2 for healthy controls (p = 0.0683). Interictal plasma amylin levels were higher in chronic migraine patients (47.1 pg/mL) than in the episodic migraine patients (28.84 pg/mL, p 
      Citation: Cephalalgia
      PubDate: 2020-12-03T03:08:19Z
      DOI: 10.1177/0333102420977106
      Issue No: Vol. 41, No. 5 (2020)
  • How does the brain change in chronic migraine' Developing disease
    • Authors: Patricia Pozo-Rosich, Gianluca Coppola, Julio Pascual, Todd J Schwedt
      Pages: 613 - 630
      Abstract: Cephalalgia, Volume 41, Issue 5, Page 613-630, April 2021.
      BackgroundValidated chronic migraine biomarkers could improve diagnostic, prognostic, and predictive abilities for clinicians and researchers, as well as increase knowledge on migraine pathophysiology.ObjectiveThe objective of this narrative review is to summarise and interpret the published literature regarding the current state of development of chronic migraine biomarkers.FindingsData from functional and structural imaging, neurophysiological, and biochemical studies have been utilised towards the development of chronic migraine biomarkers. These biomarkers could contribute to chronic migraine classification/diagnosis, prognosticating patient outcomes, predicting response to treatment, and measuring treatment responses early after initiation. Results show promise for using measures of brain structure and function, evoked potentials, and sensory neuropeptide concentrations for the development of chronic migraine biomarkers, yet further optimisation and validation are still required.ConclusionsImaging, neurophysiological, and biochemical changes that occur with the progression from episodic to chronic migraine could be utilised for developing chronic migraine biomarkers that might assist with diagnosis, prognosticating individual patient outcomes, and predicting responses to migraine therapies. Ultimately, validated biomarkers could move us closer to being able to practice precision medicine in the field and thus improve patient care.
      Citation: Cephalalgia
      PubDate: 2020-12-09T05:38:47Z
      DOI: 10.1177/0333102420974359
      Issue No: Vol. 41, No. 5 (2020)
  • It is time to consider even chronic migraine as a real chronic disease
    • Authors: Marta Altieri, Mariangela Fratino, Ilaria Maestrini, Marta Puma, Vittorio Di Piero
      Pages: 631 - 633
      Abstract: Cephalalgia, Volume 41, Issue 5, Page 631-633, April 2021.

      Citation: Cephalalgia
      PubDate: 2020-08-25T04:56:32Z
      DOI: 10.1177/0333102420953108
      Issue No: Vol. 41, No. 5 (2020)
  • Update on headache and brain tumors
    • Authors: Antonio Palmieri, Luca Valentinis, Giorgio Zanchin
      Pages: 431 - 437
      Abstract: Cephalalgia, Volume 41, Issue 4, Page 431-437, April 2021.
      Headache is one of the leading symptoms often associated with brain tumours. Secondary headaches attributed to intracranial neoplasias have been included in subchapter 7.4 of the third edition of the International Classification of Headache Disorders (ICHD-3). According to ICHD-3, the headache may be attributed to a brain tumour if it has developed in close temporal relation with the development of the neoplasia, has significantly worsened in parallel with the worsening of the tumour, and/or has significantly improved following the successful treatment of the neoplasia. Brain tumour headache was traditionally thought to display some specific clinical characteristics, including worsening in the morning and/or when lying down, being aggravated by Valsalva-like manoeuvres and accompanied by nausea and/or vomiting; however, the studies performed after the advent of modern neurodiagnostic techniques have pointed out that the “classic” brain tumour headache is uncommon, particularly at the time of clinical presentation. Therefore, it becomes critical to seek some specific factors associated with the presence of an intracranial mass (the so-called “red flags”) that can guide the physician to establish an accurate diagnosis.
      Citation: Cephalalgia
      PubDate: 2020-11-28T05:18:07Z
      DOI: 10.1177/0333102420974351
      Issue No: Vol. 41, No. 4 (2020)
  • Headache and neck
    • Authors: Fabio Antonaci, Levent Ertuğrul Inan
      Pages: 438 - 442
      Abstract: Cephalalgia, Volume 41, Issue 4, Page 438-442, April 2021.
      Cervicogenic headache (CEH) is currently identified with different diagnostic criteria. The latest one is the International classification of headache disorders (ICHD), 3rd edition (2018). At the present time, there are not enough published articles with reliable sensitivity and specificity that may support a classification for clinical and research purposes. Current literature suggests improvement to the classification(s). The ICHD criteria should be modified to reach an optimal sensitive and specific level to identify CEH as a secondary headache. The B, C1, and C2 criteria should be implemented with proposed suggestions. The C3 criterion should be upgraded. Criteria such as mechanical precipitation of pain by digital pressure on neck trigger points and specific movements, strictly unilateral pain without side-shift, diffuse unilateral shoulder and arm pain, pain starting posteriorly and spreading anteriorly should be integral part of the classification.
      Citation: Cephalalgia
      PubDate: 2020-07-30T06:04:51Z
      DOI: 10.1177/0333102420944878
      Issue No: Vol. 41, No. 4 (2020)
  • Secondary headache attributed to exposure to or overuse of a substance
    • Authors: Kati Toom, Mark Braschinsky, Mark Obermann, Zara Katsarava
      Pages: 443 - 452
      Abstract: Cephalalgia, Volume 41, Issue 4, Page 443-452, April 2021.
      BackgroundSecondary headaches attributed to exposure to or the overuse of a substance are classified under chapter eight in the International Classification of Headache Disorders 3rd edition. Three distinct sub-chapters consider: 1. Headache attributed to exposure to a substance, 2. Medication overuse headache, and 3. Headache attributed to substance withdrawal. Headache attributed to exposure to a substance refers to a headache with onset immediately or within hours after the exposure, while medication overuse headache is a headache occurring on 15 or more days per month that has developed as a consequence of regular usage of acute headache medication(s) for more than three consecutive months in a patient with a pre-existing primary headache disorder. The withdrawal of caffeine, oestrogen, and opioids is most often associated with the development of headache.DiscussionDespite the current headache classification, there is no certainty of a causal relationship between the use of any substance and the development of headache. Some substances are likely to provoke headache in patients that suffer from a primary headache disorder like migraine, tension-type headache or cluster headache, while others were described to cause headache even in people that generally do not get headaches. Toxic agents, such as carbon monoxide (CO) are difficult to investigate systematically, while other substances such as nitric oxide (NO) were specifically used to induce headache experimentally. If a patient with an underlying primary headache disorder develops a headache, in temporal relation to exposure to a substance, which is significantly worse than the usual headache it is considered secondary. This is even more the case if the headache phenotype is different from the usually experienced headache characteristics. Medication overuse headache is a well-described, distinct disease entity with only marginally understood pathophysiology and associated psychological factors. Managing medication overuse headache patients includes education, detoxification, prophylactic treatments and treating comorbidities, which is reflected in available guidelines. Viewing medication overuse headache as a separate entity helps clinicians and researchers better recognise, treat and study the disorder.ConclusionIdentification of substances that may cause or trigger secondary headache is important in order to educate patients and health care professionals about potential effects of these substances and prevent unnecessary suffering, as well as deterioration in quality of life. Treatment in case of medication overuse and other chronic headache should be decisive and effective.
      Citation: Cephalalgia
      PubDate: 2020-08-21T04:33:53Z
      DOI: 10.1177/0333102420942238
      Issue No: Vol. 41, No. 4 (2020)
  • Headache and rhinosinusitis: A review
    • Authors: Claire EJ Ceriani, Stephen D Silberstein
      Pages: 453 - 463
      Abstract: Cephalalgia, Volume 41, Issue 4, Page 453-463, April 2021.
      Purpose of reviewTo explain our current understanding of headache attributed to rhinosinusitis, an often inappropriately diagnosed secondary headache.Recent findingsRecent studies have shown that headache attributed to rhinosinusitis is often over-diagnosed in patients who actually have primary headache disorders, most commonly migraine. Failure to recognize and treat rhinosinusitis, however, can have devastating consequences. Abnormalities of the sinuses may also be treatable by surgical means, which may provide headache relief in appropriately selected patients.SummaryIt is important for the practicing physician to understand how rhinosinusitis fits into the differential diagnosis of headache, both to avoid overdiagnosis in patients with primary headache, and to avoid underdiagnosis in patients with serious sinus disease.
      Citation: Cephalalgia
      PubDate: 2020-09-21T05:54:28Z
      DOI: 10.1177/0333102420959790
      Issue No: Vol. 41, No. 4 (2020)
  • Post-traumatic headache due to mild traumatic brain injury: Current
           knowledge and future directions
    • Authors: Todd J Schwedt
      Pages: 464 - 471
      Abstract: Cephalalgia, Volume 41, Issue 4, Page 464-471, April 2021.
      Background/objectivePost-traumatic headache is one of the most common and persistent symptoms following mild traumatic brain injury. The objective of this narrative review is to provide an update on the diagnostic criteria, clinical presentation, epidemiology, pathophysiology, and treatment of post-traumatic headache, and to identify future research priorities.MethodsThis is a narrative review of the literature regarding post-traumatic headache attributed to mild traumatic brain injury.ResultsOnset of post-traumatic headache within 7 days of injury is the only evidence for a causal relationship between the injury and the headache included in the diagnostic criteria. Post-traumatic headache often resolves within the first few days of onset, whereas it persists for at least 3 months in 30–50%. The majority of insights into post-traumatic headache pathophysiology come from pre-clinical animal studies and human imaging studies, which implicate structural, functional, metabolic, and neuroinflammatory mechanisms for post-traumatic headache. There is a paucity of quality evidence for how to best treat post-traumatic headache.ConclusionsAlthough meaningful progress has been made in the post-traumatic headache field, priorities for future research are numerous, including the optimization of diagnostic criteria, a greater understanding of post-traumatic headache pathophysiology, identifying mechanisms and predictors for post-traumatic headache persistence, and identifying safe, well-tolerated, effective therapies.
      Citation: Cephalalgia
      PubDate: 2020-11-19T12:56:01Z
      DOI: 10.1177/0333102420970188
      Issue No: Vol. 41, No. 4 (2020)
  • Hypersensitivity to calcitonin gene-related peptide in chronic migraine
    • Authors: Afrim Iljazi, Håkan Ashina, Zixuan Alice Zhuang, Cristina Lopez Lopez, Josefin Snellman, Messoud Ashina, Henrik Winther Schytz
      Abstract: Cephalalgia, Ahead of Print.
      ObjectiveTo investigate if calcitonin gene-related peptide infusion induces migraine-like attacks in chronic migraine patients.MethodsFifty-eight patients with chronic migraine, either with or without headache on the experimental day, were assessed for the incidence of migraine-like attacks after an intravenous infusion with calcitonin gene-related peptide 1.5 µg/min over 20 min. The primary endpoint was the incidence of migraine-like attacks after calcitonin gene-related peptide. Exploratory endpoints were the association between the incidence of migraine-like attacks and presence of headache on the experimental day, and headache frequency in the past month. Migraine-like attack data was compared to a historic cohort of 91 episodic migraine patients without headache on the experimental day. Total tenderness score, pressure-pain threshold and supra-threshold pressure pain at baseline were investigated in relation to incidence of migraine-like attacks and presence of headache on the experimental day.ResultsIn total, 83% of the 58 chronic migraine patients developed migraine-like attacks after calcitonin gene-related peptide infusion. Migraine-like attacks were found in 92% of chronic migraine patients with headache on the experimental day compared to 65% of chronic migraine patients without headache on the experimental day (p = 0.035). No differences were observed in total tenderness score and pressure-pain threshold between chronic migraine patients with and without headache on the experimental day. The incidence of migraine-like attacks following calcitonin gene-related peptide in chronic migraine patients without headache (65%) was equal to the historic cohort of 91 episodic migraine patients without headache (67%) on the experimental day.ConclusionsChronic migraine patients are hypersensitive to calcitonin gene-related peptide. The potency of calcitonin gene-related peptide as a migraine inductor is increased in chronic migraine patients with ongoing headache. We suggest that calcitonin gene-related peptide, besides being a migraine trigger also acts as a modulator of nociceptive transmission in the trigeminal system.
      Citation: Cephalalgia
      PubDate: 2020-12-16T06:06:20Z
      DOI: 10.1177/0333102420981666
  • Identification of work accommodations and interventions associated with
           work productivity in adults with migraine: A scoping review
    • Authors: Olivia Begasse de Dhaem, Mohammad Hadi Gharedaghi, Paul Bain, Gabrielle Hettie, Elizabeth Loder, Rebecca Burch
      Abstract: Cephalalgia, Ahead of Print.
      ObjectiveTo identify factors associated with work productivity in adults with migraine, and accommodations or interventions to improve productivity or the workplace environment for them.MethodsWe conducted a scoping review by searching MEDLINE, Embase, PsycINFO, Cumulative Index of Nursing and Allied Heath Literature, and Web of Science from their inception to 14 October 2019 for studies of any design that assessed workplace productivity in adults with migraine.ResultsWe included 26 articles describing 24 studies after screening 4139 records. Five prospective cohort studies showed that education on managing migraine in the workplace was associated with an increase in productivity of 29-36%. Two studies showed that migraine education and management in the workplace were associated with increased productivity (absenteeism decreased by 50% in one study). One prospective cohort study showed that occupational health referrals were associated with more than 50% reduction in absenteeism. Autonomy, social support, and job satisfaction were positively associated with productivity, while quantitative demands, emotional demands, job instability, and non-conducive work environment triggers are negatively associated with productivity in workers with migraine.ConclusionDespite migraine being the second leading cause of disability worldwide, there is a paucity of strong data on migraine-related work factors associated with productivity.Registration: None (scoping review)
      Citation: Cephalalgia
      PubDate: 2020-12-11T05:08:44Z
      DOI: 10.1177/0333102420977852
  • Migraine in children and adults born preterm: A nationwide register
           linkage study
    • Authors: Sonja Strang-Karlsson, Suvi Alenius, Pieta Näsänen-Gilmore, Markku Nurhonen, Peija Haaramo, Kari Anne I Evensen, Marja Vääräsmäki, Mika Gissler, Petteri Hovi, Eero Kajantie
      Abstract: Cephalalgia, Ahead of Print.
      ObjectiveBeing born preterm is related to adverse health effects later in life. We studied whether preterm birth predicts the risk of migraine.MethodsIn this nationwide register study, we linked data from six administrative registers for all 235,624 children live-born in Finland (January 1987 to September 1990) and recorded in the Finnish Medical Birth Register. n = 228,610 (97.0%) had adequate data and were included. Migraine served as primary outcome variable and was stringently defined as a diagnosis from specialised health care and/or ≥2 reimbursed purchases of triptans. We applied sex- and birth year-stratified Cox proportional hazard regression models to compute hazard ratios and confidence intervals (95% confidence intervals) for the association between preterm categories and migraine. The cohort was followed up until an average age of 25.1 years (range: 23.3–27.0).ResultsAmong individuals born extremely preterm (23–27 completed weeks of gestation), the adjusted hazard ratios for migraine was 0.55 (0.25–1.24) when compared with the full-term reference group (39–41 weeks). The corresponding adjusted hazard ratios and 95% confidence intervals for the other preterm categories were: Very preterm (28–31 weeks); 0.95 (0.68–1.31), moderately preterm (32–33 weeks); 0.96 (0.73–1.27), late preterm (34–36 weeks); 1.01 (0.91–1.11), early term (37–38 weeks); 0.98 (0.93–1.03), and post term (42 weeks); 0.98 (0.89–1.08). Migraine was predicted by parental migraine, lower socioeconomic position, maternal hypertensive disorder and maternal smoking during pregnancy.ConclusionWe found no evidence for a higher risk of migraine among individuals born preterm.
      Citation: Cephalalgia
      PubDate: 2020-12-10T05:06:52Z
      DOI: 10.1177/0333102420978357
  • Peri-ictal headaches in the paediatric population – prospective
    • Authors: Marta Zawadzka, Ewa Pilarska, Seweryna Konieczna, Marta Szmuda, Agnieszka Matheisel, Anna Lemska, Sandra Modrzejewska, Maria Mazurkiewicz-Bełdzińska
      Abstract: Cephalalgia, Ahead of Print.
      IntroductionThe co-occurrence of headache and epilepsy is well-documented in the adult population. The aim of the prospective study was to analyse in the paediatric population the correlations between the types of peri-ictal headaches and types of seizures. Furthermore, an attempt was made to find trends in characteristic features of peri-ictal headaches.Material: A total of 57 children with peri-ictal headache were enrolled in the study. The participants’ guardians were asked to keep a diary of the seizure and peri-ictal headache episodes during a 180-day period. During follow-up visits, systematic history regarding peri-ictal headaches was taken.ResultsA total of 913 seizure and 325 peri-ictal headache episodes were noted during the study. Post-ictal headaches were most common, occurring in 
      Citation: Cephalalgia
      PubDate: 2020-12-10T05:06:51Z
      DOI: 10.1177/0333102420977856
  • SUNCT/SUNA: Case series presenting in an orofacial pain clinic
    • Authors: Beth R Groenke, Iryna Hryvenko Daline, Donald R Nixdorf
      Abstract: Cephalalgia, Ahead of Print.
      AimLittle is known about short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). We present our experience with SUNCT/SUNA patients to aid identification and management of these disorders.MethodsA retrospective review of patient records of one orofacial pain clinic was performed. Inclusion criteria was a diagnosis of SUNCT/SUNA confirmed with at least one follow-up visit.ResultsSix of the 2464 new patients seen between 2015–2018 met the selection criteria (SUNCT n = 2, SUNA n = 4). Gender distribution was one male to one female and average age of diagnosis was 52 years (range 26–62). Attacks were located in the V1/V2 trigeminal distributions, and five patients reported associated intraoral pain. Pain quality was sharp, shooting, and burning with two patients reporting “numbness”. Pain was moderate-severe in intensity, with daily episodes that typically lasted for seconds. Common autonomic features were lacrimation, conjunctival injection, rhinorrhea, and flushing. Frequent triggers were touching the nose or a specific intraoral area. Lamotrigine and gabapentin were commonly used as initial therapy.ConclusionsDifferentiating between SUNCT/SUNA does not appear to be clinically relevant. Presenting symptoms were consistent with those published, except 5/6 patients describing intraoral pain and two patients describing paresthesia.
      Citation: Cephalalgia
      PubDate: 2020-12-03T03:33:59Z
      DOI: 10.1177/0333102420977292
  • Prevalence and risk factors of migraine and non-migraine headache in older
           people – results of the Heinz Nixdorf Recall study
    • Authors: Sara Schramm, Isabell Tenhagen, Börge Schmidt, Dagny Holle-Lee, Steffen Naegel, Zaza Katsarava, Karl-Heinz Jöckel, Susanne Moebus
      Abstract: Cephalalgia, Ahead of Print.
      BackgroundThe prevalence of migraine and non-migraine headache declines with age.MethodsData from the third visit (2011–2015) of the population-based Heinz Nixdorf Recall study were analysed (n = 2038, 51% women, 65–86 years). Possible risk factors for headache activity (obesity, education, smoking, sports, alcohol, partnership status, living alone, having children, sleep quality, depression, hypertension, diabetes mellitus, stroke, coronary heart disease, medication), and headache symptoms were assessed. We estimated the lifetime prevalence and the prevalence of current active headache of migraine with and without aura, and non-migraine headache. The associations between possible risk factors and headache activity (active vs. inactive) were estimated by age and sex-adjusted odds ratios and 95% confidence intervals (OR [95% CI]) using multiple logistic regression.ResultsThe lifetime prevalence of migraine was 28.6% (n = 584). One hundred and ninety-two (9.4%) had still-active migraine, 168 (3.5%) had migraine with aura, and 416 (5.9%) had migraine without aura. One hundred and sixty-eight (8.2%) had “episodic infrequent migraine, 0–8 headache days/month”, 10 (0.5%) had “episodic frequent migraine, 9–14 headache days/month”, and five (0.2%) had “chronic migraine, ≥15 headache days/month”. Overall, 10 (0.5%) had “chronic headache, any headache on ≥15 days/month”. Female gender and younger age were the most important associated migraine risk factors. Depression (1.62 [1.06; 2.47]) and poor sleep (1.06 [1.00; 1.12]) were associated with migraine and headache activity in general. Antihypertensives were associated with headache remission (0.80 [0.64; 1.00]). Additionally, undertaking less sports (0.72 [0.51; 1.03]) was associated with higher migraine activity.ConclusionsHeadaches and migraines are not rare in the older population. They are related to mood and sleep disturbance, and migraine even to less physical activity. Antihypertensives are related to headache remission.
      Citation: Cephalalgia
      PubDate: 2020-12-03T03:08:17Z
      DOI: 10.1177/0333102420977183
  • Sex differences in prevalence of migraine trigger factors: A
           cross-sectional study
    • Authors: Daphne S van Casteren, Iris E Verhagen, Gerrit LJ Onderwater, Antoinette MaassenVanDenBrink, Gisela M Terwindt
      Abstract: Cephalalgia, Ahead of Print.
      AimTo examine the effect of sex on migraine trigger factors.MethodsPrevalence of 11 frequently reported trigger factors was determined in a cross-sectional study among migraine patients from a validated migraine database (n = 5725 females and n = 1061 males). Female-to-male odds ratios were calculated for each trigger, using a logistic regression model with attack frequency and migraine subtype (with or without aura) as covariates. Additionally, the effect of sex on total number of triggers per individual was determined.ResultsThe top three most reported triggers in women were menstruation (78%), stress (77%), and bright light (69%). Men reported stress (69%), bright light (63%), and sleep deprivation (60%) most frequently as provoking factors. The following triggers were more often reported by women than men: Bright light (odds ratio 1.29 [95% CI 1.12–1.48]; p = 0.003), stress (1.47 [1.27–1.69]; p 
      Citation: Cephalalgia
      PubDate: 2020-11-18T05:32:22Z
      DOI: 10.1177/0333102420974362
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