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Migraine Disorders: HELP
Articles by Michel D. Ferrari
Based on 130 articles published since 2010
(Why 130 articles?)
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Between 2010 and 2020, M. D. Ferrari wrote the following 130 articles about Migraine Disorders.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6
1 Guideline Guidelines of the International Headache Society for controlled trials of preventive treatment of chronic migraine in adults. 2018

Tassorelli, Cristina / Diener, Hans-Christoph / Dodick, David W / Silberstein, Stephen D / Lipton, Richard B / Ashina, Messoud / Becker, Werner J / Ferrari, Michel D / Goadsby, Peter J / Pozo-Rosich, Patricia / Wang, Shuu-Jiun / Anonymous6710938. ·1 Headache Science Center, C. Mondino Foundation, Pavia, Italy. · 2 Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy. · 3 Department of Neurology, University Hospital Essen, Essen, Germany. · 4 Department of Neurology, Mayo Clinic, Phoenix, AZ, USA. · 5 Jefferson Headache Center, Thomas Jefferson University, Philadelphia, PA, USA. · 6 Montefiore Headache Center, Department of Neurology and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA. · 7 Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark. · 8 Dept of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada. · 9 Hotchkiss Brain Institute, Calgary, Alberta, Canada. · 10 Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands. · 11 National Institute for Health Research-Wellcome Trust King's Clinical Research Facility, King's College Hospital, London, England. · 12 Headache Research Group, VHIR, Universitat Autònoma de Barcelona, Barcelona Spain. · 13 Neurology Department, Hospital Vall d'Hebron, Barcelona, Spain. · 14 Neurological Institute, Taipei Veterans General Hospital and Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan. ·Cephalalgia · Pubmed #29504482.

ABSTRACT: Background Quality clinical trials form an essential part of the evidence base for the treatment of headache disorders. In 1991, the International Headache Society Clinical Trials Standing Committee developed and published the first edition of the Guidelines for Controlled Trials of Drugs in Migraine. In 2008, the Committee published the first specific guidelines on chronic migraine. Subsequent advances in drug, device, and biologicals development, as well as novel trial designs, have created a need for a revision of the chronic migraine guidelines. Objective The present update is intended to optimize the design of controlled trials of preventive treatment of chronic migraine in adults, and its recommendations do not apply to trials in children or adolescents.

2 Guideline European Headache Federation consensus on technical investigation for primary headache disorders. 2015

Mitsikostas, D D / Ashina, M / Craven, A / Diener, H C / Goadsby, P J / Ferrari, M D / Lampl, C / Paemeleire, K / Pascual, J / Siva, A / Olesen, J / Osipova, V / Martelletti, P / Anonymous5320857. ·Neurology Department, Athens Naval Hospital, Athens, Greece. dimosmitsikostas@me.com. · Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. ashina@dadlnet.dk. · European Headache Alliance, President, Dublin, Ireland. audreycraven@migraine.ie. · Department of Neurology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. hans.diener@uk-essen.de. · Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, and King's Clinical Research Facility, Kings College London, Wellcome Foundation Building, King's College Hospital, London, SE5 9PJ, UK. peter.goadsby@kcl.ac.uk. · Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. M.D.Ferrari@lumc.nl. · Medical Headache Center, Hospital Sisters of Mercy, Seilerstaette Linz, Linz, 4020, Austria. christian.lampl@bhs.at. · Department of Neurology, Ghent University Hospital, Ghent, Belgium. Koen.Paemeleire@uzgent.be. · University Hospital Marqués de Valdecilla and IDIVAL, 39011, Santander, Spain. juliopascual@telefonica.net. · Department of Neurology, Cerrahpasa School of Medicine, Istanbul University, Millet Cad, 34390, Capa/Istanbul, Turkey. akselsiva@gmail.com. · Danish Headache Centre and Department of Neurology, Rigshospitalet, Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. jes.olesen@regionh.dk. · Department of Neurology, First Moscow State Medical University, Moscow, Russia. osipova_v@mail.ru. · Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy. paolo.martelletti@uniroma1.it. ·J Headache Pain · Pubmed #26857820.

ABSTRACT: The diagnosis of primary headache disorders is clinical and based on the diagnostic criteria of the International Headache Society (ICHD-3-beta). However several brain conditions may mimic primary headache disorders and laboratory investigation may be needed. This necessity occurs when the treating physician doubts for the primary origin of headache. Features that represent a warning for a possible underlying disorder causing the headache are new onset headache, change in previously stable headache pattern, headache that abruptly reaches the peak level, headache that changes with posture, headache awakening the patient, or precipitated by physical activity or Valsalva manoeuvre, first onset of headache ≥50 years of age, neurological symptoms or signs, trauma, fever, seizures, history of malignancy, history of HIV or active infections, and prior history of stroke or intracranial bleeding. All national headache societies and the European Headache Alliance invited to review and comment the consensus before the final draft. The consensus recommends brain MRI for the case of migraine with aura that persists on one side or in brainstem aura. Persistent aura without infarction and migrainous infarction require brain MRI, MRA and MRV. Brain MRI with detailed study of the pituitary area and cavernous sinus, is recommended for all TACs. For primary cough headache, exercise headache, headache associated with sexual activity, thunderclap headache and hypnic headache apart from brain MRI additional tests may be required. Because there is little and no good evidence the committee constructed a consensus based on the opinion of experts, and should be treated as imperfect.

3 Review Primary headaches. 2017

Onderwater, Gerrit L J / Van Dongen, Robin M / Zielman, Ronald / Terwindt, Gisela M / Ferrari, Michel D. ·Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands. · Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: G.L.J.Onderwater@lumc.nl. ·Handb Clin Neurol · Pubmed #29110775.

ABSTRACT: Headache disorders, characterized by recurrent headache, are among the most common disorders of the nervous system. Primary headache disorders are by definition not the result of any other underlying disease or process. In this chapter the current status of cerebrospinal fluid (CSF) research and applications for clinical practice for the three main primary headaches - migraine, cluster headache, and tension-type headache - will be described. Primary headaches are clinically diagnosed disorders, with typically normal routine CSF measurements. Research in these headaches has been focused on identifying pathophysiologic pathways with a wide array of measured molecules. CSF research in the headache field is still in the discovery phase, with most studies performed in migraine and with unreplicated findings for most of the identified molecules. From a clinical standpoint it would be of great value if CSF biomarkers could be used as disorder-specific biomarkers for difficult primary headache cases, or to predict treatment responsiveness or risk for headache chronification. These applications are currently not yet feasible. For future research into CSF biomarkers for primary headache disorders, two different strategies should be employed: hypothesis-driven and nonhypothesis-driven biochemical research, to show new avenues for treatment strategies and develop prediction models for clinical use.

4 Review Migraine biomarkers in cerebrospinal fluid: A systematic review and meta-analysis. 2017

van Dongen, Robin M / Zielman, Ronald / Noga, Marek / Dekkers, Olaf M / Hankemeier, Thomas / van den Maagdenberg, Arn Mjm / Terwindt, Gisela M / Ferrari, Michel D. ·1 Department of Neurology, Leiden University Medical Centre, the Netherlands. · 2 Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, the Netherlands. · 3 Department of Clinical Epidemiology, Leiden University Medical Centre, the Netherlands. · 4 Department of Clinical Epidemiology, Aarhus University Hospital, Denmark. · 5 Department of Human Genetics, Leiden University Medical Centre, the Netherlands. ·Cephalalgia · Pubmed #26888294.

ABSTRACT: Objective To perform a meta-analysis of migraine biomarkers in cerebrospinal fluid (CSF) and of corresponding blood concentrations. Methods We conducted a systematic search for studies that measured biochemical compounds in CSF of chronic or episodic migraineurs and non-headache controls. Subsequent searches retrieved studies with blood measurements of selected CSF biomarkers. If a compound was assessed in three or more studies, results were pooled in a meta-analysis with standardised mean differences (SMD) as effect measures. Results Sixty-two compounds were measured in 40 CSF studies. Most important results include: increased glutamate (five studies, SMD 2.22, 95% CI: 1.30, 3.13), calcitonin gene-related peptide (CGRP) (three studies, SMD: 3.80, 95% CI: 3.19, 4.41) and nerve growth factor (NGF) (three studies, SMD: 6.47, 95% CI: 5.55, 7.39) in chronic migraine patients and decreased β-endorphin (β-EP) in both chronic (four studies, SMD: -1.37, 95% CI: -1.80, -0.94) and interictal episodic migraine patients (three studies, SMD: -1.12, 95% CI: -1.65, -0.58). In blood, glutamate (interictal) and CGRP (chronic, interictal and ictal) were increased and β-EP (chronic, interictal and ictal) was decreased. Conclusions Glutamate, β-EP, CGRP and NGF concentrations are altered in CSF and, except for NGF, also in blood of migraineurs. Future research should focus on the pathophysiological roles of these compounds in migraine.

5 Review Wiping Out CGRP: Potential Cardiovascular Risks. 2016

MaassenVanDenBrink, Antoinette / Meijer, Joris / Villalón, Carlos M / Ferrari, Michel D. ·Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: a.vanharen-maassenvandenbrink@erasmusmc.nl. · Department of Neurology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. · Department of Pharmacobiology, Cinvestav-Coapa, Czda. Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 Mexico City, Mexico. ·Trends Pharmacol Sci · Pubmed #27338837.

ABSTRACT: Migraine is a common episodic neurovascular brain disorder associated with increased risk of cardio- and cerebrovascular ischemia. Migraine headache is likely caused by activation of the trigeminovascular system and release of calcitonin gene-related peptide (CGRP). Monoclonal antibodies against CGRP or its receptor are currently being evaluated for the prevention of migraine attacks. Preliminary efficacy data are promising. However, because CGRP may act as a vasodilatory safeguard during cerebral and cardiac ischemia, CGRP blockade could transform transient mild ischemic events into full-blown infarcts. Here, we review the cerebro- and cardiovascular risks that might be associated with CGRP blockade and which clinical and preclinical studies should be conducted to better assess the potential safety issues of this new promising class of drug.

6 Review Migraine pathophysiology: lessons from mouse models and human genetics. 2015

Ferrari, Michel D / Klever, Roselin R / Terwindt, Gisela M / Ayata, Cenk / van den Maagdenberg, Arn M J M. ·Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands. Electronic address: M.D.Ferrari@lumc.nl. · Department of Human Genetics, Leiden University Medical Centre, Leiden, Netherlands. · Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands. · Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. · Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands; Department of Human Genetics, Leiden University Medical Centre, Leiden, Netherlands. ·Lancet Neurol · Pubmed #25496898.

ABSTRACT: Migraine is a common, disabling, and undertreated episodic brain disorder that is more common in women than in men. Unbiased genome-wide association studies have identified 13 migraine-associated variants pointing at genes that cluster in pathways for glutamatergic neurotransmission, synaptic function, pain sensing, metalloproteinases, and the vasculature. The individual pathogenetic contribution of each gene variant is difficult to assess because of small effect sizes and complex interactions. Six genes with large effect sizes were identified in patients with rare monogenic migraine syndromes, in which hemiplegic migraine and non-hemiplegic migraine with or without aura are part of a wider clinical spectrum. Transgenic mouse models with human monogenic-migraine-syndrome gene mutations showed migraine-like features, increased glutamatergic neurotransmission, cerebral hyperexcitability, and enhanced susceptibility to cortical spreading depression, which is the electrophysiological correlate of aura and a putative trigger for migraine. Enhanced susceptibility to cortical spreading depression increased sensitivity to focal cerebral ischaemia, and blocking of cortical spreading depression improved stroke outcome in these mice. Changes in female hormone levels in these mice modulated cortical spreading depression susceptibility in much the same way that hormonal fluctuations affect migraine activity in patients. These findings confirm the multifactorial basis of migraine and might allow new prophylactic options to be developed, not only for migraine but potentially also for migraine-comorbid disorders such as epilepsy, depression, and stroke.

7 Review The comorbid relationship between migraine and epilepsy: a systematic review and meta-analysis. 2015

Keezer, M R / Bauer, P R / Ferrari, M D / Sander, J W. ·NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, Queen Square, London, UK. · Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands. · Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands. · Epilepsy Society, Chalfont St Peter, UK. ·Eur J Neurol · Pubmed #25495495.

ABSTRACT: A number of studies have suggested a pathophysiologic link between migraine and epilepsy. Our aim was to examine the relative lifetime prevalence of migraine in people with epilepsy (PWE) as well that of epilepsy in migraineurs. We carried out a systematic review, searching five electronic databases, specified bibliographies and conference abstracts in order to identify population-based studies that measured the lifetime co-prevalence of migraine and epilepsy. Two reviewers independently screened all titles and abstracts, carried out a risk of bias assessment and extracted the data. Meta-analyses were carried out using random effects models. Of the 3640 abstracts and titles screened, we identified 10 eligible studies encompassing a total of 1,548,967 subjects. Few of the studies used validated case ascertainment tools and there were inconsistent attempts to control for confounding. There was an overall 52% increase in the prevalence of migraine among PWE versus those without epilepsy [PR: 1.52 (95% CI: 1.29, 1.79)]. There was an overall 79% increase in the prevalence of epilepsy among migraineurs versus those without migraine [PR: 1.79 (95% CI: 1.43, 2.25)]. Subgroup analyses revealed that the method of ascertaining the epilepsy or migraine status of subjects was an important source of inter-study heterogeneity. Additional high quality primary studies are required, ones that use validated and accurate methods of case ascertainment as well as control for potential confounders.

8 Review Pearls and pitfalls in genetic studies of migraine. 2013

Eising, Else / de Vries, Boukje / Ferrari, Michel D / Terwindt, Gisela M / van den Maagdenberg, Arn M J M. ·Department of Human Genetics, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands. ·Cephalalgia · Pubmed #23671257.

ABSTRACT: PURPOSE OF REVIEW: Migraine is a prevalent neurovascular brain disorder with a strong genetic component, and different methodological approaches have been implemented to identify the genes involved. This review focuses on pearls and pitfalls of these approaches and genetic findings in migraine. SUMMARY: Common forms of migraine (i.e. migraine with and without aura) are thought to have a polygenic make-up, whereas rare familial hemiplegic migraine (FHM) presents with a monogenic pattern of inheritance. Until a few years ago only studies in FHM yielded causal genes, which were identified by a classical linkage analysis approach. Functional analyses of FHM gene mutations in cellular and transgenic animal models suggest abnormal glutamatergic neurotransmission as a possible key disease mechanism. Recently, a number of genes were discovered for the common forms of migraine using a genome-wide association (GWA) approach, which sheds first light on the pathophysiological mechanisms involved. CONCLUSIONS: Novel technological strategies such as next-generation sequencing, which can be implemented in future genetic migraine research, may aid the identification of novel FHM genes and promote the search for the missing heritability of common migraine.

9 Review Epigenetic mechanisms in migraine: a promising avenue? 2013

Eising, Else / A Datson, Nicole / van den Maagdenberg, Arn M J M / Ferrari, Michel D. ·Department of Human Genetics, Leiden University Medical Centre, Einthovenweg 20, Leiden 2333 ZC, The Netherlands. ·BMC Med · Pubmed #23379668.

ABSTRACT: Migraine is a disabling common brain disorder typically characterized by attacks of severe headache and associated with autonomic and neurological symptoms. Its etiology is far from resolved. This review will focus on evidence that epigenetic mechanisms play an important role in disease etiology. Epigenetics comprise both DNA methylation and post-translational modifications of the tails of histone proteins, affecting chromatin structure and gene expression. Besides playing a role in establishing cellular and developmental stage-specific regulation of gene expression, epigenetic processes are also important for programming lasting cellular responses to environmental signals. Epigenetic mechanisms may explain how non-genetic endogenous and exogenous factors such as female sex hormones, stress hormones and inflammation trigger may modulate attack frequency. Developing drugs that specifically target epigenetic mechanisms may open up exciting new avenues for the prophylactic treatment of migraine.

10 Review Headache: the changing migraine brain. 2013

Ferrari, Michel D. ·Department of Neurology, Chair Leiden Centre for Translational Neuroscience, Leiden University Medical Center, 2300 RC Leiden, Netherlands. m.d.ferrari@lumc.nl ·Lancet Neurol · Pubmed #23237889.

ABSTRACT: -- No abstract --

11 Review Right-to-left shunts and micro-embolization in migraine. 2012

Koppen, Hille / Palm-Meinders, Inge H / Ferrari, Michel D. ·Department of Neurology, Haga Hospital, The Hague, The Netherlands. h.koppen@hagaziekenhuis.nl ·Curr Opin Neurol · Pubmed #22449873.

ABSTRACT: PURPOSE OF REVIEW: The present review covers the latest studies on right-to-left shunts (RLSs) in migraine patients and different types of emboli capable of triggering migraine. RECENT FINDINGS: Although three recent studies found no increased RLS prevalence in migraine with aura patients, there remains ample evidence that the prevalence of RLS is increased in migraine with aura. Introduced emboli in the carotid artery of mice have been shown to cause cortical spreading depression, which has been considered the pathophysiological mechanism of migraine aura. In humans, iatrogenic introduced (micro)-emboli can provoke migraine attacks; available evidence, however, is limited. SUMMARY: RLS and migraine with aura (but not without) are comorbid conditions, but the biological mechanism remains speculative. Specific emboli are probably able (although infrequently) to induce migraine symptoms. There is no convincing evidence that closure of a RLS alters migraine frequency; therefore, diagnosis or treatment of RLS in migraine has no place in daily clinical practice and should only take place in controlled studies.

12 Review CADASIL and migraine: A narrative review. 2010

Liem, Michael K / Oberstein, Saskia A J Lesnik / van der Grond, Jeroen / Ferrari, Michel D / Haan, Joost. ·Leiden University Medical Center, Netherlands. m.k.liem@lumc.nl ·Cephalalgia · Pubmed #21038489.

ABSTRACT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke, cognitive decline, psychiatric disturbances and migraine. The prevalence of migraine in CADASIL is slightly higher than in the general population, and the proportion of migraine with aura is much higher. The pathophysiological mechanism that leads to increased aura prevalence in CADASIL is unknown. Possible mechanisms of the excess of migraine with aura are an increased susceptibility to cortical spreading depression (CSD) or a different expression of CSD. It is also possible that the brainstem migraine area is involved in CADASIL. Last, it is possible that the NOTCH3 mutation acts as a migraine aura susceptibility gene by itself. In this narrative review we summarize the literature about migraine in CADASIL, with a special focus on what CADASIL might teach us about the pathophysiology of migraine.

13 Review [Preventive treatment for migraine]. 2010

Mulleners, Wim M / Haan, Joost / Dekker, Frans / Ferrari, Michel D. ·Canisius-Wilhelmina Ziekenhuis, afd. Neurologie, Nijmegen, the Netherlands. w.mulleners@cwz.nl ·Ned Tijdschr Geneeskd · Pubmed #20699036.

ABSTRACT: Migraine patients who experience an average of 2 or more attacks per month are eligible for preventive treatment as well as treatment for acute attacks. The decision to offer preventative treatment is also made on the basis of the average attack duration, severity of the attacks, and response to attack treatment. Prior to initiating preventive treatment, the average attack frequency per month should be assessed, preferably by means of a headache diary over a number of months, as attack frequency is extremely variable. None of the currently available preventive drugs, such as beta-blockers, sodium valproate, topiramate and candesartan, were developed specifically for treating migraine, but were all originally intended for other indications. 50% of the migraine patients receiving preventive treatment can expect a 50% reduction in attacks, and the remaining attacks often seem to be less severe. The effects of the drugs are often unpredictable per individual, and side-effects frequently lead to early discontinuation of treatment. Drugs usually prescribed for cardiovascular disorders are often used. In the case of a disorder such as migraine with a high burden of disability, patients with cardiovascular or pulmonary comorbidity should receive medication that is optimally adjusted for both indications.

14 Review [Controversy surrounding the term 'retinal migraine']. 2010

Haan, Joost / van Santbrink, Helen / Ferrari, Michel D. ·Leids Universitair Medisch Centrum, afd. Neurologie, Leiden, the Netherlands. jhaan@rijnland.nl ·Ned Tijdschr Geneeskd · Pubmed #20699034.

ABSTRACT: The term 'retinal migraine' is probably often wrongly applied. The primary reason for this is a confusion of nomenclature. No consensus exists in the neurological and ophthalmological literature on the diagnosis of 'retinal migraine'. A diagnosis of 'retinal migraine' should be avoided if no typical migraine headache is experienced following the visual symptoms. It is also a matter of debate whether retinal migraine can lead to permanent visual loss. If a patient complains of monocular visual loss, he or she may in fact have hemianopia.

15 Review [Migraine and depression should be treated concurrently]. 2010

Louter, Mark A / Veen, Gerthe / Ferrari, Michel D / Zitman, Frans G / Terwindt, Gisela M. ·Leids Universitair Medisch Centrum, Afd. Neurologie, Leiden, the Netherlands. m.a.louter@lumc.nl ·Ned Tijdschr Geneeskd · Pubmed #20699032.

ABSTRACT: Migraine and depression are highly prevalent disorders with a strong bidirectional comorbidity: migraine patients have an increased risk for depression and patients suffering from depression have an increased risk for migraine. This comorbidity could be due to an underlying common pathophysiological mechanism. Chronification of migraine further increases the chance of developing depression, and vice versa. Misuse of migraine attack medication plays an important role in the development of chronic migraine. It is important for general practitioners, psychiatrists and neurologists to be alert to the comorbidity of migraine and depression. It is recommended that different hospital specialists should be involved in both the diagnosis and treatment of patients with comorbidity of migraine and depression.

16 Clinical Trial Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3b trial. 2019

Ferrari, Michel D / Diener, Hans Christoph / Ning, Xiaoping / Galic, Maja / Cohen, Joshua M / Yang, Ronghua / Mueller, Matthias / Ahn, Andrew H / Schwartz, Yael Carmeli / Grozinski-Wolff, Melissa / Janka, Lindsay / Ashina, Messoud. ·Leiden University Medical Centre, Leiden, Netherlands. Electronic address: m.d.ferrari@lumc.nl. · Universitätsklinikum Essen, Essen, Germany. · Teva Pharmaceuticals Industries, Frazer, PA, USA. · Teva Pharmaceuticals, Amsterdam, Netherlands. · Teva Pharmaceutical Industries, Petah Tikva, Israel. · Danish Headache Centre, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. ·Lancet · Pubmed #31427046.

ABSTRACT: BACKGROUND: Antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have shown efficacy in the prevention of migraine attacks. We investigated the efficacy and tolerability of fremanezumab, a fully humanised CGRP antibody, in patients with migraine who had previously not responded to two to four classes of migraine preventive medications. METHODS: The randomised, double-blind, placebo-controlled, parallel-group, phase 3b FOCUS trial was done at 104 sites (including hospitals, medical centres, research institutes, and group practice clinics) across Belgium, the Czech Republic, Denmark, Finland, France, Germany, Italy, the Netherlands, Poland, Spain, Sweden, Switzerland, the UK, and the USA. We enrolled participants aged 18-70 years with episodic or chronic migraine who had documented failure to two to four classes of migraine preventive medications in the past 10 years. Failure was defined as no clinically meaningful improvement after at least 3 months of therapy at a stable dose, as per the treating physician's judgment; discontinuation because of adverse events that made treatment intolerable; or treatment contraindicated or unsuitable for the preventive treatment of migraine for the patient. Participants were randomly assigned (1:1:1) by electronic interactive response technology to subcutaneously administered quarterly fremanezumab (month 1, 675 mg; months 2 and 3: placebo), monthly fremanezumab (month 1: 225 mg in episodic migraine and 675 mg in chronic migraine; months 2 and 3: 225 mg in both migraine subgroups), or matched monthly placebo for 12 weeks. The primary outcome was mean change from baseline in the monthly average number of migraine days during the 12-week treatment period. This trial is registered with ClinicalTrials.gov, number NCT03308968, and is now completed. FINDINGS: Between Nov 10, 2017, and July 6, 2018, 838 participants with episodic (329 [39%]) or chronic (509 [61%]) migraine were randomly assigned to placebo (n=279), quarterly fremanezumab (n=276), or monthly fremanezumab (n=283). Reductions from baseline in monthly average migraine days over 12 weeks were greater versus placebo (least-squares mean [LSM] change -0·6 [SE 0·3]) with quarterly fremanezumab (LSM change -3·7 [0·3]; LSM difference vs placebo -3·1 [95% CI -3·8 to -2·4]; p<0·0001) and with monthly fremanezumab (LSM change -4·1 [0·34]; LSM difference vs placebo -3·5 [-4·2 to -2·8]; p<0·0001). Adverse events were similar for placebo and fremanezumab. Serious adverse events were reported in four (1%) of 277 participants with placebo, two (<1%) of 276 with quarterly fremanezumab, and four (1%) of 285 with monthly fremanezumab. INTERPRETATION: Fremanezumab was effective and well tolerated in patients with difficult-to-treat migraine who had previously not responded to up to four classes of migraine preventive medications. FUNDING: Teva Pharmaceuticals.

17 Clinical Trial Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. 2018

Reuter, Uwe / Goadsby, Peter J / Lanteri-Minet, Michel / Wen, Shihua / Hours-Zesiger, Peggy / Ferrari, Michel D / Klatt, Jan. ·Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany. Electronic address: uwe.reuter@charite.de. · NIHR-Wellcome Trust, King's Clinical Research Facility, King's College London, London, UK. · Pain Department and FHU InvoPain, CHU Nice-Université Côte d'Azur, Nice, France; INSERM U1107 Migraine and Trigeminal Pain, Auvergne University, Clermont-Ferrand, France. · Novartis, East Hanover, NJ, USA. · Novartis Pharma, Basel, Switzerland. · Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands. ·Lancet · Pubmed #30360965.

ABSTRACT: BACKGROUND: A substantial proportion of patients with migraine does not respond to, or cannot tolerate, oral preventive treatments. Erenumab is a novel CGRP-receptor antibody with preventive efficacy in migraine. We assessed its efficacy and tolerability in patients with episodic migraine in whom previous treatment with two-to-four migraine preventives had been unsuccessful. METHODS: LIBERTY was a 12-week, double-blind, placebo-controlled randomised study at 59 sites in 16 countries. Eligible patients were aged 18-65 years and had a history of episodic migraine with or without aura for at least 12 months, had migraine for an average of 4-14 days per month during the 3 months before screening, and had been treated unsuccessfully (in terms of either efficacy or tolerability, or both) with between two and four preventive treatments. Eligible participants were randomly assigned (1:1) to receive either erenumab 140 mg (via two 70 mg injections) or placebo every 4 weeks subcutaneously for 12 weeks. Randomisation was by interactive response technology and was stratified by monthly frequency of migraine headache (4-7 vs 8-14 migraine days per month) during the baseline phase. Cenduit generated the randomisation list and assigned participants to groups. Participants, investigators, people doing various assessments, and the study sponsor were masked to treatment assignment. The primary endpoint was the proportion of patients achieving a 50% or greater reduction in the mean number of monthly migraine days during weeks 9-12. Efficacy was measured in the full analysis set, which included all randomly assigned patients who started their assigned treatment and completed at least one post-baseline monthly migraine day measurement. Safety and tolerability were assessed by recording adverse events and by physical examination, assessment of vital signs, clinical laboratory assessments, and electrocardiography. Safety was assessed in all randomly assigned patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT03096834. The trial is closed to new participants, but the open-label extension phase is ongoing. FINDINGS: Between March 20, 2017, and Oct 27, 2017, 246 participants were randomly assigned, 121 to the erenumab group and 125 to the placebo group. 95 of 246 (39%) participants had previously unsuccessfully tried two preventive drugs, 93 (38%) had tried three, and 56 (23%) had tried four. At week 12, 36 (30%) patients in the erenumab had a 50% or greater reduction from baseline in the mean number of monthly migraine days, compared with 17 (14%) in the placebo group (odds ratio 2·7 [95% CI 1·4-5·2]; p=0·002). The tolerability and safety profiles of erenumab and placebo were similar. The most frequent treatment-emergent adverse event was injection site pain, which occurred in seven (6%) participants in both groups. INTERPRETATION: Compared with placebo, erenumab was efficacious in patients with episodic migraine who previously did not respond to or tolerate between two and four previous migraine preventive treatments. Erenumab might be an option for patients with difficult-to-treat migraine who have high unmet needs and few treatment options. FUNDING: Novartis Pharma.

18 Article Abnormal cardiovascular response to nitroglycerin in migraine. 2019

van Oosterhout, Willebrordus Pj / Schoonman, Guus G / Saal, Dirk P / Thijs, Roland D / Ferrari, Michel D / van Dijk, J Gert. ·Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands. · Department of Neurology, OLVG Hospital, Amsterdam, the Netherlands. · Department of Neurology, Elisabeth Tweesteden Hospital, Tilburg, the Netherlands. · Department of Neurology, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands. · Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, the Netherlands. · Section of Clinical Neurophysiology, Leiden, University Medical Center, Leiden, the Netherlands. ·Cephalalgia · Pubmed #31594384.

ABSTRACT: INTRODUCTION: Migraine and vasovagal syncope are comorbid conditions that may share part of their pathophysiology through autonomic control of the systemic circulation. Nitroglycerin can trigger both syncope and migraine attacks, suggesting enhanced systemic sensitivity in migraine. We aimed to determine the cardiovascular responses to nitroglycerin in migraine. METHODS: In 16 women with migraine without aura and 10 age- and gender-matched controls without headache, intravenous nitroglycerin (0.5 µg·kg RESULTS: Nitroglycerin provoked a migraine-like attack in 13/16 (81.2%) migraineurs but not in controls ( DISCUSSION: Migraineurs who developed a migraine-like attack in response to nitroglycerin showed stronger systemic cardiovascular responses compared to non-headache controls. The stronger systemic cardiovascular responses in migraine suggest increased systemic sensitivity to vasodilators, possibly due to insufficient autonomic compensatory mechanisms.

19 Article Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial. 2019

Diener, Hans-Christoph / Goadsby, Peter J / Ashina, Messoud / Al-Karagholi, Mohammad Al-Mahdi / Sinclair, Alexandra / Mitsikostas, Dimos / Magis, Delphine / Pozo-Rosich, Patricia / Irimia Sieira, Pablo / Làinez, Miguel Ja / Gaul, Charly / Silver, Nicholas / Hoffmann, Jan / Marin, Juana / Liebler, Eric / Ferrari, Michel D. ·Faculty of Medicine, University Duisburg-Essen, Essen, Germany. · NIHR-Wellcome Trust King's Clinical Research Facility, King's College London, London, UK. · Danish Headache Center, Rigshospitalet Glostrup, University of Copenhagen, Copenhagen, Denmark. · Metabolic Neurology, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK. · 1st Neurology Department, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece. · Neurology Department and Pain Clinic, CHR East Belgium, Liège, Belgium. · Headache Unit, Neurology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain. · Headache Research Group, Vall d'Hebron Research Institute, Universitat Autonoma de Barcelona, Barcelona, Spain. · Clinica Universidad de Navarra, Pamplona, Spain. · Catholic University of Valencia, University Clinic Hospital, Valencia, Spain. · Migraine and Headache Clinic, Königstein, Germany. · The Walton Centre, Liverpool, UK. · electroCore, Inc., Basking Ridge, New Jersey, USA. · Leiden University Medical Center, Leiden, The Netherlands. ·Cephalalgia · Pubmed #31522546.

ABSTRACT: INTRODUCTION: Non-invasive vagus nerve stimulation (nVNS; gammaCore®) has the potential to prevent migraine days in patients with migraine on the basis of mechanistic rationale and pilot clinical data. METHODS: This multicentre study included a 4-week run-in period, a 12-week double-blind period of randomised treatment with nVNS or sham, and a 24-week open-label period of nVNS. Patients were to administer two 120-second stimulations bilaterally to the neck three times daily (6-8 hours apart). RESULTS: Of 477 enrolled patients, 332 comprised the intent-to-treat (ITT) population. Mean reductions in migraine days per month (primary outcome) were 2.26 for nVNS (n = 165; baseline, 7.9 days) and 1.80 for sham (n = 167; baseline, 8.1 days) ( CONCLUSIONS: Preventive nVNS treatment in episodic migraine was not superior to sham stimulation in the ITT population. The "sham" device inadvertently provided a level of active vagus nerve stimulation. Post hoc analysis showed significant effects of nVNS in treatment-adherent patients.

20 Article Relief Following Chronic Stress Augments Spreading Depolarization Susceptibility in Familial Hemiplegic Migraine Mice. 2019

Balkaya, Mustafa / Seidel, Jessica L / Sadeghian, Homa / Qin, Tao / Chung, David Y / Eikermann-Haerter, Katharina / van den Maagdenberg, Arn M J M / Ferrari, Michel D / Ayata, Cenk. ·Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. · Department of Neurology Leiden University Medical Center, Leiden 2300, RC, the Netherlands; Human Genetics, Leiden University Medical Center, Leiden 2300, RC, the Netherlands. · Department of Neurology Leiden University Medical Center, Leiden 2300, RC, the Netherlands. · Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA; Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA. Electronic address: cayata@mgh.harvard.edu. ·Neuroscience · Pubmed #31299346.

ABSTRACT: Cortical spreading depolarization (CSD) is the electrophysiological substrate of migraine aura, and a putative trigger of trigeminovascular activation and migraine headache. Many migraineurs report stress or relief after a stress triggers an attack. We tested whether various stress conditions might modulate CSD susceptibility and whether this is dependent on genetic factors. Male and female wild type and familial hemiplegic migraine type1 (FHM1) knock-in mice heterozygous for the S218L missense mutation were subjected to acute or chronic stress, or chronic stress followed by relief (36 h). Acute stress was induced by restraint and exposure to bright light and white noise (3 h). Chronic stress was induced for 28 days by two cycles of repeated exposure of mice to a rat (7 days), physical restraint (3 days), and forced swimming (3 days). Electrical CSD threshold and KCl-induced (300 mM) CSD frequency were determined in occipital cortex in vivo at the end of each protocol. Relief after chronic stress reduced the electrical CSD threshold and increased the frequency of KCl-induced CSDs in FHM1 mutants only. Acute or chronic stress without relief did not affect CSD susceptibility in either strain. Stress status did not affect CSD propagation speed, duration or amplitude. In summary, relief after chronic stress, but not acute or chronic stress alone, augments CSD in genetically susceptible mice. Therefore, enhanced CSD susceptibility may explain why, in certain patients, migraine attacks typically occur during a period of stress relief such as weekends or holidays.

21 Article Microstructural white matter changes preceding white matter hyperintensities in migraine. 2019

Arkink, Enrico B / Palm-Meinders, Inge H / Koppen, Hille / Milles, Julien / van Lew, Baldur / Launer, Lenore J / Hofman, Paul A M / Terwindt, Gisela M / van Buchem, Mark A / Ferrari, Michel D / Kruit, Mark C. ·From the Departments of Radiology (E.B.A., I.H.P.-M., J.M., B.v.L., M.A.v.B., M.C.K.) and Neurology (H.K.) and Laboratory for Clinical and Experimental Image Processing, Department of Radiology (J.M., B.v.L.), Leiden University Medical Center · Department of Neurology (H.K., G.M.T., M.D.F.), Haga Hospital, The Hague, the Netherlands · Laboratory of Epidemiology and Population Sciences (L.J.L.), National Institute on Aging, Bethesda, MD · and Department of Radiology (P.A.M.H.), Maastricht University Medical Center, the Netherlands. ·Neurology · Pubmed #31296653.

ABSTRACT: OBJECTIVE: We used magnetization transfer imaging to assess white matter tissue integrity in migraine, to explore whether white matter microstructure was more diffusely affected beyond visible white matter hyperintensities (WMHs), and to explore whether focal invisible microstructural changes precede visible focal WMHs in migraineurs. METHODS: We included 137 migraineurs (79 with aura, 58 without aura) and 74 controls from the Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis (CAMERA) study, a longitudinal population-based study on structural brain lesions in migraine patients, who were scanned at baseline and at a 9-year follow-up. To assess microstructural brain tissue integrity, baseline magnetization transfer ratio (MTR) values were calculated for whole brain white matter. Baseline MTR values were determined for areas of normal-appearing white matter (NAWM) that had progressed into MRI-detectable WMHs at follow-up and compared to MTR values of contralateral NAWM. RESULTS: MTR values for whole brain white matter did not differ between migraineurs and controls. In migraineurs, but not in controls, NAWM that later progressed to WMHs at follow-up had lower mean MTR (mean [SD] 0.354 [0.009] vs 0.356 [0.008], CONCLUSIONS: We did not find evidence for widespread microstructural white matter changes in migraineurs compared to controls. However, our findings suggest that a gradual or stepwise process might be responsible for evolution of focal invisible microstructural changes into focal migraine-related visible WMHs.

22 Article Treatment effects and comorbid diseases in 58 patients with visual snow. 2019

van Dongen, Robin M / Waaijer, Lindy C / Onderwater, Gerrit L J / Ferrari, Michel D / Terwindt, Gisela M. ·From the Department of Neurology, Leiden University Medical Centre, the Netherlands. · From the Department of Neurology, Leiden University Medical Centre, the Netherlands. g.m.terwindt@lumc.nl. ·Neurology · Pubmed #31213497.

ABSTRACT: OBJECTIVE: To evaluate pharmacologic treatment options for visual snow and to report prevalence of comorbid diseases. METHODS: Medical charts of patients with a diagnosis of visual snow at the neurology outpatient clinic were reviewed on prescribed medication, and comorbid migraine, tinnitus, and psychiatric conditions including depression and anxiety. RESULTS: From 2007 to 2018, 58 patients were diagnosed with visual snow. Comorbid migraine was present in 51.7% of patients, lifetime depression in 41.4%, and lifetime anxiety in 44.8%. Lamotrigine was prescribed most frequently (26/58) and resulted in partial remission of symptoms in 5/26 (19.2%). No patients reported complete remission. Adverse events occurred in 13/26 (50.0%) patients. None of the other prescribed drugs (valproate [n = 7], topiramate [n = 4], acetazolamide [n = 2], flunarizine [n = 1]) led to improvement except for topiramate in one patient, who discontinued, however, because of adverse events. CONCLUSIONS: Of medication prescribed (lamotrigine, valproate, acetazolamide, flunarizine), only lamotrigine afforded some improvement in a small minority of patients. Migraine, depression, anxiety, and tinnitus were common comorbid diseases. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for some patients with visual snow, lamotrigine resulted in partial remission of symptoms.

23 Article MRI evaluation of the relationship between carotid artery endothelial shear stress and brain white matter lesions in migraine. 2019

Hoogeveen, Evelien S / Arkink, Enrico B / van der Grond, Jeroen / van Buchem, Mark A / Ferrari, Michel D / Terwindt, Gisela M / Kruit, Mark C / Anonymous3350994. ·1 Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. · 2 Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. ·J Cereb Blood Flow Metab · Pubmed #31213163.

ABSTRACT: Although white matter lesions are frequently detected in migraine patients, underlying mechanisms remain unclear. Low carotid artery endothelial shear stress has been associated with white matter lesions. We aimed to investigate the association between carotid artery endothelial shear stress and white matter lesions in migraine. In 40 elderly migraine patients (

24 Article Stroke progression and clinical outcome in ischemic stroke patients with a history of migraine. 2019

Mulder, Inge A / Holswilder, Ghislaine / van Walderveen, Marianne Aa / van der Schaaf, Irene C / Bennink, Edwin / Horsch, Alexander D / Kappelle, L Jaap / Velthuis, Birgitta K / Dankbaar, Jan Willem / Terwindt, Gisela M / Schonewille, Wouter J / Visser, Marieke C / Ferrari, Michel D / Algra, Ale / Wermer, Marieke Jh / Anonymous1241026. ·Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands. · Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands. · Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands. · Department of Neurology, University Medical Center Utrecht, Utrecht, the Netherlands. · Department of Neurology, St Antonius Hospital, Nieuwegein, the Netherlands. · Department of Neurology, VU Medical Center, Amsterdam, the Netherlands. · Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. · Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. ·Int J Stroke · Pubmed #31132969.

ABSTRACT: BACKGROUND: Patients with migraine might be more susceptible of spreading depolarizations, which are known to affect vascular and neuronal function and penumbra recovery after stroke. We investigated whether these patients have more severe stroke progression and less favorable outcomes after recanalization therapy. METHODS: We included patients from a prospective multicenter ischemic stroke cohort. Lifetime migraine history was based on the International Classification of Headache Disorders II criteria. Patients without confirmed migraine diagnosis were excluded. Patients underwent CT angiography and CT perfusion <9 h of onset and follow-up CT after three days. On admission, presence of a perfusion deficit, infarct core and penumbra volume, and blood brain barrier permeability (BBBP) were assessed. At follow-up we assessed malignant edema, hemorrhagic transformation, and final infarct volume. Outcome at three months was evaluated with the modified Rankin Scale (mRS). We calculated adjusted relative risks (aRR) or difference of means (aB) with regression analyses. RESULTS: We included 600 patients of whom 43 had migraine. There were no differences between patients with or without migraine in presence of a perfusion deficit on admission (aRR: 0.98, 95%CI: 0.77-1.25), infarct core volume (aB: -10.8, 95%CI: -27.04-5.51), penumbra volume (aB: -11.6, 95%CI: -26.52-3.38), mean blood brain barrier permeability (aB: 0.08, 95%CI: -3.11-2.96), malignant edema (0% vs. 5%), hemorrhagic transformation (aRR: 0.26, 95%CI: 0.04-1.73), final infarct volume (aB: -14.8, 95%CI: 29.9-0.2) or outcome after recanalization therapy (mRS > 2, aRR: 0.50, 95%CI: 0.21-1.22). CONCLUSION: Elderly patients with a history of migraine do not seem to have more severe stroke progression and have similar treatment outcomes compared with patients without migraine.

25 Article Adherence to the 2008 IHS guidelines for controlled trials of drugs for the preventive treatment of chronic migraine in adults. 2019

Deen, Marie / Martinelli, Daniele / Pijpers, Judith / Diener, Hans-Christoph / Silberstein, Stephen / Ferrari, Michel D / Ashina, Messoud / Tassorelli, Cristina / Yuan, Hsiangkuo. ·1 Danish Headache Center, Department of Neurology, Rigshospitalet - Glostrup, Denmark. · 2 Headache Science Center, IRCCS C. Mondino Foundation, Pavia, Italy. · 3 Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy. · 4 Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands. · 5 Medical Faculty of the University Duisburg-Essen, Essen Germany. · 6 Department of Neurology, Thomas Jefferson University Hospital, Philadelphia, PA, USA. ·Cephalalgia · Pubmed #31042062.

ABSTRACT: INTRODUCTION: Since the definition of chronic migraine as a new disease entity in 2004, numerous clinical trials have examined the efficacy of preventive treatments in chronic migraine. Our aim was to assess the adherence of these trials to the Guidelines of the International Headache Society published in 2008. METHODS: We searched PubMed for controlled clinical trials investigating preventive treatment for chronic migraine in adults designed after the release of the Guidelines and published until December 2017. Trial quality was evaluated with a 13-item scoring system enlisting essential recommendations adapted from the Guidelines. RESULTS: Out of 3352 retrieved records, we included 16 papers in the analysis dealing with pharmacological treatment of chronic migraine. The median score was 6.5 (range 2-13). All trials were randomized, the large majority (81.25%) were placebo-controlled and double-blinded (87.5%). Adherence was lowest on i) DISCUSSION: Most clinical trials adhered to the recommendations of the IHS, whereas adherence to migraine-specific recommendations was lower. Greater awareness and adherence to the guidelines are essential to improve the quality of clinical trials, validity of publications and the generalizability of the results.

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