Migraine Disorders: Goadsby PJ

Anonymous00234, Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A, Sándor PS. · Department of Neurology, University of Münster, Germany. European Federation of NeurologicalSocieties · Eur J Neurol. · Pubmed #16796580 No free full text.

Abstract: Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients' quality of life. To give evidence-based or expert recommendations for the different drug treatment procedures of the different migraine syndromes based on a literature search and an consensus in an expert panel. All available medical reference systems were screened for all kinds of clinical studies on migraine with and without aura and on migraine-like syndromes. The findings in these studies were evaluated according to the recommendations of the EFNS resulting in level A,B, or C recommendations and good practice points. For the acute treatment of migraine attacks, oral non-steroidal anti-inflammatory drugs (NSAIDs) and triptans are recommended. The administration should follow the concept of stratified treatment. Before intake of NSAIDs and triptans, oral metoclopramide or domperidon is recommended. In very severe attacks, intravenous acetylsalicylic acid or subcutaneous sumatriptan are drugs of first choice. A status migrainosus can probably be treated by steroids. For the prophylaxis of migraine, betablockers (propranolol and metoprolol), flunarizine, valproic acid, and topiramate are drugs of first choice. Drugs of second choice for migraine prophylaxis are amitriptyline, naproxen, petasites, and bisoprolol.

Anonymous00401, Olesen J, Bousser MG, Diener HC, Dodick D, First M, Goadsby PJ, Göbel H, Lainez MJ, Lance JW, Lipton RB, Nappi G, Sakai F, Schoenen J, Silberstein SD, Steiner TJ. · Department of Neurology, University of Copenhagen, Glostrup Hospital, Demark. · Cephalalgia. · Pubmed #16686915 No free full text.

Abstract: After the introduction of chronic migraine and medication overuse headache as diagnostic entities in The International Classification of Headache Disorders, Second Edition, ICHD-2, it has been shown that very few patients fit into the diagnostic criteria for chronic migraine (CM). The system of being able to use CM and the medication overuse headache (MOH) diagnosis only after discontinuation of overuse has proven highly unpractical and new data have suggested a much more liberal use of these diagnoses. The International Headache Classification Committee has, therefore, worked out the more inclusive criteria for CM and MOH presented in this paper. These criteria are included in the appendix of ICHD-2 and are meant primarily for further scientific evaluation but may be used already now for inclusion into drug trials, etc. It is now recommended that the MOH diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication overuse. The latter is defined as previously, i.e. 10 days or more of intake of triptans, ergot alkaloids mixed analgesics or opioids and 15 days or more of analgesics/NSAIDs or the combined use of more than one substance. If these new criteria for CM and MOH prove useful in future testing, the plan is to include them in a future revised version of ICHD-2.

Goadsby PJ. · No affiliation provided · Neurology. · Pubmed #18413584 No free full text.

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Goadsby PJ. · No affiliation provided · J Neurol Neurosurg Psychiatry. · Pubmed #17314190 No free full text.

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Goadsby PJ. · No affiliation provided · Pain. · Pubmed #17069974 No free full text.

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Goadsby PJ. · No affiliation provided · Med J Aust. · Pubmed #15698351 links to  free full text

Abstract: Considering the clinical implications of new research data on migraine and brain lesions.

Goadsby PJ. · No affiliation provided · Neurology. · Pubmed #12601089 No free full text.

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Goadsby PJ. · No affiliation provided · Ann Neurol. · Pubmed #11198295 No free full text.

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Goadsby PJ. · No affiliation provided · Med J Aust. · Pubmed #10870529 links to  free full text

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Bartsch T, Paemeleire K, Goadsby PJ. · Department of Neurology, University Hospital of Schleswig Holstein, University of Kiel, Germany. · Curr Opin Neurol. · Pubmed #19434793 No free full text.

Abstract: PURPOSE OF REVIEW: Conventional management options in medically intractable chronic-headache syndromes, such as chronic migraine, chronic cluster headache and hemicrania continua, are often limited. This review summarizes the current concepts, approaches and outcome data of invasive device-based neurostimulation approaches using occipital-nerve stimulation and deep-brain stimulation. RECENT FINDINGS: Recently, there has been considerable progress in neurostimulation approaches to medically intractable chronic-headache syndromes. Previous studies have analysed the safety and efficacy of suboccipital neurostimulation in drug-resistant chronic-headache syndromes such as in chronic migraine, chronic cluster headache and hemicrania continua. The studies suggest suboccipital neurostimulation can have an effect even decades after onset of headaches, thus representing a possible therapeutic option inpatients that do not respond to any medication. Similarly, to date over 50 patients with cluster headaches underwent hypothalamic deep-brain stimulation. From these, an average of 50-70% did show a significant positive response. SUMMARY: These findings will help to further elucidate the clinical potential of neurostimulation in chronic headache.

Goadsby PJ. · Headache Group, Department of Neurology, University of California, San Francisco, 1635 Divisadero Street, San Francisco, CA 94115, USA. · Neurol Clin. · Pubmed #19289219 No free full text.

Abstract: Migraine is a common, disabling disorder of the central nervous system. The disorder has three key features. The tendency is largely inherited, the sufferer is sensitive to exogenous and endogenous triggers that very often involve challenges to normal homeostatic biology, and the attack phenotype, when severe, is the stereotypical migraine attack. The attack itself consists of an abnormal perception of otherwise normal circumstances, such as pain without evidence of primary nociceptive activation, and light and sound sensitivity without change in ambient stimuli. The disturbance in the brain is of the subcortical aminergic sensory modulatory systems, and probably includes brainstem, hypothalamic, and thalamic changes that produce the rich clinical presentation seen in practice.

Bigal ME, Ferrari M, Silberstein SD, Lipton RB, Goadsby PJ. · Global Director for Scientific Affairs-Neuroscience; Merck Research Laboratories, Whitehouse Station, NJ, USA. · Headache. · Pubmed #19161562 No free full text.

Abstract: The triptan era has been a time of remarkable progress for migraine diagnosis and treatment. In this paper, we review some of the advances achieved in migraine science during this era focusing on 3 themes: lessons from clinical practice, lessons from epidemiology and lessons from pathophysiology. Science has shown that migraine is a disorder of the brain, and that the key events happen in the the trigeminal neuronal pathways, not on blood vessels. Clinical science has led to the observation that migraine sometimes progresses or remits. This in turn led to longitudinal epidemiologic studies focusing on factors that determine migraine prognosis. In addition, these studies raised questions about the mechanisms of migraine progression, including the role of allodynia, obesity, inflammation, and medications as determinants of progression. This in turn opens a new set of scientific questions about the neurobiologic determinants of migraine, as well as of its clinical course, and exciting opportunities to develop new therapies for this highly disabling brain disorder.

Goadsby PJ. · Department of Neurology, University of California, San Francisco, CA, USA. · Brain. · Pubmed #19098031 No free full text.

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Goadsby PJ, Hargreaves R. · Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. · Headache. · Pubmed #19006557 No free full text.

Abstract: Despite increased understanding of primary headaches and their treatment, the underlying causes of refractory migraine remain unknown. This note considers potential genetic, structural, functional and pharmacological factors that could contribute to this relatively intractable condition. Further understanding of refractory migraine will require the use of medical imaging technologies, clinical experimental medicine studies on novel pharmacological agents and astute observations in clinical practice to direct potential novel therapeutic approaches.

Afridi SK, Goadsby PJ. · Institute of Neurology, Queen Square, London, WC1N 3BG, UK. · Curr Pain Headache Rep. · Pubmed #18778577 No free full text.

Abstract: Neuroimaging of migraine recently has provided us with further information regarding the pathophysiology of the disorder and posed important questions as to whether migraine is a progressive disorder. This article provides the background of imaging in migraine and discusses recent advances in the field.

Goadsby PJ. · Headache Group, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. · Cephalalgia. · Pubmed #18715331 No free full text.

Abstract: An important issue in the management of migraine is the advice given to patients as to when to take their treatment in the course of the attack. While it seems common sense almost to take treatment early in the attack, the evidence base for that advice is not as robust as could be expected. The 'Act when Mild' (AwM) Study was a randomized, four-arm, multicentre, multinational, double-blind, placebo-controlled trial of almotriptan (12.5 mg) to compare outcomes after administration of treatment when pain intensity was mild and within 1 h of headache onset (mild/early) with outcomes when pain had become moderate or severe. Of 491 migraineurs enrolled, 403 were evaluable with an intention-to-treat population (ITT) of 404. At the primary end-point, 2 h pain free, on the ITT analysis 49% of patients in the almotriptan 12.5 mg treat early/mild group and 40% in the treat moderate/severe group had responded (P = 0.21). Of these patients, 43 did not take medication according to their randomly allocated baseline pain intensity (mild or moderate/severe) and were subsequently reassigned, prior to study unblinding, to the appropriate group (AwM population) for re-analysis of the primary outcome measure: 2-h pain-free rates. In the almotriptan arms, 53% of the mild/early group and 37.5% of the moderate/severe group were pain free at 2 h (P = 0.02; AwM population). The corresponding proportions in the placebo groups were 24.7% and 17.5% (significantly lower than the respective almotriptan arms; P </= 0.01). Considering the ITT population, secondary end-points were also significantly in favour of treatment with almotriptan in the mild/early vs. the moderate/severe stage, including: sustained pain-free, 45.6% vs. 30.5% (P = 0.02); headache recurrence at 24 h, 6% vs. 24% (P = 0.0124). Adverse events were reported in < 5% of patients, with no significant differences between almotriptan and placebo and no serious events in any group. Treatment with almotriptan while migraine pain is still mild and within 1 h of onset provides statistically significant and clinically relevant enhancements in efficacy compared with waiting until pain has reached higher severity levels.

Goadsby PJ, Goldberg J, Silberstein SD. · Headache Group, Department of Neurology, University of California, San Francisco, CA 94143-0114, USA. · BMJ. · Pubmed #18583683 No free full text.

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Paemeleire K, Evers S, Goadsby PJ. · Headache Clinic, Department of Neurology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. · Curr Pain Headache Rep. · Pubmed #18474192 No free full text.

Abstract: Cluster headache (CH) is associated with the most severe pain of the primary headache disorders. Barriers to optimal care include misdiagnosis, diagnostic delay, undertreatment, and mismanagement. Medication-overuse headache (MOH) may further complicate CH and may present as increased CH frequency or development of a background headache, which may be featureless or have some migrainous quality. A personal or familial history of migraine appears to be strongly associated with the development of MOH in CH, at least with the phenotype of background headache. Patients with CH, especially those with a personal and/or family history of migraine, must be carefully monitored for MOH, and medication withdrawal should be considered if a CH patient presents with features of MOH.

Goadsby PJ. · Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. · Nat Clin Pract Neurol. · Pubmed #17982431 No free full text.

Abstract: Migraine is a common disabling brain disorder that--considering its clinical and economic impact--is understudied and in need of additional management options. Currently, treatments are classified as preventive or acute-attack therapies, although it is expected that this distinction will become blurred over time. The gap-junction blocker tonabersat, an inducible nitric oxide synthase (NOS) inhibitor and botulinum toxin A are all being investigated in clinical trials as preventive therapies. Device-based approaches using neurostimulation of the occipital nerve have provided promising results, whereas the first study of patent foramen ovale closure for migraine prevention produced disappointing results. Calcitonin gene-related peptide receptor antagonists, vanilloid TRPV1 receptor antagonists and NOS inhibitors are all being investigated in clinical trials for acute migraine. There is much cause for optimism in this area of neurology and considerable benefit awaits our patients.

Akerman S, Goadsby PJ. · Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA. · Cephalalgia. · Pubmed #17970991 No free full text.

Abstract: In the last 30 years dopamine has been considered as playing a role in the pathogenesis of migraine. The literature indicates that migraineurs are hypersensitive to dopamine agonists with respect to some of the premonitory symptoms of migraine such as nausea and yawning. There are various non-specific dopamine D(2) receptor antagonists that show good clinical efficacy in migraine, and also a number of polymorphisms of dopaminergic genes related to migraine. Animal studies have also shown that dopamine receptors are present in the trigeminovascular system, the area believed to be involved in headache pain, and neuronal firing here is reduced by dopamine agonists. There appears to be little effect of dopamine on peripheral trigeminal afferents. We assess some of the limitations of the clinical studies with regard to the therapeutics, and those found in the studies that discovered differences in genetic polymorphisms in migraine, and consider the implications of this on a dopaminergic hypothesis of migraine.

Magis D, Bendtsen L, Goadsby PJ, May A, Sánchez del Rio M, Sandór PS, Kaube H, Sandrini G, Schoonman GG, Schoenen J, Anonymous00021. · Headache Research Unit, Department of Neurology, University of Liège, Liège, Belgium. · Cephalalgia. · Pubmed #17970767 No free full text.

Abstract: Neuroimaging methods have been widely used in headache and migraine research. They have provided invaluable information on brain perfusion, metabolism and structure during and outside of migraine attacks, contributing to an improved understanding of the pathophysiology of the disorder. Human models of migraine attacks are indispensable tools in pathophysiological and therapeutic research. This review of neuroimaging methods and the attack-provoking nitroglycerin test is part an initiative by a task force within the EUROHEAD project (EU Strep LSHM-CT-2004-5044837-Workpackage 9) with the objective of critically evaluating neurophysiological tests used in migraine. The first part, presented in a companion paper, is devoted to electrophysiological methods, this second part to neuroimaging methods such as functional magnetic resonance imaging, positron emission tomography and voxel-based morphometry, as well as the nitroglycerin test. For each of these methods, we summarize the results, analyse the methodological limitations and propose recommendations for improved methodology and standardization of research protocols.

Holland P, Goadsby PJ. · Headache Group, Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK. · Headache. · Pubmed #17578557 No free full text.

Abstract: The primary headaches are a group of distinct individually characterized attack forms, which although varying in presentation, share some common anatomical basis responsible for the pain component of the attack. The hypothalamus is known to modulate a multitude of functions and has been shown to be involved in the pathophysiology of a variety of primary headaches including cluster headache and chronic migraine. It seems likely that it may be involved in other primary headache disorders due to their episodic nature and may underlie many of their diverse symptoms. We discuss the hypothalamic involvement in the modulation of trigeminovascular processing and examine the involvement of the hypothalamic orexinergic system as a key regulator of this function.

Bigal ME, Lipton RB, Holland PR, Goadsby PJ. · Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. · Neurology. · Pubmed #17515549 No free full text.

Abstract: Migraine and obesity are associated in several ways. First, both are prevalent and disabling disorders influenced by genetic and environmental risk factors. Second, migraine with aura, as obesity, seems to be a risk factor for cardiovascular events. Finally, large population-based studies suggest that obesity is a risk factor for chronic migraine after adjusting for comorbidities. In this article, we discuss plausible mechanisms that may account for this association. Several of the inflammatory mediators that are increased in obese individuals are important in migraine pathophysiology, including interleukins and calcitonin gene-related peptide (CGRP). These mediators may increase the frequency, severity, and duration of migraine attacks per se, which in turn would cause central sensitization. Repeated central sensitization may be associated with permanent neuronal damage close to the periaqueductal gray area, with poor modulation to pain. Obesity is also a state of sympathetic activation, which may contribute to increase in headache frequency. Furthermore, the levels of adiponectin are decreased in obesity. At low but not normal levels, adiponectin is nociceptive. Shared biologic predisposition may also play a major role. Orexins modulate both pain and metabolism. Dysfunction in the orexins pathways seems to be a risk factor for both conditions. Finally, conditions that are comorbid to both states (e.g., depression, sleep apnea) may also make the relationship between both diseases more complex.

Goadsby PJ, Dodick DW, Almas M, Diener HC, Tfelt-Hansen P, Lipton RB, Parsons B. · Institute of Neurology, London, UK. · Cephalalgia. · Pubmed #17381558 No free full text.

Abstract: If treatment-emergent central nervous system (CNS) symptoms following triptan therapy represent direct pharmacological effects of the drug, they should occur independent of response to active drug. However, if they represent unmasking of neurological symptoms of the migraine attack after pain is relieved, they should be more common in responders both to active drug and to placebo. To explore this issue, we evaluated the relationship between the CNS adverse events and treatment response following triptan or placebo treatment. We used pooled data from seven double-blind, placebo-controlled trials involving eletriptan 20 mg (E20, n = 402), eletriptan 40 mg (E40, n = 1870), eletriptan 80 mg (E80, n = 1393), sumatriptan 100 mg (S100, n = 275) and placebo (Pbo, n = 1024). Somnolence was more prevalent among 2 h headache responders than non-responders for all treatments, including E80 (8.8% vs. 5.0%; P < 0.05), E40 (6.4% vs. 5.0%; NS), E20 (4.0% vs. 2.0%; NS), S100 (4.7% vs. 3.2%; NS) and Pbo (7.6% vs. 3.0%; P < 0.05). Similarly, the incidence of asthenia was higher among patients who responded to treatment compared with those who did not respond to E80 (15.2% vs. 7.8%; P < 0.05), E40 (6.5% vs. 3.6%; P < 0.05), E20 (6.5% vs. 1.0%; P < 0.05), S100 (10.1% vs. 4.7%; NS) and Pbo (4.4% vs. 2.7%; NS). The generally higher rates of somnolence and asthenia in patients who respond to treatment suggests that these treatment-emergent neurological symptoms may represent the unmasking of CNS symptoms associated with the natural resolution of a migraine attack, rather than simply representing drug-related side-effects. The rate of somnolence in placebo responders is comparable to that in responders to E40 and E80, indicating that somnolence is related, at least in some important part, to headache relief and not treatment.

Goadsby PJ. · Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. · Trends Mol Med. · Pubmed #17141570 No free full text.

Abstract: Migraine is a complex, disabling disorder of the brain that manifests itself as attacks of often severe, throbbing head pain with sensory sensitivity to light, sound and head movement. There is a clear familial tendency to migraine, which has been well defined in a rare autosomal dominant form of familial hemiplegic migraine (FHM). FHM mutations so far identified include those in CACNA1A (P/Q voltage-gated Ca(2+) channel), ATP1A2 (N(+)-K(+)-ATPase) and SCN1A (Na(+) channel) genes. Physiological studies in humans and studies of the experimental correlate--cortical spreading depression (CSD)--provide understanding of aura, and have explored in recent years the effect of migraine preventives in CSD. Therapeutic developments in migraine have come by targeting the trigeminovascular system, with the most-recent being the proof-of-principle study of calcitonin gene-related peptide (CGRP) receptor antagonists in acute migraine. To understand the basic pathophysiology of migraine, brain imaging studies have firmly established reproducible changes in the brainstem in regions that include areas that are involved in sensory modulation. These data lead to the view that migraine is a form of sensory dysmodulatio--a system failure of normal sensory processing.