Peter J. Goadsby's research while affiliated with King's College and other places

Publications (942)

Article
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Unlike sleep-walkers, patients with rapid-eye-movement-behaviour disorder (RBD) rarely leave the bed during the re-enactment of their dreams. RBD movements may be independent of spatial co-ordinates of the ‘outside-world’, and instead rely on (allocentric) brain-generated virtual space-maps, as evident by patients’ limited truncal/axial movements....
Article
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Background: Whilst cranial autonomic symptoms (CAS) are typically associated with trigeminal autonomic cephalalgias (TAC's), they have also been reported in migraine. Identification and understanding of these symptoms in migraine is important to ensure timely diagnosis and effective management. Methods: Migraineurs seen in a tertiary headache se...
Article
Migraine is a common, chronic, disorder that is typically characterized by recurrent disabling attacks of headache and accompanying symptoms, including aura. The aetiology is multifactorial with rare monogenic variants. Depression, epilepsy, stroke and myocardial infarction are comorbid diseases. Spreading depolarization probably causes aura and po...
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Visual snow syndrome is characterized by a continuous visual disturbance resembling a badly-tuned analogue television and additional visual and non-visual symptoms causing significant disability. The natural course of visual snow syndrome has not hitherto been studied. In this prospective longitudinal study, 78 patients with the diagnosis of visual...
Article
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Migraine is a complex and debilitating disorder that is broadly recognised by its characteristic headache. However, given the wide array of clinical presentations in migraineurs, the headache might not represent the main troublesome symptom and it can even go unnoticed. Understanding migraines exclusively as a pain process is simplistic and certain...
Article
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Migraine is a common and disabling neurological disorder, with several manifestations, of which pain is just one. Despite its worldwide prevalence, there remains a paucity of targeted and effective treatments for the condition, leaving many of those affected underserved by available treatments. Work over the last 30+ years has recently led to the e...
Article
In 1995, a committee of the International Headache Society developed and published the first edition of the Guidelines for Controlled Trials of Drugs in Cluster Headache. These have not been revised. With the emergence of new medications, neuromodulation devices and trial designs, an updated version of the International Headache Society Guidelines...
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Objective To examine the efficacy of ubrogepant in the treatment of migraine with mild versus moderate or severe pain. Methods Phase-3, open-label, dose-blinded, 52-week extension trial. Adults with migraine were randomized 1:1:1 (usual care, ubrogepant-50mg, or ubrogepant-100mg). Participants treated up to 8 migraine attacks of any pain intensity...
Article
Primary headache disorders in particular migraine are one of the most common causes of disability worldwide. Given the high burden of migraine in terms of disability, there has been an effort to develop migraine specific therapies that has led to the availability of new drugs including 5HT1F receptor agonists-ditans (lasmiditan), small molecule cal...
Article
Background We aimed to examine the effects of repetitive cortical spreading depression on the responses of nociceptive trigeminal neurons with dural afferents and characterize the role of 5-HT 1B/1D and opioid receptors. Methods Trigeminocervical complex neurons ( n = 53) responsive to nociceptive activation of the dura mater were studied in rats...
Article
Objective: To compare the clinical phenotype of patients with chronic migraine (CM) to patients with new daily persistent headache of the chronic migraine subtype (NDPH-CM). Methods: A study was conducted of CM (n = 257) and NDPH-CM (n = 76) from a tertiary headache center in the UK, and in the US of patients with daily CM (n = 60) and NDPH-CM (...
Article
The trigeminal nerve has a key role in migraine. An atlas of cell types and gene-expression profiles for cells in this nerve in mice and humans promises to improve our understanding of head pain. Single-cell RNA sequencing of neurons in the trigeminal nerve.
Article
Introduction Cluster headache (CH) is characterised by attacks of excruciating unilateral headache, ipsilateral cranial autonomic symptoms (CAS) and/or agitation. Nitroglycerin (NTG) is known to induce CH. This study is the first single-blind placebo-controlled study using intravenous NTG in CH to characterise comprehensively NTG induced CH attacks...
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Objective: To assess the utility of the novel patient-identified (PI) most bothersome symptom (MBS) measure from PROMISE-2, a phase 3 trial of eptinezumab for the preventive treatment of chronic migraine. Background: Relief of bothersome migraine symptoms can influence satisfaction with treatment and therapeutic persistence. Understanding the im...
Article
Introduction: Chronic migraine is a highly disabling primary headache disorder that is the most common diagnosis of patients seen in tertiary headache centres. Typical oral preventive therapies are associated with many limitations that impact their therapeutic utility. Erenumab was the first available calcitonin gene-related peptide monoclonal ant...
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Objective: To provide a review of challenges in clinical trials for the preventive treatment of cluster headache (CH) and highlight considerations for future studies. Background: Current guidelines for preventive treatment of CH are largely based on off-label therapies supported by a limited number of small randomized controlled trials. Guidelin...
Article
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Migraine is a debilitating disease whose clinical and social impact is out of debate. Tolerability issues, interactions, contraindications, and inefficacy of the available medications make new options necessary. The calcitonin-gene-related peptide (CGRP) pathway has shown its importance in migraine pathophysiology and specific medications targeting...
Article
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Visual snow syndrome is a novel neurological condition characterized by a panfield visual disturbance associated with several additional symptoms. Although it is usually a continuous and primary disorder, cases of intermittent visual snow have been described in the literature, as well as rare secondary forms. This report is the first description of...
Article
Migraine is the second most disabling disorder across all age groups worldwide. Since 2018, two classes of drugs that inhibit the actions of calcitonin gene-related peptide (CGRP), which is implicated in migraine pathophysiology, have become available: gepants (CGRP receptor antagonists) and monoclonal antibodies directed against CGRP or its recept...
Article
A preference for darkness is one of the main associated features in people with migraine, the cause remaining a mystery until some decades ago. In this article, we describe the epidemiology of photophobia in migraine and explain the pathophysiological mechanisms following an anatomical structure. In addition, we review the current management of mig...
Article
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Importance: Migraine with aura may respond differently to therapies than migraine without aura. Individuals with migraine with aura have an elevated vascular risk, necessitating a safety assessment of migraine preventive treatments in this patient subgroup. Objective: To assess the efficacy and safety profiles of erenumab in patients with migrai...
Article
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Background With headache experienced by up to 75% of adults worldwide in the last year, primary headache disorders constitute a major public health problem, yet they remain under-diagnosed and under-treated. Headache prevalence and burden is changing as society evolves, with headache now occurring earlier in life. Contributing factors, mostly assoc...
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Background Cluster headache is a rare, strictly unilateral, severe episodic primary headache disorder. Due to the unpredictable and episodic nature of the attacks, nitroglycerin has been used to trigger attacks for research purposes to further our understanding of cluster headache pathophysiology. Objectives We aimed to identify regions of signifi...
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IntroductionPrevalence and burden of headache disorders in real-world settings is relatively unstudied. We explored the associations between passively collected activity data, headache burden, and quality of life in headache sufferers.Methods Data from wearable activity tracking devices and daily short questionnaires were collected over 12 weeks to...
Article
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Objective To evaluate individual and group long-term efficacy and safety of erenumab in individuals with episodic migraine (EM) for whom 2–4 prior preventatives had failed. Methods Participants completing the 12-week double-blind treatment phase (DBTP) of the LIBERTY study could continue into an open-label extension phase (OLEP) receiving erenumab...
Article
Background/Aims Beginning in April 2019, non-invasive vagus nerve stimulation was included in the NHS Innovation and Technology Payment programme. The programme guaranteed reimbursement of at least a 3-month course of treatment using gammaCore, through a prescription refill card, authorised by a headache specialist for patients with cluster headach...
Article
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Aims To gather information on useful medications to treat visual snow syndrome (VSS) as well as to validate an instrument to assess its clinical severity and the course of the disorder over time. Methods Four hundred patients with VSS were included in this web-based prospective questionnaire study. All subjects completed a treatment questionnaire...
Article
Background and purpose: Lasmiditan is a novel selective 5-HT1F receptor agonist, recently approved for the acute treatment of migraine. 5-HT1F receptors are widely expressed in the CNS and trigeminovascular system. Herein, we sought to explore the therapeutic effect of 5-HT1F receptor activation in preclinical models of migraine and cluster headac...
Article
Objective: Traditionally, the standard advice to individuals suffering from migraine and tension-type headache was that the best way to prevent headaches is to avoid the triggers. This advice has been challenged in recent years and the Trigger Avoidance Model of Headache has been proposed, which suggests that one pathway to developing a headache d...
Article
Most people who see, treat or experience migraine will be aware that its clinical manifestations exceed the symptom of head pain. However, available acute treatments so far have targeted migraine symptoms only in the context of the pain phase of an attack. The associated disability clearly involves more than just these symptoms, and the phenotype c...
Preprint
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Background Whilst cranial autonomic symptoms (CAS) are typically associated with the trigeminal autonomic cephalalgias (TAC’s), they have also been reported in migraine. Identification and understanding of these symptoms in migraine is important to ensure timely diagnosis and effective management. Methods Migraineurs seen within our tertiary headac...
Article
Background Atogepant is an oral, small-molecule, calcitonin gene–related peptide receptor antagonist that is being investigated for the preventive treatment of migraine. Methods In a phase 3, double-blind trial, we randomly assigned adults with 4 to 14 migraine days per month in a 1:1:1:1 ratio to receive a once-daily dose of oral atogepant (10 mg...
Article
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Migraine attacks can involve changes of appetite: while fasting or skipping meals are often reported triggers in susceptible individuals, hunger or food craving are reported in the premonitory phase. Over the last decade, there has been a growing interest and recognition of the importance of studying these overlapping fields of neuroscience fields,...
Article
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Background A large proportion of headache sufferers do not routinely seek medical care. App-based technologies permit the collection of real-world data over time and between countries that can help assess true burden of headache. This study used a mobile phone application to collect information on real-world burden of self-diagnosed headache and to...
Article
Introduction Migraine is a common and disabling neurological disorder. A greater understanding of the pathophysiological mechanisms underlying migraine has led to the availability of specific new drugs targeting calcitonin gene-related peptide (CGRP). The success of the CGRP inhibitors validates research efforts into migraine-specific therapies. A...
Article
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Objectives: We aimed to investigate changes in regional cerebral blood flow (rCBF) using arterial spin labelling (ASL) in patients with visual snow syndrome (VSS), in order to understand more about the underlying neurobiology of the condition, which remains mostly unknown. Methods: We performed an MRI study in which whole-brain maps of rCBF were...
Article
Introduction Primary headache disorders pose a huge burden to health systems around the world. A new model for headache care was introduced at two primary health centers (PHCs) in Dubai, UAE. Our objective is to describe the model, and the impact it had on increasing the number of patients receiving specialist care as well as on patient’s response...
Article
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Objective: To evaluate whether the 15-day threshold of headache days per month adequately reflects substantial differences in disability across the full spectrum of migraine. Background: The monthly frequency of headache days defines migraine subtypes and has crucial implications for epidemiological and clinical research as well as access to car...
Article
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Migraine is a symptomatically heterogeneous condition, of which headache is just one manifestation. Migraine is a disorder of altered sensory thresholding, with hypersensitivity among sufferers to sensory input. Advances in functional neuroimaging have highlighted that several brain areas are involved even prior to pain onset. Clinically, patients...
Article
Background Although the European Medicines Agency and the US Food and Drug Administration have cleared several devices that use neuromodulation to provide clinical benefits in the acute or preventive treatment of migraine, the Clinical Trials Committee of the International Headache Society has not developed guidelines specifically for clinical tria...
Article
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Obstructive sleep apnea is linked to cardiovascular disease, metabolic disorders and dementia. The precise nature of the association between respiratory events in obstructive sleep apnea, cortical or subcortical arousals, and cognitive, autonomic and oxidative stress consequences remains incompletely elucidated. Previous studies have aimed to under...
Article
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Objective To study the agreement between self-reported trigger factors and early premonitory symptoms amongst a group of migraineurs in both spontaneous and pharmacologically provoked attacks. Methods Fifty-three subjects with migraine with and without aura, with ≤ 22 headache days/month, with spontaneous premonitory symptoms associated with migra...
Article
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Background: Indomethacin is a nonsteroidal anti-inflammatory drug whose mechanism of action in certain types of headache disorders remains unknown. The so-called indomethacin-responsive headache disorders consist of a group of conditions with a very different presentation that have a particularly good response to indomethacin. The response is so d...
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Aims Neuronal nitric oxide synthase (nNOS) is highly expressed within the cardiovascular and nervous systems. Studies in genetically modified mice suggest roles in brain blood flow regulation while dysfunctional nNOS signaling is implicated in cerebrovascular ischemia and migraine. Previous human studies have investigated the effects of non-selecti...
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Objective To report the efficacy and safety of erenumab among episodic migraine (EM) patients who were unsuccessful on 2–4 preventive treatments observed at week 64 of Open-Label Extension Phase (OLEP) of the LIBERTY study ( ClinicalTrials.gov NCT03096834 ). Methods The OLEP evaluating monthly erenumab 140 mg for 3 years, enrolled 240 patients who...
Article
Purpose of review: Despite the development of several medications for the acute and preventive treatment of migraine, there are still many patients in whom lack of efficacy, tolerability, interactions or contraindications make other options necessary. CGRP-based drugs have opened the door to a new era of migraine-targeted treatments. Beyond CGRP,...
Article
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Objective: To determine the potential efficacy of ubrogepant for acute treatment of migraine based on historical experience with triptans. Background: Although triptans have improved migraine treatment, their efficacy and tolerability may limit their utility in some individuals. Ubrogepant is a small-molecule, oral calcitonin gene-related peptid...
Article
Cluster headache is a debilitating primary headache disorder that affects approximately 0.1% of the population worldwide. Cluster headache attacks involve severe unilateral pain in the trigeminal distribution together with ipsilateral cranial autonomic features and a sense of agitation. Acute treatments are available and are effective in just over...
Article
Migraine is a disabling neurological disorder, diagnosis of which is based on clinical criteria. A shortcoming of these criteria is that they do not fully capture the heterogeneity of migraine, including the underlying genetic and neurobiological factors. This complexity has generated momentum for biomarker research to improve disease characterisat...
Article
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Background Nitroglycerin administration allows the study of cluster headache attacks in their entirety in a standardised way. Methods A 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-he...
Article
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Background: Over the last six decades (earliest included publication from 1959), clinical trials of migraine preventive treatments have led to the regulatory approval of many medications and devices. Despite similar clinical goals, the outcomes and endpoints used in these trials are broad and not well standardized. Objective: To describe results...
Article
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Background/objective: To review the acute migraine clinical trial literature and provide a summary of the endpoints and outcomes used in such trials. Method: A systematic literature review, following a prespecified (but unregistered) protocol developed to adhere to recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-...
Article
Background Migraine is a common neurological disease that disproportionately affects females and has a peak incidence during productive years, resulting in significant burden.Objective The aim of the study was to determine the cost effectiveness of erenumab for the preventive treatment of migraine.MethodsA hybrid decision-tree plus Markov model was...
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We here present the case of a patient with a sleep disturbance attributed to the exploding head syndrome, recently redefined as ‘episodic cranial sensory shock’. The patient, who suffered with concomitant migraine, was treated for headache prevention with daily single‐pulse transcranial magnetic stimulation. Following treatment, he reported a signi...
Article
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Here we investigate brain functional connectivity in patients with visual snow syndrome (VSS). Our main objective was to understand more about the underlying pathophysiology of this neurological syndrome. Twenty‐four patients with VSS and an equal number of gender and age‐matched healthy volunteers attended MRI sessions in which whole‐brain maps of...
Article
Vagus nerve stimulation (VNS) is a promising neuromodulation approach used in the treatment of migraine, whose therapeutic mechanism is largely unknown. Previous studies suggest that VNS's anti-nociceptive effects may, in part, involved engaging opioidergic mechanisms. We used a validated preclinical model of head pain, with good translational outc...
Article
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Background Non-painful symptoms in migraine following headache resolution can last up to days. Studying the postdrome is important to appreciate the morbidity associated with migraine. Methods Fifty-three subjects ( n = 53) with migraine were studied in an experimental setting, collecting historical phenotypic information on the postdrome in their...
Article
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Background Although erenumab has demonstrated significant reduction in migraine frequency and improved quality of life in studies lasting 3‐12 months, little is known about long‐term therapy. Methods Open‐label, 5‐year treatment phase following a 12‐week, double‐blind, placebo‐controlled trial in adults with episodic migraine. Patients initially r...
Article
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Objective To evaluate the effect of erenumab on patient-reported, functional outcomes in patients with episodic migraine (EM) in whom 2–4 preventives were not useful from the Phase 3b LIBERTY study. Methods As previously reported, 246 patients with EM with 2–4 prior failed preventives were randomised 1:1 to subcutaneous erenumab 140 mg or placebo...
Chapter
Migraine pharmacology can currently be divided into medications for the acute treatment of migraine attacks and migraine preventive, or prophylactic, medications that aim to reduce the frequency and severity of the attacks. In this chapter, we review the current options for migraine treatment. A brief historical background is given for each medicat...
Article
Our knowledge of the pathophysiology of migraine and the molecules implicated in the disorder have evolved over time. Among these, calcitonin gene-related peptide has shown a crucial role that led to the development of therapies specifically targeting the molecule. Four monoclonal antibodies targeting the calcitonin gene-related peptide pathway are...
Article
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Purpose of review Among the spectrum of pain conditions, cluster headache represents one of the most severe. Targeted therapies for cluster headache are evolving thus improving the available therapeutic armamentarium. A better understanding of the currently available therapies, as well as new and emerging options, may aide physicians to manage affe...
Article
Background Rimegepant is a calcitonin gene-related peptide receptor antagonist that has shown efficacy and safety in the acute treatment of migraine. We aimed to compare the efficacy of rimegepant with placebo for preventive treatment of migraine. Methods We did a multicentre, phase 2/3, randomised, double-blind, placebo-controlled trial at 92 sit...
Article
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Background The 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. Methods ACHIEVE-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 100m...
Article
Cranial hypersensitivity is a prominent symptom of migraine, exhibited as migraine headache exacerbated with physical activity, and cutaneous facial allodynia and hyperalgesia. The underlying mechanism is believed to be, in part, activation and sensitization of dural-responsive trigeminocervical neurons. Validated preclinical models that exhibit th...
Article
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Randomized studies have reported a positive effect of candesartan, an angiotensin II receptor antagonist, in migraine prevention. The aim of our study was to explore patient subjective efficacy of candesartan in a real-world sample of migraine patients and try to identify predictors of candesartan response. We audited the clinical records of 253 pa...
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Background: Triptans, specific symptomatic medications for migraine, are not effective in a proportion of patients, or in all attacks, hence the importance of identifying predictors of response. Our aim was to investigate the association between the efficacy of oral frovatriptan 2.5 mg and clinical characteristics of migraine attacks. Methods: W...
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Objective: To assess the long-term safety, tolerability, and efficacy of fremanezumab, a fully humanized monoclonal antibody approved for the preventive treatment of migraine. Methods: A 52-week, multicenter, randomized, double-blind, parallel-group study evaluated fremanezumab monthly or quarterly in adults with chronic migraine (CM) or episodi...
Article
Background Atogepant is an orally administered, small-molecule, calcitonin gene-related peptide (CGRP) receptor antagonist under investigation for treatment of migraine. We aimed to examine a range of oral doses for safety, tolerability, and efficacy for the preventive treatment of migraine. Methods In this double-blind, phase 2b/3 trial, adults (...
Article
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Medication overuse headache is estimated to affect 2% of the population, and is ranked in the top 20 most disabling disorders due to its high level of disability. Several therapies used in the treatment of acute migraine are thought to be associated with medication overuse headache, including opioids and triptans. With limited treatment options, it...
Article
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Non-steroidal anti-inflammatory drugs, cyclo-oxygenase inhibitors, are used routinely in the treatment of primary headache disorders. Indomethacin is unique in its use in the diagnosis and treatment of hemicrania continua and paroxysmal hemicrania. The mechanism of this specific action is not fully understood, although an interaction with nitric ox...