Peter J Goadsby

IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino, Ticinum, Lombardy, Italy

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Publications (717)3882.49 Total impact

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    ABSTRACT: Objective: To evaluate whether headache exacerbation associated with IV dihydroergotamine (DHE) infusion predicts medium-term headache outcome in patients with chronic migraine. Methods: This was a retrospective chart review study of the UCSF Headache Center's use of IV DHE for chronic migraine from 2008 to 2012. Medium-term headache outcome was assessed at 6-week follow-up. Univariate and multivariate logistic regression models were used to assess for predictors of outcome. Results: Patients with chronic migraine (n = 274) were treated with a course of IV DHE. Of 214 with 6-week follow-up, 78% had medium-term headache benefit. In a univariate logistic regression model, headache exacerbation with DHE was associated with lower odds of a positive medium-term headache outcome (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.20-0.91). However, in the multivariate logistic regression model, headache exacerbation was no longer an independent predictor of treatment outcome (OR 0.65, 95% CI 0.28-1.51). Factors that independently predicted outcome were nausea (OR 0.12, 95% CI 0.02-1.00, p = 0.05), age (OR 1.68 for each decade increase in age, 95% CI 1.24-2.28), and medication overuse (OR 0.42, 95% CI 0.18-0.97). Conclusions: After controlling for nausea and other factors, headache exacerbation with DHE infusions is not an independent predictor of poor headache outcome and clinicians should not interpret its presence as a reason to stop treatment. The focus of management should be on controlling nausea as it is the most important modifiable factor in achieving a good headache outcome with an inpatient course of IV DHE for chronic migraine.
    No preview · Article · Feb 2016 · Neurology
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    ABSTRACT: The objective of this study was to compare the societal direct and indirect costs of chronic and episodic migraine in the United States. Episodic and chronic migraine are distinguished by the frequency of headache-days. Chronic migraine has a greater overall impact on quality of life than does episodic migraine. Individuals with chronic migraine also use more healthcare resources (resulting in higher direct costs) and experience greater decreases in productivity (resulting in higher indirect costs) than those with episodic migraine as shown in the American Migraine Prevalence and Prevention (AMPP) Study. The International Burden of Migraine Study utilized a web-based questionnaire to elicit data on several topics related to the burden of migraine illness, including health resource utilization and productivity losses. Potential survey participants were identified by Synovate Healthcare (Chicago, IL, USA) from a pool of registered panelists from various countries. The panelists were screened online to determine eligibility and to identify individuals with migraine (episodic or chronic), based on reported symptoms. Participants from the United States were divided into episodic and chronic migraine groups, based on reported headache-day per month frequency. Direct and indirect costs were estimated by applying estimated unit costs to reported headache-related productivity losses and resource use. Costs were compared between participants with episodic and chronic migraine. Mean [standard deviation] total annual cost of headache among people with chronic migraine ($8243 [$10,646]) was over three times that of episodic migraine ($2649 [$4634], P < .001). Participants with chronic migraine had significantly greater direct medical costs ($4943 [$6382]) and indirect (lost productivity) costs ($3300 [$6907]) than did participants with episodic migraine (direct, $1705 [$3591]; indirect, $943 [$2084]) (P < .001 for each). Unlike previous findings, direct medical costs constituted the majority of total headache-related costs for both chronic migraine (60.0%, $4943 of $8243) and episodic migraine (64.3%, $1705 of $2649) participants. A large portion of direct medical costs are attributable to pharmaceutical utilization among both chronic migraine (80%, $3925 of 4943) and episodic migraine (70%, $1196 of $1705) participants. The results of this study build on previous results of the AMPP Study, demonstrating that headache-related direct, indirect, and total costs are significantly greater among individuals with chronic migraine than with episodic migraine in the United States.
    Full-text · Article · Feb 2016 · Headache The Journal of Head and Face Pain
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    ABSTRACT: Objective: The objective of this report is to compare computed tomography (CT) and magnetic resonance (MR) myelography with radioisotope cisternography (RC) for detection of spinal cerebrospinal (CSF) leaks. Methods: We retrospectively reviewed 12 spontaneous intracranial hypotension (SIH) patients; CT and RC were performed simultaneously. Three patients had MR myelography. Results: CT and/or MR myelography identified CSF leaks in four of 12 patients. RC detected spinal leaks in all three patients confirmed by CT myelography; RC identified the CSF leak location in two of three cases, and these were due to osteophytic spicules and/or discs. RC showed only enlarged perineural activity. Only intrathecal gadolinium MR myelography clearly identified a slow leak from a perineural cyst. In eight remaining cases, the leak site was unknown; however, two of these showed indirect signs of CSF leak on RC. CSF slow leaks from perineural cysts were the most common presumed etiology; and the cysts were best visualized on myelography. Conclusion: RC is comparable to CT myelography but has spatial limitations and should be limited to atypical cases.
    No preview · Article · Jan 2016 · Cephalalgia
  • C.J. Schankin · P.J. Goadsby
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    ABSTRACT: Primary headache disorders, including migraine and the trigeminal autonomic cephalalgias, are characterized by normal clinical examination and structural brain imaging. While a central nervous system origin for these disorders has been postulated since the nineteenth century, only recently with the development of functional brain imaging has this been directly studied. Brain imaging methods have enabled the identification of structures underlying headache and hallmark symptoms, such as photophobia, premonitory symptoms, and typical migraine aura. This article gives an integrated view of the clinical presentation and associated functional changes in the brains of patients with primary headache disorders.
    No preview · Article · Dec 2015
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    ABSTRACT: Hemicrania continua (HC) is a rare chronic headache disorder, typically accompanied by cranial autonomic features and responding to therapeutic doses of indomethacin. The pathophysiology of hemicrania continua is not fully understood. We report a series of three patients who developed a continuous hemicranial headache after cranial surgery. Each case presented a similar phenotype of continuous half-sided headache, cranial autonomic symptoms with exacerbations (2/3), and a response to indomethacin. The biology of hemicrania continua may be activated post-craniotomy just as can be seen with other primary headache disorders.
    Preview · Article · Dec 2015 · The Journal of Headache and Pain
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    ABSTRACT: Single pulse transcranial magnetic stimulation (sTMS) is a novel treatment for acute migraine. Previous randomised controlled data demonstrated that sTMS is effective and well tolerated in the treatment of migraine with aura. The aim of the programme reported here was to evaluate patient responses in the setting of routine clinical practice. Migraine patients with and without aura treating with sTMS had an initial review (n = 426) and training call, and then participated in telephone surveys at week six (n = 331) and week 12 during a 3-month treatment period (n = 190). Of patients surveyed with 3 month data (n = 190; episodic, n = 59; chronic, n = 131), 62 % reported pain relief, finding the device effective at reducing or alleviating migraine pain; in addition there was relief reported of associated features: nausea- 52 %; photophobia- 55 %; and phonophobia- 53 %. At 3 months there was a reduction in monthly headache days for episodic migraine, from 12 (median, 8-13 IQ range) to 9 (4-12) and for chronic migraine, a reduction from 24 (median, 16-30 IQ range) to 16 (10-30). There were no serious or unanticipated adverse events. sTMS may be a valuable addition to options for the treatment of both episodic and chronic migraine.
    Full-text · Article · Dec 2015 · The Journal of Headache and Pain
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    ABSTRACT: Background: The physiology and pharmacology of activation or perception of activation of pain-coding trigeminovascular afferents in humans is fundamental to understanding the biology of headache and developing new treatments. Methods: The blink reflex was elicited using a concentric electrode and recorded in four separate sessions, at baseline and two minutes after administration of ramped doses of diazepam (final dose 0.07 mg/kg), fentanyl (final dose 1.11 μg/kg), ketamine (final dose 0.084 mg/kg) and 0.9 % saline solution. The AUC (area under the curve, μV*ms) and the latency (ms) of the ipsi- and contralateral R2 component of the blink reflex were calculated by PC-based offline analysis. Immediately after each block of blink reflex recordings certain psychometric parameters were assessed. Results: There was an effect due to DRUG on the ipsilateral (F3,60 = 7.3, P < 0.001) AUC as well as on the contralateral (F3,60 = 6.02, P < 0.001) AUC across the study. A significant decrement in comparison to placebo was observed only for diazepam, affecting the ipsilateral AUC. The scores of alertness, calmness, contentedness, reaction time and precision were not affected by the DRUG across the sessions. Conclusion: Previous studies suggest central, rather than peripheral changes in nociceptive trigeminal transmission in migraine. This study demonstrates a robust effect of benzodiazepine receptor modulation of the nociception specific blink reflex (nBR) without any μ-opiate or glutamate NMDA receptor component. The nociception specific blink reflex offers a reproducible, quantifiable method of assessment of trigeminal nociceptive system in humans that can be used to dissect pharmacology relevant to primary headache disorders.
    Preview · Article · Dec 2015 · The Journal of Headache and Pain
  • Pyari Bose · D. G. Palethorpe · J Marin · A Nesbitt · J Lowe · P. J. Goadsby
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    ABSTRACT: Background Indomethacin-responsive trigeminal autonomic cephalalagias (TACS), paroxysmal hemicrania (PH) and hemicrania continua (HC), are unique, important syndromes to understand. Aim Evaluation of the role of the placebo-controlled indomethacin test (P-Indotest) in the diagnosis of primary headache disorders. Method Patients notes, clinic letters and headache diaries of patients under our care (PJG) over a 20 year period across various UK Neurology tertiary care centres were examined to obtain data against an audit collection tool. A pre-determined set of data were extracted, and the test procedure reviewed for compliance against a standard with minimum data set requirement by an unblinded observer. The original test score was noted, and prospectively re-scored by a blinded observer. Results Patients (n=7; 4 female) were aged from 24 to 51 years. The majority (85%) had side locked headache. P-Indotest was positive in 78% of the cases with patients having either HC or PH. Of all patients tested, 42% had unilateral photophobia and phonophobia and all these cases had a positive response. No serious adverse events were noted. Sleepiness was often reported on the active treatment as was transient worsening of headache in unilateral chronic migraine. Further data is being compiled. Conclusion The P-IndoTest is a reliable and safe test and should in the diagnosis of patients with possible indomethacin sensitive TACs. While far from ideal, a positive indomethacin test does identify a particular biology and should be retained as a diagnostic marker of PH and HC until its basis is understood.
    No preview · Article · Nov 2015 · Journal of Neurology Neurosurgery & Psychiatry
  • Peter J Goadsby

    No preview · Article · Oct 2015 · Nature Reviews Neurology
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    ABSTRACT: Background: Migraine attacks may present different features in different patients and also within the same patient. The percentage of patients reporting stereotyped attacks and those reporting attacks with different phenotypes has not been the object of specific investigations. Objective: The objective of this article is to evaluate the percentage of migraine patients reporting the same characteristics, in terms of phenotype and response to symptomatic medications on three consecutive migraine attacks. Methods: Thirty patients with migraine without aura prospectively recorded the features of three consecutive attacks in a headache diary. Characteristics recorded were: pain intensity, presence of nausea, vomiting, photophobia, phonophophia, osmophobia, allodynia, cranial autonomic symptoms (at least one), and premonitory symptoms. Patients were allowed to take frovatriptan as symptomatic medication, whose efficacy was evaluated as the two hours pain-free status. Results: None of the patients presented identical characteristics on the three studied attacks. This was still the case if we reduced the number of variables evaluated from 11 to seven of the eight core features indicated by the ICHD. Considering just six variables: unilaterality and quality of pain, presence/absence of nausea, vomiting, photophobia and phonophobia, only two patients (6%) had identical features on three consecutive attacks.With respect to the response to frovatriptan, 39% of patients had the same response, either positive (i.e. pain free after two hours) or negative (i.e. not pain free after two hours) on three consecutive attacks. Conclusion: Migraine attacks show a high variability not just among patients, but also within the same patient. Our data indicate that stereotypy of attacks is uncommon, and reinforces the underlying logic of the current operational classification system.
    No preview · Article · Oct 2015 · Cephalalgia
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    ABSTRACT: The thalamus contains third-order relay neurons of the trigeminal system, and animal models as well as preliminary imaging studies in small cohorts of migraine patients have suggested a role of the thalamus in headache pathophysiology. However, larger studies using advanced imaging techniques in substantial patient populations are lacking. In the present study, we investigated changes of thalamic volume and shape in a large multicenter cohort of patients with migraine. High-resolution T1-weighted MRI data acquired at 3 tesla in 131 patients with migraine (38 with aura; 30.8 ± 9 years old; 109 women; monthly attack frequency: 3.2 ± 2.5; disease duration: 14 ± 8.4 years) and 115 matched healthy subjects (29 ± 7 years old; 81 women) from four international tertiary headache centers were analyzed. The thalamus and thalamic subnuclei, striatum, and globus pallidus were segmented using a fully automated multiatlas approach. Deformation-based shape analysis was performed to localize surface abnormalities. Differences between patients with migraine and healthy subjects were assessed using an ANCOVA model. After correction for multiple comparisons, performed using the false discovery rate approach (p < 0.05 corrected), significant volume reductions of the following thalamic nuclei were observed in migraineurs: central nuclear complex (F(1,233) = 6.79), anterior nucleus (F(1,237) = 7.38), and lateral dorsal nucleus (F(1,238) = 6.79). Moreover, reduced striatal volume (F(1,238) = 6.9) was observed in patients. This large-scale study indicates structural thalamic abnormalities in patients with migraine. The thalamic nuclei with abnormal volumes are densely connected to the limbic system. The data hence lend support to the view that higher-order integration systems are altered in migraine.
    No preview · Article · Oct 2015 · The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
  • Simon Akerman · Peter J. Goadsby
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    ABSTRACT: The pathogenesis of migraine is not well understood. To dissect the relative contributions of endogenous peripheral and central mechanisms in triggering migraine, we examined the effects of two pharmacologically similar, but clinically different, vasodilator neuropeptides, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide 38 (PACAP-38), on dural meningeal vessels and the response properties of central trigeminovascular neurons. Both VIP and PACAP-38 caused short-lived meningeal vasodilation mediated by VPAC2 receptors, which did not coincide with activation of central trigeminovascular neurons. Only PACAP-38 caused delayed activation and sensitization of central trigeminovascular neurons, similar to its delayed effects in inducing migraine headache. After a 90-min delay, PACAP-38 induced a robust increase in ongoing spontaneous firing and hypersensitivity to intra- and extracranial somatosensory stimulation, which did not coincide with meningeal vasodilation. Only intravenous delivery of a PAC1 receptor antagonist inhibited the peripheral meningeal vasodilatory effects of dural trigeminovascular nociception, whereas only central (intracerebroventricular) administration of the PAC1 receptor antagonist inhibited dural nociceptive-evoked action potentials in central trigeminovascular neurons. Our data suggest that the endogenous mechanisms of migraine pathogenesis are located within the central nervous system, likely in the trigeminocervical complex, and that the dural meninges and their primary afferent innervation are less likely to contribute to migraine initiation. Furthermore, the PAC1 receptor may be an appropriate molecular target for migraine therapeutics.
    No preview · Article · Oct 2015 · Science translational medicine

  • No preview · Article · Oct 2015 · Der Schmerz
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    ABSTRACT: The management of patients with migraine is often unsatisfactory because available acute and preventive therapies are either ineffective or poorly tolerated. The acute treatment of migraine attacks has been limited to the use of analgesics, combinations of analgesics with caffeine, ergotamines, and the triptans. Successful new approaches for the treatment of acute migraine target calcitonin gene-related peptide (CGRP) and serotonin (5-hydroxytryptamine, 5-HT1F) receptors. Other approaches targeting the transient receptor potential vanilloid (TRPV1) receptor, glutamate, GABAA receptors, or a combination of 5-HT1B/1D receptors and neuronal nitric oxide synthesis have been investigated but have not been successful in clinical trials thus far. In migraine prevention, the most promising new approaches are humanised antibodies against CGRP or the CGRP receptor. Non-invasive and invasive neuromodulation approaches also show promise as both acute and preventive therapies, although further studies are needed to define appropriate candidates for these therapies and optimum protocols for their use.
    No preview · Article · Sep 2015 · The Lancet Neurology

  • No preview · Article · Sep 2015 · The Journal of Headache and Pain
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    Preview · Article · Sep 2015 · The Journal of Headache and Pain

  • No preview · Article · Sep 2015 · The Journal of Headache and Pain
  • Kenneth J. Mack · Peter Goadsby
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    ABSTRACT: Cluster headache is a primary headache disorder that can occur in children and adolescents, and is a member of the broader diagnostic group of Trigeminal Autonomic Cephalalgias (TACs). It is characterized by repeated attacks typically lasting between 15-180 minutes of severe unilateral side-locked headache with cranial autonomic features. Acute treatment of the cluster attack can include the use of triptans or high flow oxygen. Preventive measures typically start with the use of verapamil. The other TACS, paroxysmal hemicrania and SUNCT/SUNA, have also been reported in children, and should be considered when the clinical presentation is at all unusual.
    No preview · Article · Aug 2015
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    ABSTRACT: As there are no biological markers, a detailed description of symptoms, particularly temporal characteristics, is crucial when diagnosing migraine aura. Hitherto these temporal aspects have not been studied in detail. We conducted a prospective diary-aided study of the duration and the succession of aura symptoms and their temporal relationship with headache. Fifty-four patients completed the study recording in a diary the characteristics of three consecutive auras (n = 162 auras). The median duration of visual, sensory and dysphasic symptoms were 30, 20 and 20 minutes, respectively. Visual symptoms lasted for more than one hour in 14% of auras (n = 158), sensory symptoms in 21% of auras (n = 52), and dysphasic symptoms in 17% of auras (n = 18). Twenty-six percent of patients had at least one aura out of three with one symptom lasting for more than one hour. In aura with multiple symptoms the subsequent symptom, second versus first one or third versus second, might either start simultaneously (34 and 18%), during (37 and 55%), with the end (5 and 9%), or after (24 and 18%) the previous aura symptom. The headache phase started before the aura (9%), simultaneously with the onset of aura (14%), during the aura (26%), simultaneously with the end of aura (15%) or after the end of aura (36%). We provide data to suggest that symptoms may last longer than one hour in a relevant proportion of auras or migraine with aura patients, and that there is a high variability of scenarios in terms of time relationship among aura symptoms and between aura and headache. © International Headache Society 2015.
    Full-text · Article · Jul 2015 · Cephalalgia
  • R Bhola · E Kinsella · S Weatherby · F Ahmed · N Giffin · F Maniyar · P J Goadsby

    No preview · Conference Paper · Jun 2015

Publication Stats

32k Citations
3,882.49 Total Impact Points


  • 2015
    • IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino
      • Headache Science Center
      Ticinum, Lombardy, Italy
    • Imperial College London
      Londinium, England, United Kingdom
  • 2014-2015
    • King's College London
      Londinium, England, United Kingdom
  • 2013-2015
    • ICL
      Londinium, England, United Kingdom
    • Stanford University
      • Stanford Prevention Research Center
      Palo Alto, California, United States
    • University of California, Los Angeles
      Los Ángeles, California, United States
  • 2007-2015
    • University of California, San Francisco
      • Department of Neurology
      San Francisco, California, United States
    • University of San Francisco
      San Francisco, California, United States
    • McLean Hospital
      • McLean Imaging Center
      Cambridge, Massachusetts, United States
  • 2011
    • San Francisco VA Medical Center
      San Francisco, California, United States
    • University of Alberta
      • Division of Neurology
      Edmonton, Alberta, Canada
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
  • 1985-2011
    • Prince Henry's Institute
      Melbourne, Victoria, Australia
  • 2002-2010
    • Leiden University
      Leyden, South Holland, Netherlands
    • Mayo Clinic - Rochester
      • Department of Neurology
      Rochester, Minnesota, United States
    • Leiden University Medical Centre
      • Department of Neurology
      Leyden, South Holland, Netherlands
  • 2009
    • California State University
      • Department of Neurology
      Long Beach, California, United States
  • 2003-2009
    • Glostrup Hospital
      • Department of Neurology
      København, Capital Region, Denmark
    • University of Münster
      • Department of Neurology
      Münster, North Rhine-Westphalia, Germany
  • 2008
    • University of Bristol
      • School of Social and Community Medicine
      Bristol, England, United Kingdom
    • University of Liège
      • Department of Neurology
      Luik, Wallonia, Belgium
    • University of Duisburg-Essen
      • Erwin L. Hahn Institute for Magnetic Resonance Imaging
      Essen, North Rhine-Westphalia, Germany
    • Ghent University
      • Neurology
      Gand, Flanders, Belgium
  • 2001-2008
    • University College London
      • Institute of Neurology
      Londinium, England, United Kingdom
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2002-2007
    • Albert Einstein College of Medicine
      • Department of Neuroradiology
      New York, New York, United States
  • 1999-2007
    • London Research Institute
      Londinium, England, United Kingdom
  • 2006
    • University of Hamburg
      Hamburg, Hamburg, Germany
    • Erasmus MC
      • Department of Farmacology and Vascular Medicine
      Rotterdam, South Holland, Netherlands
  • 2001-2005
    • Indian Broiler (IB) Group India
      Bhānpuri, Chhattisgarh, India
  • 1999-2005
    • Thomas Jefferson University
      • Department of Neurology
      Philadelphia, Pennsylvania, United States
  • 2004
    • WWF United Kingdom
      Londinium, England, United Kingdom
    • Mayo Clinic - Scottsdale
      Scottsdale, Arizona, United States
  • 1998-2003
    • Territory neurology and research Institute
      Tucson, Arizona, United States
    • University of London
      Londinium, England, United Kingdom
  • 2000-2002
    • Thomas Jefferson University Hospitals
      • Department of Neurology
      Philadelphia, Pennsylvania, United States
    • Keele University
      Newcastle-under-Lyme, England, United Kingdom
  • 1996
    • Griffith University
      • Centre for Genomics Research
      Southport, Queensland, Australia
  • 1994-1996
    • Lund University
      Lund, Skåne, Sweden
  • 1995
    • University of Cambridge
      • Department of Pharmacology
      Cambridge, England, United Kingdom
  • 1990-1994
    • Prince of Wales Hospital and Community Health Services
      • • Institute of Neurological Sciences
      • • Department of Neurology
      Sydney, New South Wales, Australia
  • 1991
    • University of South Wales
      Понтиприте, Wales, United Kingdom
  • 1983-1991
    • University of New South Wales
      • Department of Medicine
      Kensington, New South Wales, Australia