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Migraine Disorders: HELP
Articles from Istituto Neurologico Nazionale C. Mondino
Based on 65 articles published since 2008
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These are the 65 published articles about Migraine Disorders that originated from Istituto Neurologico Nazionale C. Mondino during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Current Prophylactic Medications for Migraine and Their Potential Mechanisms of Action. 2018

Sprenger, Till / Viana, M / Tassorelli, C. ·Department of Neurology, DKD Helios Klinik Wiesbaden, Aukammallee 33, 65191, Wiesbaden, Germany. till.sprenger@helios-gesundheit.de. · Headache Science Centre, IRCCS Mondino Foundation, 27100, Pavia, Italy. · Department of Brain and Behavioral Sciences, University of Pavia, 27100, Pavia, Italy. ·Neurotherapeutics · Pubmed #29671241.

ABSTRACT: A relatively high number of different medications is currently used for migraine prevention in clinical practice. Although these compounds were initially developed for other indications and differ in their mechanisms of action, some general themes can be identified from the mechanisms at play. Efficacious preventive drugs seem to either suppress excitatory nervous signaling via sodium and/or calcium receptors, facilitate GABAergic inhibition, reduce neuronal sensitization, block cortical spreading depression and/or reduce circulating levels of CGRP. We here review such mechanisms for the different compounds.

2 Review Optimizing the long-term management of chronic migraine with onabotulinumtoxinA in real life. 2018

Tassorelli, Cristina / Tedeschi, Gioacchino / Sarchielli, P / Pini, Luigi Alberto / Grazzi, Licia / Geppetti, Pierangelo / De Tommaso, Marina / Aguggia, Marco / Cortelli, P / Martelletti, Paolo. ·a Headache Science Center , National Neurological Institute C. Mondino , Pavia , Italy. · b Department of Brain and Behavioral Sciences , University of Pavia , Pavia , Italy. · c Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences , University of Campania "Luigi Vanvitelli" , Naples , Italy. · d Neurology Clinic , University Hospital of Perugia , Perugia , Italy. · e Center for Neuroscience and Neurotechnology, Polyclinic Hospital , University of Modena and Reggio Emilia , Modena , Italy. · f Headache and Neuroalgology Unit , Neurological Institute "C. Besta" IRCCS Foundation , Milan , Italy. · g Headache Center, Department of Health Sciences , University of Florence , Florence , Italy. · h Applied Neurophysiology and Pain Unit, SMBNOS Department, Polyclinic General Hospital , Bari Aldo Moro University , Bari , Italy. · i Headache Center, Neurology Department , Asti Hospital , Asti , Italy. · j Department of Biomedical and Neuromotor Sciences , University of Bologna , Bologna , Italy. · k IRCCS Institute of Neurological Sciences of Bologna , Bellaria Hospital , Bologna , Italy. · l Department of Clinical and Molecular Medicine, Sapienza University of Rome and Regional Referral Headache Center , Sant'Andrea Hospital , Rome , Italy. ·Expert Rev Neurother · Pubmed #29280408.

ABSTRACT: INTRODUCTION: Management of chronic migraine is challenging. OnabotulinumtoxinA (OBT-A) is the only medication licensed for prevention of chronic migraine, and has been widely adopted in clinical practice. Limited data is available on its long-term use. Areas covered: Data from controlled trials are combined with available data on the long-term use of OBT-A in real-life studies, with information obtained in a recent survey among Italian headache centers, and the clinical experience of the authors. Six areas were identified as relevant to patients with chronic migraine: 1) definition of responders to OBT-A; 2) management of responders to OBT-A; 3) optimal timing of prophylaxis with OBT-A; 4) position of OBT-A in prevention of chronic migraine; 5) management of medication overuse, and 6) patient education. Expert commentary: This review provides an update on the latest evidence regarding the long-term use of OBT-A in chronic migraine and analyzes the critical issues in the decision-making process that emerge from the analysis of the literature and routine practice. A treatment algorithm is proposed for the adoption in the daily practice.

3 Review Migraine with prolonged aura: phenotype and treatment. 2018

Viana, Michele / Afridi, Shazia. ·Headache Science Center, C. Mondino National Neurological Institute, Via Mondino 2, 27100, Pavia, Italy. michele.viana@ymail.com. · Department of Neurology, Guy's and St Thomas' NHS Trust, London, UK. ·Naunyn Schmiedebergs Arch Pharmacol · Pubmed #29143861.

ABSTRACT: We review the published literature on migraine with prolonged aura (PA), specifically with regards to the phenotype and treatment options. PA is not uncommon. A recent study found that about 17% of migraine auras are prolonged and that 26% of patients with migraine with aura have experienced at least one PA. The characteristics of PA are similar to most typical auras with the exception of a higher number of aura symptoms (in particular sensory and/or dysphasic). There are no well-established treatments at present which target the aura component of migraine. Other than case reports, there have been open-label studies of lamotrigine and greater occipital nerve blocks. The only randomised, blinded, controlled trial to date has been of nasal ketamine showing some reduction in aura severity but not duration. A small open-labelled pilot study of amiloride was also promising. Larger randomised, controlled trials are needed to establish whether any of the existing or novel compounds mentioned are significantly effective and safe.

4 Review Botulinum toxin for chronic migraine: Clinical trials and technical aspects. 2018

Tassorelli, Cristina / Sances, Grazia / Avenali, Micol / De Icco, Roberto / Martinelli, Daniele / Bitetto, Vito / Nappi, Giuseppe / Sandrini, Giorgio. ·Headache Science Center and Headache Unit, National Neurological Institute C. Mondino Foundation, Pavia, Italy; Dept of Brain and Behavioral Sciences, University of Pavia, Italy. Electronic address: cristina.tassorelli@unipv.it. · Headache Science Center and Headache Unit, National Neurological Institute C. Mondino Foundation, Pavia, Italy. · Headache Science Center and Headache Unit, National Neurological Institute C. Mondino Foundation, Pavia, Italy; Dept of Brain and Behavioral Sciences, University of Pavia, Italy. ·Toxicon · Pubmed #28877509.

ABSTRACT: OnabotulinumtoxinA has been approved for the prophylaxis of chronic migraine following the demonstration of efficacy in two large controlled trials. Data collected from pragmatic studies in the real-life setting have contributed important additional information useful for the management of this group of extremely disabled and challenging patients. The main findings from these studies are presented and discussed.

5 Review Botulinum neurotoxin type A for the treatment of pain: not just in migraine and trigeminal neuralgia. 2017

Sandrini, Giorgio / De Icco, Roberto / Tassorelli, Cristina / Smania, Nicola / Tamburin, Stefano. ·C. Mondino National Institute of Neurology Foundation, IRCCS, Pavia, Italy. · Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy. · Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Piazzale Scuro 10, I-37134, Verona, Italy. · Neuromotor and Cognitive Rehabilitation Research Centre, University of Verona, Verona, Italy. · Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Piazzale Scuro 10, I-37134, Verona, Italy. stefano.tamburin@univr.it. ·J Headache Pain · Pubmed #28324318.

ABSTRACT: BACKGROUND: Despite their huge epidemiological impact, primary headaches, trigeminal neuralgia and other chronic pain conditions still receive suboptimal medical approach, even in developed countries. The limited efficacy of current pain-killers and prophylactic treatments stands among the main reasons for this phenomenon. Botulinum neurotoxin (BoNT) represents a well-established and licensed treatment for chronic migraine, but also an emerging treatment for other types of primary headache, trigeminal neuralgia, neuropathic pain, and an increasing number of pain conditions. METHODS: We searched and critically reviewed evidence for the efficacy of BoNT for the treatment of chronic pain. RESULTS: Meta-analyses and randomized controlled trials (RCTs) suggest that BoNT potentially represents a multi-purpose drug for the treatment of pain in several disorders due to a favorable safety profile and a long-lasting relief after a single injection. CONCLUSIONS: BoNT is an emerging treatment in different pain conditions. Future RCTs should explore the use of BoNT injection therapy combined with systemic drugs and/or physical therapies as new pain treatment strategies.

6 Review Persistent and Repetitive Visual Disturbances in Migraine: A Review. 2017

Schankin, Christoph J / Viana, Michele / Goadsby, Peter J. ·Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. · Department of Neurology, Grosshadern, University Hospital Munich, University of Munich, Munich, Germany. · Headache Science Center, C. Mondino National Neurological Institute, Pavia, Italy. · Headache Group, NIHR-Wellcome Trust King's Clinical Research Facility, King's College London, London, United Kingdom. ·Headache · Pubmed #27714802.

ABSTRACT: Visual disturbances in migraineurs, such as visual aura, are typically episodic, that is, associated with the headache attack, and overlaid by head pain and other symptoms that impact the patient. In some patients, however, visual symptoms are dominant due to frequency (migraine aura status), duration (persistent migraine aura and other persistent positive visual phenomena), or complexity (visual snow syndrome). These syndromes are more rare and challenging to classify in clinical practice resulting in a lack of systematic studies on pathophysiology and treatment. We aim at describing clinical features and pathophysiological concepts of typical migraine aura with a focus on cortical spreading depression and differentiation from non-typical migraine aura. Additionally, we discuss nomenclature and the specifics of migraine aura status, persistent migraine aura, persistent positive visual phenomena, visual snow, and other migrainous visual disturbances. The term migraine with prolonged aura might be a useful bridge between typical aura and persistent aura. Further studies would be necessary to assess whether a return of the classification category eventually helps diagnosing or treating patients more effectively. A practical approach is presented to help the treating physician to assign the correct diagnosis and to choose a medication for treatment that has been successful in case reports of these rare but disabling conditions.

7 Review Pharmacogenomics of episodic migraine: time has come for a step forward. 2014

Viana, Michele / Terrazzino, Salvatore / Genazzani, Armando A / Grieco, Gaetano S / Cargnin, Sarah / Santorelli, Filippo M / Pierelli, Francesco / Tassorelli, Cristina / Nappi, Giuseppe / Di Lorenzo, Cherubino. ·Headache Science Centre, C. Mondino National Institute of Neurology Foundation, IRCCS, Pavia, Italy. ·Pharmacogenomics · Pubmed #24624920.

ABSTRACT: Migraine is characterized by heterogeneous behavior in response to drugs. Many resources have been invested in attempting to unravel the genetic basis of migraine, while the role of genetics in responses to currently available drugs has received less attention. We performed a systematic literature search identifying original articles pertaining to pharmacogenomics of episodic migraine. Few primary studies on the pharmacogenomics of symptomatic and preventive medication in episodic migraine were found. The number of patients studied in the individual articles ranged from 40 up to 130. There was a strong heterogeneity among these studies. We believe that pharmacogenomics studies, if properly designed, could contribute towards optimizing the treatment and reducing the burden of migraine, in turn helping patients and optimizing resources. Our knowledge on the pharmacogenomics of migraine is growing too slowly, and concerted measures should be undertaken to speed up the process.

8 Review Triptan nonresponders: do they exist and who are they? 2013

Viana, Michele / Genazzani, Armando A / Terrazzino, Salvatore / Nappi, Giuseppe / Goadsby, Peter J. ·Headache Science Center, C. Mondino National Institute of Neurology Foundation, IRCCS, Pavia, Italy. michele.viana@mondino.it ·Cephalalgia · Pubmed #23564209.

ABSTRACT: BACKGROUND: Triptans represent the best treatment option for most migraine attacks, although this is not as well studied as it might be in controlled trials. Their efficacy and tolerability vary, both between agents, and from patient to patient, with about 30%-40% of patients not responding adequately to therapy. As yet unexplained, the failure of one triptan does not predict failure with another, and therefore triptan nonresponders cannot be defined as individuals who have failed a single triptan. Five clinical studies provide evidence that switching from a triptan that is ineffective to a second one can result in effective treatment in a proportion of patients. Systematic studies investigating whether there are patients who do not respond to all triptans in all formulations are lacking. METHODS: Here we discuss the importance of identifying triptan nonresponders, the literature supporting their existence, and the issues to be resolved to design trials to investigate this. CONCLUSION: So far, no scientific data about the presence of a triptan nonresponder population are available. We propose a pragmatic study design to assess the existence of this subpopulation, recognizing the complexity of the question and the likelihood that more than one issue is at play in nonresponders.

9 Review The typical duration of migraine aura: a systematic review. 2013

Viana, Michele / Sprenger, Till / Andelova, Michaela / Goadsby, Peter J. ·Headache Science Centre, C. Mondino National Institute of Neurology Foundation, IRCCS, Pavia, Italy. ·Cephalalgia · Pubmed #23475294.

ABSTRACT: BACKGROUND: According to ICHD-II, and as proposed for ICHD-III, non-hemiplegic migraine aura (NHMA) symptoms last between five and 60 minutes whereas hemiplegic migraine aura can be longer. In ICHD-III it is proposed to label aura longer than an hour and less than a week as probable migraine with aura. We tested whether this was appropriate based on the available literature. METHODS: We performed a systematic literature search identifying articles pertaining to a typical or prolonged duration of NHMA. We also performed a comprehensive literature search in order to identify all population-based studies or case series in which clinical features of NHMA, including but not restricted to aura duration, were reported, in order to gain a complete coverage of the available scientific data on aura duration. RESULTS: We did not find any article exclusively focusing on the prevalence of a prolonged aura or more generally on typical NHMA duration. We found 10 articles that investigated NHMA features, including the aura duration. Five articles recorded the proportion of patients in whom whole NHMA lasted for more than one hour, which was the case in 12%-37% of patients. Six articles reported some information on the duration of single NHMA symptoms: visual aura disturbances lasting for more than one hour occurred in 6%-10% of patients, sensory aura in 14%-27% of patients and aphasic aura in 17%-60% of patients. CONCLUSIONS: The data indicate the duration of NHMA may be longer than one hour in a significant proportion of migraineurs. This seems to be especially true for non-visual aura symptoms. The term probable seems inappropriate in ICHD-III so we propose reinstating the category of prolonged aura for patients with symptoms longer than an hour and less than one week.

10 Review Transdermal hormonal therapy in perimenstrual migraine: why, when and how? 2012

Tassorelli, Cristina / Greco, Rosaria / Allena, Marta / Terreno, Erica / Nappi, Rossella E. ·Headache Science Centre, IRCCS National Neurological Institute C. Mondino Foundation, Pavia, Italy. cristina.tassorelli@mondino.it ·Curr Pain Headache Rep · Pubmed #22932815.

ABSTRACT: Experimental and clinical evidence is strongly in favor of a role for estrogens in migraine. It is clear that estrogen fluctuations represent trigger factors for the attacks, while the resolution of these fluctuations (menopause) may be associated to the remission or, conversely, to the worsening of the disease. However, the exact mechanisms and mediators underlying the effects of estrogens in migraine are largely unknown. The exact mechanisms and mediators underlying the effects of estrogens in migraine are largely unknown. In this review, we summarize clinical and preclinical data that are relevant for the role of estrogens in migraine and we discuss how estrogen modulation can be exploited positively to improve hormonal-related migraine.

11 Review Migraine and depression: common pathogenetic and therapeutic ground? 2011

Moschiano, F / D'Amico, D / Canavero, I / Pan, I / Micieli, G / Bussone, G. ·National Institute of Neurology, IRCCS C. Mondino Foundation, Via Mondino 2, 27100 Pavia, Italy. franca.moschiano@mondino.it ·Neurol Sci · Pubmed #21533720.

ABSTRACT: Migraine and depression are recognized as comorbid disorders on the basis of several epidemiological data and on the possibility of shared mechanisms. On the other hand, there is a lack of studies concerning therapeutic strategies in patients with this comorbidity. The aim of this paper is to briefly review the literature about the migraine and depression comorbidity and on the putative common neurobiological mechanisms, as well to discuss the possible therapeutic options in treating patients with both disorders.

12 Review The endocannabinoid system and migraine. 2010

Greco, Rosaria / Gasperi, Valeria / Maccarrone, Mauro / Tassorelli, Cristina. ·Headache Science Centre, IRCCS Neurological Institute C. Mondino Foundation, Pavia, Italy. ·Exp Neurol · Pubmed #20353780.

ABSTRACT: The recently discovered endocannabinoid system (ECS), which includes endocannabinoids and the proteins that metabolize and bind them, has been implicated in multiple regulatory functions both in health and disease. Several studies have suggested that ECS is centrally and peripherally involved in the processing of pain signals. This finding is corroborated by the evidence that endocannabinoids inhibit, through a cannabinoid type-1 receptor (CB1R)-dependent retrograde mechanism, the release of neurotransmitters controlling nociceptive inputs and that the levels of these lipids are high in those regions (such as sensory terminals, skin, dorsal root ganglia) known to be involved in transmission and modulation of pain signals. In this review we shall describe experimental and clinical data that, intriguingly, demonstrate the link between endocannabinoids and migraine, a neurovascular disorder characterized by recurrent episodic headaches and caused by abnormal processing of sensory information due to peripheral and/or central sensitization. Although the exact ECS-dependent mechanisms underlying migraine are not fully understood, the available results strongly suggest that activation of ECS could represent a promising therapeutical tool for reducing both the physiological and inflammatory components of pain that are likely involved in migraine attacks.

13 Review Eletriptan. 2009

Sandrini, Giorgio / Perrotta, Armando / Tassorelli, Cristina / Nappi, Giuseppe. ·IRCCS C Mondino Institute of Neurology Foundation, Department of Neurology, via Mondino 2, Pavia, Italy. ·Expert Opin Drug Metab Toxicol · Pubmed #19929447.

ABSTRACT: Migraine is a multifactorial chronic central nervous system disorder, characterized by recurrent disabling attacks of moderate-to-severe headache. Symptomatic acute treatment of migraine should provide rapid and effective relief of the headache pain. The introduction of the 5-HT(1B/1D) receptor agonists (triptans) expanded the armamentarium for acute migraine pain treatment. Eletriptan is a second-generation triptan with favorable bioavailability and half-life, a high affinity for 5-HT(1B/1D) receptors and selectivity for cranial arteries. Eletriptan (40 and 80 mg) has been shown to be effective as early as 30 min after administration and well tolerated when compared to placebo. In comparative clinical trials, eletriptan 40 and 80 mg were superior or equivalent to other triptans and have shown a very high safety and tolerability profile across the studies performed. Eletriptan showed the most favorable cost-effectiveness profile when compared with other agents in its class.

14 Review Migralepsy: a call for a revision of the definition. 2009

Sances, Grazia / Guaschino, Elena / Perucca, Piero / Allena, Marta / Ghiotto, Natascia / Manni, Raffaele. ·Headache Unit, IRCCS C. Mondino Institute of Neurology Foundation, Pavia, Italy. grazia.sances@mondino.it ·Epilepsia · Pubmed #19694799.

ABSTRACT: Migralepsy is an ill-defined nosologic entity, with only a few cases described in the literature. In the 2004 International Classification for Headache Disorders (ICHD-II), the International Headache Society proposed that the following diagnostic criteria should be met: (1) migraine fulfilling criteria for 1.2 Migraine with aura (MA) and (2) a seizure fulfilling diagnostic criteria for one type of epileptic attack occurs during or within 1 h after a migraine aura. Herein, by presenting a case with symptoms suggestive of migralepsy and by reviewing all previous cases described in the literature, we discuss the challenges of differentiating this condition from epileptic seizures, as well as the inaccuracy of the current ICHD-II definition.

15 Review From drug-induced headache to medication overuse headache. A short epidemiological review, with a focus on Latin American countries. 2009

Allena, Marta / Katsarava, Zaza / Nappi, Giuseppe / Anonymous4560622. ·IRCCS Neurological Institute C. Mondino Foundation, University Centre for Headache and Adaptive Disorders, Pavia Section, Via Mondino 2, 27100 Pavia, Italy. marta.allena@mondino.it ·J Headache Pain · Pubmed #19238511.

ABSTRACT: Medication overuse headache (MOH) is a daily or almost-daily type of headache that results from the chronicization, usually migraine or tension-type headache, as a consequence of the progressive increase of intake of symptomatic drugs. MOH is now the third most frequent type of headache and affects a percentage of 1-1.4% of the general population. The currently available data on the impact of chronic headache associated with analgesic overuse in specialist headache centres confirm, beyond doubt, the existence of a serious health problem. Limited amount of data exists on the burden and impact of MOH in Latin American Countries. In this review, we summarise the reliable information from the literature on the epidemiological impact of MOH.

16 Clinical Trial Monocentric Prospective Study into the Sustained Effect of Incobotulinumtoxin A (XEOMIN 2018

Ion, Ioana / Renard, Dimitri / Le Floch, Anne / De Verdal, Marie / Bouly, Stephane / Wacongne, Anne / Lozza, Alessandro / Castelnovo, Giovanni. ·Department of Neurology, Nimes University Hospital, 30900 Nimes, France. IOANAMARIA.ION@chu-nimes.fr. · Department of Neurology, Nimes University Hospital, 30900 Nimes, France. dimitri.RENARD@chu-nimes.fr. · Department of Neurology, Nimes University Hospital, 30900 Nimes, France. anne.LEFLOCH@chu-nimes.fr. · Department of Neurology, Nimes University Hospital, 30900 Nimes, France. marie.DEVERDAL@chu-nimes.fr. · Department of Neurology, Nimes University Hospital, 30900 Nimes, France. stephane.BOULY@chu-nimes.fr. · Department of Neurology, Nimes University Hospital, 30900 Nimes, France. anne.WACONGNE@chu-nimes.fr. · Neurological Institute, Foundation Casimiro Mondino, 27100 Pavia, Italy. alessandro.lozza@mondino.it. · Department of Neurology, Nimes University Hospital, 30900 Nimes, France. giovanni.castelnovo@chu-nimes.fr. ·Toxins (Basel) · Pubmed #29857565.

ABSTRACT: Refractory chronic migraine is a disabling disorder impacting quality of life. BOTOX

17 Clinical Trial The usefulness and applicability of a basic headache diary before first consultation: results of a pilot study conducted in two centres. 2008

Tassorelli, C / Sances, G / Allena, M / Ghiotto, N / Bendtsen, L / Olesen, J / Nappi, G / Jensen, R. ·University Centre for the Study of Adaptive Disorders and Headache (UCADH), IRCCS 'C. Mondino Institute of Neurology' Foundation, Pavia, Italy. cristina.tassorelli@mondino.it ·Cephalalgia · Pubmed #18624804.

ABSTRACT: We tested the usefulness and applicability of a simplified headache diary in the diagnosis of migraine (M), tension-type headache (TTH) and medication overuse headache (MOH). The diary was given to headache patients before their first consultation at the headache centre. Seventy-six naive headache patients completed the study. Their understanding of the diary proved highly satisfactory. The patients' level of compliance was also good, with 71% returning the diary completely filled in. The data entered in the diary were deemed complete for the diagnostic purpose in 93% of cases. The level of agreement between headache information gathered through clinical interview and the headache diary was satisfactory. When comparing the diary with the clinical interview, sensitivity was 92% for M, 75% for TTH and MOH. Specificity was 58% for M and TTH, 87% for MOH. Combined use of a diagnostic diary and clinical interview is recommended from the first consultation for headache.

18 Article Consistent effects of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: additional findings from the randomized, sham-controlled, double-blind PRESTO trial. 2018

Martelletti, Paolo / Barbanti, Piero / Grazzi, Licia / Pierangeli, Giulia / Rainero, Innocenzo / Geppetti, Pierangelo / Ambrosini, Anna / Sarchielli, Paola / Tassorelli, Cristina / Liebler, Eric / de Tommaso, Marina / Anonymous1350998. ·Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy. · Headache and Pain Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Rome, Italy. · Neuroalgology Unit, Carlo Besta Neurological Institute and Foundation, Milan, Italy. · IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. · Department of Neuroscience, University of Turin, Turin, Italy. · Headache Centre, University Hospital of Careggi, Florence, Italy. · IRCCS Neuromed, Pozzilli, IS, Italy. · Neurologic Clinic, Santa Maria della Misericordia Hospital, Perugia, Italy. · Headache Science Centre, IRCCS C. Mondino Foundation, Pavia, Italy. · Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy. · electroCore, Inc., Basking Ridge, NJ, USA. eric.liebler@electrocore.com. · Neurophysiology and Pain Unit, University of Bari Aldo Moro, Bari, Italy. ·J Headache Pain · Pubmed #30382909.

ABSTRACT: BACKGROUND: Non-invasive vagus nerve stimulation (nVNS) has been shown to be practical, safe, and well tolerated for treating primary headache disorders. The recent multicenter, randomized, double-blind, sham-controlled PRESTO trial provided Class I evidence that for patients with episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. We report additional pre-defined secondary and other end points from PRESTO that demonstrate the consistency and durability of nVNS efficacy across a broad range of outcomes. METHODS: After a 4-week observation period, 248 patients with episodic migraine with/without aura were randomly assigned to acute treatment of migraine attacks with nVNS (n = 122) or a sham device (n = 126) during a double-blind period lasting 4 weeks (or until the patient had treated 5 attacks). All patients received nVNS therapy during the subsequent 4-week/5-attack open-label period. RESULTS: The intent-to-treat population consisted of 243 patients. The nVNS group (n = 120) had a significantly greater percentage of attacks treated during the double-blind period that were pain-free at 60 (P = 0.005) and 120 min (P = 0.026) than the sham group (n = 123) did. Similar results were seen for attacks with pain relief at 60 (P = 0.025) and 120 min (P = 0.018). For the first attack and all attacks, the nVNS group had significantly greater decreases (vs sham) in pain score from baseline to 60 min (P = 0.029); the decrease was also significantly greater for nVNS at 120 min for the first attack (P = 0.011). Results during the open-label period were consistent with those of the nVNS group during the double-blind period. The incidence of adverse events (AEs) and adverse device effects was low across all study periods, and no serious AEs occurred. CONCLUSIONS: These results further demonstrate that nVNS is an effective and reliable acute treatment for multiple migraine attacks, which can be used safely while preserving the patient's option to use traditional acute medications as rescue therapy, possibly decreasing the risk of medication overuse. Together with its practicality and optimal tolerability profile, these findings suggest nVNS has value as a front-line option for acute treatment of migraine. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02686034 .

19 Article Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: a post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial. 2018

Grazzi, Licia / Tassorelli, Cristina / de Tommaso, Marina / Pierangeli, Giulia / Martelletti, Paolo / Rainero, Innocenzo / Geppetti, Pierangelo / Ambrosini, Anna / Sarchielli, Paola / Liebler, Eric / Barbanti, Piero / Anonymous1431007. ·Neuroalgology Unit, Carlo Besta Neurological Institute and Foundation, Milan, Italy. licia.grazzi@istituto-besta.it. · Department of Fondazione IRCCS Istituto Neurologico C. Besta, U.O. Neurologia III - Cefalee e Neuroalgologia, Via Celoria 11, 20133, Milan, Italy. licia.grazzi@istituto-besta.it. · Headache Science Centre, IRCCS C. Mondino Foundation, Pavia, Italy. · Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy. · Neurophysiology and Pain Unit, University of Bari Aldo Moro, Bari, Italy. · IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. · Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy. · Department of Neuroscience, University of Turin, Turin, Italy. · Headache Centre, University Hospital of Careggi, Florence, Italy. · IRCCS Neuromed, Pozzilli (IS), Italy. · Neurologic Clinic, Santa Maria della Misericordia Hospital, Perugia, Italy. · electroCore, Inc, Basking Ridge, NJ, USA. · Headache and Pain Unit, IRCCS San Raffaele Pisana, Rome, Italy. ·J Headache Pain · Pubmed #30340460.

ABSTRACT: BACKGROUND: The PRESTO study of non-invasive vagus nerve stimulation (nVNS; gammaCore®) featured key primary and secondary end points recommended by the International Headache Society to provide Class I evidence that for patients with an episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. Here, we examined additional data from PRESTO to provide further insights into the practical utility of nVNS by evaluating its ability to consistently deliver clinically meaningful improvements in pain intensity while reducing the need for rescue medication. METHODS: Patients recorded pain intensity for treated migraine attacks on a 4-point scale. Data were examined to compare nVNS and sham with regard to the percentage of patients who benefited by at least 1 point in pain intensity. We also assessed the percentage of attacks that required rescue medication and pain-free rates stratified by pain intensity at treatment initiation. RESULTS: A significantly higher percentage of patients who used acute nVNS treatment (n = 120) vs sham (n = 123) reported a ≥ 1-point decrease in pain intensity at 30 min (nVNS, 32.2%; sham, 18.5%; P = 0.020), 60 min (nVNS, 38.8%; sham, 24.0%; P = 0.017), and 120 min (nVNS, 46.8%; sham, 26.2%; P = 0.002) after the first attack. Similar significant results were seen when assessing the benefit in all attacks. The proportion of patients who did not require rescue medication was significantly higher with nVNS than with sham for the first attack (nVNS, 59.3%; sham, 41.9%; P = 0.013) and all attacks (nVNS, 52.3%; sham, 37.3%; P = 0.008). When initial pain intensity was mild, the percentage of patients with no pain after treatment was significantly higher with nVNS than with sham at 60 min (all attacks: nVNS, 37.0%; sham, 21.2%; P = 0.025) and 120 min (first attack: nVNS, 50.0%; sham, 25.0%; P = 0.018; all attacks: nVNS, 46.7%; sham, 30.1%; P = 0.037). CONCLUSIONS: This post hoc analysis demonstrated that acute nVNS treatment quickly and consistently reduced pain intensity while decreasing rescue medication use. These clinical benefits provide guidance in the optimal use of nVNS in everyday practice, which can potentially reduce use of acute pharmacologic medications and their associated adverse events. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02686034 .

20 Article Prolonged migraine aura: new insights from a prospective diary-aided study. 2018

Viana, Michele / Sances, Grazia / Linde, Mattias / Nappi, Giuseppe / Khaliq, Farihah / Goadsby, Peter J / Tassorelli, Cristina. ·Headache Science Center, IRCCS Mondino Foundation, Pavia, Italy. michele.viana@ymail.com. · Headache Science Center, IRCCS Mondino Foundation, Pavia, Italy. · Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway. · Norwegian Advisory Unit on Headaches, St. Olavs University Hospital, Trondheim, Norway. · Headache Group - NIHR-Wellcome Trust King's Clinical Research Facility, King's College, London, UK. · Dept of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy. ·J Headache Pain · Pubmed #30171359.

ABSTRACT: BACKGROUND: There is limited literature on prolonged aura (PA - defined as an aura including at least one symptom for > 1 h and < 7d), and there are no prospective studies. The aim of this study is to characterize prospectively the phenotype and prevalence of PA. FINDINGS: Two hundred and twenty-four patients suffering from migraine with aura were recruited from the Headache Centers of Pavia and Trondheim. Patients prospectively described, on an ad hoc diary, each aura symptom (AS), the duration of AS and headache, and headache features. Seventy-two patients recorded three consecutive auras in their diaries. 19 (26.4%) of patients suffered at least one PA. Out of 216 recorded auras, 38 (17.6%) were PAs. We compared PAs with non-PAs with respect to 20 features; PAs were characterized by a higher number of non-visual symptoms (non-VS) (p < 0.001). No other differences were found. We obtained similar results when we compared auras with at least one symptom with a duration of > 2 h (n = 23) or > 4 h (n = 14) with the the others (n = 193 and n = 202 respectively). CONCLUSION: PAs are quite common. They do not differ from the other auras (even when their duration extends to 2 and/or 4 h) with the exception of a higher number of non-VS.

21 Article New CACNA1A deletions are associated to migraine phenotypes. 2018

Grieco, G S / Gagliardi, S / Ricca, I / Pansarasa, O / Neri, M / Gualandi, F / Nappi, G / Ferlini, A / Cereda, C. ·IRCCS Mondino Foundation, Genomic and post-Genomic Center, Pavia, Italy. · IRCCS Mondino Foundation, Genomic and post-Genomic Center, Pavia, Italy. stella.gagliardi@mondino.it. · Unit of Medical Genetics, S. Anna University-Hospital, Ferrara, Italy. · IRCCS Mondino Foundation, Headache Science Center, Pavia, Italy. ·J Headache Pain · Pubmed #30167989.

ABSTRACT: BACKGROUND: Familial hemiplegic migraine type 1 (FHM1) is a form of migraine with aura caused by heterozygous mutations in 4 genes: CACNA1A, ATP1A2, SNC1A and PRRT2, but further heterogeneity is expected. Here have been described clinical and molecular features in patients suffering from migraine with Aura (MA), without (MO) and hemiplegic migraine attacks. Next Generation Sequencing by TruSeq Custom Amplicon for CACNA1A and ATP1A2 gene has been performed. All genetic variants have been confirmed by Sanger sequencing and all samples were also analyzed with MLPA assay for ATP1A2-CACNA1A genes to detect duplication or deletion. All MLPA data were verified by Real Time PCR. RESULTS: Sequencing analysis showed 3 point mutations, two novel variants and one already described in literature. Moreover, MLPA analysis showed 3 deletions in 9 sporadic hemiplegic migraine (18%), in 3 patients with non-hemiplegic migraine (4.1%) and in 3 patients affected by episodic ataxia (20%). Two sporadic patients showed a deletion in exons 41-43, while the rest of HM patients (5) showed a deletion in the terminal part of the CACNA1A gene. About episodic ataxia, we have identified deletions in exon 12-15 and in exon 47. Finally, in migraine patients, we have found different subjects affected by different phenotypes deleted in exon 47. CONCLUSION: This work highlights the importance to complement analysis as direct sequencing with quantitative analysis (MLPA). In fact, intragenic CACNA1A rearrangements have been detected. Our work demonstrated that deletions in CACNA1A gene may be associated also to different migraine phenotypes.

22 Article The headache under-response to treatment (HURT) questionnaire, an outcome measure to guide follow-up in primary care: development, psychometric evaluation and assessment of utility. 2018

Steiner, T J / Buse, D C / Al Jumah, M / Westergaard, M L / Jensen, R H / Reed, M L / Prilipko, L / Mennini, F S / Láinez, M J A / Ravishankar, K / Sakai, F / Yu, S-Y / Fontebasso, M / Al Khathami, A / MacGregor, E A / Antonaci, F / Tassorelli, C / Lipton, R B / Anonymous740937. ·Department of Neuromedicine and Movement Science, NTNU Norwegian University of Science and Technology, NO-7941, Trondheim, Norway. t.steiner@imperial.ac.uk. · Division of Brain Sciences, Imperial College London, London, UK. t.steiner@imperial.ac.uk. · Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA. · Montefiore Headache Center, Montefiore Medical Center, Bronx, NY, USA. · King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, National Guard Health Affairs, Riyadh, Saudi Arabia. · Danish Headache Centre, Department of Neurology, Rigshospitalet Glostrup University of Copenhagen, Glostrup, Denmark. · Vedanta Research, Chapel Hill, NC, USA. · Department of Mental Health and Substance Abuse, World Health Organization, Geneva, Switzerland. · CEIS EEHTA, Faculty of Economics, University of Rome "Tor Vergata", Rome, Italy. · Institute of Leadership and Management in Health, Kingston University, Kingston upon Thames, UK. · Department of Neurology, University Clinic Hospital, Catholic University of Valencia, Valencia, Spain. · The Headache and Migraine Clinic, Jaslok Hospital and Research Centre, Mumbai, India. · Lilavati Hospital and Research Centre, Mumbai, India. · Saitama International Headache Center, Tokyo, Japan. · Department of Neurology, Chinese PLA General Hospital, Bejing, People's Republic of China. · Headache Expert, Author and Headache Education Facilitator, York, UK. · Centre for Neuroscience & Trauma, Blizard Institute of Cell and Molecular Science, London, UK. · Headache Science Centre, C Mondino National Neurological Institute, Pavia, Italy. · Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy. ·J Headache Pain · Pubmed #29445880.

ABSTRACT: BACKGROUND: Headache disorders are both common and burdensome but, given the many people affected, provision of health care to all is challenging. Structured headache services based in primary care are the most efficient, equitable and cost-effective solution but place responsibility for managing most patients on health-care providers with limited training in headache care. The development of practical management aids for primary care is therefore a purpose of the Global Campaign against Headache. This manuscript presents an outcome measure, the Headache Under-Response to Treatment (HURT) questionnaire, describing its purpose, development, psychometric evaluation and assessment for clinical utility. The objective was a simple-to-use instrument that would both assess outcome and provide guidance to improving outcome, having utility across the range of headache disorders, across clinical settings and across countries and cultures. METHODS: After literature review, an expert consensus group drawn from all six world regions formulated HURT through item development and item reduction using item-response theory. Using the American Migraine Prevalence and Prevention Study's general-population respondent panel, two mailed surveys assessed the psychometric properties of HURT, comparing it with other instruments as external validators. Reliability was assessed in patients in two culturally-contrasting clinical settings: headache specialist centres in Europe (n = 159) and primary-care centres in Saudi Arabia (n = 40). Clinical utility was assessed in similar settings (Europe n = 201; Saudi Arabia n = 342). RESULTS: The final instrument, an 8-item self-administered questionnaire, addressed headache frequency, disability, medication use and effect, patients' perceptions of headache "control" and their understanding of their diagnoses. Psychometric evaluation revealed a two-factor model (headache frequency, disability and medication use; and medication efficacy and headache control), with scale properties apparently stable across disorders and correlating well and in the expected directions with external validators. The literature review found few instruments linking assessment to clinical advice or suggested actions: HURT appeared to fill this gap. In European specialist care, it showed utility as an outcome measure across headache disorders. In Saudi Arabian primary care, HURT (translated into Arabic) was reliable and responsive to clinical change. CONCLUSIONS: With demonstrated validity and clinical utility across disorders, cultures and settings, HURT is available for clinical and research purposes.

23 Article Inhibition of monoacylglycerol lipase: Another signalling pathway for potential therapeutic targets in migraine? 2018

Greco, Rosaria / Demartini, Chiara / Zanaboni, Anna Maria / Berliocchi, Laura / Piomelli, Daniele / Tassorelli, Cristina. ·1 Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, "C. Mondino" National Neurological Institute, Pavia, Italy. · 2 Department of Brain and Behavioral Sciences, University of Pavia, Italy. · 3 Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy. · 4 Department of Anatomy and Neurobiology, University of California, USA. ·Cephalalgia · Pubmed #28816506.

ABSTRACT: Background Drugs that modulate endocannabinoid signalling are effective in reducing nociception in animal models of pain and may be of value in the treatment of migraine. Methods We investigated the anti-nociceptive effects of inhibition of monoacylglycerol lipase (MGL), a key enzyme in the hydrolysis of the 2-arachidonoylglycerol, in a rat model of migraine based on nitroglycerin (NTG) administration. We evaluated c-fos expression in specific brain areas and nociceptive behavior in trigeminal and extra-trigeminal body areas. Results URB602, a reversible MGL inhibitor, did not show any analgesic effect in the tail flick test, but it inhibited NTG-induced hyperalgesia in both the tail flick test and the formalin test applied to the hind paw or to the orofacial area. Quite unexpectedly, URB602 potentiated formalin-induced hyperalgesia in the trigeminal area when used alone. The latter result was also confirmed using a structurally distinct, irreversible MGL inhibitor, JZL184. URB602 did not induce neuronal activation in the area of interest, but significantly reduced the NTG-induced neuronal activation in the ventrolateral column of the periaqueductal grey and the nucleus trigeminalis caudalis. Conclusions These findings support the hypothesis that modulation of the endocannabinoid system may be a valuable approach for the treatment of migraine. The topographically segregated effect of MGL inhibition in trigeminal/extra-trigeminal areas calls for further mechanistic research.

24 Article When cervical pain is actually migraine: An observational study in 207 patients. 2018

Viana, Michele / Sances, Grazia / Terrazzino, Salvatore / Sprenger, Till / Nappi, Giuseppe / Tassorelli, Cristina. ·1 Headache Science Center, C. Mondino National Neurological Institute, Pavia, Italy. · 2 Università del Piemonte Orientale "A. Avogadro", Department of Pharmaceutical Sciences, Italy. · 3 Department of Neurology, DKD HELIOS Klinik Wiesbaden, Germany. · 4 Deptartment of Brain and Behavioral Sciences, University of Pavia, Italy. ·Cephalalgia · Pubmed #27927894.

ABSTRACT: Introduction A large proportion of migraine patients remain undiagnosed or misdiagnosed in Italy. In our experience, many migraineurs self-diagnose their condition as "cervical pain attack" or "cervical pain syndrome" (CP), assuming cervical spine pathology as the cause. We aimed to phenotype and classify the headache of patients with self-diagnosed CP, and to describe this sample of patients. Methods Consecutive patients aged 18 to 75 years, referred to the Headache Center of the Mondino Institute (Pavia, Italy) for a first visit for headache, completed a questionnaire about CP and were subsequently examined by an experienced clinician. Results Out of 207 patients, 132 (64%) believed they suffered from CP. According to ICHD-IIIβ criteria, these patients suffered from migraine or probable migraine in 91% of cases. The great majority of patients who believed that they suffered from CP underwent unnecessary medical exams (including radiation exposure in 40% of cases) and used treatments that were inadequate for their real diagnosis. Conclusion The majority of patients with CP suffer from typical migraine. The misdiagnosis produces an economic burden (for patients and the health care system) and leads to impaired quality of life of patients.

25 Article The role of the transient receptor potential ankyrin type-1 (TRPA1) channel in migraine pain: evaluation in an animal model. 2017

Demartini, Chiara / Tassorelli, Cristina / Zanaboni, Anna Maria / Tonsi, Germana / Francesconi, Oscar / Nativi, Cristina / Greco, Rosaria. ·Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Center, "C. Mondino" National Neurological Institute, Pavia, Italy. · Department of Brain and Behavioral Sciences University of Pavia, Pavia, Italy. · Department of Chemistry 'Ugo Schiff', University of Florence, Florence, Italy. · FiorGen, University of Florence, Florence, Italy. · Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Center, "C. Mondino" National Neurological Institute, Pavia, Italy. rosaria.greco@mondino.it. · IRCCS "National Neurological Institute C. Mondino" Foundation, Via Mondino, 2, 27100, Pavia, Italy. rosaria.greco@mondino.it. ·J Headache Pain · Pubmed #28884307.

ABSTRACT: BACKGROUND: Clinical and experimental studies have pointed to the possible involvement of the transient receptor potential ankyrin type-1 (TRPA1) channels in migraine pain. In this study, we aimed to further investigate the role of these channels in an animal model of migraine using a novel TRPA1 antagonist, ADM_12, as a probe. METHODS: The effects of ADM_12 on nitroglycerin-induced hyperalgesia at the trigeminal level were investigated in male rats using the quantification of nocifensive behavior in the orofacial formalin test. The expression levels of the genes coding for c-Fos, TRPA1, calcitonin gene-related peptide (CGRP) and substance P (SP) in peripheral and central areas relevant for migraine pain were analyzed. CGRP and SP protein immunoreactivity was also evaluated in trigeminal nucleus caudalis (TNC). RESULTS: In rats bearing nitroglycerin-induced hyperalgesia, ADM_12 showed an anti-hyperalgesic effect in the second phase of the orofacial formalin test. This effect was associated to a significant inhibition of nitroglycerin-induced increase in c-Fos, TRPA1 and neuropeptides mRNA levels in medulla-pons area, in the cervical spinal cord and in the trigeminal ganglion. No differences between groups were seen as regards CGRP and SP protein expression in the TNC. CONCLUSIONS: These findings support a critical involvement of TRPA1 channels in the pathophysiology of migraine, and show their active role in counteracting hyperalgesia at the trigeminal level.

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