Margarita Sánchez Del Rio

Hospital Ruber Internacional · Department of Neurology

Background Resistant and refractory migraine are commonly encountered in specialized headache centers. Several comorbidities, mostly psychiatric conditions, have been linked to migraine worsening; however, there is little knowledge of the comorbidity profile of individuals with resistant and refractory migraine. Methods REFINE is a prospective obs...

Background The burden of migraine goes beyond the pain and associated symptoms. We aimed to describe the impact of migraine in healthcare resource utilization (HCRU), work productivity, and mood disorders, as well as its economic cost. Methods Case–control study nested in a cross-sectional analysis of patient-reported data collected between 30/12/...

Background New treatments are currently offering new opportunities and challenges in clinical management and research in the migraine field. There is the need of homogenous criteria to identify candidates for treatment escalation as well as of reliable criteria to identify refractoriness to treatment. To overcome those issues, the European Headache...

Objective: This internet survey aimed to analyze the activity of midolordecabeza.org, a specialized website for headache stakeholders. Background: eHealth tools, such as websites, can be educational for stakeholders of a specific disease, such as patients. This is particularly helpful in chronic disorders such as migraine. eHealth also enhances...

Background Erenumab was approved in Europe for migraine prevention in patients with ≥ 4 monthly migraine days (MMDs). In Spain, Novartis started a personalized managed access program, which allowed free access to erenumab before official reimbursement. The Spanish Neurological Society started a prospective registry to evaluate real-world effectiven...

IntroductionSubcutaneous galcanezumab was an effective, well-tolerated preventive treatment for adults with episodic (EM) or chronic migraine (CM) in 4 phase 3 randomized controlled trials: EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER. Number needed to treat (NNT) and to harm (NNH) are metrics of effect size used to evaluate benefit–risk profiles. This...

Migraine is a disabling primary headache disorder that directly affects more than one billion people worldwide. Despite its widespread prevalence, migraine remains under-diagnosed and under-treated. To support clinical decision-making, we convened a European panel of experts to develop a ten-step approach to the diagnosis and management of migraine...

Background New treatments are currently offering new opportunities and challenges in clinical management and research in the migraine field. There is the need of homogenous criteria to identify candidates for treatment escalation as well as of reliable criteria to identify refractoriness to treatment. To overcome those issues, the European Headache...

Background Erenumab was approved in Europe for migraine prevention in patients with ≥4 monthly migraine days (MMD). In Spain, Novartis started a personalized managed access program which allowed free access to erenumab before official reimbursement. The Headache Study Group of the Spanish Neurological Society started a registry to monitor real-worl...

Introduction: Despite advances in the management of headache disorders, some patients with migraine do not experience adequate pain relief with acute and preventive treatments. It is the aim of the present document to provide a definition of those migraines which are difficult-to-treat, to create awareness of existence of this group of patients, t...

Lasmiditan, a highly selective 5-hydroxytryptamine receptor 1F (5-HT 1F ) agonist, is the first drug in its class and is lacking triptan-like vasoactive properties. The US Food and Drug Administration (FDA) has recently approved lasmiditan for the acute treatment of migraine in adults based on positive results of two pivotal phase III trials, which...

Introduction: Medication overuse headache is a secondary headache in which the regular or frequent use of analgesics can increase the frequency of the episodes, causing the transition from episodic to chronic headache. The prevalence of medication overuse headache is approximately 1-2%, with higher rates among women aged 30-50 years and with comor...

Background OnabotulinumtoxinA is an effective preventive treatment for chronic migraine. In chronic migraine, besides a reduction in headache frequency, a decreased reliance on oral prophylactics is also indicative of treatment effectiveness. This study aimed to quantify the change in the use of oral prophylactics after treatment with onabotulinumt...

BACKGROUND Patients are key stakeholders in medical decision-making, and there is a growing emphasis on patient empowerment. The website midolordecabeza.org promotes the participation of patients with migraine with the aim of organizing the information on headache, including the latest research, making it accessible and useful for all stakeholders....

Resumen Introducción En los últimos años se ha observado que moléculas como el péptido relacionado con el gen de la calcitonina (CGRP) y, en menor grado, el péptido activador de la adenilato-ciclasa pituitaria estaban elevadas durante los ataques de migraña y en la migraña crónica tanto en líquido cefalorraquídeo como en suero y que su reducción f...

OnabotulinumtoxinA has been demonstrated to be effective as a preventive treatment in patients with chronic migraine (CM). Five years after the approval of onabotulinumtoxinA in Spain, the Headache Study Group of the Spanish Society of Neurology considered it worthwhile to gather a group of experts in treating patients with CM in order to draw up,...

Introduction: In the field of headaches, onabotulinumtoxinA (onabotA) is well established as a treatment for chronic migraine (CM). In recent years, it has been used increasingly to treat other primary headaches (high-frequency episodic migraine, trigeminal-autonomic cephalalgias, nummular headache) and trigeminal neuralgia. As this treatment will...

OnabotulinumtoxinA has been demonstrated to be effective as a preventive treatment in patients with chronic migraine (CM). Five years after the approval of onabotulinumtoxinA in Spain, the Headache Study Group of the Spanish Society of Neurology considered it worthwhile to gather a group of experts in treating patients with CM in order to draw up,...

Objectives: To analyze the trajectory to diagnosis and information provided in a series of cluster headache (CH) patients from five headache clinics. Methods: CH patients were asked to fill in an ad hoc questionnaire. Results: Seventy-five patients (mean age 41.5 years, 67 males) completed the questionnaire. Patients had visited during an aver...

The brain of migraineurs is hyperexcitable, particularly the occipital cortex, which is probably hypersensitive to light. Photophobia or hypersensitivity to light may be accounted for by an increased excitability of trigeminal, the visual pathways, and the occipital cortex. To study light sensitivity and photophobia by assessing the response to lig...

The answer to the question raised in the title is complex and subject to ongoing debate. Acute inflammation is a well-characterized process that develops in vascularized connective tissue as a protective response, closely intertwined with the process of repair and independent of the eliciting stimulus. Inflammation and repair may be potentially har...

Preventive pharmacological treatment of migraine aims at reducing the frequency, intensity and duration of the attacks by intervening, at the earliest stage possible, in migraine pathogenesis. The medications effective in migraine prevention conceivably act at multiple sites to raise the threshold for spreading cortical depression, to inhibit the m...

Background and purpose: A large number of instrumental investigations are used in patients with non-acute headache in both research and clinical fields. Although the literature has shown that most of these tools contributed greatly to increasing understanding of the pathogenesis of primary headache, they are of little or no value in the clinical se...

Preventive treatment with topiramate is effective for overall reduction of migraine frequency, but there are few data regarding its efficacy on perimenstrual migraines. To determine whether topiramate can prevent perimenstrual migraines, we analyzed data from premenopausal women as a subgroup of the Prolonged Migraine Prevention with Topiramate (PR...

The neurobiology of migraine is complex, but considerable progress has been made during recent decades with the aid of functional neuroimaging. Imaging studies have provided evidence of both abnormal brain functioning and structural changes. In migraine aura, the blood flow changes initially occur in V3A, an area also showing morphometric abnormali...

Data on the reality of chronic migraine in our clinics are scarce. AIM. To know the frequency of consultation and attitude of the neurologist regarding chronic migraine, and the opinion of patients with this condition. A total of 145 neurologists consulted electronically two questionnaires. The first tested the impact of chronic migraine and their...

Migraine is the most common neurological consultation in our country. AIM. To analyse the satisfaction level of the patient with migraine attending our clinics. A total of 160 neurologists asked 10 consecutive migraine patients to fill in a satisfaction questionnaire. The questionnaire was answered by 1330 patients. The most important factors they...

Headache is the most frequent neurological reason for consultation in our country. To obtain descriptive data on the approach and satisfaction of the neurologist regarding the diagnosis, burden and management of headaches, and migraine in particular, together with the relationship with primary care physicians (PCP). A total of 160 neurologists part...

Data from the Prolonged Migraine Prevention (PROMPT) with Topiramate trial were evaluated post hoc to determine whether topiramate could prevent migraine auras, and whether its efficacy in preventing migraine headaches was similar in patients with (MA; n = 269) and without (MoA; n = 542) aura. Migraines and auras were recorded during prospective ba...

Use of preventive therapy for migraine is often recommended for only 6-9 months, but no randomised, placebo-controlled trials have investigated migraine frequency after the end of prophylaxis. We assessed the effects of discontinuation of topiramate after a treatment period of 6 months. 818 patients who have migraines were enrolled from 88 clinics...

In the current literature, there is neither a reported systematic review comparing the efficacy of triptans at 30 minutes and 1 hour after the migraine treatment, nor data related to efficacy of new marketed triptans. The main objective of this analysis was to compare the efficacy and tolerability of currently marketed oral, non-reencapsulated trip...

Visual system is a high interest topic in neuroscience research. The new neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), allow us to quickly improve our knowledge on the visual system using non-invasive methods. This work examines the effect of small changes in the intensity of a visual stimulus over the BOLD response...

We describe a patient with Hashimoto's encephalopathy presenting as long-standing episodes of aphasia associated with migraine-like headache. Repeated thyroid hormone levels were within normal values, but high titers of antithyroid antibodies in serum, and diffuse EEG slowing and CSF abnormalities during one episode led to the diagnosis.

Previous studies have reported dilatation of the middle cerebral artery (MCA) during acute glyceryl trinitrate (GTN)-induced headache, using imaging techniques such as transcranial Doppler (TCD), positron emission tomography (PET) and single photon emission computerized tomography (SPECT). In the present study we aimed to evaluate whether magnetic...

The trochlear region is a source of distinct pain that may give rise to specific primary pain disorders (primary trochlear headache), but also modulate other pre-existing headache disorders such as migraine. The sensory innervation of this region, by a branch of the ophthalmic division of the trigeminal nerve, may explain the modulatory influence o...

This article will review new and exciting developments in migraine research, with particular emphasis on mutations associated with familial hemiplegic migraine and the role of cortical spreading depression in its pathophysiology and treatment. The recent discovery of multiple point mutations in familial hemiplegic migraine has led to the suggestion...

Objective measurements of duration of attacks have been performed in 8 (5 female and 3 male) patients suffering from primary first division (V-1) trigeminal neuralgia. The mean age of the patients was 67.5 +/- 11.4 years, and the mean age at onset 64.0 +/- 9.7 years. During the study the patients were off treatment. A total of 192 attacks were witn...

Functional neuroimaging, mainly PET and functional MRI, is the main tool that allows the capturing of neurovascular events during a headache attack. In migraine, functional imaging has clarified the underlying pathophysiology of the visual aura, whereas in migraine without aura, brainstem findings suggest a dysfunctional pain system. In cluster hea...

Progressive anarthria is defined as a clinical entity with a degenerative origin consisting in progressive difficulty in articulating while grammatical, semantic and graphic aspects of language are preserved. It is included within the group of processes affecting restricted areas of the brain although its exact nosological location is not clear. We...

Since the initial description of cortical spreading depression by Leao, evidence that cortical spreading depression is the underlying pathomechanism of migraine aura has increased. The purpose of this review is to describe the ultimate genetic and molecular mechanisms of migraine aura. It has been debated how a primarily cortical phenomenon (aura p...

The authors have observed a group of patients complaining of periorbital pain, emanating from the trochlear area, in absence of trochleitis or other orbital or systemic disease. All were previously diagnosed and treated as different types of headaches, but pain was not controlled until local treatment on the sore trochlea was performed. The authors...

The use of instrumental examinations in headache patients varies widely. In order to evaluate their usefulness, the most common instrumental procedures were evaluated, on the basis of evidence from the literature, by an EFNS Task Force (TF) on neurophysiological tests and imaging procedures in non-acute headache patients. The conclusions of the TF...

Changes in intraocular pressure (IOP) elicited by a Valsalva manoeuvre were studied in 11 male patients (mean age 39.8 years) suffering from episodic cluster headache (CH), and 12 healthy male controls (mean age 39.9 years). The tests were performed at rest and while exhaling hard through a mouthpiece connected to a mercury manometer. In the CH gro...

Migraine is a frequent condition affecting 18% of women and 6% of men in the United States. The American Migraine Study reported that 24% of migraine sufferers experience four or more migraine attacks every month. However, only 3-5% of migraine sufferers receive preventive therapy.1 Classes of agents used as preventives for migraine include beta-bl...

We analysed the adverse events of placebo in acute and preventive randomized, double-blind, placebo-controlled studies for migraine treatment. Fifty-seven trials (oral triptans, non-steroidal anti-inflammatory drugs, nasal ergot alkaloids and preventive agents) were included. From 10 to 30% of subjects reported adverse events after placebo. Most co...

The efficacy of current preventive migraine treatments is limited. In addition, tolerability problems are not infrequent. To check our experience with topiramate in the treatment of patients with refractory migraine. We offered treatment with topiramate to patients with the diagnosis of International Headache Society (IHS) migraine who had not resp...

Clinical features of different headache syndromes have been described in great detail; however, its pathophysiology remains poorly understood. We review the latest findings in both human imaging studies and experimental animals to explain the possible mechanisms involved in the genesis of headache syndromes.

In order to investigate the c-fos response within the trigeminal nucleus caudalis (Sp5C) after noxious meningeal stimulation, capsaicin (0.25, 0.5, 1 and 5 nmol) was administered intracisternally in urethane (1 g/kg) and alpha-chloralose (20 mg/kg) anaesthetized male mice. Capsaicin induced a robust and dose-dependent c-fos-like immunoreactivity (c...

Numular headache is a chronic, mild to moderate, pressurelike pain in a circumscribed cranial area of approximately 2 to 6 cm in diameter. Pain usually is limited to the parietal region, although it may appear in any cranial site. It is a benign process of usually unknown origin.

A total of 26 episodes of V-1 trigeminal neuralgia attacks have been recorded in two female patients. Autonomic phenomena were assessed according to a semiquantitative scale. Attacks lasted 17 +/- 5 s. Mild lacrimation without conjunctival hyperaemia, rhinorrhea or ptosis was observed, even in relatively long lasting episodes. This is in clear cont...

Idiopathic trochleitis is a cause of superimposed ocular pain in patients with migraine. Trochleitis usually presents as an orbital pain without obvious ocular signs. Like greater occipital neuralgia, trochleitis may sustain or trigger the pain of chronic migraine. Diagnosis is confirmed by peritrochlear steroid injection, which produces a quick re...

Chronic migraine (CM), previously called transformed migraine, is a frequent headache disorder that affects 2%-3% of the general population. Analgesic overuse, insomnia, depression, and anxiety are disorders that are often comorbid with CM. Hypothalamic dysfunction has been implicated in its pathogenesis, but it has never been studied in patients w...

Nitric oxide (NO) has been implicated in migraine pathogenesis based on the delayed development of typical migraine headache 4-6 h after infusing the NO donor nitroglycerin [glyceryl trinitrate (GTN)] to migraineurs. Furthermore, inhibiting the synthesis of NO by treatment with a NO synthase (NOS) inhibitor attenuates spontaneous migraine headaches...

Indomethacin has consistently been proven to provide complete and sustained relief of symptoms in hemicrania continua (HC) and chronic paroxysmal hemicrania (CPH), but is not devoid of side-effects. The goal of this retrospective study is to assess the dose and side-effects of prolonged indomethacin treatment of HC and CPH. Twenty-six patients with...

Crossed apraxia is an unusual alteration in praxic function due to a cerebral lesion which is contralateral to that which would be expected. We report a case of crossed apraxia due to a right parietal lesion in a left handed patient who had been obliged to be right handed. We discuss the peculiar neuropsychological profile and possible relation of...

Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (BOLD) signal changes that demo...

In intracranial structures unmyelinated C- and Adelta-fibers of the trigeminal nerve transmit pain stimuli from meninges to the trigeminal nucleus caudalis (Sp5C). Peripheral nerve endings surround meningeal vessels (the so-called trigeminovascular system) and contain vasoactive neuropeptides (calcitonin gene-related peptide, substance P and neurok...

Drug selection for the acute treatment of migraine is based on comorbid disorders, coexistent diseases, and the patient’s pain profile and specific needs and expectations. Patients should be instructed to tailor their treatment strategy to meet their specific needs by varying their medications according to pain intensity. This will aid in successfu...

Central (cortex and upper brainstem) and peripheral (trigeminovascular) mechanisms are involved in the pathophysiology of migraine. We propose that unknown migraine triggers initiate depolarization of cortical neurons followed concomitantly by a transient increase in blood flow. This transient hyperemia spreads at a rate of 3-6 mm/min followed by h...

Experimental models have been developed to study various aspects of migraine. Here we describe the most commonly used models--mostly animal models--which led to the development of a pathophysiological concept of migraine. We focus on activation studies of the trigeminovascular system, the sphenopalatine ganglion, the superior sagittal sinus, the du...

Research into migraine pathophysiology has been hampered by the episodic nature and unpredictable onset of migraine attacks. Recently, newer imaging techniques have been providing noninvasive methods of studying metabolism and hemodynamics in the brains of migraineurs during and between acute attacks. 133Xe blood flow techniques, transcranial Doppl...

We examined the effects of butalbital (30, 100, and 1000 micrograms/kg) on the number of cells expressing c-fos-like immunoreactivity (c-fos-LI), a marker of neuronal activation, within lamina I, IIo of the trigeminal nucleus caudalis and the nucleus of the solitary tract 2 hours after the intracisternal injection of capsaicin (0.1 mL; 15.25 mg/mL)...

Using perfusion weighted imaging, we studied 28 spontaneous migraine episodes; 7 during visual aura (n = 6), 7 during the headache phase following visual aura (n = 3), and 14 cases of migraine without aura (n = 13). The data were analyzed using a region-of-interest-based approach. During aura, relative cerebral blood flow (rCBF) was significantly d...

We examined the effects of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzol[f]quinoxaline-7-sulphonamide (NBQX), the kainate receptor antagonists γ-(R-)-glutamylaminomethanesulphonic acid (GAMS) and 6,7,8,9-tetrahy...

A possible mechanism of action of antimigraine drugs such as sumatriptan is inhibition of the trigeminovascular pathway. Sumatriptan's effects might be mediated by 5-HT1B, 5-HT1D or 5-HT1F receptors. To establish the relative importance of these subtypes, we compared the effects of sumatriptan with those of a selective 5-HT1F receptor agonist (LY 3...

There is little known about high altitude headache, except that it is an important and serious problem that often heralds the onset of acute mountain sickness. We do know that the brain itself is an insensate organ except for its meninges which contain sensory axons projecting from the trigeminal nerve. These nerve fibers travel in proximity to men...

The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-i mine hydrogen maleate (MK-801) was examined on c-fos-like immunoreactivity (c-fos-LI) in urethane-anesthetized Sprague-Dawley rats using a polyclonal antibody. C-fos, an indicator of neuronal activation, was asse...

Perfusion- and diffusion-weighted magnetic resonance imaging was performed during spontaneous visual auras in four migraineurs. Alterations in relative cerebral blood flow (16-53% decrease), cerebral blood volume (6-33% decrease), and tissue mean transit time (10-54% increase) were observed in the gray matter of occipital cortex contralateral to th...