Diagnosis and treatment of disorders of intracranial pressure: consensus statement of the Spanish Society of Neurology's Headache Study Group.

Primary intracranial pressure disorders include idiopathic intracranial hypertension and spontaneous intracranial hypotension. Remarkable advances have been made in the diagnosis and treatment of these 2entities in recent years. Therefore, the Spanish Society of Neurology's Headache Study Group (GECSEN) deemed it necessary to prepare this consensus statement, including diagnostic and therapeutic algorithms to facilitate and improve the management of these disorders in clinical practice. This document was created by a committee of experts belonging to GECSEN, and is based on a systematic review of the literature, incorporating the experience of the participants, and establishes practical recommendations with levels of evidence and grades of recommendation.

[New therapeutic era for migraine attacks with recently approved monoclonal antibodies, ditans and gepants]. / Nueva era terapéutica para el ataque de migraña con los recientemente aprobados anticuerpos monoclonales, ditanes y gepantes.

Treatment of migraine attacks is advised in all patients, using non-steroidal anti-inflammatory drugs when the pain is mild and triptans when the pain intensity is moderate-severe. However, the effectiveness of these drugs is moderate, a high percentage of patients have side effects, and triptans are contraindicated in people with a history of stroke, ischaemic heart disease or poorly controlled hypertension. Hence, there is an urgent need for new therapeutic alternatives. In recent years, new drugs for migraine attacks have become available, most notably ditans (lasmiditan) and gepants (ubrogepant and rimegepant). Furthermore, eptinezumab, which has been approved for the preventive treatment of migraine in adults, has also been used for migraine attacks. This manuscript reviews the efficacy and safety results of the new drugs for migraines that will soon be on the market.

TITLE: Nueva era terapéutica para el ataque de migraña con los recientemente aprobados anticuerpos monoclonales, ditanes y gepantes.El tratamiento de los ataques de migraña se aconseja en todos los pacientes, utilizando antiinflamatorios no esteroideos cuando el dolor es leve y triptanes cuando la intensidad del dolor es moderada-grave. Sin embargo, la efectividad de estos fármacos es modesta, un porcentaje elevado de pacientes presenta efectos secundarios y los triptanes están contraindicados en las personas con antecedentes de ictus, cardiopatía isquémica o hipertensión mal controlada. Por tanto, es imprescindible disponer de nuevas alternativas terapéuticas. En los últimos años han ido apareciendo nuevos fármacos para los ataques de migraña, entre los que destacan los ditanes (lasmiditán) y los gepantes (ubrogepant y rimegepant). Por otro lado, el eptinezumab, que ha sido aprobado para el tratamiento preventivo de la migraña en adultos, se ha utilizado también para los ataques de migraña. En este manuscrito se revisan los resultados de eficacia y seguridad de los nuevos fármacos para los ataques de migraña que se comercializarán próximamente.

Telemedicine in the management of patients with headache: current situation and recommendations of the Spanish Society of Neurology's Headache Study Group.

INTRODUCTION: The COVID-19 pandemic has caused an unexpected boost to telemedicine. We analyse the impact of the pandemic on telemedicine applied in Spanish headache consultations, review the literature, and issue recommendations for the implementation of telemedicine in consultations. METHOD: The study comprised 3 phases: 1) review of the MEDLINE database since 1958 (first reported experience with telemedicine); 2) Google Forms survey sent to all members of the Spanish Society of Neurology's Headache Study Group (GECSEN); and 3) online consensus of GECSEN experts to issue recommendations for the implementation of telemedicine in Spain. RESULTS: COVID-19 has increased waiting times for face-to-face consultations, increasing the use of all telemedicine modalities: landline telephone (from 75% before April 2020 to 97% after), mobile telephone (from 9% to 27%), e-mail (from 30% to 36%), and video consultation (from 3% to 21%). Neurologists are aware of the need to expand the availability of video consultations, which are clearly growing, and other e-health and m-health tools. CONCLUSIONS: The GECSEN recommends and encourages all neurologists who assist patients with headaches to implement telemedicine resources, with the optimal objective of offering video consultation to patients under 60-65 years of age and telephone calls to older patients, although each case must be considered on an individual basis. Prior approval and advice must be sought from legal and IT services and the centre's management. Most patients with stable headache and/or neuralgia are eligible for telemedicine follow-up, after a first consultation that must always be held in person.

Diagnosis and treatment of trigeminal neuralgia: Consensus statement from the Spanish Society of Neurology's Headache Study Group.

INTRODUCTION: Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder affecting one or more branches of the trigeminal nerve. Despite its relatively low global prevalence, TN is an important healthcare problem both in neurology departments and in emergency departments due to the difficulty of diagnosing and treating the condition and its significant impact on patients' quality of life. For all these reasons, the Spanish Society of Neurology's Headache Study Group has developed a consensus statement on the management of TN. DEVELOPMENT: This document was drafted by a panel of neurologists specialising in headache, who used the terminology of the International Headache Society. We analysed the published scientific evidence on the diagnosis and treatment of TN and establish practical recommendations with levels of evidence. CONCLUSIONS: The diagnosis of TN is based on clinical criteria. Pain attributed to a lesion or disease of the trigeminal nerve is divided into TN and painful trigeminal neuropathy, according to the International Classification of Headache Disorders, third edition. TN is further subclassified into classical, secondary, or idiopathic, according to aetiology. Brain MRI is recommended in patients with clinical diagnosis of TN, in order to rule out secondary causes. In MRI studies to detect neurovascular compression, FIESTA, DRIVE, or CISS sequences are recommended. Pharmacological treatment is the initial choice in all patients. In selected cases with drug-resistant pain or poor tolerance, surgery should be considered.

Calcitonin gene-related peptide in migraine: from pathophysiology to treatment.

INTRODUCTION: It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. DEVELOPMENT: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. CONCLUSIONS: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.

1st Post-European Headache Federation Meeting: a review of the latest developments presented at the 2020 European Headache Federation Congress. / I Reunión Post-European Headache Federation: revisión de las novedades presentadas en el Congreso de la European Headache Federation de 2020.

INTRODUCTION: After the European Headache Federation (EHF) Congress, renowned Spanish neurologists specialised in migraine presented the most significant latest developments in research in this field at the Post-EHF Meeting. DEVELOPMENT: The main data presented concerning the treatment of chronic and episodic migraine were addressed, with attention paid more specifically to those related to preventive treatments and real-life experience in the management of the disease. An important review was carried out of the new therapeutic targets and the possibilities they offer in terms of understanding the pathophysiology of migraine and its treatment. An update was also presented of the latest developments in the treatment of migraine with fremanezumab, a monoclonal antibody recently authorised by the European Medicines Agency. Participants were also given an update on the latest developments in basic research on the pathology, as well as an overview of the symptoms of migraine and COVID-19. Finally, the repercussions of migraine in terms of its burden on the care and economic resources of the health system were addressed, along with its impact on society. CONCLUSIONS: The meeting summarised the content presented at the 14th EHF Congress, which took place in late June/early July 2020.

TITLE: I Reunión Post-European Headache Federation: revisión de las novedades presentadas en el Congreso de la European Headache Federation de 2020.Introducción. Tras la celebración del congreso de la European Headache Federation (EHF), reconocidos neurólogos españoles expertos en el tratamiento de la migraña expusieron en la Reunión Post-EHF las principales novedades presentadas en el congreso y relacionadas con ese ámbito. Desarrollo. Se abordan los principales datos presentados relacionados con el tratamiento de la migraña crónica y episódica; concretamente, los relacionados con los tratamientos preventivos y la experiencia en vida real en el manejo de la enfermedad. Se hizo una importante revisión de las nuevas dianas terapéuticas y las posibilidades que ofrecen en cuanto al conocimiento de la fisiopatología de la migraña y su tratamiento. Asimismo, se hizo una actualización de las novedades presentadas en el tratamiento de la migraña con fremanezumab, anticuerpo monoclonal recientemente autorizado por la Agencia Europea de Medicamentos. Se hizo una actualización de las novedades en investigación básica en la patología, así como una relación de los síntomas de migraña y COVID-19. Finalmente, se abordaron las implicaciones de la migraña en la carga sanitaria asistencial y económica, y su impacto en la sociedad. Conclusiones. En la reunión se hizo un resumen del contenido presentado en el 14 Congreso de la EHF, que tuvo lugar a finales de junio y principios de julio de 2020.

Telemedicine in the management of patients with headache: current situation and recommendations of the Spanish Society of Neurology's Headache Study Group. / Aplicación de la telemedicina en la asistencia a pacientes con cefaleas: situación actual y recomendaciones del Grupo de Estudio de Cefaleas de la Sociedad Española de Neurología.

INTRODUCTION: The COVID-19 pandemic has caused an unexpected boost to telemedicine. We analyse the impact of the pandemic on telemedicine applied in Spanish headache consultations, review the literature, and issue recommendations for the implementation of telemedicine in consultations. METHOD: The study comprised 3 phases: 1) review of the MEDLINE database since 1958 (first reported experience with telemedicine); 2) Google Forms survey sent to all members of the Spanish Society of Neurology's Headache Study Group (GECSEN); and 3) online consensus of GECSEN experts to issue recommendations for the implementation of telemedicine in Spain. RESULTS: COVID-19 has increased waiting times for face-to-face consultations, increasing the use of all telemedicine modalities: landline telephone (from 75% before April 2020 to 97% after), mobile telephone (from 9% to 27%), e-mail (from 30% to 36%), and video consultation (from 3% to 21%). Neurologists are aware of the need to expand the availability of video consultations, which are clearly growing, and other e-health and m-health tools. CONCLUSIONS: The GECSEN recommends and encourages all neurologists who assist patients with headaches to implement telemedicine resources, with the optimal objective of offering video consultation to patients under 60-65 years of age and telephone calls to older patients, although each case must be considered on an individual basis. Prior approval and advice must be sought from legal and IT services and the centre's management. Most patients with stable headache and/or neuralgia are eligible for telemedicine follow-up, after a first consultation that must always be held in person.

Neuromodulation in headache and craniofacial neuralgia: guidelines from the Spanish Society of Neurology and the Spanish Society of Neurosurgery. / Neuromodulación en cefaleas y neuralgias craneofaciales: Guía de la Sociedad Española de Neurología y de la Sociedad Española de Neurocirugía.

INTRODUCTION: Numerous invasive and non-invasive neuromodulation devices have been developed and applied to patients with headache and neuralgia in recent years. However, no updated review addresses their safety and efficacy, and no healthcare institution has issued specific recommendations on their use for these 2 conditions. METHODS: Neurologists from the Spanish Society of Neurology's (SEN) Headache Study Group and neurosurgeons specialising in functional neurosurgery, selected by the Spanish Society of Neurosurgery (SENEC), performed a comprehensive review of articles on the MEDLINE database addressing the use of the technique in patients with headache and neuralgia. RESULTS: We present an updated review and establish the first set of consensus recommendations of the SEN and SENC on the use of neuromodulation to treat headache and neuralgia, analysing the current levels of evidence on its effectiveness for each specific condition. CONCLUSIONS: Current evidence supports the indication of neuromodulation techniques for patients with refractory headache and neuralgia (especially migraine, cluster headache, and trigeminal neuralgia) selected by neurologists and headache specialists, after pharmacological treatment options are exhausted. Furthermore, we recommend that invasive neuromodulation be debated by multidisciplinary committees, and that the procedure be performed by teams of neurosurgeons specialising in functional neurosurgery, with acceptable rates of morbidity and mortality.

Document of revision and updating of medication overuse headache (MOH). / Documento de revisión y actualización de la cefalea por uso excesivo de medicación (CUEM).

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 comorbid psychiatric disorders such as depression or anxiety, or other chronic pain disorders. It is important to be familiar with the management of this disease. To this end, the Spanish Society of Neurology's Headache Study Group has prepared a consensus document addressing this disorder. DEVELOPMENT: These guidelines were prepared by a group of neurologists specialising in headache after a systematic literature review and provides consensus recommendations on the proper management and treatment of medication overuse headache. The treatment of medication overuse headache is often complex, and is based on 4 fundamental pillars: education and information about the condition, preventive treatment, discontinuation of the drug being overused, and treatment for withdrawal symptoms. Follow-up of patients at risk of recurrence is important. CONCLUSIONS: We hope that this document will be useful in daily clinical practice and that it will update and improve understanding of medication overuse headache management.

Standard headache and neuralgia treatments and SARS-CoV-2: opinion of the Spanish Society of Neurology's Headache Study Group. / Tratamientos habituales utilizados en cefaleas, neuralgias y SARS-CoV-2. Posicionamiento del grupo de estudio de cefaleas de la Sociedad Española de Neurología.

INTRODUCTION: In recent months, doubts have arisen among patients, general practitioners, and neurologists as to whether some drugs commonly used in patients with headaches and neuralgia may favour or complicate the disease caused by SARS-CoV-2. MATERIAL AND METHODS: We collected information on the opinions of scientific societies and medicines agencies (American, European, and Spanish) to clarify doubts regarding the use of drugs such as lisinopril, candesartan, ibuprofen, corticosteroids, carbamazepine, and monoclonal antibodies targeting the calcitonin gene-related peptide in the context of the COVID-19 pandemic. RESULTS: We make recommendations about the use of standard headache treatments in the context of the COVID-19 pandemic, based on the current scientific evidence. CONCLUSIONS: At present, there is no robust scientific argument to formally contraindicate any of the standard treatments employed for headaches and neuralgias.

Impact of the COVID-19 pandemic on headache management in Spain: an analysis of the current situation and future perspectives. / Impacto de la pandemia COVID-19 en la atención al paciente con cefalea en España: análisis de situación con una mirada al futuro.

INTRODUCTION: The COVID-19 pandemic has had a great impact on healthcare systems. Spain, where headache is the main reason for outpatient neurology consultation, is one of the countries with the most reported cases of the disease. OBJECTIVE: This study aimed to analyse the impact of the COVID-19 pandemic on headache units in Spain and to evaluate how neurologists see the future of these units. METHODS: We conducted a cross-sectional online survey of headache units during the sixth week of the state of alarm declared in Spain in response to the pandemic. RESULTS: The response rate was 74%, with the participation of centres with different characteristics and from all Autonomous Communities of Spain. Limitations in face-to-face activity were reported by 95.8% of centres, with preferential face-to-face consultation being maintained in 60.4%, and urgent procedures in 45.8%. In 91.7% of centres, the cancelled face-to-face activity was replaced by telephone consultation. 95.8% of respondents stated that they would use personal protection equipment in the future, and 86% intended to increase the use of telemedicine. The majority foresaw an increase in waiting lists (93.8% for initial consultations, 89.6% for follow-up, and 89.4% for procedures) and a worse clinical situation for patients, but only 15% believed that their healthcare structures would be negatively affected in the future. CONCLUSIONS: As a consequence of the pandemic, headache care and research activity has reduced considerably. This demonstrates the need for an increase in the availability of telemedicine in our centres in the near future.

[Standard headache and neuralgia treatments and SARS-CoV-2: opinion of the Spanish Society of Neurology's Headache Study Group]. / Tratamientos habituales utilizados en cefaleas, neuralgias y SARS-CoV-2. Posicionamiento del grupo de estudio de cefaleas de la Sociedad Española de Neurología.

Introduction: In recent months, doubts have arisen among patients, general practitioners, and neurologists as to whether some drugs commonly used in patients with headaches and neuralgia may favour or complicate the disease caused by SARS-CoV-2. Material and methods: We collected information on the opinions of scientific societies and medicines agencies (American, European, and Spanish) to clarify doubts regarding the use of drugs such as lisinopril, candesartan, ibuprofen, corticosteroids, carbamazepine, and monoclonal antibodies targeting the calcitonin gene-related peptide in the context of the COVID-19 pandemic. Results: We make recommendations about the use of standard headache treatments in the context of the COVID-19 pandemic, based on the current scientific evidence. Conclusions: At present, there is no robust scientific argument to formally contraindicate any of the standard treatments employed for headaches and neuralgias.

Calcitonin gene-related peptide in migraine: from pathophysiology to treatment. / CGRP en migraña: de la fisiopatología a la terapéutica.

INTRODUCTION: It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. DEVELOPMENT: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. CONCLUSIONS: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.

OnabotulinumtoxinA in chronic migraine: predictors of response. A prospective multicentre descriptive study.

BACKGROUND AND PURPOSE: OnabotulinumtoxinA is a treatment specifically approved for the prophylaxis of chronic migraine in adults. The aim of this study was to assess the effectiveness of OnabotulinumtoxinA in chronic migraine after 1 year of treatment in a real-life setting and to identify clinical predictors of outcome. METHODS: We designed a prospective multicentre study performed in 13 hospitals in Spain. Patients underwent a complete medical history and examination. They were treated with OnabotulinumtoxinA every 12 weeks for 1 year. Data about outcome, adverse events, abortive medication use, emergency room use and disability were collected at 3 and 12 months. RESULTS: A total of 725 subjects completed the study. At 12 months, 79.3% showed >50% reduction in number of headaches per month and 94.9% reported no adverse events. Unilaterality of pain, fewer days of disability per month and milder headache at baseline were correlated with good outcome. Duration of disease <12 months increased the chances of response to treatment with OnabotulinumtoxinA (odds ratio, 1.470; 95% confidence interval, 1.123-2.174; P = 0.045). CONCLUSIONS: This study confirmed the effectiveness of treatment with OnabotulinumtoxinA after 1 year of treatment. The chances of a good outcome may be increased by starting treatment in the first 12 months after chronic migraine diagnosis.

Higher risk of ischaemic stroke associated with factor XI levels in dyslipidaemic patients.

BACKGROUND: Ischaemic stroke (IS) is a complex disease that involves genetic and environmental factors. The role of factor XI (FXI) in arterial thrombosis is unclear. We have investigated the risk of IS related to FXI levels in a case-control study. METHODS: We studied 445 individuals: 218 diagnosed with IS and 227 age-gender-ethnic matched control subjects. We measured factor VIIIc, fibrinogen and factor XIc levels. FXI < 144% was taken as the reference group in the statistical analysis. RESULTS: There were 104 women and 114 men in the IS group and 108 women and 119 men in the control group. The crude odds ratio (OR) of IS in dyslipidaemic patients with high levels of FXI was 4.2 [95% confidence interval (CI): 1.2-14.8] compared with dyslipidaemic controls and low levels of FXI, but the OR in the non-dyslipidaemic with high levels of FXI subgroup was 1.2 (95% CI: 0.4-3.2). The adjusted OR of IS in dyslipidaemic patients with high levels of FXI was 6.4 (95% CI: 1.6-26.1) compared with dyslipidaemic controls, but the OR in non-dyslipidaemic subgroup with high levels of FXI was 0.6 (95% CI: 0.2-2.1). CONCLUSION: We found almost a sixfold higher risk of IS in patients with dyslipidaemia and high levels of FXI. Further studies should elucidate the role of FXI in IS and therapeutic approaches should become apparent for patients with dyslipidaemia and high-FXI plasma levels.

Diagnostic yield of prothrombotic state studies in cryptogenic stroke.

OBJECTIVES: Around 30% of ischemic strokes are considered cryptogenic. We analyzed the diagnostic yield of prothrombotic state (PS) studies in patients with an initial cryptogenic stroke (CS). MATERIAL AND METHODS: We prospectively included consecutive CS patients according to the TOAST criteria. PS included plasmatic determinations of antiphospholipid (APL) antibodies and lupus anticoagulant (LA), S (SPd) and C (CPd) protein deficiencies, and genetic analysis of the prothrombin gene mutation (PT G20210A) and the factor V Leiden mutation (FV G1691A). We recorded age, sex and vascular risk factors. RESULTS: From a total of 89 patients (mean age 56.9 +/- 14.3 years, 53% men), we identified 16 PS in 15 patients (16.85%): APL-6, LA-2, SPd-2, CPd-1, PT G20210A -3 and FV G1691A -2. One patient presented an association (APL and PT G20210A). CONCLUSIONS: One of every six patients with initial CS present a PS. Age or sex and conventional cardiovascular risk factors were not related to PS study findings, supporting the relevance of such studies in all patients with an initial CS.

Aspirin or anticoagulants in stenosis of the middle cerebral artery: A randomized trial.

BACKGROUND: We report the results of an open, randomized, multicenter trial that compared the efficacy of aspirin to oral anticoagulants (OA) for the prevention of vascular events in patients with symptomatic stenosis of the middle cerebral artery (MCA). METHODS: Participants were randomly assigned to receive 300 mg/day of aspirin or a dose of OA (target INR 2-3). The MCA stenosis was demonstrated by conventional angiography or by at least two noninvasive examinations. Patients had either transient ischemic attack or cerebral infarct (CI) attributable to the MCA stenosis within 90 days before inclusion. The primary endpoint was: nonfatal CI, nonfatal acute myocardial infarct, vascular death and major hemorrhage. The patients were followed-up for a minimum of 1 year and a maximum of 3 years. RESULTS: The study included 28 patients (14 in each treatment group); the average age was 67 +/- 9.9 years. Men constituted 68% of the patients. After a mean follow-up of 23.1 +/- 10.9 months, there were no recurrences of CI in both groups. No endpoint was reported in the aspirin group, but 2 patients in the OA group (14.3%) exhibited vascular events: 1 acute myocardial infarct and 1 intracerebral hemorrhage). However, this difference was not statistically significant (p = 0.48). CONCLUSIONS: Our study suggests that aspirin is the treatment of choice for the prevention of vascular events in patients with symptomatic MCA stenosis.

Stroke and pulmonary thromboembolism after a long flight.

In the economy class syndrome (ECS) the patient presents a deep venous thrombosis (DVT) with or without pulmonary thromboembolism (PTE) during or after a long trip as a result of prolonged immobilization. Economy class stroke syndrome is an infrequent ECS variant in which ischemic stroke is associated with a patent foramen ovale (PFO). Few cases have been published in the literature to date. We present a patient who suffered a PTE and an ischemic stroke immediately after a transoceanic flight. A 36-year-old woman with no significant medical or familial history flew economy class from Lima, Peru, to Madrid, Spain. On disembarkation she presented sudden dyspnea and a depressed level of consciousness, global aphasia, and right hemiparesis. A pulmonary scintigraphy showed a PTE and a cranial MRI revealed an ischemic infarct in the left middle cerebral artery territory. We simultaneously performed a transesophageal echocardiography and a transcranial Doppler and observed a massive right-to-left shunt through a PFO. The patient was a heterozygous carrier of the C46T mutation of coagulation factor XII. The appearance of a stroke following a long trip is suggestive of paradoxical embolism through a PFO, mainly if it is associated with a DVT and/or a PTE. The cause of the initial event, the DVT, could be a prothrombotic state.