CGRP en migraña: de la fisiopatología a la terapéutica

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 farmacológica tenía una significación clínica con una mejoría en la migraña de los pacientes. Es lógico por tanto que una de las principales líneas de investigación en migraña se base en el papel del CGRP en la fisiopatología de esta entidad. Desarrollo Desde el Grupo de Estudio de Cefaleas de la Sociedad Española de Neurología nos planteamos la redacción de este documento, cuyo objetivo es abordar, basándonos en la evidencia publicada, cuestiones tan importantes como el papel del CGRP en la fisiopatología de la migraña, el mecanismo de acción de los anticuerpos monoclonales y de los gepantes, el análisis crítico de los resultados de los diferentes estudios, el perfil del paciente que podría ser candidato al tratamiento con anticuerpos monoclonales y su impacto en términos de farmacoeconomía. Conclusiones El desarrollo clínico de los gepantes, antagonistas del CGRP, para el tratamiento agudo del ataque de migraña y de los anticuerpos monoclonales contra ligando y contra el receptor del CGRP ofrecen resultados esperanzadores para nuestros pacientes. 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

The ALICE experiment at the CERN LHC

ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008

Caracterización del manejo del paciente con migraña en Atención Primaria en España. Análisis de los resultados del proyecto europeo My-LIFE anamnesis

Resumen: Introducción: La migraña afecta a más de 4,5 millones de personas en España con el consiguiente impacto socioeconómico. A pesar de la existencia de guías nacionales e internacionales, el manejo del paciente migrañoso, especialmente con migraña crónica, es inadecuado. Sujetos y métodos: Se llevó a cabo una encuesta a 40 médicos de Atención Primaria (AP) de España dentro de un proyecto europeo que involucraba a 201 médicos de 5 países. Resultados: La mayoría de los participantes diagnostican migraña episódica y migraña crónica (93% vs. 65%). El 82,5% indicó que no derivaba a los pacientes al especialista y en el 100% de casos los médicos de AP declararon ser los encargados del seguimiento del paciente. Las principales herramientas usadas en AP para el diagnóstico y seguimiento son la entrevista clínica, la guía de anamnesis y el diario del paciente. Se observó que los tratamientos prescritos no están en concordancia con las guías nacionales ni internacionales. Los participantes que no derivan al paciente estiman que solo el 48% recibe tratamiento preventivo y que la valoración de la eficacia se hace mediante la percepción del paciente. El 70% indica una necesidad de formación en migraña. Finalmente, el 100% de los participantes consideran que una guía para la anamnesis y la derivación sería imprescindible o de utilidad para el manejo de la migraña en AP. Conclusiones: Los resultados de la encuesta muestran que hay una necesidad de formación y guía en AP para mejorar el diagnóstico y manejo del paciente con migraña, especialmente con migraña crónica. Abstract: Introduction: Migraine affects more than 4.5 million people in Spain, resulting in a considerable socioeconomic impact. Although national and international guidelines have been published, the management of patients with migraine, especially those with chronic migraine, is inadequate. Subjects and methods: We conducted a survey among 40 primary care (PC) physicians in Spain as part of a European project involving 201 physicians from 5 countries. Results: Most participants issued diagnoses of episodic migraine and chronic migraine (93% vs 65%); 82.5% indicated that they did not refer these patients to specialists, and 100% of PC physicians stated that they were responsible for patient follow-up. The main tools used in PC for diagnosis and follow-up were clinical interviews, medical histories, and the patient diaries. Our data revealed that the treatments prescribed were not in accordance with the national and international guidelines. Participants who did not refer patients estimated that only 48% of patients received preventive treatment, and that the assessment of efficacy was based on patient perception. Seventy percent of respondents indicated a need for migraine training. Finally, 100% of participants considered that a guide for medical history taking and referral would be essential or useful for the management of migraine in PC. Conclusions: The survey results revealed a need for training and guidance in PC to improve the diagnosis and management of patients with migraine, particularly chronic migraine

Document of revision and updating of medication overuse headache (MOH)

Tratamiento preventivo; Cefalea con uso excesivo de medicación; OpioidesTractament preventiu; Cefalea per ús excessiu de medicaments; OpioidesPreventive treatment; Medication overuse headache; OpioidsIntroducción La cefalea con uso excesivo de medicación es una cefalea secundaria en la que el uso regular o frecuente de medicación analgésica produce un aumento de la frecuencia de una cefalea de base, pasando de episódica a crónica. La prevalencia de esta entidad está en torno al 1-2%, siendo más frecuente en mujeres entre 30 y 50 años con comorbilidades psiquiátricas como depresión o ansiedad y otros procesos de dolor crónico. Es importante conocer el manejo de esta entidad. Por este motivo, el Grupo de Estudios de Cefaleas de la Sociedad Española de Neurología ha pretendido realizar este documento de consenso sobre esta patología. Desarrollo Esta guía ha sido redactada por un grupo de expertos a partir de la revisión de la evidencia científica publicada y estableciendo recomendaciones prácticas para su adecuado manejo y tratamiento. El tratamiento de la cefalea con uso excesivo de medicación tiene varios pilares fundamentales y suele ser complejo: información y educación sobre el desarrollo de la cefalea con uso excesivo de medicación, tratamiento preventivo, suspensión del fármaco de uso frecuente y tratamiento de deshabituación. Es importante el seguimiento de pacientes con riesgo de recurrencias. Conclusiones Esperamos que este documento resulte de utilidad y permita su aplicación práctica en la consulta diaria y que sirva para actualizar y mejorar el conocimiento del manejo de esta patología.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

Comparative study of the high-pressure behavior of ZnV2O6, Zn2V2O7, and Zn3V2O8

We report a study of the high-pressure structural behavior of ZnV2O6, Zn2V2O7, and Zn3V2O8, which has been explored by means of synchrotron powder x-ray diffraction. We found that ZnV2O6 and Zn3V2O8 remain in the ambient-pressure structure up to 15 GPa. In contrast, in the same pressure range, Zn2V2O7 undergoes three phase transitions at 0.7, 3.0, and 10.8 GPa, respectively. Possible crystal structures for the first and second high-pressure phases are proposed. Reasons for the distinctive behavior of Zn2V2O7 are discussed. The compressibility of the different polymorphs has been determined. The response to pressure is found to be anisotropic in all the considered compounds and the room-temperature equations of state have been determined. The bulk moduli of ZnV2O6 (129(2) GPa) and Zn3V2O8 (120(2) GPa) are consistent with a structural framework composed of compressible ZnO6 octahedra and uncompressible VO4 tetrahedra. In contrast, Zn2V2O7 is highly compressible with a bulk modulus of 58(9) GPa, which is almost half of the bulk modulus of the other two vanadates. The large compressibility of Zn2V2O7 and its sequence of structural transitions are related to the fact that this material is less dense than the other zinc vanadates and to the penta-coordination of Zn atoms by oxygen atoms in Zn2V2O7. A comparison to the high-pressure behavior of related compounds is presented

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. (c) 2019 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/)

Documento de revisión y actualización de la cefalea por uso excesivo de medicación (CUEM).

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. 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. 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

Documento de revisión y actualización de la cefalea por uso excesivo de medicación (CUEM)

Introducción: La cefalea con uso excesivo de medicación es una cefalea secundaria en la que el uso regular o frecuente de medicación analgésica produce un aumento de la frecuencia de una cefalea de base, pasando de episódica a crónica. La prevalencia de esta entidad está en tornoal 1-2%, siendo más frecuente en mujeres entre 30 y 50 a ̃nos con comorbilidades psiquiátricas como depresión o ansiedad y otros procesos de dolor crónico. Es importante conocer el manejo de esta entidad. Por este motivo, el Grupo de Estudios de Cefaleas de la Sociedad Española de Neurología ha pretendido realizar este documento de consenso sobre esta patología. Desarrollo: Esta guía ha sido redactada por un grupo de expertos a partir de la revisión dela evidencia científica publicada y estableciendo recomendaciones prácticas para su adecuado manejo y tratamiento. El tratamiento de la cefalea con uso excesivo de medicación tiene varios pilares fundamentales y suele ser complejo: información y educación sobre el desarrollo de la cefalea con uso excesivo de medicación, tratamiento preventivo, suspensión del fármaco de uso frecuente y tratamiento de deshabituación. Es importante el seguimiento de pacientes con riesgo de recurrencias. Conclusiones: Esperamos que este documento resulte de utilidad y permita su aplicación práctica en la consulta diaria y que sirva para actualizar y mejorar el conocimiento del manejo de esta patología

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.Introducción: En los últimos a ̃nos 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 migra ̃na y en la migra ̃na crónica tanto en líquido cefalorraquídeo como en suero y que su reducción farmacológica tenía una significación clínica con una mejoría en la migra ̃na de los pacientes. Es lógico por tanto que una de las principales líneas de investigación en migra ̃na se base en el papel del CGRP en la fisiopatología de esta entidad. Desarrollo: Desde el Grupo de Estudio de Cefaleas de la Sociedad Espa ̃nola de Neurología nos planteamos la redacción de este documento, cuyo objetivo es abordar, basándonos en la evi- dencia publicada, cuestiones tan importantes como el papel del CGRP en la fisiopatología de la migra ̃na, el mecanismo de acción de los anticuerpos monoclonales y de los gepantes, el aná- lisis crítico de los resultados de los diferentes estudios, el perfil del paciente que podría ser candidato al tratamiento con anticuerpos monoclonales y su impacto en términos de farmacoe- conomía. Conclusiones: El desarrollo clínico de los gepantes, antagonistas del CGRP, para el tratamiento agudo del ataque de migra ̃na y de los anticuerpos monoclonales contra ligando y contra el receptor del CGRP ofrecen resultados esperanzadores para nuestros pacientes