Cefalea por abuso de medicamentos y sus marcadores clínicos / Medication overuse headache and its specific clinical markers

Resumen Introducción: Los marcadores clínicos de la cefalea por uso excesivo de medicación (CMA) se basan en la clasificación de las cefaleas desarrollada por la Sociedad Internacional de Cefaleas (IHS). Esta clasificación incluye sólo dos criterios: la frecuencia de los días de cefalea debe ser de 15 o más días al mes durante al menos tres o más meses; - y el número de días de uso excesivo de la medicación debe ser de 10 o 15 días al mes dependiendo del tipo de medicación. Sin embargo, los pacientes suelen tener otros marcadores clínicos asociados distintos, que la mayoría de los médicos pasan por alto durante la evaluación inicial. Metodología: Este estudio es un estudio prospectivo, longitudinal y observacional de 76 pacientes ingresados en la Unidad de Cefaleas del hospital DIPRECA. Todos ellos fueron diagnosticados de HMO según los criterios establecidos por su ICHD III beta.(1) Los pacientes recibieron un tratamiento estándar que incluía desintoxicación y medicación preventiva y fueron seguidos durante 6 meses. Se registraron los síntomas de interés en cada visita de seguimiento clínico y se administraron escalas de evaluación como Zung, MIDAS, HIT-6. Resultados: Los medicamentos sobreutilizados incluyeron antiinflamatorios no esteroideos (AINE), triptanes y cornezuelos. Los síntomas clínicos más significativos asociados fueron: despertar por la mañana con dolor de cabeza, despertar al paciente al amanecer por dolor de cabeza, dificultades de atención, depresión, dolor cervical y síndrome de dolor miofascial. Todos los síntomas mejoraron significativamente al iniciar el tratamiento, al igual que la calidad de vida medida por las escalas MIDAS y HIT-6. Discusión: Al evaluar a los pacientes con HMO, hay que tener en cuenta tanto los criterios diagnósticos de la ICHD III beta como los síntomas comunes y específicos que se observan en la mayoría de los casos de HMO.

Introduction: Clinical markers of medication overuse headache (MOH) are based on headache classification developed by the International Headache Society (IHS). This classification include only two criteria: frequency of headache days must be 15 or more days per month for at least three or more months; - and the number of days of overuse medication must be either 10 or 15 days per month depending on the type of medication. However, patients often have others distinct associated clinical markers, which are overlooked by most physicians during the initial evaluation. Methodology: This study is a prospective, longitudinal and observational study of 76 patients admitted to DIPRECA´s hospital Headache Unit. They were all diagnosed with, MOH according to the criteria established by the his ICHD III beta.(1) Patients were given standard treatment including detoxification and preventive medications and followed for 6 months. Symptoms of interest were recorded in at each clinical monitoring visit and assessment scales such as Zung, MIDAS, HIT-6 were administered. Results: Overused medications included nonsteroidal anti-inflammatory drugs (NSAIDs), triptans and ergots. The most significant clinical symptoms associated were: awaking in the morning with headache, awaking the patient at dawn by headache, attention difficulties, depression, cervical pain and myofascial pain syndrome. All symptoms significantly improved when treatment began, as did quality of life as measured by MIDAS and HIT-6 scales. Discussion: In evaluating patients with MOH consider both the ICHD III beta diagnostic criteria and the common and specific symptoms seen in most cases of MOH.

On the Application of a Diffusive Memristor Compact Model to Neuromorphic Circuits.

Memristive devices have found application in both random access memory and neuromorphic circuits. In particular, it is known that their behavior resembles that of neuronal synapses. However, it is not simple to come by samples of memristors and adjusting their parameters to change their response requires a laborious fabrication process. Moreover, sample to sample variability makes experimentation with memristor-based synapses even harder. The usual alternatives are to either simulate or emulate the memristive systems under study. Both methodologies require the use of accurate modeling equations. In this paper, we present a diffusive compact model of memristive behavior that has already been experimentally validated. Furthermore, we implement an emulation architecture that enables us to freely explore the synapse-like characteristics of memristors. The main advantage of emulation over simulation is that the former allows us to work with real-world circuits. Our results can give some insight into the desirable characteristics of the memristors for neuromorphic applications.

Indomethacin Responsive Headaches: Exhaustive Systematic Review with Pooled Analysis and Critical Appraisal of 81 Published Clinical Studies.

OBJECTIVES: The relationship between indomethacin (IMC) and headache treatment has long intrigued clinicians and clinical researchers in Headache Medicine. Why is it efficacious in many types of headache disorders when other medications are not, and what is the mechanism behind its efficacy? IMC and headache related topics that have been explored in detail in the literature include IMC-responsive headache disorders ("traditional"), pharmacology of IMC, symptomatic headaches responsive to IMC, "novel" headache conditions that respond, cluster headache and IMC, IMC provoking headache, the issue about" absolute" and "non-absolute" effect of IMC on headache disorders, and the morphing trigeminal autonomic cephalalgias (TACs). DATA SOURCE: A PubMed/MEDLINE search was used for Clinical Studies Categories and Systematic Reviews on the PubMed Clinical Queries. The search details were "indomethacin" AND "headache" spanning all previous years until February 1, 2015. Methods were in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. REVIEW METHODS: Articles were excluded if IMC had not been used to treat headache disorders in adults, if the article concerned IMC-responsive headaches but made no reference to the use of IMC, and articles not addressing the above mentioned topics. RESULTS AND CONCLUSIONS: The "velocity" of publications on IMC and headache seems to be decreasing, particularly on the use of IMC for the treatment of TACs. The science behind the understanding of the putative mechanisms of IMC's action on headache has moved forward, but the answer to why it works better than other nonsteroidal anti-inflammatory drugs has been elusive. There are case reports of other rare headache disorders that may be responsive to IMC. The dosages of IMC used as a tool for detecting IMC responsive disorders vary according to different centers of investigation. In many circumstances, headache disorders similar to "primary" IMC-responsive disorders are actually symptomatic disorders. Cluster headache as an IMC-resistant headache disorder may not be as absolute as once thought. Sometimes, IMC has been found to provoke headache; differentiating IMC-provoked headache from IMC-resistant headache can make headache diagnosis and management difficult. As for the "absolute" responsiveness of IMC, it is possible that using higher dosages leads to higher sensitivity, probably at the expense of decreased specificity. There are many reports about the occurrence of two or more IMC-responsive disorders (latu sensu) in the same patient, which may be coincidental.

Therapeutic antibodies against CGRP or its receptor.

CGRP is an extensively studied neuropeptide that has been implicated in the pathophysiology of migraine. While a number of small molecule antagonists against the CGRP receptor have demonstrated that targeting this pathway is a valid and effective way of treating migraine, off-target hepatoxicity and formulation issues have hampered the development for regulatory approval of any therapeutic in this class. The development of monoclonal antibodies to CGRP or its receptor as therapeutic agents has allowed this pathway to be re-investigated. Herein we review why CGRP is an ideal target for the prevention of migraine and describe four monoclonal antibodies against either CGRP or its receptor that are in clinical development for the treatment of both episodic and chronic migraine. We describe what has been publically disclosed about their clinical trials and future clinical development plans.

Characteristics of migraine visual aura in Southern Brazil and Northern USA.

BACKGROUND: Migraine aura, made up of one or more neurological symptoms arising from the cortex or brainstem, is a complex neurological phenomenon. Visual aura is the most frequent aura manifestation. Studying the subjective components of visual aura makes it possible to identify common characteristics. OBJECTIVE: To thoroughly describe the characteristics of migraine visual aura in patients with migraine with aura. METHODS: We performed a retrospective, descriptive study of the visual aura of 122 migraine patients collected at two headache clinics in the Americas. This study was designed to determine the characteristics of a typical visual aura. RESULTS: The most common features of the visual aura in our study are that it occurs before the headache with a gap of less than 30 minutes, lasts 5 to 30 minutes, has a gradual onset, usually begins peripherally, is unilateral, and shimmers. Furthermore, the location of typical visual aura in the visual field has no fixed relationship to headache laterality, is slightly more often without color, and is often described as small bright dots and zigzag lines. Blurred vision, not typically considered to be an aura phenomenon of cortical origin, is in fact the most frequently reported visual symptom. CONCLUSIONS: Migraine visual aura is heterogeneous and pleomorphic, and some of our findings run contrary to common beliefs.

High-altitude headache.

High-altitude headache (HAH) is an important public health problem because many of the millions of visitors to locations high above sea level get significant headaches each year. Headache is the most common symptom of acute exposure to high altitude. It may be a manifestation of acute mountain sickness (AMS), as well as of chronic mountain sickness (CMS). This article describes the clinical picture of AMS and CMS. The clinical characteristics of HAH are presented, its pathophysiology is discussed, and the acute and preventive treatment options are reviewed.

Burden of migraine in Brazil: estimate of cost of migraine to the public health system and an analytical study of the cost-effectiveness of a stratified model of care.

BACKGROUND: The search for rationality in health expenses in developing countries collides with the lack of effectively conducted epidemiologic studies. PURPOSE: To present an estimate of the impact and costs of migraine in the Brazilian public health system and to estimate the impact on these costs and the effectiveness of a model of stratified care in the management of migraine. METHODS: An analytical model of utilization of the Brazilian public health system was constructed. Data refer to 1999 and were obtained in accordance with the following steps: (1) Brazilian demographic characteristics; (2) characteristics of the public health system related to its 3 hierarchical levels-primary, secondary, and tertiary care, the last being subdivided into emergency department and hospital care; and (3) estimation of the number of migraine consultations at each complexity level. In Brazil, migraineurs seen in the public health system are most often discharged with an acute treatment, usually a nonspecific medication. We compared this treatment with a proposed stratified care model that uses a triptan as an acute care medication. We have made the following assumptions: (1) 15% of the patients would fall into the Migraine Disability Assessment (MIDAS) grade I category, 25% would fall into the MIDAS grade II category, 30% into the grade III category, and 30% into the MIDAS grade IV category; (2) the mean number of migraine attacks per year are: MIDAS I, 7.49; MIDAS II, 8.02; MIDAS III, 12.22; and MIDAS IV, 27.01. The annual costs of the treatment were calculated according to the following equation: AC = P x N x C + P x Cp + P x Cat x AMA, where P is the number of patients; N, the number of consultations per patient; C, the cost of consultation per level; Cp, the cost of preventive drugs; Cat, the cost of acute therapy drugs; and AMA is the number of migraine attacks per year. Results.-The public health system resources included 55 735 ambulatory units (primary and secondary) and 6453 emergency department and public hospital units, with a corresponding budget of US $2 820 899 621.26. The estimated cost of a consultation on the primary care level was US $11.53; on the secondary care level, US $22.18; in the emergency department, $34.82; and for hospitalization, US $217.93. The total estimated public health system expenses for migraine were US $140 388 469.60. The proposed model would imply a cost reduction of 6.2% (US $7 514 604.40) with an improvement in the quality of the public health system from the actual 18.2% to an estimated 84.5%. CONCLUSION: Migraine seems to pose a huge burden on the Brazilian public health system. The implementation of a stratified care model of treatment that would include specific acute migraine therapies could result in a dramatic increase in the quality of migraine care and a significant reduction in cost.

New migraine preventive options: an update with pathophysiological considerations

BACKGROUND: The pharmacological treatment of migraine may be acute or preventive. Frequent, severe and long-lasting migraine attacks require prophylaxis. Multiple threads of research over the last 15 years have led to the concept that migraine is generated from a hyperexcitable brain. A variety of causes for hyperexcitability of the brain in migraine have been suggested. These causes include low cerebral magnesium levels, mitochondrial abnormalities, dysfunctions related to increased nitric oxide or the existence of a P/Q type calcium channelopathy. The better knowledge about migraine pathophisiology led us to discuss new treatment options. OBJECTIVES: The aim of the present study is to present an evidence-based review of some new drugs or some agents that even though available for a long time, are not frequently used. METHODS/RESULTS: We present a review of anticonvulsants with various mechanisms of action such as lamotrigine, gabapentin, topiramate, tiagabine, levetiracetam and zonisamide. We also review natural products, like riboflavin and magnesium, botulinum toxin A, a specific CGRP antagonist and the anti-asthma medication montelukast, with pathophysiological discussion. CONCLUSIONS: We aimed to present an update of newer or less frequently used preventive migraine therapies, drugs that might reduce the burden and the costs of a disease that should be considered as a public health problem all around the world

Hemicrania continua: a report of ten new cases.

Hemicrania continua (HC) is an uncommon primary headache first described as a syndrome in 1984. Being quite unusual, its clinical characterization still demands better description. The aim of this study is to present the main clinical characteristics of 10 patients with the diagnosis of HC seen in a tertiary center, critically discussing their main features. All subjects had strictly unilateral headache without side shift and absolute response to indomethacin. Seven patients (70%) presented autonomic features during pain exacerbations. Four (40%) had migrainous symptoms during the exacerbations and one presented partial relief with dihydroergotamine. One patient had pain excruciatingly severe during the exacerbations. Although the cardinal features of HC - continuous, unilateral, indomethacin responsive, remain strongly reliable, a refinement on the clinical characterization is needful and desired.

Hemicrania continua: a report of ten new cases

Hemicrania continua (HC) is an uncommon primary headache first described as a syndrome in 1984. Being quite unusual, its clinical characterization still demands better description. The aim of this study is to present the main clinical characteristics of 10 patients with the diagnosis of HC seen in a tertiary center, critically discussing their main features. All subjects had strictly unilateral headache without side shift and absolute response to indomethacin. Seven patients (70 percent) presented autonomic features during pain exacerbations. Four (40 percent) had migrainous symptoms during the exacerbations and one presented partial relief with dihydroergotamine. One patient had pain excruciatingly severe during the exacerbations. Although the cardinal features of HC - continuous, unilateral, indomethacin responsive, remain strongly reliable, a refinement on the clinical characterization is needful and desired

New migraine preventive options: an update with pathophysiological considerations.

BACKGROUND: The pharmacological treatment of migraine may be acute or preventive. Frequent, severe and long-lasting migraine attacks require prophylaxis. Multiple threads of research over the last 15 years have led to the concept that migraine is generated from a hyperexcitable brain. A variety of causes for hyperexcitability of the brain in migraine have been suggested. These causes include low cerebral magnesium levels, mitochondrial abnormalities, dysfunctions related to increased nitric oxide or the existence of a P/Q type calcium channelopathy. The better knowledge about migraine pathophisiology led us to discuss new treatment options. OBJECTIVES: The aim of the present study is to present an evidence-based review of some new drugs or some agents that even though available for a long time, are not frequently used. METHODS/RESULTS: We present a review of anticonvulsants with various mechanisms of action such as lamotrigine, gabapentin, topiramate, tiagabine, levetiracetam and zonisamide. We also review natural products, like riboflavin and magnesium, botulinum toxin A, a specific CGRP antagonist and the anti-asthma medication montelukast, with pathophysiological discussion. CONCLUSIONS: We aimed to present an update of newer or less frequently used preventive migraine therapies, drugs that might reduce the burden and the costs of a disease that should be considered as a public health problem all around the world.

Características clínicas da enxaqueca sem aura / Clinical characteristics of migraine without aura

Um estudo aprofundado das características clínicas da enxaqueca sem aura (ESA) revela alguns dados interessantes. Um questionário foi respondido por 200 pacientes que preenchiam os critérios da Sociedade Internacional de Cefaléia para ESA. O pico do início da enxaqueca foi entre 10 e 19 anos de idade. A cefaléia era restrita a um lado em 19 por cento. Era exclusivamente bilateral em 9 por cento. A maioria (86,2 por cento) dos pacientes que descreveram cefaléias em um único local localizou-a na área fronto-temporal. Cervicalgia estava associada aos ataques de enxaqueca em 70,5 por cento e dor facial em 73,5 por cento. O caráter latejante foi notado por 81 por cento. Todos os pacientes descreveram a cefaléia como moderada a severa. Somente 55 por cento disseram que a dor era agravada por atividades físicas rotineiras. Náusea ocorreu em 91 por cento, foto e fonofobia em 77 por cento e vômitos em 50 por cento. Este olhar detalhado na ESA demonstra a grande complexidade dos seus sintomas.