Situación de partida y abordaje asistencial de la migraña en las consultas de neurología de España. Estudio PRIMERA / Initial situation and approach to the care of migraine in neurology services in Spain. The PRIMERA study

Introducción. A pesar de la alta discapacidad que conlleva, muchos pacientes con migraña nunca han consultado por este motivo. El estudio de quienes acuden por primera vez a consulta es obligado como paso previo a plantear medidas de intervención específicas para este colectivo de pacientes. Objetivo. Conocer el perfil de los pacientes con migraña que acuden por primera vez a una consulta de neurología, así como las actitudes diagnósticas y terapéuticas adoptadas por los neurólogos con respecto a ellos. Pacientes y métodos. Estudio transversal y multicéntrico, realizado en consultas de neurología de todo el territorio nacional. Participaron 168 neurólogos que reclutaron un total de 851 pacientes (74,6% mujeres; edad media: 34,0 ± 10,7 años). La discapacidad se evaluó mediante el cuestionario específico para migraña (Headache Impact Test) y el cuestionario de discapacidad genérico (Sheehan Disability Scale). Resultados. El 66,5% de los pacientes consultó por consejo médico, el 33,5% restante lo hizo por iniciativa propia. Sólo el 55,9% tenía un diagnóstico previo de migraña. Los principales motivos de consulta fueron la ineficacia del tratamiento sintomático (25%) y el incremento en la frecuencia o intensidad de las crisis (23,4%). Aunque el 70,3% de los pacientes puntuaba alta discapacidad en el Headache Impact Test, sólo el 17,4% utilizaba tratamiento específico y únicamente el 13,3% tratamiento preventivo. Conclusiones. El estudio PRIMERA ratifica, una vez más, que la migraña es una entidad infradiagnosticada e infratratada en nuestro medio, por lo que siguen siendo precisas intervenciones de tipo educativo y formativo específicas para esta patología (AU)

Introduction. Despite the high degree of disability it entails, many patients with migraine have never visited their doctor for this reason. It is necessary to conduct a study to examine the characteristics of first-time visits as a step that must be carried out prior to establishing specific intervention measures for this group of patients. Aim. To determine the profile of the patients with migraine who visit a neurology service for the first time, together with the diagnostic and therapeutic attitudes that neurologists display towards them. Patients and methods. We conducted a cross-sectional, multi-centre study of neurology services across the country. The research included 168 neurologists who recruited 851 patients (74.6% females; mean age: 34.0 ± 10.7 years). Disability was assessed by means of the specific migraine questionnaire (Headache Impact Test) and the generic disability questionnaire (Sheehan Disability Scale). Results. A third (66.5%) of the patients went for consultation following their doctor’s advice, while the remaining 33.5% went on their own accord. Only 55.9% had been previously diagnosed with migraine. The main reasons for visiting were ineffective symptomatic treatment (25%) and an increase in the frequency or intensity of the attacks (23.4%). Although 70.3% of the patients had high disability scores on the Headache Impact Test, only 17.4% used specific treatment and only13.3% were on preventive treatment. Conclusions. The PRIMERA study confirms, once again, that migraine is an under-diagnosed and under-treated condition in our setting, which means that specific educational interventions and training are still required for this pathology (AU)

Factores de personalidad, grado de discapacidad y abordaje terapéutico de los pacientes con migraña atendidos en primera consulta en neurología (estudio Psicomig) / Personality factors, degree of disability and therapeutic management of patients with migraine visiting a neurology unit for the first time (Psicomig study)

Introducción. La migraña se ha asociado recientemente a determinados perfiles de personalidad y estilos de afrontamiento. Objetivo. Explorar la asociación entre factores de personalidad, discapacidad y abordaje terapéutico en la migraña. Pacientes y métodos. Estudio epidemiológico, transversal y multicéntrico, con pacientes atendidos por primera vez en una consulta de neurología por migraña. Se recogieron datos sociodemográficos y clínicos de los pacientes. Para valorar factores de personalidad se utilizó el NEO-FFI (Neuroticism-Extroversion-Openness-Five Factor Inventory); se evaluó el grado de discapacidad mediante el Headache Impact Test (HIT-6) y la medida del número de días equivalentes a días de trabajo perdidos –lost workday equivalents (LWDE)–. Se realizaron análisis de regresión logística bivariantes. Resultados. Se reclutaron 736 pacientes, de los cuales fueron valorables para el análisis 700 (75,6% mujeres; edad media: 35,5 ± 11,5 años). Un 68,9% presentaba migraña sin aura, 1-4 crisis/mes (66,7%) y de intensidad moderada (58,1%). El 76,1% de pacientes tenía discapacidad grave según el HIT-6. De los 554 pacientes activos, la media de días equivalentesa días de trabajo perdidos en los últimos tres meses fue de 6,8 ± 8,2. Los pacientes mostraban una mayor inestabilidad emocional que la población general, y su puntuación fue menor en extraversión, apertura, amabilidad y responsabilidad. Todos los pacientes recibían tratamiento para su migraña: el 47,3%, mediante un tratamiento escalonado entre ataques; el 39,9%, intraataque, y estratificado, únicamente el 12,9%. Conclusiones. Este estudio confirma el impacto de la migraña en términos de discapacidad y en términos de pérdida de productividad laboral, así como su asociación a factores de personalidad (AU)

Introduction. Migraine has recently been associated to certain personality profiles and styles of coping. Aim. To explore the association between personality factors, disability and the therapeutic management of migraine. Patients and methods. We conducted an epidemiological, cross-sectional, multi-centre study with patients with migraine visiting a neurology unit for the first time. Socio-demographic and clinical data were collected about the patients. The NEO-FFI (Neuroticism-Extraversion-Openness Five-Factor Inventory) was used to evaluate personality factors; the degree of disability was evaluated using the Headache Impact Test (HIT-6) and the number of lost workday equivalents (LWDE) was measured. Bivariate logistic regression analyses were also performed. Results. A total of 736 patients were recruited, of whom 700 were suitable for inclusion in the analysis (75.6% females; mean age: 35.5 ± 11.5 years). In all, 68.9% presented migraine without aura, 1-4 seizures/month (66.7%) and of moderate intensity (58.1%). A total of 76.1% of patients had severe disability according to the HIT-6. Of the 554 active patients, the mean number of lost workday equivalents in the previous three months was 6.8 ± 8.2. Patients showed greater emotional instability than the general population and they scored lower on extraversion, openness, agreeableness and conscientiousness. All the patients were being treated for their migraine: 47.3% by means of stepped treatment between seizures; 39.9% intra-seizures, and stratified in only 12.9%. Conclusions. This study confirms the impact of migraine in terms of disability and in terms of loss of labour output, together with its association with personality factors (AU)

Perturbations induced by synthetic peptides from hepatitis G virus structural proteins in lipid model membranes: a fluorescent approach.

The name HGV/GBV-C remains as an acronym for hepatitis G virus (HGV) and GB virus-C (GBV-C), strain variants of this enveloped RNA virus independently but simultaneously discovered in 1995. Nowadays there is no evidence that it causes hepatitis in humans either during initial infection or after long-term carriage, but it has been recently related with HIV regarding the inhibition of progression to AIDS. The overall genomic organization of HGV/GBV-C is similar to that of hepatitis C virus (HCV) and other members of the Flavivirus family in Hepacivirus genus. Although a stretch of conserved, hydrophobic amino acids within the envelop glycoprotein of HCV has been proposed as the virus fusion peptide, the mode of entry of GBV-C/HGV into target cells is at present unknown. In the present work, sequences derived from the structural E2-protein of HGV/GBV-C have been selected by means of semiempirical methods and then synthesized manually following solid-phase methodologies. Their ability to induce perturbations in model membranes has been analysed by measuring the penetration of such peptides in lipid monolayers and by a series of experiments based on tryptophan peptide fluorescence emission spectra. Besides, release of vesicular contents to the medium was monitored by the ANTS/DPX assay. The membrane destabilization properties of these peptides was found very related with the length of the sequence.

Characterization of a putative fusogenic sequence in the E2 hepatitis G virus protein.

With the aim of better understanding the fusion process mediated by the envelope proteins of the hepatitis G virus (HGV/GBV-C), we have investigated the interaction with model membranes of two overlapping peptides [(267-284) and (279-298)] belonging to the E2 structural protein. The peptides were compared for their ability to perturb lipid bilayers by means of different techniques such as differential scanning calorimetry and fluorescence spectroscopy. Furthermore, the conformational behaviour of the peptides in different membrane environments was studied by Fourier-transform infrared spectroscopy and circular dichroism. The results showed that only the E2(279-298) peptide sequence was able to bind with high affinity to negatively charged membranes, to permeabilize efficiently negative lipid bilayers, to induce haemolysis, and to promote inter-vesicle fusion. This fusogenic activity could be related to the induced peptide conformation upon interaction with the target membrane.

Interaction of synthetic peptides corresponding to hepatitis G virus (HGV/GBV-C) E2 structural protein with phospholipid vesicles.

The interaction with phospholipid bilayers of two synthetic peptides with sequences corresponding to a segment next to the native N-terminus and an internal region of the E2 structural hepatitis G virus (HGV/GBV-C) protein [E2(7-26) and E2(279-298), respectively] has been characterized. Both peptides are water soluble but associate spontaneously with bilayers, showing higher affinity for anionic than zwitterionic membranes. However, whereas the E2(7-26) peptide is hardly transferred at all from water to the membrane interface, the E2(279-298) peptide is able to penetrate into negatively charged bilayers remaining close to the lipid/water interface. The nonpolar environment clearly induces a structural transition in the E2(279-298) peptide from random coil to alpha-helix, which causes bilayer perturbations leading to vesicle permeabilization. The results indicate that this internal segment peptide sequence is involved in the fusion of HGV/GBV-C to membrane.

Effects of overlapping GB virus C/hepatitis G virus synthetic peptides on biomembrane models.

The present study was undertaken to examine the physicochemical properties of three overlapping peptides belonging to the E2 envelope protein of Hepatitis G virus (GBV-C/HGV) and its interaction with phospholipid biomembrane models using biophysical techniques. We describe our findings concerning the surface activity and the interaction of the peptides with monolayers and liposomes composed of the zwitterionic phospholipids dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine (DMPC) and a mixture of DMPC with the anionic phospholipid dimyristoylphosphatidylglycerol. The results inform about the effect of the chain length on their interaction with biomembrane models. The longest chain peptide interacts in a higher extent with all the phospholipid studied as a result of a combination of hydrophobic and electrostatic forces.

Interaction of three beta-interferon domains with liposomes and monolayers as model membranes.

The physicochemical properties of three peptides belonging to the beta-interferon (beta-IFN) molecule, -beta-IFN(13-20), beta-IFN(40-47) and beta-IFN(109-116)-, which have been described to be antigenic epitopes of the neutralising antibodies responsible of the failure of the Multiple Sclerosis therapy, and their palmitoylated derivatives were analysed. Peptides were synthesised by solid-phase methodologies and characterized by amino acid analysis, analytical high-performance liquid chromatography and electrospray mass spectrometry. The activity of free and derivatized peptides was determined. In order to know how the synthesised peptides were able to interact with membrane models, studies of kinetics of penetration at constant area and compression isotherms were carried out. Moreover, differential scanning calorimetry (DSC) was used to investigate the thermotropic phase properties of binary mixtures of dipalmitoylphosphatidylcholine (DPPC) or dipalmitoylphosphatidylglicerol (DPPG) with the peptides.