[35S]GTPγS (Guanosine-5'-O-(γ-thio)triphosphate-[35S]) Binding Scintillation Proximity Assay Experiments in Postmortem Brain Tissue.

Heterotrimeric guanine nucleotide-binding proteins (G proteins) are the very first effector in signal transduction events triggered by G-protein-coupled receptors (GPCRs). One of the most widely used approaches for determining GPCR activity in native tissue is based on the binding of [35S]GTPγS. Classically, an heterogeneous procedure including a filtration step has been used, but a modification of the protocol including an immunoprecipitation step has allowed the specific discrimination of the contribution of the different Gα subunit subtypes to the effect of each ligand. Nowadays, that the concept of functional selectivity has been demonstrated for several ligands and GPCRs, information obtained from this methodological approach will be very useful for broadening the knowledge of GPCRs signaling profiles and describing the effect of different ligands over them. In this chapter we will describe the detailed protocol of antibody-capture [35S]GTPγS scintillation proximity assay (SPA) in order to provide the reader with comprehensive guidelines to study receptor-mediated functional activation of different Gα-protein subtypes in native mammalian brain membranes. In addition, advantages and limitations of this method will be described, as well as future direction in the application of this approach indicated.

Actualización sobre alteraciones de función visual y espesores coriorretinianos en la enfermedad de Parkinson / Update on visual function and choroidal-retinal thickness alterations in Parkinson's disease

La enfermedad de Parkinson (EP) es un proceso neurodegenerativo que afecta a unos 7,5 millones de personas en el mundo. Desde 2004, varios estudios han demostrado cambios en el espesor de diversas capas de la retina en la EP utilizando tomografía de coherencia óptica (OCT). Sin embargo, existen resultados contradictorios entre los diferentes estudios. Algunos de ellos relacionan los espesores retinianos con la severidad o duración de la enfermedad, lo cual convierte a las mediciones de la OCT en biomarcadores de progresión de la EP, inocuos y de fácil adquisición. También existen estudios que demuestran pérdida de capacidad o función visual desde fases tempranas de la enfermedad. Por último, los estudios más recientes que utilizan OCT de tecnología Swept Source demuestran aumento del espesor coroideo en la EP y aportan nueva información relacionada con el proceso degenerativo retiniano en esta enfermedad. Este trabajo pretende revisar la bibliografía existente sobre OCT y EP con el fin de determinar los parámetros retinianos y coroideos alterados en la EP y su posible utilidad clínica, así como analizar cuáles son las disfunciones visuales más relevantes en estos pacientes

Parkinson's disease (PD) is a neurodegenerative process that affects 7.5 million people around the world. Since 2004, several studies have demonstrated changes in various retinal layers in PD using optical coherence tomography (OCT). However, there are some discrepancies in the results of those studies. Some of them have correlated retinal thickness with the severity or duration of the disease, demonstrating that OCT measurements may be an innocuous and easy biomarker for PD progression. Other studies have demonstrated visual dysfunctions since early phases of the disease. Lastly, the most recent studies that use Swept Source OCT technology, have found choroidal thickness increase in PD patients and provide new information related to the retinal degenerative process in this disease. The aim of this paper is to review the literature on OCT and PD, in order to determine the altered retinal and choroidal parameters in PD and their possible clinical usefulness, and also the visual dysfunctions with higher impact in these patients

Update on visual function and choroidal-retinal thickness alterations in Parkinson's disease. / Actualización sobre alteraciones de función visual y espesores coriorretinianos en la enfermedad de Parkinson.

Parkinson's disease (PD) is a neurodegenerative process that affects 7.5 million people around the world. Since 2004, several studies have demonstrated changes in various retinal layers in PD using optical coherence tomography (OCT). However, there are some discrepancies in the results of those studies. Some of them have correlated retinal thickness with the severity or duration of the disease, demonstrating that OCT measurements may be an innocuous and easy biomarker for PD progression. Other studies have demonstrated visual dysfunctions since early phases of the disease. Lastly, the most recent studies that use Swept Source OCT technology, have found choroidal thickness increase in PD patients and provide new information related to the retinal degenerative process in this disease. The aim of this paper is to review the literature on OCT and PD, in order to determine the altered retinal and choroidal parameters in PD and their possible clinical usefulness, and also the visual dysfunctions with higher impact in these patients.

Visual dysfunction and its correlation with retinal changes in patients with Parkinson's disease: an observational cross-sectional study.

OBJECTIVES: To evaluate visual dysfunction and its correlation with structural changes in the retina in patients with Parkinson's disease (PD). METHODS: Patients with PD (n=37) and controls (n=37) were included in an observational cross-sectional study, and underwent visual acuity (VA), colour vision (using the Farnsworth and Lanthony desaturated D15 colour tests) and contrast sensitivity vision (CSV; using the Pelli-Robson chart and CSV 1000E test) evaluation to measure visual dysfunction. Structural measurements of the retinal nerve fibre layer (RNFL), and macular and ganglion cell layer (GCL) thicknesses, were obtained using spectral domain optical coherence tomography (SD-OCT). Comparison of obtained data, and correlation analysis between functional and structural results were performed. RESULTS: VA (in all different contrast levels) and all CSV spatial frequencies were significantly worse in patients with PD than in controls. Colour vision was significantly affected based on the Lanthony colour test. Significant GCL loss was observed in the minimum GCL+inner plexiform layer. A clear tendency towards a reduction in several macular sectors (central, outer inferior, outer temporal and superior (inner and outer)) and in the temporal quadrant of the RNFL thickness was observed, although the difference was not significant. CSV was the functional parameter most strongly correlated with structural measurements in PD. Colour vision was associated with most GCL measurements. Macular thickness was strongly correlated with macular volume and functional parameters (r>0.70, p<0.05). CONCLUSIONS: Patients with PD had visual dysfunction that correlated with structural changes evaluated by SD-OCT. GCL measurements may be reliable indicators of visual impairment in patients with PD.

FADD adaptor and PEA-15/ERK1/2 partners in major depression and schizophrenia postmortem brains: basal contents and effects of psychotropic treatments.

Enhanced brain apoptosis (neurons and glia) may be involved in major depression (MD) and schizophrenia (SZ), mainly through the activation of the intrinsic (mitochondrial) apoptotic pathway. In the extrinsic death pathway, pro-apoptotic Fas-associated death domain (FADD) adaptor and its non-apoptotic p-Ser194 FADD form have critical roles interacting with other death regulators such as phosphoprotein enriched in astrocytes of 15 kDa (PEA-15) and extracellular signal-regulated kinase (ERK). The basal status of FADD (protein and messenger RNA (mRNA)) and the effects of psychotropic drugs (detected in blood/urine samples) were first assessed in postmortem prefrontal cortex of MD and SZ subjects (including a non-MD/SZ suicide group). In MD, p-FADD, but not total FADD (and mRNA), was increased (26%, n=24; all MD subjects) as well as p-FADD/FADD ratio (a pro-survival marker) in antidepressant-free MD subjects (50%, n=10). In contrast, cortical FADD (and mRNA), p-FADD, and p-FADD/FADD were not altered in SZ brains (n=21) regardless of antipsychotic medications (except enhanced mRNA in treated subjects). Similar negative results were quantified in the non-MD/SZ suicide group. In MD, the regulation of multifunctional PEA-15 (i.e., p-Ser116 PEA-15 blocks pro-apoptotic FADD and PEA-15 prevents pro-survival ERK action) and the modulation of p-ERK1/2 were also investigated. Cortical p-PEA-15 was not changed whereas PEA-15 was increased mainly in antidepressant-treated subjects (16-20%). Interestingly, cortical p-ERK1/2/ERK1/2 ratio was reduced (33%) in antidepressant-free when compared to antidepressant-treated MD subjects. The neurochemical adaptations of brain FADD (increased p-FADD and pro-survival p-FADD/FADD ratio), as well as its interaction with PEA-15, could play a major role to counteract the known activation of the mitochondrial apoptotic pathway in MD.

Retinal thinning and correlation with functional disability in patients with Parkinson's disease.

AIMS: To determine whether there is an association between retinal thinning and functional rating scales in patients with Parkinson's disease (PD). MATERIALS AND METHODS: Patients with PD (n=153) and controls (n=242) underwent evaluations of the macula and retinal nerve fibre layer (RNFL) using two new-generation Fourier domain optical coherence tomography (OCT) devices (Cirrus, Carl Zeiss Meditec, Dublin, California, USA; Spectralis, Heidelberg Engineering, Heidelberg, Germany). PD severity was assessed using the Schwab-England Activities of Daily Living scale, the Unified Parkinson Disease Rating Scale, the Hoehn and Yahr (HY) scale. Retinal and RNFL thicknesses were compared between patients and controls. Correlations between structural parameters and the scores of the neurologic scales were evaluated. RESULTS: RNFL parameters were significantly reduced in patients with PD, especially when using the Spectralis OCT device. All macular parameters, except for foveal thickness, differed significantly between controls and patients with PD (p<0.001). HY scores were significantly and inversely correlated with all macular parameters when measured with the Spectralis OCT device (p<0.05) and with RNFL thickness when measured with the Cirrus OCT device (nasal quadrant, sectors 2 and 5). CONCLUSIONS: The neurodegeneration caused by PD can be detected using Fourier domain OCT. RNFL and macular thicknesses correlate with PD severity.

Use of Fourier-domain OCT to detect retinal nerve fiber layer degeneration in Parkinson's disease patients.

PURPOSE: To demonstrate axonal loss in the retinal nerve fiber layer (RNFL) of patients with Parkinson's disease (PD) and to evaluate the ability of Fourier-domain optical coherence tomography (OCT) to detect RNFL degeneration and retinal thinning in these patients. METHODS: PD patients (n=100) and healthy subjects (n=100) were included in the study and underwent visual acuity, color vision, and OCT examinations using two next-generation Fourier-domain devices (Spectralis and Cirrus). Differences in the RNFL thicknesses were compared between patients and controls. RESULTS: RNFL thicknesses were significantly reduced in PD patients compared with healthy subjects, especially those obtained using the Spectralis OCT, in the inferotemporal quadrant (155.6±16.5 µm in healthy eyes vs 142.1±24.9 µm in patients, P=0.040) and in the superotemporal quadrant (142.6±20.9 µm in healthy eyes vs 132.77±18.6 µm in PD patients, P=0.046). Significant differences were observed between controls and patients in relation to mean macular thickness (P=0.031), foveal thickness (P=0.030), and inferior outer thickness (P=0.019). CONCLUSION: PD is associated with RNFL loss and retinal thinning, which is detectable by Fourier-domain OCT measurements.

The inverse agonist effect of rimonabant on G protein activation is not mediated by the cannabinoid CB1 receptor: evidence from postmortem human brain.

Rimonabant (SR141716) was the first potent and selective cannabinoid CB1 receptor antagonist synthesized. Several data support that rimonabant behaves as an inverse agonist. Moreover, there is evidence suggesting that this inverse agonism may be CB1 receptor-independent. The aim of the present study was to elucidate whether the effect of rimonabant over G protein activation in postmortem human brain is CB1 dependent or independent. [(35)S]GTPγS binding assays and antibody-capture [(35)S]GTPγS scintillation proximity assays (SPA) were performed in human and mice brain. [(3)H]SR141716 binding characteristics were also studied. Rimonabant concentration-dependently decreased basal [(35)S]GTPγS binding to human cortical membranes. This effect did not change in the presence of either the CB1 receptor agonist WIN 55,212-2, the CB1 receptor neutral antagonist O-2050, or the CB1 allosteric modulator Org 27569. [(35)S]GTPγS binding assays performed in CB1 knockout mice brains revealed that rimonabant inhibited the [(35)S]GTPγS binding in the same manner as it did in wild-type mice. The SPA combined with the use of specific antibody-capture of G(α) specific subunits showed that rimonabant produces its inverse agonist effect through G(i3), G(o) and G(z) subtypes. This effect was not inhibited by the CB1 receptor antagonist O-2050. Finally, [(3)H]SR141716 binding assays in human cortical membranes demonstrated that rimonabant recognizes an additional binding site other than the CB1 receptor orthosteric binding site recognized by O-2050. This study provides new data demonstrating that at least the inverse agonist effect observed with >1µM concentrations of rimonabant in [(35)S]GTPγS binding assays is not mediated by the CB1 receptor in human brain.

[Quality as management tool. Actions to improve efficiency in neurological care]. / La calidad como herramienta de gestión. Actuaciones para mejorar la eficiencia en la atención neurológica.

INTRODUCTION: Quality of care involves meeting the needs and expectations of patients with the lowest consumption of resources and in accordance with scientific knowledge. In this context it is important to know if the changes in medical care procedures based on scientific and technical aspects of the quality positively impacts both efficiency measures and perceived quality. METHODS: Prospective study carried out during the 2000-2006 period at the neurology department of a public hospital with has 1303 beds. Changes in medical care introduced: adequacy of a high resolution hospitalization zone, setting up of three care pathways (transient ischemic attach [TIA], multiple sclerosis exacerbation and first epileptic seizure) and practice guidelines for stroke, and implementation of neurological care at the emergency department. RESULTS: There has been an increase in the number of patients treated in the emergency department of the hospital (17%), although the number of admissions has stabilized. In the neurology department, the number of admissions has decreased by 20%, especially those arising from TIA (decrease by 47%), the average stay has been reduced by 30% (especially in demyelinating and vascular disease, which has fallen by 50%). Adjusted average length of stay has remained below 1 and the complexity index above 1. Satisfaction with the information and health care has undergone little change. CONCLUSIONS: The changes in clinical practice to improve the quality of care have been associated with improvements in the efficiency indicators but not in patient satisfaction. The improvement in the perceived quality probably requires specific actions.

La calidad como herramienta de gestión. Actuaciones para mejorar la eficienciaen la atención neurológica / Quality as management tool. Actions to improve efficiency in neurological care

Introducción. La calidad asistencial supone satisfacer las necesidadesy expectativas de los pacientes con el menor consumo de recursosy de acuerdo al conocimiento científico. En este contexto esimportante conocer si los cambios en los procesos asistenciales basadosen aspectos científico-técnicos de la calidad repercuten positivamentetanto en medidas de eficiencia como de calidad percibida.Métodos. Estudio prospectivo durante el período 2000-2006realizado en el servicio de neurología de un hospital de tercer nivelde la red del Sistema Nacional de Salud que dispone de 1.303 camas.Cambios asistenciales introducidos: adecuación de una zona de hospitalizaciónde alta resolución, implantación de tres vías clínicas(accidente isquémico transitorio [AIT], exacerbación de esclerosismúltiple y primera crisis epiléptica) y del proceso de atención al pacientecon ictus y mejora de la atención neurológica en el servicio deurgencias.Resultados. En el hospital se ha producido un incremento en elnúmero de urgencias atendidas (17%), estabilizándose el número deingresos. En neurología ha disminuido el número de ingresos en un20%, especialmente los debidos a AIT (disminución del 47 %), la estanciamedia se ha reducido en un 30% (especialmente en patologíavascular y desmielinizante, donde ha disminuido un 50 %), elíndice de estancia media ajustada al funcionamiento se ha mantenidopor debajo de 1 y el índice de complejidad por encima de 1. La satisfaccióncon la información y atención médica han experimentadopocos cambios.Conclusiones. Los cambios de práctica clínica para mejorar lacalidad asistencial se han asociado con mejoras en los indicadores deeficiencia, pero no en los de satisfacción del paciente. La mejora decalidad percibida probablemente requiera actuaciones específicas (AU)

Introduction. Quality of care involves meeting the needsand expectations of patients with the lowest consumption of resourcesand in accordance with scientific knowledge. In this contextit is important to know if the changes in medical care proceduresbased on scientific and technical aspects of the qualitypositively impacts both efficiency measures and perceived quality.Methods. Prospective study carried out during the 2000-2006period at the neurology department of a public hospital with has1303 beds. Changes in medical care introduced: adequacy of ahigh resolution hospitalization zone, setting up of three carepathways (transient ischemic attach [TIA], multiple sclerosis exacerbationand first epileptic seizure) and practice guidelines forstroke, and implementation of neurological care at the emergencydepartment.Results. There has been an increase in the number of patientstreated in the emergency department of the hospital (17%),although the number of admissions has stabilized. In the neurologydepartment, the number of admissions has decreased by20%, especially those arising from TIA (decrease by 47 %), theaverage stay has been reduced by 30% (especially in demyelinatingand vascular disease, which has fallen by 50%). Adjustedaverage length of stay has remained below 1 and the complexityindex above 1. Satisfaction with the information and health carehas undergone little change.Conclusions. The changes in clinical practice to improvethe quality of care have been associated with improvements in theefficiency indicators but not in patient satisfaction. The improvementin the perceived quality probably requires specific actions (AU)

Seudobalismo secundario a traumatismo medular / Pseudoballism secondary to spinal trauma

Introducción. El balismo es un trastorno del movimientopoco frecuente caracterizado por movimientos de lanzamientode las extremidades, violentos y de gran amplitud,principalmente debido a lesiones en el núcleo subtalámicocontralateral o en sus conexiones aferentes o eferentes.Caso clínico. Presentamos el caso de un hombre de 50 añosque tras un traumatismo medular presentó movimientosbalísticos y posteriormente movimientos coreoatetósicos yactitud distónica en la extremidad superior izquierda. En laexploración destacaban signos de mielopatía con nivel sensitivoC2-C3 y abolición de la sensibilidad propioceptiva endicha extremidad. La resonancia magnética cervical demostróuna lesión medular a nivel C1 en forma de línea transversa,afectando a la mayor parte de su sección.Conclusiones. Este caso destaca por el amplio espectrode movimientos anormales secundarios a la lesión de la víapropioceptiva por afectación medular: movimientos balísticos,coreoatetósicos y distónicos. La aparición de movimientoscoreoatetósicos asociados a lesiones en la vía propioceptivaha recibido la denominación de seudocoreoatetosis. Se proponeel término seudobalismo para definir los movimientosque presentó el paciente en la fase aguda (AU)

Introduction. Ballism is a rare movement disorderthat presents with violent and wide amplitude flingingmovements of the limbs, mainly caused by injury in thecontralateral subthalamic nucleus or its afferent or efferentconnections Clinical case. We describe the case of a 50-year oldmale who had ballistic movements after a cervical trauma.He subsequently developed choreoathetoid movementsand a distonic attitude in the left upper limb. AC2-C3 sensory level and proprioceptive loss in this limbwere the main findings in the examination. The cervicalmagnetic resonance showed a transverse linear spinal lesionat C1 level that affected most of its section.Conclusions. This case stands outs because of thewide abnormal movements spectrum secondary to spinalproprioceptive pathway injury: ballistic, choreoathetoid,and distonic movements. Choreoathetoid movements occurringin association with loss of propioception havebeen called pseudochoreoathetosis. We propose the termpseudoballism to define the movements that were observedduring the acute phase in this patient (AU)

Gene expression patterns in brain cortex of three different animal models of depression.

Animal models represent a very useful tool for the study of depressive-like behavior and for the evaluation of the therapeutic efficacy of antidepressants. Nevertheless, gene expression patterns of these different animal models and whether genes classically associated with human major depression are present in these genetic profiles remain unknown. Gene expression was evaluated in three animal models of depression: acute treatment with reserpine, olfactory bulbectomy and chronic treatment with corticosterone. Gene expression analysis was carried out using the Affymetrix GeneChip technology. The results were evaluated using the GeneChip Operating software (Gcos 1.3) and analyzed with the GeneSpring GX v7.3 bioinformatics software (Agilent) and dChip 2005 software. Expression changes were validated with quantitative real-time polymerase chain reaction (RT-PCR) assays. Many transcripts were differentially expressed in the cortex of depressed-like animals in each model. Gene ontology analysis showed that significant gene changes were clustered primarily into functional neurochemical pathways associated with apoptosis and neuronal differentiation. When expression profiles were compared among the three models, the number of transcripts differentially expressed decreased and only two transcripts (complement component 3 and fatty acid-binding protein 7) were differentially expressed in common. Both genes were validated with RT-PCR. Moreover, five (Htr2a, Ntrk3, Crhr1, Ntrk2 and Crh) of the genes classically related to human major depression were differentially expressed in at least one of these models. The different animal models of depression share relevant characteristics although gene expression patterns are different among them. Moreover, some of the classical genes related to human major depression are differentially expressed in these models.

[Pseudoballism secondary to spinal trauma]. / Seudobalismo secundario a traumatismo medular.

INTRODUCTION: Ballism is a rare movement disorder that presents with violent and wide amplitude flinging movements of the limbs, mainly caused by injury in the contralateral subthalamic nucleus or its afferent or efferent connections. CLINICAL CASE: We describe the case of a 50-year old male who had ballistic movements after a cervical trauma. He subsequently developed choreoathetoid movements and a distonic attitude in the left upper limb later. A C2-C3 sensory level and proprioceptive loss in this limb were the main findings in the examination. The cervical magnetic resonance showed a transverse linear spinal lesion at C1 level that affected most of its section. CONCLUSIONS: This case stands outs because of the wide abnormal movements spectrum secondary to spinal proprioceptive pathway injury: ballistic, choreoathetoid, and distonic movements. Choreoathetoid movements occurring in association with loss of propioception have been called pseudochoreoathetosis. We propose the term pseudoballism to define the movements that were observed during the acute phase in this patient.

Pharmacological characterization and autoradiographic distribution of alpha2-adrenoceptor antagonist [3H]RX 821002 binding sites in the chicken brain.

Knowledge about the noradrenergic system in birds is very scarce even though their biological diversity and complex social behavior make them an excellent model for studying neuronal functions and developmental biology. While the role of norepinephrine has been described in depth in a large number of central and peripheral functions in mammals, reports for avian species are limited. The radioligand [(3)H]RX 821002 ([(3)H]1,4-[6,7(n)3H]-benzodioxan-2-methoxy-2-yl)-2-imidazol) has been used to map and characterize alpha(2)-adrenoceptors through the chicken brain using in vitro autoradiography and membrane homogenates binding assays. [(3)H]RX 821002 showed a saturable and high affinity binding to a site compatible with alpha(2)-adrenoceptor, and to a serotonergic component. The autoradiographic assays displayed a similar alpha(2)-adrenoceptor distribution than those previously reported in birds using other radioligands such as [(3)H]UK 14304 ([(3)H]5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine) or [(3)H]clonidine. [(3)H]RX 821002 binding pharmacological characterization was carried out in different chicken brain regions using membrane homogenates for competition assays with different alpha(2)-adrenoceptor agonists and antagonists drugs (oxymetazoline, BRL 44408 [2-(2H-(1-methyl-1,3-dihydroisoindole)methyl)-4,5-dihydroimidazole] ARC 239 [2-(2-4-(O-methoxyphenyl)-piperazin-1-yl)-ethyl-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione], prazosin, UK 14304 and RX 821002). The results showed alpha(2A) as the predominant alpha(2)-adrenoceptor subtype in the chicken brain while alpha(2B)- and/or alpha(2C)-adrenoceptor subtypes were detected only in the telencephalon. RX 821002, serotonin (5-HT) and 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] competition assays, and competition binding assays performed in the presence of serotonin demonstrated that [(3)H]RX 821002 binds with higher affinity to a serotonergic component, probably 5-HT(1A) receptors, than to the alpha(2)-adrenoceptors. Similar pharmacological properties for the alpha(2)-adrenoceptor component were observed both in rat and chicken brain. The results demonstrate that the different alpha(2)-adrenoceptor subtypes are present in chicken brain and suggest that these receptors are highly conserved through evolution.

Cannabinoid system in the budgerigar brain.

Cannabinoid receptor density and cannabinoid receptor-mediated G protein stimulation were studied by autoradiographic techniques throughout the budgerigar (Melopsittacus undulatus) brain. The maximal CB(1) receptor density value (using [(3)H]CP55,940 as radioligand) was found in the molecular layer of the cerebellum (Mol), and high binding values were observed in the nucleus taeniae amygdalae (TnA), nucleus preopticus medialis, and nucleus pretectalis. The highest net-stimulated [(35)S]GTPgammaS binding values induced by the selective CB(1) receptor agonist WIN55,212-2 were observed in the nucleus paramedianus internus thalami, and high values of [(35)S]GTPgammaS binding were observed in the TnA, Mol, arcopallium dorsale and arcopallium intermedium. The distribution data suggest that in the budgerigar, as previously indicated in mammals, cannabinoid receptors may be related to the control of several brain functions in the motor system, memory, visual system, and reproductive behavior. The discrepancies between the cannabinoid receptor densities and the cannabinoid receptor-mediated stimulation found in several budgerigar brain nuclei support the hypothesis, previously described for mammals, of the existence of different G(i/o) protein populations able to associate with the cannabinoid receptors, depending on the brain structure, and could reflect the relative importance that cannabinoid transmission could exerts in each cerebral area.

Importancia y factores relacionados con la fatiga crónica en la esclerosis múltiple / Importance and factors related to chronic fatigue in multiple sclerosis

Introducción. La importancia de la fatiga en la esclerosis múltiple (EM) viene determinada por la elevada frecuencia con la que aparece y por ser una causa importante de incapacidad. Objetivo. Conocer los factores relacionados con la presencia de fatiga crónica en una serie hospitalaria de pacientes con EM. Pacientes y métodos. Se incluyeron pacientes con EM atendidos de forma consecutiva en la unidad de enfermedades desmielinizantes de un hospital terciario que cumplían los siguientes criterios: EM clínicamente definida (RR o SP), duración de la EM superior a 2 años y ausencia de recaídas en el último mes. Se analizaron las siguientes variables: fatiga crónica, datos demográficos generales, sistemas funcionales, EDSS, ISS, ESS, actividad de la enfermedad, escala de depresión de Hamilton, GHQ-28, índice de calidad de sueño de Pittsburg y tratamiento con interferón. Se llevó a cabo estudio estadístico utilizando análisis bivariante y multivariante mediante regresión logística. Resultados. La serie comprende 100 pacientes (72 mujeres y 28 varones). La edad media fue 39,27 años. Un 88 % de los casos tenían una EM RR y un 12 % EM SP. El tiempo medio de evolución fue 11,2 años. El EDSS medio fue de 2,54. Un 53 % de los casos presentó fatiga crónica. Las únicas variables que se asociaron de forma estadísticamente significativa con la presencia de fatiga crónica fueron la depresión y la disfunción del sueño diurna, de forma que la presencia de depresión multiplica por 3,6 la probabilidad de fatiga crónica y cada punto de más en el PSQI-7 la multiplica por 3,5. Conclusión. La depresión y la disfunción del sueño diurna son las únicas variables que se relacionan de forma independiente con la fatiga crónica entre los pacientes con EM

Introduction. The importance of fatigue in multiple sclerosis (MS) is determined by its high frequency and it is an important cause of disability. Objective. To determine factors that are related to the presence of chronic fatigue in patients with MS. Patients and methods. The series comprises patients with MS, consecutively attended in the demyelinizating diseases unit, who met the following criteria: clinically definite MS (RR or SP), MS duration of more than two years, and no relapses during the previous month. Analyzed variables were as follows: chronic fatigue, demographic data, functional systems, EDSS, ISS, ESS, disease activity, Hamilton, depression scale GHQ-28, PSQI, and interferon. Statistical study: bivariate and multivariate analysis by logistic regression. Results. A hundred patients were inclued, 72 female and 28 male. Mean age was 39.27 years. Of the 100 patients 88 had RR disease and 12 SP disease. MS mean duration was 11.2 years. Mean EDSS 2.54. Chronic fatigue was 53 %. The presence of depression increased the probability of chronic fatigue 3.6 fold, and every point in PSQI-7 increases it 3.5 fold. Conclusion. Depression and the PSQI-7 subscale (day sleep dysfunction) are the only variables independently related to chronic fatigue in patients with MS

[Importance and factors related to chronic fatigue in multiple sclerosis]. / Importancia y factores relacionados con la fatiga crónica en la esclerosis múltiple.

INTRODUCTION: The importance of fatigue in multiple sclerosis (MS) is determined by its high frequency and it is an important cause of disability. OBJECTIVE: To determine factors that are related to the presence of chronic fatigue in patients with MS. PATIENTS AND METHODS: The series comprises patients with MS, consecutively attended in the demyelinizating diseases unit, who met the following criteria: clinically definite MS (RR or SP), MS duration of more than two years, and no relapses during the previous month. Analyzed variables were as follows: chronic fatigue, demographic data, functional systems, EDSS, ISS, ESS, disease activity, Hamilton, depression scale GHQ-28, PSQI, and interferon. Statistical study: bivariate and multivariate analysis by logistic regression. RESULTS: A hundred patients were included, 72 female and 28 male. Mean age was 39.27 years. Of the 100 patients 88 had RR disease and 12 SP disease. MS mean duration was 11.2 years. Mean EDSS 2.54. Chronic fatigue was 53 %. The presence of depression increased the probability of chronic fatigue 3.6 fold, and every point in PSQI-7 increases it 3.5 fold. CONCLUSION: Depression and the PSQI-7 subscale (day sleep dysfunction) are the only variables independently related to chronic fatigue in patients with MS.

[Sleep disorders in multiple sclerosis]. / Trastornos del sueño en la esclerosis múltiple.

INTRODUCTION: To determine the frequency of sleep disorders in multiple sclerosis (MS) patients and their relation with other manifestations of the disease. METHODS: Selected patients had clinically definite MS (relapsing-remitting and secondary progressive forms) and duration of the disease over two years. They were serially evaluated at the unit of demyelinating diseases of a third level hospital. The following scales were applied: the Pittsburgh Sleep Quality Index, the Hamilton Depression Rating Scale, EDSS, ISS and ESS. Statistical analysis by means of non parametric test and logistic regression was carried out. RESULTS: One hundred patients were included (72% women and 28% males). Mean age was 39 years. Eighty eight were relapsing-remitting forms and the rest secondary progressive forms. Mean EDSS was: 2.5. Mean duration of evolution: 11.2 years. The prevalence of sleep disorders was 36%. Age, sex, evolutionary form, degree of disability and chronic fatigue did not relate with the sleep disorders in these patients. In the multivariant analysis by means of logistic regression, we found that every point more in Hamilton's scale multiplies the probability of presenting sleep disorders by 1.2. CONCLUSIONS: Depression is the only variable that independently relates, with the presence of sleep disorders in MS patients.

[Modifications of the lipid metabolism induced by interferon beta in multiple sclerosis patients and its relationship with the disease activity]. / Modificaciones del metabolismo lipídico inducidas por interferón beta en los pacientes con esclerosis múltiple y su relación con la actividad de la enfermedad.

INTRODUCTION: It has been recently suggested that total cholesterol and low density lipoproteins (LDL) levels can behave as biological markers of activity in demyelinating diseases. Thus, our aim has been to describe the modifications of the plasma levels of total cholesterol and triglyceride due to treatment with interferon-beta in multiple sclerosis (MS) patients and to determine their relationship with the disease activity. PATIENTS AND METHODS: Study of the follow-up of MS patients under treatment with interferon-beta. Clinical and analytical controls were performed before initiating treatment and than at 1, 3, 6, 12, 18 and 24 months of its initiation. RESULTS: Fifty six patients have been studied, 41 of them women. Mean age was 37.4 years. Fifty were relapsing- remitting forms and the rest secondary progressive forms. The mean plasma levels of triglyceride increased and total cholesterol levels diminished during the 24 months of treatment with interferon, mainly in the first 3 months. No statistically significant relationship was found between disease activity and mean plasma levels of triglyceride and total cholesterol before the beginning of the treatment and during the period of follow-up. CONCLUSIONS: Treatment with interferon-beta in the MS patients originates changes in the plasma lipid profile, but neither these changes nor the plasma lipid levels before the treatment behave as biological markers of disease activity.

[Predicting factors for depression in multiple sclerosis]. / Factores predictores de depresión en la esclerosis múltiple.

INTRODUCTION: We assess frequency and intensity of depression in multiple sclerosis (MS) patients, the degree at which it is detected and its relationship to the treatment with beta interferon and other clinical and paraclinical factors. METHODS: The series comprises MS patients, seen in the Demyelinating Disease Unit of a tertiary hospital, who fulfilled the following criteria: clinically defined MS (relapsing-remitting or secondary progressive), disease duration greater than two years and absence of relapses during the month prior to the study. The variables analyzed were detection and assessment of depression with the Hamilton Depression Scale, general demographic data, functional systems, EDSS, ISS, ESS, Pittsburgh Sleep Quality Index, interferon treatment, chronic fatigue and a series of analytical variables. Statistical study: both variate and multivariate analysis by logistic regression. RESULTS: 100 patients (72 female and 28 male). Mean age: 39.27 years. RR MS form, 88%, and SPMS form, 12 %. Mean evolution time, 11.2 years. Mean EDSS, 2.54. Depression was present in 44 % of the patients in our group and was not related to neurological degree of disability, disease evolution time, clinical form, interferon treatment, or to sleep disorders. However, depression was related to the presence of both chronic fatigue and ESS scores. CONCLUSIONS: Depression is common in MS patients and is associated with the presence of chronic fatigue and a worse social status.