The determination of copeptin levels helps management decisions among transient ischaemic attack patients.

BACKGROUND: Most approaches to transient ischaemic attack (TIA) triage use clinical scores and vascular imaging; however, some biomarkers have been suggested to improve the prognosis of TIA patients. METHODS: Serum levels of copeptin, adiponectin, neopterin, neuron-specific enolase, high-sensitivity C-reactive protein, IL-6, N-terminal pro-B-type natriuretic peptide, S100ß, tumour necrosis factor-alpha and IL-1α as well as clinical characteristics were assessed on consecutive TIA patients during the first 24 h of the onset of symptoms. RESULTS: Among 237 consecutive TIA patients, 12 patients (5%) had a stroke within 7 days and 15 (6%) within 90 days. Among all candidate biomarkers analysed, only copeptin was significantly increased in patients with stroke recurrence (SR) within 7 days (P = 0.026) but not within 90 days. A cut-off point of 13.8 pmol/l was established with a great predictive negative value (97.4%). Large artery atherosclerosis (LAA) [hazard ratio (HR) 12.7, 95% CI 3.2-50.1, P < 0.001] and copeptin levels ≥13.8 pmol/l (HR 3.9, 95% CI 1.01-14.4, P = 0.039) were independent predictors of SR at the 7-day follow-up. LAA was the only predictor of 90-day SR (HR 7.4, 95% CI 2.5-21.6, P < 0.001). ABCD3I was associated with 7- and 90-day SRs (P = 0.025 and P = 0.034, respectively). The association between copeptin levels and LAA had a diagnostic accuracy of 90.3%. CONCLUSIONS: Serum copeptin could be an important prognostic biomarker to guide management decisions among TIA patients. Therefore, TIA patients with copeptin levels below 13.8 pmol/l and without LAA have an insignificant risk of 7-day SR and could be managed on an outpatient basis.

N-terminal pro-brain natriuretic peptide level determined at different times identifies transient ischaemic attack patients with atrial fibrillation.

BACKGROUND AND PURPOSE: The etiological classification of patients with transient ischaemic attack (TIA) is a difficult endeavor and the use of serum biomarkers could improve the diagnostic accuracy. The aim of this study was to correlate atrial fibrillation, the main cardioembolic etiology (CE), with different serum biomarkers measured in consecutive TIA patients. METHODS: The concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha, neuron-specific enolase, high-sensitivity C-reactive protein, IL-1-α and the N-terminal pro-B type natriuretic peptide (NT-proBNP) were quantified in the serum of 140 patients with TIA and 44 non-stroke subjects. Measurements were performed at different times throughout evolution: within 24 h of symptoms onset and at days 7 and 90. RESULTS: With the exception of IL-6, all biomarkers were higher in TIA patients than in controls. NT-proBNP was significantly related to the presence or new diagnosis of AF at all time points analyzed. Furthermore, the baseline NT-proBNP level was significantly higher than values at the 7-day and 90-day follow-up. For this reason, different cut-off values were obtained at different times: 313 pg/ml at baseline [odds ratio (OR) = 18.99, P < 0.001], 181 pg/ml at 7 days (OR = 11.4, P = 0.001) and 174 pg/ml (OR = 8.46, P < 0.001) at 90 days. CONCLUSION: High levels of NT-proBNP determined during the first 3 months after a TIA were associated with AF. Consequently, this biomarker may be useful to reclassify undetermined TIA patients as having disease of CE.

[Event-related potentials and the diagnosis of short-term verbal memory disorders in cerebrovascular disease]. / Potenciales relacionados con eventos y diagnóstico de las alteraciones de memoria verbal a corto plazo en la enfermedad cerebrovascular.

INTRODUCTION: Cerebrovascular disease can cause different memory disorders depending on the area of the brain involved. More specifically, ischemic lesions in the frontal region can be associated to short-term verbal memory disorders. PATIENTS AND METHODS: Two groups of subjects were studied, 10 of whom were patients who presented a frontal cerebral infarction and 10 healthy controls. They were administered a memory task involving word recognition. While they were performing the task the electrical activity of their brains was recorded in order to examine event-related potentials (ERP). RESULTS: The patients' performance of the task was poorer than that of the healthy control subjects. Likewise, while the latter displayed a predominantly frontal distribution of ERPs, in the patients the frontal activity diminished and was seen to be chiefly temporoparietooccipital. CONCLUSIONS: These findings allow important conclusions to be drawn about the characteristics of the memory disorder presented by these patients.

Potenciales relacionados con eventos y diagnóstico de las alteraciones de memoria verbal a corto plazo en la enfermedad cerebrovascular / Event-related potentials and the diagnosis of short-term verbal memory disorders in cerebrovascular disease

Cerebrovascular disease can cause different memory disorders depending on the area of the brain involved. More specifically, ischemic lesions in the frontal region can be associated to short-term verbal memory disorders. Two groups of subjects were studied, 10 of whom were patients who presented a frontal cerebral infarction and 10 healthy controls. They were administered a memory task involving word recognition. While they were performing the task the electrical activity of their brains was recorded in order to examine event-related potentials (ERP). The patients' performance of the task was poorer than that of the healthy control subjects. Likewise, while the latter displayed a predominantly frontal distribution of ERPs, in the patients the frontal activity diminished and was seen to be chiefly temporoparietooccipital. These findings allow important conclusions to be drawn about the characteristics of the memory disorder presented by these patients(AU)

Potenciales relacionados con eventos y diagnóstico de las alteraciones de la memoria verbal a corto plazo en la enfermedad cerebrovascular / Event-related potentials and the diagnosis of short-term verbal memory disorders in cerebrovascular disease

Introducción. La enfermedad cerebrovascular puede causar alteraciones de la memoria diferentes en función del área cerebral afectada. Las lesiones isquémicas en la región frontal pueden asociarse a alteraciones de la memoria verbal a corto plazo, específicamente. Pacientes y métodos. Se estudiaron dos grupos de sujetos, 10 de ellos pacientes que presentaban un infarto cerebral frontal, y 10 controles sanos. Se les aplicó una tarea de memoria de reconocimiento de palabras. Durante su realización se recogió la actividad eléctrica cerebral para el registro de los potenciales relacionados con eventos (PRE). Resultados. Los pacientes tuvieron una ejecución deficitaria en la tarea en comparación con los controles sanos. Igualmente, mientras éstos mostraban una distribución predominantemente frontal de los PRE, en los pacientes la activación frontal disminuía y era de preferencia temporoparietoccipital. Conclusiones. Estos resultados permiten extraer importantes conclusiones sobre las características de la alteración de la memoria presentada por los pacientes (AU)

Introduction. Cerebrovascular disease can cause different memory disorders depending on the area of the brain involved. More specifically, ischemic lesions in the frontal region can be associated to short-term verbal memory disorders. Patients and methods. Two groups of subjects were studied, 10 of whom were patients who presented a frontal cerebral infarction and 10 healthy controls. They were administered a memory task involving word recognition. While they were performing the task the electrical activity of their brains was recorded in order to examine event-related potentials (ERP). Results. The patients’ performance of the task was poorer than that of the healthy control subjects. Likewise, while the latter displayed a predominantly frontal distribution of ERPs, in the patients the frontal activity diminished and was seen to be chiefly temporoparietooccipital. Conclusions. These findings allow important conclusions to be drawn about the characteristics of the memory disorder presented by these patients (AU)

[Some considerations about the possible pathological mechanisms at work in antiphospholipid syndrome and stroke]. / Algunas consideraciones acerca de los posibles mecanismos patológicos en el síndrome antifosfolípidos e ictus.

INTRODUCTION AND DEVELOPMENT: Over the last two decades antiphospholipid syndrome (APS) has started to be recognized from the association of apparently anionic phospholipid-specific antibodies with thrombosis, thrombocytopenia and recurrent foetal losses. This syndrome affects patients with systemic lupus erythematosus and is considered to be an important cause of thromboembolic disease. Antiphospholipid antibodies are serum immunoglobulins that react with negatively charged phospholipids, albeit directly or by means of a cofactor, affect the coagulation system, and promote thrombosis. Recent research has been directed towards gaining an understanding of the mechanisms by which these antibodies are able to play a direct role in the pathophysiology of thrombosis, and the extent to which certain risk factors, such as smoking, high blood pressure, lipid disorders and so on, exert an influence over the expression of phospholipids in the cerebral endothelium. CONCLUSION: These antibodies have no single mechanism of action; different authors have described different pathological mechanisms, which help us to understand the heterogeneous clinical manifestations of APS.

Algunas consideraciones acerca de los posibles mecanismos patológicos en el síndrome antifosfolípidos e ictus / Some considerations about the possible pathological mechanisms at work in antiphospholipid syndrome and stroke

Introducción y desarrollo. En las dos últimas décadas ha comenzado a reconocerse el síndrome antifosfolípidos (SAP) por la asociación de anticuerpos con una aparente especificidad por fosfolípidos aniónicos con trombosis, trombocitopenia y pérdidas fetales recurrentes. Este síndrome afecta a pacientes con lupus eritematoso sistémico y se considera una causa importante de enfermedad tromboembólica. Los anticuerpos antifosfolípidos son inmunoglobulinas del suero que reaccionan con fosfolípidos cargados negativamente, ya sea directamente o a través de un cofactor, afectan el sistema de la coagulación y promueven la trombosis. Algunas investigaciones recientes se han encaminado a comprender los mecanismos por los que estos anticuerpos pueden desempeñar un papel directo en la fisiopatología de la trombosis, y cómo pueden influir determinados factores de riesgo como el tabaquismo, la hipertensión arterial, la hiperlipidemia, etc., sobre la expresión de los fosfolípidos en el endotelio cerebral. Conclusión. No existe un mecanismo único de acción de estos anticuerpos; diversos autores han descrito diferentes mecanismos patológicos, los cuales ayudan a comprender las heterogéneas manifestaciones clínicas del SAP (AU)

Introduction and development. Over the last two decades antiphospholipid syndrome (APS) has started to be recognized from the association of apparently anionic phospholipid-specific antibodies with thrombosis, thrombocytopenia and recurrent foetal losses. This syndrome affects patients with systemic lupus erythematosus and is considered to be an important cause of thromboembolic disease. Antiphospholipid antibodies are serum immunoglobulins that react with negatively charged phospholipids, albeit directly or by means of a cofactor, affect the coagulation system, and promote thrombosis. Recent research has been directed towards gaining an understanding of the mechanisms by which these antibodies are able to play a direct role in the pathophysiology of thrombosis, and the extent to which certain risk factors, such as smoking, high blood pressure, lipid disorders and so on, exert an influence over the expression of phospholipids in the cerebral endothelium. Conclusion. These antibodies have no single mechanism of action; different authors have described different pathological mechanisms, which help us to understand the heterogeneous clinical manifestations of APS (AU)

[Activation of T cells in experimental autoimmune encephalomyelitis and multiple sclerosis]. / Activación de la célula T en la encefalomielitis autoinmune experimental y esclerosis múltiple.

AIMS: In this study we describe the main findings from research into the autoreactive process triggered by activated T lymphocytes, which are generated in the peripheral compartment and then migrate towards the central nervous system (CNS) in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) its animal model. METHOD: The different strategies that have been developed to date for the immunological treatment of MS have been designed to intervene in the pathogenic process of the disease by blocking the activation of T cells and B cells with specific antigens, interfering with immunological effector mechanisms and inhibiting the migration of lymphocytes towards the CNS. The cause of the inflammatory response in MS has still not been defined, but the findings from EAE studies and in patients with MS suggest that the disease has an autoimmune aetiology involving autoreactive T cells which are specific for antigens in the myelin membrane. To activate these cells at least two cues are needed during antigen recognition and later the T CD4+ lymphocytes are differentiated in two subpopulations, Th1 and Th2, which differ in the pattern of secretion of cytosines depending on the stage of the disease process. The progressions of EAE and MS give rise to changes in the primary and secondary self reactive responses of the T cells during the progression of the disease. CONCLUSION: The pathological immune mechanisms mediated by activated myelin specific T lymphocytes play a key role in the progression and recuperation, as well as the mediation, of tissue damage during the course of MS and EAE.

Activación de la célula T en la encefalomielitis autoinmune experimental y esclerosis múltiple / Activation of T cells in experimental autoimmune encephalomyelitis and multiple sclerosis

Objetivo. En el presente trabajo se describen los principales hallazgos encontrados en las investigaciones acerca del proceso autorreactivo iniciado por linfocitos T activados, que se generan en el compartimento periférico y posteriormente migran hacia el sistema nervioso central (SNC) en la esclerosis múltiple (EM) y la encefalomielitis autoinmune experimental (EAE), su modelo animal. Desarrollo. Las diversas estrategias desarrolladas hasta la fecha para el tratamiento inmunológico de la EM se han diseñado para intervenir en el proceso patogénico de la enfermedad mediante el bloqueo de la activación de células T y células B por antígenos específicos, la interferencia con mecanismos efectores inmunológicos y la inhibición de la migración linfocítica hacia el SNC. La causa de la respuesta inflamatoria en la EM todavía no se ha podido definir, pero los hallazgos encontrados en EAE y en pacientes con EM han sugerido que la enfermedad presenta una etiología autoinmune mediada por células T autorreactivas específicas para antígenos de la membrana mielínica. Para la activación de dichas células se requieren al menos dos señales durante el reconocimiento antigénico y, posteriormente, los linfocitos T CD4+ se diferencian en dos subpoblaciones, Th1 o Th2, que difieren en el patrón de secreción de citocinas que dependen del estadio de la enfermedad. La progresión de la EAE y EM involucra cambios en las respuestas autorreactivas primaria y secundaria de las células T durante la progresión de la enfermedad. Conclusión. Los mecanismos patológicos inmunes mediados por linfocitos T activados específicos de la mielina desempeñan un papel importante en la progresión y recuperación, así como en la mediación del daño tisular durante la EM y la EAE (AU)

Aims. In this study we describe the main findings from research into the autoreactive process triggered by activated T lymphocytes, which are generated in the peripheral compartment and then migrate towards the central nervous system (CNS) in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) –its animal model. Method. The different strategies that have been developed to date for the immunological treatment of MS have been designed to intervene in the pathogenic process of the disease by blocking the activation of T cells and B cells with specific antigens, interfering with immunological effector mechanisms and inhibiting the migration of lymphocytes towards the CNS. The cause of the inflammatory response in MS has still not been defined, but the findings from EAE studies and in patients with MS suggest that the disease has an autoimmune aetiology involving autoreactive T cells which are specific for antigens in the myelin membrane. To activate these cells at least two cues are needed during antigen recognition and later the T CD4+ lymphocytes are differentiated in two subpopulations, Th1 and Th2, which differ in the pattern of secretion of cytosines depending on the stage of the disease process. The progressions of EAE and MS give rise to changes in the primary and secondary self-reactive responses of the T cells during the progression of the disease. Conclusion. The pathological immune mechanisms mediated by activated myelin-specific T lymphocytes play a key role in the progression and recuperation, as well as the mediation, of tissue damage during the course of MS and EAE (AU)

[The importance of antiphospholipid antibodies in strokes]. / Importancia de los anticuerpos antifosfolípidos en el ictus.

INTRODUCTION AND METHOD: The study of antiphospholipid antibodies has aroused a great deal of interest among researchers, as some of them are related to neurological diseases and in particular with cerebral ischemia. Cases of strokes in which the aetiology is unknown have been reported in young patients. Until now anticardiolipin antibodies and lupus anticoagulant have received the most attention in studies, but recently descriptions have been published of anticardiolipin antibodies with other particularities that can act as more specific immunity markers for strokes of undetermined origin in young adults. Recent research has been directed towards gaining an understanding of the mechanisms that allow these antibodies to play a direct role in the physiopathology of thrombosis and how certain risk factors smoking, high blood pressure, lipid disorders can exert an influence on the expression of phospholipids in the cerebral endothelium. Several authors have described different pathological mechanisms that help to understand the heterogeneous clinical manifestations of antiphospholipid syndrome. CONCLUSION: There is a need to study the different possible antigens of the antiphospholipid antibodies, as well as their specificities and pathological mechanisms, in greater depth in order to obtain a phospholipid immunity marker that is useful in the diagnosis of young stroke patients who are positive for these antibodies.

Importancia de los anticuerpos antifosfolípidos en el ictus / The importance of antiphospholipid antibodies in strokes

Introducción y desarrollo. El estudio de los anticuerpos antifosfolípidos ha despertado gran interés, pues algunos de ellos se relacionan con enfermedades neurológicas, fundamentalmente con la isquemia cerebral. Existen descripciones de pacientes jóvenes con ictus de etiología no definida con presencia de estos anticuerpos. Los anticuerpos anticardiolipina y el anticoagulante lúpico han sido hasta ahora los más estudiados, pero han comenzado a describirse anticuerpos antifosfolípidos con otras especificidades que pueden constituir marcadores inmunes más específicos para el ictus de causa no determinada en adultos jóvenes. Las investigaciones recientes se han encaminado a comprender los mecanismos por los cuales estos anticuerpos pueden desempeñar un papel directo en la fisiopatología de la trombosis y cómo determinados factores de riesgo -el tabaquismo, la hipertensión arterial, la hiperlipidemia- pueden influir sobre la expresión de los fosfolípidos en el endotelio cerebral. Diversos autores han descrito diferentes mecanismos patológicos, que ayudan a comprender las heterogéneas manifestaciones clínicas del síndrome antifosfolípido. Conclusión. Es necesario profundizar en el estudio de los diferentes posibles antígenos de los anticuerpos antifosfolípidos, sus especificidades y mecanismos patológicos, con el fin de contar con un marcador inmunitario fosfolipídico útil para el diagnóstico de pacientes jóvenes con ictus con positividad para estos anticuerpos (AU)

Introduction and method. The study of antiphospholipid antibodies has aroused a great deal of interest among researchers, as some of them are related to neurological diseases and in particular with cerebral ischemia. Cases of strokes in which the aetiology is unknown have been reported in young patients. Until now anticardiolipin antibodies and lupus anticoagulant have received the most attention in studies, but recently descriptions have been published of anticardiolipin antibodies with other particularities that can act as more specific immunity markers for strokes of undetermined origin in young adults. Recent research has been directed towards gaining an understanding of the mechanisms that allow these antibodies to play a direct role in the physiopathology of thrombosis and how certain risk factors –smoking, high blood pressure, lipid disorders– can exert an influence on the expression of phospholipids in the cerebral endothelium. Several authors have described different pathological mechanisms that help to understand the heterogeneous clinical manifestations of antiphospholipid syndrome. Conclusion. There is a need to study the different possible antigens of the antiphospholipid antibodies, as well as their specificities and pathological mechanisms, in greater depth in order to obtain a phospholipid immunity marker that is useful in the diagnosis of young stroke patients who are positive for these antibodies (AU)

[Immunological study of cerebrospinal fluid using a human IgM antiserum produced in Cuba. A preliminary evaluation]. / Estudio inmunológico del líquido cefalorraquídeo con el empleo de un antisuero de IgG humano producido en Cuba. Evaluación preliminar.

INTRODUCTION: The immunological study of cerebrospinal fluid (CSF) is an essential diagnostic tool for evaluating patients with neurological diseases. The quantitative determination of the albumen and immunoglobulin G (IgG) in blood serum and in CSF by single radial immunodiffusion (SRID), together with the calculation of the IgG index to evaluate the presence of intrathecal synthesis of IgG and of the albumen quotient in order to evaluate the state of functioning of the blood brain barrier are essential elements to be evaluated for diagnosis and research in neurological clinical practice, as well as in the follow up of certain neurological diseases such as multiple sclerosis. Specific antiserums from commercial firms such as Boehring, SIGMA, etc. are used for the quantitative determination of IgG and albumen both in blood serum and in CSF by SRID. The high cost and the difficulty in acquiring these immunodiagnostic kits have had an important effect on the diagnostic and research opportunities throughout the country. MATERIALS AND METHODS: In this work we present the preliminary findings of the evaluation of the human IgG antiserum obtained from a ram, by Labex laboratories, for the quantitative determination of IgG in CSF by SRID, in order to find out whether this antiserum is efficient in the quantitative determination of IgG in CSF. RESULTS AND CONCLUSIONS: The studies conducted so far show that this antiserum may be a good candidate for use in immunological studies of CSF. Further work needs to be carried out on its validation in order to resolve the problems involved in immunological studies of CSF that we highlighted above. This would be achieved with an antiserum that is cheaper than those used up to now.