[Brain metastasis and the carcinoembryonic antigen]. / Metástasis cerebrales y antígeno carcinoembrionario.

INTRODUCTION: Neurological complications have a notable repercussion on the quality of life of patients with systemic cancer, and can even become the direct cause of death. The complication that causes most concern is undoubtedly brain metastasis, because of its difficult management and because there has been an upward tendency in its incidence in the last few years. AIMS: The aim of this study is to provide a review of the literature about brain metastases and, more particularly, about the carcinoembryonic antigen (CEA) as a marker of these pathologies. DEVELOPMENT: In general it is reckoned that 60% of all brain metastases start from the lung and most of them are multiple when they are diagnosed, which suggests a possibly mistaken staging of these patients. The carcinoembryonic antigen is the prototypical tumour marker, and it is usually found in higher concentrations in the cerebrospinal fluid of patients with metastatic tumours in the central nervous system. As the CEA goes through the blood brain barrier, it behaves in a similar way to IgA due to their having homologous molecular weights. This allows us to employ the same hyperbolic distribution curve that is used as a reference for lgA to distinguish between intrathecally synthesized CEA and that which diffuses from the systemic circulation. CONCLUSIONS: In spite of the progress that has been obtained with the new therapies, brain metastases continue to have a poor prognosis. Hence, there is a need to identify new tumour markers that allow a diagnosis to be established before the clinical methods and presentations.

Metástasis cerebrales y antígeno carcinoembrionario / Brain metastasis and the carcinoembryonic antigen

Introducción. Las complicaciones neurológicas repercuten notablemente en la calidad de vida de los pacientes con cáncer sistémico, y llega a ser incluso la causa directa de muerte. Entre estas complicaciones, la más preocupante es la metástasis cerebral, por su difícil tratamiento y porque su incidencia tiende a aumentar en los últimos años. Objetivos. Aportar una revisión bibliográfica acerca de las metástasis cerebrales y en particular del antígeno carcinoembrionario (CEA) como marcador de estas patologías. Desarrollo. En general, se plantea que el 60 por ciento de las metástasis cerebrales provienen del pulmón, y la mayoría son múltiples en el momento del diagnóstico, lo que nos sugiere una posible estadificación incorrecta de estos pacientes. El antígeno carcinoembrionario constituye el prototipo de marcador tumoral, y sus concentraciones suelen elevarse en el líquido cefalorraquídeo de los pacientes con tumores metastáticos en el sistema nervioso central. El CEA se comporta en su paso por la barrera hematoencefálica de forma similar a la IgA, pues tienen pesos moleculares homólogos, lo que permite que lamisma curva de distribución hiperbólica de referencia que se usa para la IgA pueda emplearse para discernir entre el CEA sintetizado intratecalmente del que se difunde de la circulación sistémica. Conclusiones. A pesar de los progresos que se han obtenido con las nuevas terapias, las metástasis cerebrales continúan teniendo un mal pronóstico, por lo que es necesario identificar nuevos marcadores tumorales que permitan establecer el diagnóstico antes que los métodos establecidos y las manifestaciones clínica (AU)

Introduction. Neurological complications have a notable repercussion on the quality of life of patients with systemic cancer, and can even become the direct cause of death. The complication that causes most concern is undoubtedly brain metastasis, because of its difficult management and because there has been an upward tendency in its incidence in the last few years. Aims. The aim of this study is to provide a review of the literature about brain metastases and, more particularly, about the carcinoembryonic antigen (CEA) as a marker of these pathologies. Development. In general it is reckoned that 60% of all brain metastases start from the lung and most of them are multiple when they are diagnosed, which suggests a possibly mistaken staging of these patients. The carcinoembryonic antigen is the prototypical tumour marker, and it is usually found in higher concentrations in the cerebrospinal fluid of patients with metastatic tumours in the central nervous system. As the CEA goes through the blood-brain barrier, it behaves in a similar way to IgA due to their having homologous molecular weights. This allows us to employ the same hyperbolic distribution curve that is used as a reference for lgA to distinguish between intrathecally synthesized CEA and that which diffuses from the systemic circulation. Conclusions. In spite of the progress that has been obtained with the new therapies, brain metastases continue to have a poor prognosis. Hence, there is a need to identify new tumour markers that allow a diagnosis to be established before the clinical methods and presentations (AU)

[IgG subclasses intrathecal synthesis patterns in eosinophilic meningoencephalitis due to Angiostrongylus cantonensis]. / Patrones de síntesis intratecal de subclases de IgG en meningoencefalitis eosinofílica por Angiostrongylus cantonensis.

INTRODUCTION: There is a growing interest to know the characteristics of meningoencephalitis due to Angiostrongylus cantonensis because of it is an emergent disease. OBJECTIVE: To describe the intrathecal synthesis pattern of IgG subclasses in pediatric patients suffering from eosinophilic meningoencephalitis due to Angiostrongylus cantonensis. PATIENTS AND METHODS: Ten pediatric patients with the disease were studied. During the firs diagnostic lumbar puncture an eosinophilic pleocitosis was found. Simultaneously a serum sample was taken. Eight days later, a second lumbar and venous puncture was performed. To every serum and cerebrospinal fluid sample IgA, IgM, IgG, albumin and the four subclasses of IgG were quantified by immunodiffusion and a differential cell count. RESULTS: During the first diagnostic lumbar puncture, all the cases had blood cerebrospinal fluid barrier dysfunction with absence of immunoglobulins intrathecal synthesis with a mean of 450 106cells/L and 48% of eosinophils average. In the second lumbar punction there was a 40% patients with dysfunction of the blood cerebrospinal fluid barrier and with a synthesis pattern IgA+IgM+IgG in the 50% o patients and with IgA+IgG in four patients. The synthesis pattern of IgG subclasses was IgG1+IgG2 in six patients, IgG1+IgG2+IgG3 in one patient, IgG1+IgG2+IgG4 in one more patient and two patients without intrathecal synthesis. CONCLUSION: The intrathecal synthesis pattern of IgG subclasses can contribute to eosinophilic meningoencephalitis diagnosis due to Angiostrongylus cantonensis.

Patrones de síntesis intratecal de subclases de IgG en meningoencefalitis eosinofílica por Angiostrongylus cantonensis / Igg subclasses intrathecal synthesis patterns in eosinophilic meningoencephalitis due to Angiostrongylus cantonensis

Introducción. Es de interés creciente conocer las características de las meningoencefalitis por Angiostrongylus cantonensis, pues se trata de una enfermedad emergente. Objetivo. Describir el patrón de síntesis de subclases de IgG en pacientes pediátricos con meningoencefalitis eosinofílica por Angiostrongylus cantonensis. Pacientes y métodos. Se estudiaron 10 pacientes pediátricos con la enfermedad. En la punción lumbar diagnóstica se encontró pleocitosis eosinofílica. Se tomó una muestra simultánea de suero. A los ocho días se realizó una segunda punción lumbar y venosa. En cada muestra de suero y líquido cefalorraquídeo (LCR) se cuantificó IgA, IgM, IgG, albúmina y las cuatro subclases de IgG por inmunodifusión. Además, se realizó un conteo celular diferencial. Resultados. En la primera punción lumbar diagnóstica, todos los casos tenían disfunción de la barrera sangre-LCR, con ausencia de síntesis intratecal de inmunoglobulinas, con un promedio 450 × 106 células/L y un 48 por ciento de eosinófilos. En la segunda punción lumbar, el 40 por ciento permanecía con disfunción de barrera sangre-LCR, con patrón de síntesis IgA+IgM+IgG en el 50 por ciento de los casos e IgA+IgG en otros cuatro pacientes. El patrón de síntesis de subclases fue de IgG1+IgG2 en seis pacientes, de IgG1+IgG2+IgG3 en otro paciente y de IgG1+IgG2+IgG4 en otro. Hubo dos pacientes que no sintetizaron ninguna subclase a nivel intratecal. Conclusiones. El patrón de síntesis intratecal de subclases de IgG puede contribuir al diagnóstico de las meningoencefalitis eosinofílicas por Angiostrongylus cantonensis (AU)

Introduction. There is a growing interest to know the characteristics of meningoencephalitis due to Angiostrongylus cantonensis because of it is an emergent disease. Objective. To describe the intrathecal synthesis pattern of IgG subclasses in pediatric patients suffering from eosinophilic meningoencephalitis due to Angiostrongylus cantonensis. Patients and methods. Ten pediatric patients with the disease were studied. During the firs diagnostic lumbar puncture an eosinophilic pleocitosis was found. Simultaneously a serum sample was taken. Eight days later, a second lumbar and venous puncture was performed. To every serum and cerebrospinal fluid sample IgA, IgM, IgG, albumin and the four subclasses of IgG were quantified by immunodiffusion and a differential cell count. Results. During the first diagnostic lumbar puncture, all the cases had blood-cerebrospinal fluid barrier dysfunction with absence of immunoglobulins intrathecal synthesis with a mean of 450 × 106 cells/L and 48% of eosinophils average. In the second lumbar punction there was a 40% patients with dysfunction of the blood-cerebrospinal fluid barrier and with a synthesis pattern IgA+IgM+IgG in the 50% o patients and with IgA+IgG in four patients. The synthesis pattern of IgG subclasses was IgG1+IgG2 in six patients, IgG1+IgG2+IgG3 in one patient, IgG1+IgG2+IgG4 in one more patient and two patients without intrathecal synthesis. Conclusion. The intrathecal synthesis pattern of IgG subclasses can contribute to eosinophilic meningoencephalitis diagnosis due to Angiostrongylus cantonensis (AU)

[Intrathecal synthesis pattern of immunoglobulins in meningoencephalitis epidemic due to echovirus 9]. / Patrones de síntesis intratecal de inmunoglobulinas en epidemia de meningoencefalitis por echovirus 9.

INTRODUCTION: Epidemics of meningoencephalitis due to echovirus 9 were commonly occurred when a children population become susceptible for the first time in front the virus. OBJECTIVE: To present the intrathecal synthesis pattern of immunoglobulins of the epidemic that affected Cuba in 1999 and to probe the usefulness of reibergram and antibody index in the diagnostic and characterization of the outbreak. PATIENTS AND METHODS: 23 pediatric patients suffering from viral meningoencephalitis due to echovirus 9 were studied in the income moment. Serum and cerebrospinal fluid IgA, IgM, IgG, albumin and glucose were quantified. Cerebrospinal fluid total protein content and lactate were quantified. Titles of antibodies against echo 9 and Coxsackie A9 and differential cell count were performed. RESULTS: A mean of 555 cells/10 6 L mainly lymphocytes were obtained. Glucose in cerebrospinal fluid was over 50%, serum glucose and lactate levels below 2.1 mmol/L. In the reibergram an absence of intrathecal synthesis was predominant (15/23), IgM synthesis (6/23) and IgM+IgA (2/23). Blood cerebrospinal fluid dysfunction was observed in 15 patients. The mean antibody index was 1,8 for echo 9 and 0,9 for Coxsackie A9. CONCLUSIONS: The intrathecal synthesis pattern of immunoglobulins was different from other enterovirus and from echovirus 9 in non epidemic situations before this epidemic, probably with alteration of viral genome.

Patrones de síntesis intratecal de inmunoglobulinas en epidemia de meningoencefalitis por echovirus 9 / Intrathecal synthesis pattern of immunoglobulins in meningoencephalitis epidemic due to echovirus 9

Introducción. Las epidemias producidas por echovirus 9 son comunes cuando existe una población infantil susceptible que se enfrenta al virus por primera vez. Objetivo. Presentar el patrón de síntesis intratecal (SI) de inmunoglobulinas de la epidemia que afectó a Cuba en 1999 y comprobar la utilidad del reibergrama y del índice de anticuerpo en el diagnóstico y caracterización del brote. Pacientes y métodos. Se estudiaron 23 pacientes con meningoencefalitis vírica por echovirus 9 en el momento del ingreso. Se cuantificaron IgA, IgM, IgG, albúmina, glucosa en suero y líquido cefalorraquídeo (LCR), y proteínas totales y lactato en LCR. Se realizaron los títulos de anticuerpos antiechovirus 9 y Coxsackie A9 y recuento celular diferencial. Resultados. Se obtuvo un recuento celular medio de 555 células/10-6 L con predominio de linfocitos. Los valores de glucosa en LCR estuvieron por encima del 50 por ciento de la glucosa en suero y lactato menor de 2,1 mmol/L. En el reibergrama predominó la ausencia de síntesis (15/23), IgM (6/23) e IgM+IgA (2/23). Hubo disfunción de la barrera sangre-LCR en 15 pacientes. El índice de anticuerpo específico medio fue de 1,8 para echovirus 9 y 0,9 para Coxsackie A9. Conclusión. El patrón de SI de inmunoglobulinas se diferencia del de otros enterovirus y el propio echovirus 9 en situaciones no epidémicas anteriores con probable alteración del genoma vírico (AU)

[Neuroimmune epidemiological value of reibergram in the first echovirus 16 meningoencephalitis outbreak in Cuba]. / Valor neuroinmunoepidemiologico del reibergrama en la primera epidemia de meningoencefalitis por echovirus 16 en Cuba.

INTRODUCTION: During the third quarter of 2000, an outbreak of echovirus 16 meningoencephalitis was firstly occurred in Cuba and produced vomiting, headache, fever and exanthem that differentiate it from other enterovirus epidemies. OBJECTIVE: To describe the intrathecal immunoglobulin synthesis pattern of the epidemie from the reibergram. PATIENTS AND METHODS: Diagnostic serum and cerebrospinal fluid from 18 children during the acute phase by nephelometrie assay, besides cytochemical and virological study. RESULTS: A predominant absence of intrathecal immunoglobulin synthesis and two patients with IgA and IgM synthesis was produced. 66% of cerebrospinal blood barrier dysfunction, 6.26 10 3 mean albumin ratio, lactate below 2.1 mmol/L and glucose concentration in cerebrospinal fluid was 50% over glucose blood content and 168 cells 10 6 L mainly lymphocytes were observed. CONCLUSIONS: The intratecal immunoglobulin synthesis pattern differs from other enterovirus outbreaks that have affected this population and it seems the one found for the diagnostic period in adults. This finding alerts the possibility of genetic changes in echovirus 16 strain, interesting from the neuroimmunoepidemiological point of view.

Valor neuroinmunoepidemiológico del reibergrama en la primera epidemia de meningoencefalitis por echovirus 16 en Cuba / Neuroimmune epidemiological value of reibergram in the first echovirus 16 meningoencephalitis outbreak in Cuba

Introducción. En el tercer trimestre del 2000 se produce una epidemia de meningoencefalitis por echovirus 16 en Cuba, caracterizada por vómitos, dolor de cabeza, fiebre, además del exantema, que la diferencia de otras epidemias por enterovirus. Objetivo. Describir el patrón de síntesis intratecal de inmunoglobulinas en esta epidemia a partir del reibergrama. Pacientes y métodos. Se estudiaron 18 niños, a los que se les cuantificó albúmina, IgA, IgM e IgG en suero y líquido cefalorraquídeo (LCR), diagnósticos en la fase aguda por nefelometría, además del estudio citoquímico y virológico. Resultados. Hubo un predominio de ausencia de síntesis intratecal de inmunoglobulinas y dos pacientes con síntesis de IgA e IgM, con un 66 por ciento de disfunción de la barrera sangre/LCR, 6,26 × 10-3 de razón albúmina promedio, valores de lactato menores de 2,1 mmol/L y la glucorraquia por encima del 50 por ciento del valor de la glicemia, 168 células × 10-6 L promedio, fundamentalmente linfocitos. Conclusiones. El patrón de síntesis intratecal difiere de los comunicados para otros enterovirus que han afectado esta población y se asemeja al encontrado en el período diagnóstico en adultos, lo que rompe la posibilidad de cambios genéticos en la cepa de echovirus 16 de interés neuroinmunoepidemiológico (AU)

[Patterns of immunoglobulin synthesis in pediatric patients with Coxsackie A9 meningoencephalitis during the neuropathy epidemic in Cuba]. / Patrones de síntesis de inmunoglobulinas en pacientes pediátricos con meningoencefalitis por Coxsackie A9 durante la epidemia de neuropatía en Cuba.

INTRODUCTION: Simultaneously with the origin and development of the Cuban epidemic neuropathy, cases of viral meningoencephalitis with particular characteristics due to Coxsackie were found. This virus and Inoue-Melnick virus were found too in patients suffering from Cuban epidemic neuropathy. PATIENTS AND METHODS: 31 pediatric patients suffering from viral meningoencephalitis were studied. Albumin, IgA, IgM and IgG were quantified in serum and cerebrospinal fluid by nephelometry. Cytochemical studies and reibergrams were performed. RESULTS: There was a lymphocyte predominance in cerebrospinal fluid. A dysfunction of blood-cerebrospinal fluid barrier was shown in 10 patients. Twenty patients have no immunoglobulins intrathecal synthesis. The synthesis patterns were: five patients with local IgM synthesis, two patients with local IgG synthesis and IgA + IgM. IgA + IgG and IgA + IgM pattern was synthesized in one patient respectively. Two patients with low IgG synthesis percentage or IgG intrathecal fractions were reported. CONCLUSIONS: The absence of immunoglobulins intrathecal synthesis and the immunoglobulins synthesis patterns differ from other pediatric patients with enterovirus meningoencephalitis. These patterns may have relationship with modified antigenic characteristics of the virus, also found in Cuban epidemic neuropathy.

IgG2 immunodeficiency: association to pediatric patients with bacterial meningoencephalitis.

An IgG subclass deficiency is often associated with bacterial infections. We studied four pediatric patients suffering from meningoencephalitis, two of them due to Streptococcus pneumoniae and two due to Haemophilus influenzae type b. Simultaneous diagnostic serum and cerebrospinal fluid samples were taken during income. The four subclasses of IgG and albumin were quantified in both biologic fluids by radial immunodiffusion. Very low levels of seric IgG2 with non detectable cerebrospinal fluid IgG2 were found in the patients. No intrathecal IgG subclass synthesis was found in two patients. One patient with S. pneumoniae had IgG3 intrathecal synthesis. Intrathecal IgG1, IgG3 and IgG4 synthesis was found in one patient suffering from H. influenzae according with reibergrams. Substitutive therapy with intravenous gammaglobulin was given to the patients as part of the treatment.

Patrones de síntesis de inmunoglobulinas en pacientes pediátricos con meningoencefalitis por Coxsackie A9 durante la epidemia de neuropatía en Cuba / Patterns of immunoglobulin sysnthesis in paediatric patients with coxsackie Ag meningoencephalitis during the neuropathy epidemic in Cuba

Introducción. Simultáneamente a la aparición y desarrollo de la neuropatía epidémica cubana se detectaron casos de meningoencefalitisvírica por Coxsackie con características peculiares. En pacientes con neuropatía epidémica cubana se aisló este virus y también el Inoue-Melnick. Pacientes y métodos. Se estudiaron 31 pacientes pediátricos con meningoencefalitis por este virus. Se cuantificó la albúmina, IgA, IgM e IgG por nefelometría en suero y líquido cefalorraquídeo. Asimismo, se realizaron los reibergramas y un estudio citoquímico. Resultados. En el estudio citoquímico de líquido cefalorraquídeo hubo un predominio de linfocitos. Diez pacientes exhibieron disfunción en la barrera sangre-líquido cefalorraquídeo y 20 no sintetizaron inmunoglobulinas intratecalmente. Los patrones de síntesis fueron: en cinco pacientes IgM, en dos pacientes IgG, las combinaciones IgA+IgM en dos pacientes y con IgA+IgG e IgG+IgM en sendos pacientes. Dos de ellos cursaron con bajos porcentajes de síntesis o fracción intratecal de IgG. Conclusiones. La ausencia de síntesis intratecal y los patrones de síntesis de inmunoglobulinas difieren respecto a los hallados en pacientes pediátricos con meningoencefalitis producida por otros enterovirus. Estos patrones pueden estar asociados con las características antigénicas modificadas del virus, que también fue encontrado en la epidemia de neuropatía cubana (AU)

Introduction. Simultaneously with the origin and development of the Cuban epidemic neuropathy, cases of viral meningoencephalitis with particular characteristics due to Coxsackie were found. This virus and Inoue-Melnick virus were found too in patients suffering from Cuban epidemic neuropathy. Patients and methods. 31 pediatric patients suffering from viral meningoencephalitis were studied. Albumin, IgA, IgM and IgG were quantified in serum and cerebrospinal fluid by nephelometry. Cytochemical studies and reibergrams were performed. Results. There was a lymphocyte predominance in cerebrospinal fluid. A dysfunction of blood-cerebrospinal fluid barrier was shown in 10 patients. Twenty patients have no immunoglobulins intrathecal synthesis. The synthesis patterns were: five patients with local IgM synthesis, two patients with local IgG synthesis and IgA+IgM. IgA+IgG and IgA+IgM pattern was synthesized in one patient respectively. Two patients with low IgG synthesis percentage or IgG intrathecal fractions were reported. Conclusions. The absence of immunoglobulins intrathecal synthesis and the immunoglobulins synthesis patterns differ from other pediatric patients with enterovirus meningoencephalitis. These patterns may have relationship with modified antigenic characteristics of the virus, also found in Cuban epidemic neuropathy (AU)

[Haptoglobin in cerebrospinal fluid as a marker of infectious process in central nervous system]. / Haptoglobina en líquido cefalorraquídeo como marcador de procesos infecciosos en el sistema nervioso central.

INTRODUCTION: Haptoglobin is a transport protein and protects organism against iron loss and it should be involved in central nervous system infectious process. PATIENTS AND METHODS: Simultaneous serum and cerebrospinal fluid were obtained of 39 pediatric patients, 14 suffering from viral meningoencephalitis and 25 from bacterial meningoencephalitis. Five control cases were examined too. Haptoglobin, IgG and albumin were quantified in both fluids by radial immunodiffusion. Haptoglobin cerebrospinal fluid/serum ratio, haptoglobin index and haptoglobin/IgG index were calculated. Local IgG intrathecal synthesis was determined by reibergram. RESULTS: Haptoglobin index was higher not statistically significant in viral meningoencephalitis in comparison with bacterial disease but both were statistically significant with respect to control group. Increased haptoglobin/IgG index were statistically significant in bacterial meningoencephalitis in relation with viral meningoencephalitis. There were no association between haptoglobin and polymorphonuclear cells count and globular sediment speed. CONCLUSION: Haptoglobin should be considered a relevant marker of central nervous system infectious process.

[Intrathecal humoral immune response in pediatric patients with meningoencephalitis due to Coxsackie B5]. / Respuesta inmune humoral intratecal en pacientes pediátricos con meningoencefalitis por Coxsackie B5.

INTRODUCTION: Childhood is sensibly affected by viral meningoencephalitis outbreaks. OBJECTIVE: To study the intrathecal humoral immune response in a group of children suffering from Coxsackie B5 meningoencephalitis outbreak. Patients and methods. Forty eight sick children were studied. Serum and cerebrospinal IgA, IgM, IgG and albumin were quantified by radial immunodiffusion. It had been evaluated by reibergrams. RESULTS: Seventeen children has blood-cerebrospinal fluid barrier dysfunction. Four different patterns of intrathecal immune humoral response were observed mainly IgG and three major immunoglobulins class. Mean cell counts was 624 +/- 517 x 10(6) cells/l with a lymphocyte predominance. CONCLUSION: An intrathecal humoral response were reported as an early patterns like in delayed non-diagnostic puncture and in evolutive puncture in adults patterns with viral meningoencephalitis.

Respuesta inmune humoral intratecal en pacientes pediátricos con meningoencefalitis por Coxsackie B5 / Intrathecal humoral immune response in pediatric patients with meningoencephalitis due to Coxsackie B5

INTRODUCTION: Childhood is sensibly affected by viral meningoencephalitis outbreaks. OBJECTIVE: To study the intrathecal humoral immune response in a group of children suffering from Coxsackie B5 meningoencephalitis outbreak. Patients and methods. Forty eight sick children were studied. Serum and cerebrospinal IgA, IgM, IgG and albumin were quantified by radial immunodiffusion. It had been evaluated by reibergrams. RESULTS: Seventeen children has blood-cerebrospinal fluid barrier dysfunction. Four different patterns of intrathecal immune humoral response were observed mainly IgG and three major immunoglobulins class. Mean cell counts was 624 +/- 517 x 10(6) cells/l with a lymphocyte predominance. CONCLUSION: An intrathecal humoral response were reported as an early patterns like in delayed non-diagnostic puncture and in evolutive puncture in adults patterns with viral meningoencephalitis (AU)