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INTRODUCCIÓN: El diagrama de las razones de Reiber o reibergrama cobra cada día mayores usos para la caracterización de la síntesis intratecal de proteínas. El reibergrama fue definido para las clases mayores de inmunoglobulinas pero luego ha sido utilizado para evaluar otras proteínas basado en la teoría de la difusión molecular/velocidad de flujo del líquido cefalorraquídeo (LCR). MÉTODO: El C3c, producto de la degradación del factor del complemento C3 y con una masa molecular de 145 KDa, se acerca a las características moleculares de la IgG para las leyes de la difusión de Fick. Se asume las constantes de la IgG en la fórmula de Reiber para evaluar la síntesis intratecal de C3c así como su correspondiente reibergrama. Se estudiaron 27 pacientes y 27 controles a los que se les dosificó albúmina y C3c en suero y LCR por inmunodifusión radial. RESULTADOS: Con el reibergrama propuesto para el C3c se evaluaron estos pacientes. Se comprueba la validez de este reibergrama para distintas condiciones de barrera con o sin síntesis intratecal de C3c. CONCLUSION: El reibergrama y su fórmula correspondiente propuesto para la C3c puede ser usado para la evaluación de la síntesis intratecal de C3c.

INTRODUCTION: Angiostrongylus cantonensis meningoencephalitis is an emergent disease in the Americas. METHOD: Twelve children suffering from eosinophilic meningoencephalitis due to this parasite aged between 6-10 years were studied. Cerebrospinal fluid (CSF) and serum samples were taken simultaneously in the first diagnostic puncture at admission. RESULTS: All cases showed typical findings on the routine CSF and serum analysis: increased CSF total protein, increased Q (CSF/serum) albumin accompanied by eosinophilia in CSF. No intrathecal synthesis of immunoglobulins was found. Mean serum and CSF sICAM-1 values were 337.4 and 3.97 ng/mL. Qalbumin and QsICAM-1 mean values were 4.1 and 6.2 respectively. In 50% of the patients an increased brain-derived fraction of sICAM-1 was found. CONCLUSION: It may be suggested that a dynamic of the sICAM-1 brain derived fraction is perhaps associated to the immune response in the evolution of the disease.sICAM-1 may be an agent in negative feedback for eosinophils passage through the blood-CSF barrier into the inflammatory brain response.

Autism spectrum disorder (ASD) is a group of complex multifactorial neurodevelopmental disorders characterized by a wide and variable set of neuropsychiatric symptoms, including deficits in social communication, narrow and restricted interests, and repetitive behavior. The immune hypothesis is considered to be a major factor contributing to autism pathogenesis, as well as a way to explain the differences of the clinical phenotypes and comorbidities influencing disease course and severity. Evidence highlights a link between immune dysfunction and behavioral traits in autism from several types of evidence found in both cerebrospinal fluid and peripheral blood and their utility to identify autistic subgroups with specific immunophenotypes; underlying behavioral symptoms are also shown. This review summarizes current insights into immune dysfunction in ASD, with particular reference to the impact of immunological factors related to the maternal influence of autism development; comorbidities influencing autism disease course and severity; and others factors with particular relevance, including obesity. Finally, we described main elements of similarities between immunopathology overlapping neurodevelopmental and neurodegenerative disorders, taking as examples autism and Parkinson Disease, respectively.

Evolving data show a variable expression of clinical neurological manifestations in patients suffering with coronavirus disease 2019 (COVID-19) from early disease onset. The most frequent symptoms and signs are fatigue, dizziness, impaired consciousness, ageusia, anosmia, radicular pain, and headache, as well as others. Based on the high number of series of cases reported, there is evidence for the implication of the immune system in the pathological mechanism of COVID-19. Although the exact role of the immunological mechanism is not elucidated, two main mechanisms are suggested which implicate the direct effect of severe acute respiratory syndrome coronavirus 2 infection in the central nervous system and neuroinflammation. In the context of neurological manifestations associated with COVID-19, neuropsychiatric disorders show an exacerbation and are described by symptoms and signs such as depression, anxiety, mood alterations, psychosis, post-traumatic stress disorder, delirium, and cognitive impairment, which appear to be common in COVID-19 survivors. A worsened score on psychopathological measures is seen in those with a history of psychiatric comorbidities. We review the neuropsychiatric manifestations associated with COVID-19 and some critical aspects of the innate and adaptive immune system involved in mental health disorders occurring in COVID-19., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study evaluates the contribution of peripheral biomarkers to comorbidities and clinical findings in autism. Seventeen autistic children and age-matched typically developing (AMTD), between three to nine years old were evaluated. The diagnostic followed the Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DMS-IV) and the Childhood Autism Rating Scale (CARS) was applied to classify the severity. Cytokine profile was evaluated in plasma using a sandwich type ELISA. Paraclinical events included electroencephalography (EEG) record. Statistical analysis was done to explore significant differences in cytokine profile between autism and AMTD groups and respect clinical and paraclinical parameters. Significant differences were found to IL-1β, IL-6, IL-17, IL-12p40, and IL-12p70 cytokines in individuals with autism compared with AMTD ( p < 0.05). All autistic patients showed interictalepileptiform activity at EEG, however, only 37.5% suffered epilepsy. There was not a regional focalization of the abnormalities that were detectable with EEG in autistic patients with history of epilepsy. A higher IL-6 level was observed in patients without history of epilepsy with interictalepileptiform activity in the frontal brain region, p < 0.05. In conclusion, peripheral inflammatory markers might be useful as potential biomarkers to predict comorbidities in autism as well as reinforce and aid informed decision-making related to EEG findings in children with Autism spectrum disorders (ASD)., Competing Interests: The authors declare no conflict of interest.

Background: Multiple sclerosis (MS) was first reported in Cuba in 1965. The most frequent appearance is observed in the first six months of the year., Objective: To determine the seasonal distribution and evolving forms of MS patients diagnosed with the disease between April 2004 and November 2007., Method: Twenty-one patients with suspected MS and 42 outbreaks were studied. Patients were classified according to Lublin and Revingold's criteria for clinical forms and according to McDonald., Results: Most patients were classified in outbreak and remission and only two patients classified as primary-progressive multiple sclerosis. The higher number of outbreaks occurred in the first two quarters of the year., Conclusion: It is recommended to study further weather variables that may be related to the emergence of these outbreaks in our environment.

Introduction: The meningitis is one of the most severe diseases in children due to its mortality or sequels. However, timely knowledge of whether the infection is bacterial or viral in origin and applied a specific therapeutic would be beneficial for the patients and clinician. The haptoglobin/IgG index and Boyer's score have been use in this purpose., Patients and Methods: 39 pediatric patients, 14 suffering from viral meningoencephalitis and 25 from bacterial meningoencephalitis were study. Boyer's score and Hp/IgG index were applied in order to evaluate its diagnostic accuracy. The clinical relevance of haptoglobin/IgG index and Boyer's score were compared by the analysis of the receiver-operating characteristic (ROC) curves., Results: There were no association between Boyer's score and the cause of the meningitis. The sensitivity and specificity of haptoglobin/IgG index were de 71.4 and 64%, respectively. The same parametric to Boyer's score were de 28 and 100%. Increased haptoglobin/IgG index presents bigger precision for the differential diagnostic of the bacterial and viral meningitis than the scale of Boyer according to the curves ROC., Conclusion: The index haptoglobin/IgG showed its diagnostic superiority with relationship to the scale of Boyer to establish the origin of the meningoencephalitis.

The intercellular adhesion molecule is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Serum and cerebrospinal fluid (CSF) soluble intercellular adhesion molecule 1 (sICAM-1) from normal control children as well as from children with Guillain-Barré syndrome (GBS), with Coxsackie A9 virus meningoencephalitis and with Streptococcus pneumoniae meningoencephalitis were studied. sICAM-1 was quantified using an immunoenzimatic assay and albumin using the immunodiffusion technique in both biological fluids. Increased sICAM-1 values in CSF in patients with GBS correspond to an increase of the albumin CSF/serum quotient. In contrast, in inflammatory diseases like S. pneumoniae and Coxsackie A9 virus meningoencephalitis an increased brain-derived fraction was observed. In particular cases these values are 60-65% and 70-75% respectively. The results indicate an additional synthesis of sICAM-1 in subarachnoidal space during central nervous system (CNS) inflammatory process. An important role of sICAM-1 in the transmigration of different cell types into CSF during CNS inflammation in children with S. pneumoniae and Coxsackie A9 meningoencephalitis may be suggested.

Introduction: 25 years ago was first reported in Cuba and in the western hemisphere an emergent disease: eosinophilic meningoencephalitis due to Angiostrongylus cantonensis larvae., Aim: To collect in a summary form the accumulated experience and the findings of the study of this parasitosis during the period in the Western hemisphere., Development and Conclusions: There have been collected the first evidences, the parasitological and malacological findings, the experimental and molecular studies on immunology and neuroimmunology, the clinic-pathological findings in children and adults with the particularities of this diseases in our environment with special emphasis in the never-before scientific findings reported. It has been documented the testimony, the main findings among the malacological studies, the role of the immunoglobulin E and the mechanism involved in the central nervous system, the intrathecal synthesis patterns of immunoglobulins and the clinical elements in children and adults.

Introduction: Multiple sclerosis (MS) is a chronic, inflammatory and progressive disease of the central nervous system in which local inflammatory injuries of the brain white matter appears, being the most outstanding feature the myeline loss (demyelination)., Objective: To determine if the complement system might be involved in the MS immunopathogeny favouring the mechanism intervening in the myelin destruction., Method: Samples of sera and CSF from twelve patients with a diagnosis of MS obtained at the moment of the admission to the hospital at the beginning of the break out, were collected. Levels of C3c and albumin in sera and in CSF were quantified using radial immunodiffusion plates., Results: High values over 80% of intrathecal synthesis were obtained except in one of the patients., Conclusion: Intrathecal synthesis of C3c and its liberation to the CSF means that the activation of the complement system in any of the two ways has taken place, and that once performed its biological functions, has suffered a degradation process.

Introduction: Reiber's quotient diagram or reibergram has a growing apply for characterize the intratecal synthesis of proteins. Firstly reibergrama was used for the major classes of immunoglobulins but later it was used to evaluate other proteins based on the theory about molecular flux/cerebrospinal fluid (CSF) flow rate., Method: C3c is a degradation product of complement factor C3 with 145 KDa and approaches to IgG molecular characteristics according with Fick's diffusion laws. It was assumed IgG constants and graphic for IgG constants and graphic to evaluate the intrathecal synthesis of C3c. Twenty-seven patients and 27 controls were studied. Serum and CSF C3c and albumin were quantified by immunodiffusion., Results: The patients with the C3c proposed reibergram were evaluated. It has been proved its validity under several CSF blood barrier conditions., Conclusion: Reibergram for C3c can be used for the evaluation of the intrathecal synthesis of this protein.

Introduction: Angiostrongylus cantonensis meningoencephalitis is an emergent zoonotic disease in the Caribbean basin, characterized by the presence of eosinophils and third stage larva of the helmint., Objective: To analyze the IgG subclasses and IgE intrathecal synthesis patterns obtained by reibergrams in pediatric patients suffering from eosinophilic meningoencephalitis due to A. cantonensis., Patients and Methods: 20 pediatric patients with the disease were studied. During the first diagnostic lumbar puncture an eosinophilic pleocytosis was found. Simultaneously a serum sample was taken. Eight days later, a second lumbar and venous puncture was performed. IgA, IgM, IgG, albumin in serum and cerebrospinal fluid samples were quantified by immunodiffusion in addition to a differential cell count in cerebrospinal fluid. IgG subclasses were quantified in 10 patients by immunodiffusion and IgE in four patients by nephelometry., Results: During the first diagnostic lumbar puncture, all the cases had a blood-cerebrospinal fluid barrier dysfunction with absence of immunoglobulins intrathecal synthesis, a mean of 450 cells/mul and an average of 48% of eosinophils. In the second lumbar puncture 40% of the patients had a dysfunction of the blood-cerebrospinal fluid barrier and an intrathecal synthesis pattern of IgA+IgM+IgG in 50% of the patients. Eight patients had an intrathecal IgA+IgG class response. 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. Two patients from the second lumbar puncture remained without intrathecal synthesis. IgE intrathecal synthesis was observed in the four analyzed patients in the first diagnostic lumbar puncture., Conclusions: The IgG1+IgG2 and IgE intrathecal synthesis pattern demonstrated the complexity of the antigenic mosaic of the helmint and it can contribute to diagnosis of eosinophilic meningoencephalitis due to A. cantonensis.

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.

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.

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.

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.

Introduction: Transthyretin is considered an excellent marker for monitoring nutritional status in serum. In cerebrospinal fluid it is synthesized by chroroid plexus. Cuban epidemic neuropathy is an emergent disease with a hypothetically viral and nutritional origin., Objective: To know the behavior of this transport molecule in serum and cerebrospinal fluid in patients with Cuban epidemic neuropathy., Patients and Methods: Serum and cerebrospinal fluid was quantified in 11 patients with Cuban epidemic neuropathy, eight patients suffering from other neuropathies and 15 patients with Down's syndrome and 10 patients with Alzheimer's disease., Results: Serum transthyretin was diminished in patients with Cuban epidemic neuropathy, other neuropathies and Alzheimer's disease. Down's syndrome patients had significantly higher transthyretin levels in comparison with Cuban epidemic neuropathy and Alzheimer's disease. Cerebrospinal fluid transthyretin was significantly increased in patients with Cuban epidemic neuropathy in comparison with the normal values and with Alzheimer's disease patients whose values were settled below the normal values., Conclusions: The decrement of serum transthyretin in Cuban epidemic neuropathy indicates malnutrition and its higher levels in cerebrospinal fluid also indicate a viral infection. These findings support the nutrio-viral hypothesis of the disease.

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.

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.

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.

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.

Introduction: beta-trace protein or D2 prostaglandin synthase is a dual functional protein. Its role and clinical value in cerebrospinal fluid is under study., Material and Methods: Seventy four pediatric patients suffering from viral meningoencephalitis and 7 with bacterial meningoencephalitis were studied. Sera and cerebrospinal fluid samples were taken. Albumin and beta-trace protein were quantified by immunodiffusion and nephelometry respectively., Results: Increased cerebrospinal fluid beta-trace protein levels in comparison with normal value were observed. Nevertheless such expected increment was no possible seen in bacterial meningoencephalitis., Conclusions: beta-trace protein may contribute with the etiological diagnosis in meningoencephalitis.