Brain barrier dysfunction in Cuban epidemic optic neuropathy.

BACKGROUND AND PURPOSE: There are practically no references to cerebrospinal fluid (CSF) studies in tropical or nutritional neuropathies. In the present paper we present the results of CSF studies in patients with Cuban Epidemic Optic Neuropathy (CEON) during epidemic and endemic periods, with an appraisal as to the contribution of brain barriers' function in the pathophysiology of this disease. METHODS: Two hundred and five patients with CEON were studied during the epidemic period (1992-1993) and 12 patients outside the outbreak (1995-1997). CSF protein determination and electrophoresis were carried out, as well as serum and CSF albumin and immunoglobulin G (IgG) quantitation for calculating IgG and Q(alb) indexes, in order to evaluate intrathecal IgG synthesis and the permeability of the blood-CSF barrier (B-CSF B). RESULTS: One fourth of the patients had increased permeability of the B-CSF B, but damage was more frequent between 16 and 60 days from onset of disease, disappearing after 120 days. B-CSF B dysfunction was more prevalent in patients with severe neurological impairment, although it was not related to the severity of ophthalmological damage. The group of patients studied outside of the outbreak (endemic period) showed similar results. DISCUSSION: The possible association of increased permeability of the B-CSF B with oxidative stress, which lies on the basis of this epidemic outbreak, is discussed.

Circulating autoantibodies against the NR2 peptide of the NMDA receptor are associated with subclinical brain damage in hypertensive patients with other pre-existing conditions for vascular risk.

Arterial hypertension (HT) and other vascular pre-existing conditions (PEC) generate asymptomatic brain damage which increases the occurrence of stroke and cognitive decline. The aim of this work was to explore if serum antibodies against the NR2 subunit of the NMDA receptor (NR2Ab) could predict subclinical brain damage (SBD) in hypertensive patients with PEC. Forty seven neurologically asymptomatic hypertensive subjects were classified according to the number of PEC (retinopathy, overweight/obesity, diabetes mellitus and dyslipidemia). NR2A/B Ab were measured in serum employing an ELISA method. 3.0-T Brain MRI imaging was performed, and visual ratings of white matter hyperintensities (WMH) and counts of dilated Virchow-Robin spaces (DVRS) and lacunes were obtained. Brain atrophy was evaluated with cortical thickness measurements and linear measures. Higher levels of NR2Ab were associated with more severe periventricular WMH (PWMH), more DVRS and more severe SBD; while greater frontal interhemispheric fissure width (IHFW), as a linear measure of frontal atrophy, was inversely related with NR2Ab. Overall and regional cortical thickness were not significantly associated with NR2 Ab. A multivariate analyses showed that IHFW and PWMH were the only variables independently associated with serum NR2Ab concentration. ROC analysis revealed that NR2Ab (cutoff: 1.7ng/ml) predicted PWMH with a sensitivity and specificity of 65% and 87% respectively. CONCLUSIONS: Serum NR2Ab levels may reflect SBD in HT subjects with PEC, especially in younger populations at risk, where age-related cortical atrophy has not yet been fully established.

[The role of blood lipids in the different aetiologies of cerebral infarction]. / Papel de los lípidos sanguíneos en las distintas etiologías del infarto cerebral.

INTRODUCTION: In order to determine the role lipids play in cerebral infarction (CI), the different aetiological subgroups of this disease should first be separated. AIMS AND METHOD: We conducted case control studies to identify whether there is a relation between blood lipid levels and the occurrence of cerebral infarction caused by atheromatosis (CIA). Our study involved a total of 98 patients with cerebral infarction of an atherothrombotic or lacunar aetiopathogenesis that were included in the CIA category. Two control groups were set up: one consisted of 23 patients with non atheromatous cerebral infarction (NACI), which included other aetiologies (cardioembolic, unusual and unspecified), and the other was made up of 101 healthy subjects who had not had a stroke. RESULTS: The group of patients with CIA presented higher average cholesterol rates than the group of subjects with NACI (p= 0.005). Nevertheless, compared to the control group they had higher average levels of cholesterol (p= 0.003), triglycerides (p= 0.011), VLDL (p= 0.028) and LDL (p= 0.000), as well as a higher average atherogenic index (p= 0.028). Furthermore, the average levels of LDL (p= 0.030) and the atherogenic index (p= 0.008) were seen to be statistically higher in the group of subjects with NACI than in the control group. Lastly, it must be pointed out that no differences in the average HDL levels were found between the three groups studied (p= 0.500). The presence of high blood pressure and a history of ischemic heart disease in patients with CI did not modify the variations that were observed in the lipids. CONCLUSIONS: Patients with CIA have a more atherogenic lipid profile than healthy individuals, while subjects with NACI are situated midway between the two groups

[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.

[Electrophoresis of cerebrospinal fluid proteins in patients with ischemic cerebrovascular disease]. / Electroforesis de proteínas del líquido cefalorraquídeo en pacientes con enfermedad cerebrovascular isquémica.

INTRODUCTION: Cerebral infarction (CI) increases vascular permeability because of a torrent of molecular events that take place. It frequently leads to oedema, haemorrhage and neuronal death. Free radicals and proteases are also formed, which cause lesions in the blood vessels, and microvascular integrity is lost through degradation of the basal lamina and the extracellular matrix. As a result rupture of the blood brain barrier takes place. AIMS. To compare the electrophoretograms of patients with ischemic cerebrovascular disease (ICVD) with those of controls and to link the alterations in the proteinogram with the ICVD subtypes. PATIENTS AND METHODS: The CSF of 55 controls and 136 patients with ICVD was examined. The total protein (TP) concentration was determined and a polyacrylamide gel electrophoretogram was produced using Coomassie blue stain. Parallel to this, serum was prepared for haptoglobin staining. RESULTS: The TP in patients CSF rose to a significantly higher level than that of controls. Blood brain barrier damage (BBBD) was observed in 28.7% of the patients studied with CI and in 10.3% in transient ischemic attacks (TIA), while 16.2% presented oligoclonal bands. There was a difference between the two sexes: men were found to have higher TP levels, lower percentages of prealbumin 1 and more BBBD than women. CONCLUSIONS: BBBD is more frequent in infarctions than in TIA, and is predominant in men with thrombotic cerebral infarction.

Estudio evolutivo de metabolitos porfirínicos de un caso de porfiria cutánea tardía / Porphyrins in a case of porphyria cutanea tarda: follow-up study

Resumen Las porfirias son errores congénitos poco frecuentes del metabolismo de las porfirinas. La porfiria cutánea tardía (PCT) es la más frecuente dentro de este grupo de enfermedades. Reportamos el estudio evolutivo de metabolitos porfirínicos de una paciente de 51 años con porfiria cutánea tardía, cuatro años después de su diagnóstico. Durante este período, se le indicó un esquema terapéutico de flebotomías en el Instituto de Hematología e Inmunología. Uno de los exámenes complementarios para su seguimiento fue la determinación de porfirinas totales en la orina, plasma y heces. Los resultados del estudio bioquímico de las porfirinas mostraron mejoría en todos los parámetros, lo que contribuyó a corroborar la utilidad del estudio de estos metabolitos como seguimiento de esta enfermedad y efectividad del tratamiento.

Abstract Porphyrias are rare congenital errors in the metabolism of porphyrins. Porphyria cutanea tarda is the most frequent among different types of porphyrias. We report the follow-up study of porphyrin metabolites of a 51-year-old patient with porphyria cutanea tarda four years later of her diagnosis. During this period, it was indicated a therapeutic scheme of phlebotomies in the Institute of Hematology and Immunology. One of the complementary examinations for its follow-up was the determination of total porphyrins in the urine, plasma and feces. Porphyrins in plasma decreased from 13 500 nmol/L at onset of disease to 250 nmol/L four years later. Although, porphyrins in feces and plasma could not quantify, we observed non-presence of peaks at 405 nm and 615.1 nm, respectively. These results contributed to corroborate the usefulness of the study of these metabolites for monitoring of this disease and effectiveness of the treatment.

Serum neuron-specific enolase and S100 calcium binding protein B biomarker levels do not improve diagnosis of acute stroke.

BACKGROUND: The high sensitivities and specificities reported for blood biomarkers as a supportive test in the diagnosis of acute stroke do not correspond with their performance for decision-making in emergency situations. METHODS: Seventy-two patients with suspected stroke were recruited: 44 with ischaemic stroke, 17 with haemorrhagic stroke and 11 stroke mimics, as well as a high-risk control group of 79 individuals. Serum neuron-specific enolase (NSE) and S100 calcium binding protein B (S100B) biomarker levels were determined on admission, using immunoassay kits. The sensitivities and specificities of NSE and S100B for distinguishing acute stroke from stroke mimics and high-risk controls were calculated. RESULTS: For cut-off values (NSE ≤ 14 micrograms per litre and S100B ≤130 nanograms per litre) the sensitivity was 53% and 55% respectively. Specificity was 64 for both versus the stroke mimic group. Specificity was higher (79% and 86% respectively) when calculated on the basis of the control group. CONCLUSIONS: This study supports the evidence indicating that serum levels of NSE and S100B do not improve the diagnosis of acute stroke.

Electroforesis de proteínas del líquido cefalorraquídeo en pacientes con enfermedad cerebrovascular isquémica / Electrophoresis of cerebrospinal fluid proteins in patients with ischemic cerebrovascular disease

Introducción. El infarto cerebral (IC) aumenta la permeabilidad vascular al ocurrir toda una cascada de eventos moleculares, y aparece con frecuencia edema, hemorragia y muerte neuronal. También ocurre la formación de radicales libres y proteasas que causan lesiones a los vasos sanguíneos, y se pierde la integridad microvascular por degradación de la lámina basal y la matriz extracelular; todo esto conduce a la ruptura de la barrera hematoencefálica. Objetivos. Comparar el electroforetograma de pacientes con enfermedad cerebrovascular isquémica (ECVI) con los controles y asociar las alteraciones del proteinograma con los subtipos de ECVI. Pacientes y métodos. Se estudió el LCR de 55 controles y 136 pacientes con ECVI. Se determinó la concentración de proteínas totales (PT) y el electroforetograma en geles de disco de poliacrilamida con tinción de Coomassie; el suero se procesó en paralelo para tinción de haptoglobinas. Resultados. Las PT en el LCR de los pacientes se elevaron significativamente más que en los controles. El daño de barrera hematoencefálica (DBHE) se observó en el 28,7 por ciento de los pacientes estudiados con IC y en el 10,3 por ciento en los ataques isquémicos transitorios, mientras que el 16,2 por ciento presentaron bandas oligoclonales. Hubo diferencia entre ambos sexos: los hombres tuvieron los niveles de PT elevados, menor porcentaje de prealbúmina-1 y más DBHE que las mujeres. Conclusión. El DBHE es más frecuente en los infartos que en los AIT, y predominan en los hombres con infarto cerebral trombótico (AU)