Neurologic manifestation of Covid-19 pediatric patients admitted at the Philippine Children's Medical Center in the year 2020: a case series

@#<p>Covid-19 which was first documented in the Philippines in January 2020 had spread alarmingly. Severe acute respiratory symptoms were the most common presentation of this novel coronavirus infection. Reports have described neurologic manifestations of this disease involving the central nervous system as well as the peripheral nervous system. However, studies among the pediatric population are limited. In this paper, we present three pediatric patients who were diagnosed with COVID-19, via RT-PCR, presenting with seizures and behavioral changes. Two of these patients have no concomitant respiratory symptoms while the other one had Pediatric Community Acquired Pneumonia. These patients were managed as cases of acute viral meningoencephalitis and were given supportive care.</p>

Interleuquina-6 y factor de necrosis tumoral-a en el suero y líquido cefalorraquídeo de niños con meningoencefalitis viral / Interleukin-6 and tumor necrosis factor-a in serum and cerebrospinal fluid from children with viral meningoencephalitis

INTRODUCCIÓN: las meningoencefalitis virales en el niño son causadas con mayor frecuencia por enterovirus, y tienen un curso generalmente benigno y autolimitado. OBJETIVO: estimar las concentraciones de interleuquina-6 y factor de necrosis tumoral-a en suero y líquido cefalorraquídeo de niños con meningoencefalitis viral. MÉTODOS: se realizó un estudio descriptivo y transversal. Se estudiaron 61 pacientes, con edades entre 1 mes y 17 años con diagnóstico de meningoencefalitis viral por cuadro clínico, estudio citoquímico de líquido cefalorraquídeo y detección de genoma viral de enterovirus por reverso trascripción y reacción en cadena de la polimerasa. Se determinaron concentraciones de interleuquina-6 y factor de necrosis tumoral-a en 48 muestras de suero y 35 de líquido cefalorraquídeo. Para el análisis estadístico se empleó, la prueba de Wilcoxon para 2 muestras relacionadas, y la de Spearman para correlacionar las concentraciones de citoquinas. RESULTADOS: se detectó genoma viral en 3 muestras de líquido cefalorraquídeo con celularidad aumentada y predominio de polimorfonucleares, y en 3 muestras con celularidad normal. La cuantificación de interleuquina-6 en suero, fue 91,6 ± 39,0 pg/mL; y de factor de necrosis tumoral-α 106,5 ± 54,6 pg/mL. En el líquido cefalorraquídeo la cuantificación de interleuquina-6 fue de 109,65 ± 49,6 pg/mL, y de factor de necrosis tumoral-a 75,28 ± 29,9 pg/mL. CONCLUSIONES: se determinaron concentraciones elevadas de interleuquina-6 y de factor de necrosis tumoral-a en todas las muestras estudiadas. Este último se detectó más elevado en el suero, mientras la interleuquina-6 se elevó más en el líquido cefalorraquídeo, y se correlacionó positivamente con sus valores en suero y con los del factor de necrosis tumoral-a.

INTRODUCTION: viral meningoencephalitis affecting the child is caused mainly by enteroviruses and have generally self-limited benign course. OBJECTIVE: to estimate the interleukin-6 and tumor necrosis factor-a present in the serum and the cerebrospinal fluid of children suffering viral meningoencephalitis. METHOD: cross-sectional descriptive study of 61 patients aged one month to 17 years and diagnosed with viral meningoencephalitis. The diagnosis was based on their clinical picture, the cytochemical study of their cerebrospinal fluid and the detection of enterovirus viral genome through the reverse transcriptase polymerase chain reaction. Forty eight serum samples and 35 cerebrospinal fluid samples served to determine the interleukin-6 and tumor necrosis factor-a concentrations. The statistical analysis included Wilcoxon's test for 2 related samples and the Spearman's test for correlating cytokine concentrations. RESULTS: viral genome was detected in 3 cerebrospinal fluid samples with increased cellularity and predominant polymorphonuclear neutrophils and in other 3 samples with normal cellularity. The quantitation of serum interleukin-6 and of tumor necrosis factor-alpha were 91.6 ± 39.0 pg/mL and 106.5 ± 54.6 pg/mL, respectively. The interleukin-6 and tumor necrosis factor-alpha levels in the cerebrospinal fluid amounted to 109.65 ± 49.6 pg/mL, and 75.28 ± 29.9 pg/mL, respectively. CONCLUSIONS: high interleukin-6 and tumor necrosis factor-alpha levels were found in all the studied samples. The factor concentrations were higher in the serum whereas those of interleukin-6 were higher in the cerebrospinal fluid; there was positive correlation between interleukin-6 values in the serum and those of the tumor necrosis factor-alpha.

Frecuencia de enterovirus en niños con meningoencefalitis viral / Enterovirus frequency in children with viral meningoencephalitis

Introducción: el enterovirus es uno de los agentes causales que suelen afectar el sistema nervioso central. Objetivos: determinar la frecuencia de enterovirus en niños hospitalizados con meningoencefalitis. Métodos: se efectuó un estudio descriptivo-observacional de 66 infantes con meningoencefalitis viral, ingresados en el Hospital Pediátrico Provincial "Dr. Eduardo Agramonte Piña" de la provincia de Camagüey, desde enero de 2011 hasta julio de 2012. Resultados: 26,6 % de los afectados fueron aislados por enterovirus en el año 2011 y 84,3 % en el 2012. El agente diagnosticado fue ECHO virus 30, el cual afectó todas las edades con positividad entre 63,0 y 100,0 %. Prevaleció el sexo masculino (78,4 %) procedentes de 11 municipios, con positividades superiores a 70 % en Florida y Camagüey. Los síntomas predominantes fueron cefaleas, fiebre, vómitos y malestar general. A la mayoría de los pacientes se le realizó estudio citoquímico del líquido cefaloraquídeo entre 10 y 199 células por 10(6)/L con predominio linfocitario. Conclusiones: gran parte de los afectados evolucionaron satisfactoriamente con hospitalización de solo 4 días.

Introduction: the enterovirus is one of the causal agents usually affecting the central nervous system. Objectives: to determine the enterovirus frequency in children hospitalized with meningoencephalitis. Methods: a descriptive-observational study of 66 infants with viral meningoencephalitis admitted in "Dr. Eduardo Agramonte Piña" Provincial Pediatric Hospital was carried out in Camagüey province from January, 2011 to July, 2012. Results: 26.6% of the affected ones were isolated due to enterovirus in the year 2011 and 84.3% in 2012. The diagnosed agent was ECHO virus 30, which affected all the ages with positivity between 63.0 and 100.0%. The male sex prevailed (78.4%) coming from 11 municipalities, with positivities higher than 70% in Florida and Camagüey. The predominant symptoms were migraines, fever, vomits and general uneasiness. Most of the patients had a cytochemical study of the cerebrospinal fluid from 10 and 199 cells per 106/L with lymphocytes prevalence. Conclusions: great number of the affected patients had a satisfactory clinical course with hospital stay of just 4 days.

Role of IL-17 in the pathogenesy and differential diagnosis of CNS infections YOU Wen-xia, / 中华神经医学杂志

Objective To study the role of IL-17 in the pathogenesy and differential diagnosis of the 3 types of CNS infections (tubercular meningitis [TBM], cryptococcal meningitis [CM], viral meningoencephalitis [VM]). Methods One hundred and twelve patients with CNS infections,admitted to out hospital from February 2008 to December 2009, were chosen and divided into TBM group, CM group and VM group;another 36 patients without CNS infections either autoimmune disease at the same period were chosen as control group. ELISA was employed to determine the levels of IL-17,IL-12, IFN-γ in the cerebrospinal fluid in these 4 groups. Results IL-17 level in the cerebrospinal fluid of the 3 groups with CNS infections were obviously different, but all of them were significantly higher than that in control group (P＜0.05), with CM group enjoying the highest level, following by TBM group,VM group and control group. The levels of IL-12 and IFN-γ in patients with TBM and CM were higher than those in patients with VM and controls. Through the correlation analysis of IL-17, IL-12 and IFN-γ in patients with TBM, we found that IL-17 level was negatively correlated with IL-12 level (r=-0.3 11,P=0.033);the levels of these 3 cytokines were positively correlated with the quantity of leucocytes (r=0.219, 0.434 and 0.341, P=0.031, 0.027 and 0.001). ROC curves were established for differential diagnosis among these 3 groups according to CSF IL-17 levels, and all of the areas under the curve were bigger than 0.7. Conclusion Thl7 pathway is widely involved in the immune responses of CNS infection, and interacts with Thl pathway. The different levels of IL-17 in the cerebrospinal fluids in patients with various CNS infections may contribute to differential diagnosis.

White Matter Damage in Neonates in the Course of Viral Illness

Studies of brain magnetic resonance imaging (MRI) of neonatal white matter damage are few, and descriptions of this type of brain damage are limited. During the past three years, we have encountered three full-term infants with selective white matter damage over the course of their viral illness. All three neonates presented with seizures a few days after showing symptoms of a viral illness. The results of bacterial cultures of the blood, CSF, and stool were negative. Newborn screening tests for organic aciduria, amino acid metabolism disorders, and fatty acid oxidation defects were also negative. In two infants, an electroencephalogram (EEG) showed slow basic activity, which is a typical finding in patients with encephalitis/encephalopathy. The Diffusion-weighted MRI (DWI) showed abnormally high signal intensity localized to the white matter of the corpus callosum, thalamus, internal capsule, or hippocampus. The findings of DWI suggested that the neonates' lesions had occurred recently. All patients recovered completely.