Lipid droplets in Zika neuroinfection: Potential targets for intervention?

Lipid droplets (LD) are evolutionarily conserved lipid-enriched organelles with a diverse array of cell- and stimulus-regulated proteins. Accumulating evidence demonstrates that intracellular pathogens exploit LD as energy sources, replication sites, and part of the mechanisms of immune evasion. Nevertheless, LD can also favor the host as part of the immune and inflammatory response to pathogens. The functions of LD in the central nervous system have gained great interest due to their presence in various cell types in the brain and for their suggested involvement in neurodevelopment and neurodegenerative diseases. Only recently have the roles of LD in neuroinfections begun to be explored. Recent findings reveal that lipid remodelling and increased LD biogenesis play important roles for Zika virus (ZIKV) replication and pathogenesis in neural cells. Moreover, blocking LD formation by targeting DGAT-1 in vivo inhibited virus replication and inflammation in the brain. Therefore, targeting lipid metabolism and LD biogenesis may represent potential strategies for anti-ZIKV treatment development. Here, we review the progress in understanding LD functions in the central nervous system in the context of the host response to Zika infection.

Family Herpesviridae and neuroinfections: current status and research in progress

This article addresses the relationship between human herpesviruses (HHVs) and neuroinfections. Alphaherpesviruses, betaherpesviruses and gammaherpesviruses are neurotropic viruses that establish latency and exhibit reactivation capacity. Encephalitis and meningitis are common in cases of HHV. The condition promoted by HHV infection is a purported trigger for certain neurodegenerative diseases. Ongoing studies have identified an association between HSV-1 and the occurrence of Alzheimer's disease, multiple sclerosis and infections by HHV-6 and Epstein-Barr virus. In this review, we highlight the importance of research investigating the role of herpesviruses in the pathogenesis of diseases that affect the nervous system and describe other studies in progress.

Encefalitis por enterovirus: análisis clínico y paraclínico en pacientes pediátricos de un hospital de tercer nivel en Quito-Ecuador, de enero a diciembre de 2016 / Enterovirus encephalitis: clinical and paraclinical analysis in pediatric patients in a tertiary hospital in Quito-Ecuador, from January to December 2016

La encefalitis es una entidad rara con manifestaciones clínicas variables. En los niños es usualmente leve y autolimitada. En 30 a 75% se desconoce la etiología y cuando el patógeno se identifica por PCR (reacción en cadena de la polimerasa), el 80% son enterovirus. En América Latina no están disponibles métodos específicos de diagnóstico. En nuestro país muy pocos centros realizan el examen y tampoco están disponibles estadísticas reales de su incidencia. Objetivo: correlacionar la etiología con los síntomas, resultados de laboratorio, imagen y electroencefalograma. Métodos: estudio transversal; de enero a diciembre de 2016 se revisaron las historias clínicas de 63 niños de 0 a 18 años hospitalizados con sospecha de encefalitis. Una vez identificado el enterovirus por PCR, se correlacionó con los hallazgos de los exámenes de laboratorio e imagen. Resultados: se confirmó encefalitis viral en 35 pacientes, enterovirus en 49%, predominio en la edad preescolar. Síntomas más comunes: fiebre, cefalea, signos meníngeos y síntomas digestivos, 24% alteraciones de la conciencia. Biometría hemática normal en 71%, proteina C reactiva alterada en 71%. De los pacientes con estudios de imagen, 6% tuvo resultado anormal y en aquellos con electroencefalograma 80% fue anormal. Se utilizó la U de Mann Whitney para el análisis estadístico, la relación entre enterovirus y alteración de estado de conciencia y síntomas digestivos fue significativa (p=0.029). Conclusión: en los pacientes con diagnóstico de encefalitis que presenten síntomas digestivos y alteración del estado de conciencia, se debe sospechar que el enterovirus es el agente etiológico.

Encephalitis is a rare entity with variable clinical manifestations. In children it is usually mild and self-limited. In 30-75% of cases, the etiology is unknown and when the pathogen is identified by PCR (polymerase chain reaction), 80% are enteroviruses. In Latin America specific diagnostic methods are not available. In our country very few centers carry out the specific test, real statistics of their incidence are not available Objective: To correlate etiology with symptoms, laboratory results, imaging and electroencephalogram. Methods: Cross-sectional study, clinical records of 63 children between 0 and 18 years hospitalized with suspected encephalitis from January to December 2016 were reviewed. Once Enterovirus was identified by PCR, it was correlated with the findings of laboratory and imaging tests. Results: Viral encephalitis was confirmed in 35 patients, Enterovirus in 49%, predominance in pre-school age. Most common symptoms: fever, headache, meningeal signs and digestive symptoms, 24% alterations of consciousness. Normal blood count in 71%, Protein C Reactive altered in 71%. In patients with imaging studies, 6% had an abnormal result and in those who underwent electroencephalography, 80% were abnormal. The Mann Whitney U was used for the statistical analysis, the relationship between enterovirus and alteration of consciousness and digestive symptoms was significant (p: 0.029) Conclution: In patients with a diagnosis of encephalitis presenting digestive symptoms and altered state of consciousness, Enterovirus should be suspected as an etiologic agent.

Full Outline of Unresponsiveness score and the Glasgow Coma Scale in prediction of pediatric coma / 世界急诊医学杂志（英文）

@#BACKGROUND: This study was done to compare the admission Full Outline of Unresponsiveness (FOUR) score and Glasgow Coma Scale (GCS) as predictors of outcome in children with impaired consciousness. METHODS: In this observational study, children (5–12 years) with impaired consciousness of <7 days were included. Children with traumatic brain injury, on sedatives or neuromuscular blockade; with pre-existing cerebral palsy, mental retardation, degenerative brain disease, vision/hearing impairment; and seizure within last 1 hour were excluded. Primary outcomes: comparison of area under curve (AUC) of receiver operating characteristic (ROC) curve for in-hospital mortality. Secondary outcomes: comparison of AUC of ROC curve for mortality and poor outcome on Pediatric Overall Performance Category Scale at 3 months. RESULTS: Of the 63 children, 20 died during hospital stay. AUC for in-hospital mortality for GCS was 0.83 (CI 0.7 to 0.9) and FOUR score was 0.8 (CI 0.7 to 0.9) [difference between areas –0.0250 (95%CI 0.0192 to 0.0692), Z statistic 1.109, P=0.2674]. AUC for mortality at 3 months for GCS was 0.78 (CI 0.67 to 0.90) and FOUR score was 0.74 (CI 0.62 to 0.87) (P=0.1102) and AUC for poor functional outcome for GCS was 0.82 (CI 0.72 to 0.93) and FOUR score was 0.79 (CI 0.68 to 0.9) (P=0.2377), which were also comparable. Inter-rater reliability for GCS was 0.96 and for FOUR score 0.98. CONCLUSION: FOUR score was as good as GCS in prediction of in-hospital and 3-month mortality and functional outcome at 3 months. FOUR score had a good inter-rater reliability.

Manifestaciones neurológicas durante la infección por el virus del dengue / Neurological manifestations during dengue virus infection

El dengue es la enfermedad viral transmitida por mosquitos más importante en el mundo. Alrededor del 10% de los pacientes con dengue, pueden presentar alteraciones neurológicas durante o después de la infección, asociadas a la replicación viral en el tejido, a la respuesta inmunológica local, a la disfunción endotelial y a signos hemorrágicos en el tejido. En muchos de estos casos se ha detectado virus o anticuerpos en el tejido, sugiriendo la invasión del virus al encéfalo, sin embargo, no siempre es posible hacer esta relación, dando origen a una gran pregunta: ¿son los daños del tejido nervioso producto de una encefalopatía asociada a disfunción extraneural o son debidos a la infección misma del tejido? Como sigue siendo controversial la interpretación de los signos neurológicos durante el dengue, a continuación presentamos algunas generalidades del virus, sus forma clínicas y algunas evidencias clínicas y experimentales que intentan explicar y asociar la neuroinfección y la neuropatogenia por DENV.

Dengue is the most important viral infection transmitted by arthropods in the world. Some studies report that about 10% of dengue or severe dengue patients present neurological symptoms and these signs could be related with nervous system viral replication, immune response and endothelial or metabolic dysfunction in neural or extraneural tissues. These nervous system signs are more frequent in endemic zones and in some patients, viruses or specific antibodies can be detected in the brain, suggesting a direct neural invasion. However, in other cases we cannot establish a direct relationship, begging the question: are the neurological signs and nervous tissue damage secondary to extraneural organ dysfunction or are these changes related to viral replication in the brain? Given the controversy, this review is intended to present some general information on the dengue virus, the clinical characteristics of the disease and current evidence on the neurological manifestations. In addition, we will present experimental evidence to explain the dengue virus neuroinfection and neuropathogenesis.

Prevalência e estudo neuropsicológico de transtornos cognitivos decorrentes de neuroinfecções em hospital de referência / Prevalence and neuropsychology study of cognition diseases in neuroinfections in a reference hospital

JUSTIFICATIVA E OBJETIVOS: Várias doenças infecciosas e parasitárias foram descritas como possíveis causadoras de prejuízos cognitivos, destacando-se as neuroinfecções que, pela localização no sistema nervoso central (SNC), podem evoluir para quadros demenciais francos (embora passíveis de reversão). As vastas possibilidades etiológicas tem como resultado grande heterogeneidade de sintomas neuropsiquiátricos, o que pode dificultar a avaliação clínica, mas se forem utilizados os recursos de testes neuropsicológicos, aumenta-se as probabilidades de detecção de sintomas cognitivos e comportamentais e consequentemente a precisão diagnóstica. O estudo teve como objetivo estimar a prevalência de alterações cognitivas nas neuroinfecções.MÉTODO: A amostra foi composta por 60 pacientes portadores de infecção do SNC no intuito de identificar possíveis alterações do desempenho no Mini-Exame do Estado Mental (MEEM).RESULTADOS: Através da aplicação do MEEM verificou-se que 20 pacientes (33,3%) apresentaram transtornos cognitivos sem demência e 23 pacientes foram diagnosticados com demências, sendo este o quadro neuropsicológico mais prevalente (38,3). CONCLUSÃO: Observou-se alta prevalência de transtornos cognitivos entre os quadros de neuroinfecções, demonstrando a necessidade de investigação de aspectos cognitivos nos pacientes portadores de infecções do SNC.(AU)

BACKGROUND AND OBJECTIVES: Several infectious and parasitics diseases were described as possible causes of cognition losses, mainly neuroinfections, which, due to their location in the CNS, can evolve to dementia (although possible of reversal). The wide etiologic possibilities are a result of a large number of neuropsychiatric symptoms, which may complicate clinical evaluation. However, by using neuropsychological tests, the chances of detecting cognitive and behavioral symptoms are increased as well as precision in diagnosis. The study estimates the prevalence of cognition disorders in neuroinfection.METHOD: We evaluated patients with infection in CNS for identification of possible alterations in Mini Mental State (MMSE).RESULTS: based on MMSE, it was observed that 20 patients (33.3%) presented cognition diseases without dementia, and 23 patients were diagnosed with dementia, which was the most common neuropsychological alteration (38.3%).CONCLUSION: Through this study, high prevalence of cognition disorders was found among neuroinfections, which shows the need of cognitive aspects investigation in infection of the CNS.(AU)

Presentación sistémica de Aspergillus spp con semiología neurológica en un Pastor Alemán: informe de un caso clínico / Systemic presentation of Aspergillus spp with neurological involvement in a German Shepherd: clinical case report

Infections of the central nervous system are uncommon in dogs. Pathogenic fungi such as Aspergillus, Cryptococcus spp, Blastomyces dermatitidis and Coccidioides immitis have been reported. An Aspergillus infection is mainly a respiratory event and very seldom it may become disseminated, the German shepherd seems to be the more prone to this type of aspergillosis specially if an immunological deficiency is present. A 1.5 year old female German Shepherd from Cancun, Quintana Roo, State, in the southeast of Mexico was presented to the small animal hospital, she showed tetraparesis, hiporeflex and deep retarded sensitivity in all four members, loss of sensitivity in the left side of the face, absence of pupil reflex and menace reflex as well as absence of muscular tone of the vulva and anal sphincter. The third day after presentation, she died. At necropsy polyencephalomalace, mielitis and diffuse leucomielitis piogranomalotosus were found. In the cytology of lymph node and other tissues aspergilli like hiphae were observed, this was confirmed by using the highly specific double diffusion test. Then, a PCR test was carried out with tissue fixed in 10% formaldehyde, but it failed probably due to destruction of the DNA.

La infección del sistema nervioso en el perro es poco común; posibles causas son Aspergillus spp, Cryptococcus neoformans, Blastomyces dermatidis y Coccidioides immitis. La infección por Aspergillus spp afecta al aparato respiratorio y en pocas ocasiones se presenta de manera diseminada. Sin embargo, en el Pastor Alemán hay mayor incidencia de éste, pues dicha infección se asocia con una deficiencia inmunológica. Se describe el caso de una perra de raza Pastor Alemán, de 1.5 años de edad, referida de Cancún, Quintana Roo, México, con tetraparesis, hiporreflexia y sensibilidad profunda retardada en los cuatro miembros, disminución de sensibilidad en el lado derecho de la cara y ausencia de reflejo pupilar y de amenaza en ojo derecho; además de ausencia de tono vulvar y de esfínter anal. A los tres días después del ingreso la perra falleció. A la necropsia se encontró polioencefalomalacia, mielitis y leucomielitis piogranulomatosa difusa. En la citología de linfonodo y en la histopatología de diferentes tejidos se identificaron hifas compatibles con Aspergillus spp. Con el fin de dar certeza al diagnóstico, se realizó prueba de doble inmunodifusión, que es altamente específica, la cual confirmó el diagnóstico de Aspergillus spp. Posteriormente se corrió PCR a partir de una muestra de tejido en formalina al 10%, para identificar la especie, en donde no se lograron resultados, probablemente debido a la destrucción del ADN por el formaldehído.

Frequency of depression among patients with neurocysticercosis / Depressão em pacientes portadores de neurocisticercose

Neurocysticercosis (NCC) is a common central nervous system infection caused by Taenia solium metacestodes. Objective: To investigate the occurrence of depression in patients with calcified NCC form. The study group consisted of 114 patients subdivided in four groups: NCC with epilepsy, NCC without epilepsy, epilepsy without NCC and chronic headache. Method: Depression was evaluated and quantified by the Hamilton Rating Scale for Depression (HRSD-21). Results: Percentage of patients with depression was as follows: group 1 (83 percent); group 2 (88 percent); group 3 (92 percent); group 4 (100 percent). The majority of patients had moderate depression. Conclusion: Incidence of depression in all groups was higher than in the general population. It is possible that, in a general way, patients with chronic diseases would have depression with similar intensity. NCC is associated with the presence of depression.

Neurocysticercose (NCC) é uma infecção do sistema nervoso central comum causada por metacestodes da Taenia solium. Objetivo: investigar a ocorrência de depressão nos pacientes com NCC forma calcificada. O grupo de estudo é formado por 114 pacientes subdivididos em quatro grupos: NCC com epilepsia, NCC sem epilepsia, epilepsia sem NCC e cefaléia crônica. Método: A presença de depressão foi determinada e quantificada pela Escala de Depressão de Hamilton (HRSD-21). Resultados: A porcentagem de pacientes com depressão foi: grupo 1 (83 por cento); grupo 2 (88 por cento); grupo 3 (92 por cento); grupo 4 (100 por cento). A maioria dos pacientes apresentou depressão moderada. Conclusão: A incidência da depressão em todos os grupos foi mais elevada do que na população geral, contudo não houve diferença entre os grupos estudados. É possível que, de uma maneira geral, os pacientes portadores de doença crônica apresentarem a depressão em intensidade similar. NCC está associada com a presença de depressão.

Aracnoiditis y encefalitis cortical tuberculosa en un paciente con VIH / Arachnoiditis and tuberculuos cortical encephalitis in an HIV+ patient

La infección por VIH es uno de los mayores factores de riesgo para tuberculosis. Presentamos el caso de un paciente de 30 años que ingresó al hospital con datos neurológicos caracterizados por cefalea, alteración del alerta, crisis convulsivas, signos meníngeos y fiebre, a quien subsecuentemente se le diagnosticó VIH y neuroinfección. Los datos clínicos, el examen del líquido cefalorraquídeo y la neuroimagen sustentaron el diagnóstico de neurotuberculosis. La resonancia magnética de cráneo reveló aracnoiditis generalizada de predominio basal, así como encefalitis cortical. Los hallazgos de imagen desempeñan un papel fundamental en el diagnóstico integral de la tuberculosis del sistema nervioso central.

HIV infection is a major risk factor for tuberculosis. We describe the case of a 30-year-old male presenting with headache, compromised mental status, seizures, neck stiffness and fever that was subsequently diagnosed with HlV and neuroinfection. Clinical data, cerebrospinal fluid and brain imaging supported a diagnosis of neurotuberculosis. Cranial magnetic resonance imaging showed diffuse arachnoidal enhancement, mainly at the basal cisterns and cortical encephalitis. Such imaging findings play a key role in the diagnosis of central nervous system tuberculosis.

Diagnóstico etiológico de Meningitis Bacteriana en lactantes: Hospital “José María Benitez”, La Victoria, Venezuela / Ethiological diagnosis of Bacterial Meningitis among nursing children: “José Maria Benitez” Hospital, La Victoria, Aragua State, Venezuela

Veinticinco pacientes menores de 2 años fueron estudiados en el Hospital “José María Benítez” de La Victoria entre Agosto de 2006 y Mayo de 2007, dada la presencia de meningitis asépticas tratadas como bacterianas. Aunque el diagnóstico inicial fue Neuroinfección, 68% egresaron como Meningitis Bacteriana confirmada con Gram y cultivo del Líquido Cefalo Raquideo, mientras que en el resto sólo se pudo comprobar bacterias por estudios citoquímicos. Estreptococo pneumoneae (44%), Estaphilococo aureus (8%),Neisseria meningitidis, Haemophilus influenzae y Estaphilococo Coagulasa negativo (4%), fueron los de mayor incidencia. Ningún paciente presentó inmunización contra neumococo y 16% no presentaban la vacuna pentavalente. La clínica más relevante fue: Fiebre (100%), irritabilidad (64%), hiporexia (56%) y vómitos (48%). Sólo 16% de los menores presentaron complicaciones. Es necesaria una conducta médica precoz, que realice a menores con fiebre, irritabilidad e hiporexia; Punción Lumbar, estudios citoquímicos, Gram, cultivo y antibiograma, además garantizar prevención, mediante la inclusión de la vacuna contra el Neumococo en el esquema de inmunizaciones del Ministerio del Poder Popular para la Salud Venezolano.

Twenty five under two years old patients were studied in “Jose Maria Benitez” Hospital, La Victoria, between August 2006 and May 2007, in view of several cases of aseptic meningitis treated as bacterial. Although the initial diagnosis was neuro infection, 68% were discharged as Bacterial Meningitis confirmed with Gram and CRL culture. While among the remainders, presence of bacteria was confirmed only by cytochemical tests Strepfococus pneumoneae (44%), Staphilococus aureus (8%), Neisseria meningitides, Haemophilus influenzae and Staphilococus spp., coagulase negative (4%) showed the highest incidence. None of the patients o reported immunization against neumococi and 16% were not immunized with pentavalent vaccine. Most relevant clinical features were: fever (100%); irritability (64%) hyporexia (56%) and vomits (4%). Only 16% of the children developed complications. An earlier and more assertive approach in front of nursing patients with fever, irritability and hyporexia is recommended. Lumbar puncture, cytochemical tests, Gram culture and antibiogram are also suggested. Prevention through application pentavalent vaccine within the normal scheme of inmunizations of the Ministry of Health must be reinforced.

Determinación de las características clínico-epidemiológicas de la neuroinfeccción en pacientes con diagnóstico de VIH/sida en el departamento del Quindío / Determination of clinical and epidemiological features of neuroinfection in patients with diagnosis of HIV-AIDS in the department of Quindío

Objetivo general. Describir las características clínico-epidemiológicas y etiológicas de la neuroinfección de los pacientes con VIH del departamento del Quindío. Materiales y métodos. Se realizó un estudio de tipo descriptivo prospectivo de los pacientes con VIH y sospecha de neuroinfección de una Empresa Social del Estado de tercer nivel de Armenia. En el departamento del Quindío no se han reportado protocolos diagnósticos que correlacionen el costo-beneficio de los diferentes esquemas de manejo pacientes con VIH y una infección asociada del sistema nervioso central. Todos los pacientes que consultaron a la Empresa Social del Estado de tercer nivel de Armenia con dos pruebas positivas de ELISA anti-VIH o una prueba de Western blot positiva, con sospecha de enfermedad del sistema nervioso central concomitante. Se realizaron las siguientes pruebas de laboratorio en líquido cefalorraquídeo: VDRL, determinación de antígeno criptocococico mediante sistemade aglutinación de latex (Cryptococcal Antigen Latex Agglutination System (CALAS) , tinta china, coloraciónde Ziehl-Neelsen, cultivo de hongos, PCR para citomegalovirus y herpes simple, e IgG anti-Toxoplasmasérica; a todos los pacientes se les practicó tomografía cerebral simple. Resultados. De los 21 pacientes estudiados, 85,7 por ciento eran hombres; el rango de edad fue de 23 a 68 años. Los síntomas más frecuentes fueron: fiebre, compromiso de la conciencia u orientación, paresias, parestesias, compromiso de pares craneanos y reflejos neurológicos alterados. El 89 por ciento de pacientes con lesión que ocupa espacio se encontró IgG anti-Toxoplasma positiva (155-887,2UI/ml.) y los valores de los pacientescon reporte de tomografía cerebral simple normal oscilaron entre 13,8 y 36 UI/ml. Discusión. La tomografía cerebral simple, los anticuerpos séricos IgG anti-Toxoplasma y la coloración con tinta china en líquido cefalorraquídeo, permitieron diagnosticar el 85 por ciento de los pacientes.

ABSTRACTObjective: To describe clinical, epidemiologicaland etiological characteristics of neuroinfection inHIV patients from Quindío department. Materialsand methods: A descriptive-prospective studywas carried out in HIV positive patients withneuroinfection suspicion from a third level ESE ofArmenia.In Quindío department have not beenreported diagnostic protocols that correlate thecost-benefit of the various schemes of handlingpatients with HIV infection associated with thecentral nervous system (CNS).All the patients that consulted the third levelESE of Armenia with two positive anti-HIV ELISAtests or positive a Western Blot test with suspicionof concomitant CNS illness.The following laboratory tests were per-formed in cerebrospinal fluid (CSF): VDRL, Chineseink, Ziehl-Nielsen stain, fungi cultures, CMV andHerpes simplex PCR, serum IgG anti-Toxoplasma,andCryptococcal Antigen Latex AgglutinationSystem (CALAS); a simple cerebral CT scan wastaken to all patients. Results: 85.7% of thepatients were men; the age rank was between23 and 68 years. The most frequently foundsymptoms were: fever, consciousness andorientation compromise, paresis, paresthesia,cranial pairs compromise, and altered neurologicalreflexes.89% of the patients with brain spaceoccupying lesionswere IgG anti-Toxoplasmapositive( values between 155 and 887.2 UI/ml) andthe antibodies values in patients without cerebrallesion in the simple cerebral CT scan oscillatedbetween 13.8 and 36 UI/ml. Discussion: Simplecerebral CT scan, serum IgG anti-Toxoplasma andstaining of CSF with Chinese ink allowed the diag-nosis of 85% of the patients