Neurochagas: atualização clínica / Neurochagas: clinical update

A doença de Chagas ainda é uma doença tropical muito prevalente no Brasil. Pode apresentar duas fases (aguda e crônica) e exibe grandes repercussões, sobretudo as que envolvem o sistema nervoso periférico e/ou central. Com o aumento do número de pessoas vivendo em estado (transitório ou permanente) de imunossupressão, os casos de manifestações neurológicas por neurochagas aumentaram, e este tornou-se um importante diagnóstico diferencial com outras doenças oportunistas. Este artigo teve como objetivo revisar os principais aspectos clínicos e terapêuticos da doença de Chagas no sistema nervoso central.

Chagas disease is still a very prevalent tropical disease in Brazil. It can have two phases - acute and chronic ­ and shows major repercussions, especially those involving the peripheral and/ or central nervous system. With the increase in the number of people living in the (transient or permanent) state of immunosuppression the cases of neurological manifestations of Chagas disease increased and this became an important differential diagnosis with other opportunistic diseases. This article aimed to review the main clinical and therapeutic aspects of central nervous system Chagas disease

[Role of viruses in the destruction of the central nervous system and its impact on the multiple sclerosis]

Multiple sclerosis [MS] is a chronic inflammatory immune-mediated disease of the central nervous system. Despite extensive investigations, many aspects of etiology and pathophysiology remain unclear. In multiple sclerosis patients, immune system reacts against autologous proteins in the myelin membrane. Most evidences support the hypothesis that both genetic and environmental factors contribute to disease development. But after the failure of genetic findings to explain the reason for the unequal incidence of MS in identical twins, investigators focused further on environmental factors such as vitamin D deficiency, smoking, living in different latitudes and perhaps the most importantly the role of viruses in people whom are genetically susceptible to MS. There is increasing evidence that viruses may play important role in MS pathogenesis following environmental triggers. Recently, studies focused on the role of herpes virus family, especially Epstein- Barr virus, human herpes virus 6 [HHV-6] and Varicella Zoster virus, as the virus is prevalent in society. This review mainly focused on the identification of important viruses with key role in MS the mechanism behind pathogenesis and describes the animal models of MS. The results of researches are shown strong evidence of the virus or antibodies to viral components in active plaques in MS affected patients, but still cannot be stated with certainty that one or more specific viruses are simultaneously trigger the disease. Further studies are required to prove the pathogenesis of viruses in MS

Modulación de la apoptosis por cytomegalovirus en la perspectiva del sistema nervioso central / Modulation of apoptosis by cytomegalovirus, from the perspective of the central nervous system

Apoptosis is one of the most effective mechanisms against the spread of pathogens such as viruses. However, viruses have developed measures to counter the protective role of apoptosis in infected cells. Cytomegalovirus (CMV) represents the major cause of congenital infection worldwide triggering important damage in the developing central nervous system (CNS). Several mechanisms of apoptosis prevention during CMV infection have been described, among them, viral proteins and RNAs are capable of prevent apoptosis by the intrinsic and extrinsic pathways as well as the one mediated by stress in the endoplasmic reticulum. Nevertheless, the CMV pro-apoptotic effect remains enigmatic and it has been suggested as a bystander effect in non-infected cells. This review summarizes the mechanisms by which CMV modulates the signaling pathways involved in apoptosis. It also includes a brief description of the permissiveness of the CNS to CMV infection and the generated cell death after infection, which may relate to the observed damage during a congenital infection.

La apoptosis representa uno de los mecanismos de defensa más eficaces frente a la propagación de patógenos como lo son los virus. No obstante, éstos han desarrollado medidas para contrarrestar el papel protector de la apoptosis en las células infectadas. Citomegalovirus (CMV) es considerado la principal causa de infecciones congénitas a nivel mundial, afectando de forma importante el sistema nervioso central (SNC) en desarrollo. Diversos mecanismos de prevención de apoptosis durante la infección por CMV han sido descritos, entre los cuales, se encuentran proteínas y ARNs virales capaces de evitar la apoptosis por las vías intrínseca, extrínseca y la mediada por estrés del retículo endoplásmico. Sin embargo, aún representa un enigma el efecto pro-apoptótico de CMV que se sugiere actúe como un efecto espectador sobre las células no infectadas. En el presente trabajo se ofrece una revisión de los mecanismos mediante los cuales CMV modula las vías de señalización involucradas en la apoptosis. Asimismo se incluye una breve descripción de la permisividad del SNC a la infección por CMV y sobre la muerte celular generada tras la infección, que pueden relacionarse con el daño observado durante una infección congénita.

Advances and new insights in the neuropathogenesis of dengue infection / Avanços e novos aspectos na neuropatogênese da dengue

Dengue virus (DENV) infects approximately 390 million persons every year in more than 100 countries. Reports of neurological complications are more frequently. The objective of this narrative review is to bring up the advances in the dengue neuropathogenesis. DENV can access the nervous system through blood-brain barrier disturbance mediated by cytokine. The blood-cerebrospinal fluid (CSF) barrier seems to be also involved, considering the presence of the virus in the CSF of patients with neurological manifestations. As for neurotropism, several studies showed the presence of RNA and viral antigens in brain tissue and CSF in humans. In murine model, different virus mutations were associated to neurovirulence. Despite the advances in the dengue neuropathogenesis, it is still necessary to determine a more appropriate animal model and increase the number of cases of autopsy. The detection of neurovirulence markers may contribute to establish a prognosis, the disease control and vaccine development.

O vírus da dengue (DENV) infecta anualmente cerca de 390 milhões de indivíduos em mais de 100 países. Complicações neurológicas estão se tornando frequentes. O objetivo desta revisão narrativa é abordar os avanços sobre neuropatogênese na dengue. O DENV invade o sistema nervoso central através do distúrbio da barreira hemato-encefálica, mediado por citocina. A barreira hemato-liquórica (LCR) parece também estar envolvida, considerando a presença do vírus no LCR. Estudos demonstraram RNA e antígenos virais no tecido cerebral e LCR de indivíduos infectados pelo DENV, confirmando o neurotropismo viral. Em modelo murino, diferentes mutações virais foram associadas a neurovirulência. Apesar dos avanços no conhecimento da neuropatogênese da dengue, ainda são necessários a determinação de um modelo animal mais adequado e aumento do número de casos de autopsia. A determinação de marcadores de neurovirulência pode contribuir para o estabelecimento de prognóstico, controle da doença e no desenvolvimento de vacina.

Detecção de núcleoproteína-RNA do vírus rábico em diversos órgãos fora do sistema nervoso central de morcegos hematófagos infectados naturalmente / Detection of rabies virus nucleoprotein-RNA in several organs outside the Central Nervous System in naturally-infected vampire bats

Rabies is a neurological disease, but the rabies virus spread to several organs outside the central nervous system (CNS). The rabies virus antigen or RNA has been identified from the salivary glands, the lungs, the kidneys, the heart and the liver. This work aimed to identify the presence of the rabies virus in non-neuronal organs from naturally-infected vampire bats and to study the rabies virus in the salivary glands of healthy vampire bats. Out of the five bats that were positive for rabies in the CNS, by fluorescent antibody test (FAT), viral isolation in N2A cells and reverse transcription - polymerase chain reaction (RT-PCR), 100 percent (5/5) were positive for rabies in samples of the tongue and the heart, 80 percent (4/5) in the kidneys, 40 percent (2/5) in samples of the salivary glands and the lungs, and 20 percent (1/5) in the liver by RT-PCR test. All the nine bats that were negative for rabies in the CNS, by FAT, viral isolation and RT-PCR were negative for rabies in the salivary glands by RT-PCR test. Possible consequences for rabies epidemiology and pathogenesis are discussed in this work.

A raiva é uma doença neurológica, mas o vírus da raiva se dispersa para diversos órgãos fora do sistema nervoso central (SNC). Antígeno ou RNA do vírus da raiva já foram detectados em vários órgãos, tais como glândula salivar, pulmão, rim, coração e fígado. O presente trabalho teve como objetivo identificar a presença do vírus da raiva em órgãos não neuronais de morcegos hematófagos infectados naturalmente, e pesquisar a presença do vírus na glândula salivar de morcegos hematófagos sadios. Dos cinco morcegos positivos para a raiva no SNC pelas técnicas de imunofluorescência direta e isolamento viral em células N2A, 100 por cento (5/5) foram positivos para a raiva nas amostras de língua e coração, 80 por cento (4/5) no rim, 40 por cento (2/5) nas amostras de glândula salivar e pulmão, e 20 por cento (4/5) no fígado pe la técnica de RT-PCR. Todos os nove morcegos negativos no SNC, pela imunofluorescência e isolamento viral, foram negativos na glândula salivar pela RT-PCR. Possíveis consequências para a epidemiologia e patogênese da raiva são discutidas.

Frecuencia de agentes virales en niños con afectación del sistema nervioso central en el estado Zulia, Venezuela: durante el año 2007 / Incidence of viral agents in children with central nervous system affectation in the state of Zulia, Venezuela: during 2007

Diversos virus afectan el sistema nervioso central (SNC) ocasionando encefalitis, principalmente en la edad pediátrica. Determinar la implicación de agentes virales en infecciones del sistema nervioso central (SNC) en niños del estado Zulia, Venezuela durante el año 2007. Se recolectaron 109 muestras de líquido cefalorraquídeo(LCR) y suero, provenientes de pacientes entre 1 día de nacido a 14 años, que presentaron sintomatología clínica sugestiva de afectación del SNC y cuyo estudio bacteriológico convencional de LCR resultó negativo. Se determinó la relación albúmina LCR/suero a fin de descartar contaminación, resultando 24 pares óptimos para la determinación por la técnica de ELISA de anticuerpos IgM específicos para los virus Herpes Simple (VHS), Epstein Barr (VEB), Dengue, Rubéola, Sarampión y Encefalitis Equina Venezolana (EEV). De los 24 casos analizados, 15 (62,5%) resultaron positivos. Los agentes causantes de encefalitis fueron: 11 casos de Dengue (45,8%) (p<0,05), 3 de VHS (12,5%) y un caso de VEB (4,2%). No se detectaron casos de Rubéola, Sarampión, ni EEV. La pleocitocis con predominio de linfocitos fue el hallazgo más frecuente en los casos con encefalitis viral (EV) confirmada, sin diferencias significativas al relacionarlo con el agente viral infectante. Se evidencia que una proporción significativa de los niños con encefalitis es debida a agentes virales y se destaca un incremento en los casos de dengue con afectación del SNC en la región

Various viruses affect the central nervous system (CNS) causing encephalitis, mainly in pediatric patients. To determine the involvement of viral agents for central nervous system (CNS) infections in children in the State of Zulia, Venezuela during the year 2007. 109 samples of cerebrospinal fluid (CSF) and serum were collected from patients between 1 day and 14 years of age, who presented clinical symptoms suggestive of CNS involvement and whose conventional CSF bacteriological study proved negative. The CSF Albumin /serum relation ship was determined in order to rule out contamination, resulting in 24 optimal pairs for determining the IgM and IgG antibodies specific for herpes simplex virus (HSV), Epstein Barr (EBV), Dengue fever, rubella, measles and Venezuelan Equine Encephalitis (VEE) using the ELISA technique. Of the 24 cases examined, 15 (62.5%) were positive. The causative agents for encephalitis were 11 cases of Dengue (45.8%) (p<0.05), 3 VHS (12.5%) and 1 case of EBV (4.2%). There were no cases of rubella, measles or VEE. Pleocytosis with lymphocyte predominance was the most common finding in cases with confirmed viral encephalitis (VE), without significant differences related to the infecting viral agent. Results show that a significant proportion of encephalitis in children is due to viral agents, highlighting an increase in dengue cases with CNS affection in the region

Incidencia del virus herpes simplex en pacientes con infecciones agudas del sistema nervioso central / Incidence of herpes simplex virus infection in patients with acute central nervous system infections

Los Virus Herpes Simple son responsables de una variedad de infecciones a nivel de mucosas bucal y genital, son neurotrópicos, capaces de alojarse en células nerviosas y permanecer latentes con subsecuentes reactivaciones, en algunos casos pueden provocar meningitis y encefalitis. tienen una morbilidad significativa y una mortalidad elevada. El presente estudio tiene como objetivo determinar la incidencia de VHS en la etiología de los síndromes agudos del SNC mediante la detección en suero y LCR de anticuerpos específicos. Se estudiaron 93 muestras pareadas de pacientes con afecciones neurológicas que mostraron resultados negativos en el estudio bacteriológico de LCR y cuya relación Alb-LCR/Alb-suero fue <0,0075. Los anticuerpos fueron detectados por el método de inmunoensayo enzimático Elisa: Enzygnost® anti virus VHS/IgM-IgG (Behring, 1994), donde 1,2% (1/93) de las muestras de suero resultaron positivas para IgM; 89,24% (83/93)de los sueros resultaron positivos para IgG; y 27,39% (20/93) de las muestras de LCR presentaron anti-IgG positivo. La presencia de IgG en LCR sugiere la producción intratecal de estos anticuerpos en el SNC, lo que muestra una participación importante de este agente viral en las infecciones y enfermedades asociadas al SNC

Herpes simplex viruses are agents responsible for a variety of infections on buccal and genital mucosa; they are neurotropic, capable of lodging in the nerve cells and remaining latent with subsequent reactivations; in some cases, they can provoke meningitis and encephalitis; and they have a significant morbidity and are associated with a high mortality. The present project aims to determine HSV’s effect on the etiology of acute central nervous system (CNS) syndromes using the detection of specific antibodies in serum and cerebrospinal fluid. The 93 paired samples from patients with neurological affectations studied demonstrated negative results in the LCR bacteriological study and their Alb-LCR/Alb-serum relation was < 0.0075. Antibodies were detected by the enzymatic immunoassay ELISA method, where 1.2% (1/93) of the serum samples turned out positive for IgM; 89.24% (83/93) of the serum samples resulted positive for IgG; and 27.39% (20/93) of LCR samples were positive for anti-IgG. IgG presence in LCR suggested the intrathecal production of these antibodies inside the CNS, which demonstrates a significant participation by this viral agent in infections and diseases associated with the CNS

CNS involvement by novel influenza virus type A [H1N1], the first report from Iran

This is the first report of CNS involvement by the new influenza virus [influenza A [H1N1] in Iran. The patient was a 10-year-old boy with chief complaints of fever, malaise, and cranial nerve involvement, resulting in respiratory muscle paralysis and intubation. This shows that the new influenza virus, as well as the seasonal flu, can cause neurologic complications; however, the severity of the signs and symptoms is less and the disease may resolve without complications in the case of seasonal flu. Therefore, in each patient with neurological involvement and typical influenza signs and symptoms or a flu-like syndrome, diagnostic tests for H1N1 flu virus should be considered, especially during epidemics, and treatment with oseltamivir should be started

BVDV induced gastro-neuropathy outbreak in a feedlot calves around Tehran [Iran]

An outbreak of a lethal disease was reported in 4-6-month-old Holstein calves in a feedlot around Tehran. The signs of central nervous system and gastrointestinal system [GI] involvement were observed in the diseased animals. Necropsy samples of GI, liver, kidney, spleen and lung from 3 died animals were prepared for histopathological examination. Blood and formalin-fixed ear notch samples of 6 calves were submitted for RT-PCR, antigen-capture ELISA [ACE] and immunohistochemistry [IHC] for the detection of BVDV. The results of ACE on buffy coats were negative but RT-PCR of all 6 cases and IHC of 4 cases were positive for BVDV infection. Based on the clinical signs and pathological findings in the GI system and brain, we strongly suggest that the BVDV may represent a gastro-neuropathogen strain. To the best of our knowledge, this is the first outbreak of gastro-neuropathogenic BVDV infection in Iran, which may be acquired postnatally

Hallazgos patológicos en cerdos afectados con el síndrome del desmedro multisistémico postdestete de la República Argentina / Pathological findings in pigs affected by the postweaning multisystemic wasting syndrome in Argentina

El síndrome del desmedro multisistémico postdestete (PMWS) fue descrito por primera vez en Canadá en el año 1991 y desde entonces un número creciente de casos han sido diagnosticados en todo el mundo. En la Argentina, el PMWS fue reportado por primera vez recientemente. Se estudiaron 48 cerdos de 5 a 12 semanas de edad con signos característicos de PMWS procedentes de 19 granjas. Si bien se desconoce la distribución real del virus en nuestro país se observó desde el año 2001 un número creciente de granjas con PMWS y distribuidas en las principales provincias productoras. La histopatología fue una herramienta diagnóstica importante en casos sospechosos de PMWS con la observación de diferentes grados de lesión. En los animales estudiados las infecciones secundarias pudieron ser importantes, ya sea por patógenos oportunistas o por complicaciones bacterianas.

Postweaning multisystemic wasting syndrome was first described in Canada in 1991 and at present an increasing number of cases has been diagnosed worldwide. In Argentina the first cases of PMWS were reported recently. Forty eight 5 to 12 week old pigs with signs characteristic of PMWS from 19 farms were studied. Although the real distribution of the virus in our country is not known it was observed an increasing number of farms with PMWS distributed in the major producing provinces. The histopathology was an important tool in diagnosis of suspicious cases of PMWS with the observation of different degrees of lesion. In the studied animals, the secondary infections, either by opportunistic pathogens or secondary bacteria could be important.

Immune mechanisms of Theiler's virus-induced demyelination

No abstract available.

Involvement of the central nervous system in dengue fever: three serologically confirmed cases from Fortaleza, Ceara, Brazil

Neste trabalho säo descritos tres casos de dengue com manifestaçöes neurológicas incomuns durante a epidemia de dengue em Fortaleza, Estado do Ceará, em 1994. Todos os pacientes eram do sexo feminino. A paciente do primeiro caso tinha 17 anos e apresentou além da sindrome febril, sinais de comprometimento meningeo com rigidez de nuca, e sangramento genital. No segundo caso a paciente de 86 anos apresentou quadro febril, intensa dor muscular e articular, alteraçöes da consciencia, desmaio, rigidez de nuca e meningismo. A terceira, de 67 anos, teve um quadro inicial de sindrome febril, seguido de comportamento anormal, tremores de extremidades, trombocitopenia, hematocrito aumentado, leucopenia, hipotensäo arterial e choque, evoluindo para obito...

Neural spread of Junin virus in intraperitoneally inoculated rats

Una vez establecida la ruta neural como la seguida por el virus Junín (VJ) a partir de su inoculación intradérmica en ratas lactantes, resultaba de interes determinar cuál era la vía adoptada luego de inoculado intraperitonealmente. Desde la 2da semana se evidenció una enfermedad neurológica que a los 30 días post-infección alcanzó un 84 por ciento de mortalidad. En curso de ese período, se efectuaron cosechas de tejidos extraneurales y neurales para la marcación por inmunoperoxidasa del antígenos viral y el examen histopatológico, asi como la titulación de infectividad que también se extendió a sangre. En todas las muestras de tejido en que se detectó virus infectivo, sea por cocultivo o por aislamiento convencional, se logró la marcación del antígeno viral. El VJ estuvo presente en valores mínimos en bazo e hígado desde el día 2 al 5, y en sangre del 5 al 15. En tejidos neurales, el antígeno viral fue inicialmente revelado al día 5, tanto en ganglios raquídeos torácicos como en los segmentos medulares relacionados. A partir del día 7, la positividad se extendió a la médula espinal en toda su extensión; a la vez, ya había evidencias de presencia viral en tronco cerebral, con disfusión al resto de estructuras encefálicas desde el día 10. Pese a la presencia masiva del antígeno viral en neuromas, dichas células no mostraban cambios morfológicos aparentes. Dado que la infección de ganglios raquídeos y de médula espinal invariablemente precedió al acesso viral a encéfalo, y ello ocurrió en forma concomitante a la desaparición del virus en órganos linfo-reticulares y en sangre, la vía neural parece ser la adoptada por el VJ desde cavidad peritoneal hasta sistema nervioso central