RESUMO
Optic neuritis (ON) is a condition involving primary inflammation, demyelination, and axonal injury in the optic nerve which leads to retinal ganglion cell (RGC) loss, and visual dysfunction. We investigated the ability of a single microinjection of bacterial lipopolysaccharide (LPS) directly into the optic nerve to induce functional and structural alterations compatible with ON. For this purpose, optic nerves from male Wistar rats remained intact or were injected with vehicle or LPS. The effect of LPS was evaluated at several time points post-injection in terms of: i) visual pathway and retinal function (visual evoked potentials (VEPs) and electroretinograms, (ERGs), respectively), ii) anterograde transport from the retina to its projection areas, iii) consensual pupil light reflex (PLR), iv) optic nerve histology, v) microglia/macrophage reactivity (by Iba-1- and ED1-immunostaining), vi) astrocyte reactivity (by glial fibrillary acid protein-immunostaining), vii) axon number (by toluidine blue staining), vii) demyelination (by myelin basic protein immunoreactivity and luxol fast blue staining), viii) optic nerve ultrastructure, and ix) RGC number (by Brn3a immunoreactivity). LPS induced a significant and persistent decrease in VEP amplitude and PLR, without changes in the ERG. In addition, LPS induced a deficit in anterograde transport, and an early inflammatory response consisting in an increased cellularity, and Iba-1 and ED1-immunoreactivity in the optic nerve, which were followed by changes in axonal density, astrocytosis, demyelination, and axon and RGC loss. These results suggest that the microinjection of LPS into the optic nerve may serve as a new experimental model of primary ON.
Assuntos
Lipopolissacarídeos , Nervo Óptico/patologia , Neurite Óptica/induzido quimicamente , Neurite Óptica/patologia , Animais , Toxina da Cólera/metabolismo , Modelos Animais de Doenças , Eletrorretinografia , Potenciais Evocados Visuais/efeitos dos fármacos , Contagem de Leucócitos , Lipopolissacarídeos/administração & dosagem , Masculino , Microinjeções , Neurite Óptica/líquido cefalorraquidiano , Ratos , Ratos Wistar , Reflexo Pupilar/efeitos dos fármacos , Retina/patologiaRESUMO
BACKGROUND: Dengue infection is caused by a flavivirus, with 4 virus serotypes (types 1 to 4). The serotypes 2 and 3 represent the principal agents related to nervous system involvement. Neurologic involvement occurs in 4%-5% of dengue infection cases. The major mechanisms of the disease may be related to direct viral infection or postinfectious autoimmune process. The detection of intrathecal synthesis of specific antibodies has been used to support neurologic diagnosis as a proof of local reaction. It may be quantitatively calculated by the specific antibody index. OBJECTIVES: To determine if patients with neurologic manifestations associated with dengue produce specific antibodies in the CNS and to determine the antibodies' clinical and pathophysiologic relevance. METHODS: CSF and serum were evaluated for dengue immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies by ELISA and for intrathecal synthesis of IgG antibodies to the dengue virus. Subjects included 10 patients IgM seropositive for dengue virus diagnosed with myelitis, encephalitis, optic neuromyelitis, or Guillain-Barré syndrome. RESULTS: All patients had IgG and IgM antibodies to dengue virus in their sera; 7 were IgM positive and 9 were IgG positive for dengue virus in CSF. Only the 3 patients with myelitis had intrathecal synthesis of specific IgG antibodies. CONCLUSIONS: Intrathecal synthesis of antibodies to dengue virus occurs in the CNS. It may be used as a marker of myelitis associated with dengue, and it seems to be related to the pathogenesis of spinal cord disease due to direct viral invasion.
Assuntos
Anticorpos Antivirais/líquido cefalorraquidiano , Vírus da Dengue/imunologia , Dengue/imunologia , Encefalite Viral/imunologia , Síndrome de Guillain-Barré/imunologia , Mielite/imunologia , Neurite Óptica/imunologia , Adulto , Idoso , Anticorpos Antivirais/sangue , Dengue/sangue , Dengue/líquido cefalorraquidiano , Encefalite Viral/sangue , Encefalite Viral/líquido cefalorraquidiano , Ensaio de Imunoadsorção Enzimática , Feminino , Síndrome de Guillain-Barré/sangue , Síndrome de Guillain-Barré/líquido cefalorraquidiano , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulina M/sangue , Imunoglobulina M/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Mielite/sangue , Mielite/líquido cefalorraquidiano , Neurite Óptica/sangue , Neurite Óptica/líquido cefalorraquidiano , Estudos Retrospectivos , Adulto JovemAssuntos
Herpesviridae/isolamento & purificação , Mielite/líquido cefalorraquidiano , Neurite Óptica/líquido cefalorraquidiano , Anticorpos Antivirais/análise , Líquido Cefalorraquidiano/virologia , Cuba/epidemiologia , Herpesviridae/imunologia , Humanos , Mielite/epidemiologia , Mielite/virologia , Neurite Óptica/epidemiologia , Neurite Óptica/virologia , PrevalênciaRESUMO
BACKGROUND: A mysterious disease spread over Cuba from 1991 to 1993, the cause of which has not been fully established. Major symptoms were the same in patients with the Cuban disease as in patients with subacute myelo-optico-neuropathy (SMON), which had occurred in Japan nearly 30 years ago and from which Inoue-Melnick virus (IMV) type 1 was first isolated. We investigated the presence of IMV in cerebrospinal fluid samples of patients with this epidemic neuropathy in Cuba. METHODS: The established method for detecting IMV in MRC-5 fibroblasts was used throughout the study, which was conducted in two independent laboratories, one in Buffalo, NY, and the other in Kyoto, Japan. The cerebrospinal fluid samples of 20 patients and four controls were provided by Cuban researchers. RESULTS: All cerebrospinal fluid specimens from 20 Cuban patients tested were positive for IMV type 2 (100%), and four cerebrospinal fluid specimens from Cuban controls were negative for IMV (0%). These clear-cut results were identical in both laboratories. CONCLUSION: Our study indicates an important association of IMV type 2 with patients of this Cuban epidemic. The etiologic role of IMV type 2 in the epidemic neuropathy in Cuba, along with weak cytopathic effect viruses isolated by the Cuban group, remains to be elucidated.
Assuntos
Herpesviridae/isolamento & purificação , Mielite/líquido cefalorraquidiano , Neurite Óptica/líquido cefalorraquidiano , Animais , Anticorpos Antivirais/análise , Linhagem Celular , Líquido Cefalorraquidiano/virologia , Cuba/epidemiologia , Surtos de Doenças , Fibroblastos , Herpesviridae/imunologia , Humanos , Mielite/epidemiologia , Mielite/virologia , Testes de Neutralização , Neurite Óptica/epidemiologia , Neurite Óptica/virologia , Prevalência , Coelhos , SíndromeRESUMO
OBJECTIVE: To investigate the possibility of a viral agent in the central nervous system of patients with epidemic neuropathy. DESIGN: Virus isolation attempts, in cell cultures and suckling mice, from cerebrospinal fluid (CSF) of neuropathy patients and controls undergoing lumbar puncture for unrelated reasons. Serologic studies in patients, contacts, and controls. SETTING: An epidemic of optic and peripheral neuropathy affected more than 50,000 people in Cuba in 1991 through 1993. Illness was associated with dietary limitations and increased physical demands accompanying the shortages of food and fuel experienced in Cuba since 1989. Most patients responded to parenteral vitamin therapy, and the epidemic began to subside when oral vitamin supplementation was begun for the entire Cuban population. RESULTS: Coxsackievirus A9 (five isolates) and a similar, less cytopathic virus (100 isolates) were recovered from 105 (84%) of 125 CSF specimens from neuropathy patients. The strains with light cytopathic effect were antigenically related to Coxsackieviruses A9 and B4 by cross-neutralization and immunoblotting assays. Virus persisted in CSF of some patients for 1 to 12 months. Cerebrospinal fluid from patients and both types of virus from cell culture produced illness, including complete posterior flaccid paralysis, in newborn mice, and virus was reisolated from the mice. Mouse tissues and sural nerve biopsy specimens from patients were stained by immunoperoxidase and colloidal gold techniques using hyperimmune rabbit antisera against the virus with light cytopathic effect. CONCLUSIONS: Coxsackievirus A9 or an antigenically related agent with a light cytopathic effect was present in CSF of 84% of 125 patients with epidemic neuropathy. The role of these agents, probably in combination with nutritional factors, in the pathophysiology of the disease requires further investigation.
Assuntos
Infecções por Coxsackievirus/etiologia , Surtos de Doenças , Enterovirus/isolamento & purificação , Neurite Óptica/virologia , Doenças do Sistema Nervoso Periférico/virologia , Adulto , Animais , Animais Lactentes/virologia , Anticorpos Antivirais/análise , Antígenos Virais/análise , Técnicas de Cultura de Células , Líquido Cefalorraquidiano/virologia , Chlorocebus aethiops , Infecções por Coxsackievirus/líquido cefalorraquidiano , Infecções por Coxsackievirus/epidemiologia , Infecções por Coxsackievirus/patologia , Cuba/epidemiologia , Efeito Citopatogênico Viral , Enterovirus/imunologia , Enterovirus/patogenicidade , Feminino , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Neurite Óptica/líquido cefalorraquidiano , Neurite Óptica/epidemiologia , Neurite Óptica/patologia , Sistema Nervoso Periférico/patologia , Sistema Nervoso Periférico/virologia , Doenças do Sistema Nervoso Periférico/líquido cefalorraquidiano , Doenças do Sistema Nervoso Periférico/epidemiologia , Doenças do Sistema Nervoso Periférico/patologia , Coelhos , Células Vero/virologiaRESUMO
We report a partially retrospective and longitudinal study of patients with optic neuritis (ON) that developed multiple sclerosis (MS). We assessed clinical features or factors that might differentiate these patients from those with ON that did not develop MS. Of the cases followed, 110 (67%) were found to have an idiopathic origin of the disease; whereas 55 (33%) were found to develop it secondary to another disease. Of the 110 idiopathic cases, 13 (12%), developed MS over an average of 2 years. The results of these patients in the laboratory analyses of blood and CSF as well as the results of the MRI and evoked potential studies, were significantly different from the ON patients without MS. We conclude that the percentage of patients with ON in our sample that developed MS is similar to that found in Japan and is relatively low in comparison to other reports.
Assuntos
Esclerose Múltipla/fisiopatologia , Neurite Óptica/fisiopatologia , Adulto , Diagnóstico Diferencial , Progressão da Doença , Potenciais Evocados Visuais , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , México , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico , Neurite Óptica/sangue , Neurite Óptica/líquido cefalorraquidiano , Neurite Óptica/etiologia , Neurite Óptica/patologia , Estudos RetrospectivosRESUMO
Three pediatric patients with Cuban epidemic neuropathy were studied. Cerebrospinal fluid and sera were simultaneously obtained. Albumin and IgG were quantified by immunodifusion. Albumin quotient and local synthesis of IgG were calculated by Reibert/Felgenhauer formula. A patient with optic neuritis had a dysfunction of the blood-cerebrospinal fluid barrier. All the group had local synthesis of IgG.
Assuntos
Humanos , Masculino , Feminino , Criança , Doenças do Sistema Nervoso Periférico/sangue , Imunoglobulina G/biossíntese , Neurite Óptica/sangue , Albumina Sérica/análise , Cuba , Doenças do Sistema Nervoso Periférico/líquido cefalorraquidiano , Imunoglobulina G/análise , Imunoglobulina G/líquido cefalorraquidiano , Neurite Óptica/diagnóstico , Neurite Óptica/líquido cefalorraquidianoRESUMO
Desde finales de 1991 junio de 1993 se produjo la epidemia de neuropatia que afecto a 50 963 personas. Se presentaron 2 formas clinicas de la enfermedad: la forma optica (con o sin manifestaciones perifericas, 52 por ciento de los casos) y la periferica (48 por ciento). Los estudios epidemiologicos pusieron de manifiesto trastornos nutricionales, fundamentalmente deficit de vitaminas del complejo B dados por las dificultades economicas del pais en el "periodo especial". Se identificaron el habito de fumar y la ingestion de bebidas alcoholicas como factores de riesgo, en particular para las formas mas severas de la enfermedad. En los estudios virologicos de liquido cefalorraquideo (LCR) se obtuvo aislamiento en celulas Vero de virus Coxsackie A9 en el 4 por ciento y de otro agente de efecto citopatogenico ligero en el 80 por ciento de las muestras. El 67 por ciento de las muestras de LCR inoculadas en ratones lactantes produjo enfermedad o muerte de los animales. Se comprobo la persistencia viral en el LCR por un tiempo de al menos 21 dias en un grupo de pacientes y de 1 ano en otro
Assuntos
Humanos , Camundongos , Consumo de Bebidas Alcoólicas , Enterovirus/isolamento & purificação , Neurite Óptica/líquido cefalorraquidiano , Neurite (Inflamação)/líquido cefalorraquidiano , Distúrbios Nutricionais , Fumar , Células Vero , Deficiência de Vitaminas do Complexo B , CubaRESUMO
Se realizaron determinaciones de anticuerpos neutralizantes en sueros de pacientes con neuropatia epidemica y de grupos de personas aparentemente sanas, a la cepa 47/93 IPK (CA9) y la 590 productora de efecto citopatico ligero (ECP-L), asi como a las cepas de referencia de CA9 y CB1-6, por la tecnica de microneutralizacion. Los enfermos y sus contactos mostraron porcentajes significativamente superiores de anticuerpos neutralizantes a la cepa 47-93 que el grupo considerado control y los residentes en municipios de baja tasa de la enfermedad. Esta diferencia tambien se comprobo en los titulos promedio geometrico (TPG) con las cepas de referencia de CA9 y CB2-4. Se comprobo un incremento de la circulacion de la cepa 47/93 en la poblacion infantil desde 1981 a 1993. Los enfermos mostraron porcentajes y TPG significativamente menores de anticuerpos neutralizantes a la cepa 590 que el grupo control, a pesar de que en 25/28 se habian aislados agentes con ECP-L. Se plantea la posibilidad de 2 mecanismos de neutralizacion y se formula una hipotesis sobre el mecanismo por el cual estos virus puedan participar en la fisiopatologia de la enfermedad
Assuntos
Humanos , Efeito Citopatogênico Viral , Enterovirus/isolamento & purificação , Neurite Óptica/líquido cefalorraquidiano , Neurite Óptica/sangue , Neurite (Inflamação)/sangue , Neurite (Inflamação)/líquido cefalorraquidiano , Células Vero , CubaRESUMO
En el presente trabajo se reportan las caracteristicas fisico-quimicas presentadas por los agentes aislados con muestras de pacientes con neuropatia epidemica. Los Enterovirus aislados se comportaron en la forma descrita para estos virus. Los agentes productores de efecto citopatico ligero (ECP-L) se comportaron en forma variable en lo que se refiere a la sensibilidad al cloroformo, por otra parte no fueron sensibles al acido fosfonoacetico (PAA) ni al cloruro de guanidina (GHCl) y crecieron en celulas previamente tratadas con bromodeoxiuridina (BDUR). Estos resultaron sugirieron la presencia de 2 agentes que recuerdan a los Enterovirus y a virus envueltos. Se necesita continuar profundizando en los estudios de caracterizacion de estos agentes