Neurologic dengue manifestations associated with intrathecal specific immune response.

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.

[Viral agents in patients with infectious processes of the central nervous system]. / Agentes virales en pacientes con procesos infecciosos del Sistema Nervioso Central.

Local statistics report a great number of cases of neurological diseases of unidentified cause. The purpose of this research was to determine the presence of viral agents in patients with affection of the central nervous system, in Zulia State, Venezuela. In different health centers throughout the state, we collected 129 randomized samples of cerebrospinal fluid (CSF) and serum from patients ranging from 1 day to 41 years of age, showing symptoms of CNS disease and whose bacteriological test resulted negative. The serum/CSF albumin ratio was determined to exclude contaminated CSF samples, thus 54 optimal samples were obtained for the research. We determined serum IgM and CSF IgG specific for Venezuelan equine encephalomyelitis (VEE), Herpes simplex (HSV), Epstein Barr (EBV), Dengue, Rubella and Measles virus, through ELISA and indirect immunofluorescence techniques. Of the 54 samples studied, 33 (61.11%) were positive. %). The etiological agents implicated were VEE 14 cases (42.42%); HSV 11 cases (33.33%); EBV 5 cases (15.15%) and Dengue 3 cases (9.09%). We did not detect Rubella o Measles. Regarding the age distribution, the most affected group was that of children under 12 (83.34%). We analyzed the clinical manifestations and the CSF characteristics and did not find differences suggestive of an specific etiological diagnosis, even though certain signs could be considered early indications of CNS alterations due to viral causes. Our study shows that a large percentage of CNS affections of unknown etiology are produced by viral agents, indicating that in our region, most of this cases are not registered.

[Viral meningoencephalitis caused by enterovirus in Cuba from 1990-1995]. / Meningoencefalitis virales por enterovirus en Cuba en el período 1990-1995.

The results of a study on enterovirus as causal agents of viral meningoencephalitis from 1990 to 1995 are described. From the 1458 samples of patients studied, 586 were from feces, 108 from cerebrospinal fluid and 1095 were paired sera. The samples for viral isolation were inoculated in two different cellular systems. A total of 225 samples (32.42%) were found to be positive; the highest number of isolations (n = 217) was found in feces and in diploid human lung fibroblast cells (PHuE-1). Antibody determination were carried out using neutralization by micromethod test with 10 enterovirus antigens (Echovirus 4, 6, 9, 11 and Coxsackievirus B1-6). The isolated virus was also used as antigen during epidemic periods. There were 3 epidemic outbreaks: Coxsackievirus A9 (1990-1991), Echovirus 30 (1994), and Coxsackievirus B5 (1995). Coxsackievirus A9 and Echovirus 30 have been related to viral meningoencephalitis epidemics in Cuba since 1970. In paired sera 66.84% were positive, Echovirus 6 and 11 exhibited higher positivity. When positive results by isolation and serology were considered together, more than 80% of the studied cases were associated to enterovirus infection. These results show the importance of enteroviruses as cause of viral meningoencephalitis in our country.