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Background Recent studies have focused on the relationship between human herpesvirus 6 (HHV-6) and multiple sclerosis (MS). Objective To analyze HHV-6 messenger RNA expression in patients with relapsing-remitting (RR) MS vs healthy blood donors (HBDs). Design One hundred fifty-four subjects were enrolled in the study: 105 patients with RRMS (32 in relapse) and 49 HBDs. Total DNA and messenger RNA were extracted from serum and blood samples, respectively, and analyzed by quantitative real-time reverse transcription0dash;polymerase chain reaction for the detection of 3 HHV-6 immediate-early genes (U16/U17,U89/U90, and U94) and both HHV-6 variants (HHV-6A and HHV-6B). Results Active HHV-6 infection was detected in 16% of patients with RRMS vs 0% of HBDs (P = .003). Seven patients with RRMS with exacerbation had HHV-6 active replication, and the virus remained latent in only 1 of them. We did not find any statistically significant difference between HHV-6 active or latent infection for patients in remission (P = .12). Among patients with RRMS with HHV-6 active replication, viral load was higher when they experienced an acute attack than when in remission (P = .04). In those patients with RRMS who had an active infection only, HHV-6A was found. Cell-free HHV-6 DNA detected in serum samples confirmed the results. Conclusions The results show that a subset of patients with RRMS experience HHV-6 active infection, and there likely is an association between the viral active replication and relapses; therefore, HHV-6 active infection may imply a greater risk of exacerbations in a subgroup of patients with RRMS. [ABSTRACT FROM AUTHOR]

Background Herpes simplex virus 2 (HSV-2) and HSV-1 have been recognized as causes of recurrent aseptic lymphocytic meningitis (RALM). However, the role of other herpesviruses has not been systematically assessed. Objectives To evaluate the cause of RALM by using polymerase chain reaction (PCR) tests detecting varicella-zoster virus (VZV), cytomegalovirus (CMV), or human herpesvirus 6 (HHV-6), in addition to HSV, on cerebrospinal fluid (CSF) samples; and to assess the utility of PCR and antibody analyses in consecutive episodes of RALM. Design The PCR and antibody results for herpesviruses were analyzed from 14 patients having 48 episodes of RALM. Results The CSF PCR results for VZV, CMV, and HHV-6 were negative in 12, 10, and 11 patients investigated, respectively, and antibodies against VZV, CMV, and HHV-6 showed only old immunity. Herpes simplex virus 2 was detected from the CSF in 10 patients, and HSV-1 in 1 patient. In 6 of these 11 patients, the HSV PCR result was positive in more than one disease episode. A significant increase of serum antibodies for HSV was seen in only 1 of 15 episodes examined. An intrathecal antibody response to HSV was not recognized in 9 episodes investigated in these 11 patients. Conclusions We could not find evidence of VZV, CMV, or HHV-6 in the pathogenesis of RALM, although most patients were previously infected by those viruses. Herpes simplex virus 2 was detected from the CSF in most patients, and often repeatedly, which further confirms the role of this virus in RALM. The causative diagnosis was obtained only by PCR, whereas antibody analysis was not clinically useful. [ABSTRACT FROM AUTHOR]

Background: Anticonvulsant hypersensitivity syndrome (AHS) is a life-threatening, drug-induced, multiorgan system reaction. The identification of predisposing factors is clearly needed to predict the incidence and outcome of AHS; attention has recently been focused on reactivation of human herpesvirus 6 (HHV-6). Objective: To determine whether immunosuppressive conditions that can allow HHV-6 reactivation could be specifically detected in association with the onset of AHS. Design: We analyzed patients with AHS who were treated during 1997-2002. Two groups of patients receiving anticonvulsants served as controls. Setting: Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan. Patients: Ten patients with AHS. Main Outcome Measures: The results of serologic tests for antibody titers for various viruses, including HHV-6, HHV-6 DNA detection by real-time polymerase chain reaction, immunoglobulin levels by turbidimetric immunoassay, IgG subclass levels by nephelometry, and CD19[sup +] B-cell counts by flow cytometric analysis, were sequentially assessed. Results: Serum IgG levels (mean, 745 mg/dL) and circulating B-cell counts (mean, 88/µL) in patients with AHS were significantly decreased at onset compared with control groups (P<.001 and P = .007, respectively). These alterations returned to normal on full recovery. Reactivation of HHV-6 as judged by a greater than 4-fold increase in HHV-6 IgG titers was exclusively detected in most patients with AHS associated with decreased IgG levels and B-cell counts. Conclusions: A decrease in immunoglobulin levels and B-cell counts can be associated with HHV-6 reactivation and the subsequent onset of AHS. These immunological alterations might be a useful predictor of the development of AHS. [ABSTRACT FROM AUTHOR]

Drug Hypersensitivity Syndrome (DHS) can be defined as the clinical triad of fever, rash and internal organ involvement due to drug exposure. The article suggests the role of human herpesvirus (HHV) reactivation as a possible etiological factor in DHS. Although HHV occurs at the time of onset of DHS, yet its causal role in the pathogenesis of DHS remains to be demonstrated. The findings support that the pathogenesis of DHS is likely to involve a complex interaction of many factors and drug alone cannot cause DHS.

The etiology of the most common intraoral mucosal disease, recurrent aphthous ulceration (RAU), remains obscure. Here, attempts were made to diagnose reactivation of varicella zoster (VZV), cytomegalovirus (CMV), Epstein-Barr (EBV) and human hepes virus 6 (HHV-6) infections from paired sera in association with RAU recurrences. The first sample was obtained within 3 days after a new recurrence (1) and the second 10-14 days later (2). The study initially comprised 18 otherwise healthy RAU patients (gr A) and 17 sex- and age-matched healthy non-RAU individuals. Values of specific antibody subclasses (IgM, IgG, IgA) were determined by ELISA (VZV, CMV, EBV) and IFA (HHV-6). Patients and controls exhibited differences in parameters on specific VZV IgM and CMV IgM. In order to substantiate these findings, specific VZV IgM and CMV IgM were subsequently also evaluated in 17 other RAU patients (gr B). Ten patients in gr A and 11 in gr B were IgM seropositive for either VZV and/or CMV in at least one of the serum samples, whereas in the controls only one was VZV IgM positive and none CMV IgM positive. Evaluated as groups, optometric density (OD) antibody levels of VZV IgM were significantly higher in the patients (gr A (1,2) vs controls: p < 0.0001; gr B (1,2) vs controls: p < 0.001). CMV OD IgM antibody values were significantly higher in gr B only (1,2 vs controls: p < 0.01). The study lends support for reactivation of VZV and/or CMV infection associated with RAU recurrences. [ABSTRACT FROM AUTHOR]

Presents the autoimmune etiology of viral pathogens in multiple sclerosis. Impact of existence on the first instances of murine central nervous system (CNS) diseases; Virological cause of the CNS disease; Complications of the disease.