Fatal encephalitis/encephalopathy in primary human herpesvirus-6 infection.

Asano, Yoshizo; Yoshikawa, Tetsushi; Kajita, Yoshihiro; Ogura, R; Suga, S.; Yazaki, Takehiko; Nakashima, Toshihiko; Yamada, Akira; Kurata, Takeshi

doi:10.1136/adc.67.12.1484

Cited by 150 publications

(73 citation statements)

References 5 publications

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“…RI may be complicated by seizures, encephalopathy, aseptic meningitis, meningoencephalitis, and hemiplegia. 8 -11 There have also been case reports of HHV-6 associated with aseptic meningoencephalitis, [12][13][14][15] encephalitis, 16 and transverse myelitis. 17 Finally, tropism for glial cells, 18 glioblastoma cells, 19 and human fetal astrocytes 20 has been demonstrated using in vitro culture systems.…”

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confidence: 99%

Case-Control Study of Primary Human Herpesvirus 6 Infection in Children With Febrile Seizures

Hukin

Farrell²,

MacWilliam

et al. 1998

PEDIATRICS

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ABSTRACT. Rationale. Human herpesvirus 6 (HHV-6) has been demonstrated to be the causative agent in roseola infantum. It has been suggested that HHV-6 may have neurotropic properties and be involved in the pathogenesis of febrile seizures in infants. We describe a case-control study to examine the hypothesis that acute HHV-6 infection occurs more commonly in children with febrile seizures than in controls.Methods. Patients presenting with a first or second febrile seizure between 6 months and 2 years of age were entered in the study. Control patients did not have a seizure but had similar inclusion and exclusion criteria. Specimens were obtained for HHV-6 viral serology and polymerase chain reaction in the acute stage and approximately 2 weeks later. A diagnosis of HHV-6 infection was based on HHV-6-specific IgM and IgG serology and HHV-6 polymerase chain reaction of peripheral blood mononuclear cells and saliva.Results. Eighty-six patients (45 with febrile seizures; 41 controls) were enrolled. The HHV-6 infection status could be determined in only 68 patients (35 with febrile seizures; 33 controls). Acute HHV-6 infection was identified in 15 of 35 febrile seizure patients and in 15 of 33 controls. Evidence of past HHV-6 infection was demonstrated in 13 febrile seizure patients and in 8 controls.Conclusions. The incidence of primary HHV-6 infection is similar in patients with febrile seizures and agematched controls. HHV-6 does not seem to be a major factor in the pathogenesis of first and second febrile seizures. Pediatrics 1998;101(2). URL: http://www. pediatrics.org/cgi/content/full/101/2/e3; human herpesvirus 6, febrile seizures, case-control.ABBREVIATIONS. HHV-6, human herpesvirus 6; RI, roseola infantum; CSF, cerebrospinal fluid; PCR, polymerase chain reaction; PBMN, peripheral blood mononuclear cells; HSV, herpes simplex virus; CMV, cytomegalovirus; EBV, Epstein-Barr virus; ELISA, enzyme-linked immunosorbent assay; IFA, immunofluorescent assay. H uman herpesvirus 6 (HHV-6), a lymphotropic virus, is the causative agent of roseola infantum (RI).1,2 HHV-6 infection is more often associated with a nonspecific febrile illness between 6 months and 2 years of life.3 Seroprevalence studies in Japan, England, and the United States demonstrate that infection with HHV-6 is common.4 -6 HHV-6-specific IgG can be detected in almost all newborns, but the prevalence declines to less than 10% by 4 to 5 months of age, presumably as maternal antibody wanes. 4 The seroprevalence increases to 65% by 1 year of age 6 and to greater than 90% by 13 to 36 months of age. 4,6,7 Accumulating clinical and laboratory evidence suggests that HHV-6, like all other herpesviruses, may have neurotropic properties. RI may be complicated by seizures, encephalopathy, aseptic meningitis, meningoencephalitis, and hemiplegia. Febrile seizures are the commonest cause of seizures in early childhood and present before 3 years of age in more than 80% of patients. 21,22 A family history of seizures, usually febrile seizures, is observed in 30% to 50% o...

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Case-Control Study of Primary Human Herpesvirus 6 Infection in Children With Febrile Seizures

Hukin

Farrell²,

MacWilliam

et al. 1998

PEDIATRICS

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“…Primary HHV-6 infection usually has a benign and self-limited clinical course (4), but it has been shown that the virus can cause several severe complications (2,3,11,21,28) in rare instances. Clinical diagnosis of the disease is difficult before appearance of the skin rash, because a characteristic clinical feature in the acute phase of the disease is a high fever without any specific signs or symptoms (4).…”

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confidence: 99%

Rapid Diagnosis of Human Herpesvirus 6 Infection by a Novel DNA Amplification Method, Loop-Mediated Isothermal Amplification

et al. 2004

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A novel nucleic acid amplification method, termed loop-mediated isothermal amplification (LAMP), which amplifies DNA with high specificity, efficiency, and rapidity under isothermal conditions, may be a valuable tool for the rapid detection of infectious agents. LAMP was developed for human herpesvirus 6 (HHV-6), and its reliability was evaluated in this study. Although LAMP products were detected in HHV-6 B and HHV-6 A DNA, they were not detected in HHV-7 and human cytomegalovirus DNA. The sensitivity of the original HHV-6 LAMP protocol was 50 copies/tube. In order to increase the method's sensitivity, HHV-6 LAMP was modified by increasing the primer concentration. As a result of the modification, sensitivity increased to 25 copies/tube. After these initial validation studies, 13 patients with fever were tested for HHV-6 by viral isolation, serological analysis, and HHV-6 LAMP. In three of the eight patients with primary HHV-6 infection, HHV-6 DNA was detected in whole blood by the original HHV-6 LAMP protocol in not only the acute phase but also the convalescent phase. HHV-6 DNA was detected by modified HHV-6 LAMP in all eight plasma samples collected in the acute phase; however, no HHV-6 DNA was detected in plasma samples collected in the convalescent phase. Although HHV-6 DNA was detected in both the acute and convalescent phases of whole-blood samples in patients with past HHV-6 infection, it was not detected in plasma samples that did not contain latent viral DNA. Thus, detection of HHV-6 DNA in plasma by using this modified HHV-6 LAMP protocol is appropriate for diagnosis of active HHV-6 infection.

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“…Association of HHV-6 with meningitis/encephalitis Human herpesvirus-6 has been implicated as a cause of meningitis and encephalitis in children (Ishiguro et al, 1990;Huang et al, 1991;Asano et al, 1992;Yoshikawa et al, 1992b;Knox et al, 1995;McCullers et al, 1995;Yanagihara et al, 1995) and adults (Sloots et al, 1993;Drobyski et al, 1994;McCullers et al, 1995). Most descriptions in the literature are case reports.…”

Section: Association Of Hhv-6 With Seizuresmentioning

confidence: 99%

“…Following the identi®cation of HHV-6 as the causative agent of exanthem subitum, many additional instances of CNS involvement in primary HHV-6 infection have been reported (Ishiguro et al, 1990;Asano et al, 1991a;Huang et al, 1991;Asano et al, 1992;Segondy et al, 1992;Yoshikawa et al, 1992b;Kondo et al, 1993;Suga et al, 1993;Caserta et al, 1994;Hall et al, 1994;Ward and Gray, 1994;McCullers et al, 1995). Association of such neurologic ®ndings with HHV-6 is suggested by the concomitant identi®cation of virus by culture from PBMCs, by seroconversion, or, less commonly, by detection of the viral genome in CSF by PCR (Ishiguro et al, 1990;Asano et al, 1992;Yamanishi et al, 1992;Yoshikawa et al, 1992b;Caserta et al, 1994;Ward and Gray, 1994).…”

Section: Central Nervous System (Cns) Involvementmentioning

confidence: 99%

Human Herpesvirus-6: Neurologic Implications of a Newly-Described Viral Pathogen

Kimberlin

Whitley

1998

J Neurovirol

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Discovered only 12 years ago, human herpesvirus-6 (HHV-6) has been associated with central nervous system (CNS) ®ndings such as febrile seizures, encephalitis, meningitis, and possibly multiple sclerosis. These manifestations have been reported in both immunocompetent and immunocompromised individuals. The applications of such sophisticated laboratory tools as polymerase chain reaction, in situ hybridization, immunohistochemical staining, and representational difference analysis have expanded knowledge of the spectrum of CNS disease attributable to HHV-6 while delineating pathogenic mechanisms of both primary HHV-6 infection and reactivation from latency. This article reviews existing knowledge of the CNS manifestations of HHV-6, focusing on both clinical aspects of HHV-6 infection and its pathogenesis on neurologic diseases.

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Fatal encephalitis/encephalopathy in primary human herpesvirus-6 infection.

Cited by 150 publications

References 5 publications

Case-Control Study of Primary Human Herpesvirus 6 Infection in Children With Febrile Seizures

Case-Control Study of Primary Human Herpesvirus 6 Infection in Children With Febrile Seizures

Rapid Diagnosis of Human Herpesvirus 6 Infection by a Novel DNA Amplification Method, Loop-Mediated Isothermal Amplification

Human Herpesvirus-6: Neurologic Implications of a Newly-Described Viral Pathogen

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