The Not-So-Soft Spot: Pathophysiology of the Bulging Fontanelle in Association With Roseola.

Roseola infantum is a clinical syndrome characterized by high fever followed by the emergence of a rash. Case reports have documented an association between bulging fontanelles and roseola. We propose a novel mechanism for the development of intracranial hypertension caused by human herpesvirus 6-induced cytokine elevation leading to increased cerebrospinal fluid production.

Seizure susceptibility due to antihistamines in febrile seizures.

The aim of this study was to determine whether seizure susceptibility due to antihistamines is provoked in patients with febrile seizures. The study population comprised 14 patients with simple febrile seizures and 35 patients with complex febrile seizures. Detailed clinical manifestations were compared between patients with and without administration of antihistamine. The time from fever detection to the seizure onset was significantly shorter in the antihistamine group than that in the nonantihistamine group, and the duration of seizures was significantly longer in the antihistamine group than that in nonantihistamine group. Interleukin-1beta is thought to be associated with causing febrile seizures via its dual role as a pyrogen and convulsant substance. Moreover, interleukin-1beta may activate the turnover of hypothalamic neural histamine. These considerations, along with the present results, suggest that the depletion of hypothalamic neuronal histamine induced by antihistamines may increase neuronal excitability, thereby increasing seizure susceptibility in patients with febrile seizures.

A case of drug-induced hypersensitivity syndrome-like symptoms following HHV-6 encephalopathy.

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is a rare but severe disorder due to a systemic hypersensitivity reaction. We report on a case with DIHS-like symptoms following human herpes virus 6 (HHV-6) infection complicated with encephalopathy. CASE SUMMARY: An 11-month-old girl suffered from a human herpes virus 6 (HHV-6) infection (exanthema subitum) complicated with encephalopathy. We treated the patient with continuous infusion of thiopental, assisted mechanical ventilation, methylprednisolone pulse therapy, and gamma-globulin infusion therapy starting on the fifth day of the illness and started phenobarbital administration on the eleventh day. The patient developed a fever, systemic erythematous exanthema, lymphadenopathy, and eosinophilia two weeks after the start of phenobarbital administration. Steroid therapy, methylprednisolone (4 mg/kg/day) followed by oral prednisolone (1 mg/kg/day), was started on the 28th day and was tapered off on the 72nd day after admission. Serum anti-HHV-6 IgG antibody elevation and the presence of HHV-6 DNA in the peripheral blood detected by polymerase chain reaction (PCR) analysis suggested reactivation of HHV-6 after the primary infection of HHV-6. Lymphocyte transformation test for phenobarbital was positive three weeks after the DIHS crisis. DISCUSSION: HHV-6 reactivation is a unique feature in DIHS. In general one develops DIHS accompanied by reactivation of HHV-6 which has been residing in the body since the initial infection (exanthema subitum) in early childhood. This is the first report of a patient with DIHS-like symptoms which developed immediately following the primary infection of HHV-6.

Predominant human herpesvirus 6 variant A infant infections in an HIV-1 endemic region of Sub-Saharan Africa.

Human herpesvirus 6, HHV-6, commonly infects children, causing febrile illness and can cause more severe pathology, especially in an immune compromised setting. There are virulence distinctions between variants HHV-6A and B, with evidence for increased severity and neurotropism for HHV-6A. While HHV-6B is the predominant infant infection in USA, Europe and Japan, HHV-6A appears rare. Here HHV-6 prevalence, loads and variant genotypes, in asymptomatic compared to symptomatic infants were investigated from an African region with endemic HIV-1/AIDS. DNA was extracted from blood or sera from asymptomatic infants at 6 and 18 months age in a population-based micronutrient study, and from symptomatic infants hospitalised for febrile disease. DNA was screened by qualitative and quantitative real-time PCR, then genotyped by sequencing at variable loci, U46 (gN) and U47 (gO). HIV-1 serostatus of infants and mothers were also determined. HHV-6 DNA prevalence rose from 15% to 22% (80/371) by 18 months. At 6 months, infants born to HIV-1 positive mothers had lower HHV-6 prevalence (11%, 6/53), but higher HCMV prevalence (25%, 17/67). HHV-6 positive febrile hospitalized infants had higher HIV-1, 57% (4/7), compared to asymptomatic infants, 3% (2/74). HHV-6A was detected exclusively in 86% (48/56) of asymptomatic HHV-6 positive samples genotyped. Co-infections with both strain variants were linked with higher viral loads and found in 13% (7/56) asymptomatic infants and 43% (3/7) HIV-1 positive febrile infants. Overall, the results show HHV-6A as the predominant variant significantly associated with viremic infant-infections in this African population, distinct from other global cohorts, suggesting emergent infections elsewhere.

Serial changes on diffusion-weighted magnetic resonance imaging in encephalitis or encephalopathy.

It is recognized that diffusion-weighted magnetic resonance imaging is a sensitive method of detecting cerebral lesions in various neurologic disorders. This report presents two patients with acute encephalitis or encephalopathy who manifested similar serial changes on diffusion-weighted magnetic resonance imaging. Clinically, Patient 1, a 2-year-old male, was diagnosed as having hemiconvulsion-hemiplegia-epilepsy syndrome and Patient 2, a 9-month-old male, acute encephalitis associated with exanthema subitum. Despite the different etiology and the distribution of lesions, diffusion-weighted magnetic resonance imaging of these two patients revealed high-intensity lesions in the subcortical white matter in the acute phase, and then in the cortex, or basal ganglia, or both. In the convalescent phase, high-intensity lesions disappeared and brain atrophy developed. These serial changes were not recognized using other conventional methods. Although the exact mechanism for these serial changes remains unknown, these changes might reflect some pathogenic mechanism in acute encephalopathy or encephalitis.

Human herpesvirus 6 encephalitis associated with hypersensitivity syndrome.

Hypersensitivity syndrome, a serious systematic reaction to a limited number of drugs, is associated with the reactivation of human herpesvirus 6. A 56-year-old man developed acute limbic encephalitis followed by multiple organ failure during the course of toxic dermatitis induced by aromatic anticonvulsants. The clinical features of skin eruptions, high fever, eosinophilia, and atypical lymphocytosis were compatible with drug hypersensitivity syndrome. The patient showed seroconversion for human herpesvirus 6, and polymerase chain reaction detected human herpesvirus 6 DNA in the cerebrospinal fluid. To our knowledge, this is the first report of human herpesvirus 6 encephalitis associated with hypersensitivity syndrome.

Human herpesvirus 6 infection in transplantation.

Human herpesvirus 6 (HHV-6) is ubiquitous in the human population and causes exanthem subitum, a benign disease seen in infancy. The virus remains latent in the body after primary infection, and reactivates in immunocompromised patients. Infection occurs in nearly half of all bone marrow or solid organ transplant recipients 2-3 weeks following the procedure. It has been suggested that the viral infection and activation result in clinical symptoms including fever, skin rash, pneumonia, bone marrow suppression, encephalitis, and rejection. In order to control the viral infection, several studies investigating the route of viral transmission and diagnostic procedures have been carried out.

Fatal human herpesvirus 6-associated multifocal meningoencephalitis in an adult female patient.

Human herpesvirus 6 (HHV 6) is a known cause of central nervous system infection in immunocompromised patients. Less is known about the clinical course of HHV 6 encephalitis in immunocompetent patients. We report a case of meningoencephalitis in a 42-y-old immunocompetent patient associated with HHV 6 infection.

[Frequent convulsions in the post-eruptive stage of exanthem subitum].

We report here three infants with frequent convulsions in the post-eruptive stage of exanthem subitum (ES) due to human herpesvirus 6 (HHV-6) infection. Postictal electroencephalogram (EEG) showed in all the patients abnormal epileptic discharges, which disappeared in the following by three to eighteen months. In one case, brain magnetic resonance imaging (MRI) revealed focal gliosis. SPECT demonstrated hypoperfusion of the lesion. In the cerebro spinal fluid (CSF) of all the patients, HHV-6 DNA was negative on polymerase chain reaction (PCR) and HHV-6 antibodies were not significantly increased. Although encephalitis has been reported to complicate primary HHV-6 infection, our patients were not diagnosed as having encephalitis because of the clinical, CSF, EEG and CT findings. However, they had frequent convulsions. Not only virus invasion but also a secondary reaction including vasculitis may cause the central nervous system complications of HHV-6 infection. Frequent convulsions may occur in the post-eruptic stage after HHV-6 infection.

Human herpesvirus 6: An emerging pathogen.

Infections with human herpesvirus 6 (HHV-6), a beta-herpesvirus of which two variant groups (A and B) are recognized, is very common, approaching 100% in seroprevalence. Primary infection with HHV-6B causes roseola infantum or exanthem subitum, a common childhood disease that resolves spontaneously. After primary infection, the virus replicates in the salivary glands and is shed in saliva, the recognized route of transmission for variant B strains; it remains latent in lymphocytes and monocytes and persists at low levels in cells and tissues. Not usually associated with disease in the immunocompetent, HHV-6 infection is a major cause of opportunistic viral infections in the immunosuppressed, typically AIDS patients and transplant recipients, in whom HHV-6 infection/reactivation may culminate in rejection of transplanted organs and death. Other opportunistic viruses, human cytomegalovirus and HHV-7, also infect or reactivate in persons at risk. Another disease whose pathogenesis may be correlated with HHV-6 is multiple sclerosis. Data in favor of and against the correlation are discussed.

Clinical features and virological findings in children with primary human herpesvirus 7 infection.

OBJECTIVE: To elucidate clinical features of patients with primary human herpesvirus 7 (HHV-7) infection and serologic and virologic findings between HHV-7 and human herpesvirus 6 (HHV-6). MATERIALS AND METHODS: During a 19-month observation period, 71 infants and children (35 boys and 36 girls with a mean age of 14.5 months [range, 1 month to 48 months]) who had acute febrile respiratory illness with or without skin rash were examined clinically and virologically. Heparinized blood samples were used for isolation of HHV-6 and HHV-7 and detection of both virus DNA sequences by a nested polymerase chain reaction amplification. Both virus antibody activities were measured by an indirect immunofluorescent assay. RESULTS: HHV-7 infection was observed in 15 (6 boys and 9 girls with a mean age of 12.9 months [range, 7 months to 27 months]), 1 of 10 with upper respiratory infection and 14 (28%) of 50 with febrile exanthem, whereas HHV-6 infection was in 22 (44%) of the 50. Fever (37.5 degrees C) was observed in all 15, with an average maximum body temperature of 38.7 degrees C (range, 37.6 degrees C to 39.8 degrees C), which persisted for 2.9 days (range, 1 to 5 days). Papular, macular, or maculopapular rash was observed in 14 (93%) of the 15, which appeared on day 2.9 of fever (range, days 2 to 5) on the face, trunk, and extremities and persisted for 2.7 days (range, 1 to 5 days). A convulsive seizure that persisted for a few minutes developed in 1 patient on the first day of elevation of fever. HHV-6 antibody was demonstrated in 13 (87%), and a simultaneous significant increase to HHV-6 antibody titers was observed in 8 (53%) of the 15 during primary HHV-7 infection. HHV-7 and HHV-6 DNAs were almost always detected in mononuclear cells (MNCs) during acute and convalescent phases, whereas HHV-7 DNA was positive in some plasma samples obtained during the acute phase of the disease. CONCLUSIONS: Primary HHV-7 infection occurred somewhat later than HHV-6, which was confirmed by the isolation of HHV-7 from blood and/or seroconversion to the virus. Clinical features of a virologically confirmed patient with primary HHV-7 infection were comparable with those of primary HHV-6 infection. Preexisting HHV-6 antibody increased significantly in the half of patients with primary HHV-7 infection. HHV-7 DNA was detected in peripheral blood MNCs and plasma in the acute phase and persisted in MNCs thereafter.

Clinical and virological analyses of 21 infants with exanthem subitum (roseola infantum) and central nervous system complications.

Twenty-one infants who had virologically confirmed exanthem subitum and central nervous system (CNS) complications were studied to elucidate the clinical features, laboratory and virological findings, and outcome. The primary infection with human herpesvirus 6 was confirmed by isolation of the virus from blood, a significant rise in the antibody titers to the virus, or both. All convulsive seizures (15 generalized and 6 focal) occurred during the pre-eruptive stage of exanthem subitum. Four infants with encephalitis/encephalopathy had more severe clinical features with abnormalities demonstrated on electroencephalograms and cerebral computed tomograms. All infants except those with encephalitis/encephalopathy recovered without any sequelae. One infant with encephalitis/encephalopathy developed epilepsy and another one died. Human herpesvirus 6 DNA amplified by the nested polymerase chain reaction method was detected in the cerebrospinal fluid of 6 infants, including 3 with encephalitis/encephalopathy, of 11 patients examined by the fifth day of the illness. These findings suggest that CNS complications including encephalitis/encephalopathy occur at the pre-eruptive stage of exanthem subitum, that human herpesvirus 6 invades the CNS in some patients, and that the outcome is not always benign.