Large ice crystals in the nucleus of rapidly frozen liver cells

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.