Symptomatic generalized epilepsy after HHV6 posttransplant acute limbic encephalitis in children

Human herpesvirus 6 (HHV6) is the major cause of posttransplant acute limbic encephalitis (PALE) in immunosuppressed patients following hematopoietic stem cell transplant. Memory impairment and temporal lobe epilepsy following PALE are reported in adults, but sequelae in young children are unknown. We report three children with HHV6-associated PALE 20-23 days after cord blood transplantation for leukemias who developed symptomatic generalized epilepsy. Patients were followed for 2-8 years and underwent magnetic resonance imaging (MRI) and video-electroencephalography (EEG). Two patients underwent viral and autoimmune testing and immunotherapies. Generalized seizures, including tonic seizures, developed 11-18 months after HHV6-associated PALE. Seizures were frequent and resistant to multiple antiepileptic drugs (AEDs). Generalized slow spike-wave and low-voltage fast activity were recorded on interictal and ictal EEGs. The two younger patients regressed in their general abilities, synchronous with seizure evolution, whereas the older patient developed a severe amnestic syndrome that halted intellectual development. Serial MRI studies revealed bilateral signal change and atrophy in the medial temporal structures of all patients. In the two investigated patients, there was no evidence of chronic HHV6 infection, minimal evidence of cerebral inflammation, and no significant improvement with pulse with intravenous methylprednisolone and immunoglobulin. The severe and generalized seizure, cognitive, and EEG sequelae of HHV6-related PALE in these children may be due to a chronic, viral, or immune-mediated inflammatory process or developmental epileptogenesis resulting from bilateral hippocampal injury at an early age, although there was a paucity of evidence for either.