Abstracts

Rationale: Human herpes virus 6 (HHV6) is a ubiquitous pathogen of childhood. It is associated with febrile seizures and hippocampal sclerosis, and is the major cause of post-transplant acute limbic encephalitis (PALE) in immunosuppressed patients following hematologic stem cell transplant. Memory impairment and temporal lobe epilepsy following PALE are reported in adults, but sequelae in young children are unknown. Methods: We report three children who had HHV6-associated PALE, 2-4 weeks after cord blood transplant (CBT) for leukemias at ages 1, 2 and 14 years, and subsequently developed a symptomatic generalized epilepsy (SGE). Patients were followed for 2-8 years from the PALE. All patients were investigated with MRI and video-EEG in the course of their chronic epilepsy. Two patients underwent CSF and serum testing for viral and autoimmune disease 1.5 and 6 years after the PALE; they were subsequently treated with immunotherapies. These children are part of a cohort of 84 patients who underwent CBT at our institution between 2003 and 2011. 7/84 patients (8%) were diagnosed with HHV6 encephalitis. Of the four patients not reported here, one had a severe movement disorder, dying acutely, and three had HHV6-associated PALE within the last 18 months, and have not developed epilepsy to date.Results: Epileptic spasms, tonic, atonic, atypical absence and/or myoclonic seizures developed in each patient after an 11-18 month silent period following HHV6-associated PALE. Seizures increased to multiple daily frequency and were resistant to multiple antiepileptic medications. Generalized slow spike-wave and paroxysmal low voltage fast activity (LVFA) was prominent on interictal EEGs and generalised seizures with LVFA were captured on monitoring. Focal temporal lobe seizures were not seen. The two younger patients regressed in their language, social and motor abilities synchronous with the evolution of seizures, while the older patient developed a severe amnestic syndrome that halted intellectual development. Serial MRI revealed changes only in medial temporal structures. Bilateral hippocampal swelling was seen in two patients during their PALE, progressing to hippocampal atrophy 12-15 months later. The other patient, had normal MRI during the PALE but developed bilateral hippocampal swelling six years later. CSF cell count and protein were normal with negative PCR for HHV6 and other neurotropic viruses, and negative autoantibodies associated with limbic encephalitis. One patient had CSF oligoclonal bands detected twice. Neither patient improved with pulse methylprednisolone but one improved with intravenous immunoglobulin.Conclusions: These children s acute presentations were typical of HHV6-related PALE described in adults and older children, but the development of a SGE is not reported. The severe seizure, cognitive and EEG sequelae in these children may be due to an ongoing, chronic, immune-mediated inflammatory process or may reflect developmental epileptogenesis following bilateral hippocampal injury at an early age.