Human herpesvirus 6 and non-human herpesvirus 6 limbic encephalitis in children with allogeneic stem cell transplantation: A case series

Background: Post-transplant acute limbic encephalitis (PALE) has been reported, and human herpesvirus 6 (HHV-6) is one of the causes. Reports of PALE in children are still limited. In the present study, the detailed clinico-radiological findings of PALE and the neurological outcomes of four children are reported. Cases: Four patients aged three to twelve years of 142 patients who underwent allogeneic hematopoietic stem cell transplantation developed PALE. Underlying disorders were neuroblastoma in three patients and acute lymphoblastic leukemia in one. All four patients showed disorientation, behavioral changes, emotional dysregulation, anterograde amnesia, or decreased level of consciousness between 12 and 22 days after transplantation. None had clinical seizures. In all patients, MRI showed hyperintense signals in unilateral or bilateral hippocampi, especially in the CA1 area, on diffusion-weighted imaging (DWI), with a decreased apparent diffusion coefficient. Though the hippocampi were also hyperintense on T2-weighted and fluid-attenuated inversion recovery imaging, signal intensity was higher on DWI by visual inspection. Electroencephalograms showed poorly organized posterior dominant rhythm in all patients and left occipito-centro-parietal slow waves in one without epileptiform discharges. HHV-6 DNA was positive in both cerebrospinal fluid and whole blood by polymerase chain reaction in three of the four patients. Two patients had pharmaco-resistant epilepsy and cognitive impairment three years after PALE, but the other two recovered neurologically from PALE. Conclusion: A DWI abnormality of the hippocampal CA1 area is a good biomarker for the diagnosis of HHV-6-positive or -negative PALE in children. Glutamatergic dysregulation and hippocampal cytotoxic edema may be involved in PALE.