Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) occurs in children associated with infection. It is characterized by a prolonged febrile seizure in the first phase, and a cluster of seizures, deterioration of consciousness and the white matter lesions with reduced diffusion in the second phase. The patients often have severe neurological sequelae, but the prognostic indicators remain unknown. The present study aimed to clarify the characteristics of AESD patients who subsequently exhibited severe neurological sequelae. We retrospectively analyzed the clinical and laboratory findings along with the brain imaging in patients who had severe (n=8) and non-severe neurodevelopmental outcomes (n=12). Severe group more frequently showed coma (p=0.014) or involuntary movements including dystonia and oral dyskinesia (p=0.018) before the second phase than non-severe group. Severe group exhibited higher levels of serum alanine aminotransferase than non-severe group (p=0.001). Quantitatively assessed MRI in the second phase revealed that severe group had more extensive lesions than non-severe group, in the anterior (p=0.015) and posterior parts (p=0.011) of the cerebrum and basal ganglia (p=0.020). Early appearing involuntary movements or coma might account for the extension of acute brain lesions and the poor neurological outcomes in AESD patients.