Increased Ki-67 immunoreactivity in the white matter in hemimegalencephaly

Hemimegalencephaly (HMG) is a developmental brain disorder characterized by an enlarged unilateral hemisphere with cortical malformation comprising abnormal hypertrophic cells. To address the proliferative status of HMG, Ki-67 immunoreactivity was investigated in HMG specimens obtained during epilepsy surgery. Nine HMG tissues were stained with a Ki-67 antibody and Ki-67 labeling index in the malformed cortex, and the underlying white matter was measured separately and compared with tissues from focal cortical dysplasias and normal brains from autopsy. In HMG tissues, Ki-67-positive cells were scattered in both the gray and white matter, with a significantly higher Ki-67 labeling index in the white matter compared with gray matter. No dysmorphic neuron or balloon cell was stained for Ki-67. As Ki-67 immunoreactivity overlapped with that of ionized calcium-binding adaptor protein-1, Ki-67-positive cells were identified as microglia. In HMG, microglia were activated and entered into a proliferative status with higher distribution in the white matter, implying an ongoing neuroinflammatory process involving the white matter.