Hemimegalencephaly (HME)
General description
Hemimegalencephaly (HME) is a rare congenital malformation of cortical development characterized by enlargement of all or part of a cerebral hemisphere. The pathogenesis involves complex molecular mechanisms primarily centered on aberrant activation of the mTOR (mechanistic target of rapamycin) signaling pathway. This condition represents a disorder of neuroepithelial lineage and cellular growth, arising from postzygotic somatic mutations in undifferentiated premigratory neuroepithelial cells.
Clinical manifestations
The clinical presentation of HME is dominated by severe, drug-resistant epilepsy that typically manifests in early infancy. The onset of epilepsy is often within the neonatal period, though it may sometimes commence during later infancy or rarely during early childhood.
Most infants present with focal seizures involving the arm and leg contralateral to the affected hemisphere. Additional neurological manifestations include progressive contralateral hemiparesis, hemianopia, and global developmental delay. Patients commonly exhibit macrocephaly with asymmetrical or enlarged head circumference. Cognitive impairment ranges from moderate to severe intellectual disability.
Cortical malformations
The hemisphere contralateral to the symptomatic side demonstrates characteristic cortical abnormalities on MRI, such as increased cortical thickness, abnormally smooth cortical appearance, blurring of the gray-white matter junction, and polymicrogyria.
White matter abnormalities
The white matter of the affected hemisphere shows markedly increased volume and contains tissue that is isointense to cortical gray matter on imaging, consistent with gray matter heterotopia. On T2-weighted images, there is increased signal intensity in the subcortical white matter.