Decreased midbrain grey matter after prenatal exposure to antiepileptic drugs

Prenatal exposure of humans to antiepileptic drugs may cause cognitive impairment.

Ion channels, neurotransmitters and second messenger systems constitute molecular targets of antiepileptic drugs. These same targets regulate brain processes essential for learning, memory and emotional behavior. In addition, it has been shown that antiepileptic drugs trigger widespread apoptotic neurodegeneration in the developing brain when administered to immature rodents. Thus, antiepileptic drugs can influence brain function and brain development in undesired ways. To explore whether prenatal exposure to antiepileptic drugs may result in structural changes in the brain, we subjected a group of 18 healthy young adults exposed prenatally to antiepileptic drugs and a group of 18 age-matched unexposed healthy controls to magnetic resonance imaging (MRI) of the brain. Local differences in cerebral morphology associated with prenatal exposure to antiepileptic drugs were analyzed in volume-rendering MRI data by use of voxelwise comparisons of grey matter images. Contrasts for regional grey matter volume changes, i.e. exposed patients < controls, yielded significant results at a threshold of small-volume-corrected p<0.05. Regional decreases of grey matter volumes were found in the area of the lentiform nucleus, including both pallidum and putamen bilaterally, and the hypothalamus. We conclude that prenatal exposure to antiepileptic drugs results in lower grey matter volumes in the basal ganglia and the hypothalamus in humans.