Prenatal contributions to epilepsy: lessons from the bedside

Area of Science:

• Developmental neuroscience
• Epileptology
• Fetal neurology

Background:

• Epilepsy often originates from early-life adverse events, with prenatal pathogenetic mechanisms significantly impacting brain development.
• Understanding developmental epileptogenesis necessitates an ontogenetic (nature-nurture-niche) framework, integrating fetal neurology perspectives.

Purpose of the Study:

• To emphasize the importance of an ontogenetic approach in studying epilepsy from a fetal neurology viewpoint.
• To highlight the interplay of genetic and environmental factors in prenatal brain development and epilepsy causation.

Main Methods:

• Review of pathogenetic mechanisms influencing brain development during prenatal life.
• Analysis of genetic susceptibility, including pre- and post-fertilization events.
• Consideration of maternal, fetal, and placental disease contributions to brain malformations and injuries.

Main Results:

• Prenatal events and genetic factors dictate the timing and form of malformations linked to specific epileptic syndromes.
• Adverse alterations in gray and white matter structures occur during sequential prenatal development stages.
• Seizures manifest later, often accompanied by motor, cognitive, and behavioral deficits.

Conclusions:

• An ontogenetic approach is vital for epileptologists to fully grasp developmental epileptogenesis.
• Translational research must integrate acquired causes of pediatric and adult epilepsies within the patient's genetic context.
• Early-life and prenatal factors are critical determinants of epilepsy development and its associated neurological deficits.