Aspects of epileptogenesis: Maturation of neuronal circuits
W. Douglas Knowles, PhD
Departments of Brain and Vascular Research and Neurology, The Cleveland Clinic Foundation Research Institute, One Clinic Center, 9500 Euclid Avenue, Cleveland, Ohio 44195
SUSCEPTIBILITY to epileptogenesis and the propensity for acquiring particular types of epilepsies are related to developmental age. Changes in the brain’s organization, connectivity, and functional mechanisms alter the susceptibility to and the expression of epileptic activity. From clinical observation, we know that overall susceptibility to epilepsy varies greatly with age. The highest age-specific incidence of epilepsy occurs during the first year of life, declining steadily thereafter until age 60, when a second rise in incidence occurs.1–2 Different epileptic syndromes tend to occur at different developmental ages. During the neonatal period, seizures are most often the result of hypoxic-ischemic encephalopathy or intraventricular hemorrhage. While generalized tonic seizures are relatively common, they may be poorly organized, particularly in premature infants.3 The generalized syndromes tend to occur earlier in life, with more focal syndromes occurring later.2
ANIMAL MODELS OF EPILEPSY
In interpreting the implications of developmental experimental models of epilepsy, it is necessary to be able to correlate the developmental stage of the animals with the developmental age of the human patients. This is a difficult task which is often neglected, but some generalizations are possible. In common experimental animals, the brain is at various stages of development at the time of birth. Rats, mice, and rabbits are born before the main period of neuroblast differentiation. Many types of neurons, particularly local interneurons, have not yet fully differentiated. Synapse formation and axon myelination occur to a large extent after birth. Cat, guinea pig, and sheep brains are more nearly mature at birth.. . .