The incidence of epilepsy is very high in the first years of life, reaching a peak in the first year and remaining at high levels throughout infancy and early childhood. The epilepsies with onset in infancy, although a heterogeneous group, share some special characteristics, and this applies up to the age of approximately 3 to 4 years. The following chapters, therefore, are concerned with all epilepsies that begin before the age of 4 years.

The special features of the epilepsies of early onset are the result of several etiologic, anatomic, and neurophysiologic factors. One major factor is the immaturity of the infant’s brain. At this period, dendritic development is actively proceeding, and myelin formation and deposition are far from complete, which may be responsible for imperfect synchronization of the hemispheres. Brain circuitry is different from that in later life. In particular, the number of synapses increases rapidly during the first years of life and far exceeds the ultimate number.¹⁶ A high proportion of these synapses is eliminated before 8 to 10 years of age, and this pruning process depends on activity and, therefore, on environmental stimuli. There is evidence that functional synapses become stabilized, whereas unused ones disappear; this is probably one of the mechanisms of brain plasticity. Development and maturation of the brain are associated with changes in neurotransmitters and receptors and their effects. For example, some γ-aminobutyric acid (GABA) receptors have been shown to be excitatory during fetal life and the early postnatal period,¹⁹ and glutamate receptors may not be sufficient to produce brain damage through activation of the glutamate cascade. Such changes are likely profoundly to modify the excitability of the infant’s brain. The conjunction of these factors undoubtedly accounts for some of the features of early seizures, such as the generally imperfect organization of seizure discharges, the rarity of full-fledged tonic–clonic attacks, and the higher frequency of unilateral or predominantly unilateral seizures in response to diffuse systemic disturbances such as fever or metabolic imbalances. However, the infant’s brain is capable of occasionally producing 3-Hz spike-wave discharges and massive myoclonias and even, although rarely, absence attacks.² Seizures of focal origin are the most common seizures in this age range. They may be associated with focal clinical manifestations and electroencephalogram (EEG) discharges of several forms with different degrees of propagation. Many focal seizures are associated with extensive brain lesions, indicating that the infant brain may be unable to organize complete seizure sequences as observed at a later age. The atypical clinical expression of many seizures in the infantile range probably results from the neurophysiologic factors already mentioned, from the late maturation of some areas of the brain such as the frontal lobe, as well as from the inability of infants to experience or express some of the more complex features of seizures and the difficulty or impossibility for observers to detect such symptoms as loss or impairment of consciousness.²⁰ Conversely, focal brain lesions or abnormalities may be associated with diffuse clinical symptoms and with extensive EEG paroxysms, one common type being infantile spasms with the so-called hypsarrhytmic pattern of high-amplitude disorganized tracing, suggesting that focal origin of seizures may be expressed in generalized attacks and is probably even more common in young children than previously thought.¹³

The etiology of early-onset epilepsies is also responsible for many of their clinical and evolutive characteristics. As in older patients, the two main factors are a propensity to fitting (mostly genetically determined) and the presence of brain lesions; however, both have age-specific peculiarities.

The epileptogenic lesions are often extensive, even when they give rise to partial seizures. Some are destructive and may be related to mechanical or hypoxic-ischemic injuries. A majority, however, are of developmental origin, the most common being abnormalities of cortical development. These include heterotopias, diffuse pachygyria-lissencephaly, hemimegalencephaly, and focal cortical dysplasias, the latter being the most common cause of epilepsy at this age.¹⁵ It is of interest that the nature, location, and extent of organic brain damage—and not only the age of the child—are responsible, at least in part, for the ictal symptomatology. Thus, tuberous sclerosis often determines infantile spasms, and Aicardi syndrome determines a mixture of focal seizures and spasms.

The propensity to seizures of infants is mainly expressed by febrile convulsions (see Chapter 227) and less often in the form of other benign epilepsy syndromes. Febrile convulsions (FCs) are by far the most common frequent manifestation of a genetic predisposition to seizures. Although febrile seizures are not termed epilepsy because they do not fulfill the definition of a chronic unprovoked condition but are classified as occasional seizures or situation-related seizures,^1,14 they have undoubted physiopathologic and genetic relationships with the epilepsies and may be regarded as a benign expression of the main basic phenomenon. This genetic relationship is best illustrated by the occurrence of afebrile convulsions following FC, which, although rare, are much more common than in the general population and in rare instances by the syndrome of generalized epilepsy with febrile seizures plus (GEFS+).

The importance of age in the expression of infantile epilepsy is clearly shown by the age dependence of several types of seizures. West syndrome rarely begins after 1 year of age and has a well-defined modal age of onset at 5 to 6 months (Chapter 229). Several types of seizures may occur in succession in the same patient with an unchanged pathologic basis; for example, Ohtahara syndrome can precede infantile spasms, followed by the development of the Lennox-Gastaut syndrome; focal or unilateral seizures may precede the development of West or Lennox-Gastaut syndrome. Such changes may reflect not only the maturation of the brain, but perhaps also the
plasticity of the central nervous system. Some of the changes could result from the capacity for reorganization of the infant’s brain following an insult or even a prolonged dysfunction without any lesion. It is conceivable that unusual regulation and development of receptors or preferential stabilization of certain synapses as a result of prolonged abnormal epileptic activity in certain pathways may lead to altered connectivity, with corresponding clinical changes. Such a mechanism could account for some of the characteristics of epileptic deterioration, such as its spontaneous arrest after disappearance or improvement of epileptic activity and incomplete recovery in spite of apparent cure of epilepsy. Deterioration associated with, and possibly resulting from, intense epileptic activity, whether marked by seizures or only by EEG alterations, is a remarkable feature of some early epilepsies,^3,5,11 sometimes termed epileptic encephalopathies or catastrophic epilepsies (see Chapter 230). Although epileptic deterioration is not limited to young children, as shown by its occurrence in such syndromes as the Landau-Kleffner syndrome or that of continuous spike-waves of slow sleep,⁵ it is clearly prominent in this age bracket (see Chapter 242). Other factors possibly responsible for deterioration include evolution of the underlying lesions, frequency and consequences of seizures, psychological problems, side effects of drugs, and other environmental influences.