The most likely etiologies vary with age. Neonatal asphyxia, congenital malformations, and inherited metabolic disorders tend to manifest with seizures in infancy and early childhood; trauma and neoplasms are important in childhood, adolescence, and adulthood; and vascular insults are a common etiology of seizures later in life. Idiopathic epilepsies most often start in childhood and adolescence and are believed to represent genetic disorders manifesting only as seizures. With the exception of the idiopathic syndrome of benign focal epilepsy of childhood, patients of any age with partial seizures or a focal abnormality indicated on EEG should be evaluated for the possibility of a cerebral structural lesion. Magnetic resonance imaging (MRI) is the test of choice in this setting.

Throughout this chapter, the terminology is that of the current classification system of the International League Against Epilepsy. In this classification, the primary division of seizures is that between partial and generalized seizure
types. Partial seizures have an abnormal electrical activity on the EEG localized to a limited area of the cerebral cortex in one hemisphere, whereas generalized seizures begin diffusely. Partial seizures may evolve into secondarily generalized seizures when the epileptiform discharges begin on one side of the brain and spread to involve both hemispheres.

Partial seizures are further divided into simple or complex types primarily based on whether consciousness is preserved during the event. Complex partial seizures involve impairment of consciousness, defined by amnesia, but simple partial seizures do not. When the simple partial seizure is sensory in its presentation, it is called an aura. Simple partial seizures with focal jerking of a limb or one side of the face are called focal motor seizures, and when the motor activity moves sequentially through muscle groups it may be said to have a Jacksonian march. The patient remains awake and aware throughout a simple partial seizure, even if he or she is unresponsive during the event because of motor involvement of the face and throat or because of strong, distracting sensory stimuli. Even when these features are present, patients with simple partial seizures will remember an ictal event.

Complex partial (psychomotor or automotor) seizures, by definition, involve impairment of consciousness with postictal amnesia. They may be preceded by a simple partial seizure, such as an aura, which may be remembered afterward, but during the complex partial seizure, the patient has altered awareness and impaired responsiveness. Most patients with complex partial seizures also have automatisms; that is, stereotyped, repetitive, and semipurposeful motor activity. The automatisms may be gestural (including fumbling with nearby objects or picking at clothes or bedsheets), alimentary (chewing, swallowing, or lip smacking), mimicking (with facial expressions suggesting an emotion such as fear), verbal (yelling, laughing, or repetitive speech), or ambulatory (walking or running). Complex partial seizures may also involve loss of posture or abnormal face or limb movements, or autonomic phenomena. Afterward, there may be postictal confusion for minutes to hours, and this is a significant feature that distinguishes complex partial seizures from generalized absence attacks.

Generalized seizures include a wide variety of clinical types. Generalized tonic-clonic seizures or grand mal convulsions may involve several phases: a tonic phase, with sudden loss of consciousness, falling, involuntary crying-out, muscle stiffening, and altered breathing pattern; a clonic phase, with rhythmical muscle spasms and limb jerking, possible cheek or tongue biting with bleeding, foamy salivation, irregular breathing with possible cyanosis, and possible urinary or bowel incontinence; and a postictal phase, with deep hyperventilation, and gradual return of consciousness over several minutes. During the event, there may be vomiting or loss of bowel or bladder control and afterward there is temporary confusion or sleepiness. Primary generalized tonic-clonic seizures are not preceded by a simple or complex partial seizure.

Generalized absence seizures (petit mal attacks) have no warning or aura; they involve interruption of activity with loss of consciousness and amnesia, and there is no postictal confusion. Attacks are brief, rarely lasting longer than 20 seconds, and they typically occur many times a day in untreated patients. These features are useful in distinguishing between absence and complex partial seizures. In longer absence seizures, the patient may also have some loss of muscle tone, subtle myoclonic jerks, or automatisms. Because automatisms may occur in both, absence or complex partial seizures, they should not be used to differentiate the two seizure types.

Other types of generalized seizures include:

In some patients, two or more types of these generalized minor motor seizures occur together, often in the presence of mental retardation.

Epilepsy syndromes as well as seizures have been classified by the International League Against Epilepsy. With this classification, patients are grouped not just by the seizure type, but also by the presence of similar clinical, electrographic, radiographic, and pathologic findings. By this classification, certain types of epilepsy may include one or more different types of seizures.

Epilepsies are traditionally categorized in two basic ways: by etiology as either idiopathic (with no known cause) or symptomatic (with an identified underlying cause), and by type of seizure onset as either localizationrelated (with focal-onset seizures) or generalized (with diffuse-onset seizures). In patients with idiopathic epilepsy, the brain structure and neurologic examination are normal, a familial pattern may be present, and there is a typical age of onset. Idiopathic epilepsies probably are because of specific genetic abnormalities. In patients with epilepsy, there may be evidence of previous head trauma, metabolic disease, stroke, symptomatic tumor, or other brain insult, and the patient may have dementia, paresis, or sensory deficits. The onset of seizures in symptomatic epilepsy may be soon after brain injury or delayed by many years. One form of idiopathic, generalized epilepsy is childhood absence epilepsy (petit mal). This epilepsy typically has schoolaged onset, involves absence and generalized tonic-clonic
seizures (convulsions are present in approximately 50% of patients), and includes a characteristic electroencephalogram picture of a generalized 3-per-second spike-and-slow wave complexes especially during hyperventilation. Patients typically have a good response to medication, and seizures usually remit spontaneously before early adulthood. Absence seizures alone are usually controlled with the administration of either ethosuximide or valproate alone, but valproate is the preferred choice if generalized tonic-clonic seizures are also present. The newer antiepileptic medication, lamotrigine, may also be proved effective in the treatment of childhood absence epilepsy.

Another form of idiopathic, generalized epilepsy is juvenile myoclonic epilepsy. This type of epilepsy has peak onset in adolescence, involves myoclonic and generalized tonic-clonic seizures on awakening, and records an electroencephalogram with generalized poly spikes. Patients typically have a good response to medication such as valproate or benzodiazepines, but the seizures do not remit spontaneously, and lifelong medication is generally needed. Juvenile myoclonic epilepsy is especially interesting from a scientific viewpoint because it is one of the first epilepsies in which a chromosomal abnormality has been identified. Valproate has been the drug of choice, but newer alternatives include lamotrigine and topiramate.

West syndrome is an epileptic syndrome that may be either idiopathic or symptomatic. Onset is in the first year of life, the seizure type is infantile spasms, and the EEG shows hypsarrhythmia. Mental retardation is part of the definition of West syndrome, but not all infants with infantile spasms and hypsarrhythmia have an impaired intellect. Infantile spasms may be flexor (salaam, jackknife, or head nodding), extensor, or mixed (with both flexor and extensor components). The mixed type is most common. Clustering of spasms is typical and should suggest this syndrome. Spasms typically occur when the infant is awake or upon awakening or during the drowsiness period just prior to sleep.

West syndrome may be idiopathic (40% of cases) or symptomatic. Underlying etiologies include perinatal events such as hypoxia-ischemia, infection, prematurity, or hemorrhage; genetic disorders such as tuberous sclerosis or Aicardi syndrome; malformations of cortical development; and inborn metabolic errors such as phenylketonuria. Important tests to identify an etiology include an MRI scan, a dilated eye examination, and a careful Wood lamp skin evaluation of the patient and his or her family, looking for neurocutaneous stigmata, and metabolic and genetic evaluations. Video-EEG, high-resolution MRI scan, and positron emission tomography (PET) may be appropriate in refractory cases to explore the possibility of a focal structural abnormality, for example, a focal malformation of cortical development. Patients with refractory infantile spasms because of focal structural lesions may be eligible candidates for epilepsy surgery.

Medical treatment options for infantile spasms include intramuscular adrenocorticotropic hormone (ACTH), 20 to 60 U/day, or prednisone, 2 mg/kg per day, used for 6 weeks and then weaned. Other options include valproate or benzodiazepine. The prognosis of West syndrome is better when there is no known etiology. Hrachovy, et al., (1988) reported that 38% of infants with idiopathic West syndrome had a normal outcome without mental retardation, compared with only 5% of those with the symptomatic form. Among children in both groups, the infantile spasms remitted or changed to different seizure types by 2 or 3 years of age. Additionally, the hypsarrhythmic electroencephalogram pattern resolved or changed to a different abnormal pattern by 5 or 6 years of age.

Lennox-Gastaut syndrome is another type of generalized epilepsy that may be either idiopathic or symptomatic. Onset is in infancy or childhood, and patients have multiple types of generalized seizures, including atonic or myoclonic attacks. Patients have mental retardation, and the electroencephalogram shows generalized slow spike and slow wave complexes and background slowing. A similar clinical picture may also be seen in children with an electroencephalogram picture of multifocal sharp waves from each hemisphere. Possible etiologies may include the same disorders as for West syndrome. The seizures are often intractable, and sometimes require treatment with two or more drugs. It is important to avoid polypharmacy whenever possible, so that patients are less likely to have additional cognitive deficits resulting from drug toxicity. The ketogenic diet or vagus nerve stimulation may be helpful to patients with Lennox-Gastaut syndrome and other types of refractory epilepsy.

Benign focal epilepsy with centrotemporal spikes is a common type of idiopathic, localization-related epilepsy. This epilepsy typically begins at 4 to 12 years of age, with peak onset between 8 and 10 years of age; involves infrequent partial motor seizures of the face and arm or nocturnal generalized tonic-clonic seizures (80% of patients have only nighttime convulsions). The electroencephalogram shows centrotemporal sharp waves that have a typical morphology and marked activation during sleep. In these children, the brain structure and neurologic examination are usually normal. These patients generally have a good response to antiepileptic medications such as carbamazepine or gabapentin. However, in most cases treatment with medication is not needed. Identification of this syndrome is important, because if a child fits neatly into this patient group, the family can be reassured that the patient will have spontaneous remission of his or her seizures by the age of 16 years.

Temporal lobe epilepsy is a form of symptomatic, localization-related epilepsy. Onset is usually in the school age or during teenage years, but may be earlier. Seizures are typically complex partial with automatisms, and the electroencephalogram shows temporal lobe sharp waves. In some cases, the seizures may be intractable despite
treatment with maximum tolerated doses of antiepileptic medication. The rate of spontaneous remission is low. It is critical to exclude a structural lesion (e.g., tumor, malformation of cortical development, or hippocampal sclerosis) by performing an MRI scan. Many traditional and newer antiepileptic medications have been shown to be effective against partial seizures in temporal or extratemporal epilepsy, with carbamazepine usually considered a first-line choice. Patients with refractory temporal lobe epilepsy may be favorable candidates for epilepsy surgery. Extratemporal epilepsy is another form of symptomatic, localization-related epilepsy. Patients may have simple or complex partial seizures with symptoms reflecting the origin of onset, namely from the frontal, parietal, or occipital regions. Extratemporal epilepsy is similar to temporal lobe epilepsy in the age of onset, prognosis, and possibility of a structural lesion.

Once the diagnosis of epilepsy is confirmed, certain factors need to be considered when deciding whether to treat with antiepileptic medication. These include the seizure type, seizure frequency, time of seizure occurrence, predisposing factors to injury if a seizure were to occur, as well as psychosocial and social consequences of additional seizures. Taken together, this information must be weighed against the risk of antiepileptic medication-related adverse effects. If it is decided to treat with antiepileptic medication, then the next step is to select a drug effective for the patient’s seizure type (Table 33.1). Currently, not all antiepileptic medications are labeled for use in pediatric patients and even fewer of these are labeled by the U.S. Food and Drug Administration (FDA) for use in epilepsy syndromes. Therefore, in many instances antiepileptic medications are used in an off-label manner on the basis of the efficacy demonstrated in clinical practice.

It may be said that the treatment of pediatric epileptic patients is just as much art as it is science. Although there are certain doses and serum concentrations that have more commonly been found to result in seizure control with no or minimal adverse effects, these values are not universally optimal for every individual. Therefore, it is helpful to think of antiepileptic drug treatment in terms of common recommended doses and usual therapeutic ranges. These serve as initial target ranges and act as reasonable starting points for the treatment of most patients. In general, there are certain principles that may be used when initiating and switching among antiepileptic medications. These principles are as follows: