The classification that is still followed today is the 1981 classification of epileptic seizures developed by the International League Against Epilepsy (ILAE; Table 58.1). This system classifies seizures by clinical symptoms supplemented by EEG data.

Inherent in the ILAE classification are two important physiologic principles. First, seizures are fundamentally of two types: those with onset limited to a part of one cerebral hemisphere (partial or focal seizures) and those that seem to involve the brain diffusely from the beginning (generalized seizures). Second, seizures are dynamic
and evolving; clinical expression is determined as much by the sequence of spread of electrical discharge within the brain as by the area where the ictal discharge originates. Variations in the seizure pattern exhibited by an individual imply variability in the extent and pattern of spread of the electrical discharge. Both generalized and partial seizures are further divided into subtypes. For partial seizures, the most important subdivision is based on consciousness, which is preserved in simple partial seizures or lost in complex partial seizures. Simple partial seizures may evolve into complex partial seizures, and either simple or complex partial seizures may evolve into secondarily generalized seizures. In adults, most generalized seizures have a focal onset whether or not this is apparent clinically. For generalized seizures, subdivisions are based mainly on the presence or absence and character of ictal motor manifestations.

The initial events of a seizure, described by either the patient or an observer, are usually the most reliable clinical indication to determine whether a seizure begins focally or is generalized from the moment of onset. Sometimes, however, a focal signature is lacking for several possible reasons:

In 2010, the ILAE published a proposal for a revised classification of the epilepsies based on “terminology and concepts for organization.” As many epilepsy syndromes include both focal and generalized seizures, the classification distinguishing focal from generalized epilepsies was abandoned. In addition, a focal seizure was conceptualized as originating at some point within networks limited to one hemisphere. In contrast, a generalized seizure was conceptualized as originating at some point within, and then rapidly involving, networks distributed bilaterally. The three broad etiologic categories became genetic, structural/metabolic, and unknown, instead of cryptogenic, symptomatic, and idiopathic.

The term infantile spasms denotes a unique age-specific form of generalized epilepsy that may be either idiopathic or symptomatic. When all clinical data are considered, including results of imaging studies, only about 15% of patients are now classified as idiopathic. Symptomatic cases result from diverse conditions, including cerebral dysgenesis, tuberous sclerosis, phenylketonuria, intrauterine infections, or hypoxic-ischemic injury.

Seizures are characterized by sudden flexor or extensor spasms that simultaneously involve the head, trunk, and limbs. The attacks usually begin before 6 months of age. The EEG is grossly abnormal, showing chaotic high-voltage slow activity with multifocal spikes, a pattern termed hypsarrhythmia. The treatment of choice is corticotropin or prednisone; spasms are notoriously refractory to conventional AEDs. Exceptions are topiramate and zonisamide, which have been shown to be an effective alternative to corticotropin in selected cases. Vigabatrin is also effective, especially in children with tuberous sclerosis. Patients on this drug must be monitored for visual field deficits. Although treatment with corticotropin, vigabatrin, zonisamide, or topiramate usually controls spasms and reverses the EEG abnormalities, it has little effect on long-term prognosis. Only about 5% to 10% of children with infantile spasms have normal or near-normal intelligence, and more than 66% have severe disabilities.

This disorder begins most often between the ages of 4 and 12 years and is characterized predominantly by recurrent absence seizures, which, if untreated, can occur literally hundreds of times each day. EEG activity during an absence attack is characterized by stereotyped, bilateral, 3-Hz spike-wave discharges. Generalized tonic-clonic seizures also occur in 30% to 50% of cases. Most children are normal, both neurologically and intellectually. Ethosuximide and valproate are equally effective in treating absence seizures, but valproate or lamotrigine are preferable if generalized tonic-clonic seizures coexist. Topiramate, levetiracetam, and zonisamide may also be effective in generalized-onset seizures.

This term is applied to a heterogeneous group of childhood epileptic encephalopathies that are characterized by mental retardation, uncontrolled seizures, and a distinctive EEG pattern. The syndrome is not a pathologic entity because clinical and EEG manifestations result from brain malformations, perinatal asphyxia, severe head injury, central nervous system (CNS) infection, or, rarely, a progressive degenerative or metabolic syndrome. A presumptive cause can be identified in 65% to 70% of affected children. Seizures usually begin before age 4 years, and about 25% of children have a history of infantile spasms. No treatment is consistently effective, and 80% of children continue to have seizures as adults. Best results are generally obtained with broad-spectrum AEDs, such as valproate, clobazam, lamotrigine, topiramate, or zonisamide. Rufinamide may be particularly effective for atonic seizures associated with this syndrome. Despite the higher incidence of severe side effects, fel bamate is often effective when these other agents do not result in optimal seizure control. Refractory cases may be considered for vagus nerve stimulation or anterior corpus callosotomy. Both of these are palliative procedures, and complete seizure control is rare.

The juvenile myoclonic epilepsy (JME) subtype of idiopathic generalized epilepsy most often begins in otherwise healthy individuals between the ages of 8 and 20 years. The fully developed syndrome comprises morning myoclonic jerks, generalized tonic-clonic seizures that occur just after waking, normal intelligence, a family history of similar seizures, and an EEG that shows generalized spikes, 4- to 6-Hz spike waves, and multiple spike (polyspike) discharges. The myoclonic jerks vary in intensity from bilateral massive spasms and falls to minor isolated muscle jerks that many patients consider nothing more than “morning clumsiness.” Linkage studies have produced conflicting results with different groups reporting susceptibility loci on chromosomes 6p, 5q, and 15q. A mutation in the α-1 subunit of the γ-aminobutyric acid (GABA)_A receptor has been found in a large French Canadian family with JME but not in individuals with the common sporadic form of JME. Valproate is the treatment of choice and controls seizures and myoclonus in more than 80% of cases. Lamotrigine, zonisamide, levetiracetam, and topiramate can be equally effective in many patients, although lamotrigine sometimes exacerbates myoclonus.

Several “benign” focal epilepsies occur in children, of which the most common is the syndrome associated with central-midtemporal spikes on EEG. This form of idiopathic focal epilepsy, also known as benign rolandic epilepsy, accounts for about 15% of all pediatric seizure disorders.

Onset is between 4 and 13 years of age; children are otherwise normal. Most children have attacks mainly or exclusively at night. Sleep promotes secondary generalization, so that parents report only generalized tonic-clonic seizures; any focal manifestations go unobserved. In contrast, seizures that occur during the day are clearly focal, with twitching of one side of the face; speech arrest; drooling from a corner of the mouth; and paresthesias of the tongue, lips, inner cheeks, and face. Seizures may progress to include clonic jerking or tonic posturing of the arm and leg on one side. Consciousness is usually preserved.

The interictal EEG abnormality is distinctive and shows stereotyped diphasic or triphasic sharp waves over the central-midtemporal (rolandic) regions. Discharges may be unilateral or bilateral. They increase in abundance during sleep and, when unilateral, switch from side to side on successive EEGs. In about 30% of cases, generalized spike-wave activity also occurs. The EEG pattern is inherited as an autosomal dominant trait with age-dependent penetrance. The inheritance pattern of the seizures, although clearly familial, is probably multifactorial and less well understood. More than half the children who show the characteristic EEG abnormality never have clinical attacks. Linkage has been reported in some families to chromosome 15q14.

The prognosis is uniformly good. Seizures disappear by mid to late adolescence in all cases. Seizures in many children appear to be self-limited, and not all children need AED treatment. Treatment can usually be deferred until after the second or third attack. Because seizures are easily controlled and self-limited, drugs with the fewest adverse effects, such as carbamazepine, oxcarbazepine, or gabapentin, should be used. Low doses, often producing subtherapeutic blood concentrations, are generally effective. Polytherapy should be avoided.

This is the most common epilepsy syndrome of adults. In most cases, the epileptogenic region involves mesial temporal lobe structures, especially the hippocampus, amygdala, and parahippocampal gyrus. Seizures usually begin in late childhood or adolescence, and a history of febrile seizures is common. Virtually all patients have complex partial seizures, some of which secondarily generalize. Auras are frequent; visceral sensations are particularly common. Other typical behavioral features include a motionless stare, loss of awareness that may be gradual, and oral-alimentary automatisms, such as lip smacking (Video 58.3). A variable but often prolonged period of postictal confusion is the rule. Interictal EEGs show focal temporal slowing and epileptiform sharp waves or spikes over the anterior temporal region. AEDs are usually successful in suppressing secondarily generalized seizures, but most patients continue to have partial attacks. When seizures persist, anterior temporal lobe resection or selective amygdalohippocampectomy is the treatment of choice. For appropriate patients with mesial temporal sclerosis, ablation with laser or Gamma Knife has also been used, although it is not known whether these are as effective as more traditional resection in the long term. The results of a randomized controlled trial comparing seizure outcomes in patients treated either medically or surgically were striking: 58% of surgically treated patients were seizure free at 1 year compared with 8% of medically treated patients. Other series have shown that temporal lobe resection for refractory medial temporal lobe epilepsy associated with hippocampal sclerosis results in complete seizure control for at least 1 year in over 80% of patients. More controversial is the need for long-term anticonvulsant drug treatment after successful operation; a minority of patients may relapse several years later.

The particular pattern of the many types of frontal lobe seizures depends on the specific location where the seizure discharge originates and on the pathways subsequently involved in propagation. Despite this variability, the following features, when taken together, suggest frontal lobe epilepsy:

Frontal lobe epilepsy occurs in some families as an autosomal dominant syndrome. In these patients, seizures almost always occur during sleep. Most patients respond well to medication.

Seizures occur within 1 year in about 7% of civilian and in about 34% of military head injuries. The differences relate mainly to the much higher proportion of penetrating wounds in military cases. The risk of developing posttraumatic epilepsy is directly related to the severity of the injury and also correlates with the total volume of brain lost as measured by computed tomography (CT). Depressed skull fractures may or may not be a risk; the rate of posttraumatic epilepsy was 17% in one series but not increased above control
levels in another. Head injuries are classified as severe if they result in brain contusion, intracerebral or intracranial hematoma, unconsciousness, or amnesia for more than 24 hours or in persistent neurologic abnormalities, such as aphasia, hemiparesis, or dementia. Mild head injury (brief loss of consciousness, no skull fracture, no focal neurologic signs, no contusion or hematoma) does not increase the risk of seizures significantly above general population rates.

Nearly 60% of those who have seizures have the first attack in the first year after the injury. In the Vietnam Head Injury Study, however, more than 15% of patients did not have epilepsy until 5 or more years later. Posttraumatic seizures are classified as early (within the first 1 to 2 weeks after injury) or late. Only recurrent late seizures (those that occur after the patient has recovered from the acute effects of the injury) should be considered posttraumatic epilepsy. Early seizures, however, even if isolated, increase the chance of developing posttraumatic epilepsy. About 70% of patients have partial or secondarily generalized seizures. Impact seizures occur at the time of or immediately after the injury. These attacks are attributed to an acute reaction of the brain to trauma and do not increase the risk of later epilepsy.

Overt seizures should be treated according to principles reviewed later in this chapter. The most controversial issue concerns the prophylactic use of AEDs to retard or abort the development of subsequent seizures. Based on the data of Temkin et al. (1990), we recommend treating patients with severe head trauma, as just defined, with an antiepileptic medication for the first week after injury to minimize complications from seizures occurring during acute management. If seizures have not occurred, we do not continue medication beyond the initial 1 to 2 weeks because evidence does not show that longer treatment prevents the development of later seizures or of posttraumatic epilepsy. Data suggest that valproate is less effective than phenytoin in suppressing acute seizures and is also ineffective in preventing the development of posttraumatic epilepsy.

Epilepsia partialis continua (EPC) refers to unremitting motor seizures involving part or all of one side of the body. They typically consist of repeated clonic or myoclonic jerks that may remain focal or regional or may march from one muscle group to another, with the extent of motor involvement waxing and waning in endless variation (Video 58.5). In adults, EPC occurs in diverse settings, such as with subacute or chronic inflammatory diseases of the brain (Kozhevnikov Russian spring-summer encephalitis, Behçet disease) or with acute strokes, metastases, and metabolic encephalopathies, especially hyperosmolar nonketotic hyperglycemia.

The most distinctive form of EPC, known as the Rasmussen syndrome, occurs in children; it usually begins before the age of 10 years. The underlying disorder is chronic focal encephalitis, although an infectious agent has not been identified consistently. About two-thirds of patients report an infectious or inflammatory illness 1 to 6 months before onset of EPC. Generalized tonic-clonic seizures are often the first sign and appear before the EPC establishes itself. About 20% of cases begin with an episode of convulsive status epilepticus. Slow neurologic deterioration inevitably follows, with development of hemiparesis, mental impairment, and, usually, hemianopia. If the dominant hemisphere is affected, aphasia occurs. EEGs are always abnormal, but findings are not specific, and they frequently do not correlate with clinical manifestations. Magnetic resonance imaging (MRI) may be normal early but later shows unilateral cortical atrophy and signal changes consistent with gliosis. Autoantibodies to the GluR3 protein of the glutamate receptor have been found in some patients, suggesting that autoimmunity may play a role in the pathogenesis of the disorder in some patients, and immunotherapy is sometimes beneficial. AEDs are usually ineffective in controlling seizures and preventing progression of the disease, as are corticosteroids and antiviral agents. When seizures have not spontaneously remitted by the time there is a severe degree of hemiparesis, functional hemispherectomy can control seizures and leads to substantial intellectual improvement in many patients. Controversy arises in the decision about the best time for hemispherectomy, for example, whether it should be performed earlier before there is serious motor or language impairment.

Because epilepsy is fundamentally a physiologic disturbance of brain function, the EEG is the most important laboratory test in evaluating patients with seizures. The EEG helps both to establish the diagnosis of epilepsy and to characterize specific epileptic syndromes. EEG findings may also help in management and in prognosis.

Epileptiform discharges (spikes and sharp waves) are highly correlated with seizure susceptibility and can be recorded on the first EEG in about 50% of patients. Similar findings are recorded in only 1% to 2% of normal adults and in a somewhat higher percentage of normal children. When multiple EEGs are obtained, epileptiform abnormalities eventually appear in 60% to 90% of adults with epilepsy, but the yield of positive studies does not increase substantially after three or four tests. Prolonged ambulatory or inpatient recordings increase the yield of interictal epileptiform abnormalities both because of the longer sampling times but also because complete sleep-wake cycles are included. It is important to remember, therefore, that 10% to 40% of patients with epilepsy do not show epileptiform abnormalities on routine EEG. Thus, a normal or nonspecifically abnormal EEG never excludes the diagnosis. Sleep, hyperventilation, photic stimulation, and special electrode placements are routinely used to increase the probability of recording epileptiform abnormalities. Different and distinctive patterns of epileptiform discharge occur in specific epilepsy syndromes as summarized in Chapter 25.

MRI should be performed in all patients older than age 18 years and in children with abnormal development, abnormal findings on physical examination, or seizure types that are likely to be manifestations of symptomatic epilepsy. CT will often miss common epileptogenic lesions such as hippocampal sclerosis, cortical dysplasia, and cavernous malformations. Because CT is very sensitive for detecting brain calcifications, a noncontrast CT (in addition to MRI) may be helpful in patients at risk for neurocysticercosis.

Routine imaging is not necessary for children with idiopathic epilepsy, including the benign focal epilepsy syndromes (see section “Benign Epilepsy Syndromes”). Brain MRI, although more costly, is more sensitive than CT in detecting potentially epileptogenic lesions, such as cortical dysplasia, hamartomas, differentiated glial tumors, and cavernous malformations. Both axial and coronal planes should be imaged using both T1 and T2 sequences. Gadolinium injection does not increase the sensitivity for detecting cerebral lesions but may assist in differentiating possible causes.

Imaging in the coronal plane perpendicular to the long axis of the hippocampus and other variations in technique have improved the detection of hippocampal atrophy and gliosis, findings that are highly correlated with mesial temporal sclerosis (Fig. 58.5) and an epileptogenic temporal lobe. An even more sensitive measure of hippocampal atrophy is MRI measurement of the volume of the hippocampus. Hippocampal volume measurements in an individual patient then can be compared with those of normal control subjects. In patients being considered for surgery, interictal
positron emission tomography (PET) scans can add valuable localizing information, especially when the MRI scan is negative. Singlephoton emission computed tomography (SPECT) scans are also used, although resolution is less than either MRI or PET. Subtraction ictal SPECT co-registered with MRI (SISCOM) is also helpful in localizing the epileptogenic brain region in some cases.

Routine blood tests are necessary in newborns and in older patients with acute or chronic systemic disease to detect abnormal electrolyte, glucose, calcium, or magnesium values or impaired liver or kidney function that may contribute to seizure occurrence. They are rarely diagnostically useful in healthy children or adults. Serum electrolytes, liver function tests, and a complete blood count (CBC) should be obtained when infectious or metabolic abnormalities are suspected, but they are useful mainly as baseline studies before initiating AED treatment.

Any suspicion of meningitis or encephalitis mandates lumbar puncture. Urine or blood toxicologic screens should be considered when otherwise unexplained new-onset generalized seizures occur.