Chapter 557. Epidemiology of Epilepsy, Seizure Classification, Epilepsy Syndromes

Seizures

An epileptic seizure is a change in neurologic function (motor, sensory, experiential, or autonomic) that is associated with an abnormal synchronous discharge of cortical neurons. Usually that discharge can be recorded by routine electroencephalogram (EEG) using scalp electrodes, although occasionally, because the discharge’s location is on a surface distant from the scalp (eg, mesial temporal, orbitofrontal, mesial frontal, basal, or insular cortex), it can only be recorded by surgically implanted electrodes. Although the term seizure is sometimes used to refer to any paroxysmal event, in this chapter seizure always refers to an epileptic seizure, driven by an abnormal neuronal discharge. A convulsion is an epileptic seizure that results in involuntary muscle contractions. The term epileptic seizure always requires some clinical change in the patient, either observed by others or reported by the patient himself or herself. Occasionally, a seizure discharge is recorded on the EEG without any associated clinical change. Such discharges are referred to as electrographic seizures or electrographic seizure patterns.

Epilepsy

Epilepsy refers to a tendency to spontaneous, recurrent seizures usually defined by the experience of having had two or more unprovoked seizures. This definition excludes certain types of provoked seizures, such as seizures caused by fever during childhood (febrile seizures), seizures caused by a temporary metabolic derangement such as hypoglycemia or hyponatremia, or seizures that occur in the setting of an acute central nervous system (CNS) insult such as stroke, trauma, or meningitis. Seizures that occur exclusively during the newborn period are also traditionally excluded from the definition of epilepsy because the majority of these are considered provoked seizures.

A Note on the Terms Idiopathic, Cryptogenic, and Symptomatic

The term idiopathic epilepsy literally refers to an epilepsy “unto itself” (idios, Greek), meaning an epilepsy that has not occurred as a consequence of another condition or disorder (eg, head trauma) but a situation in which epilepsy is the disorder. The primary generalized epilepsies come under this category, and in this usage, the term primary is synonymous with idiopathic. The genetic focal epilepsy syndromes also belong to this category of idiopathic epilepsies. Note that the term idiopathic epilepsy does not imply an epilepsy without known cause, as the genetic underpinnings of the primary generalized (idiopathic) epilepsies are rapidly being elucidated. The term idiopathic epilepsy does not, however, simply apply to any epilepsy syndrome in which all neurological testing is negative. In some instances, an underlying cause is suspected, although it cannot be specifically identified. Such cases are referred to as cryptogenic epilepsy (the cause is hidden but presumed to exist). Finally, the term symptomatic epilepsy is used for a seizure disorder that has a clear cause (eg, the seizures that follow the occurrence of a stroke).

Variations in the reported population rates of epilepsy in children may be due to true differences in the populations studied but may also be due to differences in how cases of epilepsy are defined. Most studies define children with epilepsy as those who have experienced two or more unprovoked seizures, excluding children with febrile seizures, those whose seizures have occurred during or soon after an acute CNS process (eg, trauma, stroke, infection, or metabolic disturbances), and those whose seizures occurred exclusively in the newborn period. Epidemiologic studies quote the incidence (rate of new cases diagnosed per 100,000 children per year) or the prevalence (percentage of a population affected at a particular point in time) of epilepsy.

Across the human life span, the first year of life is associated with the highest incidence of epilepsy with approximately 80 to 120 new cases of epilepsy per 100,000 children per year.1,2 Thereafter, most studies show that the incidence rate for the remainder of the next 2 decades decreases to as little as half that rate, reaching a nadir during the third decade that does not begin to rise substantially until the age of 60 years. Incidence rates comparable to those seen in the first 10 years of life are not reached again until after age 70.1 A specific antecedent cause for epilepsy is found in only about 20% of children, and among these, half are ascribed to mental retardation or cerebral palsy. Prevalence rates of epilepsy in industrialized countries generally range between 0.5% and 1% during childhood.3

Only about 20% of children presenting with a first seizure will go on to have a diagnosis of epilepsy. The remainder either do not have a second seizure episode during childhood or are considered to have had a provoked seizure. Including all seizure types and etiologies, 4% to 10% of children will have experienced a seizure by the age of 20 years, though only 1% will have epilepsy.3

The overall recurrence risk after a first unprovoked seizure in childhood is approximately 50% (see Chapter 560). This statistic is the basis for the decision made to defer antiepileptic drug treatment after a first seizure episode in many children. Etiologies of seizure are reviewed in Chapter 558. Factors such as previous brain injury and abnormal neurologic status before the seizure increase this risk. Among those who experience a second seizure and, therefore, qualify for the diagnosis of epilepsy, 90% do so within the 2 years following the initial seizure.4,5Prevalence rates of epilepsy are higher among children with neurodevelopmental disabilities. Approximately 15% of children with mental retardation have comorbid epilepsy, with higher rates seen among those who are more severely impaired.6 Motor disabilities may independently increase the risk of epilepsy. In a series of children with cerebral palsy, 33% had epilepsy with prevalence rates increasing proportionally with the degree of motor disability. The risk of a new diagnosis of epilepsy in children with cerebral palsy persists through the second decade of life.7

Seizure remission (the cessation of seizures for an extended period of time, on or off anticonvulsant treatment) is one of the main goals of epilepsy treatment in childhood. For the majority of children, epilepsy can be controlled with medications, and a high percentage of children outgrow their epilepsy over time. For instance, in a population-based study in Finland, 64% of patients followed for almost 30 years were in a 5-year remission from seizures at last follow-up, with 47% in remission and off anticonvulsant medications.8,9 The primary predictor of outcome in epilepsy is the underlying etiology of the epilepsy with symptomatic epilepsies less likely to remit than idiopathic epilepsies. Other positive predictors of seizure remission in childhood epilepsy are onset before 10 years of age, low initial seizure frequency, and good response to first anticonvulsant.

Intractable epilepsy is generally defined as the persistence of frequent seizures despite the use of at least two appropriately chosen anticonvulsant medications with adequate therapeutic levels. Estimates of intractability vary depending on the population studied and the definition of intractability used. In population-based studies in Connecticut, 14% of 613 children were intractable to treatment at a median of 9.7 years of follow-up.10 In this group, the specific etiology or epilepsy syndrome was the most powerful predictor of intractability, followed by high initial seizure frequency, the presence of focal slowing on EEG, and a history of acute symptomatic or neonatal status epilepticus. Intractability was not associated with the absolute number of seizures prior to treatment or a prior history of unprovoked or febrile status epilepticus.11

In addition to the burden of epilepsy and its treatment, many children with epilepsy suffer from comorbid neurodevelopmental and neuropsychiatric disorders. Aside from mental retardation and cerebral palsy which is seen in 20% to 30% of children with epilepsy, there is a high rate of learning difficulties (23% to 34%),12,13 psychiatric disorders such as anxiety and depression (33%),14 behavior problems (32%),15 and attention deficit/hyperactivity disorder (10%) reported from multiple cohorts of children with epilepsy in Europe and North America.15 Social outcome, as measured by level of education achieved, employment, and domestic partnership may be adversely affected even in the setting of epilepsy remission.9 This impact was noted in all groups including those with normal intellectual function.9,16 A study of adverse behavioral and social outcome comparing children with childhood absence epilepsy with those with juvenile rheumatoid arthritis followed for 18 years showed a greater difficulty for those with a history of epilepsy, suggesting that the effect is not due solely to a chronic childhood disease.17 Social stigmatization may still be an important contributor to diminished prognosis for life success in the children with epilepsy.

It is recognized that the mortality rate in children with epilepsy is greater than that of the general pediatric population. The Connecticut study of 613 children reported an overall standardized mortality ratio (SMR) of 7.54. However, the SMR for children with symptomatic epilepsy was 33.46, in contrast to an SMR of 1.43 for those with nonsymptomatic epilepsy,18 suggesting that in children with “benign” epilepsy syndromes, the mortality rate is similar to that of the general pediatric population. The association of symptomatic epilepsy and, in particular, neurological dysfunction19 with higher mortality rates is also reported in population-based studies in the United Kingdom, Europe, and Australia.9,20,21 It is believed that the causes of death in childhood epilepsy are frequently not related directly to seizure occurrence or epilepsy, but instead reflect the general medical vulnerability of this high-risk group. Other causes of death include accidental drowning and seizure-related trauma, suicide, and homicide.

Sudden unexpected death in epilepsy (SUDEP) is rare in young children. Although estimates vary with the population reported, overall rates of SUDEP are approximately 1 per 1000 children with epilepsy per year. SUDEP is associated with young adulthood, intractable epilepsy, frequent seizures, and polytherapy.22 The underlying mechanism and the specific frequency with which these deaths are related to the occurrence of seizures is unknown.

Seizure Types and Seizure Syndromes

The most widely used systems for categorizing seizure types and seizure syndromes (or epilepsy syndromes) have been promulgated by the International League Against Epilepsy (ILAE). Although currently under revision, the ILAE seizure classification of 1981 and the epilepsy syndrome classifications of 1985 and 1989 are the basis for the categorization systems in widest use today23,24,25(eTables 557.1 and 557.2).

The term seizure type refers to the classification of an individual seizure event. Two key features of a seizure event are used to classify its seizure type: the seizure semiology (the patient’s subjective description of the experience of the seizure or the patient’s outwardly observable actions during the seizure) and any simultaneous EEG recording made during the event. The patient’s background history is not critical in diagnosing seizure type.

The 1981 ILAE classification was based on simultaneous videotape and EEG recordings of patients’ seizures with interictal EEG findings also taken into account. This approach contrasted with the earlier classification of Gastaut26 which also considered anatomic factors, age, and etiology. The 1981 classification represented a departure from this method and has the advantages of simplicity and wide acceptance, but it did not include details of seizure semiology which may allow for more accurate localization of the seizure onset zone, an increasingly important issue with the greater availability of surgical options for the treatment of focal epilepsies. In response, a task force of the ILAE has made a proposal for a new diagnostic scheme for epilepsy,27 envisaging an “axis” system to include ictal phenomenology, seizure type, epilepsy syndrome, etiology, and a measure of impairment. The proposal remains under discussion. By contrast, the diagnosis of a patient’s seizure or epilepsy syndrome is based on a cluster of signs and symptoms customarily occurring together. These may include case history; age of seizure occurrence; seizure type or types; modes of seizure recurrence; neurological, psychological, and EEG findings; and the results of neuroimaging.24 For example, a 16-year-old girl with normal intellect and a normal neurologic examination who has a history of both generalized tonic-clonic (GTC) seizures and morning myoclonic jerks since the early teenage years likely has the diagnosis of the epilepsy syndrome known as juvenile myoclonic epilepsy. In this example, the patient’s seizure syndrome includes two different seizure types: myoclonic seizures and GTC seizures. If necessary, the diagnosis of these seizure types could be confirmed by patient and observer descriptions and simultaneous video and EEG recording of the individual seizure events. The diagnosis of the epilepsy syndrome of juvenile myoclonic epilepsy, however, is best established by knowing the patient’s age at onset of the seizures, the seizure types she has, and any additional pertinent history. The terms seizure syndrome and epilepsy syndrome are often used interchangeably, although, strictly speaking, seizure syndrome is the correct term when describing a syndrome of provoked seizures (eg, febrile seizures) that technically do not represent an example of epilepsy (see definition above).

The ILAE classification of seizure types describes two broad groups: partial (focal) seizures and generalized seizures, with a smaller “unclassified” group that cannot be assigned easily to either category (see eTable 557.1). The process of assigning a seizure to either the partial or generalized category is the first step in seizure classification. Different categories of seizure types are described briefly below along with their characteristic clinical and EEG findings.

Partial Seizures

The terms partial seizure and focal seizure can be used interchangeably. Because a seizure discharge can arise from nearly any location on the cortical surface, partial seizures have a wide range of potential clinical manifestations. Motor findings are particularly common and include clonic (jerking) movements, tonic (stiffening) contraction of muscle groups, or atonic change (loss of tone) in a muscle group. Sensory or special sensory manifestations may also occur, such as tingling or pain over a region of the body, auditory or olfactory hallucinations, or seeing brightly colored shapes. Psychic features such as the experience of a feeling of fear or déjà vu may also occur. Autonomic findings such as sweating, palpitations, flushing, excess salivation, or incontinence may accompany a seizure. These findings can occur singly or in combination. If the seizure discharge flows from its region of onset into different areas of cortex, the seizure manifestations will evolve accordingly. Motor manifestations are more common than sensory manifestations during partial seizures, suggesting that motor cortex may be more epileptogenic.

Because they are produced by an active discharge, seizure manifestations tend to consist of “positive phenomena”: rather than a limb becoming paralyzed, the limb jerks and stiffens. Rather than feeling numbness, the patient may experience a paresthesia. Rather than experiencing transient blindness, the patient reports a visual hallucination. Although negative symptomatology such as paralysis or blindness may occasionally be caused by a seizure, negative symptoms during a clinical episode should lead to consideration of other causes for the symptoms beyond epileptic seizure.

The true seizure onset zone may not always match the cortical region suggested by the clinical onset of the spell. Because a significant portion of the cortical surface is functionally silent, seizure discharges involving such areas may also be clinically silent. A seizure discharge arising from one of these “silent” areas may only begin to cause clinical signs once it has propagated into a nonsilent area such as the motor strip. For this reason, when a patient’s seizure begins with clonic jerking, we can infer that the seizure discharge has involved the motor strip; however, we cannot know with certainty that the seizure discharge originated in the motor strip—the seizure discharge may have started elsewhere and later spread to involve motor cortex.

Todd’s Phenomenon

The best known manifestation of Todd’s phenomenon is Todd’s paralysis. When a motor seizure involves only part of the body, the seizure episode may be followed by a transient weakness in the involved area. In children, this weakness usually promptly resolves, typically in less than 1 hour. When invoking Todd’s paralysis as an explanation for weakness after a presumed seizure episode, steady improvement and complete resolution of the weakness are expected. In addition to the example of transient focal weakness after a partial motor seizure, a Todd’s phenomenon may involve other areas of function, such as a transient inability to move the eyes to one side after the eyes have been driven to that side during a seizure, or transient blindness after a seizure involving the visual areas.

Complex Partial Seizures

Partial seizures are further subdivided into simple partial seizures and complex partial seizures (CPS). A CPS is a partial seizure associated with diminished consciousness or responsiveness. Some of the partial seizure types described above may be associated with completely retained responsiveness, such as a simple partial seizure involving clonic spasms of the face or hand during which the patient can be completely alert and aware during the seizure. The majority of partial seizures, however, are associated with diminished responsiveness and are properly classified as CPS. Only during a minority of partial seizures is responsiveness completely maintained. During CPS, the patient may appear awake but is unresponsive (or only partially responsive) to stimulation. Only rarely does a patient appear to have lost consciousness during a CPS. CPSs may arise from any lobe of the brain, with the temporal lobe being the most common site of origin. Temporal lobe seizures classically begin with staring and unresponsiveness, possibly associated with automatic movements such as chewing or hand fumbling, although considerable variation is seen. CPS may or may not secondarily spread to motor areas to manifest tonic or clonic activity. Children are often, but not always, amnesic for CPS episodes. Especially when the seizure discharge involves both temporal lobes, it can be impossible for the brain to record new memories during the seizure. Seizure episodes associated with discharges that remain unilateral are more likely to be recalled by the patient.

Epileptic Auras

An epileptic aura is a subjective sensation that heralds the onset of a seizure. The range of sensations can be diverse, such as hearing a buzzing sound in the ears or experiencing a déjà vu phenomenon or a feeling of nausea immediately preceding a seizure. This initial, comparatively minor manifestation may then be followed by the more dramatic features of the seizure. It is incorrect to consider a seizure aura as a preseizure warning or prodrome, because the aura actually represents the onset of the epileptic seizure discharge. During the aura phase of a seizure, the abnormal electrical discharge is usually confined to a small area, often in the temporal lobe. As the discharge spreads outside of its initial confines, the clinical seizure manifestations may become more dramatic. Because the aura actually represents the onset of a clinical seizure, an epileptic aura can be considered a seizure. In some cases, the aura does not progress and represents the seizure in its entirety.

Automatisms

Automatisms are automatic behaviors that may be seen during a seizure event. Examples include fumbling of the hands, running the fingers through the hair, making humming sounds, or mechanically continuing an activity that was in progress at the time of seizure onset. Unlike most clinical features of a seizure, automatisms are not driven directly by a seizure discharge in the way that clonic jerking is driven by repetitive EEG spike-wave discharges. Rather, automatisms represent the release of automatic, preprogrammed behaviors. When cerebral cortex is functioning normally, these automatic programs are suppressed. When, however, the cerebral cortex is engulfed with seizure activity such as during a CPS or a prolonged absence seizure, such preprogrammed behaviors may be released.

Partial Seizures with Secondary Generalization

A seizure discharge may start focally and subsequently spread to involve all brain areas (generalize). A classic example of a partial seizure that spreads is the Jacksonian march: a seizure that begins with clonic activity in one limb or the face and sequentially spreads to the remainder of the involved hemibody, finally involving both sides of the body with a bilaterally synchronous convulsion. This clinical progression is mirrored by evolution of the EEG discharge from a subset of the motor strip to the whole of one hemisphere, followed by generalized involvement of both hemispheres. The clues that a seizure is of partial onset may not be appreciated in some instances in which generalization occurs rapidly. Partial seizures that secondarily generalize are classified among the partial seizures rather than the generalized seizures, as partial seizures, whether or not they generalize, have the same list of possible causes. In comparison, the list of possible causes of generalized seizures is distinctly different from that of partial seizures with or without secondary generalization—the tendency for a partial seizure to secondarily generalize usually has little to do with the etiology of the seizure.

Generalized Seizures

The category of generalized seizures includes absence seizures, myoclonic seizures, clonic seizures, tonic seizures, generalized tonic-clonic (GTC) seizures, and atonic (astatic) seizures. All generalized seizures share the fact that the discharge that drives the seizure is seen in all cortical areas at seizure onset.

Absence Seizures

In their purest form, simple absence seizures consist of a pure stare typically lasting 3 to 15 seconds associated with complete unawareness of the environment, the minimum duration only limited by the challenge of documenting unresponsiveness for the very briefest episodes. In order to distinguish them from atypical absence seizures (described below), the term typical absence seizure is sometimes used. In the past, some used the term absence to denote any seizure associated with staring; however, in modern usage, the term absence seizure refers to staring seizures associated with generalized spike-wave discharges as described below.

In addition to a pure stare, most absence seizures are associated with some combination of a low amplitude rhythmic blinking of the eyes, a mild deviation of the eyes (usually upward), or a mild slackening of the facial muscles. Upper-body myoclonic movements or a change in tone are less common accompaniments. Absence seizures are accompanied by “classic” 3 Hz generalized spike-wave discharges (see eFig. 557.1). Typical absence seizures are almost never associated with a fall. Although the patient is usually completely unaware of the environment during absence seizures, occasional patients report partial awareness and the ability to hear during episodes. In the majority of cases, patients are unaware that absence seizures have occurred, the only clue being the subjective feeling that something has been missed in the observed sequence of events.

Atypical Absence Seizures

The essential features of atypical absence seizures are also staring and unresponsiveness; however, onset and termination of the seizure are less sharply demarcated than is seen with typical absence seizures. Changes in tone with slumping of the head or shoulders is more common. Atypical absence seizures tend to occur in the setting of cognitive impairment or mental retardation. The EEG correlate of atypical absence seizures is the “slow spike-wave discharge,” firing at 2.5 Hz or less in contrast to the 3 Hz (or faster) generalized spike-wave discharge associated with typical absence.

Myoclonic Seizures

Myoclonic seizures consist of a lightning-like or shock-like contraction of the muscles. Many myoclonic seizures are generalized, though focal myoclonus is also possible. Epileptic myoclonus may consist of a single jerk or a quick series of jerks that occurs in a burst, either rhythmical or nonrhythmical. Epileptic myoclonus may manifest as a muscle jerk in nearly any part of the body, though the most common location for epileptic myoclonus is the upper shoulder girdle. In such cases, the myoclonus consists of a quick series of extensor jerks at the shoulders. During the series of jerks, there may be a tendency for a mild net abduction of the upper arms away from the body with each jerk.

Not all myoclonus is epileptic. Some myoclonus is believed to originate in the central nervous system at levels below cerebral cortex, including the subcortical areas, or from the spinal cord (segmental myoclonus). The question of whether an instance of myoclonus is epileptic in nature is best confirmed by demonstrating a concomitant EEG discharge. (No EEG discharge would be expected to accompany an episode of nonepileptic myoclonus.)

Generalized Clonic Seizures, Tonic Seizures, and Tonic-Clonic Seizures

Generalized clonic seizures are characterized by repetitive, synchronous whole-body jerks. Clonic jerks tend to have a rhythmical quality. Generalized tonic seizures consist of a tonic stiffening of the whole body, most often in extension, though tonic flexion of some muscle groups may be seen in some examples. Especially with generalized tonic seizures or seizures that begin with tonic stiffening of the whole body, tonic contraction of the diaphragm may occur, resulting in a forced inhalation causing a prolonged grunting sound.

The term generalized tonic-clonic (GTC) seizure specifically refers to the seizure sequence of whole-body tonic stiffening followed by whole-body clonic jerking. Unfortunately, this term is often misused to refer to any generalized convulsion, a use that is technically incorrect—properly, the term GTC should be reserved exclusively for the sequence of events in which whole-body stiffening is followed by whole-body clonic jerking. This distinction can be important, as some clinical events that mimic seizures, such as convulsive syncope (nonepileptic body movements associated with brief episodes of significant hypotension, ie, syncope) do not tend to manifest this specific sequence. The sequence of tonic body stiffening followed by clonic jerking is highly suggestive of epileptic seizure and should be duly noted. During a GTC seizure, the EEG shows a train of generalized rapid spikes that slow in frequency to become individual spike-wave discharges, followed by slowing. The rapid spikes are associated with the phase of tonic stiffening. As the firing rate of the spikes slows, each spike discharge is able to generate a separate clonic jerk, accounting for the progression from tonic stiffening to clonic jerking that is seen in the GTC seizure.

Atonic Seizures

Atonic seizures consist of a sudden loss of tone, usually of the axial musculature. In its mildest form, an atonic seizure may manifest as a subtle slumping of the shoulders. More frequently, an atonic seizure may manifest as a head-drop spell during which the head falls forward on the body. The most dramatic version of the atonic seizure is the drop attack (astatic seizure) in which the patient collapses to the ground, possibly resulting in injury.

There are a few seizure types that are not clearly generalized or focal and do not, therefore, fit easily into the above classification. Examples include swimming or bicycling movements, apneas, and eye-roving movements. In fact, some examples of these apparent seizure types may not represent true epileptic phenomena. In some cases, these behaviors may represent automatic movements (automatisms) rather than phenomena driven by an actual epileptic seizure discharge. The nature of some of these clinical events, therefore, remains to be clarified. Infantile spasms (or epileptic spasms) represent another seizure type that is not easily classified as generalized or focal (see section on West syndrome below).

Neonatal Seizures

The neonatal seizure classification system in most common use today was described by Volpe in 1989.28 This 1989 classification includes subtle seizures, clonic seizures (focal and multifocal), tonic seizures (focal and generalized), and myoclonic seizures (focal, multifocal, and generalized). The most important difference between this neonatal seizure classification and the general ILAE classification used for older children and adults is the presence of a “subtle seizure” category. Subtle seizures described in neonates include movements such as “swimming,” “boxing,” or “hooking” movements of the upper extremities; “bicycling” movements of the lower extremities; oro-bucco-lingual movements such as sucking or lip-smacking; eye-opening or complex eye movements; and pure apneas. Because such phenomena are usually not associated with abnormal EEG discharges, the epileptic nature of these “subtle seizure” behaviors has not been firmly established. Many of these behaviors may represent the unmasking of automatic reflex behaviors in the newborn which are released when the cerebral cortex is not functioning normally. Even though the large majority of apneas in newborns are not related to seizure activity, rarely an epileptic seizure may manifest as a pure apnea in a newborn.

Apart from showing that most “subtle seizures” are often not associated with evident electrographic discharges, simultaneous video and EEG monitoring also helped to clarify the epileptic or nonepileptic basis for other seizure types in this neonatal seizure classification. Clonic seizures, both focal and multifocal, are highly correlated with electrographic seizure discharges. Note that there is no generalized clonic category in the neonatal seizure classification—the immature neuronal circuitry of the newborn is not felt to be capable of mounting a generalized seizure discharge. Among tonic seizures, focal tonic episodes are highly correlated with electrographic seizure activity. In contrast, generalized tonic episodes (full-body tonic stiffening) do not usually manifest an electrographic seizure correlate. Myoclonic seizures are variably associated with electrographic seizure patterns.29

A patient’s epilepsy (seizure) syndrome is defined by the types of seizures experienced, age of onset, neurologic assessment, family history, progression of the disorder, and EEG patterns. Identification of a particular epilepsy syndrome will often suggest possible etiologies, a specific prognosis, and treatments to be tried or avoided30 (see eTable 556.2). Select epilepsy syndromes are discussed below, generally in order of age of onset.

Early Myoclonic Encephalopathy (EME and Early Infantile Epileptic Encephalopathy (EIEE)

Early myoclonic epilepsy (EME) and early infantile epileptic encephalopathy (EIEE) are the two major catastrophic epilepsies of early infancy. These two syndromes have much in common, but they appear to represent two distinct entities.

Early Myoclonic Encephalopathy

Infants with EME present soon after birth with both fragmentary and massive myoclonic seizures. Other seizure types also occur. The magnetic resonance imaging (MRI) scan is typically normal, and a large fraction of these babies are eventually found to have a specific metabolic disorder: nonketotic hyperglycinemia (NKH). It is thought that the group of babies with EME who do not prove to have a diagnosable metabolic disorder such as NKH may have other metabolic abnormalities that have yet to be defined. This belief is based on the observations that such babies appear to have an anatomically normal brain by MRI, and there is usually no history of a previous neurological injury. Infants with EME fail to make developmental progress, and the seizures tend to be refractory to treatment. The EEG shows an unremitting burst-suppression pattern that may continue unabated through childhood.

Early Infantile Epileptic Encephalopathy (EIEE)

EIEE, also known as Ohtahara syndrome, appears to be a “lesional” epilepsy syndrome and is often associated with an abnormal MRI scan. Tonic seizures are more prominent in EIEE as compared to EME. MRI abnormalities associated with this syndrome can include cerebral malformations or cerebral injuries, including those that may occur in babies with hypoxic-ischemic encephalopathy. Therefore, EIEE occurs as an epileptic syndrome that is believed to be symptomatic of a preexisting abnormality, be it a cerebral malformation or some type of brain injury, though recently a few cases have been associated with genetic abnormalities.31,32 Compared to EME, EIEE is more likely to evolve to West syndrome or the Lennox-Gastaut syndrome (see below). Like EME, EIEE is typically associated with a burst-suppression pattern on EEG. This pattern is more likely to evolve into other EEG background patterns later in life as compared to EME in which the burst-suppression pattern is persistent in a much higher fraction of affected patients.

Concept of the Age-Dependent Encephalopathies

EIEE may be considered one of the age-dependent epileptic encephalopathies. This group of syndromes represents the characteristic epileptic response of the brain to injury that is specific to certain age groups. For instance, when the brain is injured in the neonatal period, the response to injury may present as the EIEE syndrome. When the epileptic response to an injury or abnormality occurs later in infancy (typically after 3 months of age), the child may develop a pattern of infantile spasms or West syndrome. The epileptic response to an injury that appears after 3 years of age may present as the Lennox-Gastaut syndrome. Because different maturational states of the brain are only associated with certain syndromic patterns, West syndrome is not seen to present in young adults, and Lennox-Gastaut syndrome is not seen to present in infancy—it appears that the human brain does not mount certain types of seizure patterns at certain ages.

Pyridoxine-Dependent Seizures

The syndrome of pyridoxine-dependent seizures is extremely rare in its pure form. In the classic presentation of this disorder, a newborn is found to have refractory seizures associated with a persistent burst-suppression pattern on EEG. Administration of pyridoxine, sometimes in high doses, abruptly breaks the EEG pattern and brings about a prompt termination of the seizure activity. Without continued supplementation with pyridoxine, the seizures will relapse. Because this is an easily treatable form of what would otherwise be a catastrophic epilepsy syndrome, pyridoxine infusion is frequently carried out in newborns with seizure patterns that potentially match the phenotype of this disorder (in particular, those having a burst-suppression pattern on EEG and refractory seizures without other explanation). Later onset and partial forms of this disorder also exist and are even less commonly encountered.

Early Myoclonic Encephalopathy and Early Infantile Epileptic Encephalopathy

Early myoclonic epilepsy (EME) and early infantile epileptic encephalopathy (EIEE) are the two major catastrophic epilepsies of early infancy. These 2 syndromes have much in common, but they appear to represent 2 distinct entities.

Early Myoclonic Encephalopathy

Infants with EME present soon after birth with both fragmentary and massive myoclonic seizures. Other seizure types also occur. The magnetic resonance imaging (MRI) scan is typically normal, and a large fraction of these babies are eventually found to have a specific metabolic disorder: nonketotic hyperglycinemia (NKH). It is thought that the group of babies with EME who do not prove to have a diagnosable metabolic disorder such as NKH may have other metabolic abnormalities that have yet to be defined. This belief is based on the observations that such babies appear to have an anatomically normal brain by MRI, and there is usually no history of a previous neurological injury. Infants with EME fail to make developmental progress, and the seizures tend to be refractory to treatment. The EEG shows an unremitting burst-suppression pattern that may continue unabated through childhood.

Early Infantile Epileptic Encephalopathy (Eiee)

EIEE, also known as Ohtahara syndrome, appears to be a “lesional” epilepsy syndrome and is often associated with an abnormal MRI scan. Tonic seizures are more prominent in EIEE as compared to EME. MRI abnormalities associated with this syndrome can include cerebral malformations or cerebral injuries, including those that may occur in babies with hypoxic-ischemic encephalopathy. Therefore, EIEE occurs as an epileptic syndrome that is believed to be symptomatic of a preexisting abnormality, be it a cerebral malformation or some type of brain injury, though recently a few cases have been associated with genetic abnormalities.31,32 Compared to EME, EIEE is more likely to evolve to West syndrome or the Lennox-Gastaut syndrome (see below). Like EME, EIEE is typically associated with a burst-suppression pattern on EEG. This pattern is more likely to evolve into other EEG background patterns later in life as compared to EME in which the burst-suppression pattern is persistent in a much higher fraction of affected patients.

Concept of the Age-Dependent Encephalopathies

EIEE may be considered one of the age-dependent epileptic encephalopathies. This group of syndromes represents the characteristic epileptic response of the brain to injury that is specific to certain age groups. For instance, when the brain is injured in the neonatal period, the response to injury may present as the EIEE syndrome. When the epileptic response to an injury or abnormality occurs later in infancy (typically after 3 months of age), the child may develop a pattern of infantile spasms or West syndrome. The epileptic response to an injury that appears after 3 years of age may present as the Lennox-Gastaut syndrome. Because varying maturational states of the brain are only associated with certain syndromic patterns, West syndrome is not seen to present in young adults, and Lennox-Gastaut syndrome is not seen to present in infancy—it appears that the human brain does not mount certain types of seizure patterns at certain ages.

Pyridoxine-Dependent Seizures

The syndrome of pyridoxine-dependent seizures is extremely rare in its pure form. In the classic presentation of this disorder, a newborn is found to have refractory seizures associated with a persistent burst-suppression pattern on EEG. Administration of pyridoxine, sometimes in high doses, abruptly breaks the EEG pattern and brings about a prompt termination of the seizure activity. Without continued supplementation with pyridoxine, the seizures will relapse. Because this is an easily treatable form of what would otherwise be a catastrophic epilepsy syndrome, pyridoxine infusion is frequently carried out in newborns with seizure patterns that potentially match the phenotype of this disorder (in particular, those having a burst-suppression pattern on EEG and refractory seizures without other explanation). Later onset and partial forms of this disorder also exist and are even less commonly encountered.

Benign Neonatal Convulsions (BNC) and Benign Familial Neonatal Convulsions (BFNC)

Benign familial neonatal convulsions and benign neonatal convulsions are the two important benign seizure syndromes of the newborn. The essence of both of these seizure syndromes is similar—seizures early in the newborn period in a previously well infant followed by a generally benign outcome.

The syndrome of benign neonatal convulsions (BNC) is also referred to as fifth day fits, a reminder that the fifth day of life is the most common age of onset of this syndrome. Because a benign long-term course is a key element of the syndrome, the diagnosis must often be made in retrospect. Affected babies usually appear normal at birth and have been discharged home from the hospital uneventfully. The seizures begin in the first week of life with 90% of babies presenting between the fourth and sixth days of life. The seizures usually resolve during the first year of life, most often by 2 months of age, with continuing normal development. There is no antecedent history of a difficult delivery or birth injury, and neuroimaging is normal. A positive family history of seizures is usually absent. Apart from possible mild hypotonia, the examination is normal. A search for CNS infection is negative, and no electrolyte or other metabolic disturbances are found. The clinician is left with a story of an otherwise perfectly well newborn with unexplained onset of seizures in whom all testing is normal.

Whether or not benign neonatal convulsions represent a single, distinct syndrome has been questioned. From one point of view, it should not be surprising that the subgroup of newborns with seizures selected for having a negative history and normal testing would have a more favorable outcome than those who have an abnormal history, testing, or neuroimaging. There is also a question as to whether the incidence of later epilepsy in these infants is somewhat higher than that of the unaffected population.

The syndrome of benign familial neonatal convulsions (BFNC) has many elements in common with the BNC syndrome. In BFNC, however, there is a positive family history for seizures in the newborn period and seizure onset is somewhat earlier, typically on the second or third day of life, usually resolving by the second month, but sometimes later. Unlike BNC, BFNC may be associated with a later incidence of epilepsy as high as 10% to 15%. Also, the rate of mild developmental problems may be higher than that seen in the unaffected population. A large proportion of affected individuals have been found to have linkage to the 20q13.3 gene locus corresponding to a mutation in the potassium channel gene KCNQ2 and a smaller kindred showed linkage to the 8q24 locus and a mutation in the KCNQ3 gene. Still another kindred appeared to have no abnormality at either of these loci, suggesting that additional genetic abnormalities that cause this syndrome have yet to be identified. The typical seizure BFNC is the clonic seizure, preceded by tonic stiffening and apnea in some.33

Infantile Spasms and West Syndrome

The term infantile spasms refers to a specific seizure type; the term “West syndrome” denotes an age-dependent epilepsy syndrome that includes the triad of infantile spasms, an EEG pattern of hypsarrhythmia, and abnormal neurodevelopment. The original clinical description of this syndrome is found in a letter to the journal Lancet by W.J. West in 1841, who described the seizures in his son.34 Infantile spasms may express as flexor spasms, extensor spasms, or mixed (asymmetrical) spasms. Flexor spasms, the most common form, consist of a brief tonic contraction in flexion of the body on the hips, flexion of the head on the neck, and tensing of the shoulders, sometimes in abduction (also referred to as “jackknife seizures” or “Salaam seizures”). The flexed posture is maintained for approximately 1 second, followed by relaxation. The spasms tend to occur in clusters lasting several minutes, often after awakening from sleep. Less commonly, spasms can result in extensor rather than flexor posturing; asymmetrical spasms may also occur. The presence of asymmetrical spasms should always prompt a search for an underlying focal lesion. Other, m ilder variants of spasms can be seen, including relatively subtle bobbing of the head. Because epileptic spasms are seen in both apparently generalized and focal forms, this seizure type is difficult to categorize into one group or the other. The tensing posture assumed during infantile spasms can mimic gastrointestinal discomfort or episodes of colic. Although the large majority of such spasms occur during the first 3 years of life, occasionally spasms persist past infancy. In older children or adults, the term infantile spasms becomes awkward, and the term epileptic spasms is preferred.

West syndrome usually begins between the ages of 3 and 18 months. In many, the seizures resolve spontaneously but are often later replaced by other seizure types, such as focal seizures or the Lennox-Gastaut syndrome. Only a relatively small minority of patients are intellectually normal after West syndrome. The finding of hypsarrhythmia or one of its variants on EEG, a high-voltage, chaotic pattern that may only appear in sleep, is important to the diagnosis of West syndrome.

Benign Partial Epilepsies

The benign partial epilepsies of childhood are a group of epilepsy syndromes associated with normal neurodevelopmental status, normal neuroimaging, a favorable long-term outcome, and a specific age range of occurrence. These disorders are believed to be genetically transmitted and are often associated with distinctive EEG patterns. The two most common forms of benign partial epilepsy of childhood are benign childhood epilepsy with centrotemporal spikes (BCECTS), also known as benign rolandic epilepsy, and benign childhood epilepsy with occipital paroxysms (BCEOP).

BCECTS or benign rolandic epilepsy is one of the most common forms of childhood epilepsy. Rolandic seizures are usually seen between the ages of 5 and 13 years and almost always disappear by the age of 16 years.35 Two specific seizure types are seen in BCECTS. The first is a partial seizure usually occurring in the morning which includes speech arrest and hemifacial clonic spasms or a pulling of the face to one side. The seizure may be heralded by a sensory change in the face or on the inside of the cheek. The second seizure type is a generalized convulsion that occurs out of sleep.

It is rare for the seizures of BCECTS to persist after the teenage years, and of all seizure syndromes, BCECTS is the most likely to spontaneously remit. If a child has grand mal convulsions out of wakefulness, the diagnosis of rolandic epilepsy is unlikely.It is rare for the seizures of BCECTS to persist after the teenage years, and of all seizure syndromes, BCECTS is the most likely to spontaneously remit. Loiseau et al. were able to successfully locate 168 of the 267 patients they had earlier treated for rolandic epilepsy who were over 20 years of age at follow-up. Of these, 165 of the 168 were seizure-free; of the 3 with recurrences, 2 had only a single additional seizure. The 3 cases out of 168 who had the later seizures represented a prevalence rate that is not significantly different from the rate of epilepsy seen in the general population.35 The diagnosis of BCECTS is confirmed in children with the appropriate history by the presence of distinctive centrotemporal spikes in the EEG, although identical spikes are also found in the EEGs of many asymptomatic children.

Benign Childhood Epilepsy with Occipital Paroxysms (BCEOP)

Two types of BCEOP are recognized: a more common, early onset variety (also referred to as Panayiotopoulos type) and a late-onset form (referred to as Gastaut type). In the early onset form of BCEOP, seizures begin between the ages of 3 and 6 years. The typical seizures of early onset BCEOP include autonomic symptoms such as pallor, sweating, and irritability which may evolve to vomiting, eye deviation, and loss of consciousness and culminate in convulsions (either hemiclonic or generalized clonic). Seizures with visual symptomatology are rare in the early-onset syndrome. Nocturnal seizures are more common than daytime seizures. About two thirds of children with BCEOP manifest occipital spikes or occipital paroxysms, though it should be recalled that only a minority of the larger group of children with occipital spikes have a benign occipital epilepsy syndrome.36 In the early onset syndrome, seizures are infrequent with as few as 1 or 2 lifetime episodes and remit within a few years of presentation.

The late-onset form of BCEOP is considerably (5-fold) less common than the early-onset form with mean age of onset at 8 years of age, as compared to 5 years of age for the early onset form. In contrast to the early-onset form, seizures are much more frequent, tend to occur in the daytime, and visual phenomena with elementary or (more rarely) complex visual hallucinations are common. Blindness may occur as either an ictal or postictal phenomenon. Headache and, more rarely, nausea and vomiting can be associated seizure symptoms. Both the early and late forms of BCEOP may show a distinctive pattern of occipital spikes that suppress with eye opening, the fixation-off effect, though the finding is not diagnostic of either syndrome.

The primary generalized epilepsies are a group of genetic epilepsy syndromes characterized by generalized seizures and generalized spike-wave discharges in the EEG. Most of these idiopathic syndromes occur in cognitively normal children and are caused by disorders of ion channels (“channelopathies”) or errors in synaptic receptors.

The absence seizures of childhood absence epilepsy (CAE or pyknolepsy) usually begin between 4 and 8 years of age. The hallmark seizure of CAE is the typical absence seizure, described above, consisting of brief periods of staring and unawareness of the environment, with or without subtle rhythmic eye blinking. Children with CAE typically have as many as 100 to 200 of these brief absence seizures per day. A large fraction of children eventually grow out of the tendency to have absence seizures during the teenage years, with 90% remitting by the age of 20 years. Families and patients should be made aware of the estimated 40% to 50% lifetime risk of generalized convulsions in children with CAE, even in those in whom the absence seizures remit spontaneously.

Juvenile Absence Epilepsy (JAE)

In JAE, the absence seizures begin in the early teenage years and, compared to CAE, JAE patients are more likely to experience GTC seizures; there is an important overlap between JAE and juvenile myoclonic epilepsy (described below). In JAE, the absence seizures tend to be much less frequent (eg, once or twice per week) but of longer duration, with spells lasting as long as 20 seconds not uncommon in the JAE group.

Epilepsy with Generalized Tonic-Clonic (GTC) Seizures on Awakening

The morning GTC seizures of this syndrome are similar to those that occur in juvenile myoclonic epilepsy. This syndrome may represent the subset of juvenile myoclonic epilepsy without myoclonic or absence seizures.

Juvenile Myoclonic Epilepsy and Epilepsy with Generalized Tonic-Clonic (GTC) Seizures on Awakening

Three seizure types may be seen in juvenile myoclonic epilepsy (JME): myoclonic seizures (required for the formal diagnosis), GTC seizures, and absence seizures (in approximately one quarter). On average, the myoclonic jerks begin at 12 years of age, and the GTC seizures begin at 13 years of age. The morning myoclonic jerks that consist of quick extensor jerks of the upper arms may initially escape medical attention until the more dramatic GTC seizures occur. In epilepsy with GTC seizure on awakening the morning seizures are similar to those that occur in juvenile myoclonic epilepsy. This syndrome may represent the subset of juvenile myoclonic epilepsy without myoclonic or absence seizures. The characteristic EEG findings of JME are fast spike-wave discharges (4 to 5 Hz generalized spike-wave discharges) and high-voltage polyspikes. A minority of patients may also exhibit a photoparoxysmal response: spike-wave discharges that are triggered by strobe light stimulation.

Lennox-Gastaut Syndrome

The Lennox-Gastaut syndrome (LGS) consists of a triad of mixed seizures, a slow spike-wave pattern on EEG (firing at 2.5 Hz or less), and cognitive dysfunction, all beginning in early childhood. Seizure types seen in LGS include atypical absence seizures, atonic seizures, tonic seizures (especially occurring during sleep), and myoclonic seizures. LGS is sometimes categorized as a symptomatic generalized epilepsy, though many patients also manifest focal or multifocal EEG patterns. The seizures of LGS are often refractory to treatment. The characteristic EEG findings of JME are fast spike-wave discharges (4 to 5 Hz generalized spike-wave discharges) and high-voltage polyspikes. A minority of patients may also exhibit a photoparoxysmal response: spike-wave discharges that are triggered by strobe light stimulation.

Epilepsy with Myoclonic-Astatic Seizures or Doose Syndrome

In 1970 Doose et al. described an epilepsy syndrome with myoclonic seizures and falling spells which appeared to be distinct from the LGS.37 Children with LGS usually appeared to have a symptomatic epilepsy, but those with this new syndrome had no clear etiology for their seizures but did have a strong family history of epilepsy. Therefore, a genetic etiology was suspected.

The hallmark seizure of myoclonic-astatic epilepsy is the myoclonic-astatic seizure that consists of one or more brief myoclonic jerks followed by a loss of posture, often culminating in a fall. There is brief loss of consciousness during the attacks followed by quick recovery. Seizure onset is usually between 1½ and 5 years of age. A large variety of other generalized seizure types occur, including GTC seizures, absence seizures, and tonic seizures. Response to treatment and prognosis vary widely in this group, with some patients responding fairly well to treatment but others refractory to therapy and following a progressive downhill developmental course.

Benign Myoclonic Epilepsy of Infancy

Benign myoclonic epilepsy of infancy (BMEI) is a syndrome of relatively mild myoclonic seizures typically presenting between the ages of 1 and 5 years. The syndrome usually remits, but it is possible that learning and developmental difficulties occur at a higher frequency in affected individuals compared to the general population. The myoclonic seizures are accompanied by polyspikes, and strobe stimulation may elicit the jerks in a subset of infants. Because of the occasional occurrence of GTC seizures in children with this syndrome, benign myoclonic epilepsy of infancy may exist on a continuum with other primary generalized epilepsy syndromes.

Reflex-Induced Myoclonic Epilepsy

Reflex-induced myoclonic epilepsy may represent a subset of benign myoclonic epilepsy of infancy in which the myoclonic jerks are elicited by sound or touch. In certain infants, brushing the cheek or other tactile or auditory stimuli may elicit a train of spike-wave or polyspike-wave discharges associated with a brief run of rapid myoclonic jerks. This syndrome, too, is generally expected to remit during childhood.38

Severe Myoclonic Epilepsy of Infancy (Dravet Syndrome)

Severe myoclonic epilepsy of infancy (SMEI) is a childhood-onset epilepsy that is refractory to treatment and is associated with an ongoing neurological deterioration caused by the seizures (epileptic encephalopathy). The typical presentation begins with repetitive, prolonged febrile seizures during the first year of life. Among the generalized seizures of this syndrome, which often has a genetic basis, the presence of myoclonic seizures is not invariable. Many children with SMEI have been found to have an error in the SCN1A gene, which codes for a portion of a neuronal voltage-gated sodium channel, though children with errors in the SCN1A gene may express other epilepsy phenotypes as well.

Epilepsy with Continuous Spike Wave of Slow Sleep

Epilepsy with continuous spike wave of slow sleep (CSWS) is a relatively rare epileptic encephalopathy associated with neuropsychological impairment and a variety of possible seizure types, both generalized and focal. It shares many clinical features with the Landau-Kleffner syndrome (described below). Epilepsy with CSWS is associated with a distinctive EEG pattern during slow wave sleep termed electrical status epilepticus of sleep (ESES). CSWS is used to refer to the clinical syndrome, and ESES refers specifically to the EEG pattern. In this sleep-activated EEG pattern spike-wave discharges are so rhythmic that they could potentially be mistaken for electrographic seizure activity.

Clinical seizures in this syndrome range from rare or no seizures to seizures that occur several times per week. A wide variety of seizure types is seen, including nocturnal seizures, either hemiclonic or apparent GTC, typical absence seizures, or, in some, atypical absence spells that may be associated with falls. Tonic seizures as are seen in the LGS generally do not occur. In some, the syndrome appears to be idiopathic with normal neuroimaging, but in others symptomatic basis can be identified. High-dose diazepam therapy is effective in some.39

Acquired Epileptic Aphasia

The Landau-Kleffner syndrome (LKS)40 or acquired epileptic aphasia is a childhood epilepsy syndrome that probably exists somewhere on the spectrum that includes BCECTS and epilepsy with CSWS. The language disturbance predominates in children with LKS. In the classic pattern, a child who has developed language normally develops an aphasia that is most pronounced in the receptive realm. Concurrently or soon after, an EEG abnormality is noted over one or both temporal lobes, strongly activated by sleep. Behavior and attention may also be adversely affected. Children with LKS may also have seizures, but these are usually sporadic and few in number. In rare instances, LKS may begin before significant language has developed, and the “acquired” nature of the syndrome may not be evident, the presentation mimicking pure language delay or an autistic spectrum disorder (ASD). How often LKS plays a role in the language and behavioral regression seen in children with ASD is a matter of current debate; however, it now appears that LKS plays a role in only a very small minority of the larger population of children with ASD.

Temporal Lobe Epilepsy (TLE)

TLE is the most common localization-related (focal) epilepsy. The classic seizure associated with the temporal lobe is the CPS. When a cause for TLE can be identified, such as mesial temporal sclerosis, a glioma, hamartoma, or a dysgenetic lesion in the temporal lobe, this kind of epilepsy can be considered a symptomatic epilepsy. In cases in which all testing is normal, temporal lobe epilepsy is classified as cryptogenic epilepsy.

The classic temporal lobe seizure may begin with staring, possibly associated with automatisms such as fumbling movements of a hand or chewing or lip-smacking behaviors. During the seizure prodrome, psychic symptoms such as the subjective feeling of fear or a déjà vu phenomenon may occur. Here, the term prodrome is misleading because such psychic symptoms represent the beginning of the ictal discharge rather than a warning that one is to occur. Temporal lobe seizures may spread to ipsilateral motor cortex resulting in contralateral clonic movements or the seizure may secondarily generalize and evolve to a generalized convulsion.

Epilepsia Partialis Continua (EPC)

EPC describes refractory, highly focal, sometimes fragmentary motor seizures due to a lesion of the contralateral motor cortex. It is often associated with Rasmussen’s syndrome, a unilateral, apparently inflammatory disorder of unknown etiology occurring in childhood and associated with cognitive deterioration and progressive atrophy of the involved hemisphere.

Other Primary Generalized Epilepsies

Epilepsy with myoclonic-astatic seizures or Doose syndrome is characterized by myoclonic-astatic seizures that consist of one or more brief myoclonic jerks followed by a loss of posture, often culminating in a fall. There is brief loss of consciousness during the attacks followed by quick recovery. Seizure onset is usually between 1 and 5 years of age. A large variety of other generalized seizure types occur, including GTC seizures, absence seizures, and tonic seizures.

Benign myoclonic epilepsy of infancy (BMEI) is a syndrome of relatively mild myoclonic seizures typically presenting between the ages of 1 and 5 years. The syndrome usually remits, but it is possible that learning and developmental difficulties occur at a higher frequency in affected individuals compared to the general population. The myoclonic seizures are accompanied by polyspikes, and strobe stimulation may elicit the jerks in a subset of infants.

Reflex-induced myoclonic epilepsy may represent a subset of benign myoclonic epilepsy of infancy in which the myoclonic jerks are elicited by sound or touch. Severe myoclonic epilepsy of infancy is a childhood-onset epilepsy that is refractory to treatment and is associated with an ongoing neurological deterioration caused by the seizures (epileptic encephalopathy). The typical presentation begins with repetitive, prolonged febrile seizures during the first year of life. Epilepsy with continuous spike wave of slow sleep (CSWS) is a relatively rare epileptic encephalopathy associated with neuropsychological impairment and a variety of possible seizure types, both generalized and focal.

Epilepsy with continuous spike wave of slow sleep (CSWS) is a relatively rare epileptic encephalopathy associated with neuropsychological impairment and a variety of possible seizure types, both generalized and focal. Clinical seizures in this syndrome range from rare or no seizures to seizures that occur several times per week.

Epilepsia partialis continua describes refractory, highly focal, sometimes fragmentary motor seizures due to a lesion of the contralateral motor cortex. It is often associated with Rasmussen's syndrome, a unilateral, apparently inflammatory disorder of unknown etiology occurring in childhood and associated with cognitive deterioration and progressive atrophy of the involved hemisphere.