Seizures and epilepsy in children: Classification, etiology, and clinical features

INTRODUCTION — Children with epilepsy, particularly infants, differ from adults not only in the clinical manifestations of their seizures, but also in the presence of unique electroencephalogram (EEG) patterns, etiologies, and response to antiseizure medications. The immature brain, particularly in the neonate and young infant, differs from the adult brain in the basic mechanisms of epileptogenesis and propagation of seizures (table 1). It is more prone to seizures, but seizures are more apt to disappear as the child grows.

This topic provides an overview of the classification and etiology of seizures and epilepsy in children. The clinical diagnosis and management of new-onset seizures and epilepsy in children are presented separately. (See "Seizures and epilepsy in children: Clinical and laboratory diagnosis" and "Seizures and epilepsy in children: Initial treatment and monitoring".)

DEFINITIONS

Seizure — A seizure represents the clinical expression of abnormal, excessive or synchronous discharges of neurons residing primarily in the cerebral cortex. This abnormal paroxysmal activity is intermittent and usually self-limited, lasting seconds to a few minutes.

On electroencephalography (EEG), a seizure is characterized by sustained, abnormal electrical activity that has a relatively discrete beginning and end, with an evolution characterized by changing morphology and amplitude (voltage) of the abnormal discharges. A focal seizure has a restricted regional onset followed by spread to neighboring or remote brain regions. It may spread to deep subcortical regions and evolve to a bilateral tonic-clonic seizure (previously referred to as a secondarily generalized seizure, to differentiate it from seizures that are generalized from the onset) [1-4]. (See "Electroencephalography (EEG) in the diagnosis of seizures and epilepsy".)

●Acute symptomatic seizure – An acute symptomatic seizure (also referred to as a provoked seizure or reactive seizure) is a seizure that occurs in close temporal association with an acute systemic illness or brain insult [5]. Examples include hyponatremia, hypocalcemia, high fever, toxic exposure, intracranial bleeding, or bacterial meningitis. Acute symptomatic seizures are not classified as epilepsy unless they become a recurrent process beyond the acute illness [6]. (See "Seizures and epilepsy in children: Initial treatment and monitoring", section on 'Acute symptomatic seizure'.)

●Unprovoked seizure – An unprovoked seizure is a seizure that occurs in the absence of a potentially responsible clinical condition or occurs in relation to a preexisting brain lesion or progressive nervous system disorder beyond the time interval recognized for acute symptomatic seizure [5].

●Status epilepticus – Status epilepticus is defined by seizures that are prolonged or immediately recurrent without a return of consciousness. (See "Clinical features and complications of status epilepticus in children", section on 'Definition'.)

Epilepsy — Epilepsy is a state of an enduring predisposition to recurrent epileptic seizures [7]. An individual is considered to have epilepsy when any of the following exists [6]:

●At least two unprovoked (or reflex) seizures occurring more than 24 hours apart. Reflex seizures are seizures evoked by specific external (eg light flashes) or internal (eg, emotion, thoughts) stimuli [8].

●One unprovoked (or reflex) seizure and a probability of further seizures that is similar to the general recurrence risk after two unprovoked seizures (eg, ≥60 percent), occurring over the next 10 years. This may be the case with remote structural lesions such as stroke, central nervous system infection, or certain types of traumatic brain injury.

●Diagnosis of an epilepsy syndrome.

Epilepsy is considered to be a disease associated with lasting derangement of normal brain function [6]. It may arise from a variety of genetic, structural, metabolic, immune, infectious, or unknown causes [2-4,9]. (See 'Etiology' below.)

FORMAL CLASSIFICATION

Framework — The 2017 International League Against Epilepsy (ILAE) multi-level classification scheme, which is used by most neurologists, provides a framework (figure 1) to classify seizures and epilepsy based on the following levels [2-4]:

●Seizure type

●Epilepsy type

●Epilepsy syndromes

Etiology spans these levels and should be determined when possible by a complete evaluation including history, examination, neuroimaging studies, and laboratory investigation. (See "Seizures and epilepsy in children: Clinical and laboratory diagnosis".)

These concepts are reviewed and summarized in the sections below. The ILAE classification system is discussed in detail separately. (See "ILAE classification of seizures and epilepsy".)

Types of seizures and epilepsy — The ILAE classification divides seizures and epilepsies into four basic groups (table 2) based upon clinical and EEG data [1-4,10,11]:

●Focal

●Generalized

●Unknown (eg, epileptic spasms)

●Unclassified (ie, due to inadequate information or inability to categorize)

Focal (partial) seizures — Focal seizures originate within networks limited to one hemisphere. They may be discretely localized or more widely distributed. A focal seizure may or may not be associated with impaired awareness during the attack. When the patient is aware throughout the seizure, the seizure is described as a focal seizure without impairment of awareness (previously referred to as simple partial seizure). Focal seizures with impaired awareness correspond to what have previously been called complex partial seizures [1,2,10]. Impaired awareness is defined as the inability to respond normally to exogenous stimuli by virtue of altered awareness and/or responsiveness. "Complex" does not refer to the behavior per se, a mistake made by many physicians when describing a focal seizure.

Focal seizures are further subdivided primarily based upon the clinical signs and symptoms and the EEG localization. Examples include:

●Motor seizures may manifest as focal motor activity, sometimes with an anatomic spread or march of activity (Jacksonian), versive movement (turning of the eyes, head and/or trunk), vocalization, or arrest of speech.

●Sensory seizures can be manifest by paresthesias, feelings of distortion of an extremity, vertigo, gustatory sensation, olfactory symptoms, auditory symptoms, and visual phenomena such as flashing lights.

●Autonomic seizures may include an epigastric "rising" sensation (a common aura with medial temporal lobe epilepsy), sweating, piloerection, and pupillary changes.

●Focal seizures without impairment of awareness may also manifest higher cortical, psychic symptoms including dysphasia, feelings of familiarity ("déjà vu"), distortions of time, affective changes (particularly fear), illusions, and formed hallucinations. Such seizures are often referred to as auras.

●During focal seizures with impairment of awareness, the patient may have a variety of repetitive semipurposeful movements that are referred to as motor automatisms. These can include oral-buccal movements (chewing, swallowing, sucking), complex motor phenomena including bicycling and kicking movements, flailing of the arms, and even running, jumping, and spinning. Such seizures involve regions of both hemispheres, thus explaining the impaired awareness and the more complex and often bilateral motor symptomatology.

Focal seizures may start in a "silent" area of the brain such as the frontal lobe and become clinically apparent only when they spread to neighboring cortex such as the precentral gyrus of the frontal lobe or the hippocampus of the temporal lobe. In these cases, the EEG monitoring can be critical to the detection of a focal seizure onset.

What appears to be a generalized seizure can result from a focal seizure that has rapidly evolved into a bilateral convulsive seizure. The focal onset may not be recognized clinically. Clinical features of the seizure aura or of the postictal state are more likely to have precise localizing value than the more dramatic ictal phenomenon. The EEG typically reveals a focal onset to the seizure or localized spikes between seizures.

Generalized seizures — Generalized seizures can be conceptualized as originating at some point within, and rapidly engaging, bilaterally distributed networks. Awareness may be impaired, and this impairment may be the initial manifestation. Motor manifestations (if present) are bilateral. The ictal electroencephalographic patterns are bilateral from onset, and presumably reflect neuronal discharge which is widespread in both hemispheres.

Absence seizures manifest as episodes of sudden, profound impairment of consciousness without loss of body tone. Patients with generalized nonmotor seizures, such as absences, may have low amplitude myoclonic movements as well as mild tonic involvement of the limbs and trunk and simple motor automatisms, similar to those seen in focal seizures with impairment of awareness.

Previously used terminology of seizure classification, "secondary generalized" and "secondarily generalized," could be confusing and is no longer recognized in the ILAE classification [1,2]. The preferred way to describe a secondarily generalized seizure (ie, one that was known by EEG or by clinical symptoms to begin focally and later generalize) is "focal seizure evolving to a bilateral tonic-clonic seizure."

Unknown — With some types of epilepsy, the onset cannot be clearly determined as generalized or focal [2]. Epileptic spasms are key example. Epileptic spasms, which include infantile spasms, are seizures that involve spasms of the muscles of the neck, trunk, and extremities. (See "Infantile epileptic spasms syndrome: Clinical features and diagnosis".)

Epilepsy syndromes — The ILAE classification recognizes over 30 epilepsy syndromes, as listed in the table (table 3), each defined by a distinctive combination of clinical features, signs and symptoms, and electrographic patterns. Epilepsy syndrome classification provides invaluable prognostic, therapeutic, and in the case of familial epilepsies, genetic information. (See "ILAE classification of seizures and epilepsy", section on 'Level 3: Epilepsy syndrome'.)

Many of these syndromes begin in childhood. Epilepsy syndromes in children are reviewed in detail separately. (See "Epilepsy syndromes in children".)

Etiology — The causes of seizures and epilepsy can be broadly classified into six categories (see "ILAE classification of seizures and epilepsy", section on 'Etiology'):

●Genetic

●Structural

●Metabolic

●Immune

●Infectious

●Unknown

While some causes of seizures can affect children of any age, others have a predilection for certain age groups. In neonates, for example, most seizures are symptomatic of an identifiable etiology such as neonatal encephalopathy, a metabolic disturbance, or a central nervous system or systemic infection. In older infants and young children, febrile seizures are a common, age-dependent cause of seizure. Likewise, many of the genetic epilepsies tend to present during a relatively narrow age range (table 3).

A plethora of neurologic disorders can cause seizures. Those causes that may be less familiar to the pediatrician, particularly the developmental disorders, genetic syndromes, and brain malformations, including the cerebral dysplasias, are discussed individually below and elsewhere.

Genetic — Most of the recognized genetic epilepsies begin in childhood. Genetic epilepsies include the well-characterized epilepsy syndromes of the genetic generalized epilepsies, such as childhood absence epilepsy, juvenile absence epilepsy, and juvenile myoclonic epilepsy, as well as more severe syndromes often associated with neurodevelopmental disability and refractory seizures, such as Dravet syndrome (table 3). Routine neuroimaging is typically normal, and the cause is a known or presumed genetic ion channel or receptor defect.

More information on various genetic epilepsies affecting children can be found in the following topics:

● Overview of neonatal epilepsy syndromes

● Epilepsy syndromes in children

● Self-limited focal epilepsies of childhood

● Childhood absence epilepsy

● Juvenile myoclonic epilepsy

Structural — Virtually any insult to the cerebral cortex can cause a seizure. Acute symptomatic seizures may be triggered by a temporary cortical disturbance after minor head trauma (concussion), ischemia, or bleeding (intraparenchymal or subarachnoid hemorrhage).

Epilepsy can result from a chronic disturbance of neuronal function caused by a remote event such as perinatal asphyxia or in utero stroke or the expression of a progressive neurologic disorder, such as a tumor or a neurodegenerative or neurometabolic disease.

A small but not insignificant group of children have chronic seizures in the aftermath of acute hypoxic and toxic/metabolic events, head trauma, and vascular lesions.

Neurodevelopmental lesions — Magnetic resonance imaging (MRI) has markedly increased the ability to recognize neurodevelopmental lesions (NDL) and shifted the relative proportions of childhood epilepsy cases from cryptogenic to symptomatic. NDL are also referred to as cortical dysplasias, cortical dysgenesis, malformations, heterotopias, and disorders or malformations of cortical development [12].

Developmental lesions result from a disruption of one or more of the three major steps in the normal development of the cerebral cortex [13]:

●Proliferation of primitive stem cells (neuroblasts) in the germinal matrix near the wall of the ventricles

●Migration of these immature neurons along radial glial fibers through the white matter to the developing cortex

●Organization of the cortex.

These disorders have been classified according to MRI findings into focal, hemispheric, or generalized/multifocal. The generalized NDL include lissencephaly, pachygyria, and band, laminar, and subependymal heterotopia. The most common hemispheric NDLs are Sturge-Weber syndrome (associated with facial angiomatous nevi) and hemimegalencephaly (enlargement of an entire hemisphere from diffuse migrational and dysplastic changes). More limited NDLs include focal cortical dysplasia, schizencephaly (cleft extending from the ventricle to the cortical surface lined with dysplastic cortex), polymicrogyria, and subependymal heterotopias.

One group has provided a classification based upon the embryological, anatomical, and genetic bases of the developmental disorders [14]. They divided the malformations into four broad categories:

●Malformations caused by abnormal neuronal and glial proliferation

●Malformations caused by abnormal neuronal migration

●Malformations caused by abnormal cortical organization

●Developmental cortical malformations, not otherwise specified

The clinical and radiographic findings of 109 children with malformations of cortical development were reported from a radiological database in a major pediatric hospital [15]. Seizures were present in 75 percent, developmental delay or intellectual disability in 68 percent, abnormal neurologic findings in 48 percent, and congenital anomalies apart from the central nervous system malformations in 18 percent. The main NDLs found were heterotopic gray matter (clusters of neurons in the white matter or near the ventricular wall which failed to migrate to the cerebral mantle) in 19 percent, cortical tubers associated with tuberous sclerosis in 17 percent, focal cortical dysplasia in 16 percent, polymicrogyria (small, malformed cortical gyri) in 16 percent, agyria /pachygyria (absent, simple sulcation, or thickened cortex with broad gyri) in 15 percent, schizencephaly in 5 percent, transmantle dysplasia (a malformation extending from the wall of the lateral ventricle outward to the cortical surface) in 5 percent, and hemimegalencephalopathy in 4 percent.

Several of the NDLs are associated with recognizable somatic malformations and some with well-defined chromosomal defects [16]. In addition, germline and somatic mutations are being increasingly recognized as a cause of neurodevelopmental lesions. In one large study, next-generation sequencing was performed in 158 individuals with brain malformations, including 30 with subcortical band heterotopia, 20 with polymicrogyria with megalencephaly, 61 with periventricular nodular heterotopia, and 47 with pachygyria [17]. Causal mutations were found in 17 percent of patients, and 30 percent of mutations were somatic; mosaicism was common in peripheral blood cells and presumably exists in brain tissue as well. Some of the more commonly identified culprit genes include DCX, LIS1, FLNA, TUBB2B, DYNC1H1, PIK3CA, AKT3, PTEN, and MTOR [17-22].

Hippocampal sclerosis — Hippocampal sclerosis (atrophy of the hippocampus with neuronal cell loss and gliosis, also called mesial temporal sclerosis) is the most common lesion in adult patients referred to epilepsy surgery centers for refractory focal seizures of temporal lobe origin. Although it occurs in children, particularly teenagers, it is primarily a cause of seizures in adults. In pediatric epilepsy surgical series, approximately 20 percent of children younger than 12 years and 30 percent of children younger than 20 years have hippocampal sclerosis. The most common temporal lobe pathology was prenatally acquired abnormalities of neurogenesis [23,24].

Most younger patients (<3 years) have extratemporal seizure foci [25]. By comparison, in adults, 79 percent of surgeries were antero-temporal resections or amygdalohippocampectomies for temporal lobe epilepsy, usually associated with hippocampal sclerosis [26]. Some patients with this distinctive pathology have a history of complex febrile seizures in infancy and early childhood.

Metabolic — A number of metabolic conditions are associated with a substantially increased risk of developing epilepsy. Examples include glucose transporter deficiency, creatine deficiency syndromes, and mitochondrial cytopathies. Acute symptomatic seizures may be triggered by a transient disruption of cortical neuronal function such as a disturbed metabolic state (eg, high fever, hypocalcemia, hyponatremia)

Immune — Immune-mediated central nervous system inflammation may cause epilepsy; examples include Rasmussen encephalitis and anti-N-methyl-D-aspartate (NMDA) receptor encephalitis

Infectious — Infections are the most common cause of epilepsy worldwide. Examples include HIV, neurocysticercosis, malaria, tuberculosis, and sequelae of prior meningitis or encephalitis. Acute symptomatic seizures can occur in the setting of chemical/inflammatory excitation caused by infection (eg, meningitis, encephalitis, sepsis).

SIMPLIFIED CLASSIFICATION

Rationale — A simplified classification divides the epilepsies into five types [27]:

●Familial, which are autosomal dominant conditions

●Genetic generalized epilepsies

●Self-limited epilepsies

●Epilepsies with encephalopathy

●Focal structural epilepsies

The epilepsies are ordered this way based upon two factors: the likelihood of a familial predisposition, which is greatest at the top of the list, and the likelihood of a focal structural lesion, which is greatest at the bottom of the list (figure 2). Each type of epilepsy also has relatively distinct clinical presentations, EEG features, and outcomes [27]. The EEG features can be recognized quickly on a routine interictal EEG. The most informative aspects of the interictal EEG pattern are the background organization and the morphology and topography of epileptiform discharges (table 4).

The five types of epilepsy in the simplified classification are described in the sections that follow.

Familial epilepsies — The familial epilepsies account for a small proportion of children with epilepsy [27]. Seizures are typically focal. The EEG background is normal, and interictal epileptiform discharges (IEDs) are absent or rare. The inheritance pattern is autosomal dominant. Examples include benign familial neonatal epilepsy, benign familial infantile epilepsy, autosomal dominant nocturnal frontal lobe epilepsy, and autosomal dominant familial temporal lobe epilepsy. This category has a good prognosis for achieving seizure control but not seizure remission.

Genetic generalized epilepsies — The genetic generalized epilepsies, previously called idiopathic generalized epilepsies, are a relatively common type of epilepsy in children and adolescents [27]. They are characterized by generalized seizures, a normal EEG background, and stereotyped, generalized IEDs consisting of spike and wave discharges of 3 Hz or greater. Most genetic generalized epilepsies are responsive to broad spectrum antiseizure medications and have a good prognosis. Examples include myoclonic epilepsy in infancy, childhood absence epilepsy, and juvenile myoclonic epilepsy.

Self-limited epilepsies — The self-limited epilepsies are the most common types affecting children. Presentations vary according to age. The background EEG is normal, and IEDs are characterized by stereotyped focal or multifocal spikes [27]. The presumed genetic basis of these epilepsies is not fully described; the inheritance of spikes tends to be autosomal dominant with variable penetrance, but a lack of concordance among studies of twin pairs for a clinical predisposition to epilepsy has argued against a major genetic component. The self-limited epilepsies have an excellent prognosis with respect to seizure remission, although some affected children may have mild cognitive impairment.

Examples include benign epilepsy with centrotemporal spikes (BECTS; also known as benign rolandic epilepsy), benign occipital epilepsy of childhood (Gastaut syndrome), and Panayiotopoulos syndrome. (See "Self-limited focal epilepsies of childhood".)

Epilepsies with encephalopathy — Epilepsies associated with encephalopathy are generally more severe conditions with a diffusely slow EEG background and pleomorphic multifocal or diffuse IEDs [27]. Etiologies include genetic, metabolic, and structural abnormalities. These conditions are often associated with intractable epilepsy. Examples include Dravet syndrome, the early epileptic encephalopathies, West syndrome, late infantile epileptic encephalopathy, and Lennox-Gastaut syndrome.

Focal structural epilepsies — Focal structural epilepsies are characterized by focal seizures, in some cases accompanied by epileptic spasms. EEG findings include focal background slowing and pleomorphic focal IEDs caused by underlying structural brain lesions. Children with refractory epilepsy in this category tend to be good candidates for resective and ablative epilepsy surgery.

EPIDEMIOLOGY — In population-based studies, incidence rates of epilepsy in childhood range from approximately 0.5 to 8 per 1,000 person-years [28-31]. An estimated 0.5 to 1 percent of children and adolescents will experience at least one afebrile seizure by age adolescence. There is a 3.6 percent risk of experiencing at least one seizure in an 80-year lifespan [32].

Of all children, 3 to 5 percent will have a single febrile seizure in the first five years of life, and 30 percent will have additional febrile seizures. Epilepsy occurs more frequently in children who have had febrile seizures than in the general population; 3 to 6 percent of those with febrile seizures will develop afebrile seizures or epilepsy. (See "Clinical features and evaluation of febrile seizures" and "Treatment and prognosis of febrile seizures".).

The highest incidence of epilepsy occurs at the extremes of life [33]. The incidence in resource-abundant countries is highest in the first few months of life, particularly in the immediate postnatal period, falls significantly after the first year of life, is stable during the first decade, and then falls again in adolescence. Incidence is lowest in young and middle adulthood and begins increasing in the 50s, with a dramatic increase after age 60; by age 70, the incidence exceeds that of infancy. The incidence profile is quite different in resource-poor countries, where the peak in older adults usually is absent and the highest incidence occurs in young adults [34].

In most studies, incidence rates are slightly higher in males than in females [30]. No significant racial differences exist. The incidence is higher in lower socioeconomic groups [35].

Overall incidence figures show that focal (partial) seizures (with or without impairment of awareness) are the most common seizure type in all age groups and account for more than 50 percent of all seizures in children [36,37]. Focal seizures with alterations of awareness are the most common subtype [28]. Generalized seizures are more common in children than in adults, with generalized tonic-clonic, absence, and myoclonic seizures following focal seizures in frequency of occurrence.

CLINICAL CHARACTERISTICS

Clinical expression — Seizures are sometimes described as clinical (full clinical expression), subtle (minimal clinical expression), or subclinical (no clinical or outward manifestation of the electrical seizure activity). Clinical seizures are classified based upon the individual's ictal behavior with consideration of the electroencephalography (EEG) findings.

Clinical features of seizures — Seizures are usually stereotyped (each one is like the previous one), random (occur at any time of the day or night), and are rarely precipitated by specific environmental, psychological, or physiological events. Some individuals have several different types of seizures, but most have one type that expresses itself in partial or complete form. As an example, a full seizure may be characterized by flashing lights in one visual field (a focal seizure with occipital lobe onset), followed by eye deviation away from the side of onset (version, caused by spread to the neighboring association cortex), followed by loss of awareness of the surroundings with automatic behavior (motor automatisms such as lip-smacking and swallowing movements) caused by spread to the temporal lobe limbic system of both hemispheres, and a few seconds later culminates in a bilateral convulsive seizure. On some occasions, the patient may experience only the first stage or stages of the seizure with absence of the later stages.

Only close questioning of the patient or witnesses will uncover the valuable localizing information afforded by the first stages of the ictus, often called the seizure aura. Close questioning of children with a referral diagnosis of "grand mal seizures" may yield information indicating a focal onset. Clinical features of the seizure aura or postictal state are more likely to have precise localizing value than the more dramatic ictal phenomenon [38,39].

However, exceptions to these basic premises are numerous. Some individuals have seizures only during sleep, others only upon awakening in the morning, others always at the time of menstruation (catamenial seizures), and some following specific stimuli such as certain sounds, flashing lights, stubbing the foot, or being tapped on the shoulder (reflex seizures). While the latter seizures (sensory provoked) are rare, uncovering this information may allow the clinician to classify the child as having a specific epileptic syndrome and develop specific therapy (eg, special glasses with filtered lenses for visually provoked seizures).

Seizure variation according to age — Seizures in younger children differ significantly from those in older children and adults. Children older than six years tend to have seizures that are quite similar to those of adults, whereas younger children and infants have fewer complex behaviors, particularly with focal seizures with impairment of awareness. Determination of an alteration of awareness is difficult in infants and young children. In addition, their behaviors during a seizure tend to be less complicated and more fragmented than those in older children. Typical unprovoked generalized tonic-clonic and absence seizures are extremely uncommon in the first two years of life and never occur in the newborn [40]. These issues, unique to the child between two months and two years, have prompted proposals for classifications specifically directed to this age group (table 5) [41-43].

Children with similar seizure types often share other features, such as age of onset, level of motor and cognitive development, and EEG features, recognizable as a distinctive epilepsy syndrome [1,10].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Epilepsy in children (The Basics)")

●Beyond the Basics topics (see "Patient education: Seizures in children (Beyond the Basics)")

SUMMARY

●Definitions

•Seizure – A seizure represents the clinical expression of abnormal, excessive or synchronous discharges of neurons residing primarily in the cerebral cortex. This abnormal paroxysmal activity is intermittent and usually self-limited, lasting seconds to a few minutes. An acute symptomatic seizure (also referred to as a provoked seizure or reactive seizure) is a seizure that occurs in close temporal association with an acute systemic illness or brain insult. An unprovoked seizure is a seizure that occurs in the absence of a potentially responsible clinical condition or occurs in relation to a preexisting brain lesion or progressive nervous system disorder. (See 'Seizure' above.)

•Epilepsy – Epilepsy is a state of an enduring predisposition to recurrent epileptic seizures. Specific clinical criteria for epilepsy are defined above. (See 'Epilepsy' above.)

●ILAE classification – The 2017 International League Against Epilepsy (ILAE) multi-level classification scheme provides a framework to classify seizures and epilepsy according to three levels (seizure type, epilepsy type, and epilepsy syndromes) and seizure etiology, as depicted in the figure (figure 1). (See 'Formal classification' above and 'Framework' above.)

•Types – The ILAE classification divides seizures and epilepsy into several groups based upon clinical and electroencephalography (EEG) data (table 2):

-Focal (partial) seizures (see 'Focal (partial) seizures' above)

-Generalized seizures (see 'Generalized seizures' above)

-Unknown seizures (the onset cannot be clearly determined as generalized or focal), a category that includes epileptic spasms (see 'Unknown' above)

•Epilepsy syndromes – The ILAE classification recognizes over 30 epilepsy syndromes, as listed in the table (table 3), each defined by a distinctive combination of clinical features, signs and symptoms, and electrographic patterns. (See 'Epilepsy syndromes' above and "Epilepsy syndromes in children".)

•Etiology – The etiologic classification of seizures and epilepsy includes genetic, structural, metabolic, immune, infectious, and unknown categories (table 3). Any insult to the cerebral cortex can cause a seizure. Many epilepsy syndromes have a known or presumed genetic component. (See 'Etiology' above.)

●Simplified classification – A simplified classification divides the pediatric epilepsies into five types:

•Familial

•Genetic generalized epilepsies

•Self-limited epilepsies

•Epilepsies with encephalopathy

•Focal structural epilepsies

The EEG features that distinguish these types of epilepsies can be recognized quickly on a routine interictal EEG (table 4). (See 'Simplified classification' above.)

●Epidemiology – An estimated 1 percent of children and adolescents in the United States will experience at least one unprovoked seizure by age 14 years. The incidence is highest in the first few months of life, particularly in the immediate postnatal period, falls significantly after the first year of life, is stable during the first decade, and then falls again in adolescence. (See 'Epidemiology' above.)

●Clinical characteristics – Seizures are usually stereotyped (each one is like the previous one), random (occur at any time of the day or night), and are rarely precipitated by specific environmental, psychological, or physiological events. Most patients with loss of consciousness during a seizure awaken slowly and may appear confused or disoriented (postictal state). While there are exceptions, unusual clinical features may suggest the possibility of an alternative diagnosis. (See 'Clinical characteristics' above and "Seizures and epilepsy in children: Clinical and laboratory diagnosis", section on 'Differential diagnosis'.)

●Variation by age – Seizures in younger children differ significantly from those in older children and adults. Children older than six years tend to have seizures that are quite similar to those of adults, whereas younger children and infants have fewer complex behaviors, particularly with focal seizures with impairment of awareness. (See 'Seizure variation according to age' above.)