Paroxysmal Disorders

History

A careful description of the event or events from beginning to end, including re-enactments or videos by the parents of any unclear physical symptoms, is critical.

Pertinent questions include:

• Was this the first such event, or have there been multiple events?

• Is there a single or multiple episodes within the event?

• What was the child doing at the time of each spell—were they awake, asleep, playing, or sitting quietly?

• If they were asleep, how long had they been asleep, or what time of day or night did the spell occur?

• If abnormal tone or movements were involved, was the child rigid or limp, and which limbs were involved? Were the movements rhythmic and synchronous, or were they alternating, migratory, or stop-start?

• If the child was unresponsive or had alteration of awareness, what did the parents do to ascertain their level of responsiveness? Did the parents try touching them to regain their attention, or merely call their name?

• How long did the event last, and how did the child behave afterward?

• Did the child describe any symptoms prior to the onset of the actual event, or was there any abnormal behavior that the parents witnessed prior to the event?

• Were there any signs or symptoms of illness associated with the spell? Were any fevers documented?

• Has there been any behavioral, developmental, or academic regression since the start of the events?

• Is the child developmentally normal? If not, has the child’s development always been abnormal, or was there a regression at some point?

• Were there any problems during pregnancy or the delivery?

• Has the child ever had a significant head injury or central nervous system (CNS) infection?

• Is there any family history of similar events, or any other neurologic disorders?

Parents frequently record videos of these spells on their mobile devices, which are ideal for reviewing the episode firsthand.

Physical Examination

The physician should compare vital signs, including blood pressure and head circumference, to previous measurements if possible. Elevated blood pressure can be indicative of pain, anxiety, increased intracranial pressure, or hypertensive encephalopathy. Hypotension may suggest syncopal events or sepsis. Dramatic increases in head circumference in infants may indicate intracranial pathology.

A general physical examination, including the cardiopulmonary and abdominal examinations, should be performed; abnormalities may indicate a non-neurologic cause for spells. Dysmorphic features or cutaneous findings can provide clues toward an underlying syndromic diagnosis.

An ophthalmologic examination can be as simple as obtaining a red reflex and observation of eye movements in young children. Eye movements may be observed by having the patient track a moving object or toy; abnormalities such as deviation, nystagmus, or new-onset limitations in range of motion may indicate a structural cause for the spells such as hydrocephalus or a mass lesion. In cooperative older children, the physician should attempt a funduscopic examination. Papilledema is a clue to increased intracranial pressure but is only readily appreciable after 2–3 weeks of increased intracranial pressure; it will not be present with acute disturbances leading to increased intracranial pressure.

The child will provide important information about their mental status and developmental status through simple conversation. Conversations about toys, school, or family members in the room can provide information about orientation, aphasia, dysarthria, and fund of knowledge for age. If there are any questions about whether any facial asymmetry is new-onset, parents may be able to provide old photographs; most people have some degree of facial asymmetry at baseline that may only be noticed after a frightening event causes the parents to observe the child more closely.

Muscle strength can be ascertained by manual testing in a cooperative older child or observing natural play or strength of resistance to examination in a younger child. If a child can easily perform age-appropriate actions such as crawling, walking, running, climbing, or grabbing for objects, and strongly resists examination, they are likely to have grossly normal strength in their major muscle groups. Tone can be checked by passively moving the patient’s limbs or suspending an infant in your hands to check if they start to slide through your grip. Low tone (hypotonia) can also be detected by observing gait or observing how the child sits; “W”-sitting (sitting with knees together and heels outside of their hips) may be another clue. Low strength (weakness) should be distinguished from hypotonia or ataxia; an example of normal strength but low tone might be an infant with motor delays and head lag who vigorously opposes examination; a child with normal strength but ataxia might vigorously oppose examination but cannot accurately reach to push away the examiner.

A normal physical examination (including vital signs and mental status) does not rule out the presence of a neurologic disorder but generally indicates a disorder that does not require immediate intervention and that more time can be spent carefully evaluating all diagnostic possibilities. In children with baseline neurologic abnormalities, such as children with cerebral palsy, knowledge of their baseline physical examination, abilities, and behavior is critical in deciding how urgently they need to be evaluated further. Parents can be very helpful in determining a child’s baseline behavior in this case.

Red Flags

After obtaining a history of the events, the presence of “red flags” in the history or examination should strongly prompt referral to the emergency room:

Paroxysmal Spells of Altered Behavior or Movement

Paroxysmal neurologic symptoms can have neurologic, psychiatric, pulmonary, cardiovascular, or gastrointestinal causes (see Table 39.1 ). For this reason, during the investigation of a paroxysmal event, generic terms such as spells , convulsions , or altered mental status are more appropriate to use rather than seizures , which implies a very specific etiology and may falsely eliminate diagnostic possibilities. Witnesses may use terms such as grand mal , petit mal , or even generalized tonic-clonic (GTC) to describe events; these descriptors should not be taken at face value or thought to only describe epileptic seizures.

Epileptic Seizures

An epileptic seizure is a paroxysmal alteration in behavior, motor function, and/or autonomic function occurring in association with excessive synchronous neuronal activity in the CNS. Seizures may be considered provoked or unprovoked , referring to whether they were precipitated by an acute cause such as illness, concussion, metabolic disorder, or toxic ingestion. The term symptomatic refers to whether the seizures represent a symptom of a known chronic disorder, such as a structural, genetic, or metabolic abnormality. Epilepsy is a disorder in which there are recurrent unprovoked epileptic seizures; Figure 39.2 outlines the contextual framework when evaluating seizure disorders and Figure 39.3 provides the classification structure. Table 39.2 provides a glossary of terms frequently encountered when considering seizure disorders.

Epileptic seizures must be clearly distinguished from non-neurologic paroxysmal disorders caused by psychiatric, cardiovascular, pulmonary, or gastrointestinal causes. There are also paroxysmal disorders that are neurologic but nonepileptic in nature, such as tics, dystonias, stereotypies, or other movement disorders. The correct diagnosis is critical to avoid unnecessary testing, interventions, and medication trials. However, multiple types of events, both epileptic and nonepileptic, may occur in the same patient, necessitating that each spell be properly characterized.

Epidemiology and Causes of Seizures and Epilepsy

If febrile seizures are included, approximately 3.5% of children experience some kind of seizure by the age of 15 years; most seizures occur before the age of 3 years. Most children who present with a seizure do not have or will not develop epilepsy. Many children presenting with a seizure have febrile convulsions, which are a provoked, age-dependent paroxysmal neurologic condition; 13% of children with seizures have acute symptomatic seizures other than febrile convulsions; and 8% have single, unprovoked seizures of unknown cause. The incidence of acute symptomatic seizures is highest in the first year of life; the most common causes of these predominantly neonatal seizures are genetic, infection, and metabolic disorders. After age 4 years, head trauma is the most common cause of acute symptomatic seizures, and infection is the next most common.

The incidence of epilepsy among children younger than 15 years is 45–85/100,000 in developed countries. It is highest in younger children; in those younger than 1 year, it is ∼100/100,000. The prevalence of active epilepsy in patients taking antiepileptic drugs (AEDs) is between 4.3 and 9.3/1,000, or about 0.5–1% of the population. Traditionally, ∼60% of children with epilepsy have no identifiable etiologic factors for the disease; next-generation gene sequencing technology has moved the estimated underlying genetic etiology to approximately 40%. Of those children in whom a cause is identified, population-based studies report the following presumed causes: infection in 5%, head trauma in 3%, and miscellaneous causes (tumors, malformations of cortical development, vascular malformations, and cerebral infarction) in 2%. Epilepsy is found in association with other long-standing neurodevelopmental abnormalities in 13% of children.

Genetics

It is estimated that a genetic etiology underlies epilepsy in approximately 40% of individuals. There are certain patterns and ages of onset that might guide specific genetic consideration ( Tables 39.3 and 39.4 ), but given the wide genetic and phenotypic heterogeneity, it is more practical to do gene sequencing broadly as opposed to trying to narrow down the genetic sequencing unless there is a very clear diagnostic consideration such as Angelman or Rett syndrome. Neonatal-onset seizures require both a metabolic ( Table 39.5 ) and a genomic approach to the diagnostic evaluation because there are several epileptic encephalopathic syndromes that could be treatable and genetic testing generally has a 2–3-month turnaround for results. If rapid genome sequencing is an option, this would supplant the need for metabolic testing as the results of genomic sequencing will be available within a short enough period of time to allow for timely implementation of treatment. Molybdenum cofactor deficiency is a rare example that has a lifesaving orphan drug treatment that needs to be initiated as early as possible to prevent irreversible cystic encephalopathy. Table 39.6 outlines several of the recognizable syndromic genetic disorders as defined by the underlying pathoetiology.

In some circumstances, unique clinical phenotypes can guide the initial clinical differential diagnosis. Severe metabolic acidosis resulting in shock and requiring intubation and ventilation is seen in metabolic epileptic encephalopathic syndromes such as nonketotic hyperglycinemia, pyridoxine-5′-phosphate oxidase deficiency, molybdenum cofactor deficiency, pyridoxine-dependent epilepsy, and Leigh syndrome. Table 39.7 provides an overview of the clinical associations of metabolic disorders associated with epilepsy. The characteristic syndactyly of the second and third toes is seen in steroid metabolism disorders, Smith-Lemli-Opitz syndrome in particular, which additionally has associated genitourinary tract abnormalities. Skin exanthems are highly suggestive of biotinidase deficiency. Atypical coarse or thin hair and wormian bones are seen in copper disorders such as Menkes syndrome. Cardiomyopathy is characteristic of mitochondrial disorders including Barth syndrome and fatty acid oxidation disorders and is also seen in RASopathies and cobalamin C deficiency. Atypical fat distribution and a prominent suprapubic fat pad are seen in congenital disorders of glycosylation. The circumstances in which genetic testing is offered varies widely between centers. Gene panels are offered by several laboratories and do not all include the same genes. It is thus important to understand the benefits and limitations of the test requested. Exome sequencing should not be considered “end of the line” or “last resort,” as the window of opportunity for targeted intervention may pass while more conventional options are investigated. This is particularly relevant in new-onset intractable or refractory seizures. In addition, there are several cases with digenic seizure disorders or rare metabolic disorders that will not be easily detected through more routine analysis but benefit from early targeted intervention to reduce morbidity and improve overall quality of life. The consensus for evaluating patients with suspected congenital disorders of glycosylation, mitochondrial disorders, or otherwise complex atypical disorders is to utilize exome sequencing as a first-line diagnostic test, with yields of up to 30% in these circumstances.

Seizure Classification and Terminology

Seizures are characterized according to their clinical semiology and presumptive etiology (see Figs. 39.2 and 39.3 ). Seizures can be difficult to classify and identify without a careful description of their onset, unfolding, and aftermath. Multiple seizure types may have the same brief general description, such as “twitching” or “staring.” Without further details as to duration, additional symptoms, and postictal behavior, they may be incorrectly classified as to type, even if they are accurately determined to be seizures. This is clinically relevant because improper classification can lead to inappropriate treatment; for example, some antiepileptic medications for focal seizures will exacerbate generalized seizures. Table 39.8 aligns some of the older terminology with the newer classification.

Clonic movements are rhythmic, nonsuppressible, position-independent jerking movements (low frequency, high amplitude) caused by involvement of the motor cortex. They can be unilateral or bilateral and can start with one body part and spread. If bilateral, they are synchronous and do not alternate from one side to the other in a bicycling fashion. This should be distinguished from clonus , which is rhythmic twitching of a limb, generally the foot, caused by hyperreflexia and lack of descending cortical inhibition due to CNS injury such as is seen in cerebral palsy or stroke. This is generally provoked by movement, excitement, and positioning and can be suppressed or halted by gently repositioning the affected limb. There is no alteration of alertness with clonus. In newborns, jitteriness (high frequency, low amplitude) may also be mistaken for clonic seizure activity; this tends to be stimulus-provoked and suppressible.

The term tonic refers to a change in tone as a manifestation of seizure activity, which clinically presents as stiffening or arching. This can occur as the only manifestation of a seizure (tonic seizure) or may be followed by clonic jerking, which is the generalized tonic-clonic seizure (GTC or grand mal). Atonic seizures refer to seizures where a sudden, brief loss of tone in the neck or entire body causes a head nod or fall to the ground. This type of seizure must be distinguished from falls due to complete loss of consciousness or those due to tonic stiffening of the entire body. With atonic seizures, the loss of tone is sudden but brief, and the patient is quickly responsive afterward.

Automatisms are semipurposeful movements that usually occur with impairment of consciousness either during or after a seizure and can be very useful for identifying a spell as a seizure. They may be a perseveration of an activity in progress at ictal onset, such as turning pages of a book, or novel semipurposeful movements arising during the seizure. These novel movements are most often a mixture of masticatory, oral, and lingual movements (lip smacking or grimacing) and simple fragmentary limb movements, such as fidgeting with a held object or pulling at clothing. In infants, orofacial automatisms are more likely than complex gestures and must be distinguished from the normal behavior of infants. Automatisms can be seen both in focal seizures, specifically those of temporal lobe onset, and in some generalized seizures, specifically absence epilepsy, so they are not specific to a broad category of seizure.

Impairment of consciousness , defined as an alteration in awareness of external stimuli, may be combined with a complete loss or impairment of responsiveness to external stimuli. Assessment of consciousness during seizures is often difficult, particularly in young children. It is possible to be unresponsive because of an inability to speak or articulate clearly (aphasia, apraxia, or paralysis). It is also possible to be responsive to external stimuli but to have altered awareness, often demonstrated by complete amnesia for events immediately before, during, or after the seizure, which implies that memory was not acquired during the seizure because of ongoing neuronal dysfunction. It is possible to have complex motor behaviors without loss of complete awareness or amnesia; frontal lobe seizures commonly have this presentation and must be carefully distinguished from nonepileptic events. Both focal and generalized seizures can be associated with impairment of consciousness; the term dyscognitive is used to describe this symptom (see Table 39.2 ).

Seizure etiology was previously divided into idiopathic, cryptogenic, and symptomatic . There were also separate categories for infantile spasms and neonatal seizures. The terms genetic, structural, metabolic, and unknown are currently used to characterize presumptive etiologies ( Table 39.9 ).

Focal Seizures

Diagnostic Evaluation of a Seizure Disorder

Neuroimaging Studies

MRI is superior to CT for the evaluation of epilepsy. Any patient with a history or examination suspicious for focal-onset epilepsy should have MRI of the brain unless the syndrome is clearly that of benign focal epilepsy of childhood with centrotemporal spikes. MRI may also reveal an abnormality in patients with symptomatic generalized epilepsy. Functional neuroimaging is important in the assessment of candidates for surgical resection in patients with intractable seizures ( Fig. 39.4 ). When available, a 3.0 Tesla MRI of the brain with specific protocols dedicated to epilepsy evaluation (e.g., proper alignment of the imaging axis with the hippocampi) is preferred. It is important to note that generalized seizures associated with status epilepticus may also produce nonspecific and reversible findings on MRI ( Fig. 39.5 ).

Evaluation of the First Seizure

There is no clinical sign or diagnostic investigation that determines with certainty whether a child presenting with a first seizure has epilepsy or has had an isolated seizure. The assessment of patients with a first seizure must include a search for etiologic agents and features that may indicate the risk of recurrence. Factors to be considered include the circumstances of the seizure, the health of the child in the time before the seizure, the recent sleep patterns, the possibility of abuse or trauma, and the chance of ingestion of prescription or street drugs or syndromes such as the neurocutaneous disorders ( Table 39.11 ).

TABLE 39.11

Neurocutaneous Syndromes

Clinical Syndromes and Findings	Investigations
Sturge-Weber Syndrome
Facial hemangioma, “port-wine stain” upper face, division of cranial nerve V; bilateral in 30%, absent in 5%, associated truncal and limb hemangiomas in 45%	CT scan: calcification, MRI scan with gadolinium
	EEG: attenuation of background rhythms, epileptiform discharges
Intracranial leptomeningeal angiomatosis
Epilepsy in 70–90%, usually before 2 yr and before hemiparesis, intractable in 35%
Intellectual disability in 50–60%
Hemiparesis in 30%, often with hemisensory deficit and hemianopia
Tuberous Sclerosis
Diagnostic Criteria ∗
Any One of the Following:
Facial angiofibroma (adenoma sebaceum, nasolabial folds, and nose becomes more prominent with age) or periungual fibromas	Physical examination
Cortical tubers, subependymal nodule, giant cell astrocytoma	MRI examination: T1 and T2 sequences with gadolinium
Multiple retinal hamartomas (usually asymptomatic) or multiple renal angiomyolipomas (usually asymptomatic, may manifest as hematuria, hypertension, or renal failure)	Funduscopic examination and renal ultrasonography, abdominal CT scan
Or Any Two of the Following:
Infantile spasms (seizures in 90%, most commonly generalized; infantile spasms and myoclonus)	History and physical, EEG; focal or generalized abnormalities
Hypomelanotic papules (ash leaf spots; in 80–90%, 1–2 cm oval or leaf-shaped)	Wood lamp examination in darkened room
Single retinal hamartoma	Funduscopic examination
Subependymal or cortical calcification on CT scan	CT scan of the brain
Single renal angiomyolipomas or cysts	Renal ultrasonography or abdominal CT scan
Cardiac rhabdomyomas (single or multiple; may obstruct outflow, cause arrhythmias, or cause conduction defects)	Echocardiography, ECG
First-degree relative with tuberous sclerosis (autosomal dominant disorder, 80% of cases represent new variants)	Examination of parents; echocardiography, MRI scans
Also Associated:
Intellectual disability in 50–66%
Shagreen patches; hamartomatous skin lesion in lumbosacral region in 50%
Pulmonary involvement, fibrosis	Chest radiograph
Skeletal abnormalities	Hand, feet (cystic), long bone (sclerotic) radiographic changes
Epidermal Nevus Syndrome
Hamartomatous lesions; subclassified according to most predominant histologic and clinical features (e.g., linear nevus sebaceus, see below)	Careful examination of the scalp, skin folds, and conjunctiva; funduscopic examination
Sporadic, affects both sexes equally; CNS abnormalities are common with epidermal nevus syndrome, including seizures (25% of patients), intellectual disability, and neoplasia; also, skeletal abnormalities, including kyphoscoliosis and hemiatrophy	Spine and limb radiographs, as appropriate
Linear nevus sebaceus; hairless verrucous yellow-orange or hyperpigmented plaques on the face and scalp
Epilepsy in 76%
Intellectual disability in 60%
Associated neuronal migration disorders	MRI scan of the brain
Malignant transformation of a skin lesion
Other Neurocutaneous Syndromes Associated with Seizures
Neurofibromatosis; cutaneous lesions include café-au-lait spots, axillary freckling, neural tumors; seizure types include generalized tonic-clonic, partial complex, and partial simple-motor	MRI scan of the brain
Incontinentia pigmenti; involvement includes linear papular-vesicular cutaneous lesions at birth, later pigmentation, ocular and dental anomalies; female-to-male ratio >20:1 (boys may die in utero); seizure types include neonatal onset and later generalized tonic-clonic	Skin biopsy; ophthalmology examination
Hypomelanosis of Ito (incontinentia pigmenti achromians)

CNS, central nervous system.

∗ See http://www.tsalliance.org/healthcare-professionals/diagnosis/ .

The recurrence risk after a first unprovoked seizure, usually defined as a seizure or flurry of seizures within 24 hours in patients older than 1 month, is ∼40–50%.

The most important predictor of recurrence appears to be the existence of an underlying neurologic disorder. The existence of intellectual disability or cerebral palsy is a common antecedent to epilepsy, as is a history of significant head injury. An EEG with generalized or focal epileptiform discharges or with focal or generalized slowing is also predictive of recurrence. Focal seizures are more likely to be associated with recurrence, although patients with such seizures are also more likely to have an existing neurologic deficit or an abnormal EEG. The duration of the first seizure or a presentation in status epilepticus is not associated with a higher incidence of recurrence. A family history of epilepsy is not a predictor of recurrence. Earlier age at onset, particularly before the age of 12 months, has been associated with a higher risk of recurrent seizures.

Most authorities believe that the majority of patients with a first seizure should not be treated unless the risk of recurrence is judged to be significantly higher than average. An abnormal neurologic examination, an abnormal MRI of the brain, and abnormal EEG all increase the risk of recurrence; the greater the number of risk factors, the more likely an AED may be initiated after a first known seizure, although some neurologists will still elect to wait for a second confirmed seizure. In adults or adolescents, the issues of driving and employment may influence the decision to treat a first seizure, but in otherwise healthy and developmentally normal children, there is almost no indication for chronic AED treatment in response to a single seizure. Activities such as bathing, driving, and swimming must be carefully supervised.

The decision to begin AED therapy is usually made after a patient has had two or more seizures in a short interval of time (6–12 months). Treatment with AEDs lowers the recurrence rate by about 50% ( Fig. 39.6 ).

Status Epilepticus

Status epilepticus is a medical emergency where epileptic seizures are prolonged or occur in rapid succession without recovery between the seizures. There are two general categories of status epilepticus: convulsive and nonconvulsive (“subclinical”) status epilepticus. Convulsive status epilepticus may involve repetitive or prolonged GTC, myoclonic, or tonic seizures. Nonconvulsive status epilepticus may involve repeated or continuous absence seizures or focal dyscognitive seizures with an altered state of consciousness lasting hours or even days.

A common duration of a seizure defined as status epilepticus is 30 minutes or longer, but seizures continuing for more than 5–10 minutes warrant immediate attention, as they are statistically likely to progress to status epilepticus. The tonic-clonic phase of generalized seizures usually lasts <2 minutes; such seizures lasting ≥5 minutes usually evolve into status epilepticus. One third of children presenting with status epilepticus have no history of epilepsy, another third have a history of chronic epilepsy, and an acute illness or injury has caused status epilepticus in another third. One of the most common precipitants of status epilepticus in people with a known history of epilepsy is abrupt discontinuation of a daily AED.

Status epilepticus has a significant acute mortality rate, partly because of the underlying cause of the seizures; intracranial infections (meningitis, encephalitis), poisoning, acute metabolic disorders, and head injuries are some of the most common causes.

The goals of the emergency management of status epilepticus are as follows:

• 1.

  Maintain normal cardiorespiratory function and cerebral oxygenation.

• 2.

  Stop clinical and electrical seizure activity and prevent its recurrence.

• 3.

  Identify precipitating factors.

• 4.

  Correct any metabolic disturbances (hypoglycemia, hyponatremia) and prevent systemic complications such as cardiovascular collapse, cardiac arrhythmia, pneumonia, and renal failure.

Table 39.12 sets out a plan of initial assessment and management of convulsive status epilepticus. Lorazepam and diazepam are rapidly acting anticonvulsants when given intravenously but must be combined with a primary AED, as their duration of action is short. Side effects include sedation, depressed respiration, decreased ability to protect the airway, and hypotension.

Phenytoin, fosphenytoin, phenobarbital, or valproic acid could be used in conjunction with the benzodiazepines in providing longer-lasting anticonvulsive action.

Phenytoin is less commonly used. It has a rare but serious complication called purple glove syndrome, which occurs in 1.7–5.9% of intravenous administrations; within 2 hours of administration, there is pain, bluish discoloration, and swelling of the affected limb. Treatment involves discontinuation of the phenytoin and elevation and icing of the affected limb; compartment syndrome is a potential complication.

Fosphenytoin, a prodrug of phenytoin, can be administered either intravascularly or intramuscularly. Fosphenytoin has a maximum infusion rate of 150 mg PE/min; when it is infused faster, hypotension and arrhythmias may occur.

Valproate can be given intravenously and may be the appropriate therapy for patients with known idiopathic and symptomatic generalized epilepsies. It is also generally appropriate for children with a known static cerebral injury presenting with status epilepticus as their first seizure, such as a child with a history of neonatal hypoxic-ischemic encephalopathy who presents at age 4 in status epilepticus. It is contraindicated in children with known or suspected mitochondrial disease, multisystemic disease of unknown etiology, or known hepatic disease, or in children under the age of 2 years.

Nonconvulsive status epilepticus may arise when frequent focal dyscognitive seizures or absence seizures occur. In both settings, discrete seizures may not be identifiable; instead, the child may present with confusion, clouded consciousness, and partial responsiveness or a stuporous state, all of which can last hours or even days. It should be treated urgently as soon as it is identified, especially if focal dyscognitive status is suspected, in which case treatment should follow that outlined for convulsive status epilepticus. In absence status epilepticus, intravenous benzodiazepines are usually effective but should be used in conjunction with intravenous valproate or oral ethosuximide.

Classification of Epilepsies and Epileptic Syndromes

The clinician should attempt to determine whether the seizure disorder is focal or generalized, and then whether there is evidence of underlying brain dysfunction. Both the focal and generalized epilepsies in otherwise developmentally normal children respond favorably to treatment, and there is a good chance of long-term remission. Structural epilepsies may benefit from surgical intervention. Genetic and metabolic epilepsies respond less predictably to treatment, and the chance of remission is less certain.

Identification of one of the epileptic encephalopathies of infancy and childhood has grave prognostic significance ( Table 39.13 ). These epilepsies vary in the seizure types and EEG features but have certain features in common: specific age at onset and expression, intractable seizures, cognitive dysfunction, arrest in development, conspicuous interictal epileptic discharges on the EEG, and a poor response to treatment.