+ All Categories
Home > Documents > Pediatric Epilepsy Syndromes

Pediatric Epilepsy Syndromes

Date post: 22-Oct-2014
Category:
Upload: idno1008
View: 125 times
Download: 1 times
Share this document with a friend
27
PEDIATRIC EPILEPSY SYNDROMES CONTINUUM: Lifelong Learning in Neurology June 2010; Volume 16(3) Epilepsy; pp 57-85 Wirrell, Elaine; Nickels, Katherine C. Abstract Epilepsy syndromes denote specific constellations of clinical seizure type(s), EEG findings, and other characteristic clinical features. Most syndromes recognized in epilepsy are genetic and developmental disorders that begin in the pediatric years. Epilepsy syndromes are divided into idiopathic (primary) types, in which the presumed etiology is genetic, versus symptomatic (secondary) types, in which there is either an underlying etiology that is known or presumed based on other evidence of brain dysfunction. Epilepsies are also classified by those with generalized seizures and those with localization-related seizures. Identification of a specific syndrome is important to define the best treatment and accurately prognosticate long-term outcome for children with epilepsy. In this chapter, clinical and electrographic features as well as inheritance patterns of common pediatric epilepsy syndromes are discussed. Back to top The term epilepsy syndrome has been used by the International League Against Epilepsy (ILAE) to refer to "a complex of signs and symptoms that define a unique epileptic condition." 1 Epilepsy syndromes denote specific constellations of clinicalseizure type(s), EEG findings, other characteristic clinical features, such as age at onset, course of epilepsy, associated neurologic and neuropsychological findings, and underlying pathophysiologic or genetic mechanisms (Figure 3- 1 ).2 Identification of a specific syndrome is important to define the best treatment and accurately prognosticate long-term outcome. Most syndromes recognized in epilepsy are genetic and developmental disorders that begin in the pediatric years. FIGURE 3-1 Classification of epileptic syndromes. Epilepsy syndromes are divided into idiopathic (primary) types, in which the presumed etiology is genetic, versus symptomatic (secondary) types, in which there is either an underlying etiology
Transcript
Page 1: Pediatric Epilepsy Syndromes

PEDIATRIC EPILEPSY SYNDROMESCONTINUUM: Lifelong Learning in NeurologyJune 2010; Volume 16(3) Epilepsy; pp 57-85Wirrell, Elaine; Nickels, Katherine C.

Abstract Epilepsy syndromes denote specific constellations of clinical seizure type(s), EEG findings, and other characteristic clinical features. Most syndromes recognized in epilepsy are genetic and developmental disorders that begin in the pediatric years. Epilepsy syndromes are divided into idiopathic (primary) types, in which the presumed etiology is genetic, versus symptomatic (secondary) types, in which there is either an underlying etiology that is known or presumed based on other evidence of brain dysfunction. Epilepsies are also classified by those with generalized seizures and those with localization-related seizures. Identification of a specific syndrome is important to define the best treatment and accurately prognosticate long-term outcome for children with epilepsy. In this chapter, clinical and electrographic features as well as inheritance patterns of common pediatric epilepsy syndromes are discussed.

Back to top The term epilepsy syndrome has been used by the International League Against Epilepsy (ILAE) to refer to "a complex of signs and symptoms that define a unique epileptic condition."1 Epilepsy syndromes denote specific constellations of clinicalseizure type(s), EEG findings, other characteristic clinical features, such as age at onset, course of epilepsy, associated neurologic and neuropsychological findings, and underlying pathophysiologic or genetic mechanisms (Figure 3-1).2 Identification of a specific syndrome is important to define the best treatment and accurately prognosticate long-term outcome. Most syndromes recognized in epilepsy are genetic and developmental disorders that begin in the pediatric years.

FIGURE 3-1 Classification of epileptic syndromes.

Epilepsy syndromes are divided into idiopathic (primary) types, in which the presumed etiology is genetic, versus symptomatic (secondary) types, in which there is either an underlying etiology that is known or presumed based on other evidence of brain dysfunction, such as developmental delay. Epilepsies are also classified by those with generalized seizures and those with localization-related seizures.3

IDIOPATHIC GENERALIZED EPILEPSY SYNDROMES Table 3-1 summarizes the clinical and electrographic features, as well as inheritance patterns, of idiopathic generalized epilepsy syndromes in order of age at onset. The more common idiopathic generalized epilepsy syndromes will be described in greater detail.

Page 2: Pediatric Epilepsy Syndromes

TABLE 3-1 Idiopathic Generalized Epilepsy Syndromes in Infants and Children

Page 3: Pediatric Epilepsy Syndromes

TABLE 3-1 Continued

Page 4: Pediatric Epilepsy Syndromes

TABLE 3-1 Continued

Benign Neonatal Convulsions Two syndromes of neonatal seizures are associated with good outcome: benign familial neonatal seizures (BFNS) and benign idiopathic neonatal seizures.

BFNS, previously referred to as benign neonatal familial convulsions, typically present during the first few weeks of life with focal, multifocal, or generalized seizures. The seizures are brief but occur 20 to 30 times per day and may be difficult to control. The infant is normal interictally, including a normal neurologic examination. The EEG does not have specific features that help distinguish BFNS from other neonatal epilepsies. A family history of similar neonatal seizures is important for the diagnosis.4 BFNS, an autosomal dominant disorder with 85% penetrance, is linked to voltage-gated potassium channels KCNQ2 and KCNQ3 on chromosomes 20q and 8q, respectively.5 The outcome for BFNS is generally favorable with resolution of seizures typically in early to midinfancy and normal neurodevelopment.6 However, up to 8% to 16% of patients will later develop epilepsy as adults (Case 3-1).4,6

Case 3-1

Page 5: Pediatric Epilepsy Syndromes

A healthy, term, 2-week old boy presented to the emergency department with frequent seizures. In between the seizures the infant was alert, interactive, and continued to feed vigorously. A sepsis evaluation was negative. His MRI and EEG (Figure 3-2) were also normal. In spite of this, the baby had many seizures per day that did not respond to multiple antiseizure medications. His grandmother then visited the baby and informed his parents that his father, paternal aunt, and cousin all had similar seizures and went on to have normal growth and development.

FIGURE 3-2 Normal drowsy interictal electroencephalograph in a neonate with benign familial neonatal seizures.

Comment. BFNS present during the neonatal period in previously healthy term infants. No specific features of the EEG help with the diagnosis. The diagnosis is frequently made when the evaluation for seizures fails to reveal an etiology and there is a family history of neonatal seizures with subsequent normal growth and development. BFNS is an autosomal dominant disorder with 85% penetrance.

Benign idiopathic neonatal seizures (BINS) also occur in otherwise healthy, neurologically normal, term neonates. Symptoms typically begin on the fifth day of life, or "fifth day fits," with partial clonic seizures that may migrate, increase in frequency, and culminate in status epilepticus. Interictally the infant is neurologically normal. Like BFNS, there are no specific EEG features in BINS and comprehensive evaluations fail to demonstrate an etiology for the seizures. Unlike BFNS, there is no family history of seizures. The seizures typically resolve after 24 hours, and the children have normal neurodevelopment without increased risk of seizure recurrence.4,6

Generalized Epilepsy With Febrile Seizures Plus Generalized epilepsy with febrile seizures plus (GEFS+) is a primary generalized epilepsy syndrome characterized by febrile and afebrile seizures. Febrile seizures continue beyond the typical age of remittance, 6 years. Afebrile seizures are infrequent, brief, and include generalized tonic-clonic, myoclonic, absence, complex partial, and astatic seizures.6,7 Seizures start between 4 months and 10 years, with a mean onset of approximately 2 years. Prior to the onset of afebrile seizures, GEFS+ can be difficult to distinguish from febrile seizures unless a careful family history is taken. The interictal EEG may be normal or demonstrate generalized epileptiform discharges and does not differentiate these children from those with febrile seizures alone.7

GEFS+ is a genetically heterogenous autosomal dominant disorder with incomplete penetrance of approximately 60% to 80%.6,8 Within families multiple phenotypes with variable severity exist.6 Also, multiple chromosomal mutations are linked to GEFS+, including 19q13.1, 2q23-24.2, and 5q31.1-33.1. Of note, mutation on chromosome 2q23-24.2 involves the SCN1A gene, which is involved in Dravet syndrome, a catastrophic symptomatic epilepsy.5 The prognosis for GEFS+ is excellent in most children. Seizures typically spontaneously remit by age 11 years.6 However, up to 30% may have more severe epilepsy, suggesting a possible continuum between GEFS+ and Dravet syndrome.8

Myoclonic Astatic Epilepsy of Doose Myoclonic astatic epilepsy (MAE), a rare idiopathic generalized seizure disorder affecting 1:10,000, presents in previously neurologically healthy preschool-aged children. The children have multiple seizure types, including generalized tonic-clonic, myoclonic, absence, atonic astatic, and myoclonic astatic seizures. Myoclonic astatic seizures are the most prominent. Clinically, the seizures are similar to those seen in Lennox-Gastaut syndrome (LGS).8,9 However, the outcome and course of MAE are variable, from complete remission to intractable epilepsy with poor cognitive outcome. MAE therefore must be differentiated from LGS. This is done clinically by observing the myoclonic astatic seizures and with EEG. Whereas the interictal EEG of LGS

Page 6: Pediatric Epilepsy Syndromes

demonstrates 1.5-Hz to 2.5-Hz generalized slow spike-and-wave discharges, the EEG of MAE demonstrates 2-Hz to 3-Hz spike-and wave-discharges.9,10 Up to 32% of children with MAE have a family history of epilepsy, suggesting a genetic predisposition, but the inheritance pattern is unknown (Case 3-2).10

Case 3-2 A previously well 3-year-old boy presented with a history of two generalized tonic-clonic seizures over 4 days. His EEG was normal, and treatment with oxcarbazepine was started. Two weeks later, he had a cluster of 14 generalized tonic-clonic seizures lasting up to 5 minutes each over a 3-day period. He was admitted to the hospital. Oxcarbazepine was stopped, and valproate was loaded with improvement. Over the next 2 weeks, he developed a new seizure type during which he would jerk forward and fall to the ground. Despite increasing doses of valproate, he continued to have both myoclonic astatic as well as generalized tonic-clonic seizures. His EEG now showed slow spike-wave and some high-amplitude slow waves, and several seizures were recorded (Figure 3-3). Clonazepam was added with a marked deterioration in his behavior. He was started on the ketogenic diet with marked improvement of his clinical seizures (Video Segment 3).

FIGURE 3-3 Electroencephalograph of a child with myoclonic astatic epilepsy showing generalized slowing and slow spike-wave with a recorded myoclonic astatic seizure.

Comment. MAE presents acutely in previously well children. Initial seizure types are often generalized tonic-clonic; however, the characteristic myoclonic astatic seizure follows shortly. In distinction to LGS, children with MAE have myoclonic astatic rather than atonic seizures, rare or no tonic seizures, normal development preceding seizure onset, lack of fast frontal or generalized polyspike activity in sleep, presence of parietal theta rhythms, and a higher likelihood of photosensitivity on EEG. Although therapeutic strategies are similar for the two disorders, MAE has a more favorable prognosis.

Childhood Absence Epilepsy Childhood absence epilepsy (CAE) occurs in 2% to 15% of childhood epilepsy, typically between 4 and 10 years of age. The children are neurologically healthy.10,11 Children typically have very brief absence seizures, characterized by abrupt onset of impaired consciousness and unresponsiveness lasting approximately 10 seconds, occurring up to hundreds of times per day. However, automatisms, brief clonic jerks, and loss of postural tone can also be seen.12 The seizures can be provoked by hyperventilation in approximately 90% of children.5,13,14 The EEG demonstrates generalized symmetric 3-Hz spike-wave discharges.11

Most children with CAE only experience absence seizures.11 Children with early onset (mean age 6 years) have the best prognosis, with complete remission of their epilepsy 2 to 6 years after onset.14 However, onset of absence seizures before age 3 years is associated with an increased likelihood of neurodevelopmental abnormalities, and this likely represents a seizure syndrome other than CAE.15

Seizures can continue into adolescence and adulthood in 12% to32% of cases. If children continue to have seizures into adolescence, up to 40% will also have generalized tonic-clonic seizures. By comparison, only 3% of children with typical CAE will experience generalized tonic-clonic seizures during the period of active absences.14 Furthermore, CAE can precede juvenile myoclonic epilepsy (JME) in 11% to 18% of cases. However, this is also likely a different subsyndrome from that of other children

Page 7: Pediatric Epilepsy Syndromes

with CAE.10 If there is a myoclonic or atonic component to the seizure, if generalized tonic-clonic seizures occur at onset of absence seizures, or if there is photosensitivity on EEG, then the child is likely to have an epilepsy syndrome other than CAE and a greater risk for intractability exists.14

CAE must also be differentiated from juvenile absence epilepsy (JAE). JAE onset is typically between ages 10 and 16 years. The clinical absence seizures ofJAE are similar to those of CAE. However, the seizures occur less frequently and may be longer in duration. Children with JAE are also more likely to experiencegeneralized tonic-clonic seizures.16 Theinterictal EEG in JAE demonstrates 3.5-Hz to 4.0-Hz generalized spike- and polyspike-and-wave discharges. Although response to treatment in JAE is usually very good, the symptoms may be lifelong.10

CAE is likely inherited through an autosomal dominant pattern with incomplete penetrance linked to chromosomes 20q, 16p13.3, and 8q24.3. Up to 44% of children with CAE have a positive family history, and monozygotic twins have a 75% concordance.5,17 In addition, girls are 2 to 5 times more likely to have CAE (11.4% versus 2.5%).18 Absence seizures are caused by abnormalities in T-type calcium channels, which are responsible for rhythmic depolarizing activity in the thalamic neurons.5 Ethosuximide blocks T-type calcium channels and is an effective treatment for absence seizures. In addition, valproic acid and lamotrigine are also effective.8 Medicines such as phenytoin, carbamazepine, and oxcarbazepine are ineffective and should be avoided, as they may precipitate absence status epilepticus in patients with primary generalized epilepsy (Case 3-3).19

Case 3-3 A 6-year-old girl with normal growth and development was brought to her pediatrician for evaluation of spells. Her teachers at school were concerned because she frequently appeared to "stare off" throughout the day. She was missing questions on spelling tests and said she did not remember hearing the questions. Her parents had also noticed episodes during which she appeared to "freeze" briefly, and then returned to normal. Her pediatrician was able to elicit one of these events by asking her to hyperventilate. Her mother had a history of similar seizures. The child was treated with carbamazepine for complex partial seizures. However, her spells dramatically increased in frequency, and she was referred to the neurology department. Her EEG demonstrated frequent 3-Hz spike-and-wave discharges, as well as frequent absence seizures (Figure 3-4). The carbamazepine was discontinued, and she was treated with ethosuximide. Her seizures resolved. By age 10, ethosuximide was discontinued and she remained seizure free (Video Segment 1).

FIGURE 3-4 Generalized 3-Hz spike-and-wave discharge during a typical absence seizure.

Comment. Frequent, brief seizures without postictal symptoms are typical of absence seizures. Seizures can be provoked with hyperventilation in 90% of children with CAE. Most children have remission of their epilepsy within 2 to 6 years of onset. Medications such as phenytoin, carbamazepine, and oxcarbazepine should be avoided because they are ineffective and may precipitate absence status epilepticus.

Juvenile Myoclonic Epilepsy JME affects 4% to 10% of all patients with epilepsy and up to 26% of patients with idiopathic generalized epilepsy.19,20 Seizures typically present between 12 and 18 years of age in neurologically healthy children. Commonly, the first seizure noted is a generalized tonic-clonic seizure that occurred in the morning and was precipitated by sleep deprivation. However, careful questioning will reveal a history of myoclonic seizures and possible absence seizures occurring over the preceding months. Routine

Page 8: Pediatric Epilepsy Syndromes

EEG is abnormal in 50% to 75% of children with JME and demonstrates 4-Hz to 6-Hz generalized atypical spike- and polyspike-and-wave discharges, although focal discharges are present in 30% of cases.19,20 Photosensitivity is present in 30% to 90% and may precipitate myoclonic seizures.

The generalized tonic-clonic seizures and myoclonic seizures of JME tend to occur in the morning upon awakening.13 In children with JME, 100% will have myoclonic seizures, 96% will have generalized tonic-clonic seizures, and only 20% will experience absence seizures. Seizures are not only provoked by sleep deprivation, but also by alcohol consumption and, in women, menstruation.20

The inheritance of JME is complex. The classic form of JME is likely autosomal dominantly inherited and linked to chromosome 6p12-11. By comparison, those who present primarily with absence seizures are more likely to be related to chromosomes 15q14 or 6p21.3.21 Other chromosomes, including 2q22-23 and 5q34-35, have also been linked to JME.5

The traditional treatment for JME is valproic acid, with a response rate of 85% to 90%. However, side effects, including tremor, alopecia, weight gain, and increased risk of fetal malformation, may limit its use. Therefore, newer therapies, including lamotrigine, levetiracetam, topiramate, and zonisamide are being used more frequently. Some antiseizure medications, including carbamazepine, phenytoin, and gabapentin, may exacerbate seizures in JME.20 The response to antiseizure medications is typically excellent. However, JME is usually alifelong disorder with only 10% of patients able to discontinue antiseizure medications (Case 3-4).17

Case 3-4 A 16-year-old previously healthy boy had a generalized tonic-clonic seizure while on vacation with his family. In the emergency department he had a second generalized tonic-clonic seizure. His family acknowledged he had been staying up later than usual because of the vacation. His family also noticed that he frequently dropped his breakfast dishes. As the vacation week progressed, he seemed to be spilling things more frequently. He had had similar myoclonic jerks immediately preceding his generalized tonic-clonic seizure. EEG demonstrated 4-Hz to 6-Hz generalized atypical spike-and-wave discharges and photosensitivity (Figure 3-5). He was treated with valproic acid and became seizure free for the next 5 years. He then discontinued valproic acid because of seizure freedom but had recurrence of myoclonic and generalized tonic-clonic seizures shortly thereafter. Valproic acid was restarted but at a lower dose. He remained free of generalized tonic-clonic seizures but had rare myoclonic seizures after sleep deprivation or alcohol consumption. Video Segment 2 depicts a cluster of myoclonic seizures during photic stimulation.

FIGURE 3-5 Interictal generalized atypical spike-and-wave discharge in an adolescent with juvenile myoclonic epilepsy.

Comment. Children with JME frequently come to medical attention after generalized tonic-clonic seizures. A history of preceding myoclonic and absence seizures must be sought. Valproic acid is the traditional treatment for JME, with an excellent response. However, only 10% of children are able to remain seizure free afterdiscontinuing antiseizure medications.

IDIOPATHIC PARTIAL EPILEPSY SYNDROMES Table 3-2 summarizes the clinical and electrographic features, as well as inheritance patterns, of idiopathic partial epilepsy syndromes, in order of age at onset. The more common idiopathic partial epilepsy syndromes will be described in greater detail.

Page 9: Pediatric Epilepsy Syndromes

TABLE 3-2 Idiopathic Partial Epilepsy Syndromes in Infants and Children

Page 10: Pediatric Epilepsy Syndromes

TABLE 3-2 Continued

Benign Partial Epilepsy of Infancy/Benign Infantile Familial Convulsions Benign partial epilepsy can also occur beyond the neonatal period. Similar to the neonatal epilepsies, both sporadic and familial forms exist.

Sporadic benign partial epilepsy of infancy may occur with primarily complex partial seizures (BPEI-CPS) or may be associated with secondarily generalized seizures (BPEI-SGS).22 The seizures in BPEI present at age 3 to 20 months and are characterized by staring, loss of awareness, behavioral arrest, and cyanosis, with or without convulsive movements, and may secondarily generalize. In children with BPEI-SGS, the seizures always quickly secondarily generalize. The interictal EEG is normal. The prognosis for BPEI is excellent, with good response to antiseizure medications and resolution by 2to 3 years of age. After resolution of the seizures, development is normal and seizures do not recur.23

Benign familial infantile convulsions occur in neurologically healthy children between the ages of 3 and 20 months. The seizure semiology is similar to BPEI. In addition, head and eye deviation and diffuse hypertonia may also be present.22 The interictal EEG is typically normal butmay demonstrate occipitoparietal spike-wave discharges.22,23 The syndrome of benign familial infantile convulsions is likely autosomal dominantly inherited with incomplete penetrance. There is genetic heterogeneity, with linkage to chromosomes 19q, 16p12-q12, and 2q23-24.2,5 making this a distinct syndrome from benign familial neonatal convulsions. The prognosis is excellent, with good response to antiseizure medications, and development is normal in essentially all patients, without seizure recurrence.22,23

Page 11: Pediatric Epilepsy Syndromes

Benign Occipital Epilepsy, Early and Late Benign childhood epilepsy with occipital paroxysms has two subtypes: early onset and late onset. Early-onset benign childhood epilepsy with occipital paroxysms, or Panayiotopoulos syndrome (PS), occurs in preschool-aged children, but can occur in children aged 1 to 14 years. The seizures are characterized by autonomic symptoms, including ictus emeticus (nausea and retching), emesis, pallor, urinary incontinence, and hypersalivation, with preserved consciousness.24 The seizure progresses to gaze deviation, speech arrest, or convulsive activity, followed by loss of awareness. The autonomic symptoms may be prolonged in the form of autonomic status epilepticus. The interictal EEG is abnormal in 90% of children and demonstrates multifocal, high-amplitude epileptiform discharges.3,24 Occipital epileptiform discharges may also present and are typically suppressed with eye opening.25

PS is likely inherited, although the genetic abnormality has not been determined.26 While most patients will experience few seizures, up to 25% may have frequent seizures that may initially appear resistant to treatment. Within 1 to 2 years, the seizures will spontaneously remit in 90% of children, and all remit by later adolescence.26

Late-onset childhood epilepsy with occipital paroxysms (LOS), also called idiopathic childhood occipital epilepsy of Gastaut, is a less distinct clinical syndrome that occurs in school-aged children, although the age of onset can be from age 3 to 15 years. Children with LOS typically present with elementary visual hallucinations involving simple geometric patterns that may progress to more well-formed, complex visual hallucinations, followed by gaze deviation, ipsilateral head deviation, and possible secondary generalization. Awareness is maintained until gaze deviation occurs. Unlike the seizures in PS, children with LOS are more likely to have frequent seizures that are shorter in duration.24,25 Severe ictal and postictal headache are common findings.24 A family history of epilepsy is present in 21% to 37% of cases.24 The interictal EEG in LOS is similar to that of PS.25 Unlike PS, remission occurs in only 50% to 60% within 2 to 4 years of onset. The seizures respond well to carbamazepine, as well as the other medications used for PS.24,27 As symptomatic occipital epilepsy is difficult to distinguish clinically from LOS, neuroimaging is recommended.

Benign Childhood Epilepsy With Centrotemporal Spikes Benign childhood epilepsy with centrotemporal spikes (BCECTS), or benign rolandic epilepsy, is the most common idiopathic partial epilepsy. It typically presents between age 4 to 10 years but can present from age 1 to 16 years.6,14,24 Patients typically experience nocturnal seizures characterized by perioral paresthesias and ipsilateral facial myoclonus, as well as excessive salivation, speech arrest, and guttural noises. The seizure may spread to the ipsilateral hand and progress to a hemiconvulsion or generalized tonic-clonic seizure.14,24 The seizuresare usually brief, infrequent, and nocturnal.14 Status epilepticus has been reported in only 5% of cases.24 The EEG in BCECTS demonstrates high-amplitude, blunt, centrotemporal spikes with dramatic activation during sleep.3 Serial EEGs may demonstrate a shifting asymmetry of the spike-wave discharges.

The EEG findings of centrotemporal spikes are autosomal dominantly inherited with age-dependent penetrance.24 The syndrome of BCECTS likely has a more complicated inheritance pattern and has been linked to chromosomes 1q and 15q14.6,10,14,15,24 The seizures typically respond well to many antiseizure medications.27 Furthermore, because of the benign nature of the seizures, medication may not be necessary.6 The prognosis is excellent, with spontaneous remission occurring by age 15 to 17 years, and often much earlier.6 Some children may develop language, cognitive, or behavioral deficits, but these improve after remission of the disease (Case 3-5).24

Case 3-5 A 10-year-old healthy boy had been on vacation with his family. While sharing a hotel room, his family was awakened by the boy sitting up and making strange sounds. He was noted to have salivation and twitching of the right side of his face that seemed to spread to his right arm. Shortly thereafter, he returned to baseline. Six months later, he had a similar event. However, this seizure was longer and progressed to a generalized tonic-clonic seizure. His EEG demonstrated spikes over the bilateral centrotemporal head regions with increased activation during sleep (Figure 3-6). His parents declined treatment for their son because his older brother had similar seizures that he outgrew.

Page 12: Pediatric Epilepsy Syndromes

FIGURE 3-6 Interictal centrotemporal spike-and-wave discharges in a child with benign childhood epilepsy with centrotemporal spikes.

Comment. BCECTS presents with nocturnal partial seizures involving the rolandic area, the lower face, and occasionally the hand. The seizures are typically brief but may secondarily generalize. BCECTS is likely inherited through a complicated inheritance pattern. Children with BCECTS usually have infrequent seizures that are predominantly nocturnal. Therefore, medication may not be indicated.

SYMPTOMATIC EPILEPSY SYNDROMES Table 3-3 summarizes the clinical and electrographic features of the various symptomatic epilepsy syndromes, subdivided into age at presentation. The more common syndromes will be further discussed in the text.

Page 13: Pediatric Epilepsy Syndromes

TABLE 3-3 Symptomatic Epilepsy Syndromes in Infants and Children

Page 14: Pediatric Epilepsy Syndromes

TABLE 3-3 Continued

Page 15: Pediatric Epilepsy Syndromes

TABLE 3-3 Continued

West Syndrome West syndrome refers to the triad of infantile spasms, hypsarrhythmia, and psychomotor delay, although this last featureis not necessary for diagnosis and may be absent at presentation (Case 3-6). It is the most common epileptic encephalopathy, affecting 1 per 1900 to 1 per 3900 infants, with a peak age at 4to7months. Semiologically, the epileptic spasm consists of a transient contraction of the trunk, neck, and extremities, often followed by a brief second tonic component. Spasms may be flexor, extensor, or mixed and characteristically occur in clusters several times per day, often shortly after waking. Infants frequently cry during a cluster. Asymmetric spasms or coexistent partial seizures should suggest a focal cortical lesion.

Case 3-6 A previously healthy 7-month-old infant girl presented with recurrent clusters of spells during which she suddenly flexed at the trunk and neck and extended her arms. Over the past month, her spells had become more frequent and she was no longer rolling over or laughing like she could previously (Video Segment 7).

Comment. This infant is presenting with infantile spasms. Her interictal EEG demonstrates a slow, high-amplitude, poorly organized background with multifocal epileptiform discharges, consistent with hypsarrhythmia (Figure 3-7). In addition, she now has developmental regression and delay. The triad of infantile spasms, hypsarrhythmia, and developmental delay are consistent with West syndrome. In order to improve developmental outcome, it is important to recognize and treat infantile spasms early.

Page 16: Pediatric Epilepsy Syndromes

FIGURE 3-7 A, Interictal EEG in a child with infantile spasms demonstrating a slow, poorly organized, high-amplitude background with multifocal sharp waves and electrodecrement, consistent with hypsarrhythmia. B, Ictal EEG in a child with infantile spasms demonstrating a high-amplitude generalized sharp wave followed by electrodecrement.

Hypsarrhythmia, a pattern of disorganized, paroxysmal, high-voltage slowing, multifocal epileptiform discharge, and a lack of synchrony, is usually seen on routine EEG but may occur during non-REM sleep only, emphasizing the importance of a sleep recording. During REM sleep, hypsarrhythmia is reduced or disappears. With age, the EEG evolves to show greater interhemispheric synchronization, focal or multifocal sharp waves or high-voltage generalized slow activity, or slow spike-wave.

Most cases of West syndrome are symptomatic. Underlying etiologies include malformations of cortical development, neurocutaneous disorders such as tuberous sclerosis, preexisting brain injury due to ischemia, infection or trauma, genetic causes including Down syndrome, ARX or CDKL5 mutations, or, less commonly, inborn metabolic disorders such as mitochondrial disease, phenylketonuria, or Menkes disease. In 20% to 30% of cases, no underlying etiology is found. A small proportion of this latter group is truly "idiopathic," with no significant past medical history, normal development prior to spasm onset, symmetric spasms and EEG changes, disappearance of hypsarrhythmia between spasms, and rapid control of seizures.

In many cases, particularly those with symptomatic etiology, developmental delay precedes spasm onset. With seizure onset, further regression and visual disinterest is seen. Prognosis is poor, with motor delay and/or mental retardation in over 75% of cases.28 Between 13% and 33% of patients develop autism, and this is a particular risk with tuberous sclerosis and temporal lobe tubers. Outcome is strongly related to prognosis, with up 40% to 50% of truly idiopathic cases having a normal outcome.

Page 17: Pediatric Epilepsy Syndromes

Partial or generalized seizures predate or coexist with spasms in 12% to 42% of cases, and two-thirds ultimately develop other seizure types. Focal or multifocal seizures or a mixed generalized seizure syndrome such as Lennox-Gastaut syndrome is most common. Spasms usually disappear in the first 2 years but can rarely persist or reappear later in childhood.

An MRI should be done to evaluate for a structural abnormality, and if noninformative, metabolic and genetic studies should follow. Early initiation of treatment correlates with better long-term developmental outcome, particularly in cryptogenic or idiopathic cases. The main first-line therapeutic agents are corticotropin (ACTH) or steroids and vigabatrin, and the goal of therapy is resolution of both spasms and hypsarrhythmia. There is poor consensus regarding the dose and duration of steroid therapy.28,29 Corticotropin may be superior to oral corticosteroids.29-31 One study comparing very high-dose oral prednisolone to corticotropin, however, found no significant difference.32 The optimal dose of corticotropin remains controversial. While one single-blind study comparing high-dose (150 U/m2/d × 3 weeks followed by a 9-week taper) and low-dose corticotropin (20 U/d to 30 U/d × 2 to 6 weeks) found no significant difference in response or relapse rates,33 some epileptologists believe that high-dose corticotropin is superior. Adverse effects are more common with high-dose regimens and synthetic formulations and include hypertension, hypertrophic cardiomyopathy, gastric ulceration, immunosuppression, electrolyte disturbances, hyperglycemia, irritability, weight gain, and transient brain "shrinkage." Vigabatrin suppresses spasms in up to two-thirds of infants but appears most effective incases of cortical dysplasia or tuberoussclerosis.34 Side effects include irreversible peripheral visual field constriction (which appears minimal if the duration of treatment is kept at 6 months or less); reversible T2 hyperintensities on MRI in the brainstem, cerebellum, basal ganglia, and thalamus; sedation; hypotonia; insomnia; and irritability. In the United States, vigabatrin isavailable only through a limited numberof specialty pharmacies, and prescribing physicians must be registered with this program prior to prescribing (http://sabril.net/ ).

Despite little medical evidence for thispractice, pyridoxine (100 mg IV or 100 mg to 200 mg by mouth daily × 14 days) is commonly tried in cryptogenic or idiopathic West syndrome to rule outpyridoxine dependency. Pyridoxine should be started along with one of the first-line therapies. Surgical resection should be considered with medically intractable spasms and focal cortical lesions.

Clinically, West syndrome must bedifferentiated from nonepileptic conditions such as benign myoclonus in infancy, Sandifer syndrome and colic, self-stimulatory behaviors, and paroxysmal tonic upgaze, as well as other epilepticdisorders that may present with myoclonic seizures, including myoclonic epilepsy of infancy, Dravet syndrome, Lennox-Gastaut syndrome, myoclonic astatic epilepsy, and inborn metabolic errors.

Dravet Syndrome In Dravet syndrome, both generalized and partial seizures and EEG discharges are seen. The syndrome is said to be rare, with a reported incidence of 1 per 20,000 to 1 per 40,000, but is likely underrecognized. Approximately 80% of cases have a mutation in the sodium channel α1 subunit gene (SCN1A).35 Mutations usually involve nonsense or frameshift changes, leading to a truncated protein. However, some missense mutations may also result in this syndrome. The vast majority of mutations are sporadic. However, close relatives of children with Dravet syndrome have a higher rate of seizures than the general population, particularly GEFS+.

Dravet syndrome begins in the first year of life in a previously well infant with a generalized or focal clonic seizure that is often prolonged and frequently triggered by fever, infection, vaccination, or bathing. A diagnosis of atypical febrile seizure is frequently made. Progression to further recurrent prolonged focal seizures, which often change sides and occur both with and without fever, should suggest this diagnosis. From the end of the second year through age 5, myoclonic jerks appear, which may be frequent but variable in intensity. They may be aggravated shortly after waking, just prior to a convulsive seizure, or with photic stimulation. Atypical absence and complex partial seizures with prominent autonomic symptoms occur in over half of cases, usually beginning in the preschool years. Tonic seizures are rare. Over time, the frequency of prolonged convulsive seizures may decrease, but seizures remain refractory to treatment.

The initial EEG is typically normal. Over time, the background slows, and multifocal and generalized polyspike-and-wave discharges appear, which are frequently, but not uniformly, activated by photic stimulation and drowsiness. Neuroimaging studies are normal early on, but later show mild atrophy, and, less commonly, hippocampal sclerosis. The term borderline has been used for cases that lack a number of the key features (myoclonus, generalized spike-wave discharges, limited number or atypical seizure types). However, the prognosis seems similar.

While infants are developmentally normal at seizure onset, regression or lack of progression is seen between 1 and 4 years, with stabilization after that at a lower level of development.36 Visuomotor skills are more impacted than is language. Ataxia and corticospinal tract signs develop in most children. Hyperactivity and behavior problems are common. The mortality rate of Dravet syndrome is 16% to 18%, with deaths predominantly due to status epilepticus, drowning, and sudden unexplained death in epilepsy (SUDEP) (Case 3-7).37

Case 3-7 A 7-month-old girl presented with three bouts of status epilepticus. Her first seizure occurred at 4 months, within 24 hours of an immunization. She had twitching of her left face and arm, which progressed to become secondarily generalized and lasted 45 minutes. Her second prolonged seizure was similar and occurred at 6 months during a viral upper respiratory infection. The third occurred during a car ride on a warm summer day and began with right-sided arm and leg twitching, which secondarily generalized and lasted 65 minutes. Her electrolytes, glucose, calcium, metabolic studies, and MRI were normal, and the EEG showed some mild postictal slowing. Her mother had experienced two simple febrile convulsions in infancy. Genetic testing for SCN1A showed a frameshift mutation. She continued to have bouts of status epilepticus every 2 to 3 weeks despite valproic acid and clonazepam and ultimately stiripentol was started, which reduced her bouts of status epilepticus to less than every 6 months. At 24 months, she was

Page 18: Pediatric Epilepsy Syndromes

clearly delayed with only two words and had some nondisabling myoclonus. Her EEG showed some activation with photic stimulation (Figure 3-8). At 3½ years of age, she was found face down in the bathtub and could not be resuscitated.

FIGURE 3-8 Electroencephalograph of a 2-year-old child with Dravet syndrome showing a small amount of generalized spike-wave induced by photic stimulation.

Comment. The history of recurrent bouts of focal-onset prolonged seizures in the first year of life, often triggered by fever, should suggest a diagnosis of Dravet syndrome. This is a clinical diagnosis, although approximately 80% of patients are shown to have mutations in the SCN1A gene. Stiripentol, when used in combination with clobazam and valproate, may significantly reduce seizure frequency and duration. The initial EEG may be unremarkable. However, a significant proportion of children will show abnormalities with photic stimulation after 2 years of age. Unfortunately, the mortality rate is significant in this syndrome.

Seizures are medically refractory. Lamotrigine and carbamazepine should be avoided as they aggravate seizures. Stiripentol, a medication with orphan drug status in the United States, is an inhibitor of the cytochrome p450 system and has been helpful when used in combination with valproic acid and/or clobazam. (Both stiripentol and clobazam may be obtained from Caligor pharmacy in New York). A randomized placebo-controlled study showed a greater than50% reduction in the frequency of tonic-clonic seizures in 71% of the stiripentol-treated group versus only 5% of those on placebo, and 43% of the stiripentol group were free of tonic-clonic events.38

Lennox-Gastaut Syndrome LGS is relatively rare with an incidence of 1.9 to 2.1 per 100,000 children but accounts for approximately 6% to 7% of cases of intractable pediatric epilepsy.Onset is usually in the preschool years, and males are preferentially affected. Two-thirds of cases have preexistent brain abnormalities, including prenatal, perinatal, or postnatal insults, malformations of cortical development, neurocutaneous disorders, and metabolic or genetic conditions. One-third ofthese symptomatic cases have a history of infantile spasms. Approximately one-third of LGS cases are cryptogenic and affect children who are neurologically and developmentally normal prior to theonset of their epilepsy. Forty-eight percent of this group has a positive family history of epilepsyor febrile seizures,39 and LGS has been reported to be a phenotype of GEFS+.40

The characteristic triad of LGS consists of (1) multiple generalized seizure types, including tonic, atonic, myoclonic, and atypical absence; (2) an interictal EEG pattern of diffuse slow spike-and-wave complexes; and (3) cognitive dysfunction, which may not be present at onset but ultimately develops in most patients. This triad often takes months to evolve, making an early confident diagnosis difficult. The initialseizure types are recurrent falls or headnods, often with atypical absences or myoclonic seizures. The most characteristic seizure type is the nocturnal tonic event-its clinical manifestation isoften subtle and difficult to recognizewithout video-EEG recording. Tonicvibratory attacks have been described to occur toward the end of thenight. Nonconvulsive status epilepticus is common, and its frequency and duration appear predictive of poorer long-term developmental outcome.41 Nonconvulsive status epilepticus may be clinically subtle, particularly in children with cognitive impairment, resulting in delay in diagnosis. Tonic status epilepticus may be provoked by benzodiazepines.42

The EEG in LGS shows 1.5-Hz to 2.5-Hz polyspike- and spike-and-wave discharges on a slow background, but this pattern may take months to evolve. Early on, the EEGs may be normal or show only mild background slowing or small amounts of generalized

Page 19: Pediatric Epilepsy Syndromes

spike-wave. Low-voltage, frontally predominant, generalized paroxysmal fast activity manifesting as bursts of greater than 10-Hz rhythms is seen in slow-wavesleep and should suggest the diagnosis.

Ultimately over 80% of children are mentally handicapped, but cognitive delay may not be obvious before seizure onset.43 Factors predictive of poorer cognitive outcome include delayed development before seizure onset, history of infantile spasms, onset before 3 years of age, frequent seizures, and repeated nonconvulsive status epilepticus. Hyperkinesis, autistic features, or perseverative behaviors are common.

Seizures are generally medically intractable. Valproate is commonly used, and lamotrigine, topiramate, felbamate, and rufinamide have been shown to besuperior to placebo in randomized controlled studies.44,45 Given its potential risks of aplastic anemia and hepatotoxicity, felbamate should not be usedfirst line but is often very effective in more refractory cases. Benzodiazepines, levetiracetam, and zonisamide may reduce seizures but rarely provide complete control. Carbamazepine may lessen tonic seizures but worsen atypical absences. Ethosuximide can be tried for refractory atypical absences. Given the poor results with antiepileptic drugs, the ketogenic diet should be considered early on. Approximately half of children experience significant seizure reduction, with some achieving seizure freedom.

Patients with intractable drop seizures should be considered for corpus callosotomy. Section of only the anterior two-thirds limits adverse effects but may be less efficacious than complete callosotomy. Vagal nerve stimulation may provide modest benefit. 46 Nearly one-half of children had a 50% or greater reduction in seizures in retrospective studies.

LGS should be differentiated from MAE, which presents at a similar age withfrontally predominant slow spike-wave. Normal development before seizure onset, a positive family history of epilepsy, myoclonic astatic or prominent generalized tonic-clonic seizures, and parietal theta rhythms on EEG should suggest MAE. Drop seizures may also be seen in continuous spike-wave in sleep. However, the EEG shows continuous spike-wave in sleep and tonic seizures do not occur.

Electrical Status Epilepticus in Slow Sleep Electrical status epilepticus in slow sleep (ESES) comprises two related clinical syndromes: continuous spike-wave in sleep (CSWS) and Landau-Kleffner syndrome (LKS). In both syndromes, children present in the preschool or early school years with regression that appears coincident with very frequent electrographic discharge on EEG during slow sleep.47 In CSWS, the discharges are frontal, and a more global regression with decreased intellectual level, poor memory, hyperkinesis, impaired attention span, psychosis, and motor impairment is seen. In LKS, discharges predominantly affect the temporal region, with acquired auditory agnosia. While seizures are seen in nearly three-quarters of children with LKS, they are rarely frequent or intractable. The usual semiology is that of a nocturnal hemiclonic seizure. Seizures are moreproblematicin CSWS and may consist of partial and/or generalized seizures, including unilateralor bilateral clonic, tonic-clonic, absence, partial motor, complex partial, and atonic seizures. Tonic seizures, however, are not seen.

Some cases of CSWS are symptomatic of a prior brain insult. However, in others, particularly LKS, no etiology isfound and prior psychomotor development was normal. These cases may represent the severe end of the spectrum of benign partial epilepsy of childhood.

Early EEG may demonstrate diffuse spikes and slow waves, predominantly in centrotemporal or frontotemporal regions. However, with time, the EEG in non-REM sleep shows a picture of electrical status, with diffuse, unilateral,or focal spike-waves that occupy 85% ormore of slow sleep (Case 3-8, Figure 3-9).

Page 20: Pediatric Epilepsy Syndromes

FIGURE 3-9 Nearly continuous spike-and-wave discharges during sleep in a child with continuous spike-wave in sleep.

Case 3-8 A 6-year-old boy with a history of mild cerebral palsy secondary to perinatal, grade 3, left-sided intraventricular hemorrhage presented with two right-sided hemiclonic seizures, and carbamazepine was started. Over the next 3 months, his behavior deteriorated and he had further hemiclonic seizures, as well as numerous staring spells and several falls. His parents stated that he never listens, and at times he appears confused when they speak to him. He was aggressive with his younger brother and moved from activity to activity without being able to focus. His school performance had deteriorated to the point that he needed a full-time assistant to keep him on task.

His EEG showed left-sided frontotemporal discharge during wakefulness, which became nearly continuous in sleep (Figure 3-9). His carbamazepine was replaced with levetiracetam. However, no clinical improvement occurred. He was then treated with a course of prednisone, starting at 2 mg/kg/d for 2 weeks followed by a taper over the next 8 weeks. With this, his focus markedly improved, and he returned to his normal level of function. The levetiracetam was maintained, and seizures were controlled.

Comment. Children with CSWS present with a global regression secondary to frontal lobe dysfunction. Their seizures may be of varied semiology, and frequently a preexisting brain insult is present. It is important to obtain a sleep recording in such children to make this diagnosis and initiate appropriate therapy.

While seizures in ESES may respond to antiepileptic medications, most drugs have little impact on the electrical status and cognitive impairment. Carbamazepine or phenytoin may worsen this condition. Valproic acid, levetiracetam, or benzodiazepines are probably the best choices for seizure control. Corticosteroids are often considered the first-line treatment in CSWS, but their efficacy has only been shown in several unblinded studies.48 Other clinicians have reported efficacy with short 3- to 4-week cycles of high-dose diazepam (0.5 mg/kg) after a rectal diazepam bolus of 1 mg/kg.49 Case reports have also claimed efficacy for IV immunoglobulin,50 sulthiame (which is not routinely available in the United States for cryptogenic cases),51 and multiple subpial transection.52

Seizures and electrical status disappear in later in childhood. While improvements in language and cognitionare usually also seen, many children do not return to normal levels of function.

Rasmussen Encephalitis Rasmussen encephalitis presents with intractable focal epilepsy and progressive hemiparesis. Children show progressive intellectual decline. Visual and sensory cortical deficits and speech problems are frequent. Progressive atrophy of the affected hemisphere is seen on MRI. Seizures are typically refractory to antiepileptic drugs. Immunotherapy may slow progression. In

Page 21: Pediatric Epilepsy Syndromes

children with predominantly unilateral symptoms and disabling seizures, hemispherectomy should be considered once the family comes to terms with the permanent hemiparesis that will result from this procedure. After hemispherectomy, seizure outcome is markedly improved, with two-thirds of patients achieving seizure freedom (Case 3-9). Of 46 children undergoing hemispherectomy at a mean age of 8.8 years, all walked independently and were talking at time of last follow-up with mild to moderate speech problems at worst.53

Case 3-9 A 4-year-old girl presented with a 3-year history of focal seizures that started with rhythmic twitching of her left arm, followed by left face. At times, they were associated with loss of awareness, and they were rarely secondarily generalized. Over time, seizures increased in frequency and duration to the point they were occurring multiple times per day. She had gradual onset of a left hemiparesis over the past 2 months. On examination, she was noted to have arrhythmic twitching of her left hand and face. Seizures had persisted despite treatment with five antiepileptic drugs (Video Segment 6).

Comment. This young girl had epilepsia partialis continua of her left hand and face. Her history of progressive seizures and hemiparesis is suggestive of Rasmussen encephalitis. Her MRI showed right hemispheric atrophy (Figure 3-10), which had not been present 18 months earlier. This condition is notoriously resistant to antiepileptic drugs. While immunotherapy may result in transient response, most children ultimately require hemispherectomy. This girl underwent hemispherectomy 2 months after video was obtained and has remained seizure free.

FIGURE 3-10 A, Ictal EEG in a child with Rasmussen encephalitis with a focal motor seizure, demonstrating rhythmic muscle artifact that corresponded with frequency of hemifacial clonic seizure, but no EEG correlate. B, MRI (coronal T1) demonstrates right hemispheric atrophy.

Progressive Myoclonic Epilepsy The progressive myoclonic epilepsies encompass various metabolic or neurodegenerative conditions that present with massive myoclonus, tonic-clonic seizures, partial seizures, neurocognitive deterioration, and cerebellar impairment. Table 3-4 summarizes the clinicaland diagnostic features of these conditions.

Page 22: Pediatric Epilepsy Syndromes

TABLE 3-4 Progressive Myoclonic Epilepsies Presenting at Different Stages of Childhood

KEY POINTS * Benign familial neonatal seizures, an autosomal dominant disorder with 85% penetrance, is linked to voltage-gated potassium channels KCNQ2 and KCNQ3 on chromosomes 20q and 8q, respectively.

* Benign idiopathic neonatal seizure symptoms typically begin on the fifth day of life, or "fifth day fits," with partial clonic seizures that may migrate, increase in frequency, and culminate in status epilepticus. Seizures typically resolve after 24 hours.

* Generalized epilepsy with febrile seizures plus (GEFS+) is a primary generalized epilepsy syndrome characterized by febrile and afebrile seizures. Febrile seizures continue beyond the typical age of remittance, 6 years.

* The outcome and course of myoclonic astatic epilepsy (MAE) are variable, from complete remission to intractable epilepsy with poor cognitive outcome. MAE therefore must be differentiated from Lennox-Gastaut syndrome (LGS). This is done clinically by observing the myoclonic astatic seizures.

* Children with childhood absence epilepsy typically have very brief absence seizures, characterized by abrupt onset of impaired consciousness and unresponsiveness lasting approximately 10 seconds, occurring up to hundreds of times per day. The EEG demonstrates generalized symmetric 3-Hz spike-wave discharges.

* The generalized tonic-clonic seizures and myoclonic seizures of juvenile myoclonic epilepsy (JME) tend to occur in the morning upon awakening. In children with JME, 100% will have myoclonic seizures, 96% will have generalized tonic-clonic seizures, and only 20% will experience absence seizures during the period of active absences.

* The prognosis for benign partial epilepsy of infancy is excellent, with good response to antiseizure medications and resolution by 2 to 3 years of age.

* The syndrome of benign familial infantile convulsions is likely autosomal dominantly inherited with incomplete penetrance. There is genetic heterogeneity, with linkage to chromosomes 19q, 16p12-q12, and 2q23-24.2, making this a distinct syndrome from benign familial neonatal convulsions.

Page 23: Pediatric Epilepsy Syndromes

* In early-onset benign occipital epilepsy, seizures arecharacterized by autonomic symptoms, including ictus emeticus (nausea and retching), emesis, pallor, urinary incontinence, and hypersalivation, with preserved consciousness.

* Children with late-onset childhood epilepsy with occipital paroxysms typically present with elementary visual hallucinations involving simple geometric patterns that may progress to more well-formed, complex visual hallucinations, followed by gaze deviation, ipsilateral head deviation, and possible secondary generalization.

* Patients with benign childhood epilepsy with centrotemporal spikes typically experience nocturnal seizures characterized by perioral paresthesias and ipsilateral facial myoclonus, as well as excessive salivation, speech arrest, and guttural noises. Because of the benign nature of the seizures, medication may not be necessary.

* West syndrome refers to the triad of infantile spasms, hypsarrhythmia, and psychomotor delay. Prognosis is poor, with motor delay and/or mental retardation in over 75% of cases.

* The main first-line therapeutic agents for West syndrome are corticotropin or steroids and vigabatrin.

* Dravet syndrome begins in the first year of life in a previously well infant with a generalized or focal clonic seizure that is often prolonged and frequently triggered by fever, infection, vaccination, or bathing.

* While infants with Dravet syndrome are developmentally normal at seizure onset, regression or lack of progression is seen between 1 and 4 years, with stabilization after that at a lower level of development.

* Stiripentol, a medication with orphan drug status in the United States, is an inhibitor of the cytochrome p450 system and has been helpful when used in combination with valproic acid and/or clobazam.

* The characteristic triad of LGS consists of multiple generalized seizure types, an interictal EEG pattern of diffuse slow spike-and-wave complexes, and cognitive dysfunction, which may not be present at onset but ultimately develops in most patients. This triad often takes months to evolve, making an early confident diagnosis difficult.

* Ultimately over 80% of children with LGS are mentally handicapped, but cognitive delay may not be obvious before seizure onset.

* Seizures in LGS are generally medically intractable. Valproate is commonly used, and lamotrigine, topiramate, felbamate, and rufinamide have been shown to be superior to placebo in randomized controlled studies.

* Given the poor results with antiepileptic drugs in patients with LGS, the ketogenic diet should be considered early on.

* While seizures in electrical status epilepticus in slow sleep may respond to antiepileptic medications, most drugs have little impact on the electrical status and cognitive impairment.

* Rasmussen encephalitis presents with intractable focal epilepsy and progressive hemiparesis.

* The progressive myoclonic epilepsies encompass various metabolic or neurodegenerative conditions that present with massive myoclonus, tonic-clonic seizures, partial seizures, neurocognitive deterioration, and cerebellar impairment.

-------------------------------------------


Recommended