Pediatric Epilepsy Syndromes
Stefanie Jean-Baptiste Berry, MDPediatric Neurologist/EpileptologistNortheast Regional Epilepsy Group
IntroductionMost Recent ILAE Definition April 2014: (1) At least two unprovoked (or reflex)
seizures occurring >24 h apart (2) One unprovoked (or reflex) seizure and
a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years
(3) Diagnosis of an epilepsy syndrome
Introduction Term Epilepsy Syndrome has been used by
ILAE to refer to “a complex of signs and symptoms that define a unique epileptic condition.”
Epilepsy syndromes denote specific constellations of clinical seizure 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.
Introduction Identification of a specific syndrome is important
to define the best treatment and accurately prognosticate long-term outcome.
Idiopathic (primary) – presumed etiology is genetic
Symptomatic (secondary) types – underlying etiology is known or presumed based on other evidence of brain dysfunction, such as developmental delay.
Generalized seizures vs. Localization-related seizures.
Benign Familial Neonatal Seizures
Typically present during the first few weeks of life
Focal, multifocal, or generalized seizures Seizures are brief but occur 20 – 30 times
per day Seizures may be difficult to control
Benign Familial Neonatal Seizures
Normal neurologic exam No specific EEG features Family history of similar neonatal seizures
is important for diagnosis Autosomal dominant with 85% penetrance Linked to voltage gate potassium channels
KCNQ2 and KCNQ3 on chromosomes 20q and 8q
Benign Familial Neonatal Seizures
Outcome generally favorable Resolution of seizures typically in early to
midinfancy Normal neurodevelopment 8-16% of patients will later develop
epilepsy as adults
Benign Idiopathic Neonatal Seizures Healthy, neurologically normal term
neonates Seizures typically begin on the fifth day of
life or “fifth day fits” Partial clonic seizures that migrate,
increase in frequency and culminate in status epilepticus
Benign Idiopathic Neonatal Seizures No specific EEG features There is no family history of seizures Seizures typically resolve after 24 hours Children have normal neurodevelopment No increased risk of seizure recurrence
Generalized (Genetic) Epilepsy with Febrile Seizures Plus 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, complex partial and atonic seizures.
Generalized (Genetic) Epilepsy with Febrile Seizures Plus Seizures start 4 months and 10 years, with
mean onset of 2 years Prior to onset of afebrile seizures, GEFS+
can be difficult to distinguish from febrile seizure
Careful family history is important
Generalized (Genetic) Epilepsy with Febrile Seizures Plus Interictal EEG may be normal or
demonstrate generalized epileptiform discharges
Genetically heterogenous autosomal dominant with 60-80% penetrance
Within families multiple phenotypes with variable severity exist
Generalized (Genetic) Epilepsy with Febrile Seizures Plus Multiple gene mutations linked to GEFS+
including 19q13.1 (SCN1B gene), 2q23-24.2 (SCN1A gene) and 5q31.1-33.1
Excellent prognosis in most children Seizures typically spontaneously remit by
age 11 years Up to 30% may have more severe
epilepsy
Myoclonic Astatic Epilepsy of Doose Rare, affecting 1:10,000 Presents in previously neurologically
healthy preschool-aged children Multiple seizure types including
generalized tonic clonic, myoclonic, absence, atonic, myoclonic, myoclonic atonic
Myoclonic atonic seizures most prominent
Myoclonic Astatic Epilepsy of Doose Outcome and course are variable – complete
remission to intractable epilepsy with poor cognitive outcome
EEG demonstrates 2-3Hz spike and wave discharges
Up to 32% of children have a family history of epilepsy
Inheritance pattern is unknown
Childhood Absence Epilepsy Comprises 2-15% of childhood
epilepsy Onset is usually 4 and 10 years of age Girls 2-5 times more likely to have
absence Most patients with childhood absence
have normal neurological exams and normal intelligence scores
Childhood Absence Epilepsy
Inherited in autosomal dominant pattern with incomplete penetrance chromosomes 20q, 16p13.3, and 8q24.3
Caused by abnormalities in T-type calcium channels, which are responsible for rhythmic depolarizing activity in the thalamic neurons
Childhood Absence Epilepsy Generalized type of seizure Characterized by sudden
discontinuation of activity with loss of awareness, responsiveness, and memory, with an abrupt recovery
Automatisms, brief clonic jerks, and loss of postural tone can also be seen
Childhood Absence Epilepsy
Usually lasts 5 to 10 seconds Up to hundreds of seizures per day Seizures can be provoked by
hyperventilation in approximately 90% of children
Childhood Absence Epilepsy
Classic EEG finding in typical absence seizures is the sudden onset of 3-Hz generalized symmetrical spike and wave complexes
Interictal EEG background is normal
Childhood Absence Epilepsy
Normal EEG
Childhood Absence Epilepsy
Absence Seizure
Childhood Absence Epilepsy
Most children only experience absence seizures
3% will experience generalized tonic-clonic seizures
Childhood Absence Epilepsy With typical absence seizures, if
consistent EEG, normal intelligence, and normal neuro exam, no further work up is necessary
Primary drugs of choice are ethosuximide (Zarontin), valproic acid (Depakote), and lamotrogine (Lamictal)
Most clinicians start with ethosuximide (T-type calcium channel blocker) because of fewer incidence of side effects
Childhood Absence Epilepsy Valproic acid is the drug of choice in
patients with both absence and generalized tonic-clonic seizures
Lamictal is a safer choice for female teens
Duration of therapy is variable, although general rule is to taper off therapy after 2 seizure free years
Childhood Absence Epilepsy Absence status epilepticus is
characterized by sustained impairment of consciousness associated with generalized 3-Hz spike and wave
Patients often exhibit facial twitching, eye blinking, staring and automatisms
Treatment is usually with IV lorazepam or Depakote (not Dilantin)
Childhood Absence Epilepsy
Children with early onset (mean age 6) have the best prognosis with complete remission 2 to 6 years after onset
Onset of absence seizures before age 3 years is associated with increased likelihood of neurodevelopmental abnormalities
Childhood Absence Epilepsy
Average age of cessation is 10 years old
Typical absence seizures generally have a favorable prognosis with remission rates of approximately 80 percent
Can precede juvenile myoclonic epilepsy in 11-18% of cases
Childhood Absence Epilepsy
Risk factors for intractability: myoclonic or atonic component to seizure, generalized tonic clonic seizures occur at onset and photosensitivity on EEG
Juvenile Absence Epilepsy Onset is typically between ages 10 and 16 Clinical seizures similar to CAE Seizures occur less frequently and may be
longer duration More likely to experience generalized tonic
clonic seizures Interictal EEG, 3.5-4Hz spike and
polyspike and wave Response to treatment good, but may be
lifelong
Juvenile Myoclonic Epilepsy Affects 4 to 10% of all patients with
epilepsy and up to 26% of patients with idiopathic generalized epilepsy
Seizures typically present between 12 and 18 years
Inheritance is complex Classic form is likely autosomal dominant
and inherited and linked to 6p12-11
Juvenile Myoclonic Epilepsy
Commonly 1st seizure noted is a GTC in setting of sleep deprivation
Careful questioning will reveal a history of myoclonic seizures and possible absence seizures in the preceding months
Occurs in both genders with equal frequency
Juvenile Myoclonic Epilepsy Seizure types include generalized tonic-
clonic, myoclonic, and absence 100% have myoclonic seizures, 96%
have GTC, and only 20% with absence Generalized tonic-clonic and myoclonic
seizures tend to occur in morning upon awakening
Seizures are precipitated by sleep deprivation, alcohol ingestion and in women, menstruation
Juvenile Myoclonic Epilepsy
Myoclonic seizures are brief and bilateral, flexor jerks of the arms, which may be repetitive
Jerks sometimes affect the legs, causing the patient to fall
Consciousness is not impaired during myoclonic seizures
Juvenile Myoclonic Epilepsy Delays in diagnosis are common, often
until a generalized tonic-clonic seizure brings the child to medical attention
Interictal EEG in JME consists of generalized spike and polyspike-and-wave discharges of 4 to 6 Hz, usually maximal in the frontocentral regions
Photic stimulation often provokes a discharge (30 to 90%)
Juvenile Myoclonic Epilepsy
Generalized Polyspike and Wave Discharge
Juvenile Myoclonic Epilepsy Traditional treatment was valproic acid with
85%-90% response but many side effects Newer effective drugs include
levetiracetam, lamotrogine, topiramate and zonisamide
Carbamazepine, phenytoin and gabapentin may exacerbate seizures
Response to treatment is excellent but treatment is lifelong
Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS) Most common form of idiopathic partial
epilepsy Accounts for 13%-23% of all childhood
epilepsies Although it is clearly familial, its mode of
inheritance is unclear Onset is between 4 and 10 years Peak age of onset is 7-8 years Children are neurologically and cognitively
normal
Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS) Nocturnal seizure, usually occurring after
falling asleep or before awakening is typical Seizures described as unilateral
paresthesias of the face, unilateral clonic or tonic activity involving the face, speech arrest, drooling with preserved consciousness
Can have secondarily generalized tonic-clonic seizures
Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS)
EEG background is normal Spikes are present at the midtemporal
and central (centrotemporal) head region
Marked activation of spikes in drowsiness and sleep is characteristic, and 30% of cases show spikes only during sleep
Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS)
EEG Findings BCECTS
EEG Findings BCECTS
Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS) If typical history, normal neuro exam, and
characteristic EEG findings, an MRI is not necessary
No treatment is necessary in patients with infrequent, nocturnal, partial seizures
If seizures are frequent (20%)and disturbing to patient and family, treatment with Tegretol or Trileptal is usually successful
Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS) Excellent prognosis Spontaneous remission occurs by age 15
to 17, often much earlier Some children may develop language,
cognitive or behavioral deficits which improve after remission
Panayiotopoulos Syndrome Early-onset benign childhood epilepsy
with occipital paroxysms Average age of 3-6 years Normal development Characterized by nocturnal seizures in
two-thirds, with tonic eye deviation, vomiting (autonomic) and impaired consciousness
Hemiconvulsions and GTC seizures are common
Panayiotopoulos Syndrome Interictal EEG shows normal background
with high-amplitude occipital spike-wave complexes on eye closure
Seizures are infrequent and one third of patients will only have a single seizure
Paradoxically, seizures are frequently prolonged (status epilepticus)
Excellent prognosis –seizures usually cease within 2 years onset
Treatment with medication is not necessary
Late-Onset Childhood Epilepsy with Occipital Paroxysms - Gastaut Syndrome
Rare condition Ages 6-12 years, average 8 years 21-37% of cases have family history of
epilepsy.
Seizures characterized by visual hallucinations or ictal blindness often with gaze deviation or eyelid fluttering
Often followed by postictal headache Focal seizures often evolve into
hemiconvulsions or GTC seizures Seizures more frequent but shorter
duration
Late-Onset Childhood Epilepsy with Occipital Paroxysms - Gastaut Syndrome
Late-Onset Childhood Epilepsy with Occipital Paroxysms - Gastaut Syndrome EEG –normal background, interictal
occipital high amplitude spike wave with attenuation on eye opening
Ictal recordings show fast occipital spikes
EEG Findings Childhood Epilepsy with Occipital Paroxysms
Late-Onset Childhood Epilepsy with Occipital Paroxysms - Gastaut Syndrome
Brain MRI is normal (neuroimaging is recommended)
Seizures respond well to carbamazepine 50-60% have seizure remission within 2-4
years
Infantile SpasmsOccurs almost exclusively in infants
younger than 1 year of age Incidence is 1 in 4,000 to 6,000
birthsSpasm onset is usually within the
first 4-8 months of lifeFamilial occurrence is rare
Infantile Spasms Seizures typically described as brief,
symmetrical contractions of the neck trunk, and extremities
Flexor or extensor muscles can be involved
Asymmetrical infantile spasms are rare Spasms frequently occur immediately
upon, or soon after, arousal 80% of spasms occur in clusters
Infantile Spasms Interictal EEG is characterized
hypsarrhythmia defined as high voltage slow waves and multifocal spikes
In a small number of infants, the background activity may appear normal
Most common ictal pattern is characterized by generalized slow wave transient followed by attenuation of background activity
Infantile Spasms
Hypsarrhythmia
Infantile Spasms Etiologies of infantile spasms can be
determined in 60%-90% of cases Tuberous sclerosis is a major cause of
infantile spasms (up to 25%) Other etiologies include: lissencephaly,
Sturge-Weber, HIE, meningitis, and inborn errors of metabolism
A minority of infants have idiopathic infantile spasms
Infantile Spasms
First line is ACTH but has many side effects
Vigabatrin, Prednisone, and Topamax are also effective drugs
A challenge with a 100mg of IV pyridoxine should be considered in idiopathic cases
Infantile Spasms Overall prognosis is poor, with only
5% of the total patient population having normal outcomes
Severe or very severe impairment was observed in 67% of patients
Only factor that seems to effect long-term outcome is whether the patient is classified as cryptogenic (unknown) or symptomatic
Lennox Gastaut Syndrome
Classic Triad: 1.Multiple seizure types (tonic, atonic, and atypical absence)
2.EEG pattern of slow spike and wave discharges
3.Cognitive Impairment
Lennox Gastaut Syndrome
Onset usually between 1 and 8 years
Most cases between 2 and 5 yearsOnset rare after 10 yearsMales > females10% of childhood epilepsies
Lennox Gastaut Syndrome
Neurological symptoms may be absent initially
9-39% preceded by infantile spasms
High seizure frequency At least 1 episode of status in
50%-75%
Lennox Gastaut Syndrome
No single cause2/3 symptomatic (cortical
dysplasias, TS, metabolic, prenatal/perinatal)
Cryptogenic (unknown cause) LGS with normal brain MRI accounts for 1/3 cases
Lennox Gastaut SyndromeTonic Seizures:
1.Most characteristic – prerequisite
2.Flexor movement of the head and trunk with apnea preceded by brief cry (axial)
3.Abduction, elevation of limbs, usually arms with clenching of the fists (axorhizomelic)
4.Sustained contraction involving most
muscles, including distal (global)
Lennox Gastaut Syndrome
Atypical Absence:
1.Second most common type
2.Brief loss/lapse of consciousness
3.Difficult to identify
Lennox Gastaut SyndromeAtonic Seizures:
1.“Drop attacks”
2.Particularly hazardous
3.56% of patientsOther types:
1.Focal
2.GTC
3.Unilateral Clonic
Lennox Gastaut SyndromeEEG Findings in LGS:1.Slow background2.Diffuse slow-spike and wave, 1.5 - 2.5Hz3.Paroxysmal Fast Activity4.Focal or multifocal discharges in 14%-18%5.75% of electroclinical persists to adult
Lennox Gastaut Syndrome
Slow Spike and Wave
Lennox Gastaut Syndrome
Paroxysmal Fast Activity
Lennox Gastaut Syndrome
Seizures resistant to therapy Drugs used in combination, mostly guided by
anecdotal evidence or personal experience AED may help control one seizure type while
worsening another First line AEDs are Valproic Acid and
Benzodiazepines Rufinamide and Felbamate
Lennox Gastaut SyndromeOverall, unfavorable prognosisWorse prognosis: 1.Symptomatic 2.Infantile spasms3.Early onset seizures4.Higher seizure frequency5.Constant background slowing
Dravet Syndrome
Rare Incidence of 1 in 20,000 to 40,000 Approximately 80% of cases have
mutation in SCN1A (sodium channel) Vast majority of mutations are sporadic Close relatives have a higher rate of
seizures (GEFS+)
Dravet Syndrome
Begins in the first year of life in previously well infant
Generalized or focal clonic seizure is often prolonged
Onset frequently triggered by fever, infection, vaccination or warm bath
Progression to further recurrent prolonged focal seizures with and without fever
Dravet Syndrome
End of second year through age 5, myoclonic jerks appear
Atypical absence and complex partial seizures with autonomic symptoms occur in 50% in preschool years
Tonic seizures are rare
Dravet Syndrome
Initial EEG is typically normal Over time, background slows Multifocal and generalized polyspike and
wave discharges appear Epileptiform discharges activated by
drowsiness and photic stimulation MRI normal early, later shows atrophy
Dravet Syndrome
Infants are developmentally normal at onset
Regression or lack of progression is seen between 1 and 4 years, stabilization after at lower level
Visuomotor skills more affected than language
Dravet Syndrome Seizures are medically refractory Valproic Acid and clobazam are first line Second line AEDs include topiramate,
levetiracetam and zonisamide Lamotrigine and carbamazepine should be
avoided – can aggravate seizures Mortality rate 16-18% (status, SUDEP,
drowning)
References Wirrell, Elaine and Nickels, Katherine C.
Pediatric Epilepsy Syndromes. Continuum Lifelong Learning Neurology 2010; 16(3) 57-85.
Ebersole and Pedley, Current Practice Of Clinical Electroencephalography. Third Edition 2003.
Menke, Sarnat and Maria. Child Neurology. Seventh Edition. 2006
Pellock, Dodson and Bourgeois. Pediatric Epilepsy: Diagnosis and Therapy. Second Edition. 2001