Pediatric Epilepsy
Syndromes
Stefanie Jean-Baptiste Berry, MD
Pediatric Neurologist/Epileptologist
Northeast Regional Epilepsy Group
Introduction
Most 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
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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
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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.
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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
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Generalized (Genetic) Epilepsy
with Febrile Seizures Plus
Multiple gene mutations linked to GEFS+
including 19q13.1 (SCN1B gene), 2q2324.2 (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
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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
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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
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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
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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
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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
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Childhood Absence Epilepsy
Normal EEG
Childhood Absence Epilepsy
Absence Seizure
Childhood Absence Epilepsy
Most children only experience absence
seizures
 3% will experience generalized tonicclonic seizures
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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
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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
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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)
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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
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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
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Childhood Absence Epilepsy
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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
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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
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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
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Juvenile Myoclonic Epilepsy
Seizure types include generalized tonicclonic, 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
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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-andwave discharges of 4 to 6 Hz, usually
maximal in the frontocentral regions
 Photic stimulation often provokes a
discharge (30 to 90%)
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Juvenile Myoclonic Epilepsy
Generalized Polyspike and Wave Discharge
Juvenile Myoclonic Epilepsy
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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
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Benign Childhood Epilepsy with
Centrotemporal Spikes (BCECTS)
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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 tonicclonic 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
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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
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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
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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
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Panayiotopoulos Syndrome
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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.
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Late-Onset Childhood Epilepsy with
Occipital Paroxysms - Gastaut
Syndrome
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
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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
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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
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Infantile Spasms
 Occurs
almost exclusively in infants
younger than 1 year of age
 Incidence is 1 in 4,000 to 6,000
births
 Spasm onset is usually within the
first 4-8 months of life
 Familial 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
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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
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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
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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 longterm outcome is whether the patient
is classified as cryptogenic (unknown)
or symptomatic
Lennox Gastaut Syndrome
Classic
1.
2.
3.
Triad:
Multiple seizure types (tonic, atonic,
and atypical absence)
EEG pattern of slow spike and wave
discharges
Cognitive Impairment
Lennox Gastaut Syndrome
 Onset
usually between 1 and 8
years
 Most cases between 2 and 5 years
 Onset rare after 10 years
 Males > females
10% 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 cause
 2/3 symptomatic (cortical
dysplasias, TS, metabolic,
prenatal/perinatal)
 Cryptogenic (unknown cause) LGS
with normal brain MRI accounts for
1/3 cases
Lennox Gastaut Syndrome
Tonic
1.
2.
3.
4.
Seizures:
Most characteristic – prerequisite
Flexor movement of the head and trunk
with apnea preceded by brief cry (axial)
Abduction, elevation of limbs, usually arms
with clenching of the fists (axorhizomelic)
Sustained contraction involving most
muscles, including distal (global)
Lennox Gastaut Syndrome
Atypical
1.
2.
3.
Absence:
Second most common type
Brief loss/lapse of
consciousness
Difficult to identify
Lennox Gastaut Syndrome
Atonic
Seizures:
1. “Drop attacks”
2. Particularly hazardous
3. 56% of patients
Other types:
1. Focal
2. GTC
3. Unilateral Clonic
Lennox Gastaut Syndrome
EEG
1.
2.
3.
4.
5.
Findings in LGS:
Slow background
Diffuse slow-spike and wave, 1.5 - 2.5Hz
Paroxysmal Fast Activity
Focal or multifocal discharges in 14%18%
75% of electroclinical persists to adult
Lennox Gastaut Syndrome
Slow Spike and Wave
Lennox Gastaut Syndrome
Paroxysmal Fast Activity
Lennox Gastaut Syndrome
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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 Syndrome
Overall,
unfavorable prognosis
Worse prognosis:
1. Symptomatic
2. Infantile spasms
3. Early onset seizures
4. Higher seizure frequency
5. 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
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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
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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)
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References
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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