This document discusses several epileptic encephalopathy syndromes that occur in childhood. It defines epileptic encephalopathies as heterogeneous brain disorders occurring during development where abnormal EEG activity is responsible for cognitive and motor regression beyond what would be expected from the underlying etiology alone. It then describes several recognized epileptic encephalopathy syndromes in children including Ohtahara syndrome, early myoclonic encephalopathy, West syndrome, Dravet syndrome, Lennox-Gastaut syndrome, epileptic encephalopathy with continuous spike and wave during sleep, and Landau-Kleffner syndrome. For each syndrome, it provides details on age of onset, common seizure types and EEG patterns, potential etiologies,

1. EPILEPTIC ENCEPHALOPATHY
SYNDROMES
Dr Jo Martin Kuncheria
JR, Pediatrics

2. Epileptic encephalopathies
A group of heterogeneous brain disorders occurring at a critical period of
brain development where frequent abnormal ictal and or interictal EEG
epileptiform activity is mainly responsible for behavioral , cognitive and
motor regression
-Cannot be explained by the underlying etiology alone
-EEG paroxysmal activity that is often aggressive
-Seizures that are multiform & intractable
-Cognitive , behavioral and neurological defects that may be relentless
-Some times early death

3. RECOGNIZED EPILEPTIC ENCEPHALOPATHY
SYNDROMES
 Ohtahara syndrome
 Early myoclonic encephalopathy
 West syndrome
 Dravet syndrome
 Lennox- Gastaut syndrome
 Epileptic encephalopathy with continuous spike and wave during
sleep
 Landau-Kleffner syndrome

4. EARLY INFANTILE EPILEPTIC ENCEPHALOPATHY
( OHTAHARA SYNDROME)
Associated with very refractory epilepsy.
Early onset from intra uterine period to 3 months
Tonic spasms along with focal motor seizures , occur in sleep & wakeful state
Myoclonus is rare in the early stages of this disorder.
Burst-suppression pattern on EEG.
More likely to be associated with structural lesions – cortical dysplasia,
hemimegalencephaly, Aicardi syndrome
Developmental prognosis is poor
Many will evolve to hypsarrhythmia on EEG and accompanied by infantile spasms.
Improved outcome to cases amenable to surgical resection

5. EARLY MYOCLONIC EPILEPSY (EME)
Often present in the first few days of life.
Focal motor seizures and myoclonic seizures.
Usually affects the face and limbs.
Tonic seizures appear relatively late .
The seizures are very refractory to medications.
The EEG is characterized by a burst-suppression pattern, which may only be seen in
sleep, and, if present throughout the sleep-wake cycle, is exacerbated by sleep.
Often associated with underlying metabolic disorders (non ketotic hyperglycinemia,
organicacidemia , menkes disease, zellweger syndrome)
Can develop later into infantile spasms.
Development is severely affected, and many infants die, often within their first year.

6. WEST SYNDROME
• Most common epileptic encephalopathy in infancy
• Starts -2 and 12 mo
• Epileptic spasms in clusters
shortly after waking, tonic contractions of axial & limb
muscles
• Developmental delay present before onset of seizure
Motor deficits, impaired visual attention, microcephaly
look for NC markers of tuberous sclerosis
also organomegaly/unusual odour/dysmorphism
• ETIOLOGY – identified in over half (structural – cortical
malformations, perinatal brain injury; Genetic (SCN1A gene),
metabolic rarely)
Males- ARX gene mutations (ambiguous genitalia
&cortical migration abnormalities
Epileptic spasms
Hypsarrythmia in EEG
Developmental
regression

7. • EEG interictal -Hypsarrhythmia is a very high amplitude,asynchronous slow waves (chaotic)
with multifocal spikes and polyspikes
Ictal – high voltage often generalized sharp or slow wave followed by electrodecrement
• MRI – must in all cases. If normal may be redone every 6 months and should be done after
24-30 months when myelination is mature to detect cortical dysplasia
• OUTCOME – underlying etiology is the most critical predictor
Most have Intellectual disability and are at risk for autism
Good prognostic factors
 less time from spasm onset to diagnosis
 favourable response to initial therapy
 absence of other seizures before spasms
 absence of atypical spasms or focal seizures or asymm EEG
 Down syndrome, neurofibromatosis, PVL better prognosis
Infantile spasms resolve by ealy preschool years, but 50-90% develop other seizure types (most
commonly LGS or focal/multifocal epilepsy)
High mortality risk

8. SEVERE MYOCLONIC EPILEPSY OF INFANCY
( DRAVET SYNDROME)
• Most severe in the phenotypic spectrum of FS–associated epilepsies.
• onset -infancy.
• febrile&afebrile u/Lclonic seizures-recur every 1or2 mo.
• febrile convulsions -prolonged, more frequent, and focal and recur in clusters.
• start to occur with lower fevers and then without fever.
• During 2nd yr - myoclonus, atypical absences, and focal seizures occur frequently and
developmental delay usually follows.
• usually caused by a de novo mutation, rarely AD
• Mutations in the SCN1A gene-MCC( 80% ).
DEVELOPMENT – normal at onset of epilepsy, later deteriorate
OUTCOME – extremely pharmacoresistant
many seizure types resolve by early adulthood, high mortality

9. LENNOX-GASTAUT SYNDROME
Starts - 2 and 10 yr (peak 3-5 years)
 Cognitive impairment
 multiple seizure types (atypical absences, myoclonic, astatic,
and tonic seizures)
 specific EEG (diffuse slow spike and wave interictal pattern,
paroxysmal fast activity during sleep)
Seizures
o Tonic seizures – most common can be B/L symmetrical or
U/L
o Atypical absence seizure
o Atonic – less common, head drop to fall
o Myoclonic – rare up to 1/3
o Status – non convulsive (contionuous absence with
intermittent tonic) or convulsive

10. EEG :
Interictal 1 to2Hz spike & slow waves with frontal predominance,
Paroxysmal fast activity,polyspike bursts in sleep (characteristic) and a slow
background in wakefulness
Ictal pattern varies with seizure types
POSSIBLE ETIOLOGY
Congenital brain malformation ( focal cortical dysplasia, subcortical
band hyperopia, perisylvian polymicrogyria, hypothalamic hamartoma)
Neurocutaneous diseases ( tuberculosis sclerosis, hypomelanosis of Ito)
Meningitis/encephalitis
HIE
Genetic epilepsies
OUTCOME : long-term cognitive impairment and intractable seizures
despite multiple therapies.

11. EPILEPTIC ENCEPHALOPATHY WITH CONTINUOUS SPIKE
AND WAVE DURING SLEEP (CSWS)
 Synonymous with Electrical Status Epilepticus of Slow sleep (ESES)
 Onset 2m to 12y
 A rare cause of epileptic encephalopathy
 Diagnosis between 5 and 7 years
 Various seizure types – GTCs, atypical absence, atonic, myoclonic
 Selective regression of language and global developmental delay
 EEG hallmark – Continuous spike and wave during 85% of sleep
 Treatment: Steroids or ACTH recommended. IV Ig shows good result. Clobazam once daily
dosage at night , may require high dose 20-30mg/day
 OUTCOME : Seizures good prognosis
Neuro cognitive prognosis not good

12. LANDAU KLEFFNER SYNDROME
• Present between 3 -7 years
• Rare condition of presumed autoimmune but sometimes (GRIN2A mutations)
• Loss of language skills & verbal auditory agnosia in a previously normal child.
• Clinical seizures(70%)- focal with preserved awareness, focal to b/l TC atypical
absence, focal with impaired awareness, and occasionally myoclonic seizures.
• Attention and behavioural problems
• Continuous discharges during sleep especially in perisylvian region disrupt
networks involved in in normal language processing
• High amplitude spike& wave ( bitemporal).
• CT and MRI-normal results.

13. LANDAU KLEFFNER SYNDROME cont
TREATMENT
Main aim is to reduce or eliminate epileptiform discharges
Seizures & epileptiform abnormalities remit by 15y
Valproate, Benzodiazepines & Levetiracetam are most effective
Poor responders need ACTH or prednisolone
Multiple subpial transection for medically refractory cases
PROGNOSIS
The earlier the onset of LKS the worse prognosis with regard to
language function

14. Thank you