EPILEPTIC

ENCEPHALOPATHIES
DR SOORAJ PATIL
SR NEUROLOGY
IMS BHU

Moderator- Prof Deepika Joshi

LEARNING OBJECTIVES

• Definition of epileptic encephalopathy

• Classification according to age

• Brief overview of each epileptic encephalopathy syndromes

• EEG features and treatment

DEFINITION

• Epileptic Encephalopathy is defined as condition in which

Epileptiform activity itself contributes to severe
cognitive and behavior impairments and beyond what might
be expected from the underlying pathology alone ( eg. Cortical
Dysplasia )

ILAE classification of the epilepsies: Position paper of the ILAE Commission for
Classification and Terminology Ingrid E. Scheffer- 2017
DEFINITION
• 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 behavioural, cognitive and motor regression
• (1) Electrographic EEG paroxysmal activity that is often aggressive

• (2) Seizures that are usually multi-form and intractable

• (3) Cognitive, behavioural, and neurological deficits that may be

relentless, sometimes early death

EPILEPSY FOUNDATION 2017

 Neonatal Infantile Childhood

Ohtahara West Syndrome Lennox -Gastaut

Syndrome Syndrome
Dravet Syndrome Landau -Kleffner
Early Myoclonic Syndrome
Encephalopathy Epilepsy With
Myoclonic Status CSWS
In Non Progressive
Encephalopathies Rassmussen
encephalitis
 “Age-related” epileptic encephalopathy

Early and late childhood

Late-

infancy
onset
epilepti
c
spasms
in
clusters
West
neonatal period
Lennox–
syndrom
e Early epileptic
Gastaut
encephalopathy
syndrome

Progressive maturation of the various areas of the

brain
EARLY INFANTILE EPILEPTIC
ENCEPHALOPATHY/OHTAHARA SYNDROME
• Neonatal onset 10 days to 3 months of age, some times intrauterine
seizures

• Static structural brain damage most common

• Tonic spasm > Generalized /Lateralized, tonic clonic, myoclonic, atonic,

absences, partial, gelastic, and Jacksonians

• Disorder progressively deteriorates with increasing frequency of seizures

and severe Psychomotor Retardation
Diagnosis and Management of Epileptic Encephalopathies in Children
Puneet Jain Suvasini Sharma and Manjari Tripathi- EPILEPSY REASEARCH & TREATMENT 2013
CAUSES
• Structural- Hemimegancephaly and Cortical Dysplasia

• Metabolic- Non ketotic Hyperglycemia, Pyridoxine Deficiency , and a variety of disorders

implicating the Mitochondrial Respiratory Chain.

• Genetic Causes -ARX, CDKL5, SLC25A22, STXBP1, SPTAN1, KCNQ2, ARHGEF9,

PCDH19, PNKP, SCN2A, PLCB1, SCN8A, S3GAL3, TBC1D24, and BRAT1.

EIEE
• EEG – Burst Suppression pattern with high voltage
Paroxysmal spike/ poly-spike discharges for Up to 3-6
seconds followed by prolonged periods of nearly flat tracing
for up to 2-5 seconds.

• This pattern remains unchanged during wakefulness and

sleep
EIEE- EEG
TREATMENT
• Prognosis Poor
• Variety of antiepileptic drugs-clobazam , clonazepam ,
vigabatrin , topiramate , zonisamide , Phenobarbital,
valproate, or felbamate .
• Ketogenic diet
• Most patients -Adverse Neurocognitive outcome , early
death / may progress to WEST/ LGS
• Minority specific treatment – Hemispherectomy /
Pyridoxine supplement
EARLY MYOCLONIC ENCEPHALOPATHY
• Neonatal period up to 3 months

• Focal myoclonia of the face or extremities with random migration from

one part to another

• IEM -Most common causes( Amino Acidopathies), NKH, Zellweger

syndrome, menkes ds, pyridoxin deficiency

• Less often – structural abnormality ( cortical dysplasia)

Review Article- Pediatric Neurol 2012

Early-Onset Epileptic Encephalopathies: Ohtahara Syndrome and Early Myoclonic Encephalopathy
EME
EEG – Suppression Burst Pattern

• Back ground- Suppression Burst Pattern

• Burst suppression pattern more prominent during the sleep

• The bursts last for 1–5 seconds with longer periods of

suppression (3–10 seconds)
EIEE- EEG
EIEE VS EME
TREATMENT

• AEDS, Pyridoxin trial

• Ketogenic Diet

• Epilepsy Surgery

• Correcting Metabolic Problem

• Many children progress to WEST /LGS

Epilepsy of Infancy with Migratory
Focal seizures
• First few months of life

• Focal seizures with multiple topographical origins

• Seizures are typically prolonged and often fulfill criteria for status
epilepticus

• Genetic - mostly
Epilepsy of Infancy with Migratory
Focal seizures
• Mostly genetic mutations- SCNA1 , SCN2A , PLCB1 , TBC1D24

• EEG- prominent slowing , disorganization and multifocal

independent epileptiform discharges

• The area of ictal onset shifts from one region to another and
from one hemisphere to the other, with occasional overlapping
of consecutive seizures
 TREATMENT
• Usually drug refractory

• There are some reports of Stiripentol and bromides

• Ketogenic diet

• Vagal nerve stimulation

• Surgical options- FOCAL LESIONS

INFANTILE SPASMS (WEST SYNDROME)
William James West,
1841
• Dr West's original letter gives a vivid
clinical description of what was to become
known, over a century later as West's
syndrome
• This letter, that was a call for help about
his son to the medical profession,
appeared in The Lancet 180 years ago
Duncan. Infantile spasms: the original description of Dr West. Epileptic
Disorders. 2001;3:47-8. Article historique
Infantile spasms (IS)
• An epilepsy syndrome with onset usually in infancy
• Rarely an onset >2 years
• Main clinical manifestation: clinical spasms
• Clusters

• Most characteristic EEG finding is hypsarrhythmia

• Not always, not throughout

• Often associated with developmental arrest or

regression
West syndrome (WS)

Clustered
spasms

West
syndrome
Hypsarrhy
-thmia on
EEG
INFANTILE SPASMS (WEST SYNDROME)

• Spasm -Flexor / Extensor

• Individual spasm generally last between 0.5 and 1.0 seconds

and repeat every 5 to 30 seconds in clusters approximately 2 to
20 minutes
Infantile spasm-single spasm variant (ISSV)

ISSV=Single spasms +
hypsarrhythmia

WS= clustered spasms + hypsarrhythmia

hypsarrhythmia without IS= no spasms + hypsarrhythmia

(HWIS)
CAUSES
STRUCTURAL

• Pre, Peri And Post Natal Cerebral Ischemia

• Cerebral Malformations

• Neuro Infections Sequel

• Neurocutaneous Hamartoma

Metabolic- Biotidinase Deficiency , PKU, Mitochondrial Disorders , Menkes Disease ,NKH

GENETIC

• CDKL-5 , MeCP 2, ARX, STXBP-1 , SPTAN 1and PLC-B1

• Chromosomal Disorders : Down Syndrome , Ip 36 deletion and Pallister – Killan syndrome

Unknown
3 clinical states and corresponding EEG types

• Clinical state 1
• Weeks to months
• Clinically silent phase
• Type 1 EEG: presents with (multi-)focal epileptic discharges <50% of
NREM EEG recording time

• Clinical state 2
• Several weeks
• Beginning mental deterioration
• Type 2 EEG: with bihemispheric epileptic discharges >50% of the non-
NREM EEG recording time within abnormal background activity
(imminent hypsarrhythmia)
• Clinical state 3
• Mental deterioration
• Characterized by hypsarrhythmia

Conclusions: Infants with WS could be reliably identified several weeks

before the occurrence of hypsarrhythmia by a typical EEG pattern (type
2), thereby opening the way for early intervention studies
Type 1 EEG (clinical state 1)
• Focal or multifocal sharp-wave activity
• Occupying <50% of the non-REM EEG recording
time
• Background activity is normal or mildly abnormal
Type 2 EEG (clinical state 2)
bihemispheric sharp-wave activity
Occupying 50%–90% of the non-REM EEG
Background activity is definitely abnormal.
Type 2 EEG appears ~ modified hypsarrhythmia.
Type 3 EEG (clinical state 3)
90%–100% non-REM EEG
Irregular bihemispheric sharp-waves
hypsarrhythmia
 • ACTH High dose, Low dose
• Corticosteroids
• AEDS - Clobazam, Clonazepam ,
Valproic Acid
• VIGABATRIN- Most effective in
Tuberous Sclerosis Complex
TREATMENT • Use associated with
Irreversible Visual Loss
• Resectable surgeries for focal
etiologies like cortical dysplasia
TREATMENT
TREATMENT
• Are other forms of corticosteroids as effective as ACTH for short-term treatment
of infantile spasms?

• Are low-dose ACTH regimens effective for short-term treatment of infantile

spasms?

• Is ACTH more effective than VGB for short-term treatment of infantile spasms?

• Is there a role for the ketogenic diet or for AEDs other than VGB in managing
infantile spasms?

• Does the successful short-term treatment of infantile spasms lead to long-term

improvement of neurodevelopmental outcomes or a decreased epilepsy
incidence?
 The evidence is insufficient to recommend the use of
prednisolone, dexamethasone, and methylprednisolone
as being as effective as ACTH for short-term treatment
of infantile spasms (class 3 & 4)

Class I study showed similar efficacy between low-dose

(20–30 IU) and high-dose (150 IU/m2) natural ACTH

TREATMENT
Two Class III studies (1 from the 2004 parameter and a
later study) demonstrated that ACTH is more effective
than VGB for short-term treatment of children with
infantile spasms (excluding those with TSC)

A shorter lag time to treatment of infantile spasms with

either hormonal therapy or VGB may be considered to
improve long-term cognitive outcomes (Level C)
Start low-dose ACTH at 20- 30 IU/m2
Increase rapidly to max doses as rapidly

Treat for 14 days

Monitor ADR: infection, irritability, HTN

Repeat EEG after 2 weeks

EEG s/o hyps but no clinical IS

No clinical spasms and EEG resolved

Continue Rx for 2-4 weeks

Neuro-developmental
follow-up
SEVERE MYOCLONIC EPILEPSY OF
INFANCY/DRAVET SYNDROME
• Early infantile febrile clonic seizures (before 1 yr of age )

• Myoclonic jerks, tonic- clonic, atypical absences, focal aware /

impaired awareness

• Vaccine seizures

• Low grade fever, hot bath , warm environment

• Cognitive and neurological detioration

Retracing the natural history of Dravet syndrome: Report and review of literature
Sachin Sureshbabu, Ivy Sebastian- Neurol india 2018
Dravet Life Timeline

Age 5+
stabilizatio
n stage
Age 1- 4 yrs
(worsening • Seizures may
stage) become less
frequent
• Other seizure • Cognitive
Age 4 -8 types appear, problems
months(Feb regression of plateau
mile stones
rile stage)
• EEG abnormal
• Febrile
Seizures
• EEG normal
EEG
Progressive increase of Paroxysmal Abnormalities

• During wakefulness background activity remains normal in 50 % of the cases

/ Remaining background activity becomes slow and poorly organized.

• Generalized Fast Spike – wave or Poly – spike appears in bursts or in isolation

, sometimes with unilateral predominance/ induced by Eye Closure and
intermittent Photic stimulation.

• Focal and multi focal abnormalities such as Fast Spikes or poly – spikes
involving Asynchronously the Fronto- Central or Centro-Temporal areas.
 • Limited success AEDS-
Levetiracetam, Clobazam,
Clonazepam , Topiramate,
TREATMENT ,Valproic Acid
• Ketogenic Diet
• Vagal Nerve Stimulation
• Surgical Options
• Cannabidiol –some patients
• Avoid Na Channel
Blockers
LENNOX- GASTAUT SYNDROME
• LGS - triad of multiple drug-resistant seizure types, a specific
interictal electroencephalographic (EEG) pattern showing bursts
of slow spike-wave (SSW) complexes or generalized paroxysmal
fast activity (GPFA) and intellectual disability (ID)

• Multiple seizure types - Atypical absence , Tonic seizures (most

common) and Drop seizures , NCSE in 2/3rd

Asadi-Pooya AA. Lennox-Gastaut syndrome: a comprehensive review. Neurol Sci.

2018 Mar
LGS

• Causes are genetic, structural in 60-70 %

• 20 % may have west syndrome in past

• LGS is considered as secondary epilepsy

EEG
• The EEG background activity is probably never normal in LGS and shows a
diffuse increase in slow waves

• Characteristic EEG feature in LGS is slow (< 2.5 Hz) spike-and-wave

complexes with an abnormally slow background activity

• Hyperventilation may facilitate GSWD and Atypical Absences

EEG
• Bursts of diffuse or bilateral fast (10–25 Hz) rhythm patterns, also called
GPFA, are usually recorded during slow wave sleep
TREATMENT
• Drop seizures most difficult to control

• Topiramate/ Valproic acid / Felbamate / Lamotrigine, Benzodiazepines

• Clobazam and Rufinamide to combat Drop Seizures.

• Ketogenic diet in early age ~50% reduction in seizures, ~ 20% seizure

free

• Corpus callosotomy, VNS in refractory seizures

Asadi-Pooya AA. Lennox-Gastaut syndrome: a comprehensive review. Neurol Sci.

2018 Mar
MYOCLONIC – ASTATIC SEIZURES
(DOOSE SYNDROME)
• Normal development, Male predominant in 70-90 %
• Onset of Myoclonic , Myoclonic Atonic or Atonic seizures between the
age group of 1 and 6 yrs
• Part of GEFS +
• No tonic seizures
• Normal EEG background with generalized spike / Poly spike
discharges at 3- 7Hz with Photosensitivity
EMAS

• Initial seizures can be Febrile or Afebrile Generalized Tonic

Clonic Seizures

• Followed by characteristic seizure the Myoclonic- Atonic which

combines a symmetrical Myoclonic jerk immediately followed
by an Atonic seizure causing a Drop attack

• Episodes of NCSE lasting hours / days occur in some children.

EMAS

• EEG- Background activity is normal at the age

• Rhythmic theta activity in the parasagittal region may be the

only significant abnormality.

• Frequent paroxysms of GSWD at 3 Hz or more appear once

patient develops drop attacks
Features LGS EMAS
Type of seizures Tonic, Atonic , Atypical Absences Myoclonic,Atonic and Myoclonic-
Atonic
Tonic seizures Common and characteristic, Not Seen
diurnal and nocturnal
Developmental abnormalities Common Exceptional if any
before onset of seizures

Etiology Symptomatic ( Most Cases) Idiopathic

Genetic Predisposition None Common
Progression from West Common Incompatible
Syndrome
Prognosis
Commonly Bad Relatively Good
EEG Background Abnormal By Rule Usually Normal
Paroxysmal Fast Activity Common and Characteristic Not Seen

EEG GSWS Slow (< 2.5 Hz) Fast (> 3Hz)

LANDAU KLEFFNER SYNDROME
• Rapidly Progressive Linguistic Deterioration following seizure episode

• Onset between 2 and 8 yrs of life

• Atypical absence (50%), oral (33%), secondarily generalized tonic–clonic (SGTC)

(33%), atonic (16%), and hemiconvulsive (16%) attacks

• Diagnosis is often delayed as children are often thought to have acquired

deafness , Autistic Regression or Mutism

• Seizures ( Mostly Nocturnal ) occur in 2/3rd and easy to control

• Behavioral and Cognitive disturbances are commonly observed

LKS-EEG
• Background activity remains normal in most cases

• High amplitude , Epileptiform discharges are seen in Temporo

Parietal areas/ Centro Parietal areas ( spikes, sharp waves
/spike and sharp wave)

• EEG abnormality is enhanced by sleep deprivation

• ICTAL EEG – Focal seizures , Focal Ictal pattern from Temporo-

Parietal / Posterior Temporal areas
TREATMENT

• AEDS- BZD and VAL (does not effect language)

• High dose corticosteroids – Stabilization of Language Problems

• The prognosis is Favorable

• 17 % can have complete recovery, 63 % can develop GDD

• Poor prognosis in <4 years of age, duration > 1 years

CONTINUOUS SPIKE WAVE EPILEPSY
• Classical presentation is a child with around 5 years of age, typically
between age 4 and 7 years

• TRIAD consists of
1. Intractable seizures

2. Interictal Epileptiform Activity that becomes prominent during sleep ,

leading to EEG pattern of Electrical Status Epilepticus in sleep (ESES) or
CSWS

3. Neurocognitive Regression after 2-3 years of seizures

CONTINUOUS SPIKE WAVE EPILEPSY

• EEG abnormalities became continuous with sleep onset and

ceased to be continuous upon arousal, occupying at least 85%
of slow sleep tracing

• neurocognitive impairments are the presenting symptoms in the

absence of clinical seizures but can be seen in up to 20% of
cases
CSWS- EEG
Active stage

• Typical CSWS pattern appears on EEG 1-2 years after the first seizures

• Children with Frontal CSWS – Aggressiveness/ Disinhibition/ Inattention

• Children with Temporal CSWS- Expressive Aphasia with Non fluent speech

Remission stage

• After 3- 8 years of age seizures remit in all cases

• EEG gradually remit to normal state

 CSWS LKS

Clinical
Seizures All patients 40- 70 %

Primary language Expressive aphasia, motor, Verbal auditory agnosia

impairment cognitive decline

Behavioral deficit Nearly all patients 40- 50 %

EEG
CSWS 100% of patients 80% of patients

Spike location Frontal , centro –temporal Posterior temporal , centro -

parietal
TREATMENT

• High dose Benzodiazepines

• Corticosteroids

• AEDS= Valproate / Ethosuximide / Levetiracetam/ Lamotrigine

Continuous Spike-Wave during Slow Wave Sleep and Related Conditions

Nilika Shah Singhal* and Joseph E. Sullivan ISRN-2014
RASSMUSSENS ENCEPHALITIS

• Drug-resistant focal epilepsy, progressive hemiplegia, and

cognitive decline, with unihemispheric brain

• Affected brain shows inflammation on histology and

Autoimmune pathology (GLUR3 antibody).

• Age of onset between 6- 8 yrs and affected children have

previous normal cognition and development.

Rasmussen’s encephalitis: clinical features, pathobiology, and treatment advances-Lancet Neurol 2015
STAGES - RASSMUSSENS ENCEPHALITIS
Acute stage-

• EPC, Progressive hemiparesis , hemianopia ,

cognitive deterioration and aphasias.

• Median duration is 8- 12 months.

Residual stage-

• Permanent and stable neurological deficits and

frequent seizures , although less frequent
seizures than in acute stage

Rasmussen’s encephalitis: clinical features, pathobiology, and treatment advances-Lancet Neurol 2015
DIAGNOSTIC CRITERIA

Rasmussen’s encephalitis: clinical features, pathobiology, and treatment advances-Lancet Neurol 2015
 EEG
• Background EEG may be normal. Subsequently unilateral focal theta-
delta range slowing appears , which often becomes synchronized .

• INTER –ICTAL Discharges- Multiple independent spike/ sharp –

wave discharges are seen in the affected hemisphere

• In 30 % the discharges are bilateral.

• Activation – EEG abnormalities are enhanced by sleep deprivation as

well in sleep
Rasmussen’s encephalitis: clinical features, pathobiology, and treatment advances-Lancet Neurol 2015
Rasmussen’s encephalitis: clinical features, pathobiology, and treatment advances-Lancet Neurol 2015
TREATMENT

• Steroids and other Immunomodulators are given early in the

course of disease to reduce the inflammation , seizure activity
and severity of deficit

• Refractory seizures – Hemispherectomy

• Prognosis below the age of 10 is good who are treated well.

Rasmussen’s encephalitis: clinical features, pathobiology, and treatment advances-Lancet Neurol 2015
Immunomodulatory therapy versus surgery

Takahashi Y et al. Immunomodulatory therapy

versus surgery for Rasmussen syndrome in early childhood. Brain Dev. 2013
ALGORITHM
< 3 Months <3 months – 1
year

Burst
Suppression Infantile
Pattern Spasm

Partial
Tonic Seizures/
Spasms Erratic
Myoclonus

West
Ohtahara Early Myoclonic Syndrome
Syndrome Encephalopathy
 > 1 YR

-Myoclonic Asatic
-Atypical Febrile -Myoclonic Status Seizures
seizures - Generalized -Parasagittal
-EEG- Normal Spike< Slow wave Slowing
background > 3 -Fast Generalized
Background Spike/Polyspike
Hz Generalized
Discharges Slowing Discharges

Dravet Myoclonic Status in Non Doose

Syndrome Progressive Syndrome
Encephalopathy
 >1 yr

-Drop Attacks Partial Seizures

-GSWD, Multifocal
Discharges
-Paroxysmal Fast Activity
-Background Slowing
-EPC
Auditory
ESES on -Progressive
Agnosia+/-
EEG Neurological
ESES on EEG
Deficit

LGS
Rasmussen
LKS CSWS
Encephalitis
TAKE HOME MESSAGES

• Age of presentation and prior developmental status is most

important to diagnose epileptic encephalopathy syndromes

• EEG will help to early detection and differentiation of each

encephalopathies

• Proper treatment helps child to have a seizure free childhood

and normal development
THANK YOU