2. Content
Definition
Shared features
Classification
Syndromes
Clinical features
EEGs
Treatment
Prognosis
3. Epileptic encephalopathies
Definition:
heterogeneous group of epileptic disorders in which epileptic activity itself (ictal or
interictal) impairs cognitive and behavioral function above and beyond what is
expected from the underlying pathology alone
Underlying assumption is that aggressive ictal (seizure) and electrical
(electrographic) epileptogenic activity during brain maturation is the main
causative factor of progressive cognitive and neuropsychological deterioration
All epileptic encephalopathies have a tendency to abate, discontinue or even stop
in adolescence but often with serious neurocognitive residuals
4. Common features
start at an early age
manifest with electrographic EEG paroxysmal activity that is often aggressive
multiform and intractable seizures usually
cognitive, behavioural and neurological deficits that may be relentless
sometimes early death
EEG changes vary as per brain maturity
burst-suppression in neonatal
hypsarrhythmia in infancy
and slow generalised spike–wave discharges (GSWD) in early childhood
5.
6. Electro-clinical syndromes by age at onset
Neonatal period
Benign familial neonatal seizures (BFNS)
Early myoclonic encephalopathy (EME)
Ohtahara syndrome
Infancy
Migrating partial seizures of infancy
West syndrome
LGS, epileptic encephalopathy with CSWS including LKS
Benign infantile seizures
Benign familial infantile seizures
Dravet syndrome
Myoclonic encephalopathy in nonprogressive disorders
7. Epileptic encephalopathies include
early myoclonic encephalopathy
Ohtahara syndrome
West syndrome
Dravet syndrome
Lennox– Gastaut syndrome
epileptic encephalopathy with CSWS including Landau–Kleffner syndrome (LKS)
myoclonic encephalopathy in non-progressive disorders
8. Syndromes will be discussed as under:
Brief description
Age of onset
Gender
Incidence
causes
Seizure phenotype and variants
EEG
Treatment
Prognosis
9. Early myoclonic encephalopathy
The syndrome manifests with a triad of intractable seizures.
Erratic myoclonus appears first, followed by simple focal seizures and later
tonic epileptic (infantile) spasms
Age: usually starts in the first days of life, sometimes immediately after birth
Gender: M=F
prevalence and incidence are unknown
Causes
Inborn errors of metabolism: non-ketotic hyperglycinaemia, propionic aciduria,
methyl malonic acidaemia, D-glyceric acidaemia
Familial: autosomal recessive
10. Clinical features
Erratic or fragmentary myoclonus is the defining seizure: erratic as it shifts
from one body part to another:- face, limb, finger, toe, eyelid, eyebrow, lips
Simple focal seizures: eye deviation or autonomic symptoms such as flushing
of the face or apnoea
Tonic seizures usually appear in the first month of life with truncal tonic
contraction, usually also involves limbs
Psychomotor development may be abnormal from the onset of seizures or
arrests and deteriorates rapidly afterwards
All patients have bilateral pyramidal signs.
there is no trace of intelligent activity
11. EEG
Inter-ictal EEG consists of a repetitive BSP without physiological rhythms
BSP is probably exacerbated by sleep and does not continue in wakefulness
BSP evolves to atypical hypsarrhythmia or multifocal spikes and sharp waves
3 or 4 months from onset of the disease
However, atypical hypsarrhythmia is transient and returns to BSP, which
persists for a long time
13. Investigations
CT / MRI
Metabolic screen
serum levels of amino acids, glycine and glycerol metabolites
organic acids and amino acids in CSF
14.
15. Treatment and prognosis
There is no effective treatment
AED, ACTH are not effective
50% die within weeks or months of onset
50% develop permanent severe mental & neurological deficits
16. Ohtahara syndrome
(Early infantile epileptic encephalopathy)
Clinico-EEG features are mainly tonic spasms and continuous BSP occurring
in the sleeping and wakeful states.
Onset is mainly around the first 10 days of life, sometimes within the uterus or up
to 3 months after birth
Gender: slight male predominance
Incidence is unknown as it is a rare disorder
Causes:
cerebral development such as hemimegaloencephaly, porencephaly, FCD
metabolic disorders, genetic
Investigations: Imaging, metabolic screening
Genetic testing: STXBP1 is seen in 13 to 38% cases
17. Clinical features
Tonic spasms consist of a forward tonic flexion lasting 1–10 sec: singular or in long
clusters 10–300 times every 24 h
generalised and symmetrical or lateralised
1/3rd neonates may have erratic focal motor clonic seizures or hemiconvulsions
18. EEG
BSP has a pseudorhythmic periodicity, is continuous during wakefulness and sleep
appears at onset of disease and disappears within first 6 months of life
Bursts consist of high-amplitude slow waves mixed with spikes lasting 2–6 s
Suppression period of a flat or almost-flat EEG lasts for 3–5 s
interval between the onsets of two successive bursts is 5–10 s
Tonic spasms of variable duration are concomitant with the burst phase
19.
20.
21. Treatment and prognosis
There is no effective treatment.
ACTH and AEDs are of no benefit
Neurosurgery in FCD is sometimes beneficial
PROGNOSIS
50% die within weeks or months of onset
50% develop permanent severe mental & neurological deficits
In survivors, the clinical and EEG patterns change to West syndrome in a few
months and then to LGS at age 2 to 3 years if they survive
22.
23. West syndrome
Brief description
triad of (1) epileptic spasms, (2) hypsarrhythmia, and (3) arrest or regression
of psychomotor development.
Age of onset: between 3 and 12 months (peak at 5 months) in 90%
Gender Males (60–70%) predominate.
Incidence 3–5 per 10,000 live births
24. Causes
Pre, peri and post brain ischemia
Brain congenital anomalies
Tuberous sclerosis
Focal cortical dysplasia
Chromosomal abnormalities: Down’s syndrome
Congenital and acquired infections
CMV, rubella, HSV, adenovirus
Meningococci, pneumococci
Inborn errors of metabolism
Rarely, hypothalmic hamartoma
Cryptogenic (10 to 15%) and idiopathic (5 to 30%)
25. Seizure phenotype and variant
spasms typically occur in clusters of 1–30 /day, with each cluster having 20–150
spasms
epileptic spasms are clusters of sudden, brief (0.2–2 s), bilateral tonic
contractions of the axial and limb muscles
spasm is f/b motionlessness and diminished responsiveness lasting up to 90 s
spasms are usually symmetrical
Asymmetrical or unilateral spasms correlate with contralateral cerebral lesions of
symptomatic West syndrome
Spasms are flexor extensor (50%- commonest), flexor (40%), or extensor (10 -20%)
Focal seizures may precede or follow spasms and should suggest an underlying
focal pathology
26. Investigations
CT/ MRI/ PET Scan
Ophthalmological and UV skin examination – Woods lamp- for tuberous sclerosis
Chromosomal studies
Infectious disease including CSF
• Neurometabolic tests:
• Ammonia,
• Lactate, Pyruvate
• Urine and serum amino acid screening
• Organic acid
• LFT,
• Serum electrolytes
27. EEG
chaotic mixture of giant abnormal, arrhythmic and asynchronous electrical
activity of slow and sharp waves, multi-focal spikes and polyspikes.
There are no recognisable normal rhythms.
Symmetrical in cryptogenic or idiopathic cases
Asymmetrical in structural cases
Progress of hypsarrhythmic EEG patterns with age:
chaotic hypsarrhythmic pattern gradually becomes more organised, and
disappears with age.
By age 2 and 4 years, is replaced by slow GSWD pattern of LGS
Multi-focal independent spikes appear first, f/b gen. spike discharges from
where the slow GSWD of LGS emerges.
28. Ictal EEG patterns
last for 0.5 s to 2 min.
characteristic pattern in 72% consists of
(1) a high-voltage, generalised slow wave,
(2) episodic, low-amplitude fast beta activity and
(3) marked diffuse attenuation of EEG electrical activity (electro decremental ictal
EEG pattern)
29.
30.
31.
32.
33.
34. Treatment
First-line treatments: ACTH, prednisolone, or vigabatrin.
Vigabatrin
treatment of choice in tuberous sclerosis, seizure cessation s/i 95% cases
also effective in FCD
ACTH may have greater short-term efficacy than vigabatrin once tuberous
sclerosis is excluded- induces Sz remission in about 60 to 75% cases
In focal cortical structural abnormalities, possible surgical therapy is indicated if
both hormonal therapy and vigabatrin fail
?? Corticotropin may have direct anticonvulsant effects, perhaps via suppression of
corticotropin-releasing hormone that may provoke convulsions in immature brain.
35.
36. Prognosis
idiopathic and cryptogenic have significantly better prognosis than symptomatic (54%
versus 12.5%)
Relatively favorable symptomatic etiologies include
Down’s syndrome,
Neurofibromatosis type 1,
preterm infants with periventricular leukomalacia
neonatal hypoglycemia.
Additional factors predictive of better outcome include
Shorter treatment lag
favorable response to initial therapy
absence of other seizure types prior to spasms
absence of atypical spasms, focal seizures, or asymmetric EEG abnormalities
37. Dravet syndrome
severe myoclonic epilepsy in infancy.
rare progressive epileptic encephalopathy that is genetically determined
Affecting previously normal children
Onset - always within first year of life, peak age at 5 months
Gender M: F is 1:1
Incidence 1 per 40,900 infants
38. Clinical features
Dravet syndrome is characterized by a tetrad of seizures, s/i >50% cases:
early infantile febrile clonic convulsions
myoclonic jerks
atypical absences
complex focal seizures.
Convulsive, myoclonic or absence status epilepticus are frequent.
Classically, seizures switch sides, starting on the right with some and the left with others;
this alternating pattern is highly suggestive of Dravet syndrome.
39. First period: Pre-seismic period
lasts for 2 weeks to 6 months and manifests mainly with febrile clonic convulsions
intermixed with some tonic components.
These are mainly unilateral and less often generalised. Lasting upto 10 min
Progress to convulsive status epilepticus in 25%
40. Second period - seismic period
relentlessly aggressive , with the emergence of other multiple-seizure types and
severe neurocognitive deterioration
Various forms of febrile and non-febrile convulsive seizures, myoclonic jerks,
atypical absences and complex focal seizures occur on a daily basis and frequently
evolve to status epilepticus
41. Third period - Post-seismic period
static period
seizures may improve, but serious mental and neurological abnormalities are
irreversible
42. EEG findings in Dravet syndrome are not specific.
background is normal at epilepsy onset, but by 1 to 2 years of age, most patients
show diffuse background theta slowing.
Epileptiform discharges (usually generalized) are seen in 25% at epilepsy onset.
Between age 2 -5 yrs, an increase in paroxysmal abnormalities (which can be
generalized, focal, or multifocal) is seen.
Photic stimulation and eye closure may elicit discharges in 25%
46. Investigations
SCN1A sequencing
No metabolic abnormailites
Brain CT and MRI scans are either normal or show mild cerebral or cerebellar
atrophy, hippocampal sclerosis, loss of gray- white differentiation.
Functioning brain imaging may show focal hypoperfusion and hypometabolism,
even when MRI normal
47. Treatment: extremely pharmacoresistant
First line drugs are valproic acid or clobazam
topiramate, levetiracetam, and possibly zonisamide may also have efficacy
Stiripentol is often considered if firstline therapy is ineffective
Sodium channel blocking agents are avoided , including CRBZ,
oxcarbazepine, lamotrigine, and phenytoin, as they exacerbate seizures
ketogenic diet:
a high fat, adequate-protein (1 gram/kg), low-carbohydrate diet that produces
metabolic changes often associated with the starvation state, but which of these
metabolic changes induces Sz reduction is not known
prevented by early treatment of infectious diseases and hyperthermia
avoidance of precipitating factors like ambient hot temperatures
48. Prognosis
Cognitive and neurological deterioration is usually severe.
It develops between the second and sixth years and remains stable later.
Neurological deficits consist of ataxia, pyramidal symptoms and paroxysmal
movements
worsening and progression of the symptoms usually comes to a halt at around
the age of 11 or 12 years
49. Lennox–Gastaut syndrome
the triad of:
polymorphic intractable seizures that are mainly tonic, atonic and atypical absence
seizures
cognitive and behavioural abnormalities
EEG with paroxysms of fast activity and slow (<2.5 Hz) GSWD
Age of onset between 1 to 7 years with peak at 3 to 5 years
Gender Male : female 3:2
Incidence 2.8 per 10,000
Causes of LGS are similar to West syndrome with 1/3rd being cryptogenic or idiopathic
Investigations are similar to West syndrome but MRI/PET are almost always abnormal
50. Clinical features
Commonest Sz are tonic fits, atypical absences and atonic seizures, in that order.
Myoclonic jerks occur in 11–28% alone or in combination with other seizures.
Cognitive & behavioural abnormalities are present before seizure onset in 20–60%
50% West syndrome and other infantile epileptic encephalopathies progress to LGS
51. EEG
EEGs of abnormal background contain paroxysms of fast rhythms characterising
tonic seizures and slow (<2.5 Hz) GSWD characterising atypical absences
52. LGS- Tonic seizure with generalized spike and fast activity with EMG changes
60. Management strategy
include the following elements:
Appropriate AED
Tonic Sz- difficult to treat
Atypical absences, myoclonic and atonic seizures are more amenable to Rx
treatment of behavioural and cognitive problems with educational programmes
physical therapy
family support
61.
62.
63.
64. Prognosis
5% die
80–90% continue having seizures in adult life
85–92% have severely impaired cognition and behaviour
Cognitive impairment is more likely
in symptomatic or West syndrome-related cases,
when the onset is before 3 years of age,
Frequent seizures and status epilepticus occur
constantly EEG background showing Localised and multifocal EEG
abnormalities
65. Landau–Kleffner syndrome
LKS is a partly reversible, epileptic encephalopathy of childhood manifesting with
acquired verbal auditory agnosia and other predominantly linguistic deficits that often
occur together with other cognitive and neuropsychological behavioural abnormalities.
Seizures are infrequent and not a prerequisite for LKS
Onset is at age 2–8 years (peak at 5–7).
Gender male to female ratio 2:1.
Incidence One or two cases are seen every year in highly specialised centres
Etiology is unknown
MRI is often normal
66. Clinical features
verbal auditory agnosia, occurring in an initially normal child who had
achieved developmental milestones and had already acquired age-appropriate
speech
parents notice a gradual inability of the child to respond to their calls despite
raising their voices
Later complete word deafness; and non linguistic sounds like door bell
Finally may become entirely mute
Behavioral disorders such as hyperactivity and attention deficit are common
Seizures are mainly nocturnal and often heterogeneous
atypical absences, atonic seizures with head drop, minor automatisms and
secondarily GTCSs are reported
67. EEG
The EEG is characterised by mainly posterior temporal lobe foci of sharp–slow-
wave complexes that are often multi-focal and bisynchronous
CSWS is not a pre-requiste for diagnosis
70. Treatment
valproate is the first line option, usually in combination with clobazam
phenytoin, phenobarbital and carbamazepine may worsen the EEG discharges and
neuropsychological deficit
? ACTH
? Prednisolone
? Ketogenic diet
? multiple subpial intracortical transections in medically refractory cases
71. Prognosis
Seizures and EEG abnormalities are age dependent and often remit by age 15 yrs
Language and other neuropsychological improvement corresponds to
disappearance of EEG epileptiform activity
50% can live a relatively normal life
72. Epileptic encephalopathy with CSWS
Triad of:
EEG CSWS
seizures
neuropsychological impairment
CSW during NREM sleep is a prerequisite for diagnosis
Onset of Sz: between 2 months and 12 years
Onset of EEG abnormality: age 1 to 2 years, peak at 8 years
Gender Males 62%
Etiology- unknown
Pathology : 1/3rd have unilateral or diffuse cortical atrophy, focal porencephaly and
malformations of cortical development as can be seen on CT / MRI / PET
73. Clinical features
50% are normal before onset of disease.
50% have pre- or perinatal illness, neonatal convulsions and neurological
abnormalities such as congenital hemiparesis or tetraparesis, ataxia, psychomotor
or language deficits
acquired deterioration of cognitive function with CSWS is probably by an
alteration of maturation of one or several associative cortices, primarily involving
local interneurones and cortico-cortical associative networks
Linguistic impairment : d/t epileptogenic foci over one or both temporal lobes
Mental deterioration and autistic behaviour : d/t frontal lobe epileptogenic
foci
Motor impairment such as dyspraxia and dystonia: d/t dysfunction of motor
cortex
74. 3 stages:
First stage - before the discovery of CSWS
hemiclonic status epilepticus: unilateral, nocturnal, >30 min
Second stage - with CSWS
Increased freq of Sz, new types of Sz like GTCS, absences, NCSE, atonic Sz
Tonic Sz are incompatible with diagnosis of CSWS
Frontal or prefrontal CSWS:
damages cognitive skills, executive functioning, language
Presents as hyperkinesia, agitation, disinhibition, aggressiveness,
inattention
Temporal CSWS- linguistic disturbances: expressive aphasia rather than
verbal auditory agnosia
Motor disturbances consist of ataxia, hemiparesis and dyspraxia
Third stage of clinico-EEG remission starts after usually 2–7 years from onset
75. EEG
First stage:
•Inter-ictal awake EEG shows focal or multifocal slow spikes in more than
two-thirds of patients, mainly localized in the fronto-temporal centro-temporal
and less often in the parieto-occipital electrodes
•These are activated by sleep without altering their morphology
• Second stage
•Characteristic EEG pattern in this stage occurs during sleep
•Continuous spikes and waves during NREM sleep are the defining EEG pattern
continuous or almost continuous, bilateral and bisynchronous sharp–slow
waves with a rate of 1.5 to 2 Hz
•higher amplitude in the anterior or central regions
• Third stage
•Progressive improvement is seen towards normalization, may take >15 yrs
80. Prognosis
Spontaneous resolution of epileptiform discharges and seizures occurs in the mid-
teens, coinciding with stabilisation or improvement of behavioural and
neuropsychological deficits
Seizures reduce and finally remit in all, commonly by age 10–15
Cognitive and behavioural abnormalities show a global improvement, starting
after the end of CSWS, but is partial: never return to normal functioning in
language and attention
< 25% return to acceptable social and professional levels
81.
82. Myoclonic encephalopathy in non-progressive
disorders
c/b
a fixed, non-progressive encephalopathy
recurrent episodes of prolonged and erratic atypical myoclonic-absense status
epilepticus
Onset is from day 1 of life to 5 years of age (peak at 12 months).
Gender : M:F is 1:2
Incidence is unknown
Causes
Angelman and 4p syndromes (50%)
Pre- or perinatal brain hypoxia, malformations of cortical development (20%)
Investigations: MRI, chromosomal analysis and metabolic screening
83. Clinical features
fixed encephalopathy characterised by severe axial hypotonia, ataxia,
continuous jerky movements, tremor, and severe cognitive and learning
abnormalities
seizure :- repetitive and long (sometimes for days) episodes of atypical and subtle
myoclonic status epilepticus, consisting of myoclonic jerks and discontinuous
absences
84. EEG
The inter-ictal EEG is diffusely slow with frequent focal or multi-focal
abnormalities of slow waves and spikes
The ictal EEG shows continuous or subcontinuous brief bursts of diffuse slow
spikes and waves.
85. Treatment & Prognosis
In chromosomal abnormalities : some beneficial effect of valproate combined with
ethosuximide or clobazam, but ACTH treatment is often needed
Prognosis is poor even for those who initially appear only hypotonic
hypotonic state progressively deteriorates to, sometimes severe, neurocognitive
deficits
86.
87.
88. References
Panayiotopoulos CP. A clinical guide to epileptic syndromes and their treatment:
Based on the new ILAE diagnostic scheme. Bladon Medical Pub; 2002.
Wirrell E. Infantile, childhood, and adolescent epilepsies. CONTINUUM: Lifelong
Learning in Neurology. 2016 Feb 1;22(1, Epilepsy):60-93
Hussain SA. Epileptic encephalopathies. CONTINUUM: Lifelong Learning in
Neurology. 2018 Feb 1;24(1, Child Neurology):171-85.