WEST SYNDROME, DRAVET SYNDROME, OTHARA SYNDROME, LGS, LKS, CSWS

2.  A group of disorders in which the unremitting
epileptic activity contributes to severe
cognitive and behavioral impairments above
and beyond what might be expected from the
underlying pathology alone, and these can
worsen over time leading to progressive
cerebral dysfunction

3.  Their clinical and EEG features mirror the
specific age-related epileptogenic reaction of
the immature brain.
 Several syndromes have been described
based on their electro-clinical features
1. age of onset,
2. seizure type, and
3. EEG pattern
It may be progressive or have waxing-waning
course

5.  EEG which should include both the sleep and
wake states
 A MRI brain must be obtained to look for
structural defects
 A metabolic profile including blood ammonia,
arterial blood gas, lactate, blood tandem
mass spectrometry, and urine organic acid
analysis must be obtained to look for
inherited metabolic defects

6.  This group of disorders comprises:
1. Ohtahara syndrome or early infantile
epileptic encephalopathy (EIEE),
2. Early myoclonic encephalopathy (EME), and
3. Malignant migrating partial seizures in
infancy

7.  onset ranging from intrauterine period to 3
months of age
 Epileptic/tonic spasms are the defining
seizure type which are very frequent and
occur in both sleep and wakeful states
 Partial motor seizures, hemiconvulsions,
generalized motor seizures and rarely
myoclonic seizures may be observed

8.  The interictal EEG shows burst suppression
pattern with no sleep-wake differentiation
 The bursts last for 2–6 seconds alternating
with periods of suppression lasting for 3–5
seconds
 The EEG may evolve from the initial burst
suppression pattern to a hypsarrhythmia
pattern, typical of West syndrome

9.  The underlying causes are heterogenous
 majority of cases are attributable to static
structural brain lesions such as
1. Focal cortical dysplasia,
2. Hemimegalencephaly, and
3. Aicardi syndrome

10.  Few genetic mutations have been described
but these are not specific
 These include mutations in:
1. Syntaxin binding protein-1 (STXBP-1)
2. Aristaless-related homeobox (ARX)
3. SLC25A22-gene encoding a mitochondrial
glutamate carrier

11.  The medical management of seizures is not
rewarding.
 The dietary therapy has been tried with some
success.
 Ishii et al. reported a favourable response of
ketogenic diet in a male infant with Ohtahara
syndrome who had failed multiple
antiepileptic drugs
 Neurosurgery is sometimes favourable in
selected cases of cerebral malformations

12.  The prognosis is uniformly poor with
survivors left with severe psychomotor
retardation
 There may be age-dependent evolution to
West syndrome and then subsequently to
Lennox-Gastaut syndrome

13.  Onset within the first 3 months of age and
mostly within the neonatal period
 prenatal onset is also known
 characterized by focal myoclonus involving
limbs or face that is very frequent, sometime
continuous, shifting from one region to
another
 Fragmentary, erratic myoclonia, partial
seizures, and less frequently tonic spasms are
seen

14.  The interictal EEG shows burst suppression
pattern more prominent during the sleep
 The bursts last for 1–5 seconds with longer
periods of suppression (3–10 seconds)
 differentiating features between EEG features
of Ohtahara syndrome and early myoclonic
encephalopathy are as follows:

16.  Many of the reported cases are familial
 The inborn errors of metabolism are important
etiologies, such as:
1. Nonketotic hyperglycinemia,
2. Organic acidemia,
3. Menkes disease,
4. Zellweger syndrome,
5. Molybdenum cofactor deficiency,
6. Pyridoxine dependency and
7. Genetic factors
 Structural abnormalities are rarely found

17.  These seizures are often refractory to
conventional antiepileptic drugs
 A sequential therapeutic trial with pyridoxine,
folinic acid, and pyridoxal phosphate should
be instituted
 Limited success has been reported with
ketogenic diet

18.  rare, age-specific epileptic encephalopathy
 malignant course with onset in the first 6
months of age
 characterized by a period of normal early
development followed by nearly continuous
migrating polymorphous focal seizure which
are intractable
 subsequently psychomotor retardation and
progressive decline of head circumference
percentile in most children

19.  Interictal EEGs show diffuse slowing of the
background activity with multifocal epileptiform
discharges
 Ictal EEGs display paroxysmal discharges
occurring in various regions in consecutive
seizures in a given patient
 They start in one region and progressively
involve the adjacent areas
 The area of ictal onset shifts from one region to
another and from one hemisphere to the other,
with occasional overlapping of consecutive
seizures.

20.  Etiology is largely unknown
 SCN1A and phospholipase Cβ1 (PCB1) gene
mutations have been described in few
patients
 seizures are markedly pharmacoresistant to
conventional antiepileptic drugs
 Potassium bromide and stiripentol have been
tried with some success.
 ketogenic diet has been unsuccessful

21.  West's syndrome was first described by West
in 1841
 It is characterized by a clinical triad of:
1. epileptic spasms,
2. arrest or deterioration of psychomotor
development, and
3. characteristic EEG pattern called
hypsarrhythmia

22.  The epileptic spasms are clusters of sudden,
brief (0.2–2 seconds), diffuse or fragmented,
and tonic contractions of axial and limb
muscles
 may be accompanied by cry, laughter, or
autonomic changes
 may be flexor (most common), extensor,
mixed, or subtle
 They usually occur in arousal and in alert
states

23.  classical interictal EEG finding
 characterized by chaotic background with
nearly continuous random asynchronous
high-voltage slow waves and spikes arising
from multiple foci
 When a spasm occurs it is usually during a
period of attenuation
 The attenuation may have superimposed
high-frequency, low-voltage EEG activity
 The periods of attenuation are typically very
short in duration, lasting 1 to 2 seconds

26.  Many variations have been described. These
include:
1. increased inter-hemispheric synchronization,
2. consistent voltage asymmetries,
3. consistent focus of abnormal discharge,
4. episodes of generalized/regional or lateralized
voltage attenuation,
5. primarily high-voltage bilaterally asynchronous
slow wave activity with relatively little
epileptiform abnormalities
 Both classic and variant hypsarrhythmia have the
same prognosis
 Variation occurs because of sleep state, etiology,
disease course, and treatment.

28.  EEG becomes fragmented and more
synchronized during NREM sleep and
relatively normalizes during REM sleep
 Ictal EEG patterns are variable and may
comprise:
 classical electrodecremental pattern,
 high-voltage generalized slow-wave, or
 low-amplitude fast activity

29.  West's syndrome has been classically
classified into:
1. symptomatic (identifiable neurological
insult),
2. cryptogenic (probably symptomatic but with
no known etiology), and
3. idiopathic (normal premorbid development
and unknown etiology) forms

31.  Adrenocorticotrophin hormone (ACTH) is the
drug of choice for short-term treatment of
epileptic spasms
 Low-dose ACTH may be equally effective as high
dose ACTH
 Oral steroids may also be an alternative,
especially in resource-constrained settings
particularly in the absence of underlying known
pathology
 Vigabatrin is a second-line drug except in
children with tuberous sclerosis complex where it
is the preferred drug over ACTH.

32.  Pyridoxine and biotin trial should always be
considered in refractory spasms or when
clinically indicated
 The ketogenic diet has also shown to be
beneficial
 Resective neurosurgery may be warranted in
refractory cases with unilateral or focal
congenital or early acquired cortical lesions
 Total callosotomy may be considered in
children with persistent drop attacks

33.  The prognosis is guarded and is governed by
the underlying etiology and the treatment
 The affected children are left with variable
psychomotor retardation, epilepsy, or
psychiatric disorders
 more than 70% developing mental retardation
and other cognitive disabilities
 Small portion of patients recover quickly
without sequelae. This is more likely to
happen in the absence of brain pathology

34.  It was first described by Dravet in 1978 as
severe myoclonic epilepsy of infancy (SMEI)
 Onset is usually between 5 and 8 months of
age
 frequent, prolonged febrile unilateral clonic
convulsions with alternating pattern in a
previously normal child
 Nonfebrile seizures may also be present

35.  This stage is followed by emergence of
multiple seizure types
1. myoclonic
2. atypical absences
3. complex focal seizures
 which frequently progress to status
epilepticus and is associated with severe
psychomotor deterioration
 relentless progression stops at around 10–12
years of age with decrease in seizure
frequency and persisting neurologic sequalae

36.  The fever associated with vaccination may
cause an earlier age at onset of Dravet
syndrome, but it does not affect the eventual
course of the condition
 Borderline SMEI may include variations such
as epilepsy with the absence of myoclonic
seizures or even other seizure types

37.  The interictal EEG is normal initially
 Generalized photoparoxysmal responses and
rhythmic theta (4-5 Hz) activity may be seen in
centroparietal areas and vertex
 Soon, the EEG deteriorates with background
slowing, asymmetric paroxysms of generalized
polyspike/spike-slow-wave discharges and
multifocal epileptiform abnormalities
 Photic, pattern, and eye closure sensitivity may
be present

38.  Mutations in the SCN1A gene encoding the
alpha-1 subunit of the sodium channel are
detectable in 70–80% of patients with Dravet
syndrome
 Other reported mutations include mutations
in genes:
1. GABARG2 (encoding γ2 subunit of
GABAA receptor)
2. SCN1B
3. Protocadherin 19 (PCDH19) genes

39.  Seizures are usually refractory
 Drugs like carbamazepine, phenytoin, and
lamotrigine are contraindicated
 Stiripentol in conjunction with clobazam or
valproate has recently been licensed for use
 Early initiation of ketogenic diet has been
advocated
 Avoidance of hyperthermia and stress is
critical

40.  Syndrome is defined by a triad of:
1. Several seizure types including generalized
tonic, generalized atonic, and atypical
absence seizures
2. characteristic interictal EEG abnormality of
generalized slow spike-and-wave
discharges (<2.5 Hz) in waking and bursts
of paroxysmal fast activity(≈10 Hz) in sleep
3. cognitive dysfunction

41.  a severe form of epileptic encephalopathy
 onset between 1 and 8 years of age, mainly
between 2 and 5 years of age
 characterized by intractable polymorphic
seizures including tonic, atypical absence,
atonic and myoclonic seizures
 “Drop attacks”, tonic or atonic, are seen in
50% children, and frequently causes injuries

42.  Two-thirds of the patients may have
nonconvulsive status epilepticus
 Twenty percent of children have history of
epileptic spasms
 The cognitive deterioration/stagnation is
common and fluctuates with the seizure
frequency

43.  The pathognomonic interictal EEG finding is
bilateral, synchronous, and slow spike-and-
wave discharges (1.5–2.5 Hz) with
frontocentral voltage dominance with
abnormal background
 Paroxysmal fast activity of bilateral
synchronized bursts of 10–20 Hz frontally
dominant activity lasting for few seconds is
also seen
 It may be an ictal correlate of a tonic seizure,
especially if prolonged

47.  NREM sleep dramatically enhances all the
paroxysmal abnormalities
 Other abnormalities include:
1. sleep fragmentation of the slow spike-and-
wave bursts
2. polyspike discharges
3. pseudoperiodic appearance
4. diffuse voltage attenuation
5. focal and multifocal spikes and sharp waves
6. diffuse background slowing
7. abnormal sleep architecture with reduced or
absent REM sleep
8. severe background disorganization with a
quasihypsarrhythmic pattern

48.  etiology of LGS is heterogenous and similar to
epileptic spasms
 One-third of children have no antecedent
history or evidence of cerebral pathology

49.  Goal of treatment:
1. lowering the frequency of serious/disabling
seizures like drop attacks
2. minimizing daytime seizures
3. minimizing adverse effects of antiepileptic
drug
 Valproate and clobazam are the preferred
drugs

50.  The second-line drugs include:
1. Levetiracetam
2. Rufinamide
3. Lamotrigine
4. Topiramate
5. Zonisamide
 Steroids and intravenous immunoglobulins
may be indicated during periods of increased
seizure frequency or status epilepticus
 The ketogenic diet is a useful alternative and
may be used early in the management

51.  Nonpharmacological therapies include:
1. vagus nerve stimulation
2. electrical stimulation of centromedian
thalamic nuclei
3. complete or partial callosotomy

52.  Prognosis is guarded
 more than 80% children having persistent
epilepsy and severe neurocognitive sequalae
 Predictors of favourable outcome:
1. normal development prior to onset of
seizures
2. normal neuroimaging
3. near normal background on EEG
4. faster generalized spike-wave-activity
5. activation of generalized spike-wave-
activity by hyperventilation

53.  The common features of these related
conditions are:
1. Decline in cognitive function in association
with an EEG pattern of continuous spike-
and-wave activity during slow wave sleep
2. In both conditions the associated seizures
are often easy to control
3. The predominant clinical manifestations are
related to the EEG abnormality in sleep

55.  The condition is often called acquired
epileptic aphasia
 The peak onset is between 5 and 7 years of
age with verbal auditory agnosia in a
previously normal child
 The language function continues to
deteriorate and the course can be gradually
progressive or fluctuating
 All types of aphasia can occur
 Some children may become mute

56.  Mild behavioral abnormalities are common
 Seizures occur in 75% children
 They are infrequent and usually nocturnal
 Semiologies may include
1. generalized tonic-clonic
2. focal motor
3. atypical absences
4. head drops, and
5. subtle seizures

57.  EEG is characterized by mainly posterior
temporal epileptiform discharges
 These discharges can be multifocal,
unilateral, or bilateral
 markedly activated by NREM sleep
 They may continue into the REM sleep, a
differentiating feature from epilepsy with
CSWS

58.  Main aim of the treatment is to reduce or
eliminate the epileptiform discharges
 Valproate, benzodiazepines, levetiracetam,
ethosuximide, and sulthiame are the most
effective drugs
 Poor responders may be treated with ACTH or
prednisolone
 Steroids may be administered early in the
course of the illness

59.  Prolonged oral steroids may be required as
relapses are common on withdrawal
 The role of intravenous immunoglobulins is
unclear
 Favourable results have been reported with
ketogenic diet in small studies
 For medically refractory cases, multiple
subpial transection including the Wernicke
area have been used with some success

60.  Seizures and epileptiform abnormalities remit
by the age of 15 years
 The language disturbance will usually
progress despite good control of clinical
seizures
 Majority of children are left with permanent
language dysfunction
 The earlier the onset of LKS, the worse the
prognosis with regard to the language
function

61.  Onset is between 2 months and 12 years of
age with a peak at 4–7 years of age
 The preceding neurodevelopment is normal
in 50% children
 Seizures are the presenting symptom in 80%
children and neuropsychological deterioration
in the rest

62.  The children present with infrequent
nocturnal seizures
1. simple or complex focal
2. generalized tonic-clonic or
3. myoclonic seizures
 After 1-2 years, there is increase in seizure
frequency with emergence of new seizure
types:
1. absence or atonic seizures
2. negative myoclonus

63.  The symptoms depend on the predominant
site of epileptiform discharges
 Frontal CSWS affects the cognitive and
executive functioning
 Temporal-predominant-CSWS affects the
linguistic function

64.  The interictal EEG during wakefulness shows
more pronounced abnormalities
 It shows focal or multifocal epileptiform
discharges with accentuation during NREM
sleep
 The localization of discharges can be:
1. Frontocentral
2. Frontotemporal
3. Centrotemporal
4. Frontal

66.  During NREM sleep, EEG shows continuous,
bilateral, 1.5–3 Hz, frontally predominant,
spike-wave-discharges (CSWS) which may be
asymmetric or focal
 They are also known as electrical status
epilepticus during sleep (ESES)
 Spike wave index (SWI), a measure of the
frequency of spiking in the EEG tracing, is
usually more than 85%

67.  EEG during REM sleep shows disappearance
of ESES pattern
 This stage is followed by
clinicoelectroencephalographic remission,
usually 2–7 years after the onset
 Majority of the children, however, are left
with residual moderate-to-severe
neurocognitive deficits

68.  The etiology is unknown
 Abnormal neuroimaging is seen in 30–59%
cases which may include:
1. cerebral atrophy
2. perinatal vascular insults, and
3. cerebral malformations
 The evolution from benign childhood focal
epilepsies to ESES is also reported

69.  Early initiation of steroids/ACTH is usually
recommended
 Intravenous immunoglobulins also have
shown promising results
 The antiepileptic drugs, used for LKS, are
usually effective
 Limited response has been demonstrated
with ketogenic diet

70.  Epilepsy surgery may be considered in
medically refractory cases with focal lesions
on neuroimaging or focal EEG findings
 Hemispherectomy and focal resective
epilepsy surgery may be beneficial for
children with ESES with structural etiology
 Multiple subpial transections may be
beneficial for the cognitive impairment and
behavioural problems

71.  This syndrome is aka LGS
transient or pseudo-Lennox syndrome
 Onset is at 2–6 years of age in previously
normal child with clusters of atonic and
nocturnal focal “Rolandic-like” seizures
 Variable cognitive involvement may be seen
during periods of active seizures

72.  The interictal EEG shows centrotemporal
spikes and generalized spike-and-wave
discharges
 The centrotemporal spikes may be seen in
trains and
 may be associated with frontocentral and
centroparietal spikes
 The interictal magnetoencephalography has
localized the clusters of spike sources around
the Rolandic-sylvian fissures

73.  This is in contrast to the findings in Rolandic
epilepsy where the clusters of spike sources
have been localized along the Rolandic region
with orientation vertical to the central sulcus
 Similar condition may be induced by
lamotrigine or carbamazepine in few children
with rolandic and Panayiotopoulos syndromes

74.  Some authors consider it as a mild form of
epilepsy with CSWS
 It is still debatable whether this entity is a
separate clinical entity or part of a continuum
related to rolandic epilepsy
 Differentiating features from Rolandic
epilepsy include:
1. an earlier age of onset
2. frequent atonic seizures
3. more frequent and prolonged focal seizures
4. prominent associated behavioural problems

75.  Seizures are usually refractory to
conventional treatment
 But usually remit by adolescence
 Long-term neurocognitive outcome is usually
favourable

76.  This entity has been proposed by Nordli et al
 Onset is beyond one year of age with
classical myoclonic-tonic seizures
 The tonic component is longer than the
infantile spasms and shorter than that seen in
LGS
 It may be associated with myoclonic seizures,
epileptic spasms, and atonic seizures.

77.  The interictal EEG shows disorganized high-
amplitude slow background with multifocal
spikes more pronounced during the sleep
 The response to the conventional
antiepileptic drugs is poor
 Some response to hormonal therapy and
ketogenic diet
 The prognosis is guarded.

78.  Epileptic encephalopathies start at an early
age
 manifest with seizures, which are usually
intractable
 aggressive EEG paroxysmal abnormalities
 severe neurocognitive deficits
 The clinicoelectroencephalographic features
are age related and depend on the structural
and functional maturity of the brain
 Their recognition and appropriate
management are critical

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