Download Practice Parameter: Screening and Diagnosis of - Pediatrics

Infantile spasms
Dr/Nabil El-mansoury
Definition
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West syndrome is composed of the triad of infantile
spasms, an interictal EEG pattern termed
hypsarrhythmia, and mental retardation, although
the diagnosis can be made even if one of the 3
elements is missing (according to the international
classification).
This severe epilepsy syndrome is an age-dependent
expression of a damaged brain. The term infantile
spasms has been used to describe the seizure type,
the epilepsy syndrome, or both
the syndrome’s namesake, Dr W J West, gave the first detailed
description of infantile spasms, as they occurred in his child.[ in a
letter to the editor of The Lancet in 1841,dr West described the
events as “bobbings” that “cause a complete heaving of the head
forward towards his knees, and then immediately relaxing into
the upright position … these bowings and relaxings would be
repeated at intervals of a few seconds, and repeated from 10 to
20 or more times at each attack, which would not continue more
than 2 or 3 minutes; he sometimes has 2, 3 r more attacks in the
day.

This detailed clinical description was followed 100 
years later by the report of the typical interictal EEG
pattern termed hypsarrhythmia. Most patients with
infantile spasms have some degree of
developmental
retardation.
The West syndrome was created in the early 1960 
by Drs. Gastaut, Poirier, and Pampiglione.
Introduction


West’s syndrome is a unique, age-specific
epilepsy of early infancy.
Spasms are:
Different from myoclonic and tonic seizures
 Characterized by an initial contraction phase
followed by a more sustained tonic phase
 Divided into flexor, extensor, and mixed flexorextensor spasms and they can also be
asymmetrical
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Infantile spasms are believed to reflect abnormal interactions
between the cortex and brainstem structures. Focal lesions
early in life may secondarily affect other sites in the brain, and
hypsarrhythmia may represent this abnormal activity arising
from multiple brain sites.

The frequent onset of infantile spasms in infancy suggests that
an immature central nervous system may be important in the
pathogenesis. The brain-adrenal axis also may be involved.

One theory states that the effect of different stressors in the
immature brain produces an abnormal excessive secretion of
corticotropin-releasing hormone, causing spasms.
Incidince

Incidence of infantile spasms is estimated between 0.25 to
0.60 per 1000 live births.
Prevalence rate is 0.15-0.2 per 1000 children ten years of age
or younger.

United States
Infantile spasm constitutes 2% of childhood epilepsies but
25% of epilepsy with onset in the first year of life.
Sex
Although males are affected slightly more often than
females, no significant gender difference is noted.
Age
90% of infantile spasms begin in those younger than
12 months. Peak onset is at age 4-6 months.
Manifestations

Spasms begin with a sudden, rapid, tonic
contraction of trunk and limb musculature that
gradually relaxes over 0.5-2 seconds.
Contractions can last 5-10 seconds.
 The intensity may vary from a subtle head nodding to a
powerful contraction of the body.
 Infantile spasms usually occur in clusters, often several
dozens, separated by 5-30 seconds.
 Spasms frequently occur just before sleep or upon
awakening. They can be observed during sleep,
although this is rare.


Spasms can be flexor, extensor, or a mixture of flexion and
extension.

Flexor spasms consist of brief contractions of the flexor
muscles of the neck, trunks, and limbs, resulting in a brief
jerk. They may resemble a self-hugging motion and often
are associated with a cry. The patient then relaxes, and the
jerk repeats. These attacks occur in clusters throughout the
day and last anywhere from less than 1 minute to 10-15
minutes or longer in some patients.

-Extensor spasms consist of contractions of the extensor
muscles with sudden extension of the neck and trunk
with extension and abduction of the limbs. Extensor
spasms and asymmetric or unilateral spasms often are
associated with symptomatic cases.
 Mixed spasms are the most common type, consisting of
flexion of the neck and arms with extension of the legs,
or flexion of the legs with extension of the arms.
In different series the frequency of the 3 spasm types were
42-50% mixed, 34-42% flexor, and 19-23% ex


General physical examination
Physical examination can be important in helping to identify
specific etiologies that may have both systemic and
neurological symptoms (eg, tuberous sclerosis complex).
Often a patient with infantile spasms has normal findings on
general physical examination. No pathognomonic physical
findings are present in patients with infantile spasms.

If abnormalities in the general physical examination are noted
(eg, adenoma sebaceum, ash leaf macules), specific etiologies
may be suggested.

Patients may exhibit moderate-to-severe growth delay; this is a
nonspecific finding and more a reflection of the underlying
brain injury than of a specific epilepsy syndrome.
Neurologic
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

examination
The neurologic examination in patients with infantile spasms
demonstrates abnormalities in mental status function,
specifically deficits in cognitive function consistent with
developmental delay or regression.
Abnormalities in level of consciousness, cranial nerve
function, and motor/sensory/reflex examination are
nonspecific findings and more a reflection of the underlying
brain injury or effect of anticonvulsant medications than of
the syndrome.
No pathognomonic findings are present on neurologic
examination in patients with infantile spasm
Causes
Infantile spasms (West syndrome) can be classified
according to its suspected etiology as
 Symptomatic:, 70-75%
 cryptogenic, 8-42%
 . idiopathic. 9-14%.
Symptomatic :Patients are diagnosed with symptomatic infantile spasms if an
identifiable factor is responsible for the syndrome. any
disorder that can produce brain damage can be associated
with infantile spasms.
 The list of etiologies can be subdivided into prenatal
disorders, perinatal disorders, and postnatal disorders.

Prenatal disorders include hydrocephalus, microcephaly,
hydranencephaly, schizencephaly, polymicrogyria, Sturge-Weber
syndrome, incontinentia pigmenti, tuberous sclerosis, trisomy 21,
hypoxic-ischemic encephalopathies, congenital infections, and
trauma.

Perinatal
disorders
include
hypoxic-ischemic
encephalopathies, meningitis, encephalitis, trauma, and
intracranial hemorrhages.

Postnatal disorders include pyridoxine dependency,
nonketotic hyperglycinemia, maple syrup urine
disease,
phenylketonuria,
mitochondrial
encephalopathies,
meningitis,
encephalitis,
degenerative diseases, biotinidase deficiency, and
trauma.
Cryptogenic:

Patients have cryptogenic infantile spasms if no cause is
identified but a cause is suspected and the epilepsy is
presumed to be symptomatic.
The proportion of cryptogenic cases varies from 8-42%.
This wide range may be related to variations in the
definition of the term cryptogenic and the age of diagnosis,
since assessment of developmental level in early infancy is
difficult.
Idiopathic:

Patients may be considered to have idiopathic infantile
spasms if normal psychomotor development occurs prior
to the onset of symptoms, no underlying disorders or
definite presumptive causes are present, and no
neurological or neuroradiological abnormalities exist. Some
investigators use the terms idiopathic and cryptogenic
interchangeably.
The percentage of idiopathic cases reportedly is 9-14%.
Laboratory workup
Prior to initiating therapy, consider obtaining some or all of
the following laboratory studies:
 Complete blood count with differential, liver panel, renal
panel with electrolytes and glucose, calcium, magnesium,
phosphorus, and urinalysis with microscopic examination
 Metabolic workup including glucose, liver panel, serum
lactate and pyruvate, plasma ammonia, serum and urine
amino acids, urine organic acids, and serum biotinidase
 Blood, urine, and cerebrospinal fluid cultures if an
infection is suspected
 Cerebrospinal fluid analysis for cell count, glucose, protein,
bacterial and viral culture, lactate, pyruvate, and amino
acids
Imaging

About 70-80% of patients have abnormal findings on
neuroimaging studies.

Magnetic resonance imaging (MRI) of the brain provides
a more detailed evaluation than does a computed
tomography (CT) scan of the brain.

Imaging studies should be obtained prior to starting
ACTH or steroid therapy, as these therapies are
associated with the appearance of apparent brain
atrophy as treatment continues.
CT scan 
 Structural brain anomalies such as hydrocephalus,
hydranencephaly, schizencephaly, and agenesis of
corpus callosum can be recognized easily by CT scans.
 In addition, cerebral calcifications can be observed in
patients with tuberous sclerosis or congenital infections.
-
MRI scans
are superior to CT scans in detecting areas of cortical
dysgenesis, disorders of neuronal migration, or disorders
of myelination.
Electroencephalogram(EEG)

Interictal electroencephalogram
Hypsarrhythmia is the characteristic interictal EEG pattern
and consists of chaotic, high- to extremely high-voltage
polymorphic delta and theta rhythms with superimposed
multifocal spikes and wave discharges. Multiple variations
of this pattern are possible, including focal or asymmetric
hypsarrhythmia.
Ictal electroencephalogram
Eleven different types of ictal patterns have been
identified in patients with West syndrome.
 In one study, the most common pattern found in 38%
of patients with seizures was a high-voltage, frontal
dominant, generalized slow-wave transient followed by
voltage attenuation, also termed an electrodecremental
episode. These electrodecremental episodes were a
feature in 71% of the seizures.
No close correlation exists between the type of seizure and
the EEG pattern
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Ophthalmic examination:
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Ophthalmic
examination
may
reveal
chorioretinitis from congenital infections,
chorioretinal lacunar defects in patients with
Aicardi syndrome,
retinal tubers in patients with tuberous sclerosis.
Wood lamp

: Tuberous sclerosis is the single most common
recognizable cause of West syndrome. Therefore, a
careful examination of the skin for the characteristic
hypopigmented lesions of tuberous sclerosis is
mandatory. The unaided bedside identification of these
lesions may be more difficult in patients with light
complexions.
Treatment

The goals of treatment for infants with West syndrome are
the best quality of life with no seizures, the fewest adverse
effects from treatment, and the least number of
medications.

Medications such as ACTH and conventional antiepileptic
medications (AEDs) are the mainstay of therapy for
infants with West syndrome. Unfortunately, no one
medical treatment gives satisfactory relief for all infants
with West syndrome.


The various medical treatment options for infants with
West syndrome can be divided into 2 major groups:
Commonly used first-line treatments (ie, ACTH ,
prednisone, vigabatrin , pyridoxine [vitamin B-6]
Second-line treatments (ie, benzodiazepines, valproic acid,
lamotrigine , topiramate , zonisamide , levetiracetam

In 2007, an expert survey concluded that 1-3 trials of
monotherapy should be implemented before considering
epilepsy surgery. In patients with tuberous sclerosis or
symptomatic infantile spasms, vigabatrin was the drug of
choice. Alternative options for symptomatic spasms
included ACTH and prednisone.

Focal cortical resection: In some patients, resection of a
localized region can lead to freedom from seizures.
Vigabatrin (Sabril)

Indicated as monotherapy for children aged 1 mo to 2 y
with infantile spasms. Precise mechanism unknown.
Irreversible inhibitor of gamma-aminobutyric acid
transaminase (GABA-T). GABA-T metabolizes GABA,
an inhibitory neurotransmitter, thereby increasing CNS
GABA levels. Use must be weighed against risk of
permanent vision loss. Approved by the FDA August,
2009. Available only from restricted access program.
ACTH

A 2004 American Academy of Neurology and Child
Neurology Society practice parameter concluded that
"ACTH is probably effective for the short-term
treatment of infantile spasms and in resolution of
hypsarrhythmia and "There is insufficient evidence to
recommend the optimum dosage and duration of
treatment with ACTH for the treatment of infantile
spasms .
Prednisone

A 2004 American Academy of Neurology and
Child Neurology Society practice parameter
concluded that "there is insufficient evidence
that oral corticosteroids are effective in the
treatment of infantile spasms .
Levetiracetam (Keppra, Keppra XR)
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
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Mechanism of action: inhibition of N-type calcium
channels, modulation of GABA and glycine receptors and
binding to SVA2 protein
One small open label trial of 5 infants with new onset
cryptogenic infantile spasms showed clinical effectiveness.
Two children became seizure free, while 2 others showed a
minimum of 50% reduction in seizures. The dose ranged
from 30-60 mg/kg/d.
In another small open label trial of 7 children, 5 with
symptomatic infantile spasms, treated with 20-80 mg/kg/d
of levetiracetam, all responded to therapy. Two patients
had >75% reduction in spasms and one had complete
cessation of spasms.
Valproic acid (Depakene)
A 2004 American Academy of Neurology and Child
Neurology Society practice parameter concluded that "there
is insufficient evidence to recommend valproic acid for
treatment of infantile spasms
Pyridoxine (vitamin B-6)
A 2004 American Academy of Neurology and Child
Neurology Society practice parameter concluded that "there
is insufficient evidence to recommend pyridoxine for the
treatment of infantile spasms
 Two distinct treatment situations exist in which pyridoxine
is used in patients with West syndrome:
(1) IV administration during diagnostic EEG to assess
whether patient's seizures and EEG abnormalities are
related to pyridoxine deficiency. In this approach,
administer 50-100 mg IV during diagnostic EEG; if
dramatic improvement noted in EEG, patient believed to
have pyridoxine-dependent seizures

(2) Long-term oral administration: Effectiveness of longterm oral high-dose pyridoxine in West syndrome has been
investigated in multiple open-label studies with promising
results; most patients who respond to long-term oral highdose pyridoxine do so within 1-2 wk of initiation.
Prognosis


The long-term overall prognosis is poor and is related
directly to the etiology.
Infants with idiopathic West syndrome have better
prognosis than do infants with symptomatic West
syndrome. Only 14% of infants with symptomatic West
syndrome have normal or borderline normal cognitive
development compared with 28-50% of infants with
idiopathic West syndrome. Mental retardation is severe in
70% of patients, often with psychiatric problems such as
autistic features or hyperactivity. Infrequently spasms may
persist in adulthood. 50-70% of patients develop other
seizure types and 18-50% of patients will develop Lennox
Gastaut syndrome.
Favorable prognostic factors include cryptogenic etiology, age
of onset >4 months, absence of atypical spasms and partial
seizures, absence of asymmetric EEG abnormalities, short
time from onset to treatment, and early sustained response
to treatment.

Infants with symptomatic infantile spasms have been
shown to be at higher risk for the development of autism
spectrum disorders, compared with those infants with
cryptogenic or idiopathic spasms
This done aty 26-10-2011 (11/2 year child)
reveals marked atrophy and volume loss of left temporal and parietal
lobe,encephalmalacia .Widenining of the ipsilateral left lateral ventricle is
notead”(porencephaly)
Conclusion :-chronic sequalae of an old brain insult for clinical correlation
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