1. WEST SYNDROME Dr.Dhritiman Choudhury Tripura medical
college
2. introduction West syndrome is a severe epilepsy syndrome
composed of the triad of infantile spasms, an interictal
electroencephalogram (EEG) pattern termed hypsarrhythmia, and
mental retardation, although the diagnosis can be made even if 1 of
the 3 elements is missing (according to international
classification)
3. The syndromes namesake, Dr W J West, gave the first detailed
description of infantile spasms, which occurred in his own child.In
a letter to the editor of The Lancet in 1841, 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
alternately 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 or more attacks in the
day."
4. Classification based on etiology: Symptomatic:Patients are
diagnosed with symptomatic infantile spasms if an identifiable
factor is responsible for the syndrome. Virtually any disorder that
can produce brain damage can be associated with infantile spasms.
Hydrocephalus Microcephaly Sturge weber syndrome
5. Tuberous sclerosis HIE Congenital infections Meningitis
Encephalitis Pyridoxine deficiency Maple syrup urine disease
Phenylketonuria Biotinidase deficiency Trauma
6. Cryptogenic:Patients have cryptogenic infantile spasms if no
cause is identified but a cause is suspected and the epilepsy is
presumed to be symptomatic. 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 presumptive causes are present, and no neurologic or
neuroradiologic abnormalities exist. Some investigators use the
terms idiopathic and cryptogenic interchangeably.
7. A case study: A 5 month old baby presented with generalized
convulsion since 20 days. Frequency: 4-5/day each lasting for 2-4
min. h/o cough-10days No H/O LOC ,vomiting, fever, trauma. No
autonomic involvement Perinatal history-uneventful. Immunization up
to date. No similar history in the family. No history of drug
intake.
8. On examination: Conscious,feeding well. No bulging of
fontanel. No evidence of meningeal irritation. No pallor, cyanosis,
icterus, lymphadenopathy,hepatosplenomegaly or abdominal mass. No
evidence of any dermatologic lesion. Developmental milestones
normal.
9. Ictal manifestations: Spasms begin with a sudden, rapid,
tonic contraction of trunk and limb musculature that gradually
relaxes over 0.5-2 seconds. Spasms last for 3-4 sec. The intensity
of spasms may vary from a subtle head nodding to a powerful
contraction of the body. The spasms are of mixed variety consisting
of flexion of the neck and trunk with extension and abduction of
limbs. They are associated with a cry. The patient then relaxes,
and the jerk repeats. These attacks occur in clusters throughout
the day and last for 2-4 min.
10. These manifestations are also known as salaam or jackknife
attacks: a flexor spasm with rapid bending of the head and torso
forward and simultaneous raising and bending of the arms while
partially drawing the hands together in front of the chest. If one
imagined this act in slow motion, it would appear similar to the
ceremonial greeting (Salaam).
11. Investigations: Hb 11.0 gm% TLC 9,400/cumm DLC
52/45/01/02/00 ESR 18mm/1st hr Sr. Ca 8.9 mg/dl NCCT brain- within
normal limit. ECG- within normal limit. EEG- hypsarrhythmia.
12. hypsarrhythmia Hypsarrhythmia (seen in the image below) is
the characteristic interictal EEG pattern. It consists of chaotic,
high- to extremely high voltage, polymorphic delta and theta
rhythms with superimposed multifocal spikes and wave
discharges.
13. Treatment: Compared with other forms of epilepsy, West
syndrome is difficult to treat. To raise the chance of successful
treatment and keep down the risk of longer-lasting effects, it is
very important that the condition is diagnosed as early as possible
and that treatment begins straight away. However, there is no
guarantee that therapy will work even in this case.
14. Treatment optionsCommonly used first-line treatments for
infants withWest syndrome include the following: ACTH Vigabatrin
Prednisone Pyridoxine (vitamin B-6)Second-line treatments include
the following: Benzodiazepines Valproic acid Lamotrigine Topiramate
Zonisamide Levetiracetam
15. 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 One study found that after
approximately 2 weeks, hormonal therapy provided better relief from
spasm than did vigabatrin. The 2004 multicenter, randomized,
controlled trial compared hormonal therapy (either oral
prednisolone or IM tetracosactide depot) with vigabatrin in 107
infants with infantile spasms. More infants assigned hormonal
treatments (73%) had no spasms on days 13 and 14 than did infants
assigned vigabatrin (54%).
16. Pyridoxine Two distinct treatment situations exist in which
pyridoxine is used in patients with West syndrome. First is
intravenous (IV) administration during diagnostic EEG to assess
whether the patients seizures and EEG abnormalities are related to
pyridoxine deficiency. In this approach, administer 50-100 mg IV
during a diagnostic EEG; if dramatic improvement is noted in the
EEG, the patient is believed to have pyridoxine-dependent seizures.
Second is long-term oral administration. The effectiveness of
long-term, 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, high-dose
pyridoxine do so within 1-2 weeks of initiation.
17. Valproic acid Valproic acid is considered an effective
second-line AED therapy against spasms associated with West
syndrome. Dose-10-15 mg/kg/day PO/IV divided q6-8h Monitor:
LFTs
18. 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 "here is insufficient
evidence to recommend the optimum dosage and duration of treatment
with ACTH for the treatment of infantile spasms."
19. Corticotropin is associated with serious, potentially
life-threatening adverse effects. It must be administered
intramuscularly, and such injections are painful for the infant to
receive and are unpleasant for the parent to perform. A
prospective, single-blind study demonstrated no difference in
effectiveness between high-dose, long-duration corticotropin (150
U/m2/day for 3 wk, tapering over 9 wk) and low-dose, short-
duration corticotropin (20-30 U/day for 2-6 wk, tapering over 1 wk
with respect to spasm cessation and improvement in the patients
EEG. Hypertension was more common with larger doses
20. Vigabatrin Vigabatrin is indicated as monotherapy for
children aged 1 month to 2 year with infantile spasms. Its precise
mechanism of action is unknown. The drug is a selective,
irreversible inhibitor of gamma-aminobutyric acid transaminase
(GABA-T). GABA-T metabolizes GABA, an inhibitory neurotransmitter,
thereby increasing CNS GABA levels. Vigabatrin use must be weighed
against the risk of permanent vision loss.Vigabatrin was approved
by the US Food and Drug Administration (FDA) in August 2009. It is
available only from a restricted access program.
21. Topiramate Topiramate is a sulfamate-substituted
monosaccharide with a broad spectrum of antiepileptic activity that
may have state- dependent sodium channel blocking action, may
potentiate the inhibitory activity of the neurotransmitter GABA,
and may block glutamate activity. A 2004 American Academy of
Neurology and Child Neurology Society practice parameter concluded
that "there is insufficient evidence to recommend topiramate for
the treatment of infantile spasms."
22. Levetiracetam Levetiracetams mechanism of action is the
inhibition of N-type calcium channels, the modulation of GABA and
glycine receptors, and binding to SVA2 protein. An open-label trial
of 5 infants with new- onset, cryptogenic infantile spasms showed
levetiracetam to be clinically effective. Two children became
seizure free, while 2 others showed a minimum of 50% reduction in
seizures. The dose ranged from 30-60 mg/kg/day.
23. clonazepam Clonazepam is considered a second-line AED
therapy against spasms associated with West syndrome. However,
adverse effects and the development of tolerance limit the drugs
usefulness over time. Nitrazepam and clobazam are not approved by
the FDA but are available in many countries worldwide.
24. Treatment given Methyl prednisone 1mg/kg/day Pyridoxine
hydrochloride 10mg/day Sodium valproate 10-15mg/kg/dayThere was
only a single episode of seizure afterthe commencement of the
steroid therapy.
25. Prognosis It is not possible to make a generalised
prognosis for development due to the variability of causes, the
differing types of symptoms and etiology. Each case must be
considered individually. The prognosis for children with idiopathic
West syndrome are mostly more positive than for those with the
cryptogenic or symptomatic forms.
26. A large proportion (up to 90%) of children suffer severe
physical and cognitive impairments, even when treatment for the
attacks is successful. This is not usually because of the epileptic
fits, but rather because of the causes behind them (cerebral
anomalies or their location or degree of severity). Permanent
damage often associated with West syndrome in the literature
include cognitive disabilities, learning difficulties and
behavioural problems, cerebral palsy (up to 5 out of 10 children),
psychological disorders and often autism (in around 3 out of 10
children). Once more, the etiology of each individual case of West
syndrome must be considered when debating cause and effect.
27. Statistically, 5 out of every 100 children with West
syndrome do not survive beyond five years of age, in some cases due
to the cause of the syndrome, in others for reasons related to
their medication. Only less than half of all children can become
entirely free from attacks with the help of medication. Statistics
show that treatment produces a satisfactory result in around three
out of ten cases, with only one in every 25 childrens cognitive and
motoric development developing more or less normally. Sometimes
West syndrome turns into a focal or other generalised epilepsy.
Around half of all children develop Lennox-Gastaut syndrome.