This document provides information on West syndrome, including its classification, clinical manifestations, treatment, and prognosis. West syndrome is a severe epilepsy syndrome in infants characterized by infantile spasms, abnormal EEG findings called hypsarrhythmia, and developmental regression. It is classified based on its etiology as symptomatic, cryptogenic, or idiopathic. First-line treatment options include ACTH, vigabatrin, and corticosteroids. Prognosis depends on the underlying etiology, with idiopathic cases generally having a better prognosis than symptomatic cases. Outcomes include cognitive impairments, cerebral palsy, and in some cases mortality.

1. WEST SYNDROME
Prepared by:
D.MOAWEYAH QASIM (R3)
SUPERVISED BY:
DR.ABEER MATAR
(PEDIATRIC NEUROLOGIST)

2. • - Introduction
• - Classification.
• -clinical manifstation
• -Treatment
• - updated guidelines from 2004 till 2012 from
american academy of neurology .

3. 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)

4. • The syndrome's 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."

5. • Infantile spasms constitute a unique, age-specific
epilepsy syndrome of early infancy characterized by
epileptic spasms often accompanied by
neurodevelopmental regression and an EEG finding
of hypsarrhythmia.
– When all 3 components are present, the eponym “West
syndrome” is commonly used.
• The incidence is 2–3 per 10,000 live births , the
lifetime prevalence rate is 1.5–2 per 10,000 children.

6. • Infantile spasms are slightly more common in males,
and a family history exists in 3%–6% of cases.
• The spontaneous remission rate of infantile spasms
described in limited natural history studies is 30%.
• A 2004 AAN/Child Neurology Society parameter on
the medical treatment of infantile spasms concluded:
– Adrenocorticotropic hormone (ACTH) is probably an
effective agent for short-term treatment of infantile
spasms (Level B)

7. – Vigabatrin (VGB) is possibly effective for short-term
treatment of infantile spasms (Level C) and for treatment
of children with tuberous sclerosis (Level C)
• In children with infantile spasms and tuberous
sclerosis, 2 Class III studies from the 2004 practice
parameter showed spasms cessation at 2–3 weeks in
16 of 28 (57%) patients treated with VGB, with
overall response rate of 100% in both studies.
Therefore, VGB is possibly effective for short-term
treatment of infantile spasms in the majority of
children with tuberous sclerosis (Level C).

8. • Data were insufficient at that time to recommend
other antiepileptic drugs (AEDs), the ketogenic
diet, pyridoxine, or IV immunoglobulin (IVIg) for
short-term treatment of infantile spasms or to
assess the impact of treatment on long-term
outcomes.
• Since 2004, only one study provided evidence
higher than Class IV, a single large Class III
randomized controlled trial (RCT) comparing low-dose
and high-dose VGB for treatment of infantile
spasms.

9. – This study showed more patients in the high-dose group
achieved spasms cessation within 14 days relative to those
in the low-dose VGB group.
– In the symptomatic tuberous sclerosis complex (TSC)
subgroup, the spasm-free rate was higher in those
allocated high-dose VGB.
– A post analysis video-EEG performed at any subsequent
visit showed hypsarrhythmia resolution in 30.8% of
patients on high-dose VGB vs 13.2% on low-dose VGB.

10. 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

11. – Tuberous sclerosis
– HIE
– Congenital infections
– Meningitis
– Encephalitis
– Pyridoxine deficiency
– Maple syrup urine disease
– Phenylketonuria
– Biotinidase deficiency
– Trauma

12. • 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.

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.
•

14. Treatment options
Commonly used first-line treatments for infants with
West 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 patient's 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 patient's 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
• Levetiracetam's 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 drug's
usefulness over time. Nitrazepam and
clobazam are not approved by the FDA but are
available in many countries worldwide.

24. 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.

25. • 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.

26. • 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 children's
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.

27. • Are other forms of corticosteroids as effective as ACTH
for 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?
• What other agents are as effective as ACTH for
treatment of infantile spasms?
• Does successful early treatment of infantile spasms
lead to long-term improvement of
neurodevelopmental outcomes or decreased incidence
of epilepsy?

28. AAN Classification of Evidence
• All studies rated Class I, II, III, or IV
• Five different classification systems
– Therapeutic
• Randomization, control, blinding
– Diagnostic
• Comparison with gold standard
– Prognostic
– Screening
– Causation

29. AAN Level of Recommendations
• A = Established as effective, ineffective or harmful (or
established as useful/predictive or not useful/predictive) for
the given condition in the specified population
• B = Probably effective, ineffective or harmful (or probably
useful/predictive or not useful/predictive) for the given
condition in the specified population
• C = Possibly effective, ineffective or harmful (or possibly
useful/predictive or not useful/predictive) for the given
condition in the specified population
• U = Data inadequate or conflicting; given current knowledge,
treatment (test, predictor) is unproven
– Note that recommendations can be positive or negative

30. Translating Class to Recommendations
• A = Requires at least two consistent Class I studies*
• B = Requires at least one Class I study or two
consistent Class II studies
• C = Requires at least one Class II study or two
consistent Class III studies
• U = Studies not meeting criteria for Class I through
Class III

31. Methods
• MEDLINE and EMBASE were searched (2002–August
2011) using OVID interface
– Relevant, fully published, peer-reviewed articles
– See appendix e-3 of the published guideline for the complete
search strategy
• At least two authors reviewed each article for inclusion,
with a third author arbitrating differences
• Risk of bias was determined using the classification of
evidence scheme for therapeutic articles
• Strength of recommendations was linked directly to
levels of evidence
• Conflicts of interest were disclosed

32. AAN Classification of Evidence
for Therapeutic Interventions
• Class I: Class I: A randomized, controlled clinical trial
of the intervention of interest with masked or
objective outcome assessment, in a representative
population. Relevant baseline characteristics are
presented and substantially equivalent among
treatment groups or there is appropriate statistical
adjustment for differences. The following are also
required:
– Concealed allocation
– Primary outcome(s) clearly defined
– Exclusion/inclusion criteria clearly defined

33. AAN Classification of Evidence
for Therapeutic Interventions, cont.
– Adequate accounting for dropouts (with at least 80% of enrolled
subjects completing the study) and crossovers with numbers
sufficiently low to have minimal potential for bias.
– For noninferiority or equivalence trials claiming to prove efficacy for
one or both drugs, the following are also required*:
• The authors explicitly state the clinically meaningful difference to
be excluded by defining the threshold for equivalence or
noninferiority.
• The standard treatment used in the study is substantially similar to
that used in previous studies establishing efficacy of the standard
treatment (e.g., for a drug, the mode of administration, dose and
dosage adjustments are similar to those previously shown to be
effective).
• The inclusion and exclusion criteria for patient selection and the
outcomes of patients on the standard treatment are comparable
to those of previous studies establishing efficacy of the standard
treatment.
• The interpretation of the results of the study is based upon a per
protocol analysis that takes into account dropouts or crossovers.

34. AAN Classification of Evidence
for Therapeutic Interventions, cont.
• Class II: A randomized controlled clinical trial of
the intervention of interest in a representative
population with masked or objective outcome
assessment that lacks one criteria a–e above or a
prospective matched cohort study with masked
or objective outcome assessment in a
representative population that meets b–e above.
Relevant baseline characteristics are presented
and substantially equivalent among treatment
groups or there is appropriate statistical
adjustment for differences.

35. AAN Classification of Evidence
for Therapeutic Interventions, cont.
• Class III: All other controlled trials (including well-defined
natural history controls or patients serving as
own controls) in a representative population, where
outcome is independently assessed, or
independently derived by objective outcome
measurement.**
• Class IV: Studies not meeting Class I, II, or III criteria
including consensus or expert opinion.
*Note that numbers 13 in Class I, item 5 are required for Class II in
equivalence trials. If any one of the three is missing, the class is
automatically downgraded to Class III.
**Objective outcome measurement: an outcome measure that is unlikely to
be affected by an observer’s (patient, treating physician, investigator)
expectation or bias (e.g., blood tests, administrative outcome data).

36. Clinical Question 1
• Are other forms of corticosteroids as effective
as ACTH for treatment of infantile spasms?

37. • Only one Class III study showed similar efficacy
between ACTH and oral prednisolone.
• Data are insufficient regarding the equivalence of
other corticosteroids to ACTH (Class III and IV
evidence).
• 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
(Level U).

38. Clinical Question 2
• Are low-dose ACTH regimens effective for
short-term treatment of infantile spasms?

39. • A Class I study showed similar efficacy between
low-dose (20–30 IU) and high-dose (150 IU/m2)
natural ACTH, and a Class II study using the same
low-dose natural ACTH showed clinical and EEG
response rates of 40%. The evidence suggests
that low-dose ACTH is probably as effective as
high-dose ACTH for short-term treatment of
infantile spasms (Class I and II evidence).
• Low-dose ACTH should be considered as an
alternative to high-dose ACTH for treatment of
infantile spasms (Level B).

40. Clinical Question 3
• Is ACTH more effective than vigabatrin for
short-term treatment of infantile spasms?

41. • 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 small
Class III study and a Class IV study found no difference
in short-term outcome between ACTH and VGB.
• Previous practice parameter recommendation
remained unchanged: ACTH (Level B) or VGB (Level C)
may be offered for short-term treatment of infantile
spasms. Evidence suggests that ACTH may be offered
over VGB (Level C).

42. Clinical Question 4
• What other agents are as effective as ACTH for
treatment of infantile spasms?

43. • Data from previously reviewed and updated evidence
are insufficient to determine whether valproic acid
(VPA), vitamin B6, nitrazepam (NZP), levetiracetam
(LEV), zonisamide (ZNS), topiramate (TPM), the
ketogenic diet, sulthiame, or other novel therapies
(e.g., IV immunoglobulin, thyrotropin-releasing
hormone) are effective in the treatment of infantile
spasms (Class III and IV evidence). A single Class III
study showed better outcome for combination therapy
with ACTH and magnesium sulfate.

44. • The evidence is insufficient to recommend
other therapies (VPA, vitamin B6, NZP, LEV,
ZNS, TPM, the ketogenic diet, or
novel/combination therapies) for treatment of
infantile spasms (Level U).

45. Clinical Question 5
• Does successful early treatment of infantile
spasms lead to long-term improvement of
neurodevelopmental outcomes or decreased
incidence of epilepsy?

46. • A Class II study showed that hormonal therapy
(ACTH or prednisolone) relative to VGB
therapy leads to better neurodevelopmental
outcome in children with cryptogenic spasms.
• One previous Class III study and 1 newer Class
II study showed that shorter lag time to
treatment improves long-term cognitive
outcomes.

47. • Hormonal therapy (ACTH or prednisolone) may
be considered for use in preference to VGB in
infants with cryptogenic infantile spasms, to
possibly improve developmental outcome (Level
C).
• 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).

48. Clinical Context
• This update focuses on questions for which
data were insufficient to answer in the 2004
practice parameter.
• There was a marked paucity of randomized
treatment trials carefully designed to provide
a definitive answer to any of the questions
proposed initially.

49. • The United Kingdom Infantile Spasms Study
(UKISS) showed higher responder rates for
infants treated with high-dose ACTH and
prednisolone than with VGB (Class III).
• However, the evidence is still insufficient to
conclude that prednisolone is as effective as
ACTH, because UKISS was underpowered to
answer this question.

50. • The current literature suggests that the
underlying etiology of infantile spasms is an
important outcome determinant. Analysis of
children with cryptogenic spasms may provide
more insight into a treatment’s efficacy by
removing the confounding effect of etiology.
• Class II data from UKISS suggest that hormonal
agents (e.g., ACTH, prednisolone) are associated
with better developmental outcome than VGB.
Questions remain, however, regarding optimal
ACTH formulation, dose, and treatment duration.

51. • To date, the evidence is insufficient to support
the use of agents other than ACTH and VGB.

52. Future Research Recommendations
• Multicenter RCTs of infantile spasms with
multiple treatment arms (ACTH vs VGB vs.
prednisolone, or combination hormonal
therapy and VGB) are needed to determine
the most effective therapy for infantile spasms
and should include EEG, clinical seizure
occurrence, and standardized developmental
outcome measures.

53. • The International Collaborative Infantile Spasms
Study a multicenter RCT comparing hormonal
therapy & VGB with hormonal therapy alone, is
currently underway.
• It is hoped that this study, and the recently
concluded Canadian randomized, double-blind
trial of add-on flunarizine to prevent cognitive
deterioration associated with infantile spasms
will provide further evidence regarding the use of
combination therapy.

54. • In addition, further studies are needed to
determine the optimal duration of VGB
therapy, to minimize the retinal toxicity AE in
patients with infantile spasms.

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58. In emergency situation take a breat
take a
KitKat