WEST SYNDROME /INFANTILE SPASM

In 1841, the general practitioner W.J. West from Tunbridge wrote a letter to the editor of Lancet entitled “On a peculiar form of infantile convulsions.” West’s goal was to draw the attention of his colleagues to “a very rare and singular species of convulsions peculiar to young children.” He described his son’s symptoms in detail, in a letter conveying both the objectivity of the physician and the frustrations of a father with a severely ill child. This description includes all of the features of the entity currently called “infantile spasms”

The term Infantile spasms syndrome defines an epileptic syndrome occurring in children younger than 1 year (rarely older than 2 years), with clinical spasms usually occurring in clusters whose most characteristic EEG finding is hypsarrhythmia [the spasms are often associated with developmental arrest or regression].

Some definitions:

West syndrome: Combination of spasms in clusters and an EEG pattern of hypsarrhythmia and delayed brain development or regression

Infantile spasms single spasm variant:Spasms occur singly (no other spasms for one minute before or after)

Hypsarrhythmia without  infantile spasms: Hypsarrhythmia s incidentally recorded without any evidence of clinical spasms

Infantile spasms without hypsarrhythmia: typical clincal spasms manifest in the absence of hypsarrhythmia.

Epidemiology:

Age related spectrum of disorders- most frequent type of epilepsy in the first year of life 

Incidence estimated at 2-5/10000 newborns and prevalence around 1-2/10000 children at 10 years of age with onset within one year of life in 90% of cases

Peak between 4 to 7 months with male to female ratio of 6:4 

Late onset occurrence of spasms upto 14 yearsof age has been reported in rare cases

Clinical feature

A clinical spasm consists of an abrupt, brief contraction followed by less intense but sustained tonic contraction lasting approximately from a fraction of a second to 1-2 seconds, which involves muscles of the neck, trunk and upper and lower limbs

Spasms may be flexor, extensor or mixed (most common is flexor involving head and arms)

Jerks occur mostly in clusters, typically just before, or on awakening or just before sleep.

During an attack, arrest, deviation of the eyes and/or changes in respiratory pattern may be seen. 

Cry or scream may precede or follow

After the crisis, children may show irritability or transient hyporeactivity.

What is the characteristic clinical pattern?    

The pattern of hypsarrhythmia consists of a chaotic and disorganized basal activity with asynchronous large amplitude slow waves mixed with single, multifocal spikes and sharp waves followed by attenuation.

Atypical or modified hyparrhythmia may be seen as assymmetric, focal discharges,semi periodic burst suppression, generalized complex, and partial preservation of background rhythm.

A normal EEG excludes the diagnosis of infantile spasm.

Cognitive status:

Developmental delay is usually severe, however some patients may have partially or totally preserved cognitive profiles (Cryptogenetic group)

Psychomotor retardation can precede the onset of spasms but may occur at the same time or just later on.

Developmetal delay assessment may be unreliable-no longer regarded as a diagnostic criterion

Motor and visual defects may also be present

Etiology

May be etiologically distinguished into 3 groups:

Symptomatic: Cases resulting from an identified underlying disorder

Cryptogenic: Cases with neurological symptoms, signs or developmental delay but no proven cause or etiology

Idiopathic: Cases in which spasms occur without any identifiable underlying cause, other neurological signs or symptoms.

Common causes:

Common causes include

Hypoxic ischemic encephalopathy-10%

Chromosomal anomalies-8%

Malformation-8%

Perinatal stroke-8%

Tuberous sclerosis complex-7%

Periventricular leukomalacia or hemorrhage-5%

Immune mediated mechanisms 

Chromosomal anomalies associated with infantile spasms:

Deletion 1p36 syndrome

Williams syndrome plus(Del 7q11.23)

Pallister-Killiam syndrome(Tetrasomy 12p)

Duplication 15q syndrome

Miller Dieker syndrome(Del 17p13)

Down syndrome

Association between infantile spasms and certain inborn errors of metabolism has been recognised:

Phenylketonuria

Nonketotic hyperglycinema or Glycine encephalopathy

DEND(Developmental delay, epilepsy, neonatal diabetes)

Menke’s Disease

Organic acidemias

Methylmalonic acidemia

Maple syrup urine disease

Propionic  acidemia

Therapeutic strategies

Aim of treatment

Block epileptic attacks and their relapses

Normalize the EEG anomalies

Avoid and improve neurodevelopmental delay

Treatment response is defined effective when there is complete cessation of spasms (absence of spasms within 14 days of onset of treatment and about 28 consecutive days from the last spasm) and abolition of hypsarrhythmic pattern

ACTH THERAPY

Most effective treatment for the short term therapy of Infantile spasms

Spectrum of dosage 20-120IU/L

High dose ACTH considered more effective as it allows passage of more ACTH across blood-brain barrier leading to direct action on nervous system

Side effects include irritability, increased appetite and cushingoid features. Hypertension, hypokalemia and rarely fulminant infections secondary to immunosuppression may also occur.

Mechanisms of action

May act through the POMC-positive neurons of the arcuate nucleas of the hypothalamusand the nucleas of tractus solitarius favouring the access of ACTH into the brain

May also stmulate producton of neurosteroids in the periphery, exerting anticonvulsant action

May increase sysnthesis of deoxycorticosteroids, whch can be converted into the neurosteroid allotetrahydrodeoxycorticosterone, which in turn is a modulator or GABA and also a strong anticonvulsant

VIGABATRIN

Also considered a treatment of choice for short term therapy of Infantile spasms (Drug of choice in Iss associated with tuberous sclerosis)

Initial doasge of 50mg/kg/day upto 150mg/kg/day

Side effects include hypotonia, somnolence or insomnia along with visual field constriction

Children on vigabatrin must receive periodic full ophthalmic evaluation from the initiation of therapy:every 3 months during vigabatrin adminstration and then every 3-6 months after cessation of therapy.

OTHER OPTIONS

Topiramate(3mg/kg/day) also used as first line therapy but found to be less effective.

Sodium Valproate(20-300mg/kg/day) with fairly good results with monotherapy at 30mg/kg/day

Zonisamide(4-8mg/kg/day)

Lamotrigine(6-10mg/kg/day) is no longer recommended since the dosage should slowly be increased over two months

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