West Syndrome (Infantile Spasms)

The syndrome was classically described by Dr W J West in a letter to the editor of The Lancet in 1841.¹ He 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 attack would not continue more than 2 or 3 minutes; he sometimes has 2, 3 or more attacks in the day."

It was about 100 years later that the classical EEG was described. It is a very abnormal pattern called hypsarrhythmia that occurs even between attacks.

The incidence is around 1 in every 2,000 to 6,000 live births. The peak incidence is between 4 and 7 months old, with 90% starting under a year. It is confined to infants and very small children. A small number have idiopathic infantile spasms with normal growth and development prior to the onset of infantile spasms and no known aetiology.² Family history of infantile spasms is unusual but 14% may have a family history of epilepsy.³

Spasms begin with a sudden, rapid, tonic contraction of the trunk and limb muscles with gradual relaxation over 0.5 to 2 seconds. Contractions can last 5 or 10 seconds. They may range from a gentle nodding of the head to a powerful movement of the body.

• The spasms tend to occur in clusters. There may be dozens of them with a lapse of 5 to 30 seconds between each. They tend to occur just before sleep or on awaking. They can occur in sleep but this is unusual.
• Spasms can be flexor, extensor, or a mixture of both.
• Flexor spasms consist of brief contractions of the flexor muscles of the neck, trunks, and limbs, causing a brief jerk. They may resemble a self-hugging motion and often there is a cry. The child relaxes and the jerk repeats. These attacks occur in clusters throughout the day and last anywhere from less than 1 minute to 10 or 15 minutes or more in some patients.
• Extensor spasms are contractions of the extensor muscles with sudden extension of the neck and trunk with extension and abduction of the limbs.
• Mixed spasms are the commonest type, with flexion of the neck and arms with extension of the legs, or flexion of the legs with extension of the arms.
• Various series give the incidence of mixed spasms as around 40 to 50%, flexor spasms at about 35 to 40% and extensor spasms at 20 to 25%.

Between 70 and 90% have psychomotor delay or reversal.²
Physical examination usually reveals no abnormality although it may help with an underlying diagnosis like the adenoma sebaceum of tuberous sclerosis.

• Examination with Wood's lamp is often helpful to see the hypopigmented skin lesions of this condition.
• Mild to moderate growth retardation is common.
• Neurological examination reveals nothing pathognomonic although there may be vague and non-specific features reflecting brain damage, the effect of fits or medication.
• Ophthalmic examination may reveal evidence of one of the syndromes associated with the condition.

Causes can be divided into symptomatic, cryptogenic and idiopathic.

Symptomatic

Almost any disorder that can produce brain damage can be associated with infantile spasms.

• Prenatal conditions (including hydrocephalus, microcephaly, Sturge-Weber syndrome, tuberous sclerosis); genetic syndromes (such as Aicardi syndrome and Down's syndrome), hypoxic or ischaemic brain damage, congenital infections, and trauma.
• Perinatal disorders include hypoxia or ischaemia of the brain, meningitis, encephalitis, trauma, and intracranial haemorrhage.
• Postnatal disorders include pyridoxine dependency, maple syrup urine disease, phenylketonuria, meningitis, degenerative diseases, biotinidase deficiency, and trauma.

Cryptogenic

These are cases where an underlying cause is suspected but has not been found.
Incidence is given as between 8 and 42% and will obviously depend upon the degree of suspicion and the diligence in seeking a cause.

Idiopathic

Idiopathic infantile spasms are diagnosed if normal psychomotor development precedes the onset of symptoms, no underlying disorders or definite presumptive causes are present, and no neurological or neuroradiological abnormalities exist. Some people use the terms "idiopathic" and "cryptogenic" as synonymous.
Incidence is said to be between 9 and 14% but the same degree of circumspection should be applied as for cryptogenic.

• Blood tests include FBC, LFTs, renal function, glucose, calcium, magnesium and phosphate
• Blood cultures, urine examination and CSF analysis if infection is suspected
• Urine amino acids and organic acids and serum biotinidase
• Brain imaging with CT or, better, MRI should be obtained before treatment. Abnormalities are found in 70 to 80%.
• EEG is essential as hypsarrhythmia is crucial to the diagnosis. A prolonged study to obtain waking and sleeping traces may be required. Hypsarrhythmia is a characteristic interictal pattern 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. The ictal pattern has 11 different variations although one is present in about 40%. There is no correlation between the ictal patterns and the type of fit.

This is aimed at control of seizures with fewest side effects and best quality of life. The usual anticonvulsants are disappointing in this condition.

• First line of treatment is:
  • ACTH; this is effective in about 50 to 65% of cases. It involves a daily IM injection. The precise dose is not established although it seems that higher doses may have more side effects with no increased efficacy.⁴
  • Prednisolone
  • Vigabatrin; this has a success rate of about 50% but in tuberose sclerosis this rises to 95%⁵, and is the treatment of choice.⁶ The frequency of visual field defects after vigabatrin therapy needs be evaluated. In general there is not much difference between treatment with ACTH and vigabatrin in terms of control, outcome and severe side effects. The last is marked in both and the review suggested that ACTH was preferable.
• Second line treatment includes:
  Benzodiazepines, valproate, lamotrigine, topiramate or zonisamide

Pyridoxine (vitamin B6) may well have potential as being effective and less toxic than other treatments.⁷
In a few patients resection of part of the brain can give relief, especially in tuberose sclerosis.
The role of a ketogenic diet in this condition has not been established.^8,9

This very much depends on aetiology. An attempt has been made to get unified case definitions and outcome measures in studies of infantile spasms and West syndrome.¹⁰

• Those with the idiopathic form usually do better than those whose condition is symptomatic.
• Exceptions are Down's syndrome and neurofibromatosis type I, that seem to do well.
• Normal or borderline cognitive development occurs in just 14% of symptomatic cases compared with ¼ to ½ of idiopathic cases.
• Mental retardation is severe in 70%, often with features like autism or hyperactivity.
• 25 to 56% of patients develop other types of epilepsy, such as Lennox-Gastaut syndrome.

In a follow up of 25 to 35 years one third of the patients died, the intellectual outcome of the remaining patients was normal or slightly subnormal, and one quarter and one third of the patients were seizure free.⁴