West syndrome

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Infantile spasms; infantile epileptic encephalopathy; jackknife convulsions; massive myoclonus; salaam spasms

Overview

West syndrome, is an uncommon to rare and serious form of epilepsy in infants. The triad of developmental regression, infantile spasms and pattern of hypsarrhythmia on EEG is termed as west syndrome. The syndrome is age-related, generally occurring between the third and the twelfth month, generally manifesting around the fifth month. There are various causes ("polyetiology"). The syndrome is often caused by an organic brain dysfunction whose origins may be prenatal, perinatal (caused during birth) or postnatal.

Historical Perspecitve

West syndrome was named after the English doctor and surgeon William James West (1793-1848), who lived in Tonbridge. In 1841 he observed this type of epilepsy in his own son, who was approximately four months old at the time. He published his observations from a scientific perspective in an article in The Lancet. He named the seizures "Salaam Tics" at the time.

Pathophysiology

It is still unknown which bio-chemical mechanisms lead to the occurrence of West syndrome. It is conjectured that it is a malfunction of the neurotransmitter function, or more precisely, a malfunction in the regulation of the GABA transmission process. Another possibility being researched is a hyper-production of the Corticotropin-releasing hormone (CRH). It is possible that more than one factor is involved. Both hypotheses are supported by the effect of certain medications used to treat West syndrome.

Causes

If a cause presents itself, the syndrome is referred to as symptomatic West syndrome, as the attacks manifest as a symptom of another anomaly. These are the possible causes being considered:

• In around one third of the children, there is evidence of a profound organic disorder of the brain. This includes:
  • Microcephaly
  • Cortical dysplasia
  • Cerebral atrophy
  • Lissencephaly
  • Bacterial meningitis
  • Phakomatosis (e.g. bourneville's disease)
  • Aicardi syndrome
  • Tuberous sclerosis
  • Cephalhematoma and
  • Vascular malformation.

• Furthermore, other causes increasingly being named in the literature are:
  • Incontinentia pigmenti
  • Foix-Chavany-Marie syndrome
  • Patau syndrome (trisomy 13)
  • Sturge-Weber syndrome
  • Neurometabolic diseases
  • Congential infections (e.g. Cytomegalovirus)
  • Hypoglycemia
  • Brain damage due to asphyxiation or hypoxia (lack of oxygen, e.g. during birth), periventricular leukomalacia, cephalhematoma, cerebrovascular accident or brain damage of various types as well as that caused by premature birth.

• There are known cases in which the spasms occurred for the first time after vaccination against Measles, Mumps and Rubella or Tetanus, Pertussis, Diphtheria, Polio, Hepatitis B and Haemophilus influenzae Type B. However, stress of any kind is a common trigger for seizures, and the immunization occurs during the time-frame in which many typical cases become conspicuous. There is no causal relationship between immunization and West syndrome, since in many cases West syndrome is not recognized as iatrogenic.

West syndrome in Down syndrome babies

On average, West syndrome appears in 1 to 5 per 100 children with Down's syndrome as babies. Whereas this form of epilepsy is relatively difficult to treat in children who do not have the chromosomal differences involved in Down's syndrome, the syndrome often affects those who do far more mildly and they often react better to medication. The German Down Syndrom InfoCenter noted in 2003 that what was normally a serious epilepsy was in such cases often a relatively benign one.

EEG records for Down's syndrome children are often more symmetrical with fewer unusual findings. Although not all children can become entirely free from attacks with medication, children with Down's syndrome are less likely to go on to develop Lennox-Gastaut syndrome or other forms of epilepsy than those without additional hereditary material on the 21st chromosome. The reason why it is easier to treat children with Down's syndrome is not known.

Cryptogenic

When a direct cause cannot be determined but the children has other neurological disorder, the case is referred to as cryptogenic West syndrome, where an underlying cause is most likely but even with our modern means cannot be detected.

Sometimes multiple children within the same family develop West syndrome. In this case it is also referred to as cryptogenic, in which genetic and sometimes hereditary influences play a role. There are known cases in which West syndrome appears in successive generations in boys; this has to do with X-chromosomal heredity.

Idiopathic

Occasionally the syndrome is referred to as idiopathic West syndrome, when a cause cannot be determined. Important diagnostic criteria are:

• Regular development until the onset of the attacks or before the beginning of the therapy
• no pathological findings in neurological or neuroradiological studies
• no evidence of a trigger for the spasms

Those are becoming rare due to modern medicine.

Epidemiology and Demography

Prevalence is around 1:4000 to 1:6000.

Age

In 45 out of every 50 children affected, the spasms appear for the first time between the third and the twelfth month of age. In rarer cases, spasms may occur in the first two months or during the second to fourth year of age.

Gender

Statistically, boys are more likely to be affected than girls at a ratio of around 3:2.

Natural History, Complications and Prognosis

Complications

• Cognitive disabilities
• Learning difficulties
• Behavioural problems
• Cerebral palsy (up to 5 out of 10 children)
• Psychological disorders
• Autism

Prognosis

It is not possible to make a generalised prognosis for development due to the variability of causes, as mentioned above, 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. Idiopathic cases are less likely to show signs of developmental problems before the attacks begin, the attacks can often be treated more easily and effectively and there is a lower relapse rate. Children with this form of the syndrome are less likely to go on to develop other forms of epilepsy; around two in every five children develop at the same rate as healthy children.

In other cases, however, treatment of West syndrome is relatively difficult and the results of therapy often dissatisfying; for children with symptomatic and cryptogenic West syndrome, the prognosis is generally not positive, especially when they prove resistant to therapy.

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.

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). Severe, frequent attacks can (further) damage the brain.

As many as 6 out of 10 children with West syndrome suffer from epilepsy later in life. Sometimes West syndrome turns into a focal or other generalised epilepsy. Around half of all children develop Lennox-Gastaut syndrome.

Diagnosis

The epileptic seizures which can be observed in infants with West syndrome fall into three categories. Typically, the following triad of attack types appears; while the three types usually appear simultaneously, they also can occur independently of each other:

• Lightning attacks: Sudden, severe myoclonic convulsions of the entire body or several parts of the body in split seconds, and the legs in particular are bent (flexor muscle convulsions here are generally more severe than extensor ones).
• Nodding attacks: Convulsions of the throat and neck flexor muscles, during which the chin is fitfully jerked towards the breast or the head is drawn inward.
• 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 and/or flailing. If one imagined this act in slow motion, it would appear similar to the oriental ceremonial greeting (Salaam), from which this type of attack derives its name.

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.

Insufficient research has yet been carried out into whether the form of treatment has an effect upon the long-term prognosis. Based on what is known today, the prognosis depends mainly on the cause of the attacks and the length of time that hypsarrhythmia lasts. In general it can be said that the prognosis is worse when the patient does not react as well to therapy and the epileptic over-activity in the brain continues. Treatment differs in each individual case and depends on the cause of the West syndrome (etiological classification) and the state of brain development at the time of the damage.

Due to their side-effects, two drugs are currently being used as the first-line treatment.

• ACTH - Use primarily in United States
  • Side effects are: Weight gain, especially in the trunk and face, hypertension, metabolic abnormalities, severe irritability, osteoporosis, sepsis, and congestive heart failure.
• Vigabatrin (Sabril) - Approved in several countries, like most Europe, Canada and Mexico.
  • Side effects are: Somnolence, headache, dizziness, fatigue, weight gain, decreased vision or other vision changes

Vigabatrin is known for being effective, especially in children with tuberous sclerosis, with few and benign side effects. But due to some recent studies showing visual field constriction (loss of peripheral vision), it is not yet approved in United States. It is currently debated that a short use (6 months or less) of Vigabatrin will not affect vision. Also, considering the effect of frequent seizures on day to day life and mental development, some parents prefer to take the risk of some vision loss.

When those two are proving ineffective, other drugs may be used in conjunction or alone. topiramate (Topamax), lamotrigine (Lamictal), levetiracetam (Keppra) and zonisamide (Zonegran) are amongst the most widely use.

The ketogenic diet have been tested and his shown to be effective, up to 70% of children having a 50% or more reduction in seizure.

References

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