X-linked infantile spasm syndrome
West syndrome is characterized by a specific type of seizure (infantile spasms) seen in infancy and childhood. This syndrome leads to developmental regression and causes a specific pattern, known as hypsarrhythmia (chaotic brain waves), on electroencephalography (EEG) testing. The infantile spasms usually begin in the first year of life, typically between 4-8 months. The seizures primarily consist of a sudden bending forward of the body with stiffening of the arms and legs; some children arch their backs as they extend their arms and legs. Spasms tend to occur upon awakening or after feeding, and often occur in clusters of up to 100 spasms at a time. Infants may have dozens of clusters and several hundred spasms per day. Infantile spasms usually stop by age five, but may be replaced by other types of seizures. Many underlying disorders, such as birth injury, metabolic disorders, and genetic disorders can lead to these spasms, making it important to identify the underlying cause. In some children, no cause can be found.
The list of signs and symptoms mentioned in various sources for Infantile Spasms includes the symptoms listed below:
- Myoclonic seizures
- Cognitive impairment
- Hypsarrhythmia (chaotic electroencephalogram)
- Mental retardation
- Hypopigmented macules
- Myoclonic seizures
- Head nodding
- Mental retardation
- Visual problems
Infantile spasms are believed to reflect abnormal interactions between the cortex and brainstem structures. Focal lesions early in life may secondarily affect other sites in the brain, and hypsarrhythmia may represent this abnormal activity arising from multiple brain sites. The frequent onset of infantile spasms in infancy suggests that an immature central nervous system (CNS) may be important in the syndrome’s pathogenesis.
The brain-adrenal axis also may be involved. One theory states that the effect of different stressors in the immature brain produces an abnormal, excessive secretion of corticotropin-releasing hormone (CRH), causing spasms. The clinical response to adrenocorticotropic hormone (ACTH) and glucocorticoids can be explained by the suppression of CRH production.
The diagnosis of infantile spasms is made by a combination of the typical features with a typical EEG. The EEG shows a very disorganised pattern called ‘hypsarrhythmia’. The EEG is always abnormal in children with West syndrome but sometimes this abnormality is seen only during sleep. Infantile spasms, like many other ‘electroclinical syndromes’, have lots of different causes. A particular cause will be found in seven or eight out of every 10 children with West syndrome.
Most children with infantile spasms will need a number of tests apart from the EEG. These include brain scans, blood tests, urine tests and, sometimes, spinal fluid and other tests in order to try to identify the underlying cause. The most important brain scan is the magnetic resonance imaging (MRI) scan.
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 1 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 9%) 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. 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 1 children), psychological disorders and often autism (in around 3 out of 1 children). Once more, the etiology of each individual case of West syndrome must be considered when debating cause and effect. As many as 6 out of 1 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.
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.
Prednisone - The NINDS Infantile Spasms Information Page (published by the National Institutes of Health (U.S.) states that "Treatment with corticosteroids such as prednisone is standard, although serious side effects can occur."
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, including most of Europe, Canada, Mexico, and more recently the United States.
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 was not approved in the United States until mid-2009. 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.
Other drugs may be used in conjunction or alone. In Japan, there is a good experience with pyridoxine therapy. Further, topiramate (Topamax), lamotrigine (Lamictal), levetiracetam (Keppra) and zonisamide (Zonegran) are amongst those drugs most widely used.
The ketogenic diet has been shown to be effective in treating infantile spams, up to 70% of children having a 50% or more reduction in seizure.
See Research Publications.