West syndrome: what is it, causes, symptoms, treatment, prognosis

What is West Syndrome?

West syndrome Is a collection of symptoms characterized by epileptic / infantile spasms, abnormal brain wave patterns called hypsarrhythmias, and mental impairment.

The spasms that occur can range from violent involuntary contractions of the head, eyes, and trunk to extension of the legs and arms. These seizures usually begin in the first months after the baby is born and sometimes resolve after treatment. They can also occur in older patients; if they do, they are called "epileptic spasms" and not infantile spasms.

West syndrome most often begins in children between the ages of 4 and 8 months.

Signs and symptoms

Symptoms associated with West syndrome usually begin within the first year of life. The average age at onset of epileptic spasms is 6 months. Epileptic spasms are characterized by involuntary muscle spasmsresulting from episodes of uncontrolled electrical disturbances in the brain (seizures).

Each involuntary spasm starts suddenly and lasts only a few seconds and usually occurs in clusters that can last more than 10-20 minutes. Such episodes, which usually occur on waking or after feeding, are characterized by sudden involuntary contractions of the head, neck and trunk and / or uncontrolled extension of the legs and / or arms. The duration, intensity, and muscle groups affected by seizures vary from infant to infant.

Babies with West Syndrome also have very abnormal electroencephalogram (EEG) with high amplitude, chaotic wave-like patterns (hypsarrhythmia). Most children experience regression of skills or delays in acquiring skills that require muscle coordination and voluntary movement (psychomotor retardation).

About a third of children with West syndrome may develop recurrent seizures as they age. The syndrome often develops into Lennox-Gastaut syndrome with mixed types epilepsythat are difficult to control and are associated with mental retardation. In about a third of children with West syndrome, epileptic spasms will continue into adulthood. In the last third to a quarter of patients, seizures will go away over time, usually those patients who do not have a clear etiology (cause).

Causes

The specific cause of West syndrome can be identified in about 70-75% of patients. Any disorder that causes brain damage can be a major cause of West Syndrome, including:

• trauma;
• malformations of the brain, such as hemimegalencephaly or dysplasia of the cortex;
• infections;
• chromosomal abnormalities such as Down syndrome;
• neurocutaneous disorders such as complex tuberous sclerosis (CCC), Sturge-Weber disease;
• various metabolic / genetic diseases such as pyridoxine deficiency, non-ketotic hyperglycemia, maple syrup disease, phenylketonuria, mitochondrial encephalopathy and biotinidase deficiency, Otahar syndrome, and an abnormality (mutation) in the ARX or CDKL5 gene located on the X chromosome.

The most common disease causing West syndrome is tuberous sclerosis complex (TSC). CCC is an autosomal dominant genetic disorder associated with seizures, tumors of the eyes, heart and kidneys, and skin diseases. Dominant genetic disorders occur when only one copy of a “defective” gene is needed to cause a specific disease. The defective gene can be inherited from either parent or be the result of a mutation (change) in a gene in a sick person. The risk of passing a defective gene from a sick parent to offspring is 50% for each pregnancy. The risk is the same for men and women.

X-linked West syndrome can be caused by a mutation in the CDKL5 or ARX gene on the X chromosome. X-linked genetic disorders are conditions caused by a defective gene on the X chromosome and occur mainly in males. Women with a defective gene on one of their X chromosomes are carriers of the disorder. Carrier women usually show no symptoms because women have two X chromosomes and only one carries the defective gene. Men have one X chromosome inherited from their mother, and if a man inherits an X chromosome containing the defective gene, he will develop the disease.

Women who are carriers of X-related disorder have a 25% chance of giving birth to a carrier daughter like themselves in every pregnancy, 25% chance of giving birth to a daughter who is not a carrier of the disease, 25% chance of having a son affected by the disease, and 25% chance of giving birth healthy son.

If a man with an X-linked disorder is able to reproduce, he will pass the defective gene to all of his daughters who carry the disease. A man cannot pass on his X-linked gene to his sons because men always pass the Y chromosome instead of the X chromosome to male offspring.

Affected populations

West syndrome is a rare neurological syndrome that affects men and women. The X-linked form of West syndrome affects men more often than women.

The disease is estimated to affect 0.31 per 1,000 live births in the United States. There are no data available for Russia.

West syndrome accounts for approximately 30% of all cases of epilepsy in children.

Diagnostics

The first step is to identify the characteristics of brain activity by performing various studies. Among them:

• Electroencephalography (EEG): it is a painless and non-invasive way of recording the electrical activity of the brain. Electrodes are attached to the scalp to pick up and record electrical vibrations during periods of activity and, if you're lucky, during periods of sleep. If there is a pattern (characteristic) called hypsarrhythmia, especially during sleep, it may suggest that the patient has epileptic spasms. However, there are times when a patient may have epileptic spasms, but there is no pattern of hypsarrhythmia due to the delay between clinical symptoms and the EEG pattern. In addition, there are several diseases that mimic epileptic spasms, and long-term video EEG monitoring can confirm the diagnosis of epileptic spasms. Therefore, in the case of epileptic spasms, it is preferable to conduct long-term video-EEG monitoring during the night than the usual 20-minute EEG study.
• Brain scan, For example:
  • Computed tomography (CT). With CT, as a result of the use of X-rays, images of sections of the brain are created on a computer, from which you can find out the details of the development of the process. CT is also very good at showing areas of calcification, which in some cases can be important for diagnosis. However, CT is not as detailed as an MRI.
  • Magnetic resonance imaging (MRI). This radiological examination technique creates detailed cross-sectional or sectional images of the brain using the magnetic properties of certain atoms found in the brain. Images are more detailed than CT scans and can provide information about any malformations of brain structures or other types of lesions commonly seen in epileptic spasms.

Infection as a cause of epileptic spasms can be determined with blood tests, urine tests, and lumbar puncture.

A Wood's lamp is used to examine the skin for lesions with a lack of pigment to determine if tuberous sclerosis is a possible diagnosis.

Molecular genetic testing is available to identify mutations in the ARX and CDKL5 genes associated with X-linked West syndrome. It is also available for genes associated with tuberous sclerosis. Some genetic disorders require cerebrospinal fluid (CSF) for genetic testing.

Symptomatic Disorders

Symptoms of the following disorders may be similar to those of West Syndrome. Comparisons can be useful for differential diagnosis:

Epilepsy - a group of neurological disorders characterized by abnormal electrical discharges in the brain. It is characterized by loss of consciousness, seizures, confusion and disorders of the autonomic nervous system. Seizures are often preceded by an aura, feeling of anxiety, or sensory discomfort; an aura marks the onset of seizures in the brain. There are many different types of epilepsy, and the exact cause is usually unknown. West syndrome is a type of epilepsy.

Lennox-Gastaut syndrome (SLH) Is a rare type of epileptic disorder that occurs during infancy or early childhood. The disorder is characterized by seizures and, in many cases, abnormal delays in the acquisition of skills that require coordination of mental and muscular activity (psychomotor delays). People with the disorder can experience several different types of seizures. Lennox-Gastaut syndrome can be caused by a number of different disorders or conditions.

Myoclonic seizures (seizures) - observed in numerous types of epilepsy, ranging from myoclonic epilepsy in infancy to Dravet syndrome or myoclonic astatic epilepsy, and they are often confused with infantile infantile spasms. The seizures are manifested by rapid twitching of the arms and legs, more quickly than with infantile spasms, and sometimes occur separately, and not as with West syndrome, which usually occur in clusters.

Since epileptic spasms are very subtle seizures with small, short movements of the trunk or arms, it is easy to confuse it with gastroesophageal reflux and other types of non-neurological diseases.

Myoclonus - a neurological movement disorder in which sudden involuntary muscle contractions occur. There are many different types of myoclonus, including hereditary ones. Other causes are lack of oxygen, viruses, malignant neoplasms and central nervous system damage, as well as drugs and metabolic disorders.

Treatment of West syndrome

Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists, surgeons, and / or other healthcare professionals may need to systematically and comprehensively plan treatment for a sick child.

In some cases, treatment with anticonvulsants can help reduce or control the various types of seizure activity associated with West syndrome. The most common drugs used to treat epileptic spasms include:

• Adrenocorticotropic hormone (ACTH);
• Prednisone;
• Vigabatrin and Pyridoxine.

The benefits of a drug are weighed against the risk of side effects with each treatment.

For example, ACTH, prednisone, and other steroids are known to cause problems with immunosuppression, arterial hypertension, glucose level, gastrointestinal problems, anxiety and irritability.

Vigabatrin can cause irreversible visual field defects, irritability, and transient hyperintensity of deep structures on MRI.

There is no standard protocol for the use of ACTH or other steroids. It is also unknown whether high or low dose ACTH is effective or whether prednisone is more effective than ACTH.

In a recent multicenter study of steroid or vigabatrin treatment, it was noted that steroids can better control of seizures compared with vigabatrin after 2 weeks of treatment, but the effectiveness remains the same after a year the same. In addition, vigabatrin was more effective in patients with tuberous sclerosis or cortical dysplasia than steroids.

More recently, a multicenter European / Australian / New Zealand consortium found that hormonal Vigabatrin therapy is significantly more effective in relieving infantile spasms than hormonal therapy alone therapy.

In the United States, research continues in the field of combination hormone therapy and the use of vigabatrin.

It is believed that a shorter time interval between diagnosis and treatment will have a better effect on the course of the disease compared to a longer waiting time for treatment.

If the above medications for treatment do not work, other medications may be used, such as:

• Benzodiazepines (eg, clonazepam);
• Valproic acid;
• Topiramate;
• Rufinamide and Zonisamide.

The ketogenic diet has also helped in some cases in the treatment of epileptic spasms. Finally, in cases where there is a complex of malformations or tuberous sclerosis, surgical treatment of epilepsy can help with spasms.

Forecast

The long-term overall prognosis for patients with infantile spasms is poor and is directly related to the etiology of the condition. Children with idiopathic infantile spasms have a better prognosis than children with symptomatic spasms. Only 14% of infants with symptomatic West syndrome have normal or borderline normal cognitive development, compared with 28-50% of infants with idiopathic spasms. Mental retardation in 70% of patients is severe, often with mental problems such as autism or hyperactivity.

Rarely, seizures may persist into adulthood. It has been found that 50-70% of patients develop other types of seizures, and 18-50% of patients develops Lennox-Gastaut syndrome or some other form of symptomatic generalized epilepsy.

Subgroups of patients in the symptomatic infantile spasm group appear to have a better prognosis. A retrospective study of 17 children with trisomy 21 and infantile spasms found that 13 out of 16 survivors remained seizure-free for more than 1 year and that 10 patients no longer took anticonvulsants drugs.

A study of 15 children with type 1 neurofibromatosis and seizures also reported a relatively benign seizure and cognitive outcome.