West's syndrome

West syndrome is a severe epilepsy syndrome consisting of a triad of symptoms: infantile spasms, characteristic changes in the interictal period of the electroencephalogram (hypsarrhythmia) and mental retardation. The disease received its name thanks to the British doctor West, who first described all its symptoms in 1841, observing his sick son. This disease is also known under the following names: Gibbs' hypsarrhythmia, bowing spasms, Salaam's spasm or tic, myoclonic encephalopathy with hypsarrhythmia.

Epidemiology

The incidence is about 1:3200 to 1:3500 live births. According to statistics, the syndrome develops more often in boys than in girls in a ratio of about 1.3:1. In 9 out of every 10 affected children, spasms first appear between the 3rd and 8th month of life. In rare cases, convulsions may occur during the first 2 months.

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Causes West syndrome

It can be classified as a group of so-called encephalopathic epilepsies, when seizures occur against the background of non-inflammatory diseases of the brain.

This disease most often occurs in early childhood and has many causes:

1. Congenital pathology in the development of the brain (for example, tuberous sclerosis).
2. Genetic diseases, gene mutations and metabolic disorders.
3. Brain infections.
4. Birth intracranial hemorrhage, brain hypoxia (especially in premature babies).
5. Asphyxia.

It is the latter reason that is considered the most common in the development of this dangerous syndrome. Fetal asphyxia often develops as a result of complicated labor.

The role of genetic defects in the etiology of West syndrome is discussed. Two genetic defects have been identified. The first is a mutation in the short arm of the X chromosome. The ARX gene is associated with early onset of infantile spasms. The second is a defect in cyclin-dependent kinase and protein 5 (CDKL5).

Sometimes it is quite difficult to determine what exactly influenced the manifestation of the syndrome. In such cases, doctors diagnose idiopathic syndrome. Those patients who have no signs of the disease, but have changes in the EEG (or vice versa) are classified as risk group 1. They do not need special treatment, but they are required to undergo an annual examination.

If there are the main signs and changes in the EEG, then the patients are assigned to the 2nd risk group. They are prescribed a certain treatment. They also undergo examination twice a year. The last risk group is those who have pronounced symptoms and changes in the EEG.

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Risk factors

Prenatal disorders associated with infantile spasms include:

• Hydrocephalus.
• Microcephaly.
• Hydroanencephaly.
• Schizencephaly.
• Polymicrogyria.
• Sturge-Weber syndrome.
• Tuberous sclerosis.
• Trisomy 21.
• Hypoxic-ischemic encephalopathy.
• Congenital infections.
• Injuries.

Perinatal disorders that lead to the development of West syndrome are the following:

• Hypoxic-ischemic encephalopathy.
• Meningitis.
• Encephalitis.
• Injuries.
• Intracranial hemorrhages.

Postpartum disorders:

• Hyperglycemia.
• Maple syrup disease.
• Phenylketonuria.
• Mitochondrial encephalopathy.
• Meningitis.
• Encephalitis.
• Degenerative diseases.
• Biotinidase deficiency.
• Injuries.

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Pathogenesis

Infantile spasms are thought to arise from abnormal interactions between the cortex and brainstem structures. The main factors in the pathogenesis are immaturity of the central nervous system and impaired feedback of the brain-adrenal axis. Under the influence of various stress factors, the immature brain produces abnormal, excessive secretion of corticotropin-releasing hormone (CRH), resulting in spasms.

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Symptoms West syndrome

Among the symptoms of this disease, the following should be highlighted:

1. Frequent epileptic seizures. They are quite difficult to cure.
2. Changes in the EEG (hypsarrhythmia) characteristic of this disease.
3. Clear disturbances in psychomotor development.

Almost all children with West syndrome (90%) show symptoms almost immediately after birth (4 to 8 months). The seizures are short-lived, so it is not possible to make a correct diagnosis right away.

West syndrome is considered a serious disease that threatens the life of the patient. It is also called infantile spasms.

The attack always occurs in the same way: the child's entire body bends forward sharply, and the head bends strongly. Such convulsions usually occur when the baby wakes up or falls asleep. There can be from ten to a hundred attacks in one day.

Often during attacks, the child may lose consciousness. Because of them, infants experience delays in psychomotor development. Children with West syndrome react poorly to the environment and practically do not make contact with relatives.

First signs

The first sign of an attack of West syndrome is a child's loud crying, so doctors often diagnose such babies with colic. Standard signs of this disease include:

1. Strong forward bends of the entire body.
2. Generalized convulsions in the lower and upper limbs, the entire body.
3. The limbs involuntarily spread apart.

Usually such an attack lasts no more than one or two seconds. There is a short pause and the attack resumes again. In some cases, spasms are isolated, but most often they occur in succession.

Children with West syndrome are often very irritable, have developmental delays of varying severity, and infants with this disorder often act as if they were blind.

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Epilepsy in West syndrome

West syndrome is a variant of generalized epilepsy of a catastrophic nature. It can be symptomatic (in most cases) or cryptogenic (only up to 10% of all cases). The classic variant of West syndrome can be characterized by pronounced salaam or myoclonic spasms. Sometimes the spasms take the form of short serial head nods.

Epilepsy in West syndrome develops due to various neurological pathologies or without certain disorders in the central nervous system. Infantile spasms lead to slow development of mental and motor functions of the child, which in the future can cause a significant delay in general development.

In 80% of cases, children with West syndrome have cerebral palsy, microcephaly, atonic and atactic disorders.

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Encephalopathy in West syndrome

As mentioned above, West syndrome is also known as myoclonic encephalopathy with hypsarrhythmia. Hypsarrhythmia is a typical but not pathognomonic EEG pattern in patients with this disorder.

Standard hypsarrhythmia is characterized by continuous arrhythmic and high-amplitude slow-wave activity, and also has numerous spikes and sharp waves. At the same time, there is no synchronization between different parts of the hemispheres. Sometimes patterns may differ in amplitude asymmetry.

Hypsarrhythmia almost completely replaces the main background activity.

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Symptomatic West syndrome

As a rule, in 75% of cases, West syndrome begins during the second or third quarter of the baby's life. The first months of the child's development seem quite normal and only then do seizures appear, which are the pathognomonic first sign. Sometimes patients experience a delay in psychomotor development. Very rarely, changes in the EEG can be seen.

Myoclonus or muscle spasms affect almost the entire body. During such seizures, the baby's body and limbs bend. Spasms and contractions in the flexor muscles can be bilateral, synchronous, sudden, symmetrical and last a maximum of 10 seconds. Sometimes they are repeated up to a hundred times a day.

In some cases, a convulsive attack may affect only one muscle group. The lower and upper limbs are thrown to the sides during the convulsions, the head bends and lies on the chest. If the frequency of attacks is high, the child may fall asleep.

Today, there are three distinct variants of West syndrome, which differ from each other in the degree and nature of muscle damage:

1. Nodding - multiple flexion cramps (especially in the upper limbs and head).
2. Occipital spasms - the head is thrown back. The attacks last up to ten seconds with a one-second break.
3. Common cramps are cramps throughout the entire body. The head "lies" on the chest, and the limbs are pulled to the sides.

Children with West syndrome show delays in motor and mental development immediately after birth or after six months. Frequent seizures only make the situation worse.

Cerebellar syndrome in West syndrome

In some cases, West syndrome may be accompanied by cerebellar syndrome. This is a lesion of the cerebellum or a disruption of its connections with other parts of the brain. The main signs of cerebellar syndrome are:

1. Intentional tremors of the fingers (especially during movement).
2. Adiodochokinesis.
3. Muscle weakness and flabbiness.
4. A symptom of lack of reverse thrust appears.
5. Systemic dizziness.

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Complications and consequences

The course of West syndrome is quite severe in almost all cases, as it manifests itself in serious brain disorders. Very rarely, this disease can be cured with conservative treatment. But usually, even after effective therapy, relapses occur over time.

Almost always after the patient's recovery, serious and rather severe neurological residual effects are noted: epilepsy and its equivalents, extrapyramidal manifestations. Patients also exhibit mental disorders: idiocy or mild dementia.

Only in 2% of cases (according to Gibbs) does spontaneous complete recovery occur.

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Diagnostics West syndrome

West syndrome is diagnosed by the following doctors: neurosurgeon, epileptologist, neurologist, pediatrician, immunologist, endoscopist and endocrinologist. Thanks to the use of modern devices, a more accurate diagnosis can be made. The following are commonly used: radiomagnetic and computed tomography, cranioscopy (in very rare cases), cerebroangiography. Neurophysiological examinations are also carried out to identify the pathological focus of epileptic seizures.

The most popular methods for diagnosing West syndrome are: electroencephalography and gas encephalography.

Electroencephalography can detect hypsarrhythmia of biological curves:

1. The amplitude of biological curves is irregular.
2. There is no synchronization of the main curves. "Curve peaks" may appear during sleep or wakefulness.
3. Low efficiency of light stimulation.

In some cases, gas electroencephalography can show dilation of the cerebral ventricles. In the later stages of West syndrome, hydrocephalus is observed.

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Differential diagnosis

West syndrome can be differentiated from both non-epileptic diseases that are common in infancy (colic, motor restlessness, infantile masturbation, hyperexplexia, respiratory attack) and some epileptic syndromes (for example, focal epilepsy). Electroencephalography plays a very important role in differential diagnostics.

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Treatment West syndrome

Treatment is individual in each specific case and depends on the cause of West syndrome and the state of brain development.

The main method of treating West syndrome today is steroid therapy with adrenocorticotropic hormone (ACTH) (Sabril, vigabatrin). But such treatment should be extremely careful and takes place under strict medical supervision, since both steroid drugs and vigabatrin have many serious side effects. It is also necessary to select suitable anticonvulsants, as well as drugs that will help normalize the blood supply to the brain.

Sometimes a neurosurgeon must perform an operation during which the adhesions of the meninges are dissected and the pathological focus with congenital vascular aneurysms is removed. This procedure is performed using stereotactic surgery and various endoscopic methods. A new and rather expensive method of treating West syndrome is the use of stem cells. It is considered effective, but unpopular due to the high cost of the procedure.

The essence of this method is that the damaged area of the brain is restored with the help of stem cells.

The idiopathic form of West syndrome is usually treated with special medications:

1. Anticonvulsants – such as Epilim, Nitrazepam, Depakote (valproate), Topamax (topiramate), Zonegran (zonisamide), Onfi (clobazam), or Klonopin (clonazepam).
2. Steroid hormonal drugs - for example, Hydrocortisone, Prednisolone, Tetracosactide.
3. Vitamins – for example, vitamin B6 (pyridoxine).

Therapy is effective if the number and frequency of seizures decreases. With the right therapy, the child will develop and learn normally in the future.

But it is worth understanding that even modern drugs have many side effects:

1. Loss of concentration.
2. Fatigue.
3. Allergic skin reactions.
4. Depression.
5. Nerve damage.
6. Liver failure.

Exercise therapy for West syndrome

Physiotherapy for West syndrome should be carried out under the strict supervision of a rehabilitation specialist and a sports medicine doctor, so as not to aggravate seizures. This method of therapy is quite popular, but does not give effective results without a complex of medications.

Cases of cure

The absence of attacks for a long time with West syndrome cannot indicate that the disease has entered the remission stage. But some doctors believe that if spasms, convulsions, hypsarrhythmia and changes in the EEG have not been noticed for a month, then this can be considered recovery. Unfortunately, such cases are quite rare today. According to some sources, only 8% of all patients are completely cured, according to Gibbs this number reaches only 2%.

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Prevention

The main measure of prevention of West syndrome is its timely diagnosis and proper treatment. Epileptic seizures, which are considered the main symptom of this disease, must be stabilized.

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Forecast

The general prognosis for the development of West syndrome is quite difficult to predict, since there are different reasons for its occurrence. For example, with idiopathic syndrome, the prognosis is more favorable than in the case of symptomatic syndrome.

This can be explained by the fact that the idiopathic form of this disease is much easier: the frequency and strength of attacks are less, the child does not lag behind in development as much. Usually, the disease in such infants transforms into other forms of epilepsy. In the future, about 40% of such children do not differ from their peers.

In other cases, treatment is more complex and its results are less effective. If children with symptomatic West syndrome are found to be intolerant to drugs, then therapy is more complicated. Less than 50% of such patients achieve remission. According to research results, only 30% of patients are completely or almost completely cured with medication.

Unfortunately, 90% of all patients with West syndrome are physically or mentally retarded, regardless of the effectiveness of treatment. This is because the seizures often permanently damage parts of the brain.

60% of all children who had West syndrome will have any form of epilepsy in the future. Sometimes the disease transforms into Lennox-Gastaut syndrome.

Favorable prognostic factors:

• Cryptogenic or idiopathic etiology.
• Development of the disease at the age of more than 4 months.
• Absence of atypical seizures.
• Absence of asymmetric EEG abnormalities.
• The effectiveness of the treatment.

According to research, 5% of children with West syndrome do not survive to age five. Death occurs due to the disease or side effects of treatment. A fifth of patients die within the first year, since congenital pathologies of the brain are incompatible with life.