West syndrome is serial spastic contractions in individual muscle groups or of a generalized nature, occurring against the background of delayed neuropsychic development and accompanied by a hypsarrhythmic EEG pattern. Manifests at the age of up to 4 years, mainly at the 1st year of life. In most cases, it has a symptomatic character. Diagnosis of the syndrome is based on clinical data and EEG results. To identify the underlying pathology, CT or MRI, PET of the brain, consultation of a geneticist, a neurosurgeon are necessary. Treatment is possible with antiepileptic drugs, steroids (ACTH, prednisone), vigabatrin. According to the indications, the issue of surgical treatment (callosotomy, removal of the pathological focus) is being resolved.
General information
West syndrome is named after a doctor who observed its manifestations in his child and first described it in 1841. Due to the manifestation of the syndrome at an early age and the course of convulsions by the type of a series of individual spasms, the paroxysms characterizing West syndrome are called infantile spasms. Initially, the disease was attributed to generalized epilepsy. In 1952, a specific hypsarrhythmic EEG pattern was studied, pathognomonic for this form of epilepsy and characterized by slow-wave asynchronous activity with random spikes of high amplitude. In 1964 specialists in the field of neurology have identified West syndrome as a separate nosology.
The introduction of neuroimaging into neurological practice made it possible to determine the presence of focal lesions of the brain substance in patients. This forced neurologists to reconsider their views on West syndrome as generalized epilepsy and attribute it to a number of epileptic encephalopathies. In 1984, the evolution of the epileptic form of encephalopathy was revealed from its early variant into West syndrome, and over time into Lennox-Gastaut syndrome.
Currently, West syndrome accounts for about 2% of all cases of epilepsy in children and about a quarter of infant epilepsy. The prevalence, according to various sources, ranges from 2 to 4.5 cases per 10 thousand newborns. Boys are slightly more likely to get sick (60%). 90% of cases of manifestation of the syndrome occur in the 1st year of life, with a peak at the age of 4 to 6 months. As a rule, by the age of 3 years, muscle spasms pass or transform into other forms of epilepsy.
Causes
In the vast majority of cases, West syndrome is symptomatic. It can occur as a result of intrauterine infections (cytomegaly, herpes infection), postnatal encephalitis, fetal hypoxia, premature birth, intracranial birth trauma, asphyxia of the newborn, postnatal ischemia due to late clamping of the umbilical cord. West syndrome may be a consequence of abnormalities in the structure of the brain: septal dysplasia, hemimegaloencephaly, agenesis of the corpus callosum, etc. In some cases, infantile spasms are a symptom of phacomatosis (pigment incontinence syndrome, tuberous sclerosis, neurofibromatosis), point gene mutations or chromosomal aberrations (including Down syndrome). The literature mentions cases of phenylketonuria with infantile spasms.
In 9-15%, West syndrome is idiopathic or cryptogenic, i.e. its root cause has not been established or is not obvious. Often, there are cases of fibrillation seizures or epiprimes in the family history of a sick child, i.e. there is a hereditary predisposition. A number of researchers indicate that vaccination, in particular the introduction of DPT, can be a factor provoking West syndrome. This may be due to the coincidence of the timing of vaccination and the age of the typical onset of the syndrome. However, reliable data confirming the provoking role of vaccines have so far been obtained.
The pathogenetic mechanisms of infantile spasms are the subject of study. There are several hypotheses. One of them connects West syndrome with a disorder of the functioning of serotonergic neurons. Indeed, patients have a decrease in the level of serotonin and its metabolites. But it is not yet known whether it is primary or secondary. An immunological theory linking West syndrome with an increase in the number of activated B cells was also discussed. The positive therapeutic effect of ACTH formed the basis of the hypothesis of failures in the “brain-adrenal glands” system. Some researchers suggest that the syndrome is based on an excessive number (overexpression) of excitatory synapses and conducting collaterals that form an increased excitability of the cortex. They associate the asynchrony of the EEG pattern with a physiological lack of myelin for this age period. As the brain matures, its excitability decreases and myelination increases, which explains the further disappearance of paroxysms or their transformation into Lennox-Gastaut syndrome.
Symptoms
As a rule, West’s symptom debuts in the first year of life. In some cases, its manifestation occurs at an older age, but no later than 4 years. The clinic is based on serial muscle spasms and psychomotor development disorders. The first paroxysms often appear against the background of an already existing psychomotor development retardation (PDR), but in 1/3 of cases they occur in primarily healthy children. Deviations in neuropsychological development are most often manifested by a decrease and loss of the grasping reflex, axonal hypotension. There may be a lack of eye tracking of objects and a disorder of eye fixation, which is a prognostically unfavorable criterion.
Muscle spasms are sudden symmetrical and short-term in nature. Their seriality is typical, while the interval between successive spasms lasts at least 1 minute. Usually there is an increase in the intensity of spasms at the beginning of the paroxysm and its decline at the end. The number of spasms occurring per day varies from units to hundreds. The most common occurrence of infantile spasms occurs during falling asleep or immediately after sleep. Sharp loud sounds and tactile stimulation can provoke paroxysm.
The semiotics of paroxysms accompanied by West syndrome depends on which muscle group is contracting — extensor (extensor) or flexor (flexor). On this basis, spasms are classified into extensor, flexor and mixed. Most often there are mixed spasms, then flexor, most rarely extensor. In most cases, one child has several types of spasms and which spasm will prevail depends on the position of the body at the time of the onset of paroxysm.
There may be a generalized contraction of all muscle groups. But more often there are local spasms. So, convulsions in the flexors of the neck are accompanied by nodding of the head, spasms in the musculature of the shoulder girdle resemble a shrug of the shoulders. A typical paroxysm is a “folding knife” type, caused by a contraction of the abdominal flexor muscles. At the same time, the body seems to fold in half. Infantile spasms of the upper extremities are manifested by withdrawing and bringing the hands to the trunk; from the outside it seems that the child is hugging himself. The combination of such spasms with a paroxysm of the “folding knife” type is associated with the greeting “salaam” accepted in the East, therefore it was called the “Salaam attack”. In children who can walk, spasms can occur in the form of drop attacks – unexpected falls with the preservation of consciousness.
Along with serial spasms, West syndrome can be accompanied by convulsive seizures, manifested by a sudden stop of motor activity. Sometimes there are paroxysms, limited to twitching of the eyeballs. There may be a violation of breathing due to spasm of the respiratory muscles. In some cases, there are asymmetric spasms, manifested by the withdrawal of the head and eyes to the side. There may be other types of epiprimes: focal and clonic. They are combined with spasms or have an independent character.
Diagnostics
West syndrome is diagnosed by the main triad of signs: attacks of cluster muscle spasms, delayed psychomotor development and hypsarrhythmic EEG pattern. The age of the manifestation of spasms and their connection with sleep are important. Diagnostic difficulties arise with the late onset of the syndrome. During the diagnosis, the child is consulted by a pediatrician, a pediatric neurologist, an epileptologist, a geneticist. West syndrome should be differentiated with benign infantile myoclonus, benign rolandic epilepsy, infantile myoclonic epilepsy, Sandifer syndrome (head tilt according to the type of torticollis, gastroesophageal reflux, episodes of opisthotonus, which can be mistaken for spasms).
Interictal (inter-criminal) The EEG is characterized by the presence of disorganized, disorderly, dynamically changing spike-wave activity, both during wakefulness and during sleep. Polysomnography makes it possible to detect the absence of spike activity during the deep stages of sleep. Hypsarrhythmia is registered in 66% of cases, usually in the early stages. Later, some organization of the chaotic EEG pattern is observed, and at the age of 2-4 years, its transition into “acute-slow wave” complexes. The most frequent ictal EEG pattern (i.e. EEG rhythm during spasms) are generalized slow-wave complexes of high amplitude with subsequent inhibition of activity for at least 1 second. When registering focal changes on the EEG, one should think about the focal nature of the brain lesion or the presence of abnormalities in its structure.
CT scans of the brain in children with West syndrome can detect diffuse or focal changes in cerebral structures, but may be within the normal range. In the diagnosis of local lesions, MRI of the brain is a more sensitive method. To identify areas of hypometabolism of brain tissues, in some cases, it is possible to conduct a PET of the brain.
Treatment
West syndrome was considered resistant to ongoing therapy until the discovery in 1958 of the effect of ACTH drugs on seizures. Therapy with ACTH and prednisone leads to a significant improvement or complete cessation of infantile spasms, which is accompanied by the disappearance of the hypsarrhythmic EEG pattern. Until now, there are no unambiguous decisions among neurologists regarding the doses and duration of steroid therapy. Studies have shown that in 90% of cases therapeutic success was achieved with the use of large doses of ACTH. The duration of therapy may vary within 2-6 weeks.
A new stage in the treatment of infantile spasms began in 1990-1992 after the discovery of the positive therapeutic effect of vigabatrin. However, the advantage of treatment with vigabatrin has so far been proven only for patients with tuberous sclerosis. In other cases, studies have shown greater effectiveness of steroids. On the other hand, steroid therapy has a worse tolerance compared to vigabatrin and a higher percentage of relapses.
Of the anticonvulsants, the effectiveness is shown only in nitrazepam and valproic acid. In some patients, the therapeutic effect of large doses of vitamin B6 was described, which was noted in the first weeks of therapy. With infantile spasms resistant to therapy, with the presence of a pathological focus confirmed on tomography, a consultation with a neurosurgeon is indicated to resolve the issue of resection of the focus. If such an operation is not possible, then in the presence of drop attacks, a total callosotomy (crossing of the corpus callosum) is performed.
Forecast
Usually by the age of 3, regression and disappearance of infantile spasms are observed. But in about 55-60% of cases, they transform into another form of epilepsy, most often into Lennox-Gastaut syndrome. Pharmacoresistance is often found in infantile spasms accompanying Down syndrome. Even with successful relief of paroxysms, West syndrome has an unsatisfactory prognosis in terms of psychomotor development of the child. Cognitive and behavioral disorders, cerebral palsy, autism, learning difficulties are possible. Residual psychomotor deficiency is not observed only in 5-12% of cases. PDR is noted in 70-78% of children, motor disorders — in 50%. West syndrome has a serious prognosis, due to anomalies or degenerative changes in the brain. At the same time, the mortality rate can reach 25%.
Cryptogenic and idiopathic West syndrome have a more favorable prognosis in the absence of PDR before the appearance of spasms. In this group of patients, 37-44% of children have no residual intellectual or neurological deficit. Postponing the start of treatment adversely affects the prognosis of the disease. Prognostic assessment is complicated by the fact that the long-term consequences also depend on the underlying pathology, against which West’s symptomatic syndrome occurs.