Dysgenesis of the brain

Common neurological problems in childhood are pathologies, the appearance of which is based on abnormal intrauterine development of the brain. Such disorders are called "dysgenesis of the brain", it is a multifactorial condition that often does not have a pronounced clinical picture. In most cases, parents seek help from a doctor with complaints of learning difficulties, seizures, motor distraction, and behavioral abnormalities in the child. Dysgenesis of the brain is recognized only during CT or nuclear magnetic resonance imaging. In general, the mechanisms of the development of the disorder are not well understood.

Epidemiology

Defects in the development of the brain make up about 20% of all malformations. According to the observations of specialists, the incidence of congenital disorders of the central nervous system ranges from 1 to 2 cases per 1,000 babies born. [1], [2]

Among congenital anomalies in the development of the brain, one of the first places is occupied by cortical dysgenesis, which become the main causes of the appearance of childhood epileptic syndrome. In general, congenital brain abnormalities are found in approximately 30% of all dysgenesis diagnosed in childhood.

Cortical dysgenesis occurs in 25-40% of patients with developmental defects of the brain and is often accompanied by epileptic syndrome or other types of symptomatic epilepsy.

Among congenital anomalies of the brain, cortical dysgenesis is noted quite often, which is due to the wide practical application of neuroimaging diagnostics - in particular, neurosonography, magnetic resonance imaging, computed tomography.

Causes dysgenesis of the brain

The most obvious reasons for the appearance of cerebral dysgenesis are:

• disturbed intrauterine development of the nervous system (at the stage of laying);
• damage to the nervous system at the stage of early embryogenesis as a result of gene mutations, infectious diseases of the mother during pregnancy, exposure to radiation, traumatic injuries, exposure of the fetus to chemical agents and toxins.

Among the infections that have a damaging effect on the nervous system of the fetus, rubella, toxoplasmosis, viral hepatitis, and cytomegalovirus infection should be distinguished.

Most often, improper intrauterine development is due to the negative impact on the body of the mother and baby of adverse factors that have a teratogenic effect. Exogenous causes of the formation of dysgenesis can be:

• radioactive radiation;
• the influence of chemical agents;
• high temperature;
• exposure to high frequency currents;
• unsatisfactory environmental situation, which entails the ingestion of toxic products into the woman's body.

In addition, some medicinal drugs, as well as hormonal drugs that the expectant mother can take without knowing about the pregnancy, may have a teratogenic effect. There is evidence that many medicines cross the placenta without problems and end up in the baby's circulatory system. Danger can be posed not only by potent substances, but also by habitual drugs in high dosages, and even multivitamin complexes. [3]

Failures of metabolic processes, viral and other infections, including those that have a latent asymptomatic course, can also provoke violations of intrauterine development by the type of dysgenesis. Particularly dangerous are:

• hyperthyroidism;
• metabolic disorders;
• diabetes;
• syphilis;
• cytomegalovirus infection;
• rubella;
• listeriosis;
• toxoplasmosis.

The characteristics of the life of a pregnant woman have an extremely negative effect on the course of pregnancy and the health of the unborn child. Teratogenic effects are exerted by:

• alcohol consumption;
• smoking;
• addiction.

Risk factors

The following are considered predisposing factors for the appearance of brain dysgenesis:

• hereditary predisposition (related cases of the appearance of pathology, by an autosomal mode of inheritance, or linked to the X chromosome);
• spontaneous mutation;
• chromosomal rearrangement;
• intrauterine infection (mainly of viral origin) or traumatic injury;
• the influence of intoxication, medications, chemicals at the stage of intrauterine development;
• fatal alcohol syndrome due to maternal alcoholism during the period of gestation;
• acute lack of nutritional components in the fetus;
• pronounced metabolic disorders in the expectant mother.

Currently, scientists cannot identify any one main cause of brain dysgenesis, so it is necessary to weigh the existing risk factors. [4]

Pathogenesis

The development of the human brain starts at the prenatal stage, actively continuing after its birth. According to experts, the right cerebral hemisphere is responsible for imaginative and creative thinking, for motor coordination, balance, spatial visual and kinesthetic sensitivity. The left cerebral hemisphere determines the mathematical, sign, logical, speech, analytical abilities, provides the perception of information by ear, target settings and schematic statements. A unified brain is the work of two hemispheres, tightly interconnected with each other by the nerve-fibrous system (corpus callosum).

The corpus callosum is localized between the cerebral hemispheres in the occipito-parietal region. It includes 200 million nerve fibers and ensures the coordinated work of the brain and the transfer of information between the hemispheres. With such a violation as dysgenesis of the brain, the cognitive function of a person suffers. With improper conduction through the corpus callosum, the dominant hemisphere takes on an increased load, with the practical inaction of the other. The connection between the two brain halves is lost. As a result, spatial orientation suffers, an imbalance arises, the patient cannot correctly recognize his own body, adequately react emotionally. The function of perception of the leading limbs is impaired. [5]

Children with cerebral dysgenesis often do not crawl, they have difficulty walking, reading, writing. Information is perceived mainly through hearing and sight. In the absence of treatment and medical rehabilitation, such patients in the future have many problems associated with general development and learning. [6]

Symptoms dysgenesis of the brain

Clinical symptoms in all patients manifest themselves in different ways, therefore, the diagnosis is carried out at different times. For example, severe forms of cerebral dysgenesis are detected already in early childhood, and in adults, the disorder can be hidden and diagnosed randomly.

Children with cerebral dysgenesis during the neonatal period may look normal and quite healthy, and developmental indicators coincide with normal ones up to three months of age. Starting from 3 months, the first pathological signs may appear in the form of epileptic seizures, infantile spasms, etc.

The clinical picture can be represented by such signs:

• violation of the formation and subsequent development of the corpus callosum;
• cystic expansion of the cerebral ventricle cavity, anomaly of the brain mantle;
• hydrocephalus;
• atrophy of the optic and auditory nerves;
• microencephaly;
• tumor processes (including cysts) in the cerebral hemispheres;
• incomplete formation of convolutions;
• early sexual development;
• malformation of the spinal column (spina bifida, non-closure of the vertebral arch);
• Aicardi syndrome (early myoclonic encephalopathy);
• lipomas;
• all sorts of pathologies of the digestive system;
• inhibited psychomotor development;
• intellectual and physical retardation;
• coordination disorders;
• defects from other organs, including the musculoskeletal system;
• decreased muscle tone.

In relatively mild cases of dysgenesis, with normal mental and motor development, there may be signs of impaired information exchange between the cerebral hemispheres. [7]

First signs

Dysgenesis of the brain in infants is found most often after three months of life, although it is possible to diagnose pathology even at the stage of intrauterine development. The first signs of a problem in babies are usually:

• the appearance of seizures, infantile spasms;
• seizures;
• weakening of the cry;
• problems with vision, smell and / or touch;
• communication disorders; [8]
• signs of muscle hypotension (decreased reflex activity, abundant salivation, inhibition of physical development, weak motor activity, impaired grasping function).

At an older age, with dysgenesis, attention is drawn to the deterioration of auditory and visual memory, impaired motor coordination and thermoregulation (hypothermia).

Infantile spasms are convulsive sudden flexion-extension of the limbs. Muscular hypotension is characterized by decreased muscle tone (may be combined with loss of muscle strength).

Non-syndromic types of dysgenesis are considered more common, which remain asymptomatic for a long time and are detected almost by accident - for example, during the diagnosis of mental retardation, seizures, or a large head. Macrocephaly is due in part to the presence of giant cystic masses posterior to the third ventricle. Less commonly, endocrinological disorders may occur.

Syndromic forms of cerebral dysgenesis are as follows:

• Aicardi syndrome - occurs mainly in girls and is characterized by infantile spasms, specific choroidal lacunae, vertebral-costal defects. The outcome of the pathology is often unfavorable: the patients persist in convulsions, and profound mental retardation is noted.
• A family syndrome with genital pathology, which can manifest itself as microcephaly and other defects of the central nervous system.
• Andermann's syndrome is characterized by damage to the peripheral nervous system in combination with brain dysgenesis (or hypotrophy).
• Syndrome of periodic hyperhidrosis and hypothermia (reverse Shapiro syndrome).

Dysgenesis of the corpus callosum

Dysgenesis is a congenital pathology of the brain, as it begins to develop at the prenatal stage under the influence of various factors. Secondary dysgenesis of the corpus callosum is considered in the form of secondary destruction of the transparent septum: such a defect can be visualized with a coronary projection during neurosonography. Many pathologies are associated with dysgenesis of the transparent septum, including stenosis of the aqueduct against the background of secondary hydrocephalus, agenesis of the corpus callosum, Chiari II anomaly, migration defect, and septooptic dysplasia. With septooptic dysplasia, dysgenesis of the transparent septum and hypoplasia of the optic canals, nerve fibers and chiasm are noted. Most of the patients with this pathology additionally suffer from disorders of the pituitary-hypothalamic system. [9]

Dysgenesis of the corpus callosum in a child affects the nerve plexuses connecting the two cerebral hemispheres, namely, the corpus callosum, which has a flattened shape and is localized under the cerebral cortex. The disease can have varying degrees of severity:

1. A mild degree of dysgenesis is noted while maintaining intellectual abilities and motor activity. There are only disturbances in the transmission of impulse signals between the hemispheres.
2. The complex degree is accompanied not only by general signs of dysgenesis, but also by other abnormalities of brain development. There are marked disruptions in neural connections, seizures, and a clear inhibition of mental development.

Complications and consequences

The outcomes of congenital cerebral abnormalities can be divided into three options:

1. Almost complete recovery, with no visible disturbances and the patient's return to normal life activity.
2. Residual phenomena that do not threaten the patient's life, but to a certain extent limit his everyday and social activities.
3. Gross disorders, significant intellectual disabilities.

The severity of the consequences of dysgenesis depends on the volume of pathological changes in the brain, as well as on the cause that provoked this pathology. The timeliness of the diagnosis and the adequacy of medical procedures are of great importance. [10]

In general, in many patients with cerebral dysgenesis, there is a moderate or severe impairment of intellectual development, and there is a lag in physical terms.

Diagnostics dysgenesis of the brain

In severe cases of cerebral dysgenesis, it is possible to carry out diagnostics already with a visual examination of a newborn baby. Additional examinations can be prescribed for muscular hypotension in the neonatal period, with the appearance of seizures, with mental retardation.

The following are considered common diagnostic methods:

• screening and obstetric ultrasound examination during pregnancy;
• neurosonography through the fontanel area in the first 12-18 months of a baby's life;
• electroencephalography with possible video monitoring;
• Magnetic resonance imaging. [11]

To recognize disorders associated with dysgenesis, somatic pathologies, an ultrasound examination of the kidneys, heart, and abdominal organs is performed. Additionally, genetic counseling may be required. Laboratory tests are carried out as part of a general assessment of the state of the body: they perform general blood and urine tests, less often - a study of cerebrospinal fluid.

Instrumental diagnostics in childhood, during the period of open fontanelles, is most often represented by neurosonography - an affordable, mobile, safe and informative procedure. Neurosonography can be used both in congenital and infectious, neuroplastic or traumatic brain lesions. [12]

Differential diagnosis

During the diagnosis of brain dysgenesis in the neonatal period, differentiation should be made with the following pathological conditions:

• closure defects, cephalocele , meningocele , myelomeningocele;
• Chiari malformation;
• cerebellar anomalies, impaired ventral induction;
• Dandy-Walker anomaly ;
• cerebellar dysplasia and hypoplasia; [13]
• hypoplasia and aplasia of the corpus callosum; [14]
• holoprosencephaly;
• defects of migration, heterotopia, lissencephaly, polymicrogyria, schizencephaly;
• proliferation and neuronal differentiation;
• stenosis of the aqueduct;
• phakomatoses (Sturge-Weber syndrome);
• vascular malformations.

Treatment dysgenesis of the brain

Medicine is not able to completely cure brain dysgenesis. Doctors prescribe treatment to correct the work of the central nervous system, to eliminate pathological symptoms, to normalize the intellectual activity of patients. The therapeutic scheme is selected individually for each patient, taking into account the severity of the pathology.

In order to alleviate the condition, the following medications are prescribed:

• Phenobarbital helps reduce the frequency of infantile spasms. Most often, children are prescribed at a dosage of 50 mg per day, for adults - 200 mg per day.
• Benzodiazepines slow down psychomotor reactions and reduce the frequency of seizures. Diazepam at an initial dose of 5-10 mg corrects behavioral disorders, has a muscle-relaxing effect.
• Corticosteroid drugs eliminate even complex epileptic seizures, but require careful selection of the dosage and gradual withdrawal of the drug. Side effects occur mainly against the background of long-term use of such drugs and can be expressed in the appearance of electrolyte disturbances, hyperglycemia, impaired glucose tolerance, osteoporosis, hypertension, etc.
• Antipsychotics are used to prevent mental disorders, but treatment with such drugs should be careful, as in some cases antipsychotics can increase the frequency of seizures.
• Nootropics normalize brain function. The nootropic drug hopantenic acid Pantogam is especially widespread: its use as part of a neurometabolic corrective treatment regimen helps to improve psycho-somatic health and optimize the quality of life of children with brain dysgenesis. Neuropeptides optimize neural connections and are widely used in neuropediatrics as effective and safe agents for improving mental and motor functions in patients.

In addition to drug treatment, surgery may be prescribed.

Surgery

The help of a surgeon is required to stimulate the vagus nerve for cerebral dysgenesis. For this, a special vagus stimulator is used, consisting of a pulse generator and a battery, as well as a connecting cable with platinum electrodes. The generator is implanted in the left subclavian zone, the electrodes are fixed in the neck near the left vagus (X cranial nerve).

The implantation is performed under general anesthesia, and the intervention itself lasts about 60-90 minutes. During the operation, two incisions are made in the area of the left armpit and neck for the correct placement of the pulse generator and electrodes. The functionality of the implant is checked directly during the intervention. After the operation, the patient remains in hospital for several more days.

What does this type of treatment give for dysgenesis? The appearance of convulsive seizures is blocked, concentration of attention and mood improves, and the quality of life increases. These effects are especially evident in patients who have already taken medication and, in particular, antiepileptic drugs.

Surgical intervention is used in cases where other therapeutic methods do not bring the desired result, and the pathology of cerebral dysgenesis itself threatens complications from vital organs. [15]

Prevention

Preventive measures should be involved in preparation for pregnancy and intended conception. The primary type of prevention of dysgenesis includes the following points:

• Optimization of a woman's nutrition during the entire childbearing period, regular use of vitamin and mineral components in the form of special pharmaceutical nutritional supplements or by expanding and enriching the diet.
• Elimination of the use of unhealthy products, alcohol.
• Prevention of diabetes mellitus at the stage of preparation for pregnancy and during gestation, preventing the development of obesity.
• Prevention of intoxication and harmful effects (heavy metals, pesticides, certain medications, X-rays). Taking any medications by a woman should be as justified as possible.
• Prevention of the development of infections, early vaccination against rubella (if a woman has not been vaccinated or has not had rubella in childhood).

Forecast

If dysgenesis of the brain is not combined with other developmental disorders, then the prognosis can be characterized as favorable. More than 80% of pediatric patients have practically no serious consequences of the disease, or acquire borderline neurological disorders.

It is necessary to understand that the main danger of dysgenesis is that the child is deprived of the opportunity to consolidate the acquired skills and abilities, often a lot has to be learned again. The patient needs to constantly return to supportive treatments, which is especially important against the background of increasing brain load with age. The need for regular therapy remains at least until the age of 14, until the final formation of interhemispheric connections. Moreover, it is not possible to accelerate this process, since the consequences of such an “acceleration” may be unpredictable.

It is not possible to provide a more accurate prognosis of the disease: cerebral dysgenesis occurs relatively infrequently and they have not yet been fully studied.