Bilirubin encephalopathy (also called kernicterus) is a condition characterized by the death of brain cells due to the toxic effect of a high concentration of bilirubin (indirect fraction) on them. This condition is most common in newborns and requires immediate treatment, otherwise it can lead to disability and even death of the patient.
Etiology of disease
Possible causes of bilirubin encephalopathy in newborns are as follows:
- hemolytic disease (Rhesus or group incompatibility of mother and baby);
- maternal diabetes;
- newborn sepsis;
- traumatization of a child during childbirth with the formation of extensive hematomas;
- toxoplasmosis (intrauterine infection);
- jaundice in premature babies.
Under the influence of any of the listed processesindirect bilirubin (that is, not processed by hepatocytes) is released into the blood in large quantities, causing a neurotoxic effect on brain tissue.
Pathological features
The surface of the brain has a pale yellow tint. A section of the preparation reveals the characteristic yellow coloration of the brain structures (cerebellum, hippocampus, thalamus, trunk, and others). However, unpainted areas also undergo pathological changes.
In the affected areas, due to the death of neurons, gliosis is formed and atrophy of the nervous tissue occurs. At the same time, the pathomorphological picture is similar to that in hypoxic lesions, which means that it can be assumed with a high degree of probability that unbound bilirubin, damaging cell membranes, leads to impaired oxygen utilization in brain tissues. And hypoxic damage leads to an even greater increase in the sensitivity of neurons to the toxic effects of bilirubin.
That is, nuclear jaundice (bilirubin encephalopathy) is not only a change in the color of brain structures under the influence of bilirubin. It is also a whole range of pathological specific processes occurring at the cell level.
Bilirubin encephalopathy in adults
The causes of damage to brain structures by bilirubin in adults lie in severe decompensated liver pathologies (cirrhosis, hepatitis).
The disease in adults develops gradually and is accompanied by an increase in neurological symptoms. At the same time, mental disorders come to the foreand physical activity, manifested by insomnia, cognitive changes, decreased activity, and so on.
Clinical manifestations
Most often, the first signs of pathology occur in full-term babies on the 2-5th day, and in premature babies - on the 7th day. But the presence of hyperbilirubinemia can lead to the development of the disease throughout the neonatal period (up to 28 days).
Early symptoms of such encephalopathy are nonspecific and may coincide with those of hypoglycemia, sepsis, intracranial hemorrhage, hypoxia and other pathological acute conditions of the newborn.
As a rule, the first signs of an incipient brain injury are a decrease in the sucking reflex, drowsiness, and the disappearance of the Moro reflex. As the disease worsens (progresses), tendon reflexes disappear, breathing is disturbed, opisthotonus occurs, the large fontanelle is tense, the facial muscles and muscles of the limbs twitch convulsively, the child screams piercingly.
Then, convulsions appear, accompanied by a sharp extension of the arms and turning the hands, clenched into fists, inwards.
Further activity of the process often leads to death, otherwise the child's condition improves and development is normal. However, by the year, muscle rigidity, opisthotonus and hyperkinesis reappear. By the second year of life, convulsions and opisthotonus disappear, however, involuntary erratic movements, combined with hypotension or muscle rigidity, persist and become stable.
At the age of three, bilirubin encephalopathy in children acquires a persistent and clear character, which is manifested by hearing loss to sounds with a high frequency, choreoathetosis, convulsions, dysarthria, strabismus, oligophrenia, extrapyramidal disorders. Sometimes there is ataxia, hypotension and pyramidal disorders.
With mild bilirubin encephalopathy, the consequences can manifest as hearing loss, moderate or mild motor coordination disorders, hyperactivity syndrome combined with impaired attention (minimal brain dysfunction). These symptoms may be combined or present separately. However, encephalopathy may not be diagnosed until school entry.
Staging of the process
Pathology has four stages of development:
- Symptoms of bilirubin encephalopathy are non-specific: there is weakness, vomiting, monotonous emotionless cry. Muscle tone and appetite are reduced.
- Symptoms of encephalopathy appear, the baby's limbs are bent, it is impossible to unbend them, the chin is brought to the chest, the child cries unnaturally. In some cases, hyperthermia and episodes of apnea are possible.
- The patient's condition (usually 10-12 days of a baby's life) is noticeably improving, but this phenomenon is not associated with recovery, on the contrary, the process is progressing. Muscle stiffness recedes, there are no cramps.
- Develops at 2 months of baby's life. The symptoms are on the rise. There are signs similar to those of cerebral palsy. The child is significantly behindpsychoemotional and physical development.
Diagnostic measures
Hyperbilirubinemia can be regarded as physiological only in cases of exclusion of absolutely all pathological factors of its occurrence. Taking into account the fact that hyperbilirubinemia is most often due to hemolytic or physiological causes, the patient's examination should include the following tests:
blood test (general) with obligatory calculation of the number of reticulocytes and microscopy of a blood smear;
- Coombs test (indirect and direct);
- determining the group and Rh-affiliation of the blood of the mother and baby;
- determining the amount of indirect and direct bilirubin;
Increase in the content of bilirubin in the cord blood, the presence of symptoms of jaundice in the first day of life, if the level of the unconjugated fraction is more than 34 µmol/l, indicate the presence of pathological jaundice.
In some cases, MRI, ultrasound and CT may be prescribed for bilirubin encephalopathy.
Condition Therapy
Children's kernicterus (regardless of its stage) is treated by a pediatric neurologist. As a rule, such children are hospitalized.
Treatment of an ailment in an adult is also carried out in a hospital under the constant supervision of a doctor.
Treatment of the disease is to eliminate the causes of hyperbilirubinemia and restore the normal concentration of bilirubin in the blood. It is used as a treatmentphototherapy.
Under the influence of radiation, toxic indirect bilirubin is transformed into a special isomer that is easily excreted by the kidneys and liver and does not bind to blood albumins. In cases where the concentration of bilirubin does not decrease under the influence of phototherapy, a plasma transfusion is prescribed.
If the previous methods were ineffective, or the symptoms are rapidly increasing, the patient is prescribed direct blood transfusions.
Used drugs
If for some reason direct transfusion is not possible, drugs are prescribed that affect the synthesis and transformation of bilirubin ("Protoporphyrin").
Due to the fact that kernicterus is the result of the toxic effects of bilirubin on neurons, neuroprotectors are always used in its treatment.
Anticonvulsant treatment is given when indicated.
In case of hemolytic disease with a direct positive Coombs test, intravenous immunoglobulin infusions are effective.
Frequency of occurrence, consequences and forecasts
According to autopsy data, kernicterus occurs in newborns at any gestational age in the absence of adequate therapy for hemolytic disease and bilirubin concentrations above 25-30 mg.
The incidence of the disease in premature babies with hyperbilirubinemia varies from 2 to 16%. More precise figures cannot be determined due to the wide variety of symptoms of the disease.
The presence of a pronounced neurological symptom complex is an unfavorable prognostic sign. Thus, mortality in this case reaches 75%, and 80% of surviving patients have bilateral choreoathetosis, accompanied by involuntary muscle contractions. In addition, complications such as deafness, mental retardation and spastic tetraplegia are quite common.
Children with a history of hyperbilirubinemia should be screened for deafness.
Despite improved diagnosis, kernicterus still occurs. There is information about its occurrence against the background of hyperbilirubinemia without any reasons. Therefore, experts recommend mandatory monitoring of bilirubin on the 1-2 day of life for all newborns in order to identify patients with a high probability of developing severe hyperbilirubinemia and, as a result, encephalopathy.
Preventive measures
It is important to study the concentration of bilirubin in case of jaundice on the first day of life, and in the presence of hyperbilirubinemia - to exclude the development of hemolytic disease.
It is mandatory to monitor the condition of the baby within 3 days after discharge, especially for premature (up to 38 weeks) babies who were discharged from the maternity ward before 2 days of life.
The frequency of observation is determined by the age at which the baby was discharged and the presence of risk factors. Some children are observed during the day. Risks can be predicted by assessing the levelhourly increase in bilirubin.
