Perinatal encephalopathy

Perinatal encephalopathy (PEP) Perinatal hypoxic encephalopathy is a frequent complication of the pathology of pregnancy and childbirth and is diagnosed in newborns up to 5% of cases [1]. Perinatal brain damage accounts for more than 60% of the entire pathology of the nervous system of childhood, directly involved in the development of such diseases as infantile cerebral palsy, epilepsy, and minimal brain dysfunction.

Risk factors

To recognize the clinical signs of perinatal hypoxia, it is necessary to take into account risk factors predisposing to its development:

• The age of the mother (younger than 20 and over 35)

• Premature detachment of the placenta

• Placenta previa

• Preeclampsia

• Premature or late delivery

• Staining amniotic fluid with meconium

• Bradycardia, fetal tachycardia, muffling of fetal heart tones

• Multiple Fertility

• Long anhydrous gap

• Mother's Diabetes

• Any mother's disease during pregnancy

• Admission mother of potentially dangerous preparations for the fetus

Among the causes of violations of ventilation and oxygenation of the blood, peripheral and central hypoxia are isolated. In peripheral hypoxia, the pathology of the respiratory tract or alveolar blood flow participates, in central hypoxia, the basis is a violation of the function of the respiratory center.

Etiology of hypoxia

Peripheral	Central
1. Respiratory distress syndrome	1. Low mother pressure
2. Aspiration of amniotic fluid	2. Mother's anemia
3. Pneumothorax (with birth trauma)	3. Hypertension
4. Bronchopulmonary dysplasia	4. Placental insufficiency
5. Congenital anomalies (Pierre-Robin syndrome)	5. Malformations of the brain

Hypoxia leads to disruption of oxidative processes, the development of acidosis, a decrease in the energy balance of the cell, an excess of neurotransmitters, a violation of the metabolism of glia and neurons. Acidosis increases the permeability of the vascular wall with the development of intercellular edema and the violation of cerebral hemodynamics. Under hypoxic conditions, peroxide oxidation of lipids with accumulation of aggressive free radicals, hydroperoxides, which have a destructive effect on the membranes of neurons, is disrupted. Violations of cerebral hemodynamics ischemic - hemorrhagic character are the consequence of severe brain hypoxia.
In the antenatal period, the main etiological factor of hypoxia is placental insufficiency. Trophic insufficiency occurs with a violation of absorption and absorption of nutrients through the placenta, a deficiency in the transport of oxygen and carbon dioxide, which manifests itself in the syndrome of fetal development delay, intrauterine hypotrophy, immaturity of the lungs and surfactant. It was found that a decrease in uteroplacental blood flow serves as an objective indicator of hypoxic brain damage. Deficiency of surfactant and respiratory anoxia are the main pathogenetic factors of cerebral hypoxia of prematurity and newborns from diabetic mothers. In the pathogenesis of neonatal surfactant deficiency, the secondary hyperinsulinism of the fetus lies, which develops in response to the mother's glycemia. Insulin inhibits the synthesis of lecithin, the main element of the surfactant, the lack of which inhibits the cleavage of the alveoli, which leads to a disruption in the ventilation of the lungs.
Thus, the compensation of diabetes in pregnant women is the prevention of respiratory distress syndrome of newborns and hypoxic encephalopathy. In the neonatal period, the cause of cerebral hypoxia and ischemia can be a pronounced intrapulmonary shunt. Hypoxic cardiopathy of newborns and adrenal insufficiency play a significant role in the pathogenesis of brain hypoxia. Hypoglycemia and glycogen reserve deficiency are considered factors that increase the increased vulnerability of brain tissue to hypoxia of newborns, especially preterm infants with low body weight.

Morphology of hypoxic encephalopathy

The brain normally absorbs a fifth of the oxygen that enters the body. In young children, the share of the brain in the use of oxygen is almost half, which ensures a high level of metabolism of oxidative processes. Depending on the duration of hypoxia in the brain, changes from local edema to necrosis with hemorrhagic impregnation develop. A number of studies have shown that there is a different sensitivity of brain structures to hypoxia, which depends on the characteristics of metabolism and blood supply. The most sensitive to hypoxia are the Sommer zone of the ammon horn and the periventricular region of the adjacent blood supply between the anterior, middle and posterior cerebral arteries. With the combination of hypoxia and ischemia, foci of necrosis in the cortex, the visual hillock, the striatum, the cerebellum. The following stages of morphological hypoxic changes in the brain are distinguished: Stage I - edematous hemorrhagic, Stage II - encephalic gliosis, Stage III - Leukomalacia (necrosis), Stage IV - Leukomalacia with hemorrhage. The first two stages of acute hypoxia are curative, it is possible to restore the metabolism of neurons and glia, the III and IV stages lead to irreversible death of neurons. In antenatal hypoxia, neuronal dystrophy, glial proliferation, sclerosing phenomena, cystic cavities in places of small foci of necrosis are observed.

Clinic of hypoxic encephalopathy

In the clinical picture of hypoxic encephalopathy, three periods are singled out: acute (1 st month of life of the child), restorative (from 1 month to 1 year, and in preterm immature children to 2 years) and outcome.

In the acute period, in terms of severity, a mild form of lesions of the nervous system is distinguished, reflecting transient disorders of hemolytic dynamics; Form of medium severity with edematous hemorrhagic changes, gliosis, single leukomalacia; Heavy form, characteristic of generalized edema of the brain, multiple leukomalacia and hemorrhages. To determine the severity and severity of cerebral circulation disorders, the Apgar scale is used.
In an acute period, 5 clinical syndromes are distinguished: an increase in neuro-reflex excitability, convulsive, hypertensive-hydrocephalic, a syndrome of oppression, and coma. Usually there is a combination of several syndromes. The peculiarity of the acute period is the dominance of cerebral disorders without pronounced local symptoms. With a mild brain lesion (Apgar scores of 6-7 points), the syndrome of increased nervous reflex excitability is characteristic. The main manifestations of the syndrome are increased spontaneous motor activity, restless sleep, prolonged active wakefulness, difficulty falling asleep, frequent unmotivated crying, revival of unconditioned congenital reflexes, muscular dystonia, increased knee reflexes, tremor of limbs and chin. In preterm patients the syndrome of neural-reflex excitability in 94% of cases is a clinical sign of lowering the threshold of convulsive readiness, which is confirmed by the data of electroencephalography (EEG). Patients who, according to the EEG, have a decrease in the threshold of convulsive readiness, should be considered at risk for convulsive syndrome.

The moderate form of hypoxic encephalopathy (assessed on the Apgar scale of 4-6 points) is manifested by hypertensive-hydrocephalic syndrome and oppression syndrome.

For hypertensive-hydrocephalic syndrome characteristic is to increase the size of the head of 1 - 2 cm in comparison with the norm (or the circumference of the chest), the disclosure of sagittal suture more than 0.5 cm, and an increase in large bulging fontanelle. Typical is the brachiocephalic shape of the head with enlarged frontal tubercles or dolichocephalic - with a nape overhanging the back. There is a symptom Gref, a symptom of the "setting sun", an unstable horizontal nystagmus, a descending strabismus. Muscular dystonia is revealed, more in the distal parts of the extremities in the form of a symptom of "seal paws" and "heel piles". Most children, especially in the first days of life, combine these phenomena with paroxysms of flinches, spontaneous Moro reflex, sleep disturbance, Harlequin symptom, general and local cyanosis. The development of hypertensive-hydrocephalic syndrome on the 3-5th day of life can be a sign of periventricular hemorrhage. Hypertensive-hydrocephalic syndrome may be isolated, but more often it is combined with a syndrome of oppression or coma syndrome. oppression syndrome manifested by lethargy, physical inactivity, reduction in spontaneous activity, general muscular hypotonia, hyporeflexia, inhibition of neonatal reflexes, decreased reflexes of sucking and swallowing. There are local symptoms in the form of divergent and convergent strabismus, nystagmus, asymmetry and sagging of the lower jaw, asymmetry of mimic muscles, bulbar and pseudobulbar symptoms. The syndrome characterizes the course of an acute period of hypoxic encephalopathy and usually disappears at the end of the first month of life. In acute period, the syndrome of oppression can be a harbinger of brain edema and the development of coma syndrome.

Comatosis syndrome is a manifestation of the severe condition of the newborn, according to the Apgar scale it is estimated 1 to 4 points. In the clinical picture, pronounced lethargy, adynamia, muscle hypotension to atony, pronounced congenital reflexes are not detected, pupils are narrowed, light response is negligible or absent. There is no reaction to pain stimuli, "floating" movements of the eyeballs, horizontal and vertical nystagmus, tendon reflexes are depressed. Breathing arrhythmic, with frequent apnea, bradycardia, heart sounds deaf, pulse arrhythmic, low blood pressure. Seizures may occur with a predominance of the tonic component. The severe condition persists for 10 to 15 days, there are no reflexes of sucking and swallowing. The appearance in the acute period of hydrocephalus with the bulging and tension of the large fontanel, the divergence of cranial sutures, the protrusion of the eyeballs, the rapid growth of the head testifies to intracranial hemorrhage.

The convulsive syndrome in the acute period, as a rule, is combined with a syndrome of oppression or coma. It occurs as a result of hypoxic brain edema, hypoglycemia, hypomagnesemia or intracranial hemorrhage. It appears in the first days of life with tonic-clonic or tonic convulsions. Along with this, local clonic convulsions or hemiconvulsions are observed. Convulsive seizures in newborns are characterized by short-term, sudden onset, lack of pattern of repetition and dependence on sleep or wakefulness, feeding regimen and other factors. Seizures occur in the form of melkoamplitudnogo tremor, transient respiratory arrest, tonic spasm of eyeballs on the type of paresis gaze upward, simulating the symptom "setting sun", nystagmus, automatic chewing movements, clonus paroxysms stop vasomotor reactions. These seizures by their nature sometimes resemble spontaneous movements of the child, which makes diagnosis difficult.

The recovery period of hypoxic entsefaloratii includes the following syndromes: increased neuro-reflex excitability, hypertension-hydrocephalic, vegetovistseralnyh dysfunction, movement disorders, psychomotor retardation, epileptic.

The syndrome of increased nervous reflex excitability in the recovery period has two variants of the course. With a favorable variant of the course, the disappearance or decrease in the severity of the symptoms of increased neuro-reflex excitability is observed in the period from 4 to 6 months to 1 year. In case of an unfavorable variant, especially in premature babies, an epileptic syndrome may develop.

Hypertensive-hydrocephalic syndrome has two variants of the course:

1. Hypertensive-hydrocephalic syndrome with a favorable course, in which the disappearance of hypertensive symptoms with delayed hydrocephalus;

2. An unfavorable variant of hypertension-hydrocephalic syndrome, which is part of the symptom complex of organic cerebral syndrome.

Outcomes of hypertension-hydrocephalic syndrome:

1. Normalization of head circumference to 6 months.

2. Compensated hydrocephalic syndrome in 8 - 12 months.

3. Development of hydrocephalus.

The syndrome of vegetative-visceral dysfunctions begins to appear after 1-1.5 months of life against the background of an increase in neural-reflex excitability and hypertensive-hydrocephalic syndrome. The clinical picture is marked persistent vomiting, persistent malnutrition, respiratory failure rate and apnea, change in color of the skin, akrotsianoz, paroxysms of tachy and bradipnoe, thermoregulation disorders, dysfunction of the gastrointestinal tract, temporal baldness.

Epileptic syndrome can occur at any age (as a continuation of convulsions after birth or against a background of somatic infection). In newborns and infants, he has a so-called age person, i.e. convulsive paroxysms simulate the motor abilities that the child has at the time of their appearance.
In newborns and infants (especially in prematurity), convulsive syndrome is characterized by a variety of clinical forms of seizures. There are generalized convulsive seizures (tonic-clonic, clonic, tonic), abortive, focal, hemiconvulsive, polymorphic seizures, simple and complex absences. The frequency is dominated by polymorphic forms of seizures. In premature infants with perinatal encephalopathy, propulsive and impulsive paroxysms are not found in isolated form, but are observed only in the composition of polymorphic seizures. The greatest difficulty in diagnosis is represented by abortive and non-convulsive forms of paroxysms.
There is an imitation of unconditioned motor reflexes in the form of paroxysmally occurring manifestations of the cervical-tonic symmetrical reflex with the inclination of the head and tonic tension of the arms and legs; Cervical-tonic asymmetric reflex with a turn of the head to the side and extension of the same arm and leg; The first phase of the Moro reflex with the opening of the handles. There are paroxysms in the form of spasm of the eye and nystagmus, imitation of the "symptom of the setting sun". Often observed attacks of redness and blanching of the skin with increased sweating, sometimes regurgitation. After 3 - 4 months of life, as the ability to keep the head appear, "nods", "cleavages" appear, and from 6 to 7 months - "bows" (bending the trunk forward and back).
Features such seizures in preterm infants, as instability of clinical manifestations with prevalence of polymorphic seizures, presence of abortive forms of seizures and complex absence seizures with imitation unconditional neonatal reflexes (the first phase of the Moro reflex, asymmetric neck and tonic reflex) are probably the result of the immaturity of the structures brain. However, an increase in the frequency of seizures, the increase in the polymorphism of their manifestations, resistance to anticonvulsant therapy should alarm the formation of coarse organic forms of brain damage.
Polymorphism of seizures, their resistance to therapy is a prognostically unfavorable sign.

The syndrome of motor disorders is revealed from the first weeks of life, can occur with muscle hypotension or hypertension. When there is a syndrome of motor disorders with muscle hypotension, there is a decrease in spontaneous motor activity, suppression of tendon reflexes and congenital unconditioned reflexes of newborns. The syndrome of motor disorders with muscle hypotension occurs in isolation, as well as in combination with hypertensive-hydrocephalic syndrome, a syndrome of increased neuro-reflex excitability with lowering the threshold of convulsive readiness. Unfavorable combination of the syndrome of motor disorders and convulsive syndrome.

The increase in muscular hypertension in term infants, the emergence of the side effects of focal symptoms should be alarming in terms of the development of infantile cerebral palsy.

The syndrome of delayed psychomotor development begins to manifest from 1 to 2 months. In the structure of the syndrome there is a violation of the reduction of unconditioned congenital reflexes. A large diagnostic role is acquired by cervical-tonic symmetric and asymmetrical reflexes, delayed generation of rectifying labyrinthic chain tonic reflexes. If there is a mental retardation in the structure of this syndrome in children by the age of one month, there is insufficiently stable fixation of the sight, short-term follow-up with rapid depletion. There is no reaction to the mother's voice, auditory concentration. By 2 - 3 months of age, there is insufficient revival in communication, crying is mild, there is no walking, children look for a source of sound with their eyes without turning their heads, and a rare, hardly evoked smile appears. By the half-year - not actively interested in toys and surrounding objects, do not react enough to the presence of the mother, the walk is inactive and short, manipulation of objects is delayed, there is no active attention. If the delay in development is "tempo", it will disappear when properly nurtured. This group of children in 4 - 5 months, as it were, "jump" becomes more active, and the mental development is ahead of the motor one. There is an emotional reaction to others, interest in toys.
Age-related motor functions begin to be actively compensated after 6 to 7 months and, as a rule, are restored to 1 to 1.5 years. Prognostically unfavorable long-term retardation of mental development.

Diagnostics

Investigation of the fundus in the acute period of mild hypoxic encephalopathy of deviations does not reveal, less frequent moderate plethora of veins. With an average degree of marked development of veins, edema, individual hemorrhages. With a severe degree of damage against the background of pronounced edema of vasodilatation, streakiness of the optic nerve disk borders and hemorrhage is noted. Later, such children may show atrophy of the nipples of the optic nerves.

In the cerebrospinal fluid, changes are detected with intracranial hemorrhage. In these cases, fresh and fructose erythrocytes are present in the cerebrospinal fluid. After 7 - 10th day of life, confirmation of the hemorrhage carried is the presence of macrophages in the CSF.

Neurosonography - a two-dimensional ultrasound study of anatomical structures of the brain through a large fontanel - allows you to establish periventricular hemorrhage, foci of leukomalacia, expansion of the ventricular system - ventriculomegaly. Neurosonography allows differential diagnosis with brain defects. Signs of cerebral hypoplasia: an increase in subarachnoid spaces, an expansion of the interhemispheric fissure, ventriculomegaly, an increase in density in the brain parenchyma region without a clear differentiation of the convolutions, and panencephaly. Haloprozenzepalya - an increase in one ventricle, shadows, increased echolnostnosti from the stem structures of the brain, reducing the density of the parenchyma of the brain. Clinico-neurosonographic comparisons reveal a correlation between the number of leukomalacia and neurological outcomes. Multiple leukomalacia in both hemispheres, found in patients with neurosonography in the acute period of the disease, are combined with a syndrome of motor disturbances and a severe delay in the psychomotor development in the recovery period. Computer tomography of the brain helps to objectify hypoxic changes in brain tissue in the structures of the cerebellum and brainstem, which are not clearly identified in neurosonography.

Electroencephalographic (EEG) study reveals foci of slow wave activity, foci of reduction of cortical rhythm, foci of epileptic activity. A great importance of EEG-study has for the allocation of a risk group for seizure syndrome and diagnosis of clinically "mute" seizures. Indirect confirmation of convulsive syndrome, as well as a sign of lowering the threshold of convulsive readiness in patients is the presence of paroxysmal changes in the EEG. Repeated seizures can lead to an increase in the severity of paroxysmal activity on the EEG.

From biochemical studies in the acute period, the indicator of the depth of hypoxic disorders is the assessment of acidosis from mixed to severe decompensated metabolic. With severe hypoxia, the osmotic pressure of blood plasma increases, and the level of lactate dehydrogenase increases. Lactate dehydrogenase and other glycolysis enzymes correlate with the severity of children's condition and reflect the severity of hypoxia in the acute period of perinatal encephalopathy.

Radiography of the lungs is used to diagnose congenital atelectasis, pneumopathy and inflammatory changes in the lungs.

Treatment of acute period

In the acute period, a timely correction of the respiratory respiratory distress syndrome and adequate ventilation of the lungs are necessary. In premature infants, endotracheal administration of colfosceril palmitate is 5 ml / kg. The use of surfactant analogues leads to a significant regression of neurological syndromes of hypoxic encephalopathy.

1. Correction of homeostasis and hypovolemia: fresh frozen plasma 5-10 ml / kg, 10% albumin 5-10 ml / kg, rheopolyglucose 7-10 ml / kg, haemodez 10 ml / kg.

2. Reduction of vascular permeability: 12.5% ​​ethamylate solution intramuscularly or intravenously, 1% vicasol 0.1 ml / kg.

3. Metabolic and antioxidant therapy: piracetam 50 mg / kg, 10% glucose 10 ml / kg, actovegin intravenously, 5% vitamin E 0.1 ml per day. As an antioxidant used soybean oil 2 - 3 ml 4 - 6 days on the skin of the stomach.

4. Vascular therapy: vinpocetine 1 mg / kg intravenously.

5. Dehydration therapy: hydrocortisone 3-10 mg / kg, prednisolone 1 - 2 mg / kg, 25% magnesium sulfate 0.2 ml / kg.

6. Improve tissue metabolism of the cardiac muscle: coccarboxylase 8 mg / kg, ATP 10 mg / kg.

7. An anticonvulsant therapy: diazepam 1 mg / kg intramuscularly or intravenously, GHB 50 mg / kg, barbiturates, when benzodiazepines are ineffective, 5 mg / kg.

Treatment of the recovery period

Treatment of the recovery period is carried out according to the syndromological principle.

1. In the syndrome of increased neuro-reflex excitability with manifestations of vegetovisceral dysfunctions, sedatives are shown: diazepam 0.001 g 2 times a day, tazepam 0,001 g 2 times a day, potassium citrate - citral solution 2.0, magnesium sulphate 3.0, 10% solution Glucose 200.0 - a teaspoonful 3 times a day; With a 2-month-old age, a soothing cocktail of herbs (valerian root, motherwort, sage) is prescribed for 1 teaspoonful 3 times a day.

2. When expressed manifestations of hypertensive-hydrocephalic syndrome, acetazolamide is used at 0.02 g / kg per day, single-shot: 3 days - reception, 1 day break, course from 3 weeks to 1 - 1.5 months with panangin.

3. In the syndrome of motor disorders: vitamin B6 5 mg, vitamin B1 2 mg, ATP 0.5 ml 10-12 injections, pyrithinol 10-20 drops per 1 kg of body weight 2 times a day in the first half of the day 1 to 3 months. Massage. Medical gymnastics, the mother is trained to rehabilitation skills.

4. In the syndrome of delayed psychomotor development: piracetam 30 - 50 mg / kg in 3 doses, pyrithinol. From 6 months, cerebrolysin 0.5 ml No. 20 (contraindicated in convulsive syndrome), vitamins B6, B1. Gamma-aminobutyric acid at 0.06 g 2 - 3 times a day.

5. At a convulsive syndrome: sodium valproate 20 - 50 mg / kg, clonazepam up to 1 - 2 mg per day, phenobarbital 1 - 2 mg / kg. With resistant spasms lamotrigine 1 - 2 mg / kg.

6. Surgical treatment is used for combined periventricular hemorrhages and development of posthemorrhagic hydrocephalus, ventricular shunting is performed.

Therapeutic measures are further individualized depending on the outcome of the process. By the age of one, the majority of mature children with the appearance of verticalization and speech functions can be identified outcomes of perinatal hypoxic encephalopathy. Recovery occurs in 15 - 20% of children. The frequent consequences of the transferred encephalopathy are minimal brain dysfunction, hydrocephalic syndrome. The most severe outcomes are infantile cerebral palsy and epilepsy.

Certainly, the success of perinatal medicine, adequate management of labor and an acute period of hypoxic encephalopathy will reduce the neuropsychiatric outcomes of the disease.