Cerebral ischemia in newborns: symptoms, consequences, treatment

Violation of blood circulation in the cerebral vascular system of the child immediately after its birth, causing a lack of oxygen in the blood (hypoxemia), is defined as cerebral ischemia in newborns. The ICD-10 code is P91.0.

Since ischemia, hypoxemia and hypoxia (oxygen starvation) are physiologically interrelated (although the development of hypoxia may be in normal cerebral blood flow), the critical state of oxygen deficiency for neonatal brain in neurology is considered a clinical syndrome and is called neonatal hypoxic-ischemic encephalopathy developing within 12 -36 hours after delivery.

[1], [2], [3], [4], [5], [6], [7]

Epidemiology

In neonatal neurology and pediatrics, the epidemiology of clinical manifestations of cerebral ischemia in newborns is not recorded separately from the syndrome of hypoxic-ischemic encephalopathy, so the assessment of morbidity due to lack of criteria for their differentiation is problematic.

The frequency of neonatal encephalopathies associated with a decrease in cerebral blood flow and brain hypoxia is estimated in 2.7-3.3% of cases per 1,000 live births. At the same time, 5% of children with infantile brain pathologies suffered a perinatal stroke (one case is diagnosed for 4.5-5 thousand infants with the pathology of cerebral hemodynamics).

The frequency of perinatal asphyxia is estimated from one to six cases per thousand full-term newborns and from two to ten cases in premature infants. The global estimate is highly divergent: according to one data, neonatal asphyxia causes 840,000 or 23% of neonatal deaths worldwide each year, and according to WHO - at least 4 million, representing 38% of all deaths among children under the age of five years.

Experts from the American Academy of Pediatrics concluded that the best estimate of the frequency of neonatal brain pathology is population data: an average of three cases per thousand people. According to some Western neurophysiologists, one or other consequences of hypoxic-ischemic encephalopathy born at birth are observed in 30% of the population of developed countries and more than half of the inhabitants of developing countries.

[8], [9], [10], [11], [12], [13], [14], [15]

Causes of the cerebral ischemia in newborns

The brain needs a constant supply of blood carrying oxygen; in infants, the brain is up to 10% of body weight, has a branched vascular system and consumes a fifth of the oxygen that comes with blood to all tissues of the body. With a decrease in cerebral perfusion and oxygenation, the brain tissues lose the source of life support of their cells, and the known causes of cerebral ischemia in newborns are quite numerous. It can be:

• hypoxemia of the mother due to insufficient ventilation of the lungs for cardiovascular diseases, chronic respiratory failure or pneumonia;
• decrease in blood flow to the fetal brain and hypoxemia / hypoxia due to placental disorders, including thrombosis, detachment and placental infections;
• prolonged clamping of the umbilical cord during labor, leading to severe metabolic acidosis of the umbilical cord blood, systemic reduction of the volume of circulating blood (hypovolemia), falling blood pressure and impaired perfusion of the brain;
• acute disturbance of cerebral hemodynamics (perinatal or neonatal stroke), which occurs in the fetus from the 20th week of pregnancy, and in the newborn - within four weeks after birth;
• absence of automatic self-regulation of cerebral blood flow in premature infants;
• violation of the intrauterine blood circulation of the fetus due to narrowing of the pulmonary artery or congenital cardiac anomalies (left-sided cardiac hypoplasia, Botallov duct non-invasion, transposition of the main vessels, etc.).

[16], [17], [18], [19], [20], [21], [22]

Risk factors

There are also numerous risk factors for the development of cerebral ischemia in newborns, among which neurologists and gynecologists-obstetricians note:

• the first pregnancy is older than 35 years or under 18;
• long-term infertility therapy;
• insufficient body weight of the newborn (less than 1.5-1.7 kg);
• premature birth (before the 37th week of pregnancy) or a delayed pregnancy (more than 42 weeks);
• spontaneous rupture of membranes;
• too long or fast delivery;
• improper presentation of the fetus;
• prevalence of umbilical cord vessels (vasa previa), most often observed with in vitro fertilization;
• trauma to the skull of an infant during childbirth (as a result of obstetric errors);
• an emergency cesarean section;
• heavy bleeding during labor;
• presence of cardiovascular or autoimmune diseases in pregnant women, anemia, diabetes mellitus, functional thyroid disorders, blood coagulation disorders (thrombophilia), antiphospholipid syndrome, infectious and inflammatory diseases of pelvic organs;
• severe arterial hypotension during pregnancy and late gestosis.

Risk factors for cerebral ischemia in infants are also recognized as congenital blood diseases associated with mutations of prothrombin genes, platelet coagulation factors V and VIII, homocysteine of the blood plasma, as well as DIC syndrome and polycythemia.

[23], [24], [25], [26], [27], [28], [29]

Pathogenesis

Cerebral ischemia in newborns disrupts the metabolism of brain cells, which leads to an irreversible destruction of the structure of the nervous tissue and its dysfunction. First of all, the pathogenesis of the development of destructive processes is associated with a rapid drop in the level of adenosine triphosphate (ATP), the main energy supplier for all biochemical processes.

For the normal function of neurons, the balance between intracellular and extracellular concentrations of ions migrating through their membranes is also important. With oxygen starvation of the brain, the transmembrane gradient of potassium (K +) and sodium (Na +) ions is disrupted in neurons, and the extracellular concentration of K + increases, leading to progressive anoxid depolarization. At the same time, the influx of calcium ions (Ca2 +), initiating the release of the glutamate neurotransmitter, which affects the NMDA receptors of the brain, increases; their excessive stimulation (excitotoxicity) leads to morphological and structural changes in the brain.

Also, the activity of hydrolytic enzymes is increased, which break down the cell nucleic acids and cause their autolysis. In this case, the base of nucleic acids - hypoxanthine - is transformed into uric acid, accelerating the formation of free radicals (active forms of oxygen and nitrogen oxide) and other compounds toxic to the brain. Antioxidant protective mechanisms of the brain of newborns are not yet fully developed, and the totality of the listed processes have an extremely negative effect on its cells: gliosis of neurons, atrophy of glial cells and oligodendrocytes of white matter.

[30], [31], [32], [33], [34], [35], [36], [37], [38]

Symptoms of the cerebral ischemia in newborns

The clinical symptoms of cerebral ischemia in newborns and the intensity of their manifestation are determined by its type, severity and localization of neuronal necrosis zones.

Types of ischemia include focal or topographically limited damage to brain tissue, as well as global, spreading to many cerebro-vascular structures.

The first signs of cerebral ischemia at the birth of a child can be revealed by checking the reflexes of congenital spinal automatism. But the evaluation of their deviations from the norm depends on the degree of violation of cerebral perfusion and the physiological maturity of the newborn.

[39], [40], [41], [42], [43]

Stages

Thus, cerebral ischaemia 1 degree in a newborn (mild form of hypoxic-ischemic encephalopathy) is manifested in a full-term infant with a moderate increase in muscle tone and tendon reflexes (grasping, Moro, etc.). Symptoms include excessive anxiety with frequent limb movements, posthypoxic myoclonus (twitching of individual muscles against a background of muscle stiffness), problems when applying to the chest, spontaneous crying, intermittent sleep.

If the child was born before the term, then, in addition to reducing unconditioned reflexes (motor and sucking), there is a weakening of the general muscle tone during the first few days after birth. As a rule, these are temporary anomalies, and if the condition of the infant's central nervous system stabilizes for several days, then ischemia practically does not give neurological complications. But everything depends on the endogenous regenerative activity of the developing brain of a particular child, as well as on the development of cerebral neurotrophins and growth factors-epidermal and insulin-like.

Cerebral ischemia of grade 2 in the newborn (causing a moderately severe form of hypoxic-ischemic encephalopathy) adds to the list of already mentioned symptoms epileptic type convulsions; a decrease in the arterial and an increase in cerebral pressure (there is an increase and a marked pulsation of the fontanel); lethargy during feeding and frequent regurgitation; problems with the intestines; periods of heart rhythm disturbances and apnea (breathing in sleep); labile cyanosis and the effect of "marble skin" (due to vegetovascular disorders). The acute period lasts about ten days. In addition, neonatologists note the possibility of complications in the form of hydrocephalus (hydrocephalus), eye movements - nystagmus, skew eye deflection (strabismus).

If there is cerebral ischaemia of grade 3 in a newborn, then neonatal reflexes (sucking, swallowing, grasping) are absent, and seizures are frequent and prolonged (within 24-48 hours after birth). Then the cramps decrease, followed by a progressive decrease in muscle tone, a state of stupor, an increase in edema of brain tissue.

Depending on the location of the main foci of cerebral ischemia, there may be impairment of respiratory function (the infant often requires a hardware support of breathing); changes in heart rate; dilated pupils (poorly responsive to light) and lack of oculomotor conjugation ("puppet eyes").

These manifestations are increasing, which indicates the development of severe hypoxic-ischemic encephalopathy, which, because of cardiorespiratory failure, can be completed lethal.

[44]

Complications and consequences

The development of neonatal cerebral ischemia causes damage to its cells induced by oxygen deficiency and causes very serious, often irreversible neurological consequences and complications that correlate with the topography of lesions.

As studies have shown, cerebral ischemia in newborns is more susceptible to hippocampal pyramidal cells, Purkinje cells in the cerebellum, reticular neurons in the perirolandic region of the cerebral cortex and ventrolateral part of the thalamus, basal ganglion cells, corticospinal nerve fibers, midbrain nuclei, and neocortex and trunk neurons the brain.

In term infants, first of all, cerebral cortex and deep cores suffer, in preterm patients, diffuse destruction of cells of the white matter of the hemispheres is noted, which causes chronic disability in surviving children.

And with global ischemia of brain stem cells (in which the cents of regulation of breathing and the work of the heart are concentrated), their total death and practically inevitable lethal outcome occur.

The negative consequences and complications of perinatal and neonatal brain ischemia of 2-3 degree in young children are manifested by epilepsy, unilateral loss of vision, delayed psychomotor development, motor and cognitive impairments, including infantile cerebral palsy. In many cases, their severity can be fully assessed by the child's three years of age.

[45], [46]

Diagnostics of the cerebral ischemia in newborns

Initial diagnosis of cerebral ischemia in newborns occurs immediately after childbirth during a routine examination of the child and the definition of the so-called neurological status (according to the Apgar scale) by checking the degree of reflex excitability and the presence of certain congenital reflexes (some of them were mentioned in describing the symptoms of this pathology ). The HR and BP indices are necessarily recorded.

Instrumental diagnostics, especially non-visualization, allows to identify zones of cerebral ischemia. To this end, use:

• computed tomography of cerebral vessels (CT angiography);
• magnetic resonance imaging (MRI) of the brain;
• craniocerebral ultrasound (ultrasound);
• electroencephalography (EEG);
• echocardiography (ECG).

Laboratory tests include a general clinical blood test, as well as blood tests for electrolyte levels, prothrombin time and fibrinogen levels, hematocrit, and arterial blood gases; analysis of umbilical or venous blood at the pH level (for the detection of acidosis). Urine is also analyzed for its chemical composition and osmolality.

[47], [48], [49], [50], [51], [52], [53]

Differential diagnosis

In order to exclude the presence of perinatal infant meningoencephalitis, brain tumors, tyrosinemia, homocystinuria, congenital syndrome Zellweger, errors of metabolism of pyruvate, as well as genetically caused mitochondrial neuropathies, methylmalonic or propionic acidemia, a differential diagnosis.

Treatment of the cerebral ischemia in newborns

In many cases, in the first stages, the treatment of cerebral ischemia in newborns requires cardiopulmonary resuscitation in newborns with artificial lung ventilation and all measures to restore the hemodynamics of the cerebral vascular system, maintain hemostasis, and prevent hyperthermia, hypo and hyperglycemia.

Significantly reduces the degree of moderate and severe ischemic damage to brain cells in infants. Controlled hypothermia: cooling the body for 72 hours to + 33-33.5ºC followed by gradual bringing the temperature to the physiological norm. Such treatment does not apply to premature babies, born before 35 weeks.

Drug therapy symptomatic, for example, with tonic-clonic convulsions, anticonvulsants Diphenin (Phenytoin), Trimetine (Trimetadion) - twice a day for 0.05 g (with systematic monitoring of blood composition) are most often used.

To reduce muscle hypertonicity after three months in / m, muscle relaxant Tolperisone (Midokalm) can be administered - 5-10 mg per kilogram of body weight (up to three times a day). The drug can cause side effects in the form of nausea and vomiting, skin rashes and itching, muscle weakness, suffocation and anaphylactic shock.

Improvement of cerebral perfusion is facilitated by intravenous drip of Vinpocetin (the dosage is calculated by body weight).

To activate the functions of the brain it is customary to use neuroprotective drugs and nootropics : Piracetam (Nootropil, Nocephalus, Piroxil, Dinacel) - 30-50 mg per day. Syrup Ceraxon is prescribed for 0.5 ml twice a day. It should be borne in mind that this drug is contraindicated in hypertension of the muscles, and its side effects include allergic urticaria, lowering blood pressure and disturbing the heart rhythm.

When suppressing the functions of the central nervous system Glutan (glutamic acid, Acidulin) is used three times a day for 0.1 g (with the control of blood composition). A drug-nootropic gopantenovoy acid (syrup Pantogam) improve the oxygenation of brain tissue and exhibit neuroprotective properties.

Parenterally used vitamins B6 (pyridoxine hydrochloride) and B12 (cyanocobalamin) with a solution of glucose.

Physiotherapeutic treatment

With an easy degree of cerebral ischemia in a newborn child, physiotherapeutic treatment is mandatory, in particular a therapeutic massage that helps to reduce muscle hypertonicity. However, if there is an epileptic syndrome, massage is not applied.

Improve the state of newborns with cerebral ischemia water procedures in the form of a bath with a decoction of chamomile flowers of pharmacy, pepper or lemon mint. Herbal treatment - see Soothing means for children

Prevention

Neuropathologists believe that the prevention of development in neonatal syndrome of neonatal hypoxic-ischemic encephalopathy is problematic. Here you can talk only about proper obstetrical accompaniment of pregnancy and timely detection of risk factors: cardiovascular pathologies in the future mother, endocrine disorders, blood clotting problems, etc. To prevent the effect of anemia, high or low blood pressure or infectious inflammatory diseases is possible with timely treatment. However, many of the problems available to date are not solvable.

[54], [55], [56], [57], [58], [59]

Forecast

Alas, a favorable prognosis regarding the consequences to which cerebral ischemia in neonates leads is noted only with its mild degree.

Neonatal encephalopathy is the cause of high mortality and long-term neurological pathologies in infants throughout the world.

[60], [61], [62], [63], [64], [65]