Perinatal lesions in premature infants (IVH, PVL): causes and diagnosis. Transcript of the live broadcast with Doctor of Medical Sciences Marina Viktorovna Narogan.

Pathological processes affecting the central nervous system (CNS) affect the performance of the entire organism. Morphological changes are often irreversible, reducing the functionality of the damaged sections.

Organic brain lesions often develop against the background of impaired blood supply to the intracranial (intracranial) space. The consequence of prolonged ischemia of nerve tissue can be leukoaraiosis - structural changes in the white cerebral matter.

Signs of vascular brain damage

Timely diagnosis of the disease makes it possible to stabilize the functioning of the brachiocephalic arteries and reduce the risk of developing dangerous complications. An effective method for studying the brain is magnetic resonance imaging.

MRI involves the use of a force field that is harmless to human health. In response to a directed electromagnetic pulse, a resonance of charged particles is observed in the cells of the body. Hydrogen atoms in water molecules undergo vibrational movements that can be detected using sensitive detectors.

The information content of an MR scan depends on the fluid saturation of the structures being studied. The tissues of the brain and spinal cord contain a large volume of water, so magnetic resonance imaging makes it possible to visualize the slightest changes in the state of the central nervous system.

What is leukoaraiosis?

The cause of the development of pathological processes in the area of ​​the cerebral substance is chronic cerebral ischemia. When intracranial circulation is disrupted, foci of nervous tissue necrosis occur. Structural transformations are accompanied by a decrease in the density of white matter and destruction of the myelin sheath of neurons. The process of transmission of nerve impulses stops, and the functionality of the affected area of ​​the central nervous system decreases.

Depending on the localization of pathological phenomena, two forms of leukoaraiosis are distinguished:

• periventricular – degenerative processes occur in the lateral ventricles of the brain, focal or diffuse changes in the parenchyma are possible;
• subcortical – affects the white matter under the cortex.

Periventricular leukoaraiosis as an independent disease is rare; more often this phenomenon serves as a symptom of another brain pathology. The causes of destructive processes are considered to be:

• Alzheimer's disease;
• multiple sclerosis;
• Binswanger's disease;
• vascular dementia;
• ischemic stroke;
• hypertension;
• diabetes;
• HIV, etc.

A characteristic symptom of the listed pathologies is impaired cerebral circulation, leading to demyelination and degeneration of cerebral structures.

Periventricular process on MRI images

Negative factors that increase the risk of developing leukoaraiosis include:

• elderly age;
• smoking;
• alcoholism;
• drug use;
• diseases of the cardiovascular system;
• increased blood clotting;
• poor nutrition.

The periventricular process often develops as a result of cerebral edema, accompanied by impaired functioning of the cerebrospinal fluid of the lateral ventricles. Large lesions appear during lacunar infarction or stroke.

Periventricular leukomalacia (PVL) underlies most motor disorders in patients with perinatal pathology of the nervous system, including cerebral palsy (CP) [1, 15, 17, 18]. As studies in recent years show [12, 13, 21], not every child developing in unfavorable intrauterine conditions develops PVL. Obviously, a decisive role in the implementation of a potentially pathogenic effect is played by the genetically determined individual reactivity of the child’s body, which determines the increased “susceptibility” of the structures of the periventricular region and other parts of the brain of the fetus and newborn to hypoxia. There is evidence in the literature [5, 6] that one of the triggers for the persistence of motor deficits in cerebral palsy is genomic instability, manifested by an increase in the level of red blood cells with micronuclei (EM) and lymphocytes with chromosome rearrangements. It is assumed that this phenomenon is based on the intensification of mutagenesis processes in the body of patients with cerebral palsy due to the enhanced generation of endomutagens and the weakening of antimutagenic genome protection systems. At the same time, both the mechanisms of genome destabilization themselves and the processes that support them remain unclear.

The most likely endomutagens in conditions of a chronic ischemic process in the brain may be products of free radical oxidation. With excessive formation, free radicals affect the cell, leading to various cytogenetic damages and subsequently to its death [6, 10, 14, 16, 20]. The role of reactive oxygen species and other free radicals is manifested primarily in oxidative damage to DNA, the carrier of hereditary information and the initial matrix for the synthesis of proteins in the body as a whole, which can cause a number of chromosomal aberrations and mutation of some genes in human cells [10]. Control over the excessive production of reactive oxygen species is carried out by the antioxidant system, which includes: superoxide dismutase (SOD), catalase (CAT), peroxidase, ceruloplasmin, glutathione peroxidase, glutathione transferase, etc. [2, 8].

In recent years, reports have appeared in the literature [5] about the presence of a high level of cytogenetic disorders in peripheral blood cells in patients with cerebral palsy. The mechanisms of formation of genome instability in cerebral palsy remain poorly understood. It is known that genomic instability can maintain the persistence of motor deficits in children with spastic forms of the disease, preventing successful rehabilitation therapy. Further studies of the pathogenetic links in the formation of cerebral palsy in children with PVL should clarify the mechanisms that maintain the severity of the disease and hinder the effectiveness of treatment measures. This will make it possible to purposefully influence the identified processes involved in the formation of gross motor disorders, to reasonably prescribe drug therapy and improve the quality of life of patients.

The purpose of this study is to study the relationship between the level of EOs and the intensity of free radical oxidation processes and the activity of antioxidant enzymes in children with the early residual stage of cerebral palsy.

Material and methods

51 children (24 boys and 27 girls aged 1-5 years) with spastic diplegia were examined. The children were hospitalized in the neurological department of the Children's Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan.

The criterion for inclusion of patients in the study was the identification by neuroimaging - using neurosonography, magnetic resonance imaging (MRI) and X-ray computed tomography (CT) - of only PVL, without other pathology, and the absence of drug treatment and infectious process for 30 days.

The control group consisted of 20 healthy children. Both groups were comparable by gender and age.

A cytogenetic study of peripheral blood erythrocytes was carried out using a micronucleus test [19]. Blood sampling for the study was carried out on the 1st day of the patient’s admission to the hospital before the start of treatment. Peripheral blood smears were stained according to Romanovsky-Giemsa at pH 6.8 for 20 minutes, then washed well. For each patient, 20,000 red blood cells were examined, among which EMs were counted. The number of EMs was expressed as a percentage of the total number of erythrocytes examined.

The activity of SOD [7], CAT [9], and peroxidase [11] in blood hemolysate was studied using a biochemical method in the central research laboratory of the Kazan State Medical University using standard methods; lipid hydroperoxide [3] and malondialdehyde (MDA) in plasma [4].

Statistical processing of the results was carried out using the parametric Student t-test, non-parametric Mann-Whitney t-test and correlation analysis using the Origin 6.1 program.

Results and discussion

A cytogenetic study revealed an increased amount of EM in each examined child with cerebral palsy, which significantly (p<0.001) exceeded the rate of spontaneous mutagenesis (Table 1).

The detected cytogenetic abnormalities indicate genome destabilization. Genomic instability can occur under conditions of increased generation of endomutagens, leading to damage to the metabolic cycles of aneugenesis and, as a consequence, to an increase in the number of cells with cytogenetic rearrangements. The most likely generators of endomutagenesis in children with PVL resulting in cerebral palsy may be active free radical processes.

A study of the activity of antiradical defense enzymes (SOD, CAT, peroxidase) in the blood of patients with PVL with an outcome in cerebral palsy revealed their high level compared to the control group, indicating the activation of free radical processes. In children with PVL, significant activity of SOD, a key enzyme of antioxidant protection, was observed. Significant differences in the activity indicators of SOD (p<0.05) and CAT (p<0.05) were found in children with spastic diplegia compared to healthy ones (see Table 1). A tendency was revealed for the predominance of peroxidase activity in red blood cells in the examined children with cerebral palsy compared to controls, but no significant differences were obtained (p>0.05).

A study of the content of lipid peroxidation products (LPO) revealed an increase in both the primary (lipid hydroperoxide) and secondary (MDA) products that interact with thiobarbituric acid in the blood serum in patients with cerebral palsy. In the group of children with PVL, a significantly higher (p <0.002) MDA content was revealed compared to the control (see Table 1). The level of lipid hydroperoxide was increased, but no significant differences were found with the healthy group. This may be due to the fact that lipid hydroperoxide is an unstable product and quickly turns into a more stable and toxic product - MDA.

Based on the detected increase in the activity of antiradical defense enzymes and lipid peroxidation products (MDA), one can judge the course of severe oxidative stress in children with PVL and patients with cerebral palsy.

The obtained results of biochemical and cytogenetic studies indicate the presence of two simultaneously occurring pathological processes in children with PVL. On the one hand, this is an increase in the intensity of free radical oxidation processes, on the other hand, genome instability with a large number of cytogenetic rearrangements.

To assess the relationship between the cytogenetic status and the activity of free radical oxidation processes, a correlation analysis of these indicators in patients with PVL with the outcome in cerebral palsy was carried out. It turned out that both processes are interconnected with each other: SOD activity inversely correlates with the number of EM (r=–0.601), and the MDA content and CAT activity revealed a direct correlation with the number of red blood cells with rearrangements (r=0.67 and r=0.605, respectively ) (Fig. 1, 2).

Figure 1. Correlation curve between the amount of EM and SOD activity in children with PVL.

Figure 2. Correlation curve between the amount of EO and the level of MDA in children with PVL. The negative correlation of SOD activity with the level of cytogenetic disorders in children with PVL and patients with cerebral palsy may be associated with insufficient activity of antiradical enzymes for antimutagenic protection against the background of increased free radical oxidation processes. Under these conditions, the increased content of MDA exhibits a pronounced cytotoxic effect, causing destabilization of the genome.

The results of the analysis of the conducted studies indicate that in patients with PVL with an outcome in cerebral palsy, genome instability is formed against the background of activation of free radical processes. Pronounced processes of free radical oxidation provoke endomutagenesis and lead to an aneugenic effect in the cells of the body of patients with cerebral palsy. It is possible that pathological changes in the periventricular region can support and perhaps even initiate endomutagenesis in the body of children with PVL. The results obtained suggest that oxidative stress leads to destabilization of the cellular genome in children with PVL resulting in cerebral palsy and supports processes occurring (and possibly originating) in the periventricular region. These processes contribute to the aggravation of existing and the emergence of new pathological links in the patient’s metabolism. The above dictates the need to search for additional ways of pharmacological correction of oxidative stress and cytogenetic disorders in children with PVL.

Taking into account the actively occurring processes of free radical oxidation and endomutagenesis in the body of patients with PVL with an outcome in cerebral palsy, the further tactics of our study was an attempt to correct these disorders. For this purpose, a drug with both neurotropic and antioxidant effects was chosen - cortexin. As a result of randomization, 20 patients with PVL resulting in spastic diplegia were allocated, who received monotherapy with Cortexin for 20 days at a dose of 0.5 mg/kg per day. Blood sampling to study oxidative status and EO levels was carried out on the day of initiation of therapy (before treatment) and after 20 days of treatment.

A study of antioxidant status during therapy with Cortexin showed a significant decrease in the activity of antiradical defense enzymes compared with indicators before treatment: SOD - by 33.3% (p<0.05) and CAT - by 10% (p<0.05) (Table .2).

Peroxidase activity also decreased by 10% (p>0.05). A significant decrease in lipid peroxidation products after treatment with Cortexin was revealed: MDA activity - by 36.7% (p<0.05), lipid hydroperoxide - by 10.5% (p>0.05). The level of cytogenetic disorders during Cortexin therapy significantly (p<0.05) decreased by 40% compared to the values ​​​​obtained before treatment, but still remained higher than in healthy children.

The study demonstrated the antiradical and antimutagenic effect of cortexin, manifested in a decrease in the activity of free radical oxidation and endomutagenesis processes in patients.

Thus, oxidative stress in children with PVL resulting in cerebral palsy is important both in the initiation of the pathological process and in its progression. PVL is formed against the background of a hypoxic process in the perinatal period, which triggers free radical oxidation. It is possible that oxidative stress contributes to the development of white matter necrosis in the periventricular areas of the brain. Subsequently, in the absence of adequate therapy that inhibits oxidative stress, astrocyte degeneration occurs with the proliferation of microglia and the accumulation of lipid-containing macrophages in necrotic tissue. Since the periventricular region is a matrix region for nerve cells, its necrotic changes lead to impaired differentiation of nerve cells and, consequently, to severe neurological consequences. The positive dynamics of free radical oxidation processes during Cortexin therapy indicates that the drug reduces LPO activity and slows down the processes of oxidative endomutagenesis in the body of children with PVL. The antiradical and antimutagenic properties of cortexin reduce the cytotoxic effect of free radicals on the cell genome, reducing genome instability in patients with PVL resulting in cerebral palsy and, accordingly, preventing the progression of the disease.

Symptoms of leukoaraiosis

Destruction of white matter is characterized by disruption of brain functions. Clinical manifestations depend on the location and stage of the pathological process. The degree of damage to nervous tissue is determined using instrumental studies. When performing MRI, it is possible to diagnose leukoaraiosis at the initial stage.

The clinical picture of brain destruction is characterized by:

• motor dysfunction;
• cognitive impairment;
• psycho-emotional disorder;
• speech disorders;
• muscle weakness;
• headache;
• insomnia.

The first stage of leukoaraiosis is accompanied by slight dizziness, fatigue, and weakness. The patient notes:

• noise in ears;
• decreased concentration;
• general depression.

Speech disturbances and memory loss are possible. On examination, increased tendon reflexes are revealed.

The second stage occurs with a significant decrease in the functionality of the body. Note:

• impaired coordination of movements;
• loss of balance when walking;
• slowing of psychomotor functions;
• partial or complete loss of speech;
• decreased memory and attention.

The patient loses control of his actions. Apathy, irritability, and depression are noticeable. Frequent urination and night diuresis are possible.

The third stage is accompanied by an intensification of the listed symptoms. Observed:

• severe behavioral disorders;
• falling while walking;
• loss of speech, memory;
• urinary incontinence.

The patient is not capable of self-care.

Leukoaraiosis on MRI images

Destruction of white matter in the frontal lobe is characterized by a decrease in intellectual abilities against the background of satisfactory motor function.

Will an MRI of the brain show leukoaraiosis?

Magnetic resonance imaging is considered one of the most informative ways to study cerebral structures. As a result of MRI, layer-by-layer images are obtained with a step of 1 mm.

The scan is carried out in three mutually perpendicular projections; if necessary, the doctor reconstructs a 3D model of the area in question. Tomograms visualize the structure, shape, and dimensions of intracranial structures. Three-dimensional projection helps to assess the localization and extent of the pathological process.

Changes characteristic of leukoaraiosis are clearly visible on MRI of the brain. The method allows you to assess the state of the white matter and shows a violation of the integrity of the myelin layer of neurons. To visualize the circulatory system, MR angiography is prescribed.

The study of cerebral vessels is carried out using a contrast agent. After intravenous injection, the solution fills the bloodstream and intercellular space. Tomograms make it possible to assess the lumen, fullness, and condition of the walls of blood vessels. As a result of angiography, pathologies of cerebral veins and arteries, the consequences of cerebral circulatory disorders (ischemia, etc.) are revealed.

Scanning is used for differential diagnosis of degenerative-dystrophic, inflammatory, demyelinating processes, which may result in destruction of white matter. MRI shows structural changes in brain tissue, helping to identify affected lesions with a diameter of 3 mm.

Magnetic resonance imaging allows you to identify leukoaraiosis at the initial stage, clarify the pathogenesis of the disease and choose an effective treatment method. The effectiveness of therapeutic and surgical measures largely depends on the etiology of the destructive process.

PERIVENTRICULAR LEUCOMALACIA IN PREMATURE INFANTS

The pathology of premature newborns associated with brain damage is becoming increasingly relevant for pediatric practice in our country. Periventricular leukomalacia (PVL) (ischemic necrosis, periventricular infarction, encephalodystrophy, periventricular encephalomalacia) is local or widespread aseptic necrosis of the white matter of the cerebral hemispheres, located along the outer superior parts of the lateral ventricles.
The first description of PVL was made by Virchov in 1867. The term "periventricular leukomalacia" was introduced by B. Banker and J. Iarroche in 1962. The urgency of the problem is primarily due to the severe long-term neurological consequences of periventricular leukomalacia, as well as the fairly high frequency of this pathology.

PVL occurs mainly in premature infants. The predominant gestational age of children with PVL is 31__2 weeks, and the body weight at birth is 1555__348 g. In newborns weighing from 900 to 1500 g, its detection rate is 3-8%. With increasing gestational age, the incidence of PVL decreases. According to the results of pathological studies, in deceased children weighing less than 2000 g, the frequency of detection of PVL ranges from 17% (R. Shuman, L. Selednik) to 24-40% (W. Szymonowicz, ea).

Etiopathogenesis

The development of PVL in prematurely born children is associated with inadequate cerebral circulation due to the absence of the terminal zones of the three main cerebral arteries, imperfect mechanisms of autoregulation of cerebral blood flow, as well as high sensitivity to hypoxia of the white matter of the cerebral hemispheres, which is entering the myelination phase.

Hypoxia in premature newborns does not increase cerebral blood flow, as it does in full-term infants. A decrease in systemic blood pressure leads to cerebral hypoperfusion, primarily in the areas of adjacent blood circulation between the ventriculofugal and ventriculopetal branches of the arteries, in the so-called watershed area, at a distance of 3-10 mm from the walls of the lateral ventricles, most often in the parietal region. The development of coagulative necrosis is also facilitated by free radicals released during the oxidation of hypoxanthine and causing tissue destruction. Hypoxemia, hypercapnia, and metabolic acidosis cause microcirculation disorders in the form of venous stasis and thrombosis of small vessels. Thus, the main mechanism for the development of PVL is hypoxia as a result of hypoxemia and hypoperfusion of the brain, as well as impaired microcirculation.

But the occurrence of PVL foci can be caused not only by hypoxemia and hypercapnia, but also by hyperoxia (with mechanical ventilation or other types of respiratory support), since an increase in blood pH in the brain tissue leads to a reflex spasm of the precapillaries. A sharp change from hypoxemia to hyperoxia is especially dangerous, which is noted when oxygen therapy is carried out without clear control of the blood gas composition. Damage to brain tissue is aggravated by the difficulty of venous outflow from the cranial cavity, which is observed in newborns with respiratory distress syndrome, especially those on mechanical ventilation, as well as in cardiovascular failure. Purulent-septic infection is also indicated as a possible factor in the development of PVL.

As a result of all these reasons, coagulative necrosis of the white matter of the periventricular zones of the brain develops. Subsequently, degeneration of astrocytes occurs with the proliferation of microglia and the accumulation of lipid-containing macrophages in necrotic tissue. Phagocytosis of necrotic areas begins on the 5-7th day and leads to the formation of cysts during the first two weeks and at a later date. In the area of ​​necrosis, secondary hemorrhages often occur with the development of hemorrhagic infarctions, peri- and intraventricular hemorrhages. The incidence of hemorrhage is 28-59% of all cases of PVL.

Various authors provide data on the combination of lesions of the periventricular zone with a decrease and thickening of the germinal matrix in the area of ​​the PVL focus, ischemic lesions in the gray matter (hipocampus, thalamus optic, caudate nucleus, medulla oblongata, cerebellar cortex), softening in the cortical ganglia. It is important to note the rarity of damage to the cerebral cortex in prematurely born children. The immature cortex is less sensitive to hypoxia than the mature one, due to the large number of anastomoses between the arteries of the surface of the hemispheres, characteristic of the fetal brain and premature newborn.

Currently, most researchers believe that PVL occurs postnatally, in the first hours and days after birth, but there is evidence of its development at a later date - on the 10th day of life. Subsequently, new lesions may join existing lesions (for example, with repeated attacks of apnea), and the process may progress. Cases of the development of leukomalacia before birth, as well as at the 3-4th week of a child’s life, have been described (the later formation of leukomalacia lesions is usually associated with an infectious process).

Periventricular leukomalacia in the prenatal period causes destruction and disruption of the formation of the cerebral cortex, and its development in the natal and postnatal periods contributes to damage to motor neurons in the area of ​​the corona radiata. Risk factors for development can be divided into two groups: pathological course of pregnancy and childbirth.

Complications of pregnancy include gestosis, which results in the birth of children with PVL in 85.7% of mothers, chronic maternal infections (chronic pyelonephritis, hepatitis, salpingoophoritis) - in 43%, a burdened obstetric history (medical and spontaneous abortions) - in 43%, chronic fetoplacental insufficiency - in 64%. A pathological course of labor is observed in 92.8% of mothers (quick labor, premature rupture of amniotic fluid, weakness of labor).

The dependence of the frequency of occurrence of PVL on the time of year was also noted. Thus, leukomalacia more often develops in children whose last months of intrauterine development occur in the winter-spring period, which may be due to the influence of heliometeorological fluctuations on gestation, as well as hypovitaminosis.

An important etiological factor in the development of leukomalacia is pathological conditions requiring artificial ventilation. According to A. Safonov et al., 85.7% of children were on mechanical ventilation in the maternity hospital, and its average duration was 7 days. Thus, the main disease in these children is a condition that requires this type of respiratory therapy - respiratory distress syndrome. 69% of patients suffered from pneumonia. Most of these children are born in a state of asphyxia of varying severity. The average Apgar score was 5 points.

In the neurological status at the stage of the maternity hospital, all children had a syndrome of central nervous system depression (decreased motor activity, muscle hypotonia, hyporeflexia), 21% had a convulsive syndrome. No more often than in the general population, these children are diagnosed with congenital malformations (kidneys, hearts, etc.).

Pathomorphology

The morphological substrate of periventricular leukomalacia is foci of coagulative (less often, mainly in full-term children, liquefaction) necrosis around the lateral ventricles. The diameter of the lesions in most cases is 2-3 mm, they are located at a distance of 3-6 mm from the ependyma of the lateral ventricles in the region of the fibers of the internal capsule, corpus callosum, and less often - the superior longitudinal fasciculus. The color of the hearths is white. Sometimes, on the periphery of PVL foci, a white rim of coagulation necrosis is detected, bordering the central part of grayish coagulation necrosis. Foci of PVL are clearly visible against the background of usually venous stagnation, sometimes with symptoms of phlebothrombosis, and have a dense consistency. In most cases, lesions are located bilaterally and in symmetrical parts of the brain, often in the parietal and frontal lobes, less often in the occipital and temporal lobes.

The morphology of PVL has been better studied in full-term infants. V. Vlasyuk identifies three stages of its development:

1. Necrosis phase, during which the death of glial cells, accumulation of decay products and cellular detritus, fragmentation and clumpy disintegration of axons occur.

2. Resorption, which is characterized by an astrocytic and macrophage reaction with the accumulation of granular balls.

3. Formation of a glial scar or pseudocyst caused by the proliferation of astrocytes. Cystic degeneration of the brain is more common. The cysts are multiple, of different sizes, the number of cysts increases during dynamic observation, and in severe cases of PVL cysts occupy almost the entire periventricular zone of the lateral ventricles. In less severe variants, the cysts are isolated and localized in such typical areas as the lateral zones of the anterior and inferior horns of the lateral ventricles.

According to V.Banker, the following stages of PVL are observed in premature infants:

1.Coagulative necrosis and reactive microglial reaction, lasting about 3 hours.

2. Delimitation of the damage zone - 8 hours.

3. Capillary hyperplasia -12 hours.

4. Disintegration of lesions with the formation of cavities - 2 weeks.

5. Collapse of pseudocysts, formation of glial scars, atrophy of brain tissue - up to 2-5 months.

Clinic

It is generally accepted that PVL does not have pathognomonic clinical symptoms (N. Shabalov, F. Pidcock). Nonspecific changes in the neurological status are detected, according to L. Kazmina, in 76% of children with PVL.

Many children experience a syndrome of increased neuro-reflex excitability (41.3%). The syndrome of inhibition of neuro-reflex activity was the main clinical manifestation in 17.4% of those examined, muscle hypotonia was observed in 44% of newborns. Convulsions in the neonatal period appeared in 6% of children, and brainstem symptoms were observed with approximately the same frequency.

A few publications (L.Graziani, M.Pasto, C.Standley ea) draw attention to the absence of anomalies in the neurological status in the neonatal period in many observations.

In some clinical cases, PVL may result in death.

There is reason to believe that almost all pathological neurological symptoms in leukomalacia in newborns are caused by combined lesions of the stem formations due to hypoxia, impaired microcirculation, intoxication, etc., since as the severity of the process subsides, even in the case of the development of massive periventricular cysts, abnormalities during a neurological examination in most children it is not detected until 3-5 months of age.

According to A. Kazmin et al., in 89% of children, the acute period of central nervous system damage was followed by a period of “imaginary well-being” that lasted up to 3-4, and in some cases up to 8-9 months, after which signs of cerebral insufficiency appeared.

Brain disorders varied. Movement disorders predominated. 89% of children developed cerebral palsy of varying severity. According to the observations of J. Perlman et al., when changes in periventricular density are combined with a large cyst, cerebral palsy develops in 93% of cases. According to the same data, PVL does not lead to the formation of cerebral palsy only in 7-31% of cases. Research by I. Voronov et al. estimated the probability of developing cerebral palsy with periventricular leukomalacia at 68.5%.

Strabismus was found in 60.8% of children (mainly convergent alternating). Convulsive syndrome appeared at the age of 4-7 months of life in the form of adverse or focal convulsive seizures. Almost all children with PVL have persistent cerebroasthenic syndrome. A small group of children end up with minimal brain dysfunction. Visual impairment in children with PVL is rare and is associated primarily with retrolental fibroplasia, which also develops in premature infants who have suffered severe hypoxia. Isolated cases of cortical blindness and hemianopia have been described.

According to A.M. Kazmin et al., 4.3% of children with PVL were practically healthy.

It has been established that the nature of chronic cerebral insufficiency in PVL is determined primarily by the localization of leukomalacial cavities, and the severity of various psychoneurological disorders depends mainly on the size of the pseudocysts. The larger and more numerous the leukomalacia cavities, the more severe the cerebral disorders. In cases where the lesion is extensive, but the leukomalacia lesions are distributed more thinly around the ventricles, the prognosis is more favorable. The most severe consequences, especially in terms of motor skills, occur in cases where the thickness of the lesia reaches 1/2-1/3 of the thickness of the mantle. I. Voronov, E. Voronova drew attention to the importance for the forecast of the time period in which PVL occurred, as well as the timeliness and completeness of rehabilitation measures for children with leukomalacia.

Apparently, genetically determined and morphologically formed projection (internal capsule) and long associative (superior longitudinal fasciculus) connections of the cerebral hemispheres are the main channels for transmitting signals from the cerebral cortex to spinal motor neurons, between the anterior and posterior fields of the neocortex, respectively. . Therefore, damage to these structures in newborns leads to persistent cerebral deficit.

The development of cerebral palsy is associated with damage to the central part of the internal capsule, the medial middle and posterior frontal segments of the white matter of the cerebral hemispheres, and the severity of movement disorders clearly correlates with the number and size of leukomalacial cavities. Strabismus is caused by damage to the projection and commissural connections of the posterior adversive field. Delayed mental development is observed with damage to the lateral frontal and parietal segments of the cerebral hemispheres, with changes in the system of the superior longitudinal fasciculus. Periventricular leukomalacia leads to minor neurological disorders in the form of dyspraxia, transient changes in muscle tone, or does not cause any neurological abnormalities in young children with isolated unilateral brain damage in the medial retrofrontal and parietal segments of the cerebral hemispheres, as well as in the presence of single small pseudocysts of any location.

The time of manifestation of brain disorders in PVL apparently corresponds to the normative timing of the functional “switching on” of the corresponding pathways.

Diagnostics

Before the introduction of ultrasound examination of the brain - echoencephalography - into clinical practice, it was possible to diagnose PVL only at autopsy. There are few reports indicating the possibility of detecting leukomalacia using CT, while single pseudocysts are not detected. High radiation exposure and the need for expensive equipment do not make the CT method preferable for diagnosing PVL.

In recent years, data have emerged on the use of magnetic resonance imaging to monitor structural changes in PVL. The use of this method has convincingly confirmed that areas of impaired myelination are more extensive than pseudocysts detected on neurosonography.

Changes in the electroencephalogram are nonspecific. With extensive periventricular leukomalacia, powerful fluctuations in the delta and tetra ranges predominated in the native EEG. In newborn children, spectral and phase interhemispheric asymmetry, peaks, sharp waves, and bursts of slow oscillations were observed. In the acute stage of leukomalacia, many patients showed EEG depression and paroxysmal activity. In PVL with small, few pseudocysts, EEG changes were absent or insignificant.

Currently, the main method for diagnosing PVL is neurosonography. The accuracy of ultrasound diagnostics for PVL is estimated at 90%, sensitivity - 85%, specificity - 93%. The advantages of the method also include its accessibility, relative harmlessness for the subject, the possibility of frequent dynamic studies, including at the patient’s bedside using portable devices.

There are cases where, in the absence of ultrasound signs of leukomalacia, lesions were identified at autopsy. Perhaps, with the advent of more advanced diagnostic equipment for ultrasound examination and with the higher qualifications of the doctors conducting the examination, such findings will not be detected.

Ultrasound examination makes it possible to assess the nature of ischemic damage, its localization and stages, as well as the dynamics of the process.

Early ultrasound changes are usually detected during the first two weeks of a newborn’s life, more often on the 1st-3rd day, less often on the 4th-8th day of life. There is also evidence of a later onset of PVL development—on the 10th day (A.B. Safonov et al.).

The picture of the first stage of periventricular leukomalacia is represented by a zone of increased echogenicity in the projection of the outer corners of the lateral ventricles, which include the lateral sections of the anterior and inferior horns, the areas of the ventricular triangles. In severe cases, the entire periventricular region of the lateral ventricles is involved in the process.

The increase in echogenicity of the periventricular brain parenchyma reaches the degree of echogenicity of the choroid plexuses of the lateral ventricles and bone structures. Quite often, zones of increased echo density have a characteristic triangular shape with the base facing the cortical structures and the apex directed towards the ventricle. Such changes are clearly manifested in coronal scanning planes at the level of the anterior cranial fossa, as well as in parasagittal sections through the lateral ventricles. The process is usually bilateral and symmetrical. In cases of asymmetrical damage to the sides and the appearance of an echogenic structure extending to the peripheral parts of the brain, the possibility of hemorrhagic infarction and secondary parenchymal hemorrhage should be assumed.

In the process of diagnosing periventricular leukomalacia in premature children, it should be remembered that almost all prematurely born children have areas of increased echogenicity over the anterior, occipital horns, and bodies of the lateral ventricles during ultrasound examinations. These changes are due to the immaturity of brain structures, and not to the ischemic process. Unlike PVL, these changes are less echogenic than vascular ones

The plexuses of the ventricles are homogeneous, they decrease during dynamic observation and completely disappear by 1-2 months of life.

The subsequent stage of development of PVL is characterized by cystic degeneration of the brain. The appearance of pseudocysts is usually preceded by a decrease in the echogenicity of the periventricular areas. In this regard, during the period from the 10th to the 14th day of life, examination may create a false impression of well-being.

In most children, pseudocysts appear on the 10-14th day of life. Cases of the presence of congenital pseudocysts have been described; they can range in size from 0.3 to 2.5 cm in diameter. There are also known facts of a later onset of the stage of cystic degeneration of the brain - on the 30th and even on the 50th day of life.

Cysts in PVL are multiple, of different sizes, their diameter ranges from 2-3 mm or more. The area of ​​cystic changes is usually somewhat smaller than previously identified areas of high echogenicity. This is probably due to the fact that not all of the hyperechoic area is a zone of necrosis; part of it represents areas of perifocal venous stagnation and edema. However, the number of cysts increases during dynamic observation, creating a feeling of progression of the process. Typically, cystic changes progress over 1-2 months. Between the wall of the lateral ventricle and the wall of the pseudocyst there is almost always intact brain tissue ranging from 2 to 4 mm wide.

In severe variants of PVL, anechoic cavities occupy almost the entire periventricular region of the lateral ventricles. In other, less severe cases of leukomalacia, the cysts are isolated, localized in such typical places as the lateral zones of the anterior and inferior horns of the lateral ventricles, where they are often symmetrical, but can be asymmetrical in nature. Sometimes pseudocysts are surrounded by an echo-positive rim, but more often they are determined against the background of parenchyma of normal echogenicity.

By the 2-5th month of life, pseudocysts are not detected by neurosonography. Small single pseudocysts with a diameter of 2-3 mm may collapse to form small areas of gliosis. Multiple periventricular cysts, involving all parts of the lateral ventricles, always cause atrophy of the brain parenchyma.

Ultrasound criteria for brain atrophy are: widening of the interhemispheric fissure and subarachnoid space, development of secondary ventriculomegaly of varying degrees, widening of the sulci of the brain. In the long term of periventricular leukomalacia, cysts, as a rule, break into the cavity of the lateral ventricles, which leads to the development of porencephaly. The evolution of PVL can occur without ventriculomegaly. It is advisable to carry out the first ultrasound examination on days 1-3 of life; a repeat examination is necessary on days 7-10. In prognostic terms, neurosonography at the age of 1.5-2 months is very informative.

Treatment

There are no radical treatments for PVL due to the irreversibility of the changes. Drugs that improve cerebral circulation (nicergoline, vinpocetine, stugeron) and nootropics (piracetam) are used. There is no convincing data on the effectiveness of hormonal therapy for PVL. Data on the results of the use of antihypoxants are ambiguous.

Subsequently, they try to achieve compensation for psychomotor disorders with symptomatic means; all known methods of correcting movement disorders and rehabilitating patients with delayed psychomotor development are used.

Since periventricular leukomalacia occurs in premature infants, an important element in the prevention of PVL is prolongation of pregnancy and prevention of premature birth.

When a premature baby is born, it is necessary to adequately manage it with control of all indicators of homeostasis in order to timely correct hypoxemia, acidosis, prevent attacks of apnea and fluctuations in blood pressure, leading to cerebrovascular accidents and cerebral ischemia.

Since the most common disease complicated by periventricular leukomalacia is respiratory distress syndrome, the introduction of surfactant preparations into the treatment of these patients, which reduces the severity of respiratory disorders and reduces the need for mechanical ventilation, inspires optimism. Equipping neonatal intensive care units with modern devices for autonomous artificial ventilation (AIV) and monitors should also help reduce the incidence of this severe pathology.

Professor Vladimir SAPOZHNIKOV, Head of the Department of Pediatrics, Tula State University.

Elena NAZAROVA, head of the neonatology department of Tula City Hospital No. 1.