RU2561290C1 - Method for assessing severity of infantile cerebral paralysis (icp) and psycho-speech delay (psd) - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: clinical signs of the disease are identified at neurological examination; computed electroencephalogram is recorded; positron tomography is conducted; short-latency visual, auditory, cognitive, somatosensory (SSEP) evoked potentials are recorded, and neuromyography is performed.That is combined with virologic blood examination, including a blood serological test to detect viruses tropic to nerve cells: antibodies Jg G and Jg M, cytomegalovirus, types 1-2-6 herpes simplex, Epstein-Barr virus, varicella zoster virus, toxoplasma and mycoplasma. The blood immunoassay is performed to determine cell and antibody-mediated immunity, including the immunity to brain-specific proteins: neuron-specific enolase (NSE), S-100 protein; anti-duplex (native) DNA and anti-total myelin protein antibodies Jg G; 25-hydroxyvitamin D (vitamin D(25-0H). The measured values are compared to reference normal values, and the disease is considered to be more severe if any irregularities are observed.

EFFECT: method enables providing more reliable diagnosis that is ensured by additional virologic and immunologic blood examinations.

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Description

The invention relates to medicine, in particular to the diagnosis and treatment of cerebral palsy and delays in psycho-speech development.

In generally accepted practice, as a rule, the severity of the disease in cerebral palsy and ZPRR is assessed by clinical manifestations and neurological examination: the motor sphere in cerebral palsy is assessed: the presence and severity of paresis and paralysis, whether the child holds his head, whether he can sit, turn over, crawl, walk independently or with support, chewing, etc., and the mental sphere with cognitive functions in ZPRR: learning ability, speech, communication ability, socialization, etc. Aggravating factors are also the presence of epileptic seizures, optic nerve atrophy, sensorineural hearing loss, severe joint contractures, various concomitant diseases (heart disease, diabetes mellitus, etc.), structural changes in the brain on neurosonography, magnetic resonance imaging (MRI), or computed tomography (CT); congenital or post-stroke cysts, areas of hypoxic brain damage, hydrocephalus, hypoplasia of the lobes of the brain, etc.

A known method for diagnosing the severity of motor disorders in children with cerebral palsy of the first year of life (RF patent No. 2053713 IPC A61B 5/103 1993), in which the reflexes of oral and spinal automatism, posotonic reflexes, a symmetrical chain installation reflex and the severity of the extensor variant are studied labyrinth tonic reflex and their manifestations diagnose a severe or moderate degree of delayed motor development. - The prototype.

The known method does not allow to identify an infectious component in the etiology of cerebral palsy and ZPRR.

The technical result from the use of the invention can be expressed in determining the risk factors for the development of severe brain damage on the basis of the assessment of ante- and intrapartum factors in the pathogenesis of hypoxia, as well as in a more accurate determination of the nature and severity of the disease.

The claimed result is achieved as follows.

A method for assessing the severity of cerebral palsy (cerebral palsy) and / or delays in psycho-speech development (ZPRR) is that they reveal the clinical signs of the disease during a neurological examination; register a computer electroencephalogram (CEEG), conduct emission-positron tomography (PET); Record short-latency evoked potentials: visual (VEP), auditory (VVP), cognitive (VVP), somatosensory (SSVP), conduct neuromyography, additionally conduct blood tests:

- virological, including serological testing of blood for viruses tropic to nerve cells: to antibodies Jg G and JgM, to cytomegalovirus (CMV), to herpes simplex virus (HSV) 1-2-6 types, to Epstein-Barr virus (EBV, ) to the Varicella-Zoster virus (BBZ), toxoplasma, mycoplasma),

- immunological to cellular and humoral immunity, including immunity to brain-specific proteins: NSE-neurospecific enolase, S-100 protein ES-hundred, antibodies to DNA double helix native, Jg G antibodies to common myelin protein; on vitamin D-250H (25-hydroxyvitamin D),

after which the obtained indicators are compared with control standards and the disease is considered more severe when deviations from their norm are detected.

Conducting blood tests for brain-specific proteins, viruses, for immune status, emission positron tomography (PET) and registration of all short-latency evoked potentials: visual (VEP), auditory (SVP), cognitive (CVP), somatosensory (SSVP), allowed not only to reveal new changes in the brain and spinal cord, but also to carry out additional treatment, which contributed to the regression of neurological and mental defects and affected the quality of life of these children, significantly improving it.

For the diagnosis of cerebral palsy and ZPRR of an organic nature in children, anamnesis is very important - an analysis of the course of pregnancy and childbirth. Diagnosis of fetal hypoxia in the antenatal period is based on the following symptoms: the presence of risk factors in the history of the pregnant woman, impaired fetal heart rate (tachy or bradycardia), non-reactive non-stress test: lack of increased fetal heart rate (acceleration); the presence of late decelerations (decrease in fetal heart rate) in response to uterine contractions. The presence of fetal hypoxia is indicated by a change in the frequency of movement of the fetus (trunk, limbs and head) in the form of increased frequency and increased or severe inhibition;

- increased or decreased respiratory movements of the fetus;

- decrease in the volume of amniotic fluid, according to an ultrasound scan;

- a change in the area and volume of the placenta, a decrease in the uteroplacental and fetal blood flow;

- the presence of fetal growth retardation.

In the intranatal period, the development of asphyxia is indicated by complications during childbirth (mismatch between the diameters of the fetal head and pelvis of a woman, large fetus, brachial dystocia, abnormal presentation of the fetus or placenta, twins, bleeding, prolapse and compression of the umbilical cord loops, rapid or prolonged labor) , a change in heart rate and arrhythmia in the fetus, an admixture of meconium in the amniotic fluid.

The main clinical manifestations of various CNS lesions at birth are taken into account, which in the future can lead to the development of cerebral palsy or ZPRD: hypoxia, metabolic disorders, meningitis, sepsis, etc., such as (adynamia, akinesia, muscle hypotension, cyanosis, convulsive syndrome). These phenomena can be expressed to varying degrees. With the most severe lesions of the central nervous system, impaired consciousness (from a stupor to a coma) appears, irregular breathing, muscle hypotension, followed by atony, the absence of most congenital reflexes (sucking, Moro reflex, etc.), impaired eyeball movement (nystagmus, “wandering” gaze) are noted ), the lack of pupil response to light, in 50% of children 6-12 hours after birth, clonic multifocal or tonic convulsions are observed. With the progression of disorders, at the age of 12-24 hours, apnea appears as a result of brain stem dysfunction.

A feature in premature infants is the layering of pathological symptoms on the manifestations of immaturity of the central nervous system. In mild forms of damage, it is almost impossible to differentiate the signs of immaturity of the central nervous system from signs of damage.

The severity of emerging disorders of the respiratory system, cardiac activity and central nervous system in newborns is evaluated on the APGAR scale. It should be noted that the sensitivity of assessing the condition of the newborn on the Apgar scale is about 50%.

Methods of neuroimaging. Neurosonography

Ultrasound examination of the brain - neurosonography (NSG) is a neuroimaging technique that has long been used to diagnose brain lesions in newborns, which has become routine. This is a non-invasive, affordable and fairly informative method based on computer processing of the reflected ultrasound signal, which allows you to obtain images of brain structures in various planes. In the acute period in newborns, various conditions do not have specific clinical signs, and ultrasound scanning of the brain helps to establish the type, degree and dynamics of central nervous system damage. Ultrasound examination of the brain with ischemia has a limited range when using standard 5 MHz sensors. In this case, edema or hemorrhage is detected. An increase in echogenic density and loss of a normal anatomical structure are not always related to cerebral edema. When using sensors with a power of 10 MHz, ischemic damage to the thalamus is clearly detected (“brilliant thalamus” - hyperechoic bilateral signal), small hemorrhages corresponding to the descriptions of pathologists as status marmoratus. In patients with subarachnoid hemorrhage, an expansion of the interhemispheric and sylvian fissures, sometimes thrombi in the lateral groove, is noted.

Changes that are well detected by ultrasound include: ventriculomegaly, severe intracerebral hemorrhage, cerebral edema, cysts, cerebral infarction, severe developmental abnormalities.

Magnetic resonance imaging (MRT), computed tomography (CT)

Currently, MRT and CT are some of the most informative methods of intravital non-invasive imaging and detection of various structural abnormalities of the brain. Computed tomography of the brain has its own diagnostic “corridors” and the most accurate prognosis is on the 10th day of life. By this time, the swelling of the brain tissue is reduced, and hypodensive zones of ischemia of the cortex and white matter are detected. Ischemic damage to the basal ganglia is better determined using magnetic resonance imaging. When hemorrhages are localized in the posterior cranial fossa and pericerebellar region (these hemorrhages are mainly hypoxic-ischemic in nature), computed tomography is the method of choice.

Perinatal hypoxic-ischemic damage to the central nervous system is a process that is not limited to the first months of life: children who underwent GPPGM in the future may have noticeable neurological disorders and structural changes detected by neuroimaging methods.

Indications for the diagnosis of organic brain damage, carried out according to indications

1. Electrophysiological methods

1.1. Electroencephalography (EEG) on devices ("Nicolet", USA)

EEG is a method for studying the bioelectrical activity of the brain that occurs during its activity, with computer processing of data and a complete analysis of electroencephalography.

Computer EEG (CEEG) evaluates the functional (working) state of the brain as a whole, as well as its individual areas. KEEG is used to detect volumetric processes (tumors, cysts, etc.), inflammatory (encephalitis, meningitis, etc.), vascular (discirculatory encephalopathy) and traumatic brain diseases (suffered traumatic brain injuries).

With the help of KEEG, the epileptic foci are refined and identified with their localization and viewing the intensity of the pathological foci, as well as refining its trajectory in areas of the brain, interhemispheric asymmetry, brain maturity, etc.

1.2. Evoked Potentials (VP) Methods

- evoked potentials of the brain of various modalities: visual, auditory, somatosensory, cognitive (P300) on devices (Neurosoft, Russia). The technique of Evoked Potentials of the Brain (EP) consists in isolating and averaging weak and superweak potentials of the bioelectric activity of the brain in response to various afferent stimuli. The types of stimuli given can be either exogenous - visual, auditory, sensitive, or endogenous - cognitive.

Visual Evoked Potentials (VIZ). The method of objectification of the states of visual functions in young children and adults

Various modifications of the methods make it possible to study the syndromes of the lesion of the visual analyzer at various levels: the retina, the optic nerve, the optic tract with a cross, the occipital lobes of the brain.

This method allows you to objectively assess the condition of the optic nerve and determine the level of damage.

Auditory Evoked Potentials (SVPs)

This method allows you to accurately determine the damage to the auditory nerve in newborns (exclude congenital deafness), in children with cerebral palsy and ZPRR, it allows you to track the dynamics of the recovery and damage functions at the level of the nerve, trunk, temporal lobe in hearing-impaired and non-speaking children, and also helps to select the most accurate hearing aid.

Somatosensory Evoked Potentials (SSEP)

SSEPs are the electrical responses of nerve conductors and centers to stimulation of nerve trunks.

SSEPs are very informative in children and adults, patients with inappropriate behavior, when assessing the degree of traumatic, postpartum damage to nerves, plexuses, spinal cord, brain stem and cerebral hemispheres.

SSEPs are used to assess the restoration of nerve conduction of a paralyzed limb.

Cognitive Evoked Potentials (CEP)

Classical methods for extracting and analyzing EP, which are used to diagnose the level and degree of damage to analyzers (sensory organs), can be used to analyze higher cortical functions (thinking, memory, etc.). The processes of recognizing and remembering information, as well as making a decision, are accompanied by more or less regular neurodynamic measurements that can be objectively recorded. This method is used to determine the amount of RAM, the correspondence of the functional maturity of the brain to the calendar, to evaluate perception, recognition, differentiation, and engaging in the task to diagnose the earliest stages of personality degradation, to monitor the results of treatment of mental disorders in children and to identify side effects of drugs.

1.3. Electroneuromyography (ENMG)

- Electroneuromyography on devices (Neurosoft, Russia)

A method based on the registration and analysis of the electrical activity of muscle and peripheral nerve fibers. Distinguish between spontaneous and induced ENMG. With spontaneous ENMG, characteristics are obtained that reflect the state of peripheral nerves and muscles that are at rest or in a state of muscle tension. When called ENMG, they receive answers that arise in response to stimulation of the peripheral nerve or muscle by electric current.

The study of the functional state of the muscle, the degree of its involvement in the pathological process, the safety of innervation, or the determination of the amount of reinnervation are the main issues to be solved when conducting an electromyographic study. ENMG is widely used for differential diagnosis between neurogenic and primary muscle diseases, contributes to their early diagnosis, allows solving problems related to the pathogenesis of certain forms of neuromuscular diseases, to judge the course of the denervation and reinnervation process in the muscles under the conditions of the formation of compensatory innervation, accurately trace all stages of development and the severity of the denervation syndrome in the muscle.

Positron emission tomography (PET) of the brain, a method of image reproduction (used, in particular, for analysis of the brain), which gives a three-dimensional image, radioisotopes introduced into the circulatory system before the procedure starts are absorbed by the tissues where they emit POSITRONS that generate Photons, which can be seen on the screen.

PET studies make it possible to identify not only diseases that affect the brain in the early stages, but also evaluate the work of neurons as a functional whole system. The patient is injected intravenously from a dropper a chemical substance that spreads through his body. The scanner emits low energy gamma radiation on the parts of the body being examined. Gamma radiation causes a radioactive chemical in the patient’s blood to emit photons that are interpreted by computer programs, resulting in the display showing how various areas of the brain function. When the scanner moves along the head, cross sections of the brain appear on the screen.

To determine the amount of vitamin D, 25-hydroxyvitamin D is usually used because of its high concentration and long half-life. 25-hydroxycalciferol is an intermediate product of the conversion of vitamin D, by the level of which in the blood it is possible to judge the saturation of the body with calciferol and to identify a deficiency or excess of vitamin D. In case of a deficiency of vitamin D, the level of calcium is compensated by its mobilization from bone tissue, which can lead to osteomalacia, rickets in children and osteoporosis in adults. According to some studies, vitamin D deficiency is also associated with autoimmune and cancer diseases, hypertension, heart disease, multiple sclerosis, type 1 diabetes. The risk of developing vitamin D deficiency is high in children with malabsorption of nutrients in the intestines (for example, with Crohn's disease, exocrine pancreatic insufficiency, cystic fibrosis, celiac disease, conditions after resection of the stomach and intestines), liver diseases, and nephrotic syndrome. However, overuse of vitamin D medications has negative effects. Its excess is toxic, can cause nausea, vomiting, stunted growth and development, kidney damage, impaired calcium metabolism and the functioning of the immune system. In this regard, it is important to control the level of vitamin D in the blood, timely diagnosis of its deficiency or excess.

Neuroimmunological blood test

High infant mortality, as well as childhood disability due to infectious diseases are a serious demographic problem. Infection of the fetus and the infectious process can begin in the prenatal period, during childbirth or postnatally. These are the so-called perinatal or intrauterine infections (IUI). The most common IUIs are indicated by TORCH syndrome.

The danger of TORCH syndrome and other viral infections is that they cause 80% of congenital malformations in children. Among them, the leading place is occupied by damage to the central nervous system, congenital defects of the heart and kidneys, other organs and body systems, it was found that infection of the fetus in the first trimester of pregnancy leads to the development of micro, hydrocephalus, heart defects, gastrointestinal tract, and urogenital systems, skeleton, cataracts, deafness. Infection in the II and III trimesters causes the fetus to have hepatosplenomegaly, anemia, jaundice, malnutrition, pneumonia, meningoencephalitis, sepsis.

A high-precision virological blood test for TORCH syndrome is carried out in accordance with the rules of GCP and GLP, with the assessment of cellular, humoral immunity to exclude an autoimmune demyelinating process with a% determination of brain white matter destruction and prediction of the clinical outcome of perinatal hypoxia.

The use of neurospecific proteins (NSS) as markers of various pathological changes occurring in the central nervous system, especially the expression of neuropeptides involved in the pathogenesis of hypoxic damage to the central nervous system in children and the possibility of their use for the diagnosis of perinatal lesions and in vivo assessment of the processes that occur in the cells of the nervous tissue in postnatal period, are one of the promising areas of modern neurophysiology and medicine.

As an example, we present the results of an analysis of the examination and treatment of 105 children with a diagnosis of cerebral palsy and ZPRR. The age of children ranged from 6 months to 14 years. The patient underwent: computed electroencephalography with evoked potentials, magnetic resonance imaging (positron emission tomography was performed) of the brain, ultrasound examination of internal organs, clinical tests of blood and urine according to generally accepted methods, investigation of the STARCH complex infection by polymerase chain reaction methods and enzyme immunoassay with the determination of immunoglobulins G and M.

All children had an obstetric and perinatal history: the threat of termination of pregnancy was noted in 69% of mothers, with half of them in the I and II trimesters, severe histosis - 41%, immunoconflict - 23%, in 31% of mothers exacerbation of genital herpes , 15% were treated for infertility, more than 30% had ARVI, 5% - toxoplasmosis during pregnancy. Signs of fetoplacental insufficiency were observed in 65%, and exacerbation of chronic ureoplasmosis, chlamydia, mycoplasmosis - in 40% of mothers, chronic intrauterine hypoxia of the fetus - in 73%.

EXAMPLE No. 1.

Sh.S., one and a half years.

He was admitted with a diagnosis of cerebral palsy. Spastic diplegia. Epilepsy of unclear etiology with polymorphic seizures.

OBJECTIVE: Upon admission: asthenic, lethargic, very quickly exhausted, conscious, reacts to crying when examined, meningeal signs (-), percussion soreness of the skull on the right. Weather dependent, the gaze does not always fix. He doesn’t walk on his own, he can’t sit, he doesn’t take toys. He does not hold his head, a head with slightly enlarged frontal tubercles and an expanded subcutaneous venous network. He doesn’t walk, legs are running out.

FMN: asymmetry of the nasolabial folds, photoreactions are reduced, phonation from the soft palate is reduced, positive reflexes of oral automatism. Muscle tone in the back is low. Raised in the limbs. Tendon and periosteal reflexes are high in organic type. Pathological reflexes from the legs and arms. Abdominal reduced.

There are no sensitive disorders. Attacks with loss of consciousness persist.

Comments: the diagnosis with which the child was previously observed was made on the data of the history of the development of birth and disease, EEG, MRI (see table), despite the medication prescribed at the place of residence (antiepileptic drugs, vascular, vitamins), the absence of negative dynamics on repeated EEG and MRI, the child’s condition continues to remain quite serious - the child is significantly behind in motor and psycho-speech development (see objective data) with ongoing seizures with loss of consciousness. The results of additional examinations indicated in the formula (see table) made it possible to set up not only a complete clinical, but also a topical diagnosis.

Clinical diagnosis

The consequence of early organic lesion of the central nervous system is intrauterine mixed herpes virus (CMV, HSV type 1-2, EBV), mycoplasma neuroinfection, neurotoxoplasmosis, ventriculitis, severe dysmetabolic, hypoxic-ischemic encephalomyelopathy, with an outcome in: 1) perinuleural leukemic leukemia, and reverse cerebrospinal fluid absorption; 2) sluggish mixed neuroinfection of the type of cystic-adhesive arachnoencephalitis, with a violation of cellular immunity, with a violation of tolerance to the common myelin protein. Secondary epi syndrome. Severe prolonged intoxication of Vitamin D. Toxic encephalopathy.

Syndrome of motor disorders in the form of spastic tetraparesis: 2 degrees in the arms, 3 degrees in the legs with impaired motor function of 3 degrees. Moderate pseudobulbar syndrome. Hypertension syndrome with hemorrhagic distension. Persistent cerebral asthenia syndrome with a cerebral component.

Topical diagnosis

- defeat of the commissural paths between the right and left hemispheres;

- partially selective damage to the parasagittal fibers of the pyramidal pathway in the periventricular zone, which are excessively stretched with the expansion of the lateral ventricles, due to impaired absorption of cerebrospinal fluid;

- violation of the conduct on the posterior cords of the spinal cord (Gaulle and Burdach bundles);

- partial damage to the descending paths of the extrapyramidal system;

- the connection between the frontal gyrus, the cerebellar hemispheres, the upper right and lower parietal lobes is broken;

- violation of transneuronal connections due to the low functional activity of the inserted neurons of the spinal cord C2-C4, on which the fibers of the pyramidal and rubrospinal tract end, leading to spasticity in the legs;

- low functional activity of the anterior-internal group of cells of the anterior horn C2-D8, leading to hypotension of the back muscles.

Thus, additional examinations revealed:

- sluggish mixed neuroinfection according to the type of cystic-adhesive arachnoencephalitis, with impaired cellular immunity, with impaired tolerance to the common myelin protein (i.e., determine the cause of ongoing epi-seizures);

- pronounced prolonged intoxication of Vitamin D, leading to toxic encephalopathy;

- signs of a pronounced diffuse decrease in the metabolic activity of the brain (see PET);

- incomplete myelination with demyelination elements (according to NSE, S-100, MBP);

- low axon regeneration and a significant decrease in the number of pool of motor neurons excited by stimulation of afferent Ja-fibers (according to Hp).

All this significantly aggravates the condition of the child, proves the severity of the disease and explains the significant lag in motor and psycho-speech development. The main thing is that it allowed to prescribe the correct treatment and improve his well-being (see below).

After further examination

Recommended treatment:

- Drink magnesium B6 in 1/3 of the ampoule day and evening - 2 months.

- cycloferon 2.0 v / m No. 10 on even days in alternation with

- Derinat 2, .5, v / m No. 10 on odd days,

- dexometasone 0.7 ml / m No. 5 on even days,

- vit. B12 for 400 g / m No. 5 on odd days.

- acyclovir, isoprinazine, cytotect, detoxification therapy, mexifine according to the scheme.

After the course of treatment, the child’s condition improved significantly: he had epi-seizures, got better, began to hold his head, fix his gaze, became calmer, more active.

EXAMPLE No. 2

B.A., three years.

Observed at the place of residence with a diagnosis of cerebral palsy. Spastic tetraparesis. Severe degree. Delay in psycho-speech development. Episyndrome.

Objectively: in consciousness, meningeal signs (-) are asthenic, emotionally labile, quickly depleted, are interested in toys - picks up, throws them away. He listens to poems, partially understands the addressed speech, speaks 4 words. The pronunciation is somewhat blurry, time-stretched, fuzzy, with a nasal tinge. Physically rapidly depleted due to moderate exhaustion of nervous processes. Attention is erratic. A moderate violation of spatial gnosis was revealed, motor, ideator, constructive apraxia is diagnosed. It doesn’t stand on its own, sits with support, does not creep, can walk with support - first on toes, then puts on a full stop, periodically walking with a cross. When walking by the handles can hold your back. Head with dilated subcutaneous venous network, painful percussion of the skull, meteosensitive. FMN: convergent squint, PROS OU, gaze fixes, hypersalivation, lowered phonation from the soft palate, periodically chokes, chews on its own. Muscle tone is of a mixed type, decreased in the muscles of the back, increased in the limbs, more in the legs. Tendon and periosteal reflexes are animated by the organic type, in the lower extremities more than in the upper ones. Pathological reflexes from the legs. There are no sensitive disorders. Moderate trunk statomotor and sensitive ataxia.

As a result of the examination, a clinical diagnosis was made:

The consequence of perinatal damage to the central nervous system - (IUI as a transferred generalized mycoplasma infection), severe hypoxic-ischemic encephalomyelopathy of premature infants, ventriculitis, dislocation of the spine in segments C2-C3, C3-C4, L4-L5 with hemodynamic impairment in these segments, with outcome

1) periventricular leukopathy, Arnold-Chiari anomaly of 1 st., Ventriculomegaly with normotensive hydrocephalus with impaired reverse cerebrospinal fluid absorption;

2) chronic persistent sluggish mycoplasma neuroinfection according to the type of convexital arachnoiditis, inactive phase with immune deficiency in the cellular and humoral types without autoneuroimmune aggression, but with a violation of tolerance to the main myelin protein and persistent moderate violation of permeability.

Syndrome of motor disorders in the form of central tetraparesis: 1 degree in the arms, 2 degrees in the legs with impaired motor function of 2 degrees. Syndrome of moderate cerebellar and posterior column failure 2 degrees. Hypertension syndrome with hemorrhagic distension. Visual Disorder Syndrome (retinopathy of prematurity). Episindroma, drug remission.

Topical Diagnosis

- partially selective damage to the parasagittal fibers of the pyramidal pathway in the periventricular zone, which are excessively stretched with the expansion of the lateral ventricles, due to impaired absorption of cerebrospinal fluid;

- violation of the conduct on the posterior cords of the spinal cord (Gaulle and Burdach bundles);

- violation of transneuronal connections due to the low functional activity of the inserted neurons of the spinal cord C2-C4, on which the fibers of the pyramidal and rubrospinal tract end, leading to spasticity in the legs;

- low functional activity of the anterior-internal group of cells of the anterior horn C2-D8, leading to hypotension of the back muscles;

- violation of the connections between the frontal gyrus, cerebellar hemispheres, right upper and lower parietal lobes.

Comments: the diagnosis with which the child was previously observed was made on the basis of data on the history of the development of birth and disease, EEG, MRI (see table), the severity of the lesion was initially unreasonably overestimated, taking into account this, the prognosis for further development of the child would be considered unfavorable, despite for further rehabilitation. The medication prescribed at the place of residence included a wide range of drugs (antiepileptic drugs, vascular, vitamins), which, apparently due to the general effect, did not improve the condition of the child. The results of additional examinations indicated in the formula (see table) revealed the following changes:

1A) - persistent cerebral hypoxia of preterm NSEs, sluggish mycoplasma neuroinfection of the type of convexital arachnoiditis with impaired tolerance to the common myelin protein (i.e., to determine the cause of the delay in motor development and epi-seizure);

- a significant deficiency of Vitamin D, exacerbating the existing delay in motor development and leading to increased muscle weakness;

2.B) - signs of a moderate decrease in the metabolic activity of the brain (see PET);

- incomplete myelination (according to NSE, S-100, MBP);

- low axon regeneration and the normal number of motoneuron pool excited by stimulation of afferent Ja-fibers (according to Hp), non-coarse changes in CEEG, absence of demyelination processes (MBP).

The changes indicated in paragraph 1A) allowed the appointment of pathogenetic drugs that act on the cause: antibiotics (summed), antioxidants (solcoseryl, mexifine, mildronate, neuromultivitis, wobenzim) and correction of vitamin D deficiency, after which improvement was noted (was re-examined after 3 months): increased motor activity, decreased spasticity in the extremities, began to roll better, lower the heel lower when walking, less cross when walking, more trying to crawl, trying to sit up from a lying position, sit "Turkish" 5 minutes with a support on hand, to strengthen the muscles of the back, neck, improved voice activity, say 5-6 words, it is better understood what was discussed.

The changes indicated in paragraph 1B) made it possible to “lower” the severity of the lesion set earlier, and taking into account this, the prognosis for the further development of the child is considered favorable.

EXAMPLE No. 3

Shch.A., eight years old.

Observed in the community with a diagnosis of Delayed psycho-speech development, hyperdynamic syndrome.

On examination: in the mind, meningeal signs (-), hyperactive, disinhibited, friendly, intrusive, reduced criticism of their behavior, prone to affects. Very anxious, afraid of the new. He speaks about himself in the 3rd person. Active speech in the form of ready-made forms of words or phrases (from cartoons), uses them as integral units. Frequent echolalia. Self-conscious, phrasal speech is poor. The meaning of complex inverted speech is partially understood. Mechanical visual memory is high. Attention is extremely unstable due to the rapid exhaustion of nervous processes. A violation of spatial gnosis was revealed, motor, ideator, constructive apraxia is diagnosed. Disorientation right-left. Revealed moderate dynamic ataxia, dysmetria, asynergy, adiadokhokinez. Walks independently. Mostly used with one hand. Emotionally very labile. Visual-figurative thinking, abstagation is not available. The head is somewhat hydrocephalic with an expanded subcutaneous-venous network and enlarged frontal tubercles, painful on the right, percussion of the skull. He dresses partially, can run away. Very selective in food. Recently I began to look at books and become interested in children. It is hard to remember verses.

FMN: asymmetry of the nasolabial folds, photoreactions are normal, phonation from the soft palate is reduced. Positive reflexes of oral automatism. There are no paresis. Muscle tone is of a mixed type, with a tendency to decrease. Tendon and periosteal reflexes are animated by the organic type. Pathological reflexes from the legs and arms. Abdominal slightly reduced. There are no sensitive disorders.

Clinical diagnosis

Organic personality disorder as a consequence of post-vaccination and chickenpox neuroinfection, hypoxic-ischemic encephalopathy with a transition to chronic persistent sluggish neuroinfection, such as demyelinating encephalocerebella with immune deficiency in the cell and humor-specific hemorrhagic immune syndromes insufficiency in the vertebrobasilar basin.

Cerebellar insufficiency syndrome. Pseudobulbar syndrome.

Hypertension-hydrocephalic syndrome with hemoliquor distension. Grade 2 cognitive disorder with abnormal behavior. Grade 2 speech disorder with elements of an autistic type of defect in the form of a mixed sensory-mnestic and semantic alalia. Anxiety-phobic syndrome. Alexia, dysgraphia.

Topical diagnosis

- violation of the conduct on the posterior cords of the spinal cord (Gaulle and Burdach bundles);

- partial damage to the descending paths of the extrapyramidal system;

- communication between the frontal gyrus, cerebellar hemispheres, right upper and lower parietal lobes is broken.

- Associative connections between the motor and sensory centers of speech are broken (fields 44, 45, 46, 6, 37 and, in part, Field 21 according to Broadman), as well as with the visual analyzer;

- total defeat of the temporal-parietal-occipital region on the left (field 39 according to Broadman);

- violation of the frontal-cerebellar pathway from field 8 on Broadman;

- violation of the conduct in the posterior section of the middle frontal gyrus near field 6 (the center provides automatic writing and is functionally connected to Brock's center).

Comments: the diagnosis with which the child was previously observed was made on the basis of the history of birth and disease, EEG, MRI (see table), initially it was not fully specified, the reason for the delay in psycho-speech development was not clarified, the severity of the lesion was “underestimated” With this in mind, the prognosis for the further development of the child was considered favorable, i.e. the child should have started talking and studying at school. But despite further medical treatment prescribed at the place of residence (nootropics, vascular, vitamins), the condition of the child did not improve (see objective data), at the time of examination, the child remains practically uneducated. The results of additional examinations indicated in the formula (see table) revealed the following changes:

1A) - persistent cerebral hypoxia according to NSE;

- establish the cause: the consequence of post-vaccination and chickenpox neuroinfection;

- establish the current disease leading to a developmental delay: chronic persistent sluggish neuroinfection of the type of demyelinating encephalo-cerebellitis with immune deficiency in the cellular and humoral types with autoneuroimmune aggression to brain-specific proteins;

2B) - signs of a moderate decrease in the metabolic activity of the brain (see PET);

- incomplete myelination with demyelination elements (according to NSE, S-100, MBP).

The changes indicated in paragraph 1A) allowed the appointment of pathogenetic preparations (acting on the cause): antiviral (acyclovir), antioxidants (solcoseryl, mexifine, mildronate, neuromultivitis, wobenzym), immunocorrectors (cycloferon, derinat, hydrocortisone), nootropics ( , cortexin) and behavioral correctors (risplept, adaptol), after which improvement was noted (was re-examined after 3 months): it became calmer, more balanced, more assertive - it assimilates new material more, speech activity increased - I started talking times the deliberately increased vocabulary began to understand better the complex facing it - poems, short stories, significantly reduced anxiety, reduced selectivity in the food.

The changes indicated in clause 1B) made it possible to “make heavier” the diagnosis made earlier and, taking this into account, draw up further treatment courses and social adaptation.

Most often, in the examined sick children (45%), a chronically persistent cytomegalovirus or herpetic infection with the effects of sluggish leukoencephalitis and arachnoiditis was verified. In 21% of children - neuroinfection due to listeriosis, ureoplasmosis, chlamydia. In 18% of cases, children in utero suffered toxoplasmosis, candidiasis, mycoplasmosis, complicated by urosepsis, pneumonia with pulmonary edema, gastric and intestinal bleeding, as well as meningitis and meningoencephalitis. In 5% of cases during the neonatal period, acute meningoencephalitis was diagnosed, and in 3%, acute radiculoganglioneuritis caused by the association of herpetic viruses (herpes simplex virus, Varicella-Zoster, Epstein-Barr). A third of children are diagnosed with intrauterine pneumonia, malnutrition; 40% - neonatal jaundice, hepatosplenomegaly, thymomegaly and subclinical thyroid dysfunction; heart defects and connective tissue dysplasia were found in 10% of patients, in 6% - malformations of the genitourinary system. In 30% of children - pathology of the organs of vision (glaucoma, microphthalmia, coloboma, atrophy of the optic nerves), etc.

According to neuroimaging data, in 56% of the examined patients subcortical cysts were found in the brain parenchyma, in 42% - subatrophy of the cerebral cortex, ventriculomegaly - 46%, foci of gliosis and periventricular leukomalacia - 52%, thinning of the corpus callosum - 27%, congenital malformations 11%, intraventricular hemorrhage - 65%, cerebrospinal fluid occlusion - 2%.

In most children with IUI, the formation of a gross neurological defect was clinically observed (up to 77% of the total number of patients) in the form of central tetraparesis, paraparesis, hemiparesis or spastic diplegia, hemiplegia, other signs of pyramidal insufficiency, statomotor and sensory ataxia, hyperkinesia, and an increase in and vestibulotonic reflexes.

45% observed intellectual and behavioral disorders, epileptic syndrome - 55%. With a milder outcome of transferred IUI, in 33% of cases the syndrome of minimal cerebral dysfunction (MMD) was revealed in the form of attention deficit hyperactivity disorder. These disorders were distinguished by persistence of manifestations and resistance to drug treatment, as well as in 15% of those who turn into behavioral disorders.

The immunological status in children was determined using monoclonal antibodies CD3, CD4, CD8, CD19, CD16, CD20 and a white blood cell count in a blood smear. Immunoglobulins were determined by the method of radial diffusion in a gel according to Manchin. All children were divided into 3 groups depending on age. The first group included children under 1.5 years of age, whose average age was 13.4 months. The second group included children from 1.5 to 6 years old, whose average age was 46.7 months. The third group consisted of children aged 6 to 14 years, whose average age was 10.8 years.

In the first group, the average immunological parameters did not go beyond the scatter of normal values in healthy children. Only one third of children experienced a sharp decrease in the total pool of lymphocytes both in percentage (20% versus 48% of the lower limit of normal) and in absolute terms (1180 versus 4860, 2 × 10 6 / l of the lower normal range). Accordingly, below the norm were CD3 in% and in absolute terms. The absolute values of CD 16 (NK cells) were also reduced. This clinically coincided with the active phase of viral neuroinfection. On average, in the 2nd group, half of the children (50%) showed a decrease in the number of CD4 (helpers / inductors) in percent and in absolute terms, and the immunoregulatory index (IRI) 1.6 0.1 versus 2.4 0.1 normal, which indicates a violation of the ratio of immunoregulatory subpopulations of CD4 / CD8. In addition, there was a decrease in the absolute value of B-lymphocytes (CD 19) in 30% of children and JgA in 48% of patients.

In the 3rd group, against the background of relative leukocytosis, significant lymphocytosis was noted. On average, in the group 47.2 2.5 versus 30.2 1.9 in 25% of cases, lymphocytosis was higher than 50%. The subpopulation of CD4 (helpers / inducers) in 26% of cases was below normal in both relative and absolute terms. The subpopulation of CD8 (cytotoxic suppressor lymphocytes) on average in the group was reduced and amounted to 25.0 1.9% versus 31.5 2.2% normal, and in 26% of cases, CD8 was significantly reduced, less than 17.5%. IRI in 60% of cases was below normal. The number of B-lymphocytes (С019) was reduced in 26% of cases, which affected the amount of immunoglobulins in the blood serum of sick children. JgA production in 50% of cases was below normal. JgM levels in 38.4% of children were above normal, and JgG in 23% of cases below normal. A decrease in the number of NK cells (CD 16) was noted in relative terms in 25% of cases, and in absolute terms in 49% of children. Which corresponded to the active phase of viral neuroinfection. The severity of neuroinfection and neurological defect correlated with the severity of violations of immunoregulatory subpopulations of NK cells, a decrease in CD4 and CD8.

Viruses and some other causative agents of infection can persist in the body and live either in the ganglia (nerve nodes) of the cranial nerves in the case of herpes, or in the salivary glands with cytomegalovirus, etc. Hidden viruses, when the opportunity arises (hypothermia, hyperinsolation, stress, acute respiratory infections, etc.) begin to become active, multiply and penetrate the brain hematogenously or periaxonally. This is facilitated by the imperfection of immunity in this group of children, which causes the development of chronic sluggish or recurrent neuroinfection, which leads to aggravation and progression of damage to all brain matter, a decrease in the function of the blood-brain barrier, destruction of axial myelin sheaths, and a decrease in general immunity. As well as dysfunctions of the cells of the vascular plexuses of the ventricles of the brain, which leads to the hypersecretory or aresorptive effect of cerebrospinal fluid dynamics with the development of hemoliquor distension. These changes cause decompensation of the existing hydrocephalus or lead to it. Enlarged intracerebral ventricles constantly compress the pathways, which does not help to compensate for motor disorders and other concomitant disorders of the brain. It was found that the level of S-100 Protein in children is indicative of brain damage during neuroinfection: an increase in the level of this antigen in the early neonatal period was noted.

S-100 protein level directly correlates with the severity of brain damage and vice versa - with the restoration of neurological status. The concentration of S-100 to predict the course of the disease can be determined in blood serum, cerebrospinal fluid and urine. Currently, it has been shown that S-100 is a group of acidic calcium-binding proteins that are unique to nervous tissue, differing in charge and weight, but immunologically identical. Their concentration in the brain is 100,000 times higher than the content in other tissues and amounts to 90% of the soluble fraction of nerve cell proteins. One representative of the S-100 group is S-100β, the most specific brain tissue protein. It is known that during the destruction of brain tissue S-100β along with other proteins of this group can be found in the blood and cerebrospinal fluid of patients. Protein S-100β is of particular interest in connection with the recent discovery of its neuro growth and neurotrophic properties of the factor (CNTF-ciliary neurotrophic factor). Growth factors support the life of neurons, which in their absence cannot exist. Trophic dysregulation is one of the universal components of the pathogenesis of damage to the nervous system. With the loss of trophic support of mature cells, biochemical functional dedifferentiation of neurons with changes in the properties of innervated tissues develops. Trophic dysregulation affects the state of macromolecules involved in membrane electrogenesis, active ion transport, synaptic transmission and effector function.

Thus, the study of neurotrophic factors in the early neonatal period is very important because it will reveal the mechanisms of the damaging effects of hypoxia on the brain and determine the degree of influence of the level of neurotrophins on the prognosis of the formation of structural posthypoxic changes in the brain.

Chronic IUIs with a secondary immunodeficiency state not only support the severity of existing neurological and mental defects in the child, but also further aggravate their degree and are a factor in the progradient or recurrent course of cerebral palsy. This can explain the appearance of new concomitant syndromes of cerebral palsy.

It must be emphasized that in cases of adverse, progressive course of cerebral palsy in the child, the absence of a positive effect under the influence of generally accepted (standard) habits programs, it is necessary to exclude the infectious component in the etiology of cerebral palsy.

Perinatal hypoxic-ischemic damage to the central nervous system is a process that is not limited to the first months of life: children who underwent GPPGM in the future may have noticeable neurological disorders and structural changes detected by neuroimaging methods.

Changes that are well detected by ultrasound include: ventriculomegaly, severe intracerebral hemorrhage, cerebral edema, cysts, cerebral infarction, severe developmental abnormalities.

In such cases, in addition to instrumental examination of the brain and spinal cord (including MRI and PET), a blood test should be performed on the STARCH syndrome (in accordance with the rules of GCP and GLP), with an assessment of cellular, humoral immunity to exclude autoimmune demyelinating process, with a percentage determining the destruction of the white matter of the brain and predicting the clinical outcome of perinatal hypoxia. All this will clarify not only the nature of the disease, but also its further severity.

Thus, a sufficiently detailed study of the mechanisms of hypoxic peri- and postnatal brain damage in children, with an assessment of the role of ante- and intrapartum factors in the pathogenesis of hypoxia, allows us to form clear ideas about the molecular mechanisms that can subsequently lead to irreversible structural changes in the brain brain. The timely and correct assessment of the state of the prenatal period, the determination of risk factors for the development of severe brain damage and the possibility of early diagnosis largely determine the management tactics and prognosis of children with cerebral palsy and ZPRR.

Claims (1)

A method for assessing the severity of cerebral palsy (cerebral palsy) and / or delays in psycho-speech development (ZPRR), which consists in the following: detecting clinical signs of the disease during a neurological examination; register a computer electroencephalogram (CEEG); conduct emission positron tomography (PET); short-latent evoked potentials are recorded: visual (VEP), auditory (VVP), cognitive (VVP), somatosensory (SSVP); carry out neuromyography, additionally carry out blood tests: - virological, including serological blood tests for viruses tropic to nerve cells: antibodies Jg G and JgM, cytomegalovirus (CMV), herpes simplex virus (HSV) 1-2-6 types, Epstein-Barr virus (VEB), Varicella-Zoster virus (BBZ), Toxoplasma, Mycoplasma; - immunological to cellular and humoral immunity, including immunity to brain-specific proteins: neuron-specific enolase (NSE), protein S-100; Jg G antibodies to double-stranded (native) DNA, to total myelin protein; on 25-hydroxyvitamin D (vitamin D (25-0H); compare the obtained indicators with control standards and the disease is considered more serious when detecting deviations from the norm.