Diagnostic technique for acute cerebral vasculitis in children with neuroinfections

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to neuroinfectious pathology, and can be used for life-time diagnostics of acute cerebral vasculitis in children with neuroinfections. It involves acute thrombocyte count - X1 (×109/l), blood D-dimer index - X2 (mcg/l), circulating endotheliocyte count - X3 (cells), state of consciousness - X4 (1 - clear, 2-clouding, 3 - semicoma, 4 - coma), observed pareses - X5 (0 - no pareses, 1 - observed pareses), and discriminant function calculation by formula: LDF1=-15.510+0.021·X1+0.003·X2+3.975·X3+1.033·X4-2.851·X5 LDF2=-46.301+0.055·X1+0.012·X2+4.914·X3-1.307·X4+3.610·X5. If LDF1 > LDF2 is stated, no cerebral vasculitis is diagnosed, while LDF1 < LDF2 shows cerebral vasculitis to be diagnosed.

EFFECT: invention allows more accurate diagnosing, technique is less traumatic, low-cost, most reliable and available, allows the well-timed administration of a required therapy.

5 tbl, 5 ex

 

This invention relates to medicine, namely to neyroinfektsionnyh pathology, and can be used for in vivo diagnosis of cerebral vasculitis in the acute period in neuroinfections in children.

CNS-infections are the most severe disease in children that is associated with the threat to the vital functions of the body. Among the infectious diseases of the nervous system in children population, the most common are bacterial purulent meningitis or viral encephalitis, the frequency of which reaches 43%. The severity of disease, morbidity and mortality (8-36%) and frequency of organic lesions of the Central nervous system (26-75%) determine the relevance of their study.

In recent years particular emphasis on vascular factors in the pathogenesis of various somatic diseases, including infectious diseases, which is related to the development of vasculitis, i.e. inflammation of the vascular wall. It is known that the vascular endothelium is a highly specialized, metabolically active immune layer lining all blood vessels of the human body and is an independent body, which plays a Central role in the regulation of vascular tone, permeability, processes of coagulation, thrombolysis, inflammation and regeneration. In the development of neuroinfections is set as the ability of a virus or BA the criteria for cytopathic effect and tropism to the blood vessels of the nervous system. The basis of the pathological process is the predominant interaction between antigens of microorganisms and antibodies of the immune system. The result is the activation of not only the system of mononuclear phagocytes, but also of blood coagulation and fibrinolysis, the down-regulation of vascular tone. A powerful release of TNF-alpha, surpassing in intensity of the action of infecta, entails the destruction of the cell walls of the microvessels of the brain, which are the earliest target of the pathological effects of the pathogen. The defeat of the brain parenchyma with purulent bacterial meningitis and viral encephalitis occurs as a result of spread of inflammation in the blood vessels of the brain with the development of vasculitis and thrombosis, leading to an increased risk of adverse course of the disease and even deaths, especially in children, because it may result not only large but also small vessels. Therefore early diagnosis, especially in the early stages of the disease, is essential for the timely appointment of differential treatment.

Known methods of diagnosis of systemic vasculitis in adults who may not be used in children, as they involve dopolnitelnyekonsultatsii on the child's body, that can lead to serious complications.

For in vivo diagnosis of vasculitis in addition to clinical and neurological data have value and paraclinical parameters, which may allow suspected vasculitis, including cerebral. Patients often revealed elevated erythrocyte sedimentation rate, positive C-reactive protein, and antibodies in the blood, in rare cases, can be identified anemia. However, the changes in the blood does not help in nosological diagnosis of vasculitis. Almost 80% of patients with vasculitis are marked diffuse changes in the EEG, however, this method for cerebral vasculitis is neither specific nor sensitive and does not guarantee the accuracy of diagnosis. (Joseph F.G., Scolding N.J. Cerebral vasculitis: a practical approach // Pract. Neurol. - 2002. - Vol.2. - P.80-93)

Known methods of diagnosis of cerebral vasculitis, which includes clinical and neurological examination and MRI of the brain. (Ferro J.M. Vasculitis of the central nervous system // J.Neurol. - 1998. - Vol.245. - P.766-776)

How is that complicated form of vasculitis with the development of cerebral hemorrhage is reflected both in clinical and computer tomography (CT) and magnetic resonance tomography (MRI). As a rule, no changes on magnetic resonance tomograms virtually excludes the presence of cerebral vasculitis However, among patients with proven vasculitis 35% by CT and 25-30% - MRI pathological changes are not detected.

Closest to the proposed method for the diagnosis of cerebral vasculitis is a contrast angiography, which MRI is considered to be a very informative method of investigation (Siva A. Vasculitis of the nervous system // J.Neurol. - 2001. - Vol.248. - P.451-468). The method consists in the fact that intravenous contrast agent, which, spreading to the bloodstream, penetrate and cerebral vessels. A false-negative diagnosis of cerebral vasculitis according to angiography reaches 30-40%. However, the method differs insufficient sensitivity (about 24-33%), wide use of cerebral angiography prevents trauma - complications such as transient neurological disorders observed in 10% of patients, and 1% neurological defect is persistent. In addition, this method does not provide sufficient accuracy of diagnosis in children, especially in the acute period of the disease, as neyroinfektsionnyh process is the defeat not only large but also small vessels, and the use of contrast angiography is not possible to identify them.

The above methods are widely used in practice to identify cerebral vasculitis in different pathologies in adults, but in children the diagnosis of annehathaway in neuroinfections in the available sources, we have not identified. Because of neuroinfections are some of the serious diseases, especially in children, it is important to diagnose the condition as early as possible and differentiated appropriate etiotropic and pathogenetic therapy to improve outcomes and prognosis of the disease.

To address the shortcomings of existing diagnosis of cerebral vasculitis, including children, the authors first proposed in vivo diagnostics them in neuroinfections in the acute period of the disease without invasive methods, the introduction of contrast agents, as well as the use of anesthesia during MRI of the brain in young children, the use of which in neyroinfektsionnyh pathology more may aggravate the patient's condition and prognosis of the disease.

The authors propose a new method for the diagnosis of cerebral vasculitis in the acute period in neuroinfections in children. The method involves the use of the most significant clinical and neurological indicators such as the level of consciousness, presence of paresis and paralysis, as well as koagulogicheskie blood counts such as the number of circulating endothelial cells, platelets and D-dimer with further calculation according to the formula.

The technical result of the invention is to improve informative the importance of clinico-neurological and koagulogicheskie indicators accordingly, the accuracy and limitations of trauma.

This is achieved by the fact that along with the assessment of clinical neurological picture, study the clinical analysis of blood during the acute period of the disease additionally determine the number of platelets - X1 (×109/l)figure D-dimer in the blood - x2 (µg/l), the number of circulating endothelial cells - X3 (cells), the level of consciousness - X4 (1 - clear, 2 - stun, 3 - spoor, 4 - coma), the presence of paresis - X5 (0 - no paresis, 1 - paresis available) with the subsequent calculation of the linear discriminant functions by the formula:

LDF=-15,510+0,021·X1+0,003·x2+3,975·X3+1,033·X4-2,851·X5

LDF=-46,301+0,055·X1+0,012·x2+4,914·X3-1,307·X4+3,610·X5

and when the values LDF>LDF diagnose the absence of cerebral vasculitis, with values LDF<LDF diagnose the presence of cerebral vasculitis.

In children with neyroinfektsionnyh pathology diagnosis of cerebral vasculitis in the acute period of the disease was never made.

The authors in their research found that the performance assessment of endothelial dysfunction, such as circulating endothelial cells, D-dimer and platelets, in combination with clinical and neurological characteristics of the patient are the most important and can be used for the diagnosis of vasculitis in children in the acute period. The authors have established the ligature between endothelial cells and blood clotting, when amplification of the coagulation cascade, with excessive formation of fibrin. Therefore, the authors proposed D-dimer and platelets as one of the main indicators in the diagnosis of vasculitis. It is this combination ensures the accuracy of diagnosis in the acute period of the disease.

The authors first established that only a comprehensive analysis of these indicators in the early stages of the disease enables timely and accurately diagnose vasculitis and prescribe appropriate therapy. The authors, in contrast to the prototype MRI-ways, having some difficulty in holding them in children (use of anesthesia, the administration of contrast material, the inability to identify the defeat of small vessels), offer a less invasive method of diagnosis of vasculitis.

The authors have shown that impairment of consciousness and the presence of paresis and paralysis in combination with the most informative laboratory parameters are the most important signs of vasculitis that may be associated with loss of vital neurons and formation of infarction lesion resulting from endothelial dysfunction in the background of neuroinfections.

A fundamentally new and non-obvious is that in the stepwise discriminant analysis, the authors obtained statistically the truth is s (p< 0,0000) and informative formulas linear classification functions, which have included the most important for the diagnosis of vasculitis indicators, namely: level of consciousness, presence of paresis and paralysis, the number of circulating endothelial cells, platelets and D-dimer in the blood, which allows timely and accurate diagnosis of vasculitis in the acute period in children.

We studied 40 children aged 1 month to 17 years with infection of the Central nervous system of various etiologies, including encephalitis and bacterial purulent meningitis. The period from the moment of disease before the study our results ranged from 1 to 5 days, i.e. the acute period of the disease. The study of clinical neurological and koagulogicheskie indicators showed that almost 30% of the cases had impaired consciousness in children and the presence of paresis and paralysis, but 80% of patients changes of consciousness and motor disorders was not, but there was an increase of platelets, D-dimer and circulating endothelial cells compared with normal. When conducting MRI examination in 45% of patients with signs of vasculitis were observed. In this regard, the authors were asked to use clinical-neurological and laboratory findings together. The authors first established that a comprehensive analysis taking into account clinical and neurological disorders level of consciousness, the presence or absence of paresis), changes in blood coagulation tests (the number of circulating endothelial cells, platelets D-dimer) increases the accuracy of diagnosis of cerebral vasculitis, which makes 96.4% and exceeds the accuracy of the other known methods.

This method is as follows. When the primary clinical-neurological examination of the child with CNS infection in the emergency Department of the hospital determine the level of consciousness and the presence of musculoskeletal disorders. The next step is additionally carry out blood collection in special tubes to determine the number of circulating endothelial cells, platelets and D-dimer. The next step with the help of a calculator or personal computer produce multiplying the digital values of each sign corresponding to the sign of the coefficient for the presence or absence of vasculitis and the data are entered in the appropriate table cell. Then in each column individually, these works summarize, the amount of the gain constant, the final amount compare and choose the most belongs to a particular patient. In other words, the outcome is determined by the largest absolute value of one of the two linear discriminant functions. Thus, diagnose the presence or absence of vasculitis is.

The method can be supported by the following examples.

Example 1: A. Child, was in NEEDY with a diagnosis of pneumococcal meningitis. Admission: a serious condition. Impairment of consciousness to spoor. Meningeal symptoms strongly positive, paresis and paralysis no. When conducting additional analyses of blood: platelet - 450×109/l, D-dimer, 1700 µg/l, circulating endothelial cells (CETC) - 7 cells. Based on the above characteristics was compiled table 1. The results of the calculations indicated the presence of vasculitis: LDF<LDF. However, after a routine examination of the patient, in particular brain MRI-pathological formations was not found.

Example 2: Child b was in NEEDY with a diagnosis of Haemophilus influenzae meningitis. Was admitted in serious condition. Sluggish, drowsy. Bothered by a headache, mainly in the frontal area. Meningeal symptoms dramatically polozitelnye. Of paresis and paralysis no. In clinical blood analysis additionally revealed: the platelet - 211×109/l, D-dimer, 2500 µg/l, CATZ - 9 cells. The results of the calculations indicated the presence of cerebral vasculitis: LDF<LDF (table 2). On brain MRI: MRI signs of pathological lesions and focal changes in brain tissue is not you who go.

Table 2
The name of the characteristiccharacteristic valueThe coefficients, constants
LDF - absence of vasculitisLDF the presence of vasculitis
platelets2110,0214,4230,05511,710
D-dimer25000,0037,9010,01230,987
circulating endothelial cells93,97535,7794,91444,224
the level of consciousness21,0332,065-1,307-2,614
the presence of paresis/paralysis0 -2,8510,0003,6100,000
constant-15,510-46,301
forecast34,738,01

Example 3: Child M was in NEEDY with a diagnosis of vetrenary encephalitis, cerebellar form. Admission: a serious condition. Consciousness is preserved, is focused, but the contact is not involved. Team refuses to perform. Please it understands. Marked salivation. Clonic reaction with 2 sides S=D. Meningeal symptoms - negative. The monotonous cry. Dynamic ataxia when walking. Easy intentsionnogo tremor when performing coordinatory samples. In addition the analyses performed blood: platelet - 485×109/l, D-dimer, 1400 µg/l, CATZ - 6 cells. When calculating according to the formula LDF<LDF, i.e. the presence of cerebral vasculitis (table 3). However, brain MRI: MRI signs of focal cerebral lesion was not detected.

Table 3
The name of the characteristiccharacteristic valueThe coefficients, constants
LDF - absence of vasculitisLDF the presence of vasculitis
platelets4850,02110,1660,05526,917
D-dimer14000,0034,4250,01217,353
circulating endothelial cells63,97523,8534,91429,483
the level of consciousness11,0331,033-1,307-1,307
the presence of paresis/paralysis0-2,8510,0003,6100,000
is Constanta -15,510-46,301
forecast24,026,14

Example 4: the Child Was enrolled in NEEDY with a diagnosis of encephalitis. Admission: a serious condition. During the day, drowsy, very irritable. In contact with others does not enter. It is a separate word. The head does not hold, not sitting, not standing. Muscular hypotonia. Deep reflexes - high, pathological stop signs, decrease in muscle strength in the extremities to 2-3 points. Spastic tetraparesis. Platelets - 350×109/l, D-dimer, 1800 µg/l, CATZ - 7 cells. On brain MRI: Cystic glioznogo changes in deep sections of the right hemisphere of the brain. Multifocal brain damage. MRI in vascular mode and the introduction of contrast - occlusion of the middle cerebral artery. Diffuse atrophic process. Areas of ischemia in the areas of blood flow of the middle cerebral artery, accumulating contrast. Cerebral vasculitis. Based on the above characteristics was compiled from the summary table below (table 4), and the results of the calculations indicated the pain is th the probability of the presence of vasculitis, because LDF<LDF.

Table 4:
The name of the characteristiccharacteristic valueThe coefficients, constants
LDF 1 - absence of vasculitisLDF the presence of vasculitis
platelets3500,0217,3360,05519,425
D-dimer18000,0035,6890,01222,311
circulating endothelial cells73,97527,8284,91434,396
the level of consciousness21,0332,065-1,307-2,614
the presence of paresis/paralysis 1-2,851-2,8513,6103,610
constant-15,510-46,301
forecast24,630,83

Example 5: the Child Century, was in NEEDY with a diagnosis of vetrenary meningoencephalitis. Was admitted in serious condition. Sluggish, drowsy. It staccato. Installation nystagmus in extreme abduction. Severe ataxia in the trunk and extremities. Yourself not sitting. When the finger-nose test - miropomazanie. Positive meningeal symptoms. In the tests: platelet - 236×109/l D-dimer - 1500 µg/l, CATZ - 6 cells. When calculating according to the formula LDF>LDF, i.e. the absence of cerebral vasculitis (table 5). On brain MRI: MRI signs of focal lesions not detected.

Table 5:
The name of the characteristiccharacteristic valueCoefficie is you, constants
LDF - absence of vasculitisLDF the presence of vasculitis
platelets2360,0214,9470,05513,098
D-dimer15000,0034,7410,01218,592
circulating endothelial cells63,97523,8534,91429,483
the level of consciousness21,0332,065-1,307-2,614
the presence of paresis/paralysis0-2,8510,0003,6100,000
constant-15,510 -46,301
forecast20,1of 12.26

The proposed method for the diagnosis of cerebral vasculitis in neuroinfections in children developed by the Federal state institution "research Institute of children's infections, Roszdrav" and passed clinical tests in the diagnosis of cerebral vasculitis in the acute period neyroinfektsionnyh disease in 40 patients. This method has an accuracy that is less traumatic for children, low-cost, highly informative, the most reliable and affordable and allows timely and appropriate therapy. The results obtained here confirm its usefulness: actual and projected results coincided in 96% of cases.

Developed a fundamentally new method can be recommended for wide use in neyroinfektsionnyh wards.

A method for the diagnosis of cerebral vasculitis in the acute period in neuroinfections in children, including the assessment of the clinical-neurological picture, study the clinical analysis of blood, characterized in that in the acute period of the disease determine the number of platelets X1 (·109/l)figure D-dimer in the blood - x2 (µg/l), the number of circulating is their endothelial cells - X3 (cells), the level of consciousness - X4: 1 - clear, 2 - stun, 3 - spoor, 4 - Koma, the presence of paresis - X5: 0 - no paresis, 1 - paresis available, with subsequent calculation of the linear discriminant functions by the formula:
LDF=-15,510+0,021·X1+0,003·x2+3,975·X3+1,033·X4-2,851·X5
LDF=-46,301+0,055·X1+0,012·x2+4,914·X3-1,307·X4+3,610·X5,
and when the values LDF>LDF diagnose the absence of cerebral vasculitis, with values LDF<LDF diagnose the presence of cerebral vasculitis.



 

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3 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, in particular to cardiology, neurology, ophthalmology, is used to carry out diagnostics of predisposition to ischemic neuroopticopathy in elderly people with ischemic heart disease (IHD), arterial hypertension (AH) and dyscirculatory encephalopathy (DEP). Blood is sampled from ulnar vein, blood samples are forms, from which DNS is separated, amplification of DNA fragments is pertformed, after that genotyping on polymorphisms del-425 and 3'-UTR of c-fms geneand polymorphism 64V of CCR2 gene is carried out, if in elderly women heterozygous genotype 64V/641 of polymorphism 64V of CCR2 gene, and heterozygous genotype 12 of polymorphism 3'-UTR of c-fms gene are detected, predisposition to ischemic neuroopticopathy is diagnosed.

EFFECT: detection of predisposition to ischemic neuroopticopathy in elderly people for administration of adequate preventive treatment.

7 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to biochemical investigations in oncology, and can be used in determination of activation or stabilisation of pathologic process in patients with primary-resistant Hodgkin's lymphoma. In patients with primary-resistant Hodgkin's lymphoma at stages of treatment, by radioimmune method determined is content in blood of thyroid gland hormones - triiodothyronine and thyroxine, and adrenocortical hormone - cortisol, their concentration is summed up and in case of total level of hormones is within 278.2 nmole/l - 0 333.0 nmole/l conclusion about activation of malignant process is made, if total level of said hormones is 432.4 nmole/l - 833.2 nmole/l conclusion about absence of process activation is made.

EFFECT: prediction of process activation or stabilisation in patients with primary-resistant Hodgkin's lymphoma is an informative test for evaluation of pathologic process state and can be recommended for monitoring of patients at treatment stages.

1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to obstetrics, and can be used for prediction of preterm effusion of amniotic fluid in pregnant women with gestation term 32-36 weeks. Essence of invention lies in the following: in blood serum of pregnant women with gestation term 32-36 weeks IL-8 level is determined, and if its value equals or is lower than 15.4 ng/ml, preterm effusion of amniotic fluid is predicted.

EFFECT: method is simple in implementation and allows to predict development of preterm effusion of amniotic fluid with high accuracy, sensitivity and specificity, which makes it possible to select correct tactics of monitoring women with risk of said obstetrics pathology development, to avoid complications of labour activity and perinatal pathology.

1 tbl, 4 ex

FIELD: medicine, clinical toxicology.

SUBSTANCE: at patient's hospitalization one should gather the data of clinical and laboratory values: on the type of chemical substance, patient's age, data of clinical survey and laboratory values: body temperature, the presence or absence of dysphonia, oliguria being below 30 ml/h, hemoglobinuria, erythrocytic hemolysis, exotoxic shock, glucose level in blood, fibrinogen and creatinine concentration in blood serum, general bilirubin, prothrombin index (PTI), Ph-plasma, the state of blood clotting system. The state of every sign should be evaluated in points to be then summed up and at exceeding the sum of points being above "+20" one should predict unfavorable result. At the sum of "-13" prediction should be stated upon as favorable and at "-13" up to "+20" - prediction is considered to be doubtful.

EFFECT: higher accuracy of prediction.

2 ex, 3 tbl

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