RU2473895C1 - Method for detecting neurosyphilis in patients infected by treponema pallidum - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: venous blood is sampled; test samples are prepared for serologic examination. It is followed by microprecipitation test (MT), complement fixation (CF) with Pangborn's (P) and treponemal (T) antigens, passive hemagglutination test (PHT) in qualitative and quantitative versions and enzyme-linked immunosorbent assay (ELISA). The patient is clinically examined. The serologic examination results, historical data and nervous system information used as relevant values are recorded and divided on four groups. Each of the values detected in the patient are scored by a degree of effect on the examination result. Within each group, the points are summed up, and diagnostic coefficients are prepared for each of four groups DC₁, DC₂, DC₃, DC₄. The coefficients are compared to the reference values. A criterion for the presence of neurosyphilis is the relation of the values of four patient's diagnostic coefficients to the reference values: DC₁≥4, DC₂≥8, DC₃≥35, DC₄≥-4. The absence of neurosyphilis in the patient is shown by the values of a set of the diagnostic coefficients less than the related reference values.

EFFECT: method enables objective assessment of the patient's state without sampling cerebrospinal fluid by lumbar puncture, and arriving at diagnosis on the basis of the derived findings.

3 ex, 4 tbl

Description

The invention relates to medicine, namely to neurology, venereology, dermatology, infectious diseases, experimental medicine, and can be used to detect neurosyphilis in patients infected with treponema treponema pallidum, with a verified diagnosis of syphilis.

In Russian medical literature, neurosyphilis (NS) is presented as a collective designation of damage to the nervous system during syphilitic infection, which can occur at any stage of development of this infection and depends on the ingestion of the causative agent of syphilis - pale treponema - in the tissue of the nervous system and the state of immunity in a sick person. Erased and latent forms with insignificant or absent symptoms often prevail in the structure of the incidence of NS. NS is characterized by a tendency to progression in the absence of adequate treatment. The main role in the diagnosis of NS plays a laboratory study of blood serum and cerebrospinal fluid (CSF) - cerebrospinal fluid [Rodionov AN Syphilis / Chapter: Syphilis of the nervous system. SPb., 2007. S.204-213; Kaziev A.Kh. Complex diagnostics and therapy of neurosyphilis (neurophysiological and immunological aspects): author. dis. doc honey. Sciences: 11.10.2010. M., 2010.52 p .; Rodionov A.N., Smirnova T.S., Telichko I.N. etc. Diagnosis, clinic and treatment of early neurosyphilis at the present stage. Journal of Dermatovenereology and Cosmetology, 2001. No. 2. S.36-38].

In foreign patent literature [international application for the invention WO No. 0075666, made by the Center for the Control and Prevention of Diseases of the Government of the United States of America, European patent EP No. 1185872, CN patent CN No. 1195986, Canadian patent CA No. 2375448, the same invention claimed in Russia , - RF patent No. 2244933] the following information is given:

syphilis is a sexually transmitted disease caused by the bacterium Treponema pallidum. More than one hundred thousand cases of syphilis in adults worldwide are reported annually. The inability to receive antibiotic treatment in the early stages of the disease leads to the progression of the disease, to irreversible damage to organs, nervous system, death. An infected individual can infect others during the primary and secondary stages of syphilis. During tertiary syphilis and NS, the bacterial infection is not contagious, however, invasion of the microorganism into organs, tissues and the brain can have fatal consequences, such as serious cardiovascular disorders or neurological disorders.

During the early stages of syphilis infection, bacteria can affect the nervous system. In the absence of treatment, HC may develop. The progression of the disease towards HC can last up to twenty years, and some people with HC cannot recognize recognizable symptoms, which makes the diagnosis very difficult. Those who actually show symptoms may complain of a headache, neck pain, or fever that results from inflammation of the meninges. Epileptic seizures and signs of a stroke, such as impaired sensation, weakness or vision problems, can also affect patients with NS. Most cases of syphilis are first diagnosed serologically, then cerebrospinal fluid tests are performed.

The Russian patent information also presents a number of patents for the diagnosis of HC.

The well-known "Method for the diagnosis of early forms of neurosyphilis" [RF patent for the invention No. 2352243], which includes conducting an ophthalmological examination, including the study of visual evoked cortical potentials (VECS) on a reversible chess pattern, making a preliminary diagnosis of an early form based on the results of the VECP study. NS, which is then clarified by the results of the CSF study.

However, this method is applicable for a limited number of patients, namely for those who have symptoms of early NA "visual" nature. With asymptomatic NS, which occurs quite often, this diagnostic method is unsuitable.

Also known is the "Method for the differential diagnosis of early and late forms of neurosyphilis" [RF patent for the invention No. 2141660], consisting in the study of CSF, determining the level of luminescence induced by hydrogen peroxide native CSF, and making on the basis of the results of the study the diagnosis of the form of NS.

Also known is the "Method for the diagnosis of neurosyphilis" [RF patent for the invention No. 2230323], which consists in lumbar puncture, the study of the amount of sphingomyelin in the CSF of patients using flow thin-layer chromatography, which is used to diagnose syphilis or NS in a patient.

Also known is the "Method for diagnosing changes in the central nervous system (CNS) in syphilis" [RF patent for the invention No. 2315303]. This method consists in determining in biological fluid molecular markers of changes in the central nervous system (acetyl tryptophan, indoleacetic acid, indolebutyric acid and acetylmorpholine) with syphilis. Moreover, to identify early and latent changes in the central nervous system, the above markers are determined by gas chromatographic and mass spectrometric methods in the cerebrospinal fluid and, based on the results, the changes in the central nervous system are diagnosed.

Also known is the "Diagnostic Method for Early Congenital Syphilis" [RF patent for the invention No. 2168177]. This patent proposes a method for early laboratory diagnosis of damage to the nervous system based on CSF indicators: cytosis, protein content, specific reaction results. At close to normal values of cerebrospinal fluid in the latter determine the content of cytokines: interleukin-4β, and / or interleukin-1β, and / or tumor necrosis factor-α. The increased content of the above cytokines in the cerebrospinal fluid increases the quality of early diagnosis of damage to the nervous system in syphilis.

Also known is the "Method of serodiagnosis of early neurosyphilis" [RF patent for the invention No. 2205409]. The method includes determining the presence of antibodies in blood serum and CSF to antigens of the causative agent of syphilis. Antibodies to antigens of the syphilis pathogen with a molecular weight of 15, 17, 41 and 47 kD are determined and, when antibodies to two or more antigens are detected in the blood serum, and only to the 17 kD antigen in CSF, early syphilitic CNS damage is verified.

There is also a method of detecting NS [Loseva OK, Taktamysheva E.Sh. Modern neurosyphilis: clinic, diagnosis, treatment. Breast cancer, 1998. Volume 6, No. 5. S.21-23]. The method includes blood sampling, serological non-treponemal reactions: complement binding reactions (CSCs), precipitation microreactions (MRI), and treponemal reactions: pale treponemal immobilization reactions (RIT), immunofluorescence reactions (RIF), passive hemagglutination reactions (RPHA), immuno IFA). Then, when syphilis is confirmed, cerebrospinal fluid is sampled by lumbar puncture and a general cerebrospinal fluid analysis, glucose and cerebrospinal fluid glucose, RSK, MPI, IFA, RPGA, RIF with cerebrospinal fluid are performed. In the presence of lymphocytic pleocytosis of more than 5 cells in 1 mm ³ , an increase in the protein content (hyperproteinorrhea) to a level of more than 0.4 g / l, plasmacytosis, as well as positive nontreponemal and treponemal reactions, the diagnosis of HC is considered proven. In the absence of the changes described above, CSF NS is excluded.

The closest analogue to the claimed invention is a method for identifying NS [Bells OV, Sholomov II, Bakulev A.L. et al. Neurosyphilis: problems of diagnosis and classification. Saratov Journal of Medical Scientific Research, 2010. V. 6, No. 3. S.632-636]. This method includes examination (clinical and neurological) of the patient by a dermatovenerologist, neurologist, optometrist and therapist, conducting a serological test for syphilis - precipitation microreaction (MRI), complement fixation reaction (CSC) with cardiolipin (K) and treponemal (T) antigens, immunoenzyme (ELISA), passive hemagglutination reaction (RPHA). Clinical and neurological examination consists of determining the following indicators: the age of the patients, the duration of the disease, receiving outpatient treatment for syphilis earlier, the presence of pathognomonic clinical manifestations of NS, in particular Argyll Robertson syndrome, the presence of impaired cranial nerve function, namely oculomotor, visual disturbances, insufficiency facial nerve function, hearing loss, sublingual nerve function deficiency, etc., autonomic function disorders and manifestations are neurosis-like x disorders, the severity of ataxia, pyramidal insufficiency, paresis, the presence of a decrease in knee and Achilles reflexes, a decrease in muscle tone, a violation of sensitivity, cortical disorders. In addition, lumbar puncture is performed, followed by a general analysis of cerebrospinal fluid, determination of glucose and chloride levels, staging of MRI, RSK, ELISA, RPGA with cerebrospinal fluid.

All of the above methods are characterized by the study of cerebrospinal fluid.

However, there are groups of patients with contraindications for lumbar puncture. You can not conduct these studies in patients with axial dislocation of the brain, spinal cord and local focus of infection in the lumbar region, including skin, subcutaneous tissue, bones and epidural space. In addition, cerebrospinal fluid should be taken with extreme caution in patients with a threat of axial dislocation of the brain and spinal cord, an occlusal form of hydrocephalus, impaired cerebrospinal fluid pathology in the spinal cord and spinal canal, congestion in the fundus, decreased vision of less than 10%, and the presence of volumetric formation posterior cranial fossa, confirmed by CT and / or MRI, hemorrhagic syndrome of any etiology. In the presence of acute infectious disease, pregnancy, menstruation, diseases and conditions requiring emergency medical care (hypertensive crisis, paroxysm of cardiac arrhythmias, vomiting, etc.), a planned lumbar puncture should be delayed until these conditions are resolved.

Lumbar puncture even in patients without contraindications can lead to serious complications, such as syncope, damage to blood vessels, damage to nerve roots, damage to the intervertebral discs. In addition, puncture is associated with difficulties of a technical and organizational nature, in particular, it requires the fulfillment of aseptic and antiseptic conditions. In addition, an indispensable condition for obtaining reliable results of CSF studies on syphilis is to prevent accidental ingress of blood into the cerebrospinal fluid, which is not always avoided.

The task of the invention is to develop a method for detecting neurosyphilis, suitable for the above groups of patients who are contraindicated in performing lumbar puncture.

The essence of the claimed invention is characterized by the fact that in the method for detecting neurosyphilis in patients infected with Treponema pallidum, venous blood is collected, sample samples are prepared for serological studies: precipitation microreaction (MCI); complement binding reactions (CSCs) with cardiolipin (K) and treponemal (T) antigens; passive hemagglutination reactions (RPHA); enzyme immunoassay (ELISA); carry out the above reactions in qualitative and quantitative versions; carry out a clinical examination of the patient; the obtained results of serological studies, anamnesis data and information about the state of the nervous system, which serve as significant indicators, are recorded and divided into four groups, united by a significant community within each group, and the number of points identified in the patient’s indicators is assessed by the degree of influence on the study result:

group 1 are indicators taken from the anamnesis:

group 2 are the following indicators:

group 3 are the following indicators:

group 4 are indicators obtained by serological studies:

moreover, from the series of values of each indicator, a value is selected that corresponds to the most pronounced picture characterizing the patient’s condition and the corresponding evaluation points, add them inside each group and receive diagnostic coefficients for each of the four groups - DK ₁ , DK ₂ , DK ₃ , DK ₄ , they are compared with control values, and the criterion for evaluating the presence of neurosyphilis is the ratio of the values of all four diagnostic coefficients of the patient with the control values:

DC ₁ ≥4,

DC ₂ ≥8,

DC ₃ ≥35,

DC ₄ ≥-4;

the patient’s absence of neurosyphilis is judged with values from a set of diagnostic coefficients that are less than the corresponding control values.

The technical result of the claimed invention.

The presence of a technical nature in the proposal of the authors is not limited to taking samples for serological studies. To implement the method, it is necessary to use one of the most modern technologies for processing blood samples by ELISA and RPGA, MRI, RSK. The presence of other actions for the selection of indicators further hones, refines, summarizes, and corrects the results of a medical examination that are not taken into account in the process of serological studies. Despite this, the new indicators are also highly informative. Previously, before the authors of this application, such a set of indicators was not used in the technology for assessing a patient with syphilis for its specific form - NS, which is characterized by a high percentage of asymptomatic course.

The absence in the claimed method of the operation of taking and processing cerebrospinal fluid is not its drawback, but its advantage due to the impossibility of carrying it out to certain groups of patients. It seemed that the loss of information due to the lack of such an informational complex of indicators related to cerebrospinal fluid should have reduced the accuracy of the proposed method. However, the absent operation of CSF taking is compensated by sets and groups of other indicators, the collection of which is harmless for the named groups of patients who are contraindicated in lumbar puncture. Replacing and compensating indicators describe the condition of a patient with NS quite informative. As shown by experimental practice, the proposed method has high accuracy.

Distinctive features of the proposed method.

The novelty of the method, which significantly distinguishes it from the closest analogue and all methods associated with the detection of NS, is an evaluation criterion in the form of a set of indicators, not only directly but also indirectly related to the blood test and the patient’s condition, assessed as subjective by the patient himself (according to complaints ), and objectively doctors - specialists: a neurologist, venereologist, dermatologist, ophthalmologist, ENT specialist, psychiatrist, neurosurgeon. Studies of a greatly expanded set of identified indicators for patients with NS, the connection of the latter with the condition of patients not previously described in the medical and patent literature, allow us to consider the data collection technology for detecting NS as original and significantly different from existing ones.

A new feature of the proposed method is the presence of combined indicators not previously used in the assessment of NS, namely the presence of: symptoms of oral automatism along with the absence of abdominal reflexes; asymmetries of Achilles and carporadial reflexes; Romberg symptom, along with dysmetria or with Argyle Robertson syndrome, or with asymmetry of carporadial reflexes, or with high knee reflexes; atactic gait along with muscle hypotension or with Argyle Robertson syndrome, or with symmetric knee reflexes, or with Romberg symptom; dysmetria along with muscle atrophy.

The inventive method is illustrated using tables 1-8, where table 1-4 presents the indicators of each of groups 1-4 for the general case, and tables 5-8 contain data on significant indicators of groups 1-4 of the patients presented in examples No. 1-3:

table 1 - indicators of group 1, obtained from the anamnesis;

table 2 - indicators of group 2, characterizing lesions of the nervous system, felt by the patient subjectively;

table 3 - indicators of group 3, characterizing lesions of the nervous system, determined objectively by experts;

table 4 - indicators of group 4 obtained by serological studies,

table 5 - indicators of group 1, obtained from the anamnesis of 3 patients from examples No. 1-3;

table 6 - indicators of group 2, characterizing the lesions of the nervous system felt by each of the patients (examples No. 1-3) subjectively;

table 7 - indicators of group 3, characterizing the lesions of the nervous system of patients from examples No. 1-3, determined objectively by experts;

table 8 - indicators of group 4 obtained by serological studies of samples of patient samples (examples No. 1-3).

A detailed description of the proposed method.

For patients who are contraindicated in performing lumbar puncture, the authors of the proposed method previously in the process of developing the technology, a list of significant indicators was formed, the data on which, as it turned out, indicate the presence of NS in a patient infected with pale treponema. This list of indicators includes both the results of laboratory tests and the information obtained during the clinical examination. Some indicators characterize the presence or absence of a specific symptom, such as the presence or absence of a headache complaint, the presence or absence of Romberg symptom. The other part of significant indicators, for example, the result of setting MPI in a qualitative variant or the age of the patient, can take different values. The latter, for the unification of the analysis, were, as far as possible, divided into characteristic discrete or continuous ranges, as, for example, for MCI - negative (-), doubtful (1+), weakly positive (2+), positive (3+), sharply positive (4+) research results on a 4-cross system or, as it is called in a number of other publications, a 4-plus system; for the age of the patient, these are ranges up to 30 years, from 30 to 45 years, more than 45 years, into which the age of the patient under study falls.

The influence of the value of each of the selected indicators was evaluated after the experiments for the convenience of analysis, unification and simplicity in points. In this case, methods were used, including probability theory, in particular, the sequential recognition procedure.

The more points the indicator “weighs”, the higher its impact on the final diagnosis of NS. As a characteristic of the value of the indicator corresponding to the patient not suffering from NS, a negative score was chosen.

Final verification and scoring was carried out in the process of developing the technology of the method using control lots of patients. The first batch consisted of 165 patients with a reliably established diagnosis of neurosyphilis, who were hospitalized. The inclusion criteria in the first batch were: age of patients older than 16 years, a reliably positive result of a blood test and CSF for syphilis. The second batch consisted of 99 syphilis patients with a reliably excluded diagnosis of neurosyphilis. All patients underwent CSF research, since they had no contraindications for lumbar puncture. The above indicators and the scores assigned to them were checked, worked out, refined experimentally by comparing the results with the analysis of CSF of patients from control lots.

The obtained indicators were divided according to the degree of generality into four groups: group 1 - indicators taken from the anamnesis; group 2 - indicators characterizing the lesions of the nervous system felt by the patient subjectively; group 3 - indicators characterizing lesions of the nervous system, determined objectively by experts; group 4 - indicators obtained by serological studies.

Table 1 Indicators Points Availability coronary pathology fifteen tuberculosis eleven lesions of the peripheral nervous system 5 toxic encephalopathy, polyneuropathy four intracranial injury 3 drug use fourteen antisyphilitic therapy has not been previously conducted four syphilis diagnosed during the first 3 years of infection -one after 3 years of infection 5 patient age at the time of the study less than 30 years -2 from 30 to 45 years -one more than 45 years four at the time of infection less than 30 years -2 30 years and more 3

table 2 Indicators Points the presence of patient complaints imbalance when closing eyes 19 gait unsteadiness 13 difficulty performing precise movements eleven limb weakness eleven noise in ears 7 dizziness four numbness in the limbs four trembling four decreased vision 3 hearing loss 3 headache 2

An assessment of the influence of each group of indicators is given by the diagnostic coefficient (DC), which is the sum of the points of the indicators corresponding to the whole group. Analysis by the authors of the proposed method of case histories, including patients of the above control groups, made it possible to develop a new criterion for assessing the presence of NS in a patient. This criterion is the simultaneous equality or excess of the total diagnostic coefficients of all four groups of control values, respectively: for a group of indicators taken from the anamnesis - a value of 4 points, 8 points - for a group of indicators characterizing the damage to the nervous system felt by the patient subjectively, 35 points - for a group of indicators characterizing lesions of the nervous system, determined objectively by experts, (-4) points for a group of indicators obtained in serological studies. The absence of NS is indicated by the values of all four diagnostic coefficients, which are lower than the control ones.

The method is carried out technically as follows.

4-8 ml of blood are taken on an empty stomach, or not earlier than 4 hours after eating, in a patient who has had or is currently diagnosed with syphilis. Then prepare samples of samples - 2-3 ml of blood serum - for serological reactions, namely for:

precipitation microreactions (MCI);

complement binding reactions (CSCs) with treponemal (T) and cardiolipin (K) antigens;

passive hemagglutination reactions (RPHA);

enzyme immunoassay (ELISA).

The above studies are carried out according to modern legal methods, in particular, for Russia [see URL: http: //www.roszdravnadzor.ru], where a list of the necessary regulatory legal acts on this subject is given, as well as in the medical literature [Tkachev V.K., Vyatkina T.G. ELISA diagnosis of syphilis. Koltsovo, 2005.S. 48; Mardanly S.G., Dmitriev G.A. Laboratory diagnosis of syphilis. M., 2009. p. 28; Obryadina A.P., Chepurchenko N.V., Frigo N.V. and others. Diagnosis of syphilis. Nizhny Novgorod, 2007. p.44], etc.

MRI, RSK T and K, RPGA carried out in qualitative and quantitative versions.

The result of setting the MCI in a qualitative version is estimated by the amount of precipitate formed and the size of the flakes according to the 4-cross system (4 plus system). The result of the staging of MCI in a quantitative version is the last dilution of the serum where the precipitate was found.

During the formulation of CSCs with cardiolipin and treponemal antigens, the presence or absence of hemolysis is qualitatively determined, the result is expressed in a 4-cross system (4 plus system), where 4+ (sharply positive reaction) corresponds to a complete delay in hemolysis, 3+ (positive ) - significant delay, 2+ (weakly positive) - partial delay, 1+ (doubtful) - slight delay, - (negative) - complete hemolysis. The results of stating CSCs in quantitative terms consider the last highest titer of reagins of the test serum, which delayed hemolysis.

The results of the RPGA staging are qualitatively evaluated visually by the appearance of the erythrocyte sediment at the bottom of the well: sharply positive — an even layer (“umbrella”) of agglutinated red blood cells distributed along the bottom of the well (4+); positive - red blood cells are located on most of the bottom of the hole, while a noticeable ring (3+) forms on the periphery of the sediment; weakly positive - erythrocytes are located on a small part of the bottom of the hole, in the central part a dense ring is formed from a erythrocyte sediment with noticeable enlightenment in the central part (2+); dubious (indefinite) - the presence of a small loose sediment of red blood cells with fuzzy edges in the central part of the hole with a slight clearance in the center on a red background free from red blood cells (1+); negative - compact sediment (“button”) in the central part of the bottom of the well against a clean surrounding background. The quantitative version of the RPHA formulation is the last dilution of the test serum, which yielded a weakly positive (2+) result.

To interpret the results obtained for each patient, use table 4. From it select the evaluation points corresponding to the above results obtained by setting each reaction, first in a qualitative way, then in a quantitative way. When choosing evaluation points for the results of the reaction in a quantitative version, the following considerations are guided.

According to the above sources of literature, when staging serological reactions in quantitative form, dilution is carried out to the following highest titers: to titer 1: 516 for MCI, to titer 1: 320 for RSK, to titer 1: 2560 for RPGA. However, as shown by the results of experimental studies, dilutions above titer 1:16 for MCI, titer 1:80 for CSC K and T, 1: 320 for RPGA were uninformative for detecting NS.

The ELISA is carried out as follows.

To determine antibodies to pale treponema by ELISA, a set of reagents is used, the basis of which are recombinant pale treponema antigens. Specific immunoglobulins of classes M, G and A for pale treponema are detected in blood serum due to their simultaneous interaction with recombinant antigens immobilized on the surface of the strip wells and included in the conjugate. The result of ELISA is recorded using a spectrophotometer and an instrumental assessment of the results is used in the form of digital optical density (OD) values. When the reaction results are automatically taken into account by the value of the digital OD indicators in the wells with the tested samples, the concentration of specific antibodies in the test blood serum is judged, which allows us to classify this version of the formulation. OD is measured according to the instructions for the reagent kit. Then, according to the magnitude of the OD, using the instructions, the ELISA result is evaluated: positive — the presence of total antibodies — or negative — their absence, which is analogous to setting the reaction in a qualitative way. In addition, using the instructions determine the coefficient of positivity (KP).

A clinical examination of a patient with an established diagnosis of syphilis is carried out by a dermatovenerologist and a neurologist. If necessary, other specialists are involved in the examination, including an otorhinolaryngologist, psychiatrist, neurosurgeon, therapist and ophthalmologist. When collecting data on the history of the disease, it is noted whether antisyphilitic therapy was previously carried out, and if it was, its timing is noted (during the first 3 years of infection with pale treponema or in a later period); determine the age of the patient at the time of infection (less than 30 years or 30 years or more), fix the age of the patient at the time of examination (less than 30 years, from 30 to 45 years or more than 45 years).

Information on the history of life is collected according to generally accepted methods. When interviewing the patient, as well as those accompanying him, and studying the medical documentation of the patient, special attention is paid to the presence of coronary pathology in the patient's history, including including coronary heart disease (CHD); tuberculosis lesions of the peripheral nervous system (PNS); toxic encephalopathy, polyneuropathy; intracranial injury (intracranial injury). If necessary, reliably clarify the history data, additional examinations are carried out, regulated by the standards of medical care for patients with the above nosological forms. In addition, the fact of drug use is noted.

Complaints are collected according to generally accepted methods. When interviewing the patient and his companions, as well as studying the patient’s medical documentation, special attention is paid to the presence of complaints of imbalance when closing the eyes, unsteady gait, numbness in the extremities, weakness in the extremities, difficulty in performing precise movements, tinnitus, dizziness , internal trembling, decreased vision, hearing loss and headache. To obtain information, use both an oral survey and a written questionnaire according to tables 1-3.

Neurological examination is carried out according to the generally accepted method [Triumfov A.V. Topical diagnosis of diseases of the nervous system. M .: Medpress-inform, 2007.264 s .; Skoromets A.A. Topical diagnosis of diseases of the nervous system. St. Petersburg: Polytechnic, 2002.399 p .; Samuels M. Neurology. M.: Practice, 1997. 640 S.].

When analyzing cranial nerve function, the most attention is paid to the presence of strabismus, Argyle Robertson syndrome, peripheral, central prozoparesis, deviation of the tongue when protruding from the oral cavity, symptoms of oral automatism (for example, palmar-chin symptom of Marinescu-Radovici, proboscis symptom of ankylosing spondylitis, nasolabial syndrome ) The presence of symptoms of oral automatism along with the absence of abdominal reflexes is noted especially. This is one of the new combined features of the proposed method.

In the analysis of reflex-motor disorders, the presence of paresis of the limbs is assessed. Attention is drawn to the asymmetry of physiological periosteal and tendon reflexes of the extremities, including carporadial, knee, and Achilles reflexes. Especially note the presence of asymmetry of the carporadial reflexes along with the asymmetry of the Achilles reflexes. Assess the nature of the reflex response, especially noting the missing knee, Achilles reflexes, as well as high carporadial reflexes. Attention is drawn to the absence of skin abdominal reflexes, as well as the presence of pathological foot reflexes (for example, Babinsky symptom, Oppenheim symptom, Gordon symptom, Scheffer symptom, Rossolimo symptom, Zhukovsky symptom, ankylosing spondylitis), malnutrition, hypotension of the limb muscles.

Investigate the system of balance and coordination, evaluating the presence of Romberg symptom, dysmetria, nystagmus, intentional tremor, and atactic gait. Particular attention is paid to the joint presence of the Romberg symptom with dysmetria or Argyle Robertson syndrome, or asymmetry of carporadial reflexes, or high knee reflexes, and / or muscle hypotension. The joint presence of atactic gait and Argyle Robertson syndrome, asymmetry of carporadial reflexes, symmetric knee reflexes and / or Romberg symptom are noted; as well as a combination of dysmetria with muscle atrophy. These combinations of indicators are also new in the present method and are scored additionally.

During an ophthalmological examination, special attention is paid to the presence of uveitis, atrophy of the optic nerve.

When evaluating the sensory sphere, disorders of proprioceptive sensitivity and disturbances of extroceptive sensitivity, as well as radicalism, a pain syndrome caused by damage to the roots, are distinguished.

In addition, attention is drawn to the presence of a sensitive ataxia syndrome, characterized by a combination of disorders of proprioceptive sensitivity with Romberg symptom, dysmetria, aggravated by closing the eyes, punching gait, pseudo-aethetosis, inhibition of knee and achilles reflexes.

In addition, the presence of autonomic dysfunction, neurosis-like disorders, cognitive impairment, meningeal syndrome is assessed.

According to the research results, the values of the indicators of all four groups are determined. Then, using the table 1-4 select the appropriate evaluation points and determine the diagnostic coefficients of each group. A comparison is made with control values (-4 points for a group of blood indicators, 13 for a group of patient complaints, 35 for a group of indicators of a neurological examination, 4 for a group of indicators from the anamnesis data). With the simultaneous excess of all diagnostic coefficients over control values, a conclusion is drawn - in a patient with NS.

If all four diagnostic coefficients are less than the control values, the patient does not suffer from NS.

Examples.

Example 1

Patient N. was hospitalized in the clinic of skin and sexually transmitted diseases to clarify the form of syphilis. With MRI of the head, a volumetric formation of the right leg of the cerebellum was detected, and therefore lumbar puncture was contraindicated and was not performed. The indicators obtained as a result of the survey were processed, scored according to the degree of influence on the final result of the claimed invention and are listed in table 5-8 in the column "example 1".

The patient was examined by a dermatovenerologist, neurologist, therapist and ophthalmologist. 4 ml of venous blood were taken, sample samples were prepared and serological studies were performed: MRI, DSC with cardiolipin (K) and treponemal (T) antigens, RPGA and ELISA according to the standard technologies described in the description.

Clinical examination of the patient allowed to obtain answers to a number of questions. The age of the patient at the time of infection is 18 years.

Antisyphilitic treatment was not carried out. The age of the patient at the time of the study is 23 years. Of the concomitant diseases listed in Table 5, a lesion of the peripheral nervous system in the form of right-sided Erb-Duchenne plexopathy was found.

During a neurological examination, special attention was paid to a list of questions on the identification of subjective symptoms of a nervous system lesion in the form of patient complaints. In particular, numbness and weakness in the right hand were found, as well as a headache.

Signs of damage to the corticonuclear pathways were revealed - symptoms of oral automatism; reflex-motor disorders - peripheral right-sided superior monoparesis, asymmetry of carporadial reflexes, absence of abdominal reflexes; sensory disorders - a violation of exteroceptive sensitivity in the right upper limb; disorders of balance and coordination - Romberg symptom, nystagmus. Particular attention was paid to the presence of symptoms of oral automatism in the absence of abdominal reflexes.

An ophthalmologic examination revealed atrophy of the optic disc.

A comparison was made of the obtained diagnostic coefficients of the patient with control values.

DK ₁ = 10, i.e. > 4, DK ₃ = 93, i.e. > 35,

DK ₂ = 17, i.e. > 8, DK ₄ = 71, i.e. > -4.

The values of the obtained diagnostic coefficients exceed all four control values, which indicates the presence of neurosyphilis in the patient.

Example 2

Patient P. was hospitalized in the clinic of skin and sexually transmitted diseases to clarify the form of syphilis. Lumbar puncture was not performed due to the pregnancy of the patient. The indicators of serological studies obtained as a result of the examination were processed, scored according to the degree of influence on the final result in accordance with the claimed invention and are listed in tables 5-8 in the column "example 2".

The patient was examined by a dermatovenerologist, neurologist, therapist and ophthalmologist. 4 ml of venous blood were taken, sample samples were prepared and serological studies were performed: MRI, DSC with cardiolipin (K) and treponemal (T) antigens, RPGA and ELISA according to the standard technology described in the description.

Clinical examination of the patient allowed to obtain answers to a number of questions. The age of the patient at the time of the study is 33 years. Syphilis was diagnosed 2 years after infection, at the age of the patient 24 years. Antisyphilitic treatment was carried out. Concomitant diseases listed in table 5 were not found.

During a neurological examination, special attention was paid to a list of questions on the identification of subjective symptoms of a nervous system lesion in the form of patient complaints. In particular, a headache has been identified.

Signs of damage to the cranial nerves, reflex-motor disorders, sensory disturbances, disorders of balance and coordination, as well as other signs of damage to the nervous system were not found.

A comparison was made of the obtained diagnostic coefficients of the patient with control values.

DK ₁ = -4, i.e. <4, DK ₃ = 0, i.e. <35,

DK ₂ = 2, i.e. <8, DK ₄ = -101, i.e. <-4.

The values of the obtained diagnostic coefficients do not exceed the control values, which indicates the absence of neurosyphilis in the patient.

Example 3

Patient M. was hospitalized in the department of the clinic of skin and sexually transmitted diseases to clarify the form of syphilis. The survey indicators were processed, scored according to the degree of influence on the final result of the claimed invention and are listed in table 5-8 in the column "example 3".

The patient was examined by a dermatovenerologist, neurologist, therapist and ophthalmologist. 4 ml of venous blood were taken, sample samples were prepared and serological studies were performed: MRI, DSC with cardiolipin (K) and treponemal (T) antigens, RPGA and ELISA according to the standard technology described in the description.

Clinical examination of the patient allowed to obtain answers to a number of questions. The age of the patient at the time of the study is 58 years. Syphilis was diagnosed 10 months after infection, at the age of the patient 36 years. Antisyphilitic treatment was carried out in a hospital. Concomitant diseases listed in table 1 were not found.

During a neurological examination, attention was paid, including to the list of questions on identifying subjective symptoms of a nervous system lesion in the form of patient complaints. In particular, difficulties were found in performing precise movements and decreased vision.

Signs of damage to the cranial nerves were revealed - symptoms of oral automatism, reflex motor disorders - asymmetry of Achilles reflexes, lack of abdominal reflexes, sensory disturbances, balance and coordination disorders - Romberg symptom, nystagmus; cognitive impairment. Particular attention was paid to the presence of symptoms of oral automatism in the absence of abdominal reflexes.

A comparison was made of the obtained diagnostic coefficients of the patient with control values.

DK ₁ = 6, i.e. > 4, DK ₃ = 60, i.e. > 35,

DK ₂ = 14, i.e. > 8, DK ₄ = 85, i.e. > -4.

The values of the obtained diagnostic coefficients exceed the control values, which indicates the presence of neurosyphilis.

To assess the accuracy of the proposed method, the data in example 3 were taken from a patient who was not contraindicated with lumbar puncture, which allowed CSF sampling and compare the results of the study with the method stated in this application with the results of a standard study accepted at present to obtain data as a result of CSF analysis . A clear, colorless CSF was obtained under a pressure of 180 mm H ₂ O.

The level of cerebrospinal fluid protein was 0.45 g / l; Nonne-Apelt reaction 2+; 42 lymphocytes / mm ^{3 were} detected, glucose level - 5.2 mmol / L. MRI is negative, CSC with cardiolipin (K) and treponemal (T) antigens is negative, RPGA 2+ (titer 1:40), ELISA is positive (OD = 0.89, KP = 3.21). These results indicate the presence of NS in the patient. The conclusions coincided - the NS was detected in both ways.

The exhaustive scope of questions and response information, its ranking, and assessment of the degree of importance of answers and indicators in points allows without further complications in the subsequent automation of data processing. This will make the assessment of a difficult-to-recognize disease effective and modern, optimize the doctor’s work, reducing the time for assessing the patient’s condition and allow choosing the appropriate treatment for the disease.

additional literature

1. Order of the Ministry of Health of the Russian Federation No. 87 dated 03/26/2001 "On improving the serological diagnosis of syphilis."

2. Order of the Ministry of Health of the Russian Federation of 25.07.2003 No. 327 "On approval of the protocol for the management of patients" Syphilis ".

3. Order of the Ministry of Health and Social Development of the Russian Federation dated December 08, 2006 No. 829 “On approval of the standard of medical care for patients with late syphilis (in the provision of specialized care)”.

4. Order of the Ministry of Health and Social Development of the Russian Federation dated December 8, 2006 No. 830 “On approval of the standard of medical care for patients with latent syphilis, unspecified as early or late (when providing specialized care)”.

Claims (1)

A method for detecting neurosyphilis in patients infected with Treponema pallidum treponema pallidum, characterized in that venous blood is sampled, samples are prepared for serological studies: precipitation microreaction (MCI); complement binding reactions (CSCs) with cardiolipin (K) and treponemal (T) antigens; passive hemagglutination reactions (RPHA); enzyme immunoassay (ELISA); carry out the above reactions in qualitative and quantitative versions; carry out a clinical examination of the patient; the obtained results of serological studies, anamnesis data and information about the state of the nervous system, which serve as significant indicators, are recorded and divided into four groups, united by a significant community within each group, and the number of points identified in the patient’s indicators is estimated by the degree of influence on the study result:
Group 1 consists of indicators taken from the anamnesis:

Group 2 consists of the following indicators:

Group 3 consists of the following indicators:

at the same time, combinations of indicators are additionally evaluated:

Group 4 are indicators obtained by serological studies:

moreover, from the series of values of each indicator, a value is selected that corresponds to the most pronounced picture characterizing the patient’s condition and the corresponding evaluation points, add them inside each group and receive diagnostic coefficients for each of the four groups - DK ₁ , DK ₂ , DK ₃ , DK ₄ , they are compared with control values, and the criterion for evaluating the presence of neurosyphilis is the ratio of the values of all four diagnostic coefficients of the patient with the control values:
DC ₁ ≥4,
DC ₂ ≥8,
DC ₃ ≥35,
DC ₄ ≥-4;
the patient’s absence of neurosyphilis is judged with values from a set of diagnostic coefficients that are less than the corresponding control values.