A method for diagnosing and forecasting the development of epilepsy in patients with preclinical stage of the disease

 

(57) Abstract:

The invention relates to medicine, namely to psychiatry and neurology, and can be used as a method of revealing hidden epileptogenesis. Perform EEG monitoring, processing the received EEG method of fractal analysis and obtain the values of the fractal dimension (D). Additionally consist of the values of the test paroxysmal activity (PAT) content in the blood of patient autoantibodies to quisqualate-binding membrane protein. Calculate the index of epileptic activity (IE) according to the formula IE=PATM. When set IE=132,545,32 diagnosed with clinical stage epilepsy, values IE=45,053,31 indicate the health of the patient, and intermediate values of the pre-clinical stage of epilepsy. The method improves the accuracy of diagnosis of the development of epilepsy in patients with preclinical stage of the disease. table 4.

The invention relates to medicine, namely to psychiatry and neurology, and can be used as a method of revealing hidden epileptogenesis, giving an opportunity to assess the degree of compansionate or mobility, allowing to improve the diagnosis of epilepsy Luchino detected spontaneous paroxysmal activity in the electroencephalogram (EEG); 2) about the same seizures without changes on EEG and 3) of febrile convulsions in children.

These state of the disease are not fully clinically established syndromic and because they cannot be distributed nosological principle diagnosis.

Another complicating factor is that, according to the Helsinki Declaration on human rights, which was signed by our country, the doctor can not stand without the consent of the patient diagnosis, which clinically is insufficiently substantiated, and especially one that may infringe on his rights and negatively affect quality of life.

Up to the present time there is no recognized and undisputed definition of the disease, norms and health.

The most recognized and prevalent in the medical literature the terms are "predpolozhenie status", "diagnosis", "subclinical", "conditionally pathological", "premorbid".

In order to answer the questions of what the disease is, to define its boundaries, to establish a typology of these disorders, it is necessary first to solve the General conceptual issues and to form a certain position, so as predvoleny is not only a concept, but a concept that in many ways can the bookmark. The disease is a disorder of normal psychosomatic condition and ability of the individual optimal (within reason) to satisfy the material and spiritual needs of the individual. They note that the concept of "disease" and "health" are complicated with the introduction of such gradations as "predvoleny" [1].

VP of Petrenko, and I. Tsaregorodtsev believe that illness is a reflection of the attempts of the body and personality of the whole person to adapt to individually changed for him the conditions of the external environment [2].

There are other definitions: biologically disease is the objective manifestation of dysfunction [3]; the disease is "the disparity between the stimuli and the ability actions" [4].

Along with this, health is defined as a state of complete physical and social well-being.

The above definition of "disease" cannot be extended to consider paroxysmal States, because there's not much they change in the lives of persons, where they are marked. However, in adults, having a degree of risk for epilepsy (driver, guard, and others), one registered a seizure with convulsions and loss of consciousness can radically change the socio-labour celuutsya attempts to find out the reason the availability on the spontaneous EEG paroxysmal activity in the absence of seizures or other symptoms of epilepsy (personality changes, and others), but most convincing solution to the question is not given or is given a formal response.

So, in due time, the American scientist R. Hess [5] on the question of whether to treat individuals with paroxysmal changes in EEG, replied that necessary to treat the patient, not the EEG. Formally this is correct, but the answer to the question how to regard the appearance of paroxysmal changes on EEG was not given. The fact that this is not the norm, obviously. N. P. Bekhtereva et al. [1], putting forward the concept of sustainable pathological condition in diseases of the brain comes to the conclusion that when the brain fixture is not due to fill in the missing links, and the resulting formation of a new "homeostasis", the new steady state, ensuring the best possible in terms of disease adaptation to the environment [6]. Here the author solidarized settings B. N. Petrenko and G. I. Tsaregorodtseva [2]. In its opinion, the stability stable pathological condition associated with formation of the corresponding matrix in long-term memory. If the pathological process progresses, the systems providing sustainable pathological condition first occurs quantitative changes. Support with quality reconstructions and the exhaustion of the compensatory-hyperactive systems, i.e. decompensation.

According to theory, N. Kryzhanovsky [7] about epileptogenesis you can imagine that under the influence of endo - or exogenous factors comes epileptische neurons, not reaching the stage of formation of the epileptic focus, i.e. does not fully decompensation protection mechanisms of the brain and does not develop the disease, epilepsy, and is formed stable compensated pathological condition. Apparently, the pathogenic factor wore coming, that is temporary. Most likely this pathogenic effects could occur during birth [8].

Compensated condition may remain indefinitely and even to progress, although in some cases, under the influence of the additional hazards may come coming decompensation in a single attack.

Apparently, accidentally recorded spontaneous paroxysmal activity on EEG can be attributed to this stage.

Attempts to understand psycho-physiological stage of epilepsy has been done previously. So, such as Miridonov believes that the diagnostic criterion of this stage is the period from the beginning of the development of the first cerebral seizures to the WTO is poison risk characteristics of the development of epilepsy (36) and giving each a certain importance in points, identified groups of subjects with maximum and minimum possibility of carrying in itself the epileptic process, clinically not yet fully designed [10]. Unfortunately, these researchers failed to visualize hidden leaky epileptogenic, in routine EEG is not giving any graphelement typical EEG of a patient with epilepsy.

Well-known set of PA-test (PAT) for the diagnosis of epilepsy [11], namely, that in the blood of the patient determine the content of autoantibodies to quisqualate-binding membrane protein.

A disadvantage of the known PA-test is that it cannot reliably predict the development of disease in patients with preclinical stage of epilepsy, such as: 1) accidentally detected spontaneous paroxysmal activity on EEG; 2) one convulsive seizures without changes on EEG and 3) febrile convulsions in children.

The closest to the invention is a method of diagnosis and prognosis of epilepsy and its preclinical stage, including electroencephalographic monitoring and subsequent processing of the EEG method of fractal analysis [12].

A disadvantage of the known methods for the th disease, especially in the paroxysmal three conditions: 1) accidentally detected spontaneous paroxysmal activity on EEG; 2) one convulsive seizures without changes on EEG and 3) febrile convulsions in children.

The technical result of the present invention is to improve the reliability and accuracy of forecasting the development of epilepsy in patients with preclinical stage of the disease, mainly with the following paroxysmal States: 1) accidentally detected spontaneous paroxysmal activity on EEG; 2) one convulsive seizures without changes on EEG and 3) febrile convulsions in children.

This result is achieved in that in the method for the diagnosis and forecasting of the development of epilepsy in patients with preclinical stage of the disease, including electroencephalographic monitoring and subsequent processing of the EEG method of fractal analysis to obtain the values of the fractal dimension, according to the invention additionally determine blood from the patient the content of autoantibodies to quisqualate-binding membrane protein using test paroxysmal activity and calculate the index of epileptic activity using the following formula:

IE=PATTR,

Stalnoy dimension (D)

the values IE=132,545,32 testify to the changes of the immune and Central nervous system in epileptic type that corresponds to the clinical stage of the disease; values IE=45,053,31 indicate the safety of these systems, which indicates the health of the patient, and intermediate values indicate moderate violations, unable to realize the clinical manifestation of epilepsy at this stage.

In addition, when the following indicators: D>0,70, PAT>150 and the IE>105 begin antiepileptic therapy to prevent getting the disease in the clinical stage of epilepsy.

This study allowed us to theoretically substantiate the notion of the pre-clinical stage of epilepsy ("predvoleny"), implying that objectify criteria in order to identify the epileptic nature of spontaneous paroxysmal States, not reaching in its manifestations clinical symptom of epilepsy. Mean paroxysmal EEG changes without seizures, one unprovoked seizure seizures and febrile convulsions.

Research methods: the method of clinical observation, the method of fractal analysis of EEG (FA EEG), a test of five groups: 1) spontaneous paroxysmal (parasitophobia) violations on EEG (MO) - 33 people (16 men, 17 women); 2) unprovoked epileptic seizure without changes in the EEG (NEP) 39 (18 men, 21 women) and 3) febrile seizures in early life (FS) - 66 (32 men, 34 women). The observed group includes at 138 (66 men, 72 women) aged from 15 to 46 years.

For the reliability analysis, we introduce two control groups: 1) patients with epilepsy, 2) healthy. Analyzed the observed should take between them like an intermediate position according to the above concept of "predvoleny".

Control group were: 1) epilepsy patients with clinically detected attacks and the duration of the disease prior to the year 68 (38 men, 30 women) aged 15 to 59 years - clinical stage of epilepsy (CTU); 2) healthy (volunteers), 30 patients (16 men, 14 women) aged 16 to 40 years - norm control (ZV).

We all studied twice with a 3-year interval) produced a five-minute digitized recording of EEG (method F EEG), at the same time improved method PA-test determined the titer of autoantibodies (AutoIt) to glutamate-binding membrane protein (GMB).

The results of the study were evaluated conditional units is Oksana.

Results. As follows from the table. 1, in the control group 3 (ZV) the dependence of the spectral density of frequency fluctuations of the square of the amplitude (power) of the alpha rhythm has a spectral index b, equal 3,950,11 (frequency - 1-4 Hz), which corresponds to the fractal dimension D 0,530,06. Although the physiological role of fluctuations of this type are not completely clear, it is known that they are closely associated with the underlying processes in the brain and can reflect subtle changes in its functional activity [6].

Fractal structure of fluctuations in the power of the alpha rhythm patients CTU (see gr. table 2. 1) differs significantly from the norm: the index b in this group surveyed clearly reduced (3,380,06), the values of the fractal dimension, respectively, is increased compared with the latest in healthy subjects (0.810,03) - p<0,05 (gr. table 1. 1). The identified difference indicates that the degree of autocorrelation is significantly lower in control in patients with epilepsy (CTU) than in control of the surveyed volunteers (ZV). Fluctuations in the amplitude of alpha waves in the group of patients with clinically detected attacks (control) show a low level of predictability, which indicates the misalignment of the cerebral mechanisms of control is closely related, well shows the change in the target groups the average titre of AutoIt to GMB. Noted for its steady growth of 1.4 times in the preclinical stage of epilepsy and 1.9 in patients with recorded attacks. Further observation (gr. B) this trend stores.

It should be noted that not always there is a marked change in immunological and neurophysiological status of the human body with increasing epileptogenesis. In some cases, not necessarily at the highest values of the PAT register adequately high values of the fractal dimension, and Vice versa. Most likely indicators of titre AutoIt to GMB and fractal analysis are complementary. Therefore, in order to obtain uniform characteristics assess the severity of the disease process, we offer integral exponent of epileptic disorders - epileptic activity index (EI). This index is formed by multiplying the values of the PAT and the fractal dimension: IE=PATM. The obtained high values of the IE indicates a change of state of the immune and Central nervous system in epileptic type - gr. A -(CTU - 132,545,32), low - about the safety of these systems (ZV - 45,053,31), Prohm is NII them in one of them, but not able to implement the clinical manifestations of epilepsy.

An important diagnostic factor is the stability of these parameters in control group (gr. B) during a long period of time, in this case 3 years.

Exponential growth dynamics of the fractal dimension (D) in subgroups representing LTO in the table. 2.

All three subgroups have D values exceeding the normal range, showing the growth of its values from subgroups 1,3 - FS (0,630,02) to subgroup 1, 2 - NEP (0,770,03) - p<0,05 - gr. A. After 3 years these figures statistically increased (p<0,05), as is the PAT and IE. In General, the group LTO shows intermediate values of b, D, PAT and IE between the same parameters of the control groups (ZV) and patients with clinically diagnosed epilepsy (CTU) at both stages of the study.

The direction of growth of the value of the titre of AutoIt to GMB in subgroups LTO meets, as a rule, increase changes neurophysiological indicators (102,092,18-FS; 118,173,02-MO; 138,122,09-NEP).

Extremely important is the change of the investigated parameters observed with LTO (see tab. N 3), with the most important risk factors (heredity, otyagoshennuyu and in the future, start epileptogenesis, the significant role of traumatic brain injuries, infections (tonsillitis, rheumatism, malaria, inflammation of the sinuses, colds, and so on), as well as developing a mixed type of encephalopathy. Presented in table. 3 results show higher growth rates D, PAT and IE in gr. with FR and it is from this group after 3 years in subjects was marked by the transition LTO in CTU.

Analysis of the dynamics of brain processes in the studied groups (see tab. 4), carried out three years later, showed that out of 138 people in 12 (8,7%) had values IE from 80 to 129 were registered numerous epileptic seizures, with a corresponding increase in IE from 127 to 135. 34 (24,6%) patients showed a growth IE to 86-124, but he was not accompanied by the occurrence of attacks and therefore related to LTO with increasing epileptogenesis. Along with this, at 79 (57,3%) significant changes IE not happened, and this group can be considered as having stable compensated condition. 13 (9.4%) of people marked regression of paroxysmal States and, apparently, you can eliminate the risk of epilepsy. Thus, the increase of epileptogenesis or decompensation (illness) was recorded in 46 people (thrope NEP - 5 (12.8%) are observed.

It should be noted that persons with LEP for the greatest outcome of the pathological process in the CSE. All 12 patients clinically registered epilepsy carry the risk factors of epilepsy: 1) morphological changes of the brain (MI), 2) heredity, hereditary epilepsy (NOE). In the subgroup of PN, except paroxysmal disorders EEG revealed NOE and MI brain, in the subgroup of NEP in all patients revealed morphological changes in the brain and in 2 NOE, in the subgroup FS all identified MI brain, and 2 had NOE.

As noted above, simultaneously with the increase of epileptogenesis part of the observed (9,4%), in contrast, is attenuation, which shows the decrease in the values of IE to levels close to those of the ZV (43 to 58).

In this group of 3 people (LOI) was determined by one risk factor for epilepsy - NOE, 2 NEP identified MI and in 1 patient with FC - MI.

The data obtained in our opinion, suggests that the period of clinical manifestations of epilepsy preceded by a relatively long, individually oscillating in time, the latent phase (LTO), during which there is a progressive estimates the diagnostic indicator IE is sensitive to the dynamics of brain processes related to different stages of epileptogenesis. The most important is the ability to use IE for early prediction of the onset of crisis in the development of the disease, i.e., phase transitions: health (ZV) - preclinical stage of the disease (LTO) - clinical stage of the disease (CTU), presents the full symptom complex.

According to theory about epileptogenesis, we can assume that the DCE includes the step epileptic activity of neurons, pathological changes which are not able to be realized in clinical manifestations. That is, of the four sequential phases of neurophysiological and neuromorphological changes: epileptische neurons, the formation of an epileptic focus, a nervous system, epileptic activity of the brain [8] the first one or two are the basis of LTO. Point to this circumstance, and some researchers [8], noting that the epileptic focus can last for a lifetime, not clinically accompanied by paroxysms. The state of the preclinical phase of epilepsy may continue indefinitely and be determined by many endogenous and exogenous factors and, above all, protective compensatory abilities of the body the isms leads to a transition in the CSE, the preservation or enhancement to additional compensation and, often, to the regression of the pathological process and return to health.

Thus, patients with stable pathological conditions (FS, MO on EEG NEP) in respect of which previously did not have a single point of view, both in terms of diagnosis and treatment, we are using modern methods (traditional, PAT, F), divided depending on the results of the study and the presence of risk factors (heredity, hereditary epilepsy, morphological changes of the brain) into three groups: 1) persons who can be expected recourse registered changes (9,4%), are excluded from the group of observation; 2) with the sustainable pathological conditions without the tendency to increase epileptogenesis that do not require a diagnosis of epilepsy at risk and in need of control observations not less than 1 time per year (57,3%); 3) patients with progressive epileptogenesis, accompanied by increasing values of D and PAT - preclinical stage of epilepsy, status, compensation, apparently, require preventive treatment. With further progression of the pathological process may shift in decomposion the willows and in connection with the social significance of the diagnosis of its wording should be agreed with the patient. Taking into account the possible etiopathogenic factors arising from history and survey results, we can recommend pathogenic variant of diagnosis ("the consequences of traumatic brain injury, CNS-infections"; "encephalopathy mixed Genesis with a tendency to paroxysmal States" and so on).

Our research leads us to conclude that in the case of registration of the examined compensated epileptogenesis enough only dynamic observation. If detected in patients status (FS, MO on EEG, NEP) is complicated NOE and MI brain and contain the indices D (F EEG)>0,70, PAT>150, IE (- PAT)>105 indicating the progression of epileptogenesis, you should think of moving compensation to decompensation, i.e., in epilepsy. In this case, you need preventive treatment with the mandatory use of monotherapy AED, which should be carried out to the maximum normalization and stabilization of the values of the above indicators.

In conclusion, it is necessary to emphasize that the proposed method of identifying hidden epileptogenesis and giving an opportunity to assess the degree of compansionate or mobility can improve diagnosis clinical stage development of epilepsy.

Thus, the proposed method for the diagnosis and forecasting of the development of epilepsy in patients with preclinical stage of the disease can increase the reliability and accuracy of forecasting the development of epilepsy in patients with preclinical stage of the disease and to initiate timely profilakticheskogo treatment which should be carried out to the maximum normalization and stabilization of the values of all indicators.

A method for diagnosing and forecasting the development of epilepsy in patients with preclinical stage of disease developed by the authors and has been tested in research psychoneurological Institute. C. M. Bekhterev.

References

1. Klonowski A. N. , Starchenko A. A. Conciencia disease damaged brain. St. Petersburg: Izd-vo "DOE", 1999-256 C.

2. Petrenko B. N. , Tsaregorodtsev, And. Philosophy of medicine. - Kiev: "Health", 1979.-230 C.

3. Sim J. The concept of health //Physiotherapy. - 1990, vol.76, 7. - p. 423-428.

4. Hegel So-Century Science of logic // works of different years: in 2 volumes. So 1. - M. , 1970.-608 C.

5. Hess R. - CIT. in P. M. Sarajishvili, T. W. Geladze. Epilepsy. - M.: Medicine, 1977. - 304 S.

6. Bekhterev N. P. , Kambarov, D. K., Pozdeev C. K. Sustainable pathological is in the pathology of the nervous system: generating mechanisms neuropathologically syndromes. - M., 1980. - 360 C.

8. Gromov S. A., Lobzin Century C. Treatment and rehabilitation of patients with epilepsy. - SPb: "Education", 1993. - 238 S.

9. Miridonov Century So Prenosological period of epilepsy in children. - Perm, 1998. - 172 S.

10. Zenkov L. R. Pathogenesis and multiparameter diagnosis of epileptic and nonepileptic seizures // Ukr. Terra medica nova. - 1997. - 4. - C. 32-34. - 1998. 1. C. 44-46.

11. RU Patent 2112243, class a 61 K 39/00, 1995

12. RU Patent 2156607, class a 61 K 5/0476, 1999 prototype.

A method for diagnosing the development of epilepsy in patients with preclinical stage of the disease, including electroencephalographic monitoring, processing the received EEG method of fractal analysis and obtaining the values of the fractal dimension (FD), characterized in that an additional count values of the test paroxysmal activity (PAT) content in the blood of patient autoantibodies to quisqualate-binding membrane protein, calculate the index of epileptic activity (IE) according to the formula

IE= PATTR

and when the value of IE= 132,545,32 diagnosed with clinical stage epilepsy, values IE= 45,053,31 indicate the health of the patient, and intermediate values of the pre-clinical stage of epilepsy.

 

Same patents:

The invention relates to medicine, in particular to obstetrics

The invention relates to medicine, in particular to Microbiology, and can be used to determine the titer of specific antibodies in acute and chronic Sapa in the reaction of indirect haemagglutination

The invention relates to medicine, in particular to Microbiology and relates to methods of preparation of immune sera

The invention relates to medicine, namely to pulmonology, and can be used to address the question about the effectiveness of therapy glucocorticoid hormones and selection of adequate doses of glucocorticoid hormones in patients with bronchial asthma (BA)

The invention relates to medicine, namely to pulmonology, and can be used to address the question about the effectiveness of therapy glucocorticoid hormones and selection of adequate doses of glucocorticoid hormones in patients with bronchial asthma (BA)

The invention relates to medicine, namely to pulmonology, and can be used to address the question about the effectiveness of therapy glucocorticoid hormones and selection of adequate doses of glucocorticoid hormones in patients with bronchial asthma (BA)
The invention relates to medicine, in particular to medical Parasitology

The invention relates to medicine, in particular to immunology

The invention relates to medicine, in particular to surgery

The invention relates to the field of medicine and is intended to determine the state of the human brain and detection of pathological changes in its system activity
The invention relates to medicine, in particular to clinical neurophysiology, and can be used to identify contraindications for electrical stimulation in children and adolescents (7 - 18 years) without epileptiform brain activity

The invention relates to medicine, in particular for neurology and Pediatrics
The invention relates to medicine, in particular to methods of correction of the physiological state of the human body with the use of electromyostimulation his Central nervous system

The invention relates to medicine, namely to Nephrology, neurosurgery, and may find application in the study of structural and functional brain changes

The invention relates to medicine, namely to psychiatry and neurology
The invention relates to medicine, in particular to the field of medical and psycho-physiological diagnostics, and for diagnosing the degree of psycho-physiological maladjustment in patients with primary chronic cerebrovascular pathology
The invention relates to medicine, in particular to methods of objective diagnostics of disorders of sleep a night person

The invention relates to the field of diagnosis of acute CNS, namely to research methods diphtheria polyneuropathy (SFD) in children, and is intended for forecasting of the current cash flow with timely therapeutic correction

FIELD: medicine, neurology, psychopathology, neurosurgery, neurophysiology, experimental neurobiology.

SUBSTANCE: one should simultaneously register electroencephalogram (EEG) to detect the level of constant potential (LCP). At LCP negativization and increased EEG power one should detect depolarizational activation of neurons and enhanced metabolism. At LCP negativization and decreased EEG power - depolarized inhibition of neurons and metabolism suppression. At LCP positivation and increased EEG power - either repolarized or hyperpolarized activation of neurons and enhanced metabolism. At LCP positivation and decreased EEG power - hyperpolarized suppression of neurons and decreased metabolism of nervous tissue. The method enables to correctly detect therapeutic tactics due to simultaneous LCP and EEG registration that enables to differentiate transition from one functional and metabolic state into another.

EFFECT: higher accuracy of diagnostics.

5 dwg, 1 ex, 1 tbl

Up!