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. Register the EEG in a patient's condition passive wakefulness. Method the cross-correlation analysis of process fragments EEG lasting no more than one minute, which do not contain paroxysmal activity. Get factors crosscorrelate (HCC) alpha activity between the leads of the left frontal and left occipital regions. The obtained values HCC ranging from -1,00 to -0,35 indicate the health of the patient, when values of HCC from 0.34 to 0,00 diagnose preclinical stage of epilepsy, but values HCC from 0.01 to 1.00 - clinical stage of epilepsy. The method improves the accuracy of diagnosis of epilepsy development. table 2.

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 in its preclinical stage.

In this izobreteniya on the electroencephalogram (EEG); 2) about the same seizures without changes on EEG and 3) of febrile convulsions in children.

A practical physician in such cases, in addition to the diagnostics have to decide if treatment is needed. The lack of scientific interpretation and the unified medical tactics against observed facts negatively affects the work of the doctor and therefore the effectiveness of therapy.

So the inevitable question about the possible existence of latent, clinically manifested period of epilepsy occurring depending on the compensatory abilities of the body at different speeds first, biochemical, and then and ultrastructural levels changes cells. Similar is observed when the incubation period of infectious diseases and complies with asymptomatic primary for many diseases.

The study of epilepsy and its etiopathogenesis is devoted considerable number of works [1, 2, 3], which cannot be said about the period preceding it, i.e. the stage of pre-existing disease. In the literature sometimes there are articles in which attempts are made to find out the reason the availability on the spontaneous EEG paroxysmal activity in the absence of seizures or other is P. Bekhtereva et al. [4], proposing 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. 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 reactions of the organism are considered compensatory. Further progress of the disease can be associated with the quality of the reconstructions and the exhaustion of the compensatory-hyperactive systems, i.e. decompensation.

According to theory, N. Kryzhanovsky [5] 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 not developing new condition may remain indefinitely and even progress, although in some cases under the influence of the additional hazards may occur transient 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 already been done. 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 before the second unprovoked epileptic seizure, and an average of 1-2 years [6]. L. P. Zenkov, combining a number of features of the risk of developing 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 [7] . Unfortunately, these researchers failed to visualize hidden leaky epileptogenic, in routine EEG is not giving any graphelement typical of bioelectric activity of a brain of the patient with epilepsy.

It is known that normal bioelectric brain activity h is to promote the strengthening of synchronous rhythmic flow processes with a tendency to increase in amplitude and sharpening of the peaks of the action potentials and, in particular, the advent of hypersynchronous alpha rhythm [8, 9]. You probably have a common physiological mechanisms underlying the synchronization of the alpha rhythm and hypersynchronous epileptic activity.

Hidden leaking epileptogenic at the preclinical stage of the disease should also lead to certain disorders synchronization of the EEG. Therefore, the search for new neurophysiological criteria that allow to analyze cerebral dysfunction at the stage of minimal manifestations of neuronal hypersynchronization is important from the point of view of improvement of diagnostics of epilepsy, especially in its preclinical stage, and early influence on the course of the pathological process.

Quantitative and qualitative characteristics of the synchronization of the EEG can be estimated using the method of correlation analysis, the advantage of which is the ability to identify periodic oscillations even when their amplitude is many times smaller than the amplitude of the irregular fluctuations. Thus, the application of this method is possible with any type of bioelectrical activity of the brain, even in case of insufficient representation of the alpha rhythm is their phase shift and to quantify the degree of Association or similarity of the two processes [10], particularly attuned to the functioning of neurons in different areas of the cerebral cortex, that is, to identify the features of spatial synchronization of the EEG.

The closest to the invention is a method of diagnosis and prognosis of epilepsy, including electroencephalographic monitoring and subsequent processing of the received EEG [11].

The disadvantage of this method is the inability to reliably predict the development of disease in patients with preclinical stage of the disease, especially in the paroxysmal three conditions: 1) accidentally detected spontaneous paroxysmal activity on EEG; 2) a single 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 d is tranceparency monitoring and subsequent processing of the received EEG according to the invention of the electroencephalogram processing carried out by the method of cross-correlation analysis, this process lead signals of the left and right frontal (F3 and F4), Central (C3 and C4), parietal (P3 and P4) and occipital (O1 and O2) regions in a state of passive wakefulness in areas that do not contain paroxysmal activity, the duration of the considered fragments not more than one minute, and using cross-correlation analysis estimate of selected characteristics of the signal of the alpha rhythm (8-13 Hz) to obtain the coefficients of crosscorrelate alpha activity between selected leads, moreover, the values of the coefficients of crosscorrelate (HCC) between the signal lead of the left frontal region (F3) and the left occipital region (O1), which is in the range from -1,00 to -0,35 evidence indicates the health of the patient, when values of HCC between F3 and O1 from 0.34 to 0,00 - preclinical stage of epilepsy, and the values HCC between F3 and O1 from 0.01 to 1.00 correspond to the clinical stage of the disease.

This study helped to identify an objective measure of the degree of epileptic activity brain-based quantitative assessment of the level of synchronization of the EEG in the range of the alpha rhythm method crosswa paroxysmal States, not reaching in its manifestations clinical symptom of epilepsy. Mean accidentally detected paroxysmal EEG changes that are not accompanied by seizures, one unprovoked seizure seizures and febrile convulsions.

Clinical research is presented to a group of subjects with preclinical stage of epilepsy (LTO) having two or more risk factor for epilepsy high importance, such as spontaneous paroxysmal (parasitophobia) violation of EEG, one unprovoked epileptic seizure without changes on EEG and febrile convulsions in the early period. The observed group includes 114 (51 men, 63 women) aged from 16 to 52 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 illness before the year is 59 people (30 men, 29 women) aged from 17 to 54 years - clinical stage of epilepsy (CTU); 2) healthy (volunteers) - 30 Las monopolar on multi-computer electroencephalograph "Encephalan 131-01" with the electrodes according to the international system "10-20" and the use of reference electrodes, located on the earlobe. Recording was carried out in a state of passive wakefulness, when exposed to 3-minute hyperventilation and rhythmic photostimulation.

Material for further processing served as lead signals F3 and F4 (left and right frontal region, respectively), C3 and C4 (right and left Central region), P3 and P4 (left and right parietal areas), O1 and O2 (left and right occipital region) in a state of passive wakefulness in areas that do not contain paroxysmal activity. The duration of the considered fragments EEG was 1 min was Estimated characteristics selected from the signal of the alpha rhythm (8-13 Hz). Using cross-correlation analysis were obtained factors crosscorrelate alpha activity between selected leads. Determination of the degree of reliability of differences of averages was carried out on the level of p<0,05, t-test, Student.

The results of the cross-correlation analysis of EEG in the range of the alpha rhythm showed (table. 1) that in all three groups surveyed, there is a high level of positive correlation relationships between symmetric regions of the hemispheres. There is a small discovery.

Received positive crosscorrelation alpha rhythm between adjacent regions of the same hemisphere showed a slight increase in the values of the coefficients of crosscorrelate in the group with LTO (predvoleny) and even greater in the group with CTU (illness). Especially clearly increased correlative relationships in the process of increasing epileptic activity brain can be traced between the leads C3 and P3, C4, and P4.

Significant intergroup differences in the cross-correlation coefficients found between the leads F3 and O1, F4 and O2. Moreover, in the group of healthy subjects there are negative correlations in the alpha range between these areas (respectively

-44,285,94 and -34,856,59), declining in the group of patients with LTO (-22,252,93 and -13,533,27) and acquires positive values in the group with CTU (21,044,13 and 16,146,02).

According to the results of the cross-correlation analysis we can talk about the complexity and ambiguity of the physiological processes at the LTO. So, revealed a small decrease in interhemispheric EEG synchronization between frontal and occipital departments, may be a consequence of the prevalence of disorders of the brain in one of its hemispheres of education ease, more clearly traceable between the Central and parietal regions, probably due to the increase in constrained neural activity nearby areas, preceding the emergence of hypersynchronous paroxysmal discharges.

Especially significantly transformed the nature of the relationship between the anterior and posterior divisions of the cerebral cortex. Reciprocal of fronto-occipital connections, which are characteristic of healthy people and are a sign of a reverse phase relationship of the alpha rhythm [12, 13], change significantly during the growing epileptogenesis, weakening already at an early stage of the epileptic process (LTO) and disappearing in the emergence of clinically recorded seizures (CPS). Violation of the changing phases of the alpha rhythm in fronto-occipital direction in epilepsy is associated with the formation of paroxysmal activity and can be explained by the change in the activity of deep brain structures.

Thus, based on data from the cross-correlation analysis is most pronounced hidden leaky epileptogenic reflected in violation of spatial synchronization of alpha activity between frontal and occipital regions of the cortex of the right and left hemisphere, which allows Ient crosscorrelation between F3 and O1 (HCC).

From table. 2 shows that the values of HCC from -1,00 to -0,35 corresponds to physiological flow of bioelectrical processes of the brain (ZV), from 0.34 to 0,00 reflect the violation of their course in the period of LTO and from 0.01 to 1.00 - CTU (it should be noted that in individual cases the values of HCC may not fit within these parameters).

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 (febrile seizures, paroxysmal activity on EEG, unprovoked epileptic seizure) complicated hereditary load epilepsy and morphological changes in the brain and are accompanied by positive values of HCC, 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 with anti-epileptic drugs, which should be carried out to the maximum normalization and stabilization of the values of the above indicators.

In General, crosscore bioelectric paroxysmal activity associated with increasing epileptische brain. This method EEG is of great practical importance, allows you to assess the dynamics of brain processes at different stages of epileptogenesis. Diagnostic accuracy of the method is not lower than 72%. The possibility of a diagnosis of epilepsy at the preclinical stage of the disease can significantly influence the course of disease process and in some cases to achieve blocking its further development.

In conclusion, it is necessary to emphasize that the proposed method of identifying hidden epileptogenesis, giving an opportunity to assess the degree of compansionate or mobility, allows to improve the diagnosis of epilepsy at least 26.5% of patients, and the imposition of preventive therapy anti-epileptic drugs ensures the prevention of the development of the clinical stage 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 begin early preventive treatment, which is the OS the diagnostics and forecasting of 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.

Sources of information

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4. Bekhterev N. P. , Kambarov, D. K., Pozdeev C. K. Sustainable pathological condition in diseases of the brain. - L.: Medicine, 1978. - 240 S.

5. Kryzhanovsky, N. Determinate patterns in pathology of the nervous system: generating mechanisms neuropathologically syndromes. - M., 1980. - 360 C.

6. Miridonov Century So Prenosological period of epilepsy in children. Dis.... Dr. of Sciences. Ivanovo, 1997, 232 S.

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

8. Binaurally, R., Wayne A. M., Gafurov, B., A. R. Rahimdjanov. Epilepsy and the functional state of the brain. - So: Medicine, 1985. - 239 S.

9. Zenkov L. R. Clinical electroencephalography with elements of epilepsy. Taganrog, 1996. - 357 S.

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11. RU Patent 2156607, class. And 61 In 5/0476, 1999. the prototype.

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13. Barlow J., Estrin Th. Comparative phase characteristics of induced and intrinsic alpha activity // Electroenceph. Clin. Neurophysiol. 1971, v. 30. P. 1-9.

A method for diagnosing and forecasting the development of epilepsy in patients with preclinical stage of the disease, including the registration of the electroencephalogram (EEG) in the patient's condition passive wakefulness and subsequent processing of the EEG, characterized in that the method of cross-correlation analysis of process fragments EEG lasting no more than one minute, which do not contain paroxysmal activity, get the coefficients crosscorrelation (HCC) alphaactivity between the leads of the left frontal and left occipital regions and the obtained values HCC ranging from -1,00 to -0,35 indicate the health of the patient, when values of HCC from 0.34 to 0,00 diagnose preclinical stage of epilepsy, but values HCC from 0.01 to 1.00 - clinical stage of epilepsy.

 

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