[Conservative and surgical treatment of patients with resistant epilepsy].

AIM: To optimize drug treatment in early (6 months) and late (up to 3 years) stages of postoperative period and to study its efficacy. MATERIAL AND METHODS: There were selected 72 patients with resistant epilepsy and epileptic encephalopathy symptoms from 467 patients operated for epilepsy. RESULTS: By the end of a 3-year follow-up observation, we found the reduction in seizure frequency and seizure control in 66.3% of patients; regression of EEG paroxysmal activity in 56.8% and reduction in mental disorder symptoms (anxiety and depression) in 12.7%. CONCLUSION: The data obtained substantiate the necessity to optimize antiepileptic and pathogenetic drug treatment of patients with resistant epilepsy and encephalopathy symptoms during the 3-year postoperative period.

Growth-stimulating phase of macrophage response to activation: the phenomenon and its implications for tumour growth and immunotherapy.

The dynamics of growth-stimulating and cytotoxic activity of mouse peritoneal macrophages (PMo) in response to in vivo and in vitro bacillus Calmette-Guérin (BCG) or bestatin treatment was studied. It was shown that BCG and bestatin induce cytotoxicity in PMo, and that after the cytotoxic response strong growth-stimulating activity develops. PMo, rendered cytotoxic in vivo and afterwards cultivated in vitro, displayed the same switch from a cytotoxic to a growth-stimulating phase. These results suggest that the growth-stimulating phase is the obligatory PMo response to biological response modifiers (BRM) at least to BCG and bestatin. The growth rate of tumours, transplanted into mice during the cytotoxic phase of the response to BCG, was suppressed, whereas tumours transplanted during the growth-stimulating phase were stimulated. It appears that the development of a growth-stimulating phase after the cytotoxic phase of response to activation by BRM could be one of the reasons for the limited effectiveness of immunotherapy based on the application of macrophage activators.

The presence of autoantibodies to N-terminus domain of GluR1 subunit of AMPA receptor in the blood serum of patients with epilepsy.

We have analyzed the serum from patients with refractory epilepsy for the presence of autoreactive antibodies to AMPA glutamate receptor subunits. The presence and the level of autoantibodies were assessed using immunoblot and ELISA with synthetic peptides specific for subregions of AMPA glutamate receptor subunits. Patients with refractory epilepsy exhibited strong immunoreactivity to GluR1 subunit compared to healthy donors and patients with Parkinson's disease and Alzheimer's disease. Weak immunoreactivity to other AMPA glutamate receptor subunits was also detected and the signal was diminished in the raw GluR4>GluR3>GluR2. The occurrence of autoantibodies to specific neurotransmitter subunits in the sera of patients with refractory epilepsy suggest that autoimmune process may underlie this disorder.

[Effect of BCG and cyclophosphamide on the antitumor activity of mouse peritoneal macrophages]. / Vliianie BTsZh i tsiklofosfamida na protivoopukholevuiu aktivnost' peritoneal'nykh makrofagov myshei.

Peritoneal macrophages activated by BCG and cyclophosphamide were unable to complete elimination of small numbers of tumour cells in spite of high level of cytotoxicity and cytostatic activity of these cells. It is appeared useful to evaluate the influence of new immunomodulators and combinations of immunomodulators with chemotherapeutic drugs not only on the cytotoxic and cytostatic, but also on the "feeder" activity of macrophages.

[Differentiated treatment of epilepsy taking into account the nature of the attacks]. / Differentsirovannoe lechenie épilepsii s uchetom kharaktera pristupov.

According to the data available in Soviet and foreign literature and the author's personal experience, the issues of combined pharmacological treatment of different types of epileptic seizures are discussed. General knowledge of the pharmacokinetics of antiepileptic drugs in the patient's body is taken into account as well as EEG data. Possible interchangeability of the drugs is reviewed.

[Rehabilitation of epileptic patients in an outpatient setting]. / O reabilitatsii bol'nykh épilepsiei v ambulatornykh usloviiakh.

The work is devoted to the rehabilitation of epileptic patients under outpatient conditions. On the basis of the data of epidemiologic studies the author considers the specific nature of rehabilitation measures provided to patients on an outpatient basis, describes the drawbacks of drug therapy, and proposes new forms of the organization of specialized cost-effective medical care to patients (a regional epilepsy centre).

[Various aspects of the biological basis for rehabilitating epileptics]. / Nekotorye aspekty biologicheskogo obosnovaniia reabilitatsii bol'nykh épilepsiei.

Using the clinical data on 270 epileptic patients, the author offers the biological validation of occupational treatment, determines the role of the psychological effects in the system of patients' rehabilitation and validates the significance of the EEG as a method for objective assessment of the degree of the regression of the clinical and subclinical manifestations of epilepsy in the process of biological therapy. It has been established that: 1) psychosocial effects, in particular, the patients' occupational activity help to decrease the frequency of attacks and inhibit the paroxysmal activity on the EEG during an experiment simulating a working process; 2) a long-term (up to 8 years) absence of seizures according to the EEG readings is not always attended with the regression of the subclinical manifestations of epilepsy; 3) the realization of rehabilitation programmes should be evaluated, appart from the duration of the attack-free period, by the EEG readings as well.

[The importance of psychological research in the system of rehabilitating epileptics]. / Znachenie psikhologicheskogo issledovaniia v sisteme reabilitatsii bol'nykh épilepsiei.

The authors consider the results of the psychological analysis of individual characteristics of intellectual and mnemonic activity, of emotional response, behaviour and the system of relations determined with the help of 10 experimental psychological techniques in 239 epileptic patients with a variable clinical picture of the disease in the process of their rehabilitation. The data obtained by the psychologist are correlated with the assessment of mental disorders by both the patient himself and the doctor. A conclusion is made that the psychological diagnosis is more accurate and its results may be used as an important criterion in the process of rehabilitation of epileptic patients.

[Hexamidine content of the blood plasma and cerebrospinal fluid in patients with epilepsy]. / O soderzhanii geksamidina v plazme krovi i likvore u bol'nykh épilepsiei.

In 74 patients with different attack rates and patterns mean levels of hexamidine in the blood plasma and cerebrospinal fluid were 15.9 micrograms/ml and 7.86 micrograms/ml, respectively, the former almost twice as high as the latter. Both were found to correlate with the drug daily doses and other anticonvulsants administration.

[Concentration of benzonal in the blood of epileptic patients at different daily doses and with other anticonvulsants]. / Kontsentratsiia benzonala v krovi bol'nykh épilepsiei pri raznykh sutochnykh dozakh i prieme drugikh antikonvul'santov.

A study involving 36 epileptic patients and 8 control subjects was devoted to the optimization of antiepileptic drug therapy with the help of determining the blood levels of anticonvulsants (benzonal, phenobarbital). The daily dose of an anticonvulsant directly correlated with its blood levels. Blood levels of benzonal increased upon the additional administration to patients of hexamidine or hexamidine and diphenylhydantoin mixtures. A reduction in the daily dose of benzonal by 2/3 was attended by a 50% decline in its blood levels.

[Clinico-electroencephalographic correlations in the process of rehabilitation of patients with epilepsy]. / O kliniko-élektroéntsefalograficheskikh korreliatsiiakh v protsesse reabilitatsii bo'lnykh épilepsiei.

A total of 50 patients with epilepsy underwent an electroencephalographic investigation at the rehabilitation stage during remission. EEG tests established that the discontinuation of epileptic seizures was followed by a stepwise compensatory EEG rearrangement. In patients that had had rare seizures, the EEG normalization was characteristic of the 2 to 3 years-long remissions. With frequent polymorphic seizures, the background activity was normalized in the steady remission of many (5 and more) years duration. The cessation of antiepileptic therapy should be effected under a mandatory EEG control. The absence of negative EEG changes on anticonvulsants discontinuation is a sign of correct treatment paradigm.

[Improving the organization and increasing the quality of the treatment of patients with epilepsy]. / K sovershenstvovaniiu organizatsii i povysheniiu kachestva lecheniia bol'nykh épilepsiei.

The authors suggest a program of improving health services for patients suffering from epilepsy (the setting up of the Regional Epileptological Centre). The clinical material provided by 1350 patients with epilepsy is analyzed for cost and therapeutic efficacy of the conducted organizational measures. Improvement of the treatment and diagnostic work, upgrading of the patients' examination quality have been demonstrated. The economic efficiency has been computed.

[Therapeutic and pharmacological monitoring of individual monotherapy of epilepsy with hexamidine]. / Terapevticheskii i farmakologicheskii monitoring pri individualizatsii monoterapii geksamidinom bol'nykh épilepsiei.

The treatment with primidone alone of 53 epileptic patients with generalized tonic-clonic seizures, partial attacks with elementary symptomatology, and partial fits with complex symptomatology removed them completely in 75, 64.2, and 36.9% of the patients, respectively. The number of attacks was decreased as a result by 50% and over in 90, 78.6, and 73.7% of the patients, respectively. The attainment of such high efficacy of the monotherapy (called by the author intensive in contrast to routine or inadequate therapy carried out, as a rule, in standard doses) appeared possible only under the conditions of individualization of the drug doses which ranged within 250-2500 mg/day. The concentration of phenobarbital, the main end metabolite of primidone, in the blood serum of patients, in whom the attacks were completely arrested and who developed no clinical side effects with no toxic action on the internal organs, ranged from 14 to 59.1 mg/l. In partial fits with complex symptomatology, primidone appeared least effective for those types of fits in the treatment of which it was viewed as most adequate.

[Pathogenic role of the endogenous convulsant kynurenine in the mechanisms of development of epileptic attacks in alcoholics]. / Patogeneticheskaia rol éndogennogo konvul'santa kinurenina v mekhanizmakh razvitiia épilepticheskikh pripadkov u bol'nykh alkogolizmom.

The role of the endogenous convulsant kynurenine (K) in the mechanisms of the development of epileptic seizures in alcoholic persons was studied on a clinical material of 63 patients suffering from alcoholism with the presence on the EEG of paroxysmal alterations without epileptic fits (n = 28) and alcoholic epilepsy (n = 35), epileptic patients not abusing alcohol (n = 20), and practically healthy subjects (n = 10). There was a significant increase of the K concentration in alcoholic patients with paroxysmal disturbances on the EEG or convulsive seizures. That increase directly correlated with the rate of convulsive epileptic fits. The rise of K in patients with alcoholic epilepsy was lower than in epileptic patients, being, however, significantly higher than in practically healthy subjects abusing alcohol and having but paroxysmal alterations on the EEG (without seizures).

[A clinico-pharmacological basis for optimizing the treatment of therapy-resistant forms of epilepsy]. / Kliniko-farmakologicheskoe obosnovanie optimizatsii lecheniia rezistentnykh k terapii form épilepsii.

On 44 epileptic patients antiepileptic phenobarbital, finlepsin, diphenine, hexamidine were studied. The alterations in the level of free and bound fractions under the drug application in maximal tolerance daily doses, depending on changes in the administration frequency during the day, were recorded. It was established that level fluctuations of the total preparation occur mainly owing to level alterations in the fraction not bound to serum proteins. An increase in the drug administration frequency under the constant daily dose leads to a distinct reduction in the free fraction level fluctuations between doses, to a decrease in the intensity or removal of side effects, and makes it possible to further build up the daily dose to obtain the required effect.

[Effect of modifiers of natural biological response on the functional activity of macrophages (oncological aspect)]. / Vliianie modifikatorov biologicheskogo otveta prirodnogo proiskhozhdeniia na funktsional'nuiu aktivnost' makrofagov (onkologicheskii aspekt).

Induction of cytotoxicity by biological response modifiers (BRMs) is only one aspect of macrophage activation. After the use of BRMs there were other changes in the functional activity of cells and in particular their increased production or secretion of a number of growth factors. Thus, activation of macrophage antitumor activity induced by BCG vaccine was transitory while activation of growth factor production was more stable in time which finally led to increased proliferation of tumor cells. Combined use of cyclophosphamide and BCG vaccine significantly increased not only the toxicity induced by BCG vaccine but also their liberation of the growth factors. Such macrophages lost their ability to control the growth of a small number of the tumor cells cultivated in their presence. Development of ways for directed activation of macrophages aimed at elimination of the tumor cells which survived the chemotherapy should include evaluation of the combined effect of various BRMs and chemotherapeutics on both antitumor and protumor activity i. e. ability to produce the factors stimulating the tumor growth.

[Modern aspects of the rehabilitation of patients with epilepsy].

A conception of rehabilitation of epileptic patients, which corresponds to the realities of their life, has been elaborated on the basis of clinical data on 4348 epileptic patients with long-time follow-up period. An algorithm of treatment and rehabilitation programs based on medical-biopsychosocial approaches and studying of QOL was proposed and scientifically substantiated. The system of rehabilitation was tested in practice and its high efficacy was shown.