Невросайт

 

J Nonlinear Phenomena in Complex Systems, 2011. – Vol. 14, № 3. – P. 269-277.

 

Anticonvulsive effects of experimental transcranial magnetic stimulation

 

Volha Kistsen¹, Victor Evstigneev¹, Boris Dubovik², Elena Kravchenko³, Vladimir Ulashchik⁴

 

 

kistsen@tut.by

¹Belarusian medical academy of postgraduate education, P. Brovki str. 3/3, Minsk, Belarus

²Belarusian Medical University, str., Dzerjinskogo, 83, Minsk, Belarus

³Institute of Pharmacology and Biochemistry of National Academy of Sciences, Kuprevicha str., 2, Minsk, Belarus

⁴Institute of Physiology of National Academy of Sciences, Akademicheskaia str., 28, Minsk, Belarus

 

Abstract

In the article experimental findings about repetitive transcranial magnetic stimulation (rTMS) anticonvulsive effects are presented. We used the maximal electroshock seizure (MES) test in rats and pentylenetetrazole model in mice which underwent of repetitive TMS various parameters of frequency, intensity and procedures number. Our results indicate of rTMS inhibitory effects in different experimental models of convulsions. Various frequencies of pulsed magnetic fields can differentially change the latency, structure and duration of experimental convulsions periods. Continuation of rTMS anticonvulsive effects investigation provide with ample opportunity to use defined magnetic stimulation patterns in clinical epileptology.

Key words: experimental seizures, magnetic stimulation

 

Introduction

According to modern presentations, epilepsy is a relatively curable disease, as even rational and accurate therapy leads to reduction of convulsive attacks only in 60-70% of patients [8]. Taking into consideration the peculiarities of the effect of anticonvulsants, it’s clear that all of them have numerous side effects and take part in pathological modulation of the entire brain activity. What is more, it has become evident recently that modern state of the principles of epileptic therapy is not enough relatively to the mechanisms of epileptic genesis and is partial symptomatic treatment. That is why; a search for new methods of control of epileptic genesis is being carried out. These methods are mainly brain micropolarization and repetitive transcranial magnetic stimulation (rTMS).

TMS is a noninvasive method, allowing stimulating formations of a nervous system by the electric current induced with a pulsed magnetic field (PMF). TMS has been known for a quarter of a century and it positions itself as an original clinical method of focal cortical stimulation. Diagnostic aspects of magnetic stimulation are well-known, are widely used and are being developed [7]. Therapeutic effects of rTMS have been registered in the treatment of neurologic, psychiatric and other diseases. RTMS is safe, keeping to the recommendations of its usage; that is why it has a high clinical potential [4]. Some mechanisms of magnetic stimulation, its safety have been studied and are still being studied in experimental models. Antidepressant and anticonvulsive effects are of great attention [1-3].

A low-frequency rTMS can reduce cortical excitability and it has an anticonvulsive effect. Experimental data about anticonvulsive effects of rTMS is limited to a few published works, devoted to the study of anticonvulsive effects of pulsed magnetic fields (PMFs) in genetic, chemical seizure and in the models of electric kindling. The investigations, dedicated to the anticonvulsive effects of rTMS are presented in several published works. So, Akamatsu N. with the co-authorship showed that rTMS with 0.5 Hz frequency, which had been carried out half an hour before pentylenetetrazole was injected, increased reliably the time of cramping in comparison with the control and prevented the development of the epileptic status in 60% of the experimental rats, which took place in 100% of the control animals [6]. Rotenberg with the co-authorship compared the anticonvulsive effects of rTMS with 0.25, 0.5, 0.75 Hz frequency in the model of the kainate convulsions in rats. It was shown that the magnetic stimulation with 0.5 and 0.75 Hz frequency slowed down considerably the development of the convulsions in comparison with the control and blocked the epileptic activity on EEG [10]. Nowadays there aren’t any published works, concerning the value of anticonvulsive effects of PMF in an electroconvulsive model.

The aim our research was to reveal the mechanism of anticonvulsive effects of pulsed magnetic fields with different frequency and intensity parameters in an electroconvulsive (test of maximal electroshock seizure – MES) model and a pentylenetetrazole model of convulsions. The given convulsive models are screening models, recommended by ADDP (Antiepileptic Drug Development Program) and the researchers of our country for valuing of anticonvulsants [5].

The epileptic attack course with MES has several stages: the maximal tonic extension of animals` forefeet and hind limbs and also tonic tension of body muscles appear after transcranial electric stimulation, then the stage of clonic twitching in the muscles of limbs and body comes, after that an animal turns over and starts moving.

The main component for valuing of anticonvulsive effectiveness in the test of MES is the absence of the maximal tonic extension of hind limbs (MTEHL) in 50% of animals.

It was considered earlier that the usage of MES was limited to the testing of drugs, influencing on Na⁺ canals; however modern anticonvulsants with different mechanisms of effect have also shown the effectiveness in the test of MES. The investigations, devoted to the functional “anatomy” of convulsions in a MES model, show that different brain zones are active during the attack and, moreover, the involvement of substantia nigra is of great importance [9].

According to the manual on the experimental pre-clinical study of new pharmaceutical substances, a pentylenetetrazole test is used for determining of the ability of the anticonvulsant, being studied, to increase the threshold of the readiness for convulsions. The main component for valuing of anticonvulsive effects is the absence of clonic convulsions with the duration more than 3 s without the loss of a turning-over reflex in 50% of animals (effective dose in 50% of animals – ED₅₀). Pentylenetetrazole is a selective blocker of chloric canals, combined with GABA-receptor. Being injected in a certain dose, pentylenetetrazole can arouse a complex of convulsive manifestations, growing from myoclonuses to generalized tonic-clonic seizures. The research, devoted to the functional “anatomy” of pentylenetetrazole convulsions showed that the mediators of an extensive zone, including a diencephalic area, surrounding anteromedial parts of thalamus, back parts of hypothalamus, reticular formation and stem structures, connected with descending motoric tracts are active during the attack.

 

Materials and methods of investigation

MES was used on pedigreeless sexually mature white rats – males with the body mass of 200-300 g. The pentylenetetrazole test was carried out on pedigreeless sexually mature white mice – males with the body mass of 19-24 g.

The rules of carrying out work with the usage of experimental animals were kept to while conducting the experiment. The experimental carrying out was approved of the committee on the ethics of Belarusian medical academy of postgraduate education.

Experimental animals (n=150) were divided into subgroups (n=10) depending on frequency (0.1, 0.3, 0.5, 1.0 and 10.0 Hz) and intensity (10%, 20% and 40% from maximal magnetic induction (MMI) of a circular coil) of a pulsed magnetic field. Ten rTMS procedures were carried out in each subgroup.

RTMS was conducted during 5 minutes by a pulsed magnetic field by biphasic impulses with the duration of 250 msec. The apparatus “Neuro-MS” (Russia) was used for rTMS. The installation, developed by us, was used for optimization of procedure performance. It allowed to fix a laboratory animal and to place the inductor so, that the influence of PMF was the same for each of them. Moreover, the given installation allowed performing numerous influences, which were carried out every day at the same time and maximally fast (10 minutes for each subgroup daily). A special hypomagnetic pad, suggested by us, was placed under the inductor to exclude the influence of PMF on animals` bodies.

The control group was composed of 42 rats and 93 mice in the test of maximal electroshock in the pentylenetetrazole test, respectively.

Electroshock was applied on animals and pentylenetetrazole was injected subcutaneously (“Sigma”, USA) after a 5 minutes` influence of PMF.

The electric stimulus was given transcranially for MES, and then the values of parameters of the development of a generalized tonic-clonic attack (latency, duration and structure of its stages, presence and absence of specific phenomena and phases, general seizure duration) were registered.

A latent period, a number and duration of convulsions, their maximal severity and end time of the convulsions were registered visually in each animal, placed in a separate container in the pentylenetetrazole test during 30 minutes. The value of convulsive severity was estimated in points:

1 point – myoclonic jerk;

2 – rare clonic convulsions of the whole body;

3 – a number of clonic convulsions of the whole body or clonic convulsions of upper limbs;

4 – tonic-clonic convulsions with raising on hind limbs;

5 – tonic-clonic convulsions with falling of the animal on its side;

6 – repeat of the convulsions with the severity of 5 points and/or death.

The statistical analysis was executed on the algorithms of the program Statistica 6.0. A one-way ANOVA was used with post-hoc analysis by Tukey`s criterion.

 

Results and their discussion

Test of maximal electroshock. The transcranial influence of PMF led to the absence of MTHLE (maximal tonic hind limbs extension) in 50% of animals in several regimens after 10 sessions:10 Hz and 20% intensity from MMI, 0.5 Hz and 10% intensity from MMI (p=0.014). Moreover, MTHLE was not developed in 60% of rats in certain regimens: 10 Hz and 40% intensity from MMI and 0.1 Hz and 40% intensity from MMI (p<0.01). The presence of the given effect takes place in multiple frequency characteristics (10 and 0.1 Hz) and equal intensity of PMF (40% from MMI).

We also noticed the phenomenon called “the delay of the development of maximal tonic extension” in the experimental group in each frequency regimen. Here MTHLE was developed not immediately after the supply of the electric stimulus, as it was observed in the control group, but 5-7 s later (Table 1). The greatest delay of MTHLE development was in the subgroup of rTMS with 10 Hz frequency and 10% intensity from MMI and 0.1 Hz and 20% intensity from MMI, it took place in the same frequency regimens, in which the absence of MTHLE was also observed, but the influence with a more intensive PMF (40% from MMI) was necessary for that. That’s why, we consider, that the absence of MTHLE is a dosedependent effect on the value of a magnetic field. The animals of all subgroups had the attack; however, there were phenomena of the absence of a tonic phase and a generalized clonic phase with the loss of a turning – over reflex in the experimental rTMS group (Table 1).

Table 1 – Structure of attacks after ten sessions` transcranial magnetic stimulation in the test of maximal electroshock

Characteristics of PMF		Absence of MTEHL,%	Absence of a tonic convulsive phase, %	Absence of a generalized clonic convulsive phase, %	Delay of MTHLE, %	Phenomenon of «pedalling», %
Frequency, Hz	Intensity,% from MMI
10.0	40, (n=10)	6 (60%)*	3 (30%)	3 (30%)	2 (20%)	4 (40%)*
	20, (n=10)	5 (50%)*	1 (10%)	1 (10%)	4 (40%)	5 (50%)*
	10, (n=10)	2 (20%)	1 (10%)	1 (10%)	7 (70%)*	3 (30%)*
1.0	40, (n=10)	3 (30%)	2 (20%)	1 (10%)	0 (0%)	7 (70%)
	20, (n=10)	4 (40%)	1 (10%)	1 (10%)	0 (0%)	0 (0%)*
	10, (n=10)	2 (20%)	0 (0%)	0 (0%)	5 (50%)*	3(30%)*
0.5	40, (n=10)	1 (10%)	1 (10%)	1 (10%)	6 (60%)*	3 (30%)*
	20, (n=10)	4 (40%)	2 (20%)	2 (20%)	4 (40%)	4 (40%)*
	10, (n=10)	5 (50%)*	3 (30%)	3 (30%)	3 (30%)	3 (30%)*
0.3	40, (n=10)	3 (30%)	1 (10%)	2 (20%)	2 (20%)	4 (40%)*
	20, (n=10)	2 (20%)	2 (20%)	2 (20%)	6 (60%)*	2 (20%)*
	10, (n=10)	3 (30%)	1 (10%)	0 (0%)	6 (60%)*	3 (30%)*
0.1	40, (n=10)	6 (60%)*	2 (20%)	0 (0%)	2 (20%)	5 (50%)*
	20, (n=10)	2 (20%)	0 (0%)	0 (0%)	7 (70%)*	7 (70%)
	10, (n=10)	5 (50%)*	5 (50%)*	5 (50%)*	4 (40%)	5 (50%)*
Control (n=42)		0 (0%)	0 (0%)	0 (0%)	0 (0%)	42 (100%)

* p<0.05

The presence of such phenomenon was significantly different from the control only in the group with 0.1 Hz frequency and 10% intensity from MMI (p<0.05).

The phase duration of tonic convulsions in the control group was 14.12±0.31 according to (Mean±Standard Error of Mean). Significant shortening of this phase of the attack was observed in the subgroup with rTMS, having 0.1 Hz frequency and 10% intensity from MMI and 1.0 Hz frequency and 10% intensity from MMI (multiple regimens with equal intensity of PMF). It’s necessary to emphasize, that the combination of 0.1 Hz frequency and 10% intensity from MMI has already been mentioned above as the regimen, in which almost half of the animals had the attack without the loss of a turning-over reflex.

The duration of a clonic convulsive phase with the loss of a turning-over reflex in the control group was 98.27±2.95 s. All experimental regimens, being studied by us, aroused the shortening of the given stage of a convulsive attack with the absence of intergroup differences. That indicated the presence of universal brain mechanisms, blocking clonuses and being activated by PMF of different frequency and intensity. Moreover, the influence even of a low-intensive PMF (10% from MMI) arouses the shortening of the phase of generalized clonuses with the loss of a turning-over reflex (Table 2).

Table 2 – The duration of convulsive phases in the test of maximal electroshock after ten sessions` transcranial magnetic stimulation

Characteristics of PMF		Duration of a tonic convulsive phase, s	Duration of the phase of generalized clonic convulsions with the loss of a turning-over reflex, s	Duration of a clonic convulsive phase without the loss of a turning-over reflex, s	General duration of the seizure, s
frequency, Hz	intensity,% from MMI
10.0 n=30	10	13.44±0.96	57.61±4.7*	25.99±6.44	109.92±10.88
	20	11.15±0.57	61.33±3.49*	16.06±5.16*	108.66±10.92
	40	11.58±0.9	69.13±5.36**	28.9±4.07	85.39±16.17*
1.0 n=30	10	12.36±0.62*	50.46±3.62*	30.96±3.35	93.75±5.94*
	20	13.38±0.68	52.8±3.49*	16.2±3.93**	58.84±12.6*
	40	12.43±0.66	45.8±5.78*	23.02±5.81	85.21±7.85*
0.5 n=30	10	9.53±2.72	39.65±8.4*	21.5±5.15	71.12±8.57*
	20	11.12±1.96	40.4±7.3*	23.1±4.19	74.6±7.86*
	40	11.37±1.33	42.22±5.58*	20.14±2.56***	73.73±5.76*
0.3 n=30	10	11.78±1.39	42.78±5.12*	36.39±5.96	90.96±10.14*
	20	9.53±1.7	40.4±7.1*	22.8±2.8	72.6±9.9*
	40	10.18±1.8	38.2±6.8*	29.7±6.3	79.02±12.3*
0.1 n=30	10	8.3±2.32*	33.62±9.75*	26.73±3.28	68.65±11.92*
	20	13.2±0.63	51.2±3.65*	26.49±3.2	90.9±5.25*
	40	10.7±1.37	40.54±6.63*	27.37±5.58	80.82±12.51*
Control, n=42		14.12±0.31	98.27±2.95	35.59±3.8	134.79±6.8

*** p<0.05; **p<0.02; * p<0.0001; * p<0.001

 

The phase of tonic and generalized clonic convulsions was absent in some experimental subgroups, but the group with rTMS, having 0.1 Hz frequency and 10% intensity from MMI, in which 5 (50%) animals had the phenomenon «running on the spot» and «dying out», was the most significant.

All the control animals had the phenomenon of «pedalling» with hind limbs (clonic convulsions) during the phase of generalized clonuses. All the regimens of the experimental group led to significant diminution of the representation of the given phenomenon, except two of them (0.1 Hz frequency and 20% intensity from MMI and 1.0 Hz frequency and 40% intensity from MMI). The regimen with the absence of the given phenomenon, in which the PMF parameters were 1.0 Hz frequency and 20% intensity from MMI, was the most significant.

The duration of the phase of the convulsive attack was 35.59±3.8 s after the renewal of a turning-over reflex in the control group. Only 3 regimens shortened this stage to a great extent after 10 procedures: with 0.5 Hz frequency and 40% intensity from MMI, 10 and 1.0 Hz frequency and 20% intensity from MMI (p<0.05). RTMS with 10 Hz frequency and 20% intensity differed from the other groups during the intergroup comparison (p=0.0001).

The general seizure duration was 134.79±6.8 s in the control. It’s important to mention, that all the regimens used by us, except the regimen with 10 Hz frequency and 10 and 20% intensity from MMI, led to significant shortening of the entire experimental paroxysm.

Pentylenetetrazole test. The results of PMF influence on the course of the experimental attack (phases with the severity of 1, 3 and 5 points) in a pentylenetetrazole model of convulsions are represented in this chapter.

The control animals had the first convulsive attack 62.63±1.22 s. later. The time of coming of the convulsive manifestations increased considerably in all the subgroups of the experimental group except the cases with 0.1 Hz frequency and 40% intensity from MMI. The received results are represented in table 3 in the form of M±S.E.M. (Mean±Standard Error of Mean).

 

 

 

Table 3 – Characteristics of convulsive attacks in a pentylenetetrazole model after 10 sessions` rTMS

Characteristics of PMF		Latent period of the first myoclonuses ( 1 point ), s	Latent period of the first clonuses ( 3 points ), s	Latent period of the convulsions in 5 point , s	Maximal degree of severity of the convulsive attack	End time of the convulsive manifestations , s	General number of convulsive attacks	Total duration of the convulsive attack
frequency, Hz	% from MMI
10.0 n=30	10	106.2±7.22*	265.2±18.79	346.0±22.7	3.5±0.45*	790.5±28.76*	15.5±1.21*	22.8±2.5*
	20	142.3±13.88*	538.13±58.46*1	654.75±143.98*1	3.8±0.36*	828.1±49.48*	16.5±1.69	24.0±2.74*
	40	94.5±8.3*	356.5±61.14*	533.6±139.7*	3.8±0.44*	785.8±35.46*	14.3±1.6*	20.6±2.17*
1.0 n=30	10	97.5±5.87*	351.5±67.62*	524.0±86.28*	4.2±0.29	988.9±44.32	23.2±1.3*	35.3±2.23*
	20	116.0±14.17*	443.0±2.97*	454.0±12.7	3.3±0.47*	816.5±38.49*	18.8±3.3	25.58±4.33
	40	90.8±6.78*	254.14±62.4	279.4±56.03	4.9±0.1	612.9±28.9*	11.6±2.1	27.3±1.9*
0.5 n=30	10	96.8±7.2*	320.7±22.1*	429.17±50.22*	4.4±0.27	966.6±19.1*	17.5±0.97*	32.5±2.66*
	20	94.7±3.6*	250.16±15.85*	362.88±35.48	4.8±0.2	726.0±33.17*	13.6±2.0	29.4±2.7
	40	190.2±11.55*1	340.5±31.26*	400.5±35.5	4.1±0.4	631.0±24.9*	11.8±1.1*	18.9±1.97*
0.3 n=30	10	78.0±4.01*	265.2±11.73	267.44±37.68	4.8±0.2	646.3±33.1*	11.5±1.4*	28.1±1.92*
	20	125.1±9.79*	470.7±47.5*	481.0±52.2*	3.7±0.3*	739.7±40.8*	17.2±1.65	25.3±2.94*
	40	113.5±5.74*	357.0±53.9*	310.0±10.0	2.9±0.35*	596.0±22.7*	10.8±1.16*	13,4±2.23*
0.1 n=30	10	101.9±9.94*	330.75±23.05*	374.5±41.15	4.8±0.13	804.8±17.54*	17.0±1.6*	32.8±2.12*
	20	118.6±11.38*	309.67±17.76*	328.67±100.8	3.5±0.4*	774.2±37.25*	14.9±1.73	22.4±3.4*
	40	70.5±1.24	240.88±15.76*	363.3±65.0	4.7±0.15	996.1±21.26	15.8±1.33*	32.7±1.99*
Control, n=93		62.63±1.22	179.03±8.32	269.23±13.85	4.7±0.1	1114.8±18.04	25.04±1.03	47.11±1.8

*р<0.01 – comparison with the control; ¹р<0.02 – intergroup analysis

 

While estimating such value as a latent period of the first convulsions (myoclonuses), it turned out that only one regimen of rTMS (0.5 Hz frequency and 40% intensity from MMI) differed from all the others (p<0.028). The mean value of the latent period of the myoclonuses for the given regimen was 190.2±11.55 s it exceeded the control value in 2.7 times.

One more effective regimen were the parameters of 10 Hz frequency and 20 % intensity from MMI (the mean value of the latent period of the myoclonuses was 142.3±13.88 s, p<0.02).

The convulsions with the severity of 3 points appeared 179.03±8.32 s later in the control group. The majority of the PMF parameters, used by us, led to the delayed onset of the clonuses without the loss of a turning – over reflex after 10 procedures, except the following regimens: 10 Hz frequency and 10% intensity from MMI, 1 Hz and 40% intensity from MMI and 0.3 Hz and 10% intensity from MMI. The most effective regimen was one with 10 Hz frequency and 20% intensity from MMI among all PMF parameters, used by us. It put off maximally the approach of the clonic convulsions, the mean value of the parameter, being investigated, was 538.13±58.46 s. (p<0.02).

The first clonuses with the loss of a turning-over reflex (convulsions with 5 points` severity) appeared 269.23±13.85 s later in the control group. The analysis of the latent period of this phase showed the reduction of the effective regimens, used by us.

Thereby, the PMF regimen with 10 Hz frequency and 20% intensity from MMI turned out to be the most effective, allowing to prolong the latent period of the convulsions with 5 points` severity maximally.

While estimating the influence of the conducted rTMS procedures on maximal attack severity, which was estimated in points, all the regimens with 10 Hz frequency decreased the attack severity significantly. Besides, a significant decrease of the attack severity was observed in the PMF regimens with 1 Hz frequency and 20% intensity from MMI and 0.3 Hz and 20% intensity from MMI in comparison with the control (p<0.01) without significant intergroup differences.

The end time of the convulsive manifestations was 1114.8±18.04 s in the control group. The time reduction of the convulsive manifestations was registered statistically significantly. That phenomenon was observed in all subgroups (p<0.01), except the cases with 1 Hz frequency and 10% intensity from MMI, 0.5 Hz and 10% intensity from MMI and 0.1 Hz frequency and 40% intensity from MMI with the absence of considerable differences among the subgroups.

The general number of convulsive attacks reduced practically in all subgroups of animals, which received rTMS, in comparison with the control (p<0.01) without considerable differences among the experimental subgroups. It’s necessary to mention that rTMS with 20% intensity from MMI in all frequency regimens and 1 Hz frequency and 40% intensity from MMI led to a great change in comparison with the control.

The total duration of the convulsive attacks shortened significantly under the influence of all rTMS parameters, except 1 Hz and 20% intensity from MMI and 0.5 Hz frequency and 20% intensity from MMI. The regimen with 0.3 Hz and 40% from MMI was the most effective, it reduced the duration of the convulsive period actively (p<0.013).

It’s shown visually in table 3, that the combination of such PMF parameters as 10 Hz frequency and 40% intensity from MMI leads to a significant improvement of all above examined characteristics of the course of pentylenetetrazole convulsions.

The received data showed that PMF influenced on all phases of the convulsive attack. It’s necessary to emphasize that the latency of clonuses with the loss of a turning-over reflex and a maximal degree of severity of the attack were the most important among all the indices, which reacted to certain modality of PMF.

The maximal stimulation with 10 Hz frequency and 20% intensity from MMI was the most effective as regards the time of the convulsive manifestations with the severity of 1, 3 and 5 points. It’s important that the increase of magnetic induction to 40% from MMI improves significantly all main indices of the phases of a paroxysmal state in comparison with the control.

High anticonvulsive effectiveness of the regimen with 10Hz frequency, in our opinion, is connected with a great number of stimuli, received during this procedure. The similar effect, directed at the interruption of a convulsive attack, can be achieved with electric brain stimulation, bringing on long-term synaptic changes.

Only two regimens, investigated by us, protect 50% of experimental animals from the development of clonuses, lasting more than 3 s, they meet the requirements, made to the potential anticonvulsants: 1.0 Hz frequency and 20% intensity from MMI and 0.3 Hz and 40% intensity from MMI.

The safety confirmation of rTMS was the absence of convulsions during its carrying out.

We consider that anticonvulsive effects of rTMS influence are connected with its ability to interrupt pathologic cortical excitability like long-term synaptic depression (LTD).

RTMS effectiveness with different frequency with respect to the experimental convulsions confirms the supposition about the presence of specific paradigms in brain work and, apparently, pertains to the mechanisms of epileptic genesis.

The values of PMF intensity have been chosen on the ground of the mathematical calculations on brain models, performed by us. The calculations allowed us to determine supraliminal and subliminal values. The results, received by us, showed, that anticonvulsive effects appeared with all above mentioned values of the intensity of the magnetic field, however the frequency of the magnetic field is predominating in this process, what supposes the caring out of further investigations.

Conclusion

Thus, rTMS provides the activation of inhibitory antiepileptic brain systems, moreover, certain frequency PMF characteristics, allowing starting up this physiologic protective mechanism, are important factors. Particularly, this range in MES test are 0.1, 1.0 and 10 Hz frequency with different intensity from MMI; and 0.5 Hz frequency and 40% intensity from MMI, bringing on the inhibition of different phases of the development of a paroxysmal state. The received data allows to use these parameters in valuing of anticonvulsive effectiveness of PMF in clinical practice and to substantiate the protocol of multimodality therapy of epilepsy with the usage of TMS methodology.

The achieved rTMS result lies in selective activation of modifying inhibitory influence on a convulsive threshold of the experimental attack, its character and course (decrease of a number, duration and a maximal attack point and also the time shortening of the convulsive manifestations). The received results will allow using purposefully certain PMF parameters in prevention and treatment of epileptic attacks.

 

References

1. О.В. Кистень, В.В. Евстигнеев, В.С. Улащик, Б.В. Дубовик Новости медико-биологических наук, № 4, С. 99 – 108, 2009.

2. О.В. Кистень ArsMedica, 32, № 12, С. 8-12, 2010.

3. О.В. Кистень Известия национальной академии наук Беларуси, № 2, С. 64-68, 2011.

4. С.С. Никитин, А.Л. Куренков Магнитная стимуляция в диагностике и лечении болезней нервной системы М.: САШКО, 374 с., 2003.

5. Р.У. Хабриев Руководство по экспериментальному доклиническому изучению новых фармакологических веществ. М., С. 277-280, 2005.

6. N. Akamatsu, Y. Fueta, Y. Endo et al. Neurosci. Lett., Vol. 310, № 3, P. 153-156, 2001.

7. V. Di Lazzaro, U. Ziemann, R.N. Ziemann Brain Stimulation. Vol. 1, № 4, Р. 345–362, 2008.
8. К. Malmgren [et al.] Epilepsia. Vol. 44, № 5, P. 727–731, 2003.

9. J.W. Miller, A.C. McKeon, J.A. Ferrendelli Ann Neurol., Vol. 22, № 5, P. 615-621, 1987.

10. A. Rotenberg, P. Muller, D. Birnbaum et al. Clin Neurophysiol., Vol. 119, № 12, P. 2697-2702, 2008.