Muratova T. Pathogenetic mechanisms for the implementation of transcranial magnetic stimulation in optimizing the treatment of various forms of pharmaco-resistant epilepsy (clinical and experimental study)

The dissertation is devoted to the identification of pathogenetic mechanisms for the implementation of transcranial magnetic stimulation effects in overcoming the pharmacokresistance to antiepileptic drugs in order to increase the effectiveness of treatment of patients with various forms of pharmaco-resistant epilepsy. The study examined 150 patients with pharmacokinetic epilepsy with generalized and focal attacks receiving levetiracetam in the treatment of AED. Significant violations of the autonomic nervous system, quality of life, cognitive functions by the method of measuring the cognitive potential P300, oxidative stress activation, significant disturbances in the exchange of activating and inhibitory mediators, and an increase in the number of pro- and anti-inflammatory cytokines in patients with drug-resistant forms of epilepsy were revealed. Within the experiment on different models of epileptic activity, it was proved that the complex application of electro- and magnetic stimulation of the cerebral cortex with levetiracetam and nicotinamide significantly (P <0.01) enhances the anticonvulsant effect of each of the methods with a separate application of 67.2%. TMS courses allowed at least 68% of follow-up attacks after the first course, after an additional (6 months after the first) in 80% of patients within the first three months. The main mechanisms for implementing the antiepileptic action of TMS in the cerebellum were found to stabilize the functioning of the autonomic nervous system in the form of a reliable (P <0.01) decrease in the manifestations of autonomic dysfunction and a reliable (P <0.01) normalization of reactivity up to six months after the base TMS course and up to one year after an additional TMS course. Also, the normalization of the ratio of excitatory and inhibitory amino acid mediators after the TMS course, reduction of inflammation in the form of reducing the content of inflammatory and increasing the content of anti-inflammatory cytokines after TMS courses was revealed. According to the results of the study, algorithms for treatment of patients with pharmacokinetic epilepsy with focal and generalized attacks were substantiated, developed and implemented, which will significantly improve the effectiveness of treatment of these patients.