Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number


Applicant for


  • 222 - Медицина


Specialized Academic Board

ДФ 64.609.038

The Kharkiv Medical Academy of Postgraduate Education


The purpose of the work - on the basis of analysis and comprehensive evaluation of the results of clinical and neurological, psychodiagnostic, enzyme immunoassay studies, to substantiate the effectiveness of TMS in the rehabilitation of patients with multiple sclerosis. A comprehensive examination of MS patients (confirmed by McDonald's criteria, 2017) was conducted in compliance with the principles of bioethics and deontology and on the basis of informed consent. The study included 4 stages. During the first stage, 110 MS patients were selected who received disease-modifying therapy in different periods of the disease, considering the recommendations of the European MS Treatment Guidelines Released, in combination with pulse therapy with methylprednisolone in case of exacerbation. During the second stage, patients were divided into two groups. Experimental group included 30 MS patients who received conventional basic drug and symptomatic therapy. Study group included 80 MS patients, who received a course of TMS along with conventional drug therapy. At this stage the parameters and zones of influence and their safety conditions in the key MS syndromes were worked out, and the TMS-therapy personalization approach was developed. During the third stage, the comparative analysis of efficiency of the therapy was conducted in both groups on the basis of complex clinical and neurological, psychodiagnostic and laboratory examination. Clinical and neurological examination included assessment of neurological deficit (FS scale), and assessment of the MS severity (EDSS scale); psychodiagnostic study included assessment of the severity of depression using the Hamilton Depression Rating Scale (HDRS), anxiety using the Hamilton Anxiety Rating Scale (HARS), the severity of psychopathological symptoms using the Symptom Check List-90-Revised questionnaire, cognitive disorders using the Trail making test (TMT), Verbal fluency test, (VFT), the Stroop test, the Luria test for memorizing ten unrelated words, as well as the quality of life using the Quality of Life Index (Mezzich et al. adapted by N.O. Maruti), a laboratory study of serum to determine the concentration of cortisol, thyroid-stimulating hormone (TSH), total thyroxine (T4) and BDNF. The tolerability and safety of rTMS in MS patients were also evaluated. The fourth stage included a comprehensive assessment of the results of clinical and neurological, psychodiagnostic and neuroimmune studies. The role of TMS in comprehensive rehabilitation of MS patients considering the "TMS-therapy personalization" was determined. The rTMS was used for the purpose of non-invasive neuromodulation in the process of treatment and rehabilitation in combination with the pathogenetic and symptomatic therapy prescribed to the examined patients. The course of treatment was performed with a MagVenture, MagPro X100 and an 8-shaped inductor (coil). All patients were tested using an adapted safety questionnaire and selected according to the indications and contraindications for rTMS. Based on the clinical signs and symptoms, different rTMS protocols were used, which could be combined in one patient during a course of non-invasive neuromodulation. Protocols with high-frequency stimulation of the dorsolateral prefrontal cortex and primary motor cortex, M1 zone (D,S) with a frequency of 10 Hz, 90-100% amplitude of motor evoked potential, duration of 10 sessions, from 1600 to 2000 stimuli per session were selected. As clinical and neurological examination showed, the average age of the examined patients at the time of the study was 39.7±9.2 years; patients with primary progressive multiple sclerosis (PPMP) were older, and patients with remitting regressive multiple sclerosis (RRMP) were younger (p>0.05). The average duration of the disease was 6.7±4.2 years. Analysis of lateralization revealed a predominance of left-sided (43.6%), right-sided (30.9%), and symmetrical (25.5%) lesions. The overall EDSS-based severity in the examined patients was moderate, 5.1±1.9 points: severe in patients with progressive multiple sclerosis (6.9±1.3 and 6.2±1.0 points, respectively) and mild in patients with RRTP (3.9±1.7). In general, 30.0% of examined patients, 7.1% of PPMP patients, 5.4% of SPMS patients, and 50.7% of RRTP had fully intact gait function. The MFIS score showed quite high indicators of asthenia with MS on all subscales: physical subscale - 16.5±11.2 points, cognitive subscale - 23.8±10.1 points, psychosocial subscale - 4.0±2.1 points. The overall MFIS score in the examined patients was 44.3±23.0 points. There was a clear trend towards significantly more severe asthenia in patients with PMS and less severe asthenia in patients with RRMP. The overall FSS and SCS scores in all patients were 40.7±13.7 and 76.1±20.9 points, respectively.


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