[The application of high-frequency and iTBS transcranial magnetic stimulation for the treatment of spasticity in the patients presenting with secondary progressive multiple sclerosis]. / Primenenie transkranial'noi magnitnoi stimulyatsii v lechenii sindroma spastichnosti pri vtorichno-progredientnom rasseyannom skleroze.

Spasticity is considered to be a common manifestation of multiple sclerosis. Muscle relaxants are not sufficiently effective; more than that, some of them often cause a variety of adverse reactions. Transcranial magnetic stimulation (TMS) can be a promising new tool for the treatment of spasticity. The objective of the present study was to compare the effectiveness of the two TMS protocols: rhythmic (high-frequency) TMS (rTMS) and stimulation with the theta bursts (iTBS) in terms of their ability to reduce spasticity in the patients presenting with multiple sclerosis. PATIENTS AND METHODS: Twenty two patients with secondary-progressive multiple sclerosis were pseudo-randomized into two groups: those in the first (high-frequency) group received the treatment with the use of rTMS therapy at a frequency of 10 Hz; the patients of the second group, underwent stimulation with the theta bursts (iTBS). All the patients received 10 sessions of either stimulation applied to the primary motor area (M1) of both legs. The effectiveness of TMS protocols was evaluated before therapy and after 10 sessions of stimulation based on the Modified Ashworth scale (MAS), the expanded disability status scale (EDSS), and the Kurtzke functional scale (Kfs). In addition, the patients were interviewed before treatment, after 10 rTMS sessions, immediately after and within 2 and 12 weeks after the completion of the treatment using questionnaires for the evaluation of spasticity (SESS) , fatigue, and dysfunction of the pelvic organs (severity of defecation and urination disorders), fatigue. RESULTS: The study has demonstrated a significant reduction in spasticity in the patients of both groups at the end of the TMS protocol based on the MAS scale. There was no significant difference between the outcomes of the two protocols. Both had positive effect on the concomitant «non-motor¼ symptoms (fatigue, dysfunction of the pelvic organs). CONCLUSION: High-frequency transcranial magnetic stimulation (10 sessions of rTMS therapy at a frequency of 10 Hz) and stimulation with the theta-bursts applied to the M1 area in both legs can be an effective alternative treatment of spasticity in the patients with secondary-progressive multiple sclerosis. Further research is needed to detect more accurately the differences between the outcomes of the two stimulation protocols and the development of indications for their application on an individual basis.

[Experience in the use of high-frequency selective percutaneous rhizotomy in trigeminal neuralgia associated with multiple sclerosis].

OBJECTIVE: the study was aimed at assessment of the efficacy of percutaneous high frequency selective rhizotomy (PHFSR) after failure of conservative treatment of trigeminal neuralgia (TN) in multiple sclerosis (MS). MATERIAL AND METHODS: A retrospective analysis of 28 patients with TN associated with MS who underwent percutaneous rhizotomy in the period from 2000 to 2014 was performed. All patients were definitely diagnosed with MS according to the McDonald criteria (version of 2001, 2005, and 2010). The patients were divided by age, gender, and the trigeminal nerve branches involved in the process. The patients' condition was evaluated at different times after surgery. RESULTS: Good outcomes in the form of pain syndrome regression were achieved in 100% of the patients. A disease recurrence was observed in 6 (21%) patients during a follow-up period of 3 months to 14 years. Dysesthesia complications occurred in 4 (14%) patients. There were no deaths and severe complications. The percentage of minor complications was low. CONCLUSION: These data confirm that PHFSR is a safe, repeatable, and effective method of symptomatic neurosurgical treatment of TN associated with MS and may be recommended in the case of failure/intolerance of medication.

[Physical rehabilitation in multiple sclerosis: general principles and high-tech approaches].

In a chronic and disabling disease like multiple sclerosis, rehabilitation programs are of major importance for the preservation of physical, physiological, social and professional functioning and improvement of quality of life. Currently, it is generally assumed that physical activity is an important component of non-pharmacological rehabilitation in multiple sclerosis. Properly organized exercise is a safe and efficient way to induce improvements in a number of physiological functions. A multidisciplinary rehabilitative approach should be recommended. The main recommendations for the use of exercise for patients with multiple sclerosis have been listed. An important aspect of the modern physical rehabilitation in multiple sclerosis is the usage of high-tech methods. The published results of robot-assisted training to improve the hand function and walking impairment have been represented. An important trend in the rehabilitation of patients with multiple sclerosis is the reduction of postural disorders through training balance coordination. The role of transcranial magnetic stimulation in spasticity reducing is being investigated. The use of telemedicine capabilities is quite promising. Due to the fact that the decline in physical activity can lead to the deterioration of many aspects of physiological functions and, ultimately, to mobility decrease, further research of the role of physical rehabilitation as an important therapeutic approach in preventing the progression of disability in multiple sclerosis is required.

Pathophysiological aspects of the formation of neurological deficit in multiple sclerosis.

The results of complex studies were used to formulate a concept of the development of neurological impairments in multiple sclerosis (MS). Acutely developing impairments to spike propagation, reaching the level of conduction blockade, due to the active pathological process with demyelinating and axonal damage to the CNS lead to the formation of neurological impairments in exacerbations of MS, while complete or partial reversion (regression) of these symptoms in the stage of remission results from compensatory changes in the nature of conduction, which were not, however, accompanied by recovery of electrophysiological measures. The development of stable neurological deficit in secondary-progressive MS is determined by impairments to spike conduction processes associated with significant levels of demyelination and atrophic changes in the CNS, with myelin loss and axon death. Finally, the severity of cognitive changes is determined by differences in the severities of both the focal demyelinating process and diffuse damage to brain substance in MS, including the neurodegenerative component. The main factor in transient increases in symptoms is the universal lability of electrophysiological parameters, including those developing on the background of ion and neurotransmitter imbalance.

[The role of the otoneurological method in early diagnosis of multiple sclerosis].

Complete vestibulometric, audiological and otoneurological examinations were made in 48 patients with multiple sclerosis (MS). Central cochlear-vestibular syndrome was diagnosed in all the examinees. The otoneurological examination and comparison of changes in the acoustic and vestibular functions revealed specific symptoms characteristic for demyelinating disease of the central parts of the cochleovestibular analyzer. MR-tomography visualization of the demyelination foci in the brain confirmed affection of the cochleovestibular analyzer.

[Pathogenesis and treatment of multiple sclerosis (state of the art in 2000)]. / Patogenez i lechenie rasseiannogo skleroza (sostoianie problemy na 2000 g.).

Multiple sclerosis is universally accepted to be a multifactorial disease whose pathogenesis is due to a complex of immunopathological and pathochemical reactions. The key assumption is that only early stages of immunopathological chain reactions involve specific recognition of antigens by autoreactive T cells and antibodies. These early events trigger a demyelinating process at whose later stages of importance are macrophages and glial cells, particularly those of microglia, which produce a great deal of biologically active substances and inflammatory mediators. A deeper insight into the pathogenesis of multiple sclerosis has provided new therapeutical approaches to treating this disease. In addition to that there are effective IFN-beta drugs (Betaferon, Rebif, Avonex) and Copaxone, other pathogenetically justified approaches are still under search. The next step of further studies is to identify subtypes of multiple sclerosis and to choose a therapy in accordance with its pathogenetical mechanisms.

[No support for the hypothesis of chronic cerebrospinal venous insufficiency in multiple sclerosis]. / Nedokazannost' gipotezy khronicheskoi tserebrospinal'noi venoznoi nedostatochnosti pri rasseiannom skleroze.

Objective. To evaluate the jugular veins (IJV) using duplex sonography in patients with multiple sclerosis (MS). Material and methods. The study included 21 MS patients with different disease course, degree of disability and disease duration. A control group consisted of 8 healthy volunteers. Results. IJV changes that meet the CCSVI criteria have not been found. These findings are consistent with the results of recently published large studies. Possible reasons of non-confirmation of this hypothesis are discussed. Conclusion. Currently vascular intervention in MS is not recommended.

[Atrophy of the central nervous system in multiple sclerosis: MRI-morphometry results]. / Atrofiia tsentral'noi nervnoi sistemy pri rasseiannom skleroze: dannye MRT-morfometrii.

Nowadays the majority of multiple sclerosis (MS) research pays attention to the neurodegenerative component, using a magnetic resonance imaging voxel-based morphometry for its assessment. Cerebral atrophy occurs in the earliest stages of MS in different clinical phenotypes and progresses three times faster than in healthy individuals. WM atrophy involved almost all brain regions, but is less pronounced than GM loss. GM atrophy has distinct patterns of regional distribution in patients with different clinical phenotypes, more extensive in the progressive than in the relapsing disease phenotypes. Deep GM atrophy is demonstrated to correlate with WM lesion as well as cortical atrophy. GM atrophy shows significant correlations with T2 lesion volume, cognitive function and measures of physical disability. In addition to cerebral loss, MS patients frequently develop spinal cord atrophy, which also correlates with clinical impairment. However, the order of GM and WM involvement still remains unclear. And further research of atrophy MRI-predictors is needed in order to monitor clinical course of MS.

[Compensatory mechanisms in multiple sclerosis(review)].

Neuroprotective mechanisms of delay of neurodegeneration and recovery of function in multiple sclerosis are reviewed. Different adaptive reactions(neuroprotective autoimmunity, neuroplasticity, sodium channels expression and function changes, remyelination) are described. The possibility of neurogenesis, axonal regeneration and synaptic changes is discussed. Understanding the compensatory mechanisms in multiple sclerosis is fundamental basis for the development of new therapeutic approaches.

[Diffusion-tensor magnetic resonance tomography and tractography in multiple sclerosis: a review].

Multiple sclerosis is the most common chronic progressive inflammatory demyelinating disease of the central nervous system characterized by different clinical phenotypes, degrees of central nervous system damage and disease progression. Conventional magnetic resonance imaging has become a useful tool for diagnosis, differential diagnosis and monitoring disease progression. Recent innovations in magnetic resonance imaging give an opportunity to specify certain aspects of multiple sclerosis pathogenesis. This article is a review of diffusion-tensor magnetic resonance tomography and tractography usage in the brain and spinal cord of patients with different clinical phenotypes of multiple sclerosis. Main features of pathologically damaged white and grey matter observed using diffusion-tensor magnetic resonance tomography and tractography, correlations between different diffusion indices and disability are described. The problems of pathogenesis are discussed.

[Cortical reorganization in multiple sclerosis with movement disorders detected by functional MRI (own observations and literature data)].

Cortical reorganization in multiple sclerosis (MS) has been recently suggested as an additional potential contributor to the recovery or maintenance of function in the irreversible tissue damage. Functional cortical changes have been demonstrated in all MS phenotypes using motor fMRI paradigms. Data from available studies suggest that movement-associated cortical reorganization in patients with MS seems to vary across individuals at different stages of disease. Cortical reorganization may play a role in limiting the impact of structural tissue damage in MS patients and, conversely, its progressive exhaustion with disease progression may be one of the factors contributing to the accumulation of irreversible disability. The enhancement of any beneficial effects of this cortical adaptive plasticity should be considered as a potential target of therapy for MS.

[Clinical significance of adhesive properties of leukocytes and blood serum in patients with multiple sclerosis].

Adhesive blood properties have been studied in 100 MS patients with the help of the new method developed on the basis of the leucocyte adherence inhibition (LAI) test, which was based on the calculation of the ratio of adhesive cells to non-adhesive ones. The value obtained was called the Index of Spontaneous Adhesion (ISA), while the respective indicator reflecting the effect of adhesion strengthening under the influence of autoserum, being expressed by 30% and more, was named the Effect of the Adhesion Strengthening (ES-a). Blood samples of 54 donors and 31 patients with other neurological diseases were used as controls. Statistically significant increase of ISA values of MS patients was detected as compared to the group of donors. The highest indices of ISA and ES-a were found in the primarily progressive course and at the stage of MS exacerbation in the remitting course. Correlation between levels of adhesion and clinical features as well as parameters of clinical and humoral immunity are described. A role of membrane and soluble forms of adhesion molecules in initiation and progression of the immunologic process in MS is discussed.

[Structural and functional analysis of the cortico-spinal tract in multiple sclerosis].

The study aimed at comparison of transcranial magnetic stimulation (TMS) parameters to MRI data in multiple sclerosis (MS), taking into account clinical course of the disease. TMS was conducted in 56 patients and in 10 age- and sex-matched healthy controls. According to stage of activity and variant of the course, the patients were divided into 2 groups: one at the stage of exacerbation and another--at the stage of remission with secondary progressive MS. Latency of segmental evoked motor response was similar in patients and controls. Statistically significant between-group difference or trend toward changing of some TMS parameters were found that indicates a slow-down of the impulse conducting along the cortico-spinal tract, which is characteristic of demyelinization process. The changes were more pronounced in secondary-progressive MS. According to MRI data, a square of the spinal cord on the level of the intervertebral disk center C2/C3 was significantly smaller in the group of patients with secondary progressive MS than in that with exacerbation of the disease. The TMS parameters correlated both with the level of the focal demyelinization process and with the square of the spinal cord on a level selected. It allows to estimate expression of atrophic changes caused, in its turn, not only by myelin loss but also by axon loss.

[A comparative analysis of rebif 22-mcg and copaxone efficacy in multiple sclerosis].

A comparative analysis of efficacy and tolerability of such immunomodulating compounds as rebif 22-mcg and copaxone used in the treatment of multiple sclerosis is presented. The analysis was based on the data obtained in the 2-year study of copaxone (145 patients) and rebif 22-mcg (74 patients) therapy carried out in the Neurology Institute, Russian Academy of Medical Sciences.

[Vestibular cochlear disturbances in multiple sclerosis].

To specify the character of vestibular cochlear disturbances in multiple sclerosis (MS) and mechanisms of their formation, the objective quantitative evaluation of experimental caloric nystagmus using the computer electronystagmographic method and a comparison of hearing impairment with asymmetry of vestibular reactions were conducted in 48 patients with MS. The peculiarities of vestibular disturbance found in the study suggest a predominance of central vestibular syndrome with both subtentorial and supratentorial traits. The influence of the heat stimulus of vestibular analyzer (hot water caloric test) in multiple sclerosis revealed during computer electronystagmography may have diagnostic value.

[Mechanisms of lability of neurological symptoms in multiple sclerosis]. / Mekhanizmy labil'nosti nevrologicheskikh simptomov pri rasseiannom skleroze.

Pathophysiological peculiarities of demyelinated axons determine their high sensitivity to different exogenous factors and are the reason of instability of neurological signs in MS. One of the typical MS sing is high sensitivity to elevated temperature of the body. Even temporary elevation in body temperature may cause changes in impulse conduction in demyelinated fibres, which was proved by studies of evoked potentials and stabilometric studies. These disturbances may be associated with disorder of ions channels function. The role of other factors (metabolic and immunological disturbances, levels of cytokines and neurotransmitters) in temporary block of nerve conduction in MS is discussed. Further studies of the mechanisms of the lability of neurological sings in MS may lead to elaboration of new approaches to MS treatment.

[Progressive course of multiple sclerosis]. / Progredientnoe techenie rasseiannogo skleroza.

The mechanisms of MS progression are now studied with great attention and the treatment strategies at this stage of MS are widely discussed. The clinical peculiarities, genetic profile, immunological and biochemical changes, data of pathomorphological and MRI studies are discussed in this review. The data of own original immunological, biochemical and MRI studies, comparing relapsing-remitting and progressive MS course are presented. The role of axonal degeneration in the disease progression and data of the last trial of beta-interferons in secondary progressive MS are also discussed.