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.

[A DTI study of the spinal cord lesion in patients with multiple sclerosis during the follow-up after relapse]. / Porazhenie spinnogo mozga u patsientov s rasseyannym sklerozom posle obostreniya po dannym diffuzionno-tenzornoi magnitno-rezonansnoi tomografii.

UNLABELLED: Spinal cord involvement is frequent in multiple sclerosis (MS) but the correlation between spinal cord damage on conventional MRI and clinical symptoms is not always obvious. Diffusion tensor imaging (DTI) is a sensitive technique for revealing tissue damage. OBJECTIVE: to investigate spinal cord DTI changes in MS patients during the relapse and in the follow-up. MATERIAL AND METHODS: Data were acquired from 25 patients with relapsing-remitting MS during the relapse characterized by unilateral light hand palsy, in three and twelve months after it. All patients underwent full neurological examination and MRI including conventional head and neck MRI and DTI of the brain and upper spinal cord in the sagittal plane. Twelve healthy subjects entered the control group. RESULTS AND CONCLUSION: Spinal cord sagittal DTI provides a reliable information about significant changes in MS patients compared tothe control group both inside demyelinating lesions and in the normal appearing spinal cord. These differences are preserved both in 3 and 12 months after the relapse and together with clinical recovery create evidence of functional compensatory mechanisms development. A tendency towards DTI parameters normalization together with faster fine motor skills recovery in patients without the asymmetrical decrease in vibration sense shows an important role that afferentation plays in recovery after the relapse.

[Comparative, placebo-controlled clinical study of efficacy and safety of glatiramer acetate 20 mg in patients with relapsing-remitting multiple sclerosis: results of the first year of the study]. / Sravnitel'noe platsebo-kontroliruemoe klinicheskoe issledovanie effektivnosti i bezopasnosti preparatov glatiramera atsetata 20 mg u patsientov s remittiruyushchim rasseyannym sklerozom: rezul'taty pervogo goda nablyudeniya.

The article presents the results of international multicenter randomized double-blind, active and placebo-controlled, comparative phase 3 trial. The goal of the study was to demonstrate non-inferiority of BCD-063 (glatiramer acetate, manufactured by JSC «BIOCAD¼, Russia) to copaxone-Teva (Teva Pharmaceutical Enterprise Co., Ltd., Israel) in patients with relapsing-remitting multiple sclerosis. METHODS: 158 patients with relapsing-remitting multiple sclerosis were randomly assigned into 3 groups: BCD-063, copaxone-Teva and placebo, at a ratio of 2:2:1, respectively. RESULTS AND CONCLUSION: Efficacy analysis after 48 weeks of therapy demonstrated no differences between BCD-063 group and copaxone-Teva group in both MRI parameters and frequency of relapses. The mean (SD) of number of MRI-confirmed relapses per patient per year (the primary endpoint) in BCD-063 group was 0.098361 (0.351422), in copaxone-Teva group - 0.098361 (0, 351 422) and in placebo group - 0.178571 (0.390021). There were also no differences between the groups for all other efficacy parameters (EDSS and MSFC). Both investigational BCD-063 and copaxone-Teva demonstrated a favorable safety profile. The data obtained from the present study confirm the therapeutic equivalence of BCD-063 (CJSC BIOCAD, Russia) and copaxone-Teva, that is important for further implementation of glatiramer acetate generic in the clinical practice of multiple sclerosis therapy.

[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.

[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.