[Nociceptive and mixed pains in patients with multiple sclerosis]. / Notsitseptivnye i smeshannye bolevye sindromy u patsientov s rasseyannym sklerozom.

Nociceptive and mixed pain syndromes (NMPS) whose pathogenesis is linked with the formation of plaques of demyelination in the CNS are commonly present in patients with multiple sclerosis (MS). NMPS of diverse locations, mechanisms and clinical features significantly worse patients' disability and impair their social adaptation. At the same time, clinicians do not pay enough attention to these syndromes in routine practice. Early diagnosis of NMPS may be important not only for early and appropriate NMPS' therapy and improvement of patients' quality of life, but, possibly, for the diagnosis of the onset or relapsing phase of MS, in cases when NMPS are the symptoms of MS and are the signs of active demyelinating process. This review addresses contemporary views of the main types of NMPS in MS (headaches, musculoskeletal pains, painful tonic spasms, pain with spasticity). Epidemiologic data, pathogenesis, clinical manifestations and diagnostic options of NMPS in patients with MS are described along with current views on MS and NMPS comorbidity theories. Existing approaches to treatment of NMPS based on randomized trials data are analyzed.

[New opportunities in the treatment of patients with multiple sclerosis (Resolution of the Council of Experts on April 23, 2022, Moscow, JSC «BIOCAD¼)]. / Novye vozmozhnosti v terapii patsientov s rasseyannym sklerozom¼ (Rezolyutsiya soveta ekspertov 23 aprelya 2022 goda, Moskva, AO «BIOKAD¼).

One of the target areas for the development of the Russian pharmaceutical industry at present is the development of next-in-class drugs medicines. These are original, patent-protected drugs that act on known biological targets, improved or modified in structure and mechanism of action compared to existing, successfully proven medicine. The article presents the results of an expert council on the management of patients with multiple sclerosis and the place of new original medicines of the JSC BIOCAD company (SamPEG-IFN-ß1a and divozilimab) in multiple sclerosis therapy algorithm.

Vaccination and Multiple Sclerosis - Current Situation.

Active immunization of patients with autoimmune diseases is a current challenge. Vaccination of patients with multiple sclerosis (MS) has been shown not to be associated with increased risk of exacerbation. A personalized approach to immunization of this group of patients is required, taking account of ongoing therapy and the nature of the course of illness. MS is not an absolute contraindication for vaccination against the new coronavirus infection. Vaccination can be with any of the currently authorized immunoformulations.

[Neuropathic pain syndromes in patients with multiple sclerosis]. / Neiropaticheskie bolevye sindromy u patsientov s rasseyannym sklerozom.

Among the numerous pain syndromes (PS) of various localizations and types, observed in patients with multiple sclerosis (MS), the greatest attention of researchers is attracted by neuropathic PS. Neuropathic PS are often present already in the early stage of MS, significantly reduce the quality of life, hinder the social adaptation of patients, poorly respond to therapy. Central neuropathic PS, which pathogenesis is closely related with plaques in the central nervous system, are most common in patients with MS. Diagnostics of neuropathic PS in MS is based mainly on typical clinical symptoms; MRI and neurophysiological methods data are of secondary importance. This review focuses on modern concepts of three main neuropathic PS in MS: ongoing extremity pain, trigeminal neuralgia and Lhermitte's sign. Clinical symptoms of neuropathic PS, current ideas about their pathogenetic mechanisms, MRI and neurophysiological techniques data and the existing approaches to conservative therapy and surgical treatment based on randomized trials data are presented.

[Vaccination and multiple sclerosis at the present stage]. / Vaktsinatsiya i rasseyannyi skleroz na sovremennom etape.

Immunization of the patients with autoimmune diseases is rising a lot of concerns. It was previously demonstrated that vaccination in MS patients was not associated with an increased risk of exacerbations. A personalized approach is needed to define the immunization schedule. A decision should be made based on the course of the disease and the treatment used. Multiple sclerosis is not an absolute contraindication to vaccination. Any authorized vaccine can be used in MS patients.

[Homocysteine and markers of endothelial dysfunction in multiple sclerosis]. / Gomotsistein i markery endotelial'noi disfunktsii pri rasseyannom skleroze.

OBJECTIVE: To identify hyperhomocysteinemia and to assess its possible association with the course and other markers of endothelial damage in multiple sclerosis. MATERIAL AND METHODS: Analysis of blood serum for homocysteine, for the content of adhesion molecules sPECAM-1, matrix metalloproteinase 9, blood plasma test for von Willebrand factor antigen in patients with multiple sclerosis. The values of these indicators were analyzed depending on the course and activity of the demyelinating process, the severity of neurological disorders, as also depending on the therapy received. RESULTS: Hyperhomocysteinemia was found in more than half of patients with multiple sclerosis. A significantly higher homocysteine level was found in male patients, and hyperhomocysteinemia was associated with the activity of the process in patients with highly active multiple sclerosis. CONCLUSION: The results of the study suggest a possible association of hyperhomocysteinemia with high process activity and disease progression, as well as with mechanisms of neurodegeneration. Determination of homocysteine concentration may be one potential marker for predicting the course of the disease.

The Novel Coronavirus Infection (COVID-19) and Nervous System Involvement: Mechanisms of Neurological Disorders, Clinical Manifestations, and the Organization of Neurological Care.

The new coronavirus SARS-CoV-2 and the disease it causes COVID-19 involves not only respiratory system damage, but can also lead to disorders of the central and peripheral nervous system, as well as the muscular system. This article presents published data and our own observations on the course of neurological disorders in COVID-19 patients. There is a relationship between the severity of COVID-19 and the severity and frequency of neurological manifestations. Severe neurological disorders are mostly seen in severe cases of COVID-19 and include acute cerebrovascular accidents (aCVA), acute necrotizing encephalopathy, and Guillain-Barré syndrome. Factors potentially complicating the course of COVID-19 and increasing the development of neurological complications include arterial hypertension, diabetes mellitus, and chronic cardiac and respiratory system diseases. Questions of the possible effects of human coronaviruses on the course of chronic progressive neurological diseases are addressed using multiple sclerosis (MS) as an example. We discuss the management of patients with aCVA and MS depending on the risk of developing coronavirus infection.

[Registry-based comparison of multiple sclerosis epidemiology trend data in 1999 and 2019: the case of Yaroslavl]. / Dinamika osnovnykh epidemiologicheskikh pokazatelei rasseyannogo skleroza po rezul'tatam sravneniya registrov patsientov 1999 i 2019 gg. v Yaroslavle.

OBJECTIVE: To compare the epidemiological indicators of multiple sclerosis (MS) in Yaroslavl when comparing the 1999 and 2019 registers to study the pathomorphism of the disease in this territory. MATERIAL AND METHODS: During the work, the data of the 1999 and 2019 registers were used, including the age of the debut, the date of diagnosis, the form of the disease, clinical characteristics, the treatment received and its duration. In 1999, 257 patients living in the city of Yaroslavl (155 women and 102 men) were included in the MS registry with a reliable diagnosis of MS according to Poser's criteria with confirmation according to neuroimaging data. In 2019, 479 people living in the territory of Yaroslavl (342 women and 137 men) were included in the register with a diagnosis of MS based on the criteria of MacDonald 2005, 2010, 2017. As of 01.01.19, 970 patients (530 women and 440 men) were included in the patient register of the Yaroslavl region. RESULTS AND CONCLUSION: Clinical and epidemiological review of Yaroslavl MS Registry data in 1999 and 2019 showed significant changes in disease pattern. The prevalence rate increased from 42.6 to 78.5 cases per 100,000 people. The morbidity rate rose from 1.58 to 3.28 cases per 100,000 people. The reasons for the increase are improvement in the diagnostic quality, new diagnostic criteria and the true growth of prevalence and morbidity. The use of disease modifying drugs (DMDs) has extended «the time to EDSS 3,0¼ by 4 years, «the time to EDSS 6,0¼ by 5-8 years.

[Effect of different groups of first line DMT on endothelial damage in multiple sclerosis]. / Vliyanie razlichnykh grupp PITRS pervoi linii na povrezhdenie endoteliya pri rasseyannom skleroze.

INTRODUCTION: Vascular changes, including destabilization of the blood-brain barrier, are common pathological signs in multiple sclerosis (MS). There are prerequisites, which indicate the direct effects of disease modifying therapy (DMT) on the state of the vascular wall and reduce the damage to the endothelium in MS. AIM OF THIS STUDY: Was to identify and evaluate the relationship of endothelial dysfunction in patients with multiple sclerosis with used DMT. MATERIALS AND METHODS: The study included 85 patients with a reliable diagnosis of MS according to the McDonald criteria of 2010 (56 women, 29 men) aged from 17 to 62 years (average age 36.3±1.2 years). All patients underwent a comprehensive clinical and neurological examination, laboratory tests (blood serum analysis for the content of adhesion molecules sICAM-1, sPECAM-1, sE-selectin, sP-selectin, for the content of homocysteine and matrix metalloproteinase 9 (MMR-9) by ELISA; blood plasma analysis for Von Willebrand factor antigen (vWf) by ELISA).The results of the study indicate a decrease of endothelial damage in MS during interferon therapy. Its also allow the use of indicators such as von Willebrand factor antigen, sPECAM-1, sE-selectin levels as potential markers of the effectiveness of DMT.

[Novel coronavirus infection (COVID-19) and nervous system involvement: pathogenesis, clinical manifestations, organization of neurological care]. / Novaya koronavirusnaya infektsiya (COVID-19) i porazhenie nervnoi sistemy: mekhanizmy nevrologicheskikh rasstroistv, klinicheskie proyavleniya, organizatsiya nevrologicheskoi pomoshchi.

Novel coronavirus SARS-CoV-2 and COVID-19, besides affecting the respiratory system, may lead to central and peripheral nervous system disorders and also cause muscular symptoms. The authors review the literature and own clinical case with respect to nervous system involvement in COVID-19 patients. There is a correlation between the severity of COVID-19 and the severity and frequency of neurologic complications. Severe neurologic symptoms are primarily observed in patients with severe COVID-19. Neurologic-associated symptoms may include stroke, acute necrotizing encephalopathy, and Guillen-Barre syndrome. Diseases that potentially aggravate COVID-19 and increase the risk of neurologic complications include arterial hypertension, diabetes, chronic diseases of the heart and respiratory system. The probable impact of human coronaviruses on chronic and progressive diseases of the nervous system with particular respect to multiple sclerosis is reviewed. A triage plan for stroke and MS patients during the COVID-19 pandemic, depending on the risk of coronavirus infection, is presented.

[Epidemiological and clinical aspects of chronic neuroborreliosis with parkinsonism in the Yaroslavl region]. / Epidemiologicheskie i klinicheskie aspekty khronicheskogo neiroborrelioza s sindromom parkinsonizma v Yaroslavskoi oblasti.

OBJECTIVE: To study clinical and epidemiological features of chronic neuroborreliosis (CB) with parkinsonism (PS) in the Yaroslavl region. MATERIALS AND METHODS: The study included the main group of patients (n=5) with CB and PS of the average age of 61±3/4, the comparison group (n=6) with Parkinson's disease (PD) of the average age of 54.7±8.3 and a group of 6 healthy people. Diagnostic criteria of Lyme disease based on the recommendation of the US Centers for Disease Control and Prevention and criteria for the diagnosis of PS were used. PD was diagnosed by the criteria of the Parkinson's UK Brain Bank. Serological diagnosis of CB was carried out using immunoenzyme assay and immunoblotting in dynamics. The following scales were administered: HOEHN and YAHR, MMSE, MFI-20, CGI. All patients underwent MRI of the brain and spinal cord. RESULTS AND CONCLUSION: PS in patients with CB in the Yaroslavl region was observed in 2.17% of cases among patients with CB and amounted to 0.25% of all cases of the revealed PS. The features that complicate the diagnosis of PS within chronic borreliosis were: the absence of erythema migrans in the history of 80% of patients and in more than half of the cases of the acute period of the disease, the presence in most patients (60%) of asymmetric onset of the PS with rest tremor in 40% cases and a significant reduction in the severity of PS as a result of therapy with levodopa. The onset of complete regression of the clinical manifestations of PS and reduction of the titer of antibodies and obtaining the negative results during dynamic serological study in response to prolonged antibiotic therapy provided a basis to verify the diagnosis of borreliosis with PS in these patients.

[New directions of immunocorrection in multiple sclerosis]. / Novye napravleniia immunokorrektsii pri rasseiannom skleroze.

Multiple sclerosis is a central nervous system disease with autoimmune and neurodegenerative mechanisms of development. This disease can lead to severe disability and neurological defects. Although its etiology and pathogenesis remain unclear, research data show that multiple sclerosis is a multifactorial disease, the development of which depends on environmental factors, as well as a genetic predisposition. The impact of these factors lead to the death of neural cells, accompanied by demyelination of nerves and neuronal dysfunction. Therapy of multiple sclerosis is based on the use of anti-inflammatory and immunomodulating substances, however, there are certain disadvantages associated with the constant use of these drugs and a possible change in dosage over time. This review discusses the pathogenesis of multiple sclerosis and the role of various subpopulations of immune cells in the development of diseases, as well as existing approaches to therapy. It is noted that immunoreconstitution therapy has advantages over immunomodulation and immunosuppression maintenance therapy for some patients. Thus, short courses of therapy provide more adequate treatment for patients and lower risks of adverse events associated with chronic immunosuppression. The review also discusses the data of clinical studies on the immunoreconstitution therapy drugs, such as alemtuzumab, ocrelizumab and cladribine. It is noted that nowadays the exact mechanisms underlying this type of therapy remain unclear. In this regard, further studies are needed to explain the therapeutic effects. It is assumed that patients with a high risk of multiple sclerosis progression are the optimal group of patients for the early use of selective immunoreconstitution therapy. Thus, immunoreconstitution therapy may be the treatment of choice for many patients with highle active multiple sclerosis.

[Cerebral perfusion, arterial hypertension and endothelial dysfunction in rheumatoid arthritis]. / Mozgovaia perfuziia, arterial'naia gipertenziia i éndotelial'naia disfunktsiia pri revmatoidnom artrite.

To study the relationship between cerebral perfusion with arterial hypertension (AH) and the state of endothelium in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Seventy-eight patients with RA were divided into two groups: with- and without AH.The functional methods included ultrasonic duplex angioscanning and dopplerografy of the extracranial and intracranial arteries of the head and neck and daily 24 hour monitoring of arterial blood pressure (BP). C-reactive protein (CRP), vascular endothelial adhesion molecule type 1 (sVCAM-1), von Willebrand Factor antigen (vWF AG), interleukin-8 (Il-8), rheumatoid factor (RF) IgG, endothelin-1 (ET-1) were determined by immunoenzyme analysis and velocity of sedimentation (VS). The dysfunction of endothelium was evaluated by calculation of the number of desquamated endotheliocytes cells (DE). RESULTS: AH occurred in 46 (59%) patients. Cerebral hypoperfusion was observed in patients with RA in whom the reduction in the high-speed indices of blood flow were correlated with BP increase. There were negative correlations between the linear speed of blood flow on the common carotid arteries and average day and night systolic BP, average day and night diastolic BP, indices of time systolic BP and diastolic BP and avariability of BP. The same results were established for the intracranial arteries: inverse correlations between the linear speed on the anterior cerebral arteries and average day systolic BP. The signs of endothelial dysfunction represented by significant differences among the indices of activation of endothelium in RA patients in comparison with the control group were shown. Content of ET-1, sVCAM-1, vWF AG, Il-8, CRP was higher in RA. The number of DE was significantly higher as well. These indices showed significant differences depending on RA activity. Correlation analysis revealed that the markers of endothelium activation sVCAM-1, vWF AG were positively correlated with the indices of immune inflammation. CONCLUSION: An increase in the activity of inflammatory process in RA leads to endothelial dysfunction, which contributes to the increase in the peripheral vascular resistance of cerebral arteries, reduction in the high-speed indices of blood flow, growth of BP variability and the increase in load by pressure.

[Sonographic characteristics of non-traumatic focal hourglass-like nerve constriction]. / Sonograficheskie kharakteristiki netravmaticheskoi fokal'noi konstriktsii nerva po tipu 'pesochnykh chasov'.

AIM: To describe the sonographic phenomenon of the focal 'hourglass-like constriction' of the peripheral nerves (FCPN). MATERIAL AND METHODS: The authors described 7 patients meeting the criteria for the diagnosis of neuralgic amyotrophy with unilateral FCPN identified with ultrasound in 4 cases and detected intraoperatively in 3 cases (preliminary ultrasound was not performed). The US scanner Sonoscape Pro mode gray scale in the transverse and longitudinal scanning, linear probe 8-15 MHz and Logiq9 scanner with elastography were used. RESULTS: FCPN was detected in the single nerve in 4 patients, in two nerves in 2 patients and in 3 nerves in one patient. Among all the nerves involved in the pathological process, the radial nerve and its branches were affected in 73% (8 nerves); the ulnar nerve was involved in 18% (2 nerves) and the musculo-cutaneous nerve in 9%. The length of the constriction of the peripheral nerve did not exceed 1.7 mm. The deformation coefficient (DC) of constriction area was 3.8 to .,9; the change in the elasticity in the form of an increase of DC to 5.9 when compared to the intact portion of the nerve and a decrease in echogenicity were observed in one patient. CONCLUSION: High-resolution ultrasound of the nerve can be an informative method for the diagnosis of idiopathic non-traumatic FCPN mononeuropathy.

[Primary-progressive multiple sclerosis in Russia: a medical-sociological study involving patients and neurologists]. / Pervichno-progressiruiushchii rasseiannyi skleroz v Rossii: mediko-sotsiologicheskoe issledovanie s uchastiem patsientov i nevrologov.

The main results of a medical-sociological study aimed at the evaluation of the level of satisfaction with treatment in patients with primary progressive multiple sclerosis (PPMS) are presented. The survey was conducted in 19 regions of the Russian Federation and involved 437 patients with confirmed diagnosis of PPMS and 80 neurologists specialized in multiple sclerosis. The research was carried out by the All-Russian Public Organization of Disabled People with Multiple Sclerosis with the participation of the Russian Committee for Treatment and Research in Multiple Sclerosis. This is the first medical-sociological study in the Russian Federation involving patients with PPMS and neurologists. The study revealed typical medical and social problems patients with PPMS faced. A significant decrease in quality-of-life of PPMS patients was shown.

[Provision of alemtuzumab safety is one of the main components of pharmacovigilance]. / Obespechenie bezopasnosti terapii alemtuzumabom - odna iz glavnykh sostavliaiushchikh farmakonadzora.

Modern multiple sclerosis therapy with disease-modifying drugs is characterized by the risks of dangerous infectious complications. In the last 5 years, there have been several reports of severe, sometimes lethal, listeriosis infection in patients treated with alemtuzumab. This article presents a clinical case of lethal listeriosis meningoencephalitis, which developed within 7 days after the completion of the first cycle of alemtuzumab therapy. In January 2018, a meeting of the expert Council was held, at which the clinical recommendations published in 2017 were revised and updated.

[Steps to personalized therapy of multiple sclerosis: predicting safety of treatment using mathematical modeling]. / Shagi k personifitsirovannoi terapii rasseiannogo skleroza: prognozirovanie bezopasnosti terapii s ispol'zovaniem matematicheskogo modelirovaniia.

AIM: To construct a mathematical model capable of predicting the drug safety of a patient receiving multiple sclerosis disease modifying drugs (DMD), on a model of flu-like syndrome (FLS). MATERIAL AND METHODS: The study included 457 patients with multiple sclerosis (MS), aged from 18 to 68 years, mean 38.79 years, the mean duration of disease 122.58 months. All patients received first-line injections drug (interferon-beta). The sample included data from a three-year prospective dynamic observation with a frequency of observation of 1 every 6 months, with only the data of those examinations for which the presence or absence of FLS was known for the next 6 months (1203 cases). At the first step, the frequency of factors in the compared groups using the W Wald-Wolkovitz test, then the prognostic coefficients (PC) and the Kulbak informativity coefficient (CI) were calculated for each factor gradation. To determine the predictive ability of signs, the Spearman's R criterion was used. At the second step, a model of a two-layer neural network was constructed based on the data obtained. RESULTS: A simple static model and algorithm were developed to assess the risks of the onset and persistence of FLS during the next 6 months of interferon beta therapy. An attempt was also made to create an active model using neural network technology. Both models showed good sensitivity and specificity - 81.2% and 80.6% for the neural network, and 73.4 and 71.6% for the static model. CONCLUSION: Using of these algorithms allows to significantly increase the possibility of predicting the occurrence of AE at the time of drug prescribing. From the mathematical point of view, for the first time the mechanism and possibilities of using a neural network in conditions of incomplete initial information were determined.

[Polymorphic variants of the immune response genes as risk factors for primary progressive multiple sclerosis]. / Polimorfnye varianty genov immunnogo otveta kak faktory riska razvitiia pervichno-progressiruiushchego rasseiannogo skleroza.

AIM: To analyze the involvement of immune response genes in the pathogenesis of primary progressive multiple sclerosis (PPMS). MATERIAL AND METHODS: This multicenter study included 111 patients with PPMS from the Russian ethnic group. The association of PPMS with genes of immune system was analyzed by the study of polymorphic variants of genes of cytokines and genes of antigen-presenting cells. RESULTS AND CONCLUSION: The genotypes of IL-4 (rs2243250)*C/C and CLEC16A (rs6498169)*G/G were associated with PPMS in Russians. The association between the HLA-DRB1*15 and PPMS found out in other populations was confirmed in Russians.

[An effect of disease-modifying drugs on the development of children born to mothers with multiple sclerosis]. / Vliianie na razvitie rebenka terapii preparatami, izmeniaiushchimi techenie rasseiannogo skleroza, u materei s rasseiannym sklerozom.

AIM: To evaluate an effect of mother's treatment with disease-modifying drugs (DMD) on the mental and physical development of the child in the first year of life. MATERIAL AND METHODS: Thirty pregnancies resulted in birth of live babies in patients with multiple sclerosis (MS) were studied. The diagnosis of MS was made to the mother before conception of the child. Seven mothers did not receive DMD at the moment of conception (controls), 13 mother were treated with interferon-beta (IFN) and 10 with glatiramer acetate. A structure interview, examination of the child with the assessment of common anthropometric indices, the WHO scale for achievement of six milestones, medical history and statistical analysis were used. RESULTS AND CONCLUSION: The data on the negative effect of MS on the growth and development of the fetus and the positive impact of treatment of the mother with DMD in the early stages of pregnancy on anthropometric indices and development of the child in the first year of life were confirmed. It has been concluded that DMD positively influence the disease course of the female patient and potentially improve the prognosis for her future offspring.