[Ischemic stroke in men 18-50 years of age]. / Ishemicheskii insul't u muzhchin 18­50 let.

OBJECTIVE: To evaluate the main modifiable risk factors for ischemic stroke (IS) and features of the course in atherothrombotic, cardioembolic, and lacunar subtypes of IS in men aged 18-50 years. MATERIAL AND METHODS: The study included 125 men (the mean age was 42.6±5.3 years) who were admitted to the Vascular department before the COVID-19 pandemic and survived for the first 30 days after IS. Information on patients' baseline characteristics, traditional vascular risk factors, and lifestyle risk factors was systematically collected. Neuroimaging, ultrasound and laboratory tests were performed. RESULTS: Atherothrombotic subtype was identified in 60 patients, lacunar subtype in 46 patients and cardioembolic subtype in 19 patients. In the group as a whole, major risk factors included arterial hypertension (83.2%), dyslipidemia (50.4%), smoking (67.2%), alcohol consumption (29.6%), obesity (16.8%), heart rhythm disorders (12%), and diabetes mellitus (8%). CONCLUSION: The study revealed the main risk factors, the frequency of which differed depending on the stroke subtype and the age of the patients.

[Treatment of sleep disturbances associated with chronic non-specific low back pain: results of prospective randomized multicenter open-label clinical trial]. / Lechenie narushenii sna, svyazannykh s ostrym nespetsificheskim bolevym sindromom v poyasnichno-kresttsovom otdele spiny: rezul'taty prospektivnogo mnogotsentrovogo randomizirovannogo otkrytogo sravnitel'nogo v parallel'nykh gruppakh klinicheskogo issledovaniya.

OBJECTIVE: A comparative study of the effectiveness and safety of novel combination naproxen sodium and diphenhydramine in subjects with low back pain along with transient insomnia. MATERIAL AND METHODS: It was an open label, randomized, comparative, parallel group and multi-center clinical study. Subjects were randomised into one of three treatment arms: naproxen sodium 440 mg/diphenhydramine 50 mg, naproxen sodium 550 mg, Paracetamol 1000 mg/diphenhydramine 50 mg. All the subjects were advised to apply study drug ones before sleep for 3 days. All subjects also received naproxen sodium 275 mg as background therapy. The primary end-point was wake time after sleep onset (WASO) measured by actigraphy. Other secondary sleep and pain end-points were also assessed. RESULTS: Efficacy analysis was performed for intent-to-treat population (n=235 subjects). naproxen sodium 440 mg/diphenhydramine 50 mg combination showed significant improvements in WASO vs. naproxen sodium 550 mg (-42 min p=0.0174), while differences vs. Paracetamol 1000 mg/diphenhydramine 50 mg (-30 min, p=0.0891) were not significant. According to the average pain intensity difference in the lumbosacral spine combination product naproxen sodium 440 mg/diphenhydramine 50 mg was significantly improved compared with naproxen sodium 550 mg (-9.42, p<0.001) and Paracetamol 1000 mg/diphenhydramine 50 (-7.15, p<0.05). CONCLUSION: Naproxen sodium 440 mg/diphenhydramine 50 mg combination demonstrated improvement in sleep maintenance (WASO) vs. naproxen sodium 550 mg and higher efficiency in average daily pain reduction compared with the comparison groups. The treatment was well tolerated There were no serious or unexpected adverse events reported in the study.

[Therapy of moderate cognitive impairment and asthenia in patients with cerebrovascular pathology: results of a prospective observational study]. / Terapiya umerennykh kognitivnykh narushenii i astenii u patsientov s tserebrovaskulyarnoi patologiei: rezul'taty mnogotsentrovoi otkrytoi prospektivnoi nablyudatel'noi programmy.

OBJECTIVE: Obtaining additional data on the efficacy and safety of the drug Prospekta in the treatment of moderate cognitive impairment (MCI) and asthenia in patients with cerebrovascular disease (CVD). MATERIAL AND METHODS: A prospective observational study in more than 40 Russian cities enrolled 232 patients (mean age 61.5±10.0 years) with mild cognitive impairment (MCI), asthenia on ongoing basic nootropic therapy. The presence of MCI was confirmed by the Montreal Cognitive Assessment Scale (MoCA), asthenia - by 10-point Visual Analog Scale (VAS). All patients were prescribed the nootropic medication Prospekta 2 tablets 2 times a day for 8 weeks in addition to the therapy they received. Ultrasound Doppler sonography of the main arteries of the head and magnetic resonance imaging (MRI) of the brain were also assessed. At the end of treatment, the Clinical Global Impression Efficacy Index (CGI-EI) was assessed and the safety of the treatment was evaluated. RESULTS: The baseline severity of cognitive impairment according to the MoCA scale was 21.6 points, severity of asthenia according to the VAS was 6.3 points. According to Doppler flowmetry findings, hemodynamically significant stenosis was revealed in 105 (49.3%) patients, and narrowing of the main vessels without changes in hemodynamic parameters was revealed in 108 (50.7%) patients. According to MRI results, single vascular lesions in the brain matter were detected in 102 (44.0%) patients. The medications with nootropic effect were administered to 144 (62.1%) patients. A positive therapeutic response as improvement of cognitive functions was seen in 93.3% of patients after 8 weeks of taking Prospekta, including 39.4% of patients who had cognitive functions restored to the normal level. No side effects were registered during the observational study. CONCLUSIONS: The nootropic medication Prospekta is effective and safe in treatment of MCI in patients with asthenia with CVD, and improves cognitive function in patients with asthenia with CVD, both in monotherapy and in combination with other nootropic agents.

[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.

[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.

[The results of an open prospective study of ß-interferon biosimilars (an Yaroslavl' cohort)]. / Rezul'taty otkrytogo prospektivnogo issledovaniya bioanalogov ß-interferonov.

OBJECTIVE: to study safety and efficacy of the biosimilars of disease-modifying drugs (DMDs) in the prospective nonrandomized open long-term study of patients with multiple sclerosis in the Yaroslavl oblast (an Yaroslavl' cohort). MATERIAL AND METHODS: The study included 203 patients treated with DMD biosimilarsduring 30 months according to the instruction for using. The efficacy was assessed by the relapse frequencychanges in EDSS scores, changes of lesions on MRI T2-weighted images (T2-WI). The safety was assessed by the determination of the percentage of patients with side-effects due to the treatment. Results at baseline and month 30 visit were compared. RESULTS: There was a significant decrease in the frequency of relapses in patients treated with biosimilars compared to baseline (cinnovex by 0.03, genfaxon by 0.29, ronbetal/interferon by 0.13, infibeta by 0.36). For all biosimilars, with the exception of infibeta,EDSS scores significantly increased (cinnovex +0.31, genfaxon +0.38, ronbetal/interferon +0.66, infibeta +0.26). MRI results revealed an increase in the number of lesions in patients treated with cinnovex (+16.6%), genfaxon (+14.4%) and ronbetal (+10.6%) and a decrease of lesions on T2-WI in patients treated with infibeta (-14.5%). The most marked generalized reasponses were in the cinnovex group (flu-like syndrome - 66% of the patients), local reactions were most marked in the genfaxon group (82%). CONCLUSION: The differences between some biosimilars and original DMDs in the safety profile and efficacy suggest that attention should be drawn to the thorough study of drug effects in clinical trilas and postmarketing studiesincluding registers of patients treated with DMDs managed independently from pharmaceutical companies.

[Differential diagnosis of late-stage neuroborreliosis with affection of the central nervous system].

Chronic neuroborreliosis is an actual problem in neurology due to its under-investigation in Russia, variety of clinical forms, and the absence of well established diagnostic criteria. We present clinical and laboratory differential diagnostic criteria of chronic borrelial encephalomyelitis in comparison with multiple sclerosis. Distinguishing characteristics of Lyme encephalopathy versus vascular encephalopathy are considered. Problems and possibilities of immunological methods for identification of B. burgdorferi are discussed. The results of the antibiotic treatment of different clinical forms of neuroborreliosis with affection of the central nervous system are described.

[Clinical and instrumental characteristics of chronic neuroborreliosis].

The impairment of the nervous system is the main clinical presentation of chronic Lyme borreliosis. Frequency and characteristics of neuroborreliosis in Russia are still under-investigated. The article contains the analysis of 160 cases of chronic Lyme borreliosis with detailed descriptions of different neurologic syndromes - radiculopathy, polyneuropathy, encephalopathy and encephalomyelitis. Epidemiology of this disease as well as its laboratory and instrumental diagnosis are discussed. Extraneural signs and symptoms of late stages of neuroborreliosis are presented. The results of antibacterial treatment of different forms of chronic neuroborreliosis are outlined.

[Side-effects of the treatment with disease modifying drugs in patients with multiple sclerosis: an analysis of register data in the Yaroslavl region].

Authors have followed up 230 patients with multiple sclerosis treated with disease modifying drugs (DMD) using the data of the Multiple sclerosis register of the Yaroslavl oblast during 2009-2011. Original drugs and their generics registered in Russia are used. Patients received interferon-beta 1a for intramuscular introduction (avonex - 3.0%), interferon-beta 1a for hypodermic injection (rebif - 19.2%, genfakson - 8.5%), interferon-beta 1b (betaferon - 16.5%, extavia - 18.2%, ronbetal - 18.0%), glatimer acetate (copaxone - 16.7%). Adverse effects were recorded and subjective tolerability of the drug by the patient was assessed. Statistically significant differences in the safety profile between some bioanalogues and original DMD were identified. This finding suggests that effects of different DMD should be studied in depth in clinical and post marketing trials.

[Lyme disease in patients with multiple sclerosis: clinical, diagnostic and therapeutic features].

Lyme disease is one of the most frequent infections in the Russian Federation. In patients with multiple sclerosis, the Borrelia infection may act as a trigger in some cases and also worsens the clinical course of multiple sclerosis. One hundred patients with definite multiple sclerosis were examined including 19 patients with the combination of multiple sclerosis and Lyme disease. The difficulties of diagnosis, clinical features and treatment of Lyme disease in patients with multiple sclerosis are discussed.

[Differential aspects of multiple sclerosis and chronic borrelial encephalomyelitis].

The Yaroslavl region is an endemic area for Lyme disease (LD) with one of the highest levels of morbidity in Russia. Chronic neuroborreliosis can mimic multiple sclerosis and cause considerable difficulties in differential diagnosis. A comparative clinical-instrumental analysis of patients with definite multiple sclerosis (n=65) and chronic borrelial encephalomyelitis (n=11) was carried out. The key differential-diagnostic features of multiple sclerosis and borrelial encephalomyelitis were specified. Migrating erythema and tick's bite in the anamnesis, combined with lesions of the central and peripheral nervous systems, the absence of retrobulbar neuritis in the anamnesis, artralgia and myalgia, the high blood sedimentation rate were not characteristic of multiple sclerosis. A patient with abovementioned findings should be tested for the presence of antibodies to Borrelia burgdorferi in the blood serum and, if necessary, in the cerebrospinal fluid to exclude the diagnosis of Lime disease.

[Methylenebisphosphonic acid alters the pattern of pericellular glycosaminoglycans and binding properties of CD44 in human endothelial cells].

The effect of methylenebisphosphonic acid (MBPA) on glycosaminoglycan metabolism, adhesive and proliferative properties of human endothelial cells has been investigated. It was demonstrated that MBPA (100 microM) inhibited the synthesis of all studied groups of glycosaminoglycans, but promoted the accumulation of heparan sulphate in endothelial pericellular matrix. Simultaneously, the redistribution of hyaluronic acid from pericellular matrix to the conditioned medium was observed. The decreased adhesion of endothelial cells to immobilized hyaluronic acid was not mediated by the alterations of CD44 expression. It was also demonstrated that MBPA affected the proliferative properties of endothelial cells. The alterations of glycosaminoglycan metabolism are considered to be involved in antiangiogenic effects of MBPA.

[The comparative clinico-laboratory characteristics of Lyme arthritis and reactive arthritis]. / Sravnitel'naia kliniko-laboratornaia kharakteristika Laim-artrita i reaktivnogo artrita.

The paper presents comparative clinical and laboratory characteristics of 17 cases of Lyme-arthritis (LA) and 28 cases of reactive arthritis (RA). LA and RA patients differed by age and sex. LA arose after the tick bite followed by erythema migrans or infection symptoms. In RA patients the above symptoms were absent. In LA patients arthritis was associated with typical symptoms of neuroborreliosis. The articular syndrome manifested similarly in LA and RA: arthritis was preceded by arthralgias, low limb joints and periarticular tissues were involved most frequently. The differences were: monoarthritis, elbow and shoulder joints, muscles lesions occurred more frequently in LA; polyarthritis, arthritis of hand and foot joints, talalgia were more common in RA. RA ran more actively, joint syndrome more frequently gave rise to fever. Prevalence of chlamydial infection in LA was close to that in RA. LA may run as RA, is frequently combined with Chlamydia trachomatis infection.

[The characteristics of peripheral nervous system involvement in Lyme borreliosis in an endemic region of Russia]. / Osobennosti porazheniia perifericheskoi nervnoi sistemy pri Laim-borrelioze v éndemichnom raione Rossii.

Clinical and laboratory data are available on affection of the peripheral nervous system (PNS) in 27 patients with Lyme-borreliosis (LB) in the endemic region of Russia. PNS disorders arose early, 88.9% of the patients had them within one month of the disease. 9 (37.5%) patients had meningoradiculoneuropathy (MRN) which emerged in the acute period in 77.8% of the patients. Inflammation in the cerebrospinal fluid was registered only in patients with clinical signs of meningitis. MRN developed more frequently in facial nerve neuritis (FNN) than in radiculopathy (RP)-80.0% and 14.3%, respectively, p = 0.01. Intrathecal synthesis of antibodies to B. burgdorferi in combination with pleocytosis was found only in FNN patients (16.7%). In 6 (37.5%) of 16 patients with neuroborreliosis concentrations of C-reactive protein were elevated. Its high level occurred significantly more frequently in RP (83%) than in FNN (17%) (p = 0.05). 5 out of 14 LB patients exhibited high level of Willebrand factor antigen. No clear clinical relations between this value and PNS lesions in LB were found.