[Role and place of ipidacrine in the therapy of diseases of the peripheral nervous system. The resolution of the expert council]. / Rol' i mesto ipidakrina v terapii zabolevanii perifericheskoi nervnoi sistemy. Rezolyutsiya Soveta ekspertov.

The resolution of the expert council is devoted to discussing aspects of the use of ipidacrine for the treatment of mononeuropathies, polyneuropathies and radiculopathies of various etiologies. Specialists prepared recommendations for ipidacrine's application in treating peripheral nervous system disorders.

[Efficacy and safety of Cytoflavin in the treatment of diabetic polyneuropathy: results of a multicenter, double-blind, placebo-controlled, randomized CYLINDER study]. / Effektivnost' i bezopasnost' primeneniya Tsitoflavina v terapii diabeticheskoi polineiropatii: rezul'taty mnogotsentrovogo dvoinogo slepogo platsebo-kontroliruemogo randomizirovannogo issledovaniya TsILINDR.

OBJECTIVE: The purpose of the present double-blind, placebo-controlled, randomized clinical trial was to evaluate the efficacy and safety of Cytoflavin in patients with diabetic polyneuropathy (DPN). MATERIAL AND METHODS: Investigational therapy was administered in two steps: intravenous infusions of experimental drug/placebo for 10 days followed by oral administration for 75 days. In 10 clinical centers, 216 patients aged 45-74 years with a diagnosis of type 2 diabetes mellitus, symptomatic distal sensorimotor DPN, confirmed no earlier than 1 year before screening, on stable therapy (no change of drugs and doses) by oral hypoglycemic drugs, intermediate-acting, long-acting or extra-long-acting insulin, and/or GLP-1 receptor agonists. RESULTS: By the end of treatment, the change of the Total Symptom Score (TSS) in the experimental group was -2.65 points, in the placebo group -1.73 points (p<0.001). Improvement of symptoms in the experimental group was achieved regardless of the degree of compensation for type 2 diabetes (both in those with Hb1Ac <8.0% and in those with Hb1Ac ≥8.0%), but demonstrated better results in patients with less severe baseline symptoms (TSS <7.5). Improvement in the components of the TSS scale «paresthesia¼ and «numbness¼ occurred as early as on day 11 of therapy; by the end of treatment, a significant decrease in the «burning¼ component was also demonstrated. The experimental drug had a positive safety profile. CONCLUSION: Cytoflavin, intravenous solution and enteric-coated tablets (SPTF Polysan Ltd.) is indicated for the symptomatic treatment of DPN.

[Early diagnosis of diabetic polyneuropathy based on the results of corneal nerve fibers examination]. / Vozmozhnosti rannei diagnostiki diabeticheskoi polineiropatii na osnove issledovaniya nervnykh volokon rogovitsy.

Laser corneal confocal microscopy (CCM) is a method of objective visualization of thin corneal nerve fibers (CNF), the structure of which changes in patients with diabetes mellitus (DM). PURPOSE: To conduct comparative analysis of the results of CNF assessment using CCM and other known neurological instrumental techniques as well as evaluate their applicability to the early diagnosis of diabetic polyneuropathy (DPN). MATERIAL AND METHODS: We examined a total of 46 patients (85 eyes) with type 1 DM and either subclinical (24 patients), or clinical-stage DPN (22 patients) and 50 patients (87 eyes) with type 2 DM (subclinical DPN in 27 patients and clinical-stage DPN in 23 patients). The control group consisted of 34 healthy volunteers (68 eyes). All patients underwent standard ophthalmological examination, CCM with nerve tortuosity assessment (including calculation of coefficients of CNF orientation anisotropy, KΔL, and symmetry, Ksym) and interocular asymmetry, electroneuromyography (ENMG), and quantitative sensory testing (QST). RESULTS: Analysis of the CCM results revealed a reliable decrease in the average KΔL values in patients with type 1 and type 2 DM compared with the control group. In the group of patients with type 1 DM and subclinical DPN, correlations were revealed between the CNF tortuosity coefficients and a number of ENMG parameters, such as the M-response amplitude of the peroneal nerve (r=0.73, p≤0.02), M-response amplitude of the tibial nerve (r=0.58, p≤0.01), residual latency (r= -0.62, p≤0.05), and peroneal nerve conduction velocity (r=0.57, p≤0.01). Ksym values correlated with the warm sensitivity threshold (r=0.6, p≤0.008). Among patients with type 2 DM and subclinical DPN, the KΔL coefficient correlated with the peroneal nerve conduction velocity (r=0.46, p≤0.02), M-response amplitude of the tibial nerve (r=0.6, p≤0.04), and residual latency of the peroneal nerve (r=-0.56, p≤0.05). CONCLUSION: The state of thin corneal nerves correlates with functional changes in the peripheral nerves. Pathological changes in CNF in patients with DM can be detected at an early (subclinical) stage of DPN using laser CCM and a program for corneal nerve tortuosity analysis.

['Point of no return' in diabetic neuropathies: a dangerous delusion]. / 'Tochka nevozvrata' pri diabeticheskikh neiropatiiakh: opasnoe zabluzhdenie.

Polyneuropathy in patients with diabetes mellitus is manifested by a lesion of peripheral sensory, motor and autonomic nervous system. Different severity of damage of sensory, motor and autonomic fibers in typical and atypical forms of diabetic polyneuropathy, requires a differentiated approach to therapy, but not the rejection of its implementation. In an interdisciplinary consensus, consultations are held with physicians from different regions of the Russian Federation, and modern methods of diagnosing and assessing the severity of diabetic polyneuropathies, which determine the algorithm for treating patients, are discussed.

[Segawa's syndrome]. / Sindrom Segavy.

The authors present a case-report of Segawa's syndrome. Clinical characteristics, genetic background and treatment options with special emphasis on a differential diagnosis are discussed.

[Diabetic and non-diabetic neuropathies in patients with diabetes mellitus]. / Diabeticheskie i nediabeticheskie polineiropatii u patsientov s sakharnym diabetom.

Diabetic polyneuropathy is the most often complication of diabetes mellitus. However, patients with diabetes may have other neuropathies, which need to be recognized and treated. Chronic nnflammatory demyelinating polyneuropathy is the most common non-diabetic polyneuropathy in patients with diabetes. The article discusses the classification, clinical features of diabetic and nondiabetic polyneuropathies, modern methods of diagnosis and approaches to treatment.

[α-Lipoic acid as the main pharmacological drug for in- and outpatient treatment of diabetic polyneuropathy]. / Al'fa-lipoevaia kislota - osnovnoe farmakologicheskoe lechenie diabeticheskoi polineiropatii v statsionare i poliklinike.

α-Lipoic acid, or thioctic acid, (ALA) is the most applicable pharmacological drug for treatment of diabetic polyneuropathy. The article explores the results of experimental studies on the α-lipoic acid effect on mechanisms of peripheral nerves affection in hyperglycemia as well as the data of numerous randomized controlled trials and meta-analyses on studying ALA efficacy in symptomatic diabetic polyneuropathy. It has been shown that amelioration of patients with diabetic polyneuropathy is observed both for ALA infusions and tableted form of the drug. The authors conclude that α-lipoic acid is a drug for treatment of pathogenetic development mechanisms of diabetic polyneuropathy with the best proven efficacy.

[Efficacy of thiolepta in diabetic polyneuropathy: results of the study ETIKA].

Thiolepta (alpha-lipoic acid preparation) was used in treatment of 205 patients, 134 women and 71 men, mean age 59.3±10.1 years; 196 patients with diabetes mellitus (DM) type II and 9 patients with DM type I. Treatment duration was 4 weeks. Dosage of the drug was 600 mg daily. Patients were assessed neurologically and with psychometric scales. Special attention was drawn to the severity of positive and negative symptoms of neuropathy and sleep disorders. The results demonstrated the efficacy of thiolepta in diabetic polyneuropathy assessed by all parameters. The effect remained during 3 months after the end of treatment. Good tolerability and safety of the drug are highlighted.

[Association of the T(-365)C POLG1, G(-25)A ANT1 and G(-605)T PEO1 gene polymorphisms with diabetic polyneuropathy in patients with type 1 diabetes mellitus].

The aim of this study was the search of association of polymorphic markers T(-365)C of POLG1 gene, G(-25)A of ANT1 gene and G(-605)T of PEO1 gene with diabetic polyneuropathy (DPN) in type 1 diabetes mellitus (T1DM) patients. All patients were ethnic Russians from Moscow, with a T1DM record of no more than 5 years and DPN or a T1DM record of more than 10 years but without DPN. We have found that polymorphic marker T(-365)C of POLG1 gene was associated with DPN in Russian patients with T1DM. The carriers of C allele and CC genotype had higher risk of DPN development (OR = 1.62; CI = 1.11-238; and OR = 1.76; CI = 0.99-3.13; relatively). On the contrary, the carriage of T allele and TT genotype were associated with the lower risk of DPN development (OR = 0.62, CI = 0.42-0.90; and OR = 0.61; CI = 035-1.07; relatively). We have not found any association of polymorphic markers G(-25)A of ANT1 gene and G(-605)T of PEO1 gene with DPN in Russian patients with T1DM living in Moscow.

[Familial transthyretin amyloidosis].

A case of familial transthyretin amyloidosis with TTR Cys 114 gene polymorphism is described (first in Russia and third in the world). The clinical picture of the proband was dominated by symptoms of autonomous polyneuropathy (orthostatic hypotension, erectile dysfunction, diarrhea, tachycardia, foot dyshydrosis) and of somatic nerve lesions (dumbness, impaired surface and deep sensitivity in the limbs). The patient presented with vitreous body opacity, disturbed eye movements, lateralized sensory symptoms, and difficulty of speech (baryphonia). Electromyographic quantitative autonomous testing and measurement of evoked sympathetic skin potentials confirmed affection of peripheral nerves. Heart ultrasound revealed restrictive amyloid cardiopathy. Histological analysis showed amyloid deposition in the intestines and sural nerve. The proband, his daughter, brother (monozygous twin), and brother's daughter had mutant TTR Cys 114 gene. The brother also had amyloid deposits in the absence of clinical signs of the disease. Analysis of familial medical history demonstrated autosomal dominant inheritance of this mutation in 4 generations. Its possible origin and clinical features of the disease are discussed.

[Association of polymorphous markers Pro72Arg and C(-594)CC OF TP53 gene with diabetic polyneuropathy in patients with type 1 diabetes mellitus living in Moscow].

The aim of this study was the search of association of polymorphous markers Pro72Arg and C(-594)CC of TP53 gene with diabetic polyneuropathy (DPN) in patients with type 1 diabetes mellitus with or without clinical signs of DPN. We have found that polymorphous marker Pro72Arg of TP53 gene was associated with DPN in Russian patients with type 1 diabetes mellitus living in Moscow. The carriers of Arg allele and Arg/Arg genotype had higher risk of DPN development (OR = 1.96; CI = 1.32-2.90; and OR = 2.14; CI = 1.23-3.73; relatively). On the contrary, the carriage of Pro allele was associated with the lower risk of DPN development (OR = 0.51; CI = 0.34-0.76). We have not found any association of polymorphous marker C(-594)CC of TP53 gene with DPN in Russian patients with type 1 diabetes mellitus living in Moscow.

The 262T>C promoter polymorphism of the catalase gene is associated with diabetic neuropathy in type 1 diabetic Russian patients.

OBJECTIVE: Oxidative stress plays an important role in the development of diabetic neuropathy (DN). Antioxidant enzymes reduce enhanced oxidative stress in the peripheral nerve. Genetic variations within the antioxidant genes therefore could be implicated in the pathogenesis of DN. METHODS: Using a PCR-RFLP assay, a total of 216 Russian type 1 diabetic (T1D) patients with DN and 250 T1D individuals without DN have been tested to verify whether the -262T > C and 1167C > T polymorphisms of the catalase (CAT), 197Pro > Leu amino acid substitution of the glutathione peroxidase 1 (GPX1) and +/null polymorphism of the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genes contribute to susceptibility to DN. RESULTS: Association between the -262T > C polymorphism of the CAT gene and DN was shown. The -262TT genotype of the CAT gene was significantly associated with higher erythrocyte catalase activity in blood of DN patients compared to the -262CC genotype (17.8 +/- 2.7 x 104 IU/g Hb vs. 13.5 +/- 3.2 x 104 IU/g Hb, P = 0.0022). CONCLUSIONS: These data suggest a protective role of the -262T allele of the CAT gene against the rapid development of DN in T1D (Odds Ratio = 0.7 [95% confidence interval 0.54-0.9], P = 0.002).

[Polymorphic markers of the NO synthase genes and genetic predisposition to diabetic polyneuropathy in patients with type 1 diabetes mellitus].

The allele and genotype frequencies of polymorphic markers of NOS1, NOS2 and NOS3 genes, encoding three types of NO synthases, were compared in type 1 diabetes patients with and without diabetic polyneuropathty. 180 type 1 diabetes patients (T1DM) of Russian or Eastern Slavonic origin, living in Moscow city, were divided into two groups using non-overlapping (polar) phenotypes. 86 patients had overt DPN and T1DM duration in this group was less than 5 years (DPN+ group) and 94 patients had no clinical DPN and T1DM duration was more than 10 years (DPN- group). We have not found the significant differences of allele and genotype frequencies of polymorphic markers (CA)n of NOS1 gene, (CCTTT)n of NOS2 gene, ecNOS4a/4b and Glu298Asp of NOS3 gene that indicates that all these markers are not associated with diabetic polyneuropathty. Only in the case of (CCTTT)n marker of NOS2 gene we have found a tendency for the association of 14 allele with DPN development. The carriers of this allele have the lower risk of DPN in T1DM.

[Association of polymorphic markers of lipid metabolism genes with diabetic polyneuropathy in type 1 diabetes mellitus].

The aim of this study was the search of association with diabetic polyneuropathy of the polymorphic markers epsilon2/epsilon3/epsilon4 of apolipoprotein E (APOE) and I/D of apolipoprotein B (APOB) genes in groups of type 1 diabetes patients with diabetic polyneuropathy (n = 86) and without its clinical signs (n = 94). We have not found significant association with diabetic polyneuropathy (DPN) of epsilon2/epsilon3/epsilon4 marker of APOE gene. However the comparison of allele and genotype frequencies of I/D marker of APOB gene showed that the carriers of I allele and II genotype had higher risk (OR = 1.66 and 2.01, relatively; p < 0.027), whereas the carriers of D allele had lower risk of DPN (OR = 0.60; p < 0.018). Our findings show that APOB gene, encoding one of the main components of lipid metabolism system, is involved into the diabetic polyneuropathy development in type 1 diabetes mellitus.

[Search for the association of polymorphic markers for genes coding for antioxidant defense enzymes, with development of diabetic polyneuropathies in patients with type 1 diabetes mellitus]. / Poisk assotsiatsii polimorfnykh markerov genov, kodiruiushchikh fermenty antiokislitel'noi zashchity, s razvitiem diabeticheskoi polineiropatii u bol'nykh sakharnym diabitom tipa 1.

The allele and genotype frequency distributions of polymorphic markers of genes coding for antioxidant enzymes were compared for type 1 diabetes mellitus patients with or without diabetic polyneuropathy (DPN). The groups (total 180 patients) had nonoverlapping (polar) phenotypes. Group DPN+ included 86 patients with DPN and diabetic record no more than 5 years. Control group DPN- included patients without DPN and diabetic record of at least 10 years. Comparative analysis with Fisher's exact test revealed a significant difference in allele and genotype frequency distributions of the T(-262)C polymorphic marker of the CAT gene. Polymorphic markers C1167T of the CAT gene, Pro/Leu of the GPX1 gene, 0/+ of the GSTT1 gene, and 0/+ of the GSTM1 gene showed no significant difference in allele or genotype frequency distribution. On this evidence, these markers were not associated with DPN in the sample examined.

[Association of the SOD2 Ala(-9)Val and SOD3 Arg213Gly polymorphisms with diabetic polyneuropathy in patients with diabetes mellitus type 1]. / Assotsiatsiia polimorfnykh markerov Ala(-9)Val gena SOD2 i Arg213Gly gena SOD3 s diabeticheskoi polineiropatiei u bol'nykh sakharnym diabetom tipa 1.

Single-nucleotide polymorphisms of the genes for mitochondrial (SOD2) and extracellular (SOD3) superoxide dismutases were tested for association with diabetic polyneuropathy (DPN) in diabetes mellitus (DM) type 1. Patients (n = 180) were divided into two groups with nonoverlapping (polar) phenotypes. Group DPN+ included 86 individuals with DPN and DM type 1 record of no more than 5 years. Group DPN-included 94 patients with DM type 1 record of more than 10 years but without clinical signs of DPN. Fisher's exact test revealed significant differences in allele and genotype frequencies for the two groups. Higher frequencies of SOD2 allele Val and genotype Val/Val and of SOD3 allele Arg and genotype Arg/Arg were established for group DPN+. On this evidence, SOD2 and SOD3 were associated with DPN in DM type 1.

Predisposing genetic factors for diabetic polyneuropathy in patients with type 1 diabetes: a population-based case-control study.

Oxidative stress plays a key role in the development of microvascular complications of diabetes mellitus (DM). Antioxidant enzymes protect against the rapid onset of diabetic polyneuropathy (DPN) by reducing oxidative stress. Genetic variations that affect activity or expression levels of the antioxidant enzymes may therefore be associated with susceptibility to DPN. We examined polymorphic markers Ala(-9)Val in SOD2 gene and Arg213Gly in SOD3 gene for possible relation to DPN in Russian type 1 diabetic patients. Four hundred Russian white patients with type 1 diabetes were studied using neurological examination according to recommendations of the San Antonio Conference on Diabetic Neuropathy. Two groups were formed from the general sample. Definition of frequency distribution of the polymorphic markers was performed in these groups using the polymerase chain reaction. Genes encoding the enzymes Mn-SOD and extracellular superoxide dismutase (EC-SOD) were found to be associated with the pathogenesis of DPN.