[Thalamic lesion in tick-borne encephalitis]. / Dvustoronnee porazhenie talamusa pri kleshchevom entsefalite.

Signal enhancement on T2-weighted images of the thalamus on one or both sides by magnetic resonance imaging (MRI) is among the most frequently observed neuroradiological findings in patients with acute tick-borne encephalitis. The article presents a clinical case of a patient who had an encephalo-polyoencephalomyelitic form of tick-borne encephalitis with MRI picture of a typical bilateral thalamic lesion. Such changes according to neuroimaging studies may have a clinical differential-diagnostic value, and the knowledge of these features by neuroradiologists and neurologists will contribute to the correct diagnosis of acute tick-borne encephalitis, especially most severe forms.

[Clinical manifestations of COVID-19 in children]. / Nevrologicheskie proyavleniya COVID-19 u detei.

The neurological symptoms of COVID-19 in children (in Dyurtyuli area, Republic of Bashkortostan) are analyzed and brief review of the literature is undertaken in the paper. 137 children underwent swab test for COVID-19. The disease was diagnosed in 9 of them. Only respiratory symptoms were observed in 3 children, a combination of respiratory with anosmia or/and headache - in 3, asymptomatic form - in another 3. A case of a 7-years old girl suffering from COVID-19 with respiratory symptoms as well as anosmia and headache is presented. According to the review of the literature, COVID - 19 in children is usually milder than in adults, but in some cases may lead to neurological consequences. Multisystem inflammatory syndrome may lead to the development symptoms of encephalopathy (altered mental status, headache) and stroke. Autoimmune complications such as Gillian-Barre syndrome develop simultaneously or after resolving of the infectious process. The development of viral meningoencephalitis in COVID-19 is questionable.

[L-2-hydroxyglutaric aciduria caused by a new mutation in the L2HGDH gene]. / Sluchai L-2-gidroksiglutarovoi atsidurii, obuslovlennoi novoi mutatsiei v gene L2HGDH.

The authors present a case-report of 13 year-old girl with L-2-hydroxyglutaric aciduria [MIM#236792], a rare autosomal/recessive metabolic disorder caused by mutations in the L-encoding 2-hydroxyglutarate dehydrogenase (L2HGDH, 14q21.3). Clinical signs of the disease are presented by predominantly neurological symptoms (epilepsy, cerebellar ataxia, cognitive impairment). The distinctive feature is the specific multifocal lesion of the white matter detected on MRI. The characteristic neuroimaging picture and positive results of biochemical and molecular genetic diagnosis were identified.

[Anxiety and depressive disorders in Parkinson's disease]. / Depressiia i trevozhnost' pri bolezni Parkinsona.

This review presents the most recent data of worldwide research on anxiety and depressive disorders in patients with Parkinson's disease. Their characteristics and epidemiology, pathogenetic and clinical features, methods of diagnosis and treatment are presented. Depression occurs in 40-50% of patients with PD, anxiety in 17-43% of patients. Pramipexole, a dopamine agonist, is only one drug recommended for depression treatment. Nortriptyline and desipramine, belonging to the group of tricyclic antidepressants (TCAs), are considered to be possibly effective. There are no clear recommendations for treatment of anxiety. In general, methods of therapy of anxiety and depressive disorders in PD are not well understood which determines the conduct of large-scale studies in the future.

[Clinical and epidemiological characteristics of hereditary motor-sensory neuropathy 1X caused by the mutation c. 259C> G (p. P87A) in the GJB1 gene of patients from the Republic of Bashkortostan]. / Kliniko-épidemiologicheskie kharakteristiki nasledstvennoi motorno-sensornoi neiropatii 1Kh tipa, obuslovlennoi mutatsiei s. 259S>G (r. R87A) v gene GJBI, u patsientov Respubliki Bashkortostan.

BACKGROUND: Hereditary motor-sensory neuropathy 1X (НМСН 1X) is the second frequent form of hereditary motor-sensory neuropathies caused by mutations in the GJB1 gene (gap junction B1 type). The authors have established earlier that the с.259C>G (р.P87A) mutation is the most frequent cause of НМСН 1Ð¥ (92%) in patients from the Republic of Bashkortostan. AIM: To study in details the territorial ethnic distribution and clinical manifestations of the с.259C>G (р.P87A) in the GJB1 gene in patients with НМСН 1Ð¥ from the Republic of Bashkortostan. MATERIAL AND METHODS: Clinical/neurological data were assessed in 52 patients (32 men and 20 women) from 13 families with this НМСН 1Ð¥ mutation in accordance to the diagnostic criteria of the European neuromuscular center. Twenty-three patients underwent standard electroneuromyographic study ('Nicolet Viking quest') using cutaneous electrodes. Data analysis was performed with Statistica ver.6.0 ('Stat Soft, Inc.', 2003) software. RESULTS: The с.259C>G (р.P87A) mutation was more frequent in Bashkir (61%) and Russian (31%) families from 6 areas of the Republic of Bashkortostan. The age-at-onset was 13.24±4.33 years in men. In women, the age-at-onset varied from 7 to 45 years, it was difficult to detect this parameter in several patients due to the absence of complaints and symptoms of disease. A comparative analysis revealed the higher degree of peripheral nerve lesions in men compared to women. There was the distinct difference in electrophysiological parameters (excitation spreading velocity and M-response amplitude) along motor fibers of the middle nerves between men and women that indicated the predominantly demyelinating character of the pathological process in men and the axonal character in women. CONCLUSION: Clear clinical/electrophysiological sex differences (intra- and inter family) were shown in patients with НМСН IX with the с.259C>G (р.P87A) mutation in the GJB1 gene. The disease was less severe and often with the absence of symptoms in women. Genetic testing for mutations in the GJB1 gene, including the с.259C>G (р.P87A) mutation, can be recommended to female patients with excitation spreading velocity >38m/s.

[Autonomic dysfunction in patients with multiple sclerosis]. / Vegetativnaia disfunktsiia u patsientov s rasseiannym sklerozom.

AIM: To optimize the early diagnosis of the autonomic dysfunction in patients with MS. MATERIAL AND METHODS: The main group consisted of 46 patients: 15 men and 31 women with MS (McDonald, 2005), the average age was 33.35±9.9 years, the average score of the Expanded disability scale (EDSS) was 2.8±1.17 points. The control group consisted of 24 healthy subjects matched by age and sex with the main group. A study of the autonomic nervous system was carried out using the Scheme for detection of signs of autonomic disorders (A.M. Vein, 1998) and analysis of heart rate variability (HRV) at rest and after active orthostatic test (AOT). RESULTS: Autonomic dysfunction was found in 73% of the patients. The overall score of the Scheme was significantly higher in MS patients (31.32±9.43 points) compared to the comparison group (2.36±4.39 points, p<0.05). According to HRV, the contribution of brainstem autonomic centers in the regulation of stress-response during AOP was significantly reduced (p<0.05) and was characterized by the lack of activation of the sympathetic division of the ANS. In patients with MS, cerebral influences were dominating on HRV baseline records, evaluated by the domination of the VLF component in the spectrum. During AOP, VLF was almost leveled in both groups, and the VLF changes in patients before and after the AOP reached statistical significance (p<0.05). CONCLUSION: The use of the Scheme is preferable in outpatient clinics to screen the large numbers of patients with MS, and then selected patients could be referred to the instrumental methods of investigation.

[Two novel mutations in gene SPG4 in patients with autosomal dominant spastic paraplegia].

Hereditary spastik paraplegias (HSP) are a group of neurodegenerative disorders with primary lesion of the pyramidal tract. The most frequent autosomal dominant form of the disease in Europeans is HSP associated with mutations in the spastin gene (SPG4). Analysis of the gene SPG4 was carried out in 52 unrelated families with HSP from Bashkortostan by SSCP and following sequencing. Previously undescribed frameshift mutations c.322del29 (p.Val108SerfsX18) and c.885del10 (p.Thr295ThrfsX16) were detected in two unrelated families. Clinical studies have shown that, in both families, the disease corresponds to an uncomplicated form of hereditary spastic paraplegia, a main feature of which is the lower spastic paraparesis without any other symptoms.

[Cancer diseases in patients with multiple sclerosis in the Bashkortostan Republic]. / Onkologicheskaia patologiia u bol'nykh rasseiannym sklerozom v Respublike Bashkortostan.

A database on patients with multiple sclerosis (MS) of the Republican center of multiple sclerosis (Ufa city) is analyzed. The database includes 1436 patients. For the period 2005-2012, 4 female patients with cancer, including 2 patients with thyroid gland cancer, 1 patient with rectum tumor and 1 patient with breast cancer, were identified. Clinical features of MS in these cases were studied. In two patients, cancer developed during the treatment with Β-interferon-1b. A possible association of cancer with MS and multiple sclerosis disease modifying drugs is discussed.

[Smoking as a risk factor of development and progression of multiple sclerosis (a review and experimental data)].

Epidemiological data on smoking influence on the development and course of multiple sclerosis (MS) are presented. The relative risk (RR) of MS for smokers was calculated as 1.3-1.8 in various cohort studies. Smoking was positively correlated with MS progression. The RR of the transition of remitting-relapsing MS to secondary progressive MS was in the range of 2.5-3.6. The RR of the transition to clinically isolated syndrome authentic MS was 1.8. Results of the MRI study of 239 MS patients (102 smokers and 137 non-smokers) revealed the higher level of disability on EDSS, higher rate of disease progression and lesser cases with remitting course in the group of smokers. The primary progressive MS course was more often observed in the group of smoking patients. The more favorable prognosis in terms of sensitivity and visual symptoms of disease onset were found in nonsmokers.Forms with a late onset prevailed in smokers.

[MFN2 gene analysis in patients with hereditary motor and sensory neuropathy from Bashkortostan Republic].

Hereditary motor and sensory neuropathy (HMSN) type IIA is caused by mutations in the mitofusin type-2 (MFN2) gene and represents one of the most common axonal forms of HMSN. We determined the spectrum and frequency of MFN2 gene mutations in patients from the Bashkortostan Republic (BR). Four different mutations were revealed in 5 out of 170 unrelated patients, i.e., c.2113G>A (p.Val705Ile) (1.2% among all types of H MSN in the total sample of patients and 2% among patients of Tatar ethnicity). This mutation was described previously; c.775C>T (p.Arg259Cys) (0.6%, in the total sample of patients and 2% among the patients of Tatar ethnicity); c.776G>A (p.Arg259His) (0.6% in the total sample of patients and 1.5% among the patients of Russians ethnicity); and c.2171T>C (p.Leu724Pro) (1.2% in the total sample of patients and 7.4% among the patients of Bashkirs ethnicity). These are new mutations that were not observed among healthy family members and in control samples of healthy subjects. Five identified nucleotide substitutions represent single nucleotide polymorphisms of the gene, including c.892G>A (p.Gly298Arg), c.957C>T (Gly319Gly), and c1039-222t>c, which were described previously, while c.175+28c>t and c.2204+15t>c represent new nucleotide substitutions in the intron regions of the gene.

[The rate of free-radical oxidation in hereditary motor-sensor neuropathies and myotonic dystrophy].

The rate of free-radical oxidation in the blood of patients with hereditary motor-sensor neuropathies (HMSN) and myotonic dystrophy (MD) type I was evaluated by the generation of active oxygen forms, the content of the products of lipid peroxidation and the total blood antioxidant activity. The change in the generation of active oxygen forms was characterized by the increase in the spontaneous blood chemiluminescence in patients with HMSN compared to controls. In patients with MD, the concentration of the products reacted with thiobarbituric acid was identified. In most cases, no correlations between the parameters studied and clinical/genetic characteristics were found. This fact suggests that the changes are individual and the prescription of drugs with antioxidant activity to patients with HMSN and MD should be substantiated.

[Cognitive disorders in patients with myotonic dystrophy type I: a clinical and magnetic resonance study].

We studied 20 patients with myotonic dystrophy (MD) type I, mean age 34.4±12.3 years. A control group consisted of 10 healthy people, mean age 35.2±13.7 years. Cognitive status was assessed using the Brief Cognitive Rating Scale (BCRS), the Frontal Assessment battery (FAB), the Clock drawing test, the Luria memory ten-word retrieval test. The characteristic signs for cognitive deficit in MD were disturbances of visual-spatial functions revealed even in patients with high score on BCRS and FAD, the decrease in verbal fluency, generalization ability and the volume of auditory-speech memory. MRI data indicate the involvement of the gray matter (cortex athrophy) and the white matter (dilatation of the ventricular system, strengthening of the perivascular spaces, areas of T2 and FLAIR hyperintensity) in the pathological process. The lesion of the white matter in MD is similar to the imaging of demyelinization that should be taken into account in making the diagnosis by experts in neuroimaging, neurologists and geneticists.

[Randomized blind placebo-controlled study of the effectiveness of transcutaneous adaptive electrostimulation in the treatment of nonspecific low back pain].

The effectiveness of dynamic transcutaneous electrostimulation was compared to its imitation in patients with low back pain. Patients were randomized into two groups: 21 patients were treated with transcutaneous electrostimulation and 21 patients received placebo. Patients had one session of electrostimulation (20 minutes) daily during 7-10 days. Pain was assessed by the Visual Analogous scale (VAS) daily. The Oswestry Low Back Pain Scale, the Beck Depression scale and the Spilberger-Khanin Anxiety test were used as well before and after the treatment. The significant improvement on the VAS (p=0,048) and the Oswestry scale (p=0,047) was found in the main group compared to the placebo one. No side-effects of transcutaneous electrostimulation were observed.

[Polymorphism of the prion protein PRNP gene and risk of multiple sclerosis development in ethnic Russians from Bashkortostan].

M129V polymorphism of prion protein gene PRNP has been studied in patients with multiple sclerosis (MS) and healthy ethnic Russians from Bashkortostan using allele-specific PCR. The genotype frequency distribution of the examined polymorphism in Russians from Bashkortostan was similar to that in European populations. MM, MV, and VV genotype frequencies in control group and in the MS patients were 50.24%, 42.58%, 7.18% and 43.33%, 45.83%, 10.84%, respectively. It was shown that in the group of MS patients with onset of the disease at the age of 21 and older, the frequency of the VV genotype was higher than in the control group (14.3% versus 6.18%, respectively, P = 0.041). We suggest that the VV genotype is associated with higher risk factor of MS development in the patients aged 21 years and older.

[Spectrum and frequency of mutations in the connexin 32 gene (GJB1) in hereditary and sensory neuropathy type 1X patients from Bashkortostan].

Hereditary motor and sensory neuropathy type 1X (HMSN 1X) is the second most frequent form of demyelinating polyneuropathies and is caused by mutations in the gene for connexin 32 protein (Cx32, GJB1). The contribution of HMSN 1X to the structure of HMSN in the Republic of Bashkortostan was determined. The GJB1 mutations were detected in 18 out of 131 unrelated patients, which constituted 13.7%. The four missense mutations identified were represented by: Pro87Ala (c.259C>G) with the frequency of 10%; Arg22Gln (c.65G>A) (2.98%); Arg15Gln (c.44G>A); and Thr86Ile (c.257C

[Quality of life of patients with primary headaches, strokes and myotonic dystrophy].

Results of the first comparative study using a Russian validated version of the Medical Outcomes Study Short Form-36 (MOS SF-36) are presented. Two hundreds and seventy-four patients with several neurological disorders - primary cephalgias (124 patients), strokes (120) and myotonic dystrophy (30) were examined. A remarkable decrease of quality of life (QOL) in all groups as well as between-group differences on QOL domains (physical, psychological, social and others) were observed. These data might serve as a basis of support programs for patients.

[Analysis of the association of allelic variants of apolypoprotein E and interleukin 1 beta genes with multiple sclerosis in ethnic Tatars].

Multiple sclerosis (MS) is a multifactorial disease of the central nervous system. The apolipoprotein E (APOE) and interleukin 1 beta (IL1B) genes are considered to be candidate genes of MS. The aim of the study was to examine the hypothesis of the importance of APOE and IL1B gene polymorphisms in MS development in ethnic Tatars. DNA samples isolated by phenol-chloroform extraction from peripheral blood of 383 ethnic Tatars (120 MS patients and 263 healthy donors) were studied. 112C/R and 158R/C APOE gene polymorphisms as well as -511T/C IL1B gene polymorphism were analyzed by polymerase chain reaction (PCR) followed by PCR product digestion by endonuclease. Odds ratio (OR) values were used for evaluation of the relative risk of alleles and(or) genotype combinations. It has been shown that APOE*2/*3 genotype is associated with low risk of the disease development (OR = 0.20) in women. A combined effect of APOE and IL1B allelic variants has been discovered indicating the increased risk of the disease development in the carriers of APOE*4 and IL1B*T/*T alleles (OR = 4.76).

[Polymorphism of APOE gene and risk of development of the multiple sclerosis at ethnic Russians].

The multiple sclerosis is a complex disease of the central nervous system with the pronounced hereditary predisposition. The purpose of our research consisted in acknowledgement of the assumption on importance of apolipoprotein E gene (APOE) polymorphism in exon 4 in development of the multiple sclerosis in ethnic Russians. Research was lead on the samples independently collected in Moscow (106 patients and 189 persons of control group), Sverdlovsk area (54 and 109, accordingly) and republic Bashkortostan (119 and 285, accordingly). 2059C/T and 2197C/T polymorphisms of APOE gene, which determine aminoacid substitutions C112R and R158C in apolipoprotein E, were determined by polymerase chain reaction with the following restriction analysis of amplicons. There was not detected statistically significant distinctions on genotypes frequencies and alleles frequencies between control group and group of patients with multiple sclerosis. APOE*4 allele is not assosiated with risk of development of the multiple sclerosis at ethnic Russians.

[Multiple sclerosis in ethnic groups of Bashkortostan Republic].

Clinical presentations and course of multiple sclerosis (MS) have been studied in ethnic groups of Bashkortostan Republic. An analysis of 4 groups of patients, 234 Tartars, 80 Bashkirs, 22 Chuvashes and 237 Russians, revealed that the prevalence of MS was the least in the Bashkirs--3 times less than in Tartars (chi2 = 7.84; p < 0.05) and 2 times less than in Russians (chi2 = 2.95; p < 0.05). In all the groups, the disease more often developed in women. Mean age at disease onset in women was less in Tartars and Chuvashes and by 1 year more in Bashkirs. In debut, polysymptomatic beginning and movement disorders prevailed in patients with different ethnic origin. The higher prevalence of MS in Tartars, Russians and Chuvashes as compared to Bashkirs is probably caused by historically developed isolation of populations in the territory of the republic and by the features of marriage traditions.

[Glycosaminoglycans and their fractions in patients with hereditary neuromuscular disorders]. / Glikozaminoglikany i ikh fraktsii u patsientov s nasledstvennymi nervno-myshechnymi zabolevaniiami.

Hereditary neuromuscular disorders (HNMD), with population incidence 1:3000, are characterized in most cases by progressive course and treatment resistance and patient's disabling. To study the involvement of the tissue-connecting structures in the pathogenesis, glycosaminoglycans and their fractions were determined in blood serum. The test group involved 40 patients with hereditary myotonia, myodystrophy, neuropathy and spinal muscular atrophy and control one consisted of 27 healthy age- and sex-matched subjects. The study was conducted using anion exchange chromatography on DEAE-cellulose. Comparing to controls, significant increase of total glycosaminoglycans and decrease of gilauronic acid fraction (p < 0.05) were found in HNMD patients, with no differences being detected between nosologic entities. Reverse correlation (r = -0.46) was revealed between patient's age and glycosaminoglycans concentration in blood serum. We concluded on intracellular and intercellular matrix heteropolyglycans metabolism dysregulation in the patients and suggested a part of HNMD pathogenesis scheme.