[Efficiency evaluation of the Neuromidin in the treatment of pain of the patients with discogenic lumbosacral radiculopathy: results of a multicenter post-registration prospective open comparative trial]. / Otsenka effektivnosti Neiromidina pri lechenii bolevogo sindroma u patsientov s diskogennoi poyasnichno-kresttsovoi radikulopatiei: rezul'taty mnogotsentrovogo postregistratsionnogo prospektivnogo otkrytogo sravnitel'nogo issledovaniya.

OBJECTIVE: Evaluation of the effect of Neuromidine on the dynamics of pain syndrome in the treatment of patients with discogenic lumbosacral radiculopathy. MATERIAL AND METHODS: Patients with a confirmed diagnosis of discogenic lumbosacral radiculopathy no more than one year old and moderate intensity of pain syndrome on a visual analog scale were included in the main group (OH, n=62, age - 53.1±15.6 yrs) and the comparison group (HS, n=40, age - 53.7±12.9 yrs). OG patients received Neuromidine (15 mg/1 mL 1 once a day IM for 10 days, then 20 mg 3 times a day for 8 weeks) in addition to the standard drug therapy, HS patients received only standard drug therapy. The duration of the study was 8 weeks. The degree of decrease in the intensity and dynamics of pain syndrome, activity and frequency of pain in the lumbar spine, changes in the level of physical activity, and the severity of emotional disorders were evaluated. The level of inflammatory markers in the blood and the dynamics of monosynaptic spinal H-reflex parameters were evaluated. RESULTS: Before the study, there were no statistically significant differences there were no results of clinical and laboratory-instrumental examination between groups. After 8 weeks, the reduction of pain by VAS in the main group was statistically significant in contrast to the comparison group (p=0.0001). In the main group there was a statistically significant increase in the mean cognitive impairment score (p=0.0029), as well as an improvement in psycho-emotional state with a significant decrease in GAD-7 (p=0.0002) and PHQ-9 (p=0.0096). After 8 weeks of therapy, IL-6 level in the main group was statistically significantly lower (p=0.0027) than in the comparison group. The results of H-reflex study revealed an increase in its amplitude and some shortening of latency at the end of Neuromidine therapy. The drug had no undesirable side effects and was well tolerated. CONCLUSION: Administration of Neuromidine 15 mg/1 ml once a day intramuscularly for 10 days followed by 20 mg 3 times a day for 8 weeks has an effective analgesic effect as adjuvant therapy in patients with discogenic lumbosacral radiculopathy. The inclusion of Neuromidine in the complex treatment of patients with pain syndrome in discogenic radiculopathy is superior in efficacy to standard drug therapy.

[Genetic background of dyslexia and dysgraphy in children]. / Geneticheskie predposylki disleksii i disgrafii u detei.

The review is devoted to one of the current problems of pediatric neurology - reading and writing disorders in children as part of a partial developmental disorder. With the development of neuroscience, the paradigm of «brain damage¼ in the understanding of a number of pathological conditions was replaced by the concept of «evolutionary neurology¼. The dominance of the ontogenetic approach caused the appearance of a new section in ICD-11 - «Neurodevelopmental disorders¼. Twenty-one genes associated with the acquisition of reading and writing skills have been identified. Modern studies demonstrate the connection of neuropsychological prerequisites for reading and writing, and clinical phenotypes of dyslexia with changes in specific loci. It is assumed that there are different molecular genetic bases for dyslexia and dysgraphia depending on ethnicity, orthographic features of language, including logographic features. Pleiotropy of genes is a cause of comorbidity of reading and writing disorders with attention deficit and hyperactivity disorder, specific speech articulation disorders, and dyscalculia. A key function of many of the identified genes is their involvement in the processes of neurogenesis. Their dysfunctions cause atypical neuronal migration, ectopic formation, inadequate axonal growth, and dendrite branching at the early stage of brain development. Morphological changes can distort the correct distribution and/or integration of linguistic stimuli in critical brain areas, leading to abnormalities in phonology, semantics, spelling, and general reading comprehension. The knowledge gained can form the basis for the development of risk models for dysgraphia and dyslexia formation and be used as a diagnostic and/or screening tool, which is important for evidence-based correction, optimization of academic performance, and mitigation of psychosocial consequences.

[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.

[Biomarkers of the development and progression of diabetic polyneuropathy]. / Biomarkery razvitiya i progressirovaniya diabeticheskoi polineiropatii.

OBJECTIVE: To study the diagnostic potential of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGFA) and their high affinity receptors (TrkB, VEGFR2) in the development and progression of diabetic polyneuropathy. MATERIAL AND METHODS: The main group consisted of 65 patients with diabetes mellitus and confirmed DPN. The comparison group included 14 people with diabetes mellitus without DPN. The control group consisted of 15 healthy individuals. Clinical characteristics of DPN were evaluated with VAS, PainDetect, TSS, NSS, NDS scores. The degree of polyneuropathy was verified by electroneuromyography. Serum levels of the growth factors and their receptors were studied using enzyme-linked immunosorbent assay. RESULTS: Elevated expression of serum BDNF, VEGFA and TrkB was found in patients with DPN, regardless of the presence of symptoms. The severe stage of DPN is characterized by painless form of polyneuropathy, the deficiency of serum BDNF, VEGFA and VEGFR2 and the high serum level of TrkB. The high expression of BDNF affects the intensity of neuropathic pain, the severity of the clinical signs of DPN and is associated with the severity of axonal damage to sensory nerve fibers. The increase in the TrkB level is associated with the painless form of neuropathy and the degree of nerve fiber demyelination. CONCLUSIONS: Enhanced serum expression of BDNF and VEGFA is proposed as a biomarker for the development of DPN, while different concentrations of TrkB and VEGFR2 receptors can be considered as predictors of DPN severity.

The Level of Neuregulin-1 after Traumatic Brain Injury and Formation of Post-Traumatic Epilepsy.

We evaluated the serum level of neuregulin-1 in humans with traumatic brain injury. The highest levels of neuregulin-1 were revealed in patients with developing post-traumatic epilepsy and the lowest concentrations of this peptide were found in healthy controls. The patients with traumatic brain injury not aggravated by the development of post-traumatic epilepsy had intermediate levels of neuregulin-1.

[Dynamics of the cognitive sphere indicators and neurotrophic factors in the course of balneotherapy of dyscirculatory encephalopathy]. / Dinamika pokazatelei kognitivnoi sfery i neirotroficheskikh faktorov v protsesse bal'neoterapii pri distsirkuliatornoi éntsefalopatii.

BACKGROUND: The natural factors of therapeutic significance play an important role in the rehabilitation of the patients suffering from chronic disorders of cerebral circulation since they are known to promote the development of the compensatory and adaptive processes. However, there is virtually no information in the relevant literature publications about the influence of balneotherapy on the dynamics of the cognitive sphere indicators and neurotrophic factors. AIMS: The objective of the present study was to evaluate the effectiveness of balneotherapy as a component of the combined treatment of the patients presenting with discirculatory encephalopathy based on the investigations into dynamics of the neuropsychological status and the quantitative content of the neurotrophic factors in the peripheral blood, with special reference to the brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), in the patients receiving the balneotherapeutic treatment based at they at the 'Kluchi' health resort. MATERIAL AND METHODS: A total of 72 patients presenting with the 1st and 2nd stages of chronic cerebral ischemia were examined (including 9 men and 63 women at the mean age of 62.2±2.1 years). They were given the health resort -based treatment during 14 days while staying at the 'Kluchi' resort located in the Perm region. The examination of all the patients included the psychometric testing and the determination of blood serum neurotrophic factors (BDNF and CNTF). The patients were allocated to three groups depending on the character of the prescribed treatment. The first group consisted of 29 subjects, who were given the conventional therapy (the alternation of hydrogen sulphide muds and baths number 7, daily massage of the neck-collar region in the combination with exercise therapy). The second group was comprised of 32 persons who received the standard course of chloride-sodium bromine baths number 7. The third group was composed of 11 persons suffering from chronic cerebral ischemia who received no balneo- or peloid therapy whatever. RESULTS: The study has revealed the different stages of cognitive and emotional disorders combined with the initially reduced level of BDNF in the blood serum of the examined patients. The level of BDNF in the peripheral blood of the patients comprising the first group increased from 3.68±2.15 to 5.02±2.88 ng/ml after the course of balneotherapy. These values were significantly higher than before the treatment (p=0.000). In the patients of the second group, the level of situational and personal anxiety estimated with the use of the Spielberger-Khanin test decreased in association with the improvement in the cognitive sphere after they received the standard course of balneotherapy including the usual chloride-sodium bromine baths. Simultaneously, the level of BDNF in the peripheral blood of these patents increased from 4.00±2.3 to 5.39±2.44 ng/ml (p=0.02). The patients of the third group, who were given no treatment whatever displayed no statistically significant changes of the studied parameters. CONCLUSION: The health resort-based treatment including the course of chloride-sodium bromine baths has a direct beneficial influence on the neuroreparative and neuroprotective functions in the patients presenting with chronic cerebral ischemia owing to the increase in the level of neurotrophic factors in the blood.

[A rare case of neurological manifestations of acute intermittent porphyria]. / Redkii sluchai nevrologicheskikh proiavlenii ostroi peremezhaiushcheisia porfirii.

The authors describe a rare and diagnostically difficult variant of neurological symptoms of acute intermittent porphyria complicated by rhabdomyolysis. Diagnostic criteria of the disease are highlighted. A differential diagnosis with diseases with similar clinical manifestation was made.

[Associations of single nucleotide polymorphisms of KIF1B gene with the severity of clinical manifestations of multiple sclerosis]. / Assotsiatsii odnonukleotidnykh polimorfizmov gena KIF1B s vyrazhennost'iu klinicheskikh proiavlenii rasseiannogo skleroza.

BACKGROUND: Multiple sclerosis (MS) is one of the most common neurological diseases, which development and features depend on various factors, including genetic ones. AIM: To identify associations of single nucleotide polymorphisms rs10492972 and rs117525287 of the KIF1B gene with the development and severity of clinical manifestations of MS patients in the Perm krai. MATERIAL AND METHODS: The study group consisted of 197 patients with MS, the control group included 80 healthy volunteers. Clinical characteristics were assessed by DDS, EDSS, SCRIPPS, FSS and Arm-index. A genetic study was carried out by real-time polymerase chain reaction using a CFX96 detection amplifier (Biorad, USA) and the CFX Manager 2.1 software package (Biorad, USA). RESULTS AND CONCLUSION: The study group was characterized by a moderate degree of disability: EDSS 4 [3; 6], SCRIPPS 62 [50; 79] points and moderate progression rate 0.42 [0,28; 0,67] points /year. A significant prevalence of the heterozygous genotype T/C (rs10492972) in the group of healthy people was established. The influence of the dominant T allele of rs10492972 on the severity of clinical manifestations on EDSS and SCRIPPS was found. No associations of the polymorphisms with the clinical parameters assessed by EDSS, SCRIPPS, FSS and Arm-index, as well as with the rate of disease progression were obtained. Significant differences in the frequencies of rs10492972 genotypes in groups of MS patients and healthy people were identified; their effect on the severity of MS was not determined.

[The state of the serotonin system in the patients presenting with chronic polypous rhinosinusitis]. / Sostoianie serotoninergicheskoi sistemy u patsientov s khronicheskim polipoznym rinosinusitom.

This article presents the results of the study designed to determine the concentration of the neuromediator serotonin in the blood serum and tissue homogenates prepared from the polypous tissue harvested in the patients presenting with chronic polypous rhinosinusitis (CPR). The study included 51 patients with this pathology while 11 patients with chronic maxillary rhinosinusitis (CMR) and deflection of the nasal septum (DNS) made up the group of comparison. The serum serotonin levels were measured and compared in the patients of the main and both control groups. The results obtained give evidence of the significant inverse correlation between serotonin levels in the sera and tissue homogenates on the one hand and the history of allergic diseases in individual patients on the other hand.

[Monitoring of neurotrophic factors and cognitive function in patients with traumatic brain injury]. / Monitorirovanie neirotroficheskikh faktorov i kognitivnykh funktsii u patsientov s cherepno-mozgovoi travmoi.

AIM: To study the neurological and cognitive status in comparison to the quantitative content of blood serum neurotrophic factors of patients with acute and long-term brain injury during treatment with cerebrolysin. MATERIAL AND METHODS: Eighty patients, 56 men and 24 women, aged from 18 to 64 years, were examined in acute and long-term periods of the brain injury of moderate severity. An open, comparative, randomized study was performed before and after treatment with cerebrolysin. RESULTS AND CONCLUSION: Cognitive impairment, dysregulation type in the acute and long-term brain injury of mild to moderate severity was associated with the low content of brain-derived neurotrophic factor. These disorders were clinically more pronounced in patients with the damage of the frontal and temporal lobes. After treatment with cerebrolysin, a significant positive dynamics on the scale of frontal dysfunction and increased levels of serum brain-derived neurotrophic factor were identified.

[The efficacy of botulinotherapy in the correction of the pain syndrome and quality of life of patients with cervical dystonia]. / Éffektivnost' botulinoterapii v korrektsii stepeni bolevogo sindroma i kachestva zhizni patsientov s tservikal'noi distoniei.

AIM: To evaluate the severity of pain, emotional status and humoral serotonin in patients with cervical dystonia (CD) before and after the botulinotherapy. MATERIAL AND METHODS: A simple, open, comparative study of clinical characteristics of hyperkinesis, pain and emotional status, quality of life and contents of serum and blood platelet serotonin in 48 patients (32 women and 16 men) with CD, in age from 37 to 53 years, before and one month after the botulinotherapy with disport in dose of 500--1000 U was carried out. A control group included 15 healthy people. RESULTS: All patients (100%) complained of involuntary movements and pain in the neck. The overall score on a scale of dystonic movements in the group of patients was 16,7±7,7 points, on TWSTRS - 46,48±6,2 points, on the Visual Analogue Scale, the average level of pain was 6,4±1,08 points. The degree of depression according to the Hamilton scale was significantly higher (p<0.05) compared to the control group. The level of trait and state anxiety measured with the Spielberger-Khanin scale was significantly higher (p<0.005) in patients with CD than in the controls. The correlation analysis revealed a direct dependence of the intensity of pain subscale TWSTRS with the degree of anxiety on the Hamilton scale and the amount of final points of dystonic movements. The level of serotonin in the serum was significantly lower in patients compared to the controls. After botulinotherapy, pain scores, anxiety and depression have significantly decreased and the level of blood platelet serotonin has increased. CONCLUSION: Botulinotherapy with dysport in CD patients reduces the degree of pain, depression, improves quality of life and stimulates the serotoninergic system.

[The value of immune enzyme testing of qualitative content of blood serotonin and liquor, in differentiate diagnostic of craniocerebral injury].

The sample of 72 patients with craniocerebral injury of light and medium degree in acute period was used to study the content of serotonin in blood serum and spinal liquor. The increase of the level of serotonin in blood serum depending on degree of severity of trauma was established. This occurrence can be used as a technique of differential diagnostic of concussion and contusion of brain.