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Amyotrophic lateral sclerosis (ALS) and myasthenia gravis are diseases with similar clinical features but different prognosis and approach to treatment. It is possible as an extremely rare combination of these diseases, as well as myasthenia gravis with signs of ALS (MuSK-positive), as well as ALS, accompanied by myasthenic syndrome. Latter option is the most common. Myasthenic syndrome accompanying the ALS characterized by pathological muscle fatigue signs, symptoms variability during the day, partial sensitivity to neostigmine, M-wave decrements detection during electromyographyc study. We present a case of a patient with terminal ALS and myasthenic syndrome. The main pathogenesis theories of this condition and the differential diagnosis of ALS and myasthenia gravis are discussed.

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The formation and accumulation of unfolded, misfolded, or damaged cellular proteins leads to development of endoplasmic reticulum stress (ER stress). A series of protective reactions is initiated in response to ER stress. These reactions are aimed at restoring the balance between protein synthesis and degradation, which is key to maintaining protein homeostasis (proteostasis). The main protective mechanisms are the attenuation of protein synthesis, increase of chaperone levels, and activation of protein degradation systems. Insufficiency or malfunction of these mechanisms induce apoptosis. Proteostasis dysregulation accompanied by protein aggregation and subsequent cell death in specific regions of the nervous system is a common pathogenetic hallmark of most neurodegenerative diseases. We discuss targeted regulation of the ER stress signaling pathways as a potential therapeutic strategy that can slow or even halt the disease progression.

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We analyzed the relationship between white matter hyperintensities in T2-weighted MR-images (according to Fazekas score) and the state of cognitive functions (total MOCA score) in 65 asymptomatic individuals. A relationship between the presence/number of lesions in the deep white matter of the brain and cognitive status according to the total MOCA score was revealed. The results of cognitive functions assessment also correlated with MRI evaluation of the severity of brain cortex atrophy. The severity of deep white matter lesions according to the Fazekas scale were also associated with end-diastolic blood flow velocities in the middle cerebral, vertebral, and basilar arteries.

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AIM: To analyze the polymorphism in exon 4 of the gamma-synuclein gene (SNCG) in patients with autoantibodies against the gamma-synuclein protein. MATERIAL AND METHODS: To identify autoantibodies against gamma-synuclein, the serum from patients with chronic cerebral ischemia and cervical osteochondrosis was used. All patients were women of the Slavic ethnic group, mean age 61±5 years. The isolated genomic DNA was used to determine the point mutation in exon 4 by the restriction endonuclease HphI and subsequent sequencing of the resulting fragments to confirm the results. RESULTS AND CONCLUSION: Antibodies against gamma-synuclein were identified in 2 patients with chronic cerebral ischemia and 3 with cervical osteochondrosis. All five patients had a T to A substitution at position 371, which was detected by the restriction endonuclease HphI resulting in a hydrolysis of the amplicon and the formation of two fragments. The subsequent sequencing of exon 4 of the SNCG revealed no other mutations and confirmed the T to A substitution. This single nucleotide polymorphism results in the amino acid substitution of glutamic acid to valine at position 110 (out of 127), changing its physicochemical properties and the ability to form aggregates as well as post-translational modifications. The obtained results provide grounds for further association studies of SNCG polymorphism in patients with various diseases of the nervous system.

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The review is devoted to axon growth inhibitors in the CNS, including a physiological role of myelin-associated proteins (Nogo-A, MAG, OMgp) and their involvement in the pathogenesis of various diseases (spinal injuries, stroke, neurodegenerations).

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AIM: To clarify clinical polymorphism of amyotrophic lateral sclerosis (ALS). MATERIAL AND METHODS: The study was based on records of a hospital personalized register. Ninety-four patients, aged from 25 to 81 years, diagnosed with ALS according to El Escorial criteria were included. Electromyography and, if necessary, transcranial magnetic stimulation and magnetic-resonance tomography were used to confirm the diagnosis. Disease progression was assessed with the ARSFRS. Age at disease onset, progression rate and duration of survival of patients, rare symptoms of ALS ('extramotor'), time for palliative care (gastrostomy, non-invasive and invasive lung ventilation) and provision of the care to the patient, family history were recorded in a specially designed questionnaire. RESULTS: Most of the patients had sporadic ALS, only two familial cases were identified. Spinal onset ALS was found in 66.0% of the patients, bulbar onset in 29.8%, diffuse onset (spinal and bulbar motor neurons were affected simultaneously) in 4.2%. Moderate ALS progression was observed in 42.6% of the patients, mean time till death was 3.0±1.2 years. A slow progression was found in patients with cervical, low back and bulbar onset. A rapid and even 'momentary' type of progression was in diffuse and breast onset. An extremely slow progression with the long-term hospital treatment and survival >5 years was found in 9.7%. Rare ALS symptoms were represented by specific cognitive and psychological impairments, a type of frontal/temporal dysfunction, but only 5 (5.3%) patients were diagnosed with ALS-dementia. Signs of pathological muscle fatigue (myasthenic syndrome) were identified in 18 (19.1%), extrapyramidal disorders in 5 (5.3%), coordination disorders in 4 (4.3%), pain in 12 (12.8%), sensory symptoms in 5 (5.3%) of the patients. CONCLUSION: ALS is a multisystemic neurodegeneration disease though the progressive motor neuron death determines the fatal outcome.

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Certain forms of amyotrophic lateral sclerosis (ALS) are associated with an altered compartmentalization of FUS and its aggregation in the cytoplasm of motoneurons. FUS is a DNA/RNA-binding protein that is involved in DNA repair and the regulation of transcription, splicing, RNA transport, and local translation. Two theories have been proposed to explain the mechanism of the pathophysiological process in ALS. The theories attribute degeneration of motor neurons to either loss or gain of FUS function. The review describes the main physiological functions of FUS and considers evidence for each of the theories of ALS pathogenesis.

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AIM: To evaluate an effect of dimebon on the onset of symptomatic stage in FUS.1-513 transgenic mice - a new genetic model of neurodegeneration, and to study the dynamics of disease progression in the terminal stage. MATERIAL AND METHODS: The study was carried out on males of line FUS1-513 with the contribution of genes from CD1 strains. Mice of the experimental group (n=28) received dimebon with water in the concentration of 70 mcg/ml starting from the 35th day of life. The control group (n=25) did not receive the drug. Age, body mass of animals at the start of symptomatic stage and duration of symptomatic stage were assessed. RESULTS: Application of dimebon can delay the onset of the manifestation of clinical symptoms of the neurodegenerative process in the experimental group (127.6±4.6 days) compared to the control group (110.6±4.2 days). The body mass was similar in both groups. CONCLUSION: Dimebon leads to an increase in the duration of presymptomatic stage and delays the manifestation of clinical symptoms. The changes in the dynamics of the pathological process in the symptomatic stage are not detected.

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In this study, we analyzed serum for the presence of antibodies to gamma-synuclein in patients with amyotrophic lateral sclerosis (ALS) compared to the control group of patients with other neurological diseases and healthy control donors. As a result, antibodies against gamma-synuclein are not an ALS-specific feature and have been identified in patients with ALS as well as in the control group patients. Patients with the impaired cerebral circulation showed increased incidence of autoantibodies to gamma-synuclein, yet the difference lacks statistical representativeness due to limited sample size.

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AIM: Neurological symptoms of genetic syndromes, including congenital cleft lip and palate (CLP) are well-studied while neurological characteristics of patients with non-syndromal CLP are not described. The authors studied neurological disturbances in CLP. MATERIAL AND METHODS: Twenty-one patients with CLP, mean age 12.0±4.7 years (the main group) were compared to healthy people (the control group). RESULTS AND CONCLUSION: Elements of bulbar syndrome (atrophy and deviation of the tongue, sagging of the soft palate, specific speech disturbances) and mimic innervation abnormalities (hypomimia or hypermimia, face asymmetry), microfocal neurological symptoms occurred significantly more frequently (p<0.01) in patients of the main group. Bulbar disorders, identified in 100% of the patients, were most characteristic of CLP. The neurological features of patients with CLP demonstrate the involvement of the brain stem, mimic innervation, bulbar cranial nerves and defects of the development of the neural tube.

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UNLABELLED: BACKGROUND AND ОBJECTIVE: Loss of conformation and function of sufficient number of proteins with high aggregation capacity plays an important role in the pathogenesis of many neurodegenerative disorders (NDD). Due to a recent discovery of new array of proteins with the capacity to form aggregates of nonamyloid type, new NDD models as well as a new level of understanding in vivo models which are already exist is needed. DNA/RN A binding proteins - FUS and TDP-43 play a crucial role in the pathogenesis of some forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. The objective of the study was to develop a new ALS transgenic model. MATERIAL AND METHODS: In cell culture experiments, we studied mutant FUS proteins capable to form intracellular deposits morphologically similar to those observed in the autopsy material of ALS patients. RESULTS AND CONCLUSION: We created a transgenic mice line, in which a pathogenic form of human FUS protein was expressed in the nervous system. That led to the aggregation of FUS protein in spinal cord and motor neurons with the following degeneration and development of a phenotype, similar to the human ALS disease phenotype, in young grown-up animals. This neurodegenerative phenotype corresponds to a great number of clinical manifestations of human ALS and is an adequate transgenic model of the disease.

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Frequency and nosological attribution of demyelinating polyneuropathies in patients with diabetes mellitus and alcoholism were determined. Eighty-six inpatients with alcoholic (n=46) and diabetic (n=40) polyneuropathy were examined clinically and using electroneuromyography (ENMG). A demyelinating pathogenetic variant was identified by clinical and ENMG data in 27 (31%) patients. Nine patients (33%) had dysimmune polyneuropathies (acute and chronic inflammatory demyelinating polyneuropathy). Polyneuropathies were specified as toxic/metabolic with the prevalence of a demyelinating component within the main disease in 18 (67%) patients. Clinical and ENMG-signs of the demyelinating variant of alcoholic and diabetic neuropathy are presented. The efficacy of the antioxidant berlition was shown for toxic/metabolic polyneuropathies while the addition of immune modulators was needed for treatment of dysimmune polyneuropathy.

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The authors present results of a pilot study on biomechanics of non-cyclic movements of the human consequent verticalization in the ontogenesis of patients with post-stroke hemiparesis (10 patients in the acute stage of cerebral stroke) and 10 healthy volunteers without neurologic and orthopedic pathology. Some movements of therapeutic exercises Balance (a model of ontogenetic kinesitherapy) have been selected for the study. Cinematic parameters have been recorded using a system of motion 3D video analysis, a kinematic model was build in accordance to standard protocols. The skin (native and straightened) electromyogram (EMG) was recorded synchronously with kinematic data using 16-channel electromyography from the following pairs of muscles: mm. sternocleido-mastoideus, trapezius (горизонтальная порция), biceps brachii, triceps brachii, rectus femoris, adductor magnus. Major differences in the EMG picture between patients and controls were: 1) the EMG "monotony" with the involvement of multiple additional muscles in locomotions with the prevalence of the peculiar "tonic" muscle activity (low amplitudes without distinct peaks), stretching along the whole cycle of movement. In controls, EMG demonstrated variability and had mostly "phasic" character with distinct 1 or 2 peaks; 2) the asymmetry of EMG profile in symmetric movements. i.e. when performed simultaneously from the right and from the left sides. The latter feature may be considered as predictive because it was never found in healthy people. It allows to identify objectively weak muscles even in the absence of visible parethis during the routine neurological examination.

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An objective of the study was to work out a complex program of gait restoration in patients with stroke using robot-driven mechanized gait trainers. The study included patients in the acute period of stroke (the mean age 59+/-10,4 years) who were not able to walk without assistance; 53 patients of the main group and 25 patients of the control group. The mean interval from the disease onset to the beginning of gait retraining sessions with mechanized gait trainers was 14+/-1,6 days depending on the adequacy of functional probes. The restoration program included everyday 30 minute sessions of exercise therapy. Patients of the main group received 20 min sessions using mechanized gait trainers Motomed Viva 2 and Gait Trainer 1 (GT1) with continuous monitoring of blood pressure and cardiac beat frequency. The number of sessions with GT1 was from 5 to 12, mean 7+/-1 sessions. After the complex restoration treatment, significant positive changes on scales of standing balance, functional categories of gait, Berg, Barthel (p< or =0.01) were observed in patients of the main group compared to controls. All patients of the main group became able to walk with a support or independently. The significant decrease (p< or =0.05) of a number of patients with disorders of proprioceptive sensitivity (from 37,7 to 9,4%) and with ataxia of the low extremities (from 37 to 11,3%) was observed in the main group, while no changes were seen in the control group. It has been concluded that the complex use of reflex kinesitherapy and robot-driven mechanotherapy in patients in the acute period of stroke allows to increase the functional activity and the level of self-service already prior to the discharge from hospital.

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