Validity and reliability of the Russian version of the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).

OBJECTIVE: The aim of this study is to elaborate a valid and reliable Russian version of the ALSFRS-R. METHODS: Russian adaptation of the ALSFRS-R was applied twice in 50 ALS patients followed by the test-retest analysis with a 7-day interval between applications and internal consistency analysis. RESULTS: Test-retest analysis showed very strong correlation for all of the ALSFRS-R variables. The intra-class correlation coefficient was 0.83. CONCLUSION: The elaborated Russian version of the ALSFRS-R has shown to be comparable with the original English version of the scale.

Yoga vs Physical Therapy in Multiple Sclerosis: Results of Randomized Controlled Trial and the Training Protocol.

Background: Yoga originated in the territory of modern India more than 3,000 years ago uses techniques for working with the musculoskeletal system, cardiorespiratory system, and attention. Currently, the effectiveness and safety of yoga in patients with various neurological disorders, including multiple sclerosis (MS), is of interest to many scientists and clinicians. Purpose: The main aim of this study is to examine the effect of yoga on symptoms and quality of life in patients with MS vs physical therapy (exercise therapy) and no exercise. Methods: The patients were randomly assigned to three groups (yoga, physical therapy (PT), or waiting list). After 12 weeks of regular exercises (or the absence of them), the effect of yoga and PT on the functional status and quality of life of patients were evaluated. The data were collected during the patients' two visits to the study center - before the start of the study and at the end of the 12-week period. The in-person examination included a doctor's assessment of the Expanded Disability Status Scale (EDSS), the SF-36 quality of life questionnaire, the fatigue scale, the Berg balance scale, and the 6-min walking test. Results: A total of 36 patients finished the clinical study: thirty women and six men. There was no statistically significant difference between the groups in terms of improvement in MS symptoms as measured by the balance, walking test, and fatigue scales. However, in the analysis of eight criteria of SF-36 quality-of-life questionnaire by the covariation analysis, statistically significant differences were found in favor of the yoga group in terms of physical functioning (PF) (p = .003), life activity (VT) (p < .001), mental health (MH) (p = 013), and social functioning (SF) (p = .028). Conclusion: Thus, regular yoga classes under the guidance of qualified staff are a promising method of non-drug rehabilitation of patients with MS with motor disorders.

Home-Based Music Therapy to Support Bulbar and Respiratory Functions of Persons with Early and Mid-Stage Amyotrophic Lateral Sclerosis-Protocol and Results from a Feasibility Study.

Respiratory failure, malnutrition, aspiration pneumonia, and dehydration are the precursors to mortality in ALS. Loss of natural communication is considered one of the worst aspects of ALS. This first study to test the feasibility of a music therapy protocol for bulbar and respiratory rehabilitation in ALS employs a mixed-methods case study series design with repeated measures. Newly diagnosed patients meeting the inclusion criteria were invited to participate, until the desired sample size (n = 8) was achieved. The protocol was delivered to participants in their homes twice weekly for six weeks. Individualised exercise sets for independent practice were provided. Feasibility data (recruitment, retention, adherence, tolerability, self-motivation and personal impressions) were collected. Bulbar and respiratory changes were objectively measured. Results. A high recruitment rate (100%), a high retention rate (87.5%) and high mean adherence to treatment (95.4%) provide evidence for the feasibility of the study protocol. The treatment was well tolerated. Mean adherence to the suggested independent exercise routine was 53%. The outcome measurements to evaluate the therapy-induced change in bulbar and respiratory functions were defined. Findings suggest that the protocol is safe to use in early- and mid-stage ALS and that music therapy was beneficial for the participants' bulbar and respiratory functions. Mean trends suggesting that these functions were sustained or improved during the treatment period were observed for most outcome parameters: Maximal Inspiratory Pressure, Maximal Expiratory Pressure, Peak Expiratory Flow, the Center for Neurologic Study-Bulbar Function Scale speech and swallowing subscales, Maximum Phonation Time, Maximum Repetition Rate-Alternating, Maximum Repetition Rate-Sequential, Jitter, Shimmer, NHR, Speaking rate, Speech-pause ratio, Pause frequency, hypernasality level, Time-to-Laryngeal Vestibule Closure, Maximum Pharyngeal Constriction Area, Peak Position of the Hyoid Bone, Total Pharyngeal Residue C24area. Conclusion. The suggested design and protocol are feasible for a larger study, with some modifications, including aerodynamic measure of nasalance, abbreviated voice sampling and psychological screening.

Clinical trials in pediatric ALS: a TRICALS feasibility study.

Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information.

The epidemiology of amyotrophic lateral sclerosis in Moscow (Russia).

Objectives: To estimate the incidence of amyotrophic lateral sclerosis (ALS) in Moscow by investigating multiple sources of cases. Incidence rates from previous Russian studies ranged from 0.3 to 0.7 per 100,000/year. Methods: A retrospective study of the incidence of ALS was performed in the South district of Moscow (population, 1,760,000, 2015). Several data sources were investigated. The medical records of the calendar year 2015 were examined by an ALS expert who accepted only patients with definite or probable ALS according to the revised El Escorial criteria. Crude and standardized incidence rates were calculated, the latter adjusted to the Russian and the European population. Results: Twenty-two patients were found, accounting for a crude incidence of 1.25/100,000/year (95% CI 0.78-1.89) and a standardized incidence of 1.22 (Russia) and 1.28 (Europe). The sample included 11 men and 11 women aged 36-73 years (mean 56). Five patients (23%) had bulbar onset ALS. The mean diagnostic delay was 12.8 ± 9.2 months (8.5 ± 4.8 in men and 17.2 ± 10.6 in women) (p = 0.02). Family history of ALS was present in two cases. Conclusion: The incidence of ALS in the Russian Federation is higher than previously reported but lower than in other countries. Poor diagnostic ascertainment, particularly in women, and the shorter life expectancy of the Russian population are possible explanations.

Interleukin-6, S-Nitrosothiols, and Neurodegeneration in Different Central Nervous System Demyelinating Disorders: Is There a Relationship?

BACKGROUND AND PURPOSE: A few groups have suggested that activated cytokines and nitrosative stress are closely involved in the pathogenesis of different demyelinating disorders induced by the neuroinflammatory destruction of neurons. The purpose of this study was to elucidate the associations of cytokines and S-nitrosothiols (RSNO) with the severity of neurodegeneration during relapse in demyelinating disorders of the central nervous system. METHODS: We measured levels of interleukin-6 (IL-6), erythropoietin, RSNO, and phosphorylated neurofilament heavy chain (pNfh) in cerebrospinal fluid (CSF) samples obtained from patients with different demyelinating disorders: multiple sclerosis (MS, n=52), acute disseminated encephalomyelitis (ADEM, n=9), and neuromyelitis optica spectrum disorders (NMOSD) with aquaporin-4 immunoglobulin G (AQP4-IgG, n=12). We compared these levels with those measured in a control group (n=24). RESULTS: We found that IL-6 in CSF was elevated in NMOSD with AQP4-IgG and ADEM patients as well as in MS patients after the destruction of soluble IL-6. Erythropoietin levels were lower in MS, while RSNO levels were higher in NMOSD with AQP4-IgG and MS patients than in the control group. CSF pNfh levels were elevated in MS and ADEM patients. CONCLUSIONS: These results confirm that IL-6 is activated in different demyelinating disorders, with this elevation being more prominent in the CSF of NMOSD with AQP4-IgG and ADEM patients. Moreover, S-nitrosylation is activated in demyelinating disorders with spinal-cord injury and neurodegeneration in these patients. However, we found no correlation between these biochemical markers, and so we could not confirm whether IL-6-mediated nitric oxide production is involved in spinal-cord lesions.

Coexistence of multiple sclerosis and ankylosing spondylitis: Report of four cases from Russia and review of the literature.

Multiple sclerosis is a chronic demyelinating disorder of the central nervous system. There are many cases of multiple sclerosis - like syndrome and demyelinating disorders in systemic lupus erythematosus, Sjogren disease, Behcet disease and other autoimmune conditions. Coexistence of ankylosing spondylitis and multiple sclerosis usually is rare but in this article we report 4 Russian patients with concomitant multiple sclerosis and ankylosing spondylitis diseases. None of these patients received anti-tumor necrosis factor alpha therapy prior to diagnosis of multiple sclerosis. Pathogenesis, diagnostic and treatment challenges are discussed.

Increased S-nitrosothiols are associated with spinal cord injury in multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated disorder associated with inflammation, demyelination and axonal damage. In search of potential biomarkers of spinal cord lesions in MS related to nitric oxide metabolites, we measured total nitrite and nitrate levels, and protein-bound nitrotyrosine and S-nitrosothiol concentrations in the serum of MS patients at different stages of the disease. Sixty-eight patients and 36 healthy volunteers were included in the study. Total nitrite and nitrate levels were augmented in relapsing-remitting MS, while increased S-nitrosothiol concentrations were found both in relapsing-remitting and secondary-progressive MS. Further analysis demonstrated that S-nitrosothiol levels were selectively increased in patients with spinal cord injury. The data suggest that high S-nitrosothiol concentration may be a potential serum biomarker for spinal cord injury in MS.