Diet and omega-3 and vitamin D supplement use predict five-year fatigue and disability trajectories in people with multiple sclerosis.

BACKGROUND: Fatigue and disability are indicators of disease progression experienced by many people with multiple sclerosis (pwMS). Understanding trajectories of these outcomes, and their predictors, may provide insight to potential interventions for MS management. METHODS: Survey data from 839 pwMS from the Health Outcomes and Lifestyle in pwMS study were analysed. Fatigue was defined as mean Fatigue Severity Scale >5, and severe disability as Patient Determined Disease Steps >5. Group-based trajectory modelling was used to identify fatigue and disability trajectories over five-years. Dietary predictors associated with outcome trajectory group membership were assessed using log-binomial regression. Demographic and clinical characteristics were considered in multivariable models. RESULTS: Distinct trajectories for fatigue and disability were identified. For fatigue, 58 % of pwMS were assigned to low-, and 42 % to high-, fatigue trajectory groups. For disability, 85 % of pwMS were assigned to low-, and 15 % to high-, disability groups. Baseline high-quality diet, and omega-3 and vitamin D supplement use, were associated with reduced risk of being in high-fatigue and high-disability trajectories, while meat and dairy consumption were associated with increased risk. CONCLUSIONS: A high-quality diet, avoiding meat and dairy, and omega-3 and vitamin D supplement use, individually predict better fatigue and disability trajectories. Dietary modifications should be considered in MS management.

The Study of Remyelinating Therapies in Multiple Sclerosis: Visual Outcomes as a Window Into Repair.

INTRODUCTION: Amelioration of disability in multiple sclerosis requires the development of complementary therapies that target neurodegeneration and promote repair. Remyelination is a promising neuroprotective strategy that may protect axons from damage and subsequent neurodegeneration. METHODS: A review of key literature plus additional targeted search of PubMed and Google Scholar was conducted. RESULTS: There has been a rapid expansion of clinical trials studying putative remyelinating candidates, but further growth of the field is limited by the lack of consensus on key aspects of trial design. We have not yet defined the ideal study population, duration of therapy, or the appropriate outcome measures to detect remyelination in humans. The varied natural history of multiple sclerosis, coupled with the short time frame of phase II clinical trials, requires that we develop and validate biomarkers of remyelination that can serve as surrogate endpoints in clinical trials. CONCLUSIONS: We propose that the visual system may be the most well-suited and validated model for the study potential remyelinating agents. In this review, we discuss the pathophysiology of demyelination and summarize the current clinical trial landscape of remyelinating agents. We present some of the challenges in the study of remyelinating agents and discuss current potential biomarkers of remyelination and repair, emphasizing both established and emerging visual outcome measures.

Eye movement desensitization and reprocessing for depressed individuals with multiple sclerosis: A pilot study.

BACKGROUND: Multiple studies have highlighted elevated rates of depression among individuals with Multiple Sclerosis (MS), with its associated symptoms posing a significant threat to overall well-being. Moreover, existing literature suggests a potential interconnection between depressive manifestations and the decline of physical functionalities in the context of MS. OBJECTIVE: to examine the viability of the Eye Movement Desensitization Reprocessing (EMDR) therapy protocol for the treatment of depressive disorders (DeprEND) for alleviating depression in individuals with MS. METHODS: We conducted a process-outcome study to examine the feasibilty and effectiveness DeprEND enrolling 13 individuals with MS and depressive symtpoms. Psychological and physical assessment pre-, post-intervention and 3-month follow-up were included. Pre- and post-magnetic resonance imaging (MRI) scans were conducted to analyze potential alterations in brain function. RESULTS: The EMDR DeprEND treatment showed a high level of adherence and feasibility. Significant reductions in depressive symptoms were found at post-intervention and at 3 months follow-up. No significant differences were observed in terms of physical symptoms. A significant modulation observed in parietal and premotor areas when examining negative valence stimuli post-treatment was found. CONCLUSION: for The EMDR DeprEND protocol may represent a feasible and cost-effective treatment for reducing depressive symptoms in MS patients and improving their mental well-being.

Effect of Acupuncture on Sensorimotor Function and Mobility in Patients with Multiple Sclerosis: A Pilot Study.

Introduction: Multiple sclerosis (MS) is a progressive disease of the central nervous system that can result in highly variable effects on mobility and sensorimotor function. Persons with MS (pwMS) often use complementary and alternative approaches, such as acupuncture, to address these symptoms. However, studies of acupuncture on these symptoms have been hindered by methodologic flaws, which have limited the ability to draw conclusions about its efficacy. The purpose of this study was to examine the feasibility of an acupuncture intervention on a wide range of sensorimotor and mobility measurements in pwMS. Methods: Using a randomized crossover design, subjects experienced acupuncture or a no treatment control condition twice weekly for 4 weeks, followed by a 4-week washout period, and then crossed over to the other condition for 4 weeks. Strength, sensation, spasticity, gait, and balance were measured for all subjects, both before and after each condition. Results: Seven of the 12 subjects who started the program completed all phases. No subjects experienced adverse effects. No statistically significant changes were observed in the gait or balance measures. Small statistically significant changes were observed in upper extremity strength. Sensation and spasticity were unaffected. Discussion: The variability of MS suggests that a wide array of testing procedures be utilized, however, this may have led to difficulty with completing all phases of the study. Acupuncture did not result in changes in mobility in pwMS. Some improvements in upper extremity strength were observed. It is unclear whether these changes represent the effect of acupuncture or the inherent variability of MS.

Dopaminergic Receptor Targeting in Multiple Sclerosis: Is There Therapeutic Potential?

Dopamine is a neurotransmitter that mediates neuropsychological functions of the central nervous system (CNS). Recent studies have shown the modulatory effect of dopamine on the cells of innate and adaptive immune systems, including Th17 cells, which play a critical role in inflammatory diseases of the CNS. This article reviews the literature data on the role of dopamine in the regulation of neuroinflammation in multiple sclerosis (MS). The influence of dopaminergic receptor targeting on experimental autoimmune encephalomyelitis (EAE) and MS pathogenesis, as well as the therapeutic potential of dopaminergic drugs as add-on pathogenetic therapy of MS, is discussed.

Is Aerobic or Resistance Training the Most Effective Exercise Modality for Improving Lower Extremity Physical Function and Perceived Fatigue in People With Multiple Sclerosis? A Systematic Review and Meta-analysis.

OBJECTIVE: The purpose of this systematic review was to investigate whether aerobic training (AT) or resistance training (RT) is most effective in terms of improving lower limb physical function and perceived fatigue in persons with multiple sclerosis (PwMS). DATA SOURCES: Nine databases (MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health, Allied and Complementary Medicine Database, Physiotherapy Evidence Database, SPORTDiscus, PsycINFO, Web of Science, and Scopus) were electronically searched in April 2020. STUDY SELECTION: Included studies were randomized controlled trials (RCTs) involving PwMS attending 1 of 2 exercise interventions: AT or RT. Studies had to include at least 1 objective or self-reported outcome of lower extremity physical function and/or perceived fatigue. DATA EXTRACTION: Data were extracted using a customized spreadsheet, which included detailed information on patient characteristics, interventions, and outcomes. The methodological quality of the included studies was independently assessed by 2 reviewers using the Tool for Assessment of Study Quality for Reporting on Exercise rating scale. DATA SYNTHESIS: Twenty-seven articles reporting data from 22 RCTS (AT=14, RT=8) including 966 PwMS. The 2 modalities were found to be equally effective in terms of improving short walk test (AT: effect size [ES]=0.33 [95% confidence interval (CI), -1.49 to 2.06]; RT: ES=0.27 [95% CI, 0.07-0.47]) and long walk test performance (AT: ES=0.37 [95% CI, -0.04 to 0.78]; RT: ES=0.36 [95% CI, -0.35 to 1.08]), as well as in reducing perceived fatigue (AT: ES=-0.61 [95% CI, -1.10 to -0.11]; RT: ES=-0.41 [95% CI, -0.80 to -0.02]). Findings on other functional mobility tests along with self-reported walking performance were sparse and inconclusive. CONCLUSIONS: AT and RT appear equally highly effective in terms of improving lower extremity physical function and perceived fatigue in PwMS. Clinicians can thus use either modality to target impairments in these outcomes. In a future perspective, head-to-head exercise modality studies are warranted. Future MS exercise studies are further encouraged to adapt a consensus "core battery" of physical function tests to facilitate a detailed comparison of results across modalities.

Influence of Multiple Sclerosis on Spatiotemporal Gait Parameters: A Systematic Review and Meta-Regression.

OBJECTIVE: To quantify the effect of multiple sclerosis (MS) on spatiotemporal gait characteristics accounting for disability severity and fall classification. DATA SOURCES: MEDLINE (1946-August 2018), Allied and Complementary Medicine Database (1985-2018 August), and PsycINFO (1806-August 2018) were searched for terms on MS and gait. STUDY SELECTION: Dual independent screening was conducted to identify observational, cross-sectional studies that compared adults with MS grouped according to Expanded Disability Status Scale (EDSS) level or fall history, reported on spatiotemporal gait characteristics, and were published in English. The search retrieved 5891 results, of which 12 studies satisfied the inclusion criteria. DATA EXTRACTION: Two authors worked independently to extract and verify data on publication details, study methodology, participant characteristics, gait outcomes, conclusions, and limitations. Risk of bias was assessed using the QualSyst critical appraisal tool. A random-effects meta-regression and meta-analysis were conducted on pooled data. DATA SYNTHESIS: All studies received quality ratings of very good to excellent and collectively examined 1513 individuals with MS. With every 1-point increase in EDSS, significant changes (P<.05) were observed in gait speed (-0.12 m/s; 95% confidence interval (CI), 0.08-0.15), step length (-0.04 m; 95% CI, 0.03-0.05), step time (+0.04 seconds; 95% CI, 0.02-0.06), step time variability (+0.009 seconds; 95% CI, 0.003-0.016), stride time (+0.08 seconds; 95% CI, 0.03-0.12), cadence (-4.4 steps per minute; 95% CI, 2.3-6.4), stance phase duration (+0.8% gait cycle; 95% CI, 0.1-1.5), and double support time (+3.5% gait cycle; 95% CI, 1.5-5.4). Recent fallers exhibited an 18% (95% CI, 13%-23%) reduction in gait speed compared with nonfallers (P<.001). CONCLUSIONS: This review provides the most accurate reference values to-date that can be used to assess the effectiveness of MS gait training programs and therapeutic techniques for individuals who differ on disability severity and fall classification. Some gait adaptations could be part of adopting a more cautious gait strategy and should be factored into the design of future interventions.

Spatial constraints and cognitive fatigue affect motor imagery of walking in people with multiple sclerosis.

Motor imagery (MI) is the mental simulation of an action without any overt motor execution. Interestingly, a temporal coupling between durations of real and imagined movements, i.e., the so-called isochrony principle, has been demonstrated in healthy adults. On the contrary, anisochrony has frequently been reported in elderly subjects or those with neurological disease such as Parkinson disease or multiple sclerosis (MS). Here, we tested whether people with MS (PwMS) may have impaired MI when they imagined themselves walking on paths with different widths. When required to mentally simulate a walking movement along a constrained pathway, PwMS tended to overestimate mental movement duration with respect to actual movement duration. Interestingly, in line with previous evidence, cognitive fatigue was found to play a role in the MI of PwMS. These results suggest that investigating the relationship between cognitive fatigue and MI performances could be key to shedding new light on the motor representation of PwMS and providing critical insights into effective and tailored rehabilitative treatments.

Dietary supplementation with L-carnosine improves patient-reported outcomes, autonomic nervous system performance, and brain metabolism in 3 adult patients with multiple sclerosis.

This pilot trial reports the effects of L-carnosine administration on autonomic nervous system performance, brain metabolism, and various patient- and clinician-reported outcomes in a case series of patients with multiple sclerosis (MS). We hypothesized that medium-term L-carnosine supplementation would improve selected patient- and clinician-reported outcomes in MS patients, with no negative effects on self-reported side effects. L-carnosine (2 g/day) was administered orally for 8 weeks in 2 women and one man suffering from MS. The intensity of symptoms and signs of MS after L-carnosine administration diminished in 5 out of 7 domains in CASE 1, in 3 out of 7 domains in CASE 2, and one domain in CASE 3; general fatigue was reduced in all 3 cases at the follow-up. This was accompanied by an improved walking distance to exhaustion in all patients, with values improved for 51.1% in CASE 1, 19.5% in CASE 2, and 2.1% in CASE 3 at 8-week follow-up. Tests of autonomic cardiovascular reflexes demonstrate normalized parasympathetic modulation and balanced sympathetic function after L-carnosine intervention in all MS cases. An increase in serum total antioxidant capacity (TAC) was found at 8-week follow-up in all patients (from 4.6 to 49.6%); this was accompanied by lower blood lactate at post-administration in all cases (23.5% on average). Single-voxel 1.5 T MR spectroscopy revealed increased brain choline-contained compounds (18.9% on average), total creatine (21.2%), and myo-inositol levels (12.3%) in girus cinguli at 8-week follow-up in all MS cases. This case study demonstrates that an 8-week intervention with L-carnosine appears to be a safe and beneficial therapeutic strategy with regard to the reduction of presence and severity of symptoms of MS.

Marine n-3 polyunsaturated fatty acids: Efficacy on inflammatory-based disorders.

Inflammation is a physiological response to injury, stimulating tissue repair and regeneration. However, the presence of peculiar individual conditions can negatively perturb the resolution phase eventually leading to a state of low-grade systemic chronic inflammation, characterized by tissue and organ damages and increased susceptibility to non-communicable disease. Marine n-3 polyunsaturated fatty acids (n-3 PUFAs), mainly eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), are able to influence many aspects of this process. Experiments performed in various animal models of obesity, Alzheimer's disease and multiple sclerosis have demonstrated that n-3 PUFAs can modulate the basic mechanisms as well as the disease progression. This review describes the available data from experimental studies to the clinical trials.

Detrended fluctuation analysis of gait dynamics when entraining to music and metronomes at different tempi in persons with multiple sclerosis.

In persons with multiple sclerosis (PwMS), synchronizing walking to auditory stimuli such as to music and metronomes have been shown to be feasible, and positive clinical effects have been reported on step frequency and perception of fatigue. Yet, the dynamic interaction during the process of synchronization, such as the coupling of the steps to the beat intervals in music and metronomes, and at different tempi remain unknown. Understanding these interactions are clinically relevant, as it reflects the pattern of step intervals over time, known as gait dynamics. 28 PwMS and 29 healthy controls were instructed to walk to music and metronomes at 6 tempi (0-10% in increments of 2%). Detrended fluctuation analysis was applied to calculate the fractal statistical properties of the gait time-series to quantify gait dynamics by the outcome measure alpha. The results showed no group differences, but significantly higher alpha when walking to music compared to metronomes, and when walking to both stimuli at tempi + 8, + 10% compared to lower tempi. These observations suggest that the precision and adaptation gain differ during the coupling of the steps to beats in music compared to metronomes (continuous compared to discrete auditory structures) and at different tempi (different inter-beat-intervals).

Brain activation patterns of female multiple sclerosis patients with voiding dysfunction.

AIMS: We compared brain activation patterns between female multiple sclerosis (MS) patients with voiding dysfunction (VD) and those without. We aim to expand current knowledge of supraspinal correlates of voiding initiation within a cohort of female MS patients with and without VD. MATERIALS AND METHODS: Twenty-eight ambulatory female MS patients with stable disease and lower urinary tract dysfunction were recruited for this study. Subjects were divided into group 1, without VD (n = 14), and group 2, with VD (n = 14), defined as postvoid residual urine of ≥40% of maximum cystometric capacity or need for self-catheterization. We recorded brain activity via functional magnetic resonance imaging (fMRI) with simultaneous urodynamic testing. Average fMRI activation maps (the Student t test) were created for both groups, and areas of significant activation were identified (P < .05). A priori regions of interest (ROIs), identified by prior meta-analysis to be involved in voiding, were selected. RESULTS: Group-averaged blood-oxygen level-dependent (BOLD) activation maps demonstrated significant differences between groups 1 and 2 during initiation of voiding with group 2 showing significantly lower levels of activation in all ROIs except for the left cerebellum and right cingulate gyrus. Interestingly, group 2 displayed negative BOLD signals, while group 1 displayed positive signals in the right and left pontine micturition center, right periaqueductal gray, left thalamus, and left cingulate gyrus. The activation map of group 1 was similar to healthy controls. CONCLUSIONS: Our results support the hypothesis that distinct supraspinal activation patterns exist between female MS patients with VD and those without.

Is diet associated with physical capacity and fatigue in persons with multiple sclerosis? -Results from a pilot study.

BACKGROUND: Diet may have immunomodulatory effects in persons with multiple sclerosis (PwMS) and studies suggest that diet may be considered a complementary treatment to control the progression of the disease. The role of nutrition in MS and related symptoms have been reported by several studies but remains controversial. OBJECTIVE: To explore the association between dietary intake and physical capacity and fatigue in PwMS. METHODS: An explorative cross-sectional pilot study was conducted, in which 23 ambulatory PwMS were enrolled. Dietary intake was assessed using a 4-day food record. Outcome variables included a 6-Minute Walk Test (6MWT), a VO2max test, and self-reported questionnaires assessing fatigue severity (Fatigue Severity Scale, FSS) and impact (Modified Fatigue Impact Scale, MFIS). Associations between variables were determined using simple and multiple regression analyses. RESULTS: In the simple but not the multiple (adjusted for sex and age) regression analyses the carbohydrate intake (% of total energy intake) was positively associated with physical capacity (i.e. the 6MWT and VO2max test), whereas fat intake (% of total energy intake) was inversely associated with physical capacity. In the multiple regression analyses the absolute intake of ω-3 and vitamin D showed trends towards a positive association with the MFIS physical subscale and VO2max, respectively. CONCLUSION: Although not consistent across analyses, these findings suggest that better physical capacity most often is associated with a diet rich in carbohydrates and reduced fat content. Further research and randomized controlled trials are required to fully assess the role and the efficacy of diet quality and content on physical capacity in PwMS.

Gene Therapy with Single-Subunit Yeast NADH-Ubiquinone Oxidoreductase (NDI1) Improves the Visual Function in Experimental Autoimmune Encephalomyelitis (EAE) Mice Model of Multiple Sclerosis (MS).

Mitochondrial dysfunction mediated loss of respiration, oxidative stress, and loss of cellular homeostasis contributes to the neuronal and axonal degenerations permanent loss of function in experimental autoimmune encephalomyelitis model (EAE) of multiple sclerosis (MS). To address the mitochondrial dysfunction mediated visual loss in EAE mice, self-complementary adeno-associated virus (scAAV) containing the NADH-dehydrogenase type-2 (NDI1) complex I gene was intravitreally injected into the mice after the onset of visual defects. Visual function assessed by pattern electroretinogram (PERGs) showed progressive loss of function in EAE mice were improved significantly in NDI1 gene therapy-treated mice. Serial optical coherence tomography (OCT) revealed that progressive thinning of inner retinal layers in EAE mice was prevented upon NDI1 expression. The 45% optic nerve axonal and 33% retinal ganglion cell (RGC) loss contributed to the permanent loss of visual function in EAE mice were ameliorated by NDI1-mediated prevention of mitochondrial cristae dissolution and improved mitochondrial homeostasis. In conclusion, targeting the dysfunctional complex I using NDI1 gene can be an approach to address axonal and neuronal loss responsible for permanent disability in MS that is unaltered by current disease modifying drugs.

Functional neuroplasticity in response to cerebello-thalamic injury underpins the clinical presentation of tremor in multiple sclerosis.

BACKGROUND: Tremor is present in almost half of multiple sclerosis (MS) patients. The lack of understanding of its pathophysiology is hampering progress in development of treatments. OBJECTIVES: To clarify the structural and functional brain changes associated with the clinical phenotype of upper limb tremor in people with MS. METHODS: Fifteen healthy controls (46.1 ± 15.4 years), 27 MS participants without tremor (46.7 ± 11.6 years) and 42 with tremor (46.6 ± 11.5 years) were included. Tremor was quantified using the Bain score (0-10) for overall severity, handwriting and Archimedes spiral drawing. Functional magnetic resonance imaging activations were compared between participants groups during performance of a joystick task designed to isolate tremulous movement. Inflammation and atrophy of cerebello-thalamo-cortical brain structures were quantified. RESULTS: Tremor participants were found to have atrophy of the cerebellum and thalamus, and higher ipsilateral cerebellar lesion load compared to participants without tremor (p < 0.020). We found higher ipsilateral activation in the inferior parietal lobule, the premotor cortex and supplementary motor area in MS tremor participants compared to MS participants without tremor during the joystick task. Finally, stronger activation in those areas was associated with lower tremor severity. CONCLUSION: Subcortical neurodegeneration and inflammation along the cerebello-thalamo-cortical and cortical functional neuroplasticity contribute to the severity of tremor in MS.

Combined upper limb and breathing exercise programme for pain management in ambulatory and non-ambulatory multiple sclerosis individuals: part II analyses from feasibility study.

PURPOSE: The present small semi-controlled feasibility study investigated a possible efficacy of a combined upper limb and breathing exercise programme in managing pain in ambulatory and non-ambulatory patients with EDSS from 0.0-8.0. METHOD: People with MS (N = 19) were enrolled in this single-blind randomized controlled study and divided into 2 groups: exercise group (5 ambulatory, 5 non-ambulatory; Expanded Disability Status Scale (EDSS), 1.0-8.0) and related control group that performed no exercise (4 ambulatory, 5 non-ambulatory; EDSS, 1.0-7.5). The exercise group performed combined upper limb and breathing exercises in a group led by a physiotherapist (2 days/week, 60 min/session) accompanied by independent home exercises (3 days/week, ≥ 20 min/session). Participants underwent measures of pain level (visual analogue scale) for physical pain, functional independence of daily activities (Barthel index) and handgrip strength (HGS) for dominant (D) and non-dominant (ND) hand evaluated by a dynamometer before and after the 4-week period by the blinded assessor. RESULTS: The VAS for pain showed statistically significant group-by-time interaction only in non-ambulatory (p = .049) individuals, but with large intervention effects on both subgroups (ambulatory, p = .159; non-ambulatory, d = 0.97). Functional independence in daily activities (Barthel index) showed statistically non-significant group-by-time interaction in ambulatory (p = .195, d = 0.89) and non-ambulatory (p = .102, d = 1.64) individuals, but despite the absence of statistical significance, there were large intervention effects. Handgrip strength was significantly improved for both hands in ambulatory (D, p = .012; d = 2.07; ND, p = .025, d = 1.77) and only non-dominant hand in non-ambulatory individuals (D, p = .288, d = 0.83; ND, p = .012, d = 2.21). CONCLUSION: This small pilot study provides preliminary proof-of-concept data supporting low-intensity upper limb and breathing exercise programme for potential reduction of pain and improvement of functional independence in both ambulatory and non-ambulatory individuals with MS in a larger sample and that strengthening the upper limbs might be an additional pain relief mechanism. TRIAL REGISTRATION: NTC03222596.

Fatigue in multiple sclerosis: The role of thalamus.

Fatigue is very common in multiple sclerosis (MS) and is often considered as its most disabling symptom. Over the last 20 years, an increasing number of studies have evaluated the pathogenetic bases of MS-related fatigue. Converging evidence from neurophysiology and neuroimaging research suggests that a dysfunction in a cortico-subcortical pathway, centered on thalamus, is involved in the pathogenesis of fatigue. However, type and significance of such dysfunction remain unknown, and some studies reported an increase in the activity and connectivity within the thalamic network, whereas others suggested its reduction. Hereby, we review the results of neuroimaging studies supporting the different hypotheses about the role of thalamic network in the pathophysiology of MS-related fatigue and discuss limitations and shortcomings of available data, highlighting the key challenges in the field and the directions for future research.

Sensory nerve stimulation causes an immediate improvement in motor function of persons with multiple sclerosis: A pilot study.

BACKGROUND: Multiple sclerosis (MS) symptoms reported in the first year of the disease include sensory impairment, fatigue, reduced mobility, and declines in hand function. The progressive reduction in motor function experienced by persons living with MS is invariably preceded by changes in sensory processing, which are strongly associated with the declines in both walking performance and manual dexterity. AIMS: To assess the influence of concurrent sensory stimulation using augmented transcutaneous electrical nerve stimulation (aTENS) applied to leg and hand muscles on clinical tests of motor function in individuals whose mobility was compromised by MS. METHODS: Thirteen persons with MS (52 ±â€¯8 years; 6 women) and 12 age- and sex-matched healthy adults (52 ±â€¯9 years) met the inclusion criteria. Participants visited the lab on two occasions with one week between visits. Each visit involved the participant performing four tests of motor function and completing two health-related questionnaires (PDDS and MSWS-12). The tests assessed walking performance (6-min test and 25-ft test), dynamic balance (chair-rise tes, and manual dexterity (grooved pegboard test). aTENS was applied through pads attached to the limbs over the tibialis anterior and rectus femoris muscles of the affected leg, and over the median nerve and the thenar eminence of the dominant hand. The pads were attached during both visits, but the current was only applied during the second visit. The stimulation comprised continuous asymmetrical biphasic pulses (0.2 ms) at a rate of 50 Hz and an intensity that elicited slight muscle contractions. RESULTS: At baseline and during both treatment sessions, the performance on all four tests of motor function was worse for the MS group than the Control group. The MS group experienced significant improvements in all outcomes during the aTENS session with medium-to-large effect sizes. PDDS ratings improved (from 2.8 ±â€¯1.3 to 2.0 ±â€¯1.5; effect size d = -0.70) and the MSWS-12 scores declined (from 36 ±â€¯11 to 28 ±â€¯12; effect size d = -1.52). The concurrent application of aTENS enabled the MS group to walk further during the 6-min test (from 397 ±â€¯174 m to 415 ±â€¯172 m; effect size d = 0.81), to complete the 25-ft test in less time (6.7 ±â€¯3.0 s to 6.3 ±â€¯2.9 s; effect size d = -0.76), to increase the counts in the chair-rise test (from 11.2 ±â€¯3.8 to 13.6 ±â€¯4.8; effect size d = 1.52), and to perform the grooved pegboard test more quickly (from 110 ±â€¯43 s to 99 ±â€¯37 s; effect size d = -0.98). The only significant effect for the Control group was a significant increase in the 6-min walk distance (from 725 ±â€¯79 to 740 ±â€¯82 m; effect size d = 0.87). CONCLUSIONS: Stimulation of sensory fibers with aTENS evoked clinically significant improvements in four tests of motor function and the self-reported level of walking limitations in persons who were moderately disabled by MS. Moreover, the improvements in function elicited by the concurrent application of aTENS were immediate.

Mechanisms of pathophysiology of blood vessels in patients with multiple sclerosis treated with ozone therapy: a systematic review.

Multiple sclerosis (MS) defines as an intricate disease with numerous pathophysiological processes, including: inflammation, demyelination, oxidative stress, axonal damage, and repair mechanisms that interfere in this disease and highly related to the pathogenesis of MS. In parallel, recent studies have shown that the ozone administration could be very useful in treating neurological disorders and inflammatory and degenerative neurological diseases. In this review, we examine the recent literature on the pathophysiology of blood vessels in patients with multiple sclerosis treated with ozone therapy.