Rehabilitation Improves Mitochondrial Energetics in Progressive Multiple Sclerosis: The Significant Role of Robot-Assisted Gait Training and of the Personalized Intensity

Abstract

Abnormal levels of pyruvate and lactate were reported in multiple sclerosis (MS). We studied the response of markers of mitochondrial function to rehabilitation in relation to type, intensity and endurance performance in severely disabled MS patients. Forty-six progressive MS patients were randomized to receive 12 walking sessions of robot-assisted gait training (RAGT, n = 23) or conventional overground therapy (CT, n = 23). Ten healthy subjects were also studied. Blood samples were collected to determine lactate, pyruvate, and glutathione levels and lactate/pyruvate ratio pre–post rehabilitation. In vivo muscle metabolism and endurance walking capacity were assessed by resting muscle oxygen consumption (rmVO2) using near-infrared spectroscopy and by six-minute walking distance (6MWD), respectively. The levels of mitochondrial biomarkers and rmVO2, altered at baseline with respect to healthy subjects, improved after rehabilitation in the whole population. In the two groups, an enhanced response was observed after RAGT compared to CT for lactate (p = 0.012), glutathione (<0.001), lactate/pyruvate ratio (p = 0.08) and rmVO2 (p = 0.07). Metabolic biomarkers and 6MWD improvements were exclusively correlated with a training speed markedly below individual gait speed. In severely disabled MS patients, rehabilitation rebalanced altered serum metabolic and muscle parameters, with RAGT being more effective than CT. A determinable slow training speed was associated with better metabolic and functional recovery. Trial Registration: ClinicalTrials.gov NCT02421731.

Effectiveness of Dry Needling versus Placebo on Gait Performance, Spasticity, Electromyographic Activity, Pain, Range-of-Movement and Quality of Life in Patients with Multiple Sclerosis: A Randomized Controlled Trial Protocol

“…The clinical management of MS-related disorders includes pharmacological and non-pharmacological interventions. In severely disabled patients, rehabilitation aims to rebalance the altered metabolic and muscle parameters [ 11 ], and the main goal is to improve functional independence and QOL [ 12 ]. Overall, physiotherapy treatments can be categorized into four domains: physical training (fitness, endurance, or resistance training), neuroproprioceptive facilitation or inhibition, motor skill acquisition, also called guided individualized therapy, and technology-based interventions [ 13 ].…”

Motor Cortical Activation Assessment in Progressive Multiple Sclerosis Patients Enrolled in Gait Rehabilitation: A Secondary Analysis of the RAGTIME Trial Assisted by Functional Near-Infrared Spectroscopy

“…Yang and Dunn hypothesized that StO 2 may reflect a change in the pattern of supply and demand of oxygen delivery, and indirectly, of the level of inflammation [21]. Differences in StO 2 were observed in different MS subtypes, as well as reduced blood flow accompanied by local hypoxia [51]; further confirmation was found in the form of high peripheral lactate levels, possibly linked to a systemic hypoxic state [34]. Therefore, the hyperactivation observed in the dynamic state may represent a compensatory response, particularly evident in patients with a more severe disability or a shorter duration of disease.…”

“…Relative training intensity was calculated as the ratio of the subject's average speed during the training sessions to the gait speed measured using the timed 25-foot walk test at baseline or the highest speed theoretically attainable by that subject [34]. For the RAGT group, the value obtained was corrected for body weight support (e.g., for 50% of body weight support, the value was multiplied by 0.50).…”

“…For the RAGT group, the value obtained was corrected for body weight support (e.g., for 50% of body weight support, the value was multiplied by 0.50). Training intensity was categorized as high or low for each treatment according to a two-quantile distribution, with the median as the cutoff [34].…”

Vascular Biomarkers: Physics Parameters and Circulating Molecules Can Be Two Faces of the Same Coin

“…Manfredini and co-workers, by using the term “training prescription”, permit readers to understand how in the future of patients, especially with co-existing vascular problems, exercise intensity and modality needs more science behind it in order to transform the training into a powerful drug. More precisely, mitochondrial biomarkers demonstrated the superiority of personalized gait training in respect to exaggerated exercise training prescribed in primary progressive MS patients [ 13 ].…”