Effects of Supervised Progressive Resistance Training on Central Nervous System Functioning (Corticospinal Excitability) and Walking Capacity in Persons With Multiple Sclerosis

Brief Summary

Detailed Description

Neurodegeneration is a hallmark of multiple sclerosis (MS), affecting both structure and function of the central nervous system (CNS). Neurodegeneration is the main driver of disability progression in MS, evidenced by studies showing deleterious structural and functional CNS changes, ultimately reducing quality of life. Consequently, the interaction between the nervous system and muscular system undergoes deleterious changes causing reduced neuromuscular function (i.e., ability to develop muscle strength and power) and physical function. The functional CNS changes have been evidenced by using the non invasive brain stimulation technique Transcranial Magnetic Stimulation, showing decreased corticospinal excitability alongside increased central motor conduction time. Moreover, functional peripheral nervous system (PNS) changes have been evidenced by nerve conduction methods, revealing decreased amplitude of compound muscle action potential and increased latency of nerve signaling. In an ongoing exploratory study (unpublished), the investigators have observed that functional CNS and PNS outcomes deteriorate with disability progression from healthy to mildly to moderately disabled people with MS (PwMS). Exercise is beneficial from both an individual and a societal perspective, and has proven to be both safe and without any noticeable side effects in PwMS. Resistance training (RT) appears particularly effective in improving neuromuscular function (mainly muscle strength) and physical function (especially walking capacity). Whilst RT and other exercise modalities may elicit positive effects on CNS structure in PwMS, it seems to require a long-term (≥ 6 months) exposure. In contrast, CNS (and potentially PNS) function may adapt much more rapidly, despite a scarcity of studies (and with heterogeneous findings) involving PwMS. Interestingly, an exploratory exercise study (non-controlled, low sample size, 10 weeks treadmill walking intervention) assessed corticospinal excitability in PwMS, and observed substantial improvements after the intervention. Apart from this study, a major knowledge gap exists in terms of elucidating the potential beneficial effects of exercise (RT in particular) on CNS (and PNS) function. Based on evidence from healthy young individuals, substantial improvements in corticospinal excitability have been shown following 2-12 weeks of RT, supporting that RT-induced improvements in corticospinal excitability can also be seen in PwMS. Lastly, as existing exercise guidelines for PwMS fails to refer to evidence on dose-response to exercise, and a recent systematic review on exercise studies found no dose-response studies in PwMS (n=202), this aspect is also of great clinical relevance.

Primary Outcomes

Secondary Outcomes

• Voluntary activation II(Change from Baseline to 10 weeks)
• Voluntary activation I(Change from Baseline to 10 weeks)
• MEP amplitude (active)(Change from Baseline to 10 weeks)
• Ultrasound(Change from Baseline to 10 weeks)
• Resting Motor Threshold (rMT)(Change from Baseline to 10 weeks)
• Short-interval intracortical Inhibition (SICI)(Change from Baseline to 10 weeks)
• Central Motor Conduction Time (CMCT)(Change from Baseline to 10 weeks)
• Six spot step test (SSST)(Change from Baseline to 10 weeks)
• Muscle strength(Change from Baseline to 10 weeks)
• Rate of Force Developement(Change from Baseline to 10 weeks)
• MEP latency (active)(Change from Baseline to 10 weeks)
• Cortical Silent Period (CSP)(Change from Baseline to 10 weeks)
• 5 sit-to-stand (5STS)(Change from Baseline to 10 weeks)
• 9-step stair ascend (9SSA)(Change from Baseline to 10 weeks)
• The Physical Activity Enjoyment Scale (PACES)(Change from Baseline to 10 weeks)
• Force Steadiness(Change from Baseline to 10 weeks)
• MEP latency (resting)(Change from Baseline to 10 weeks)
• MEP amplitude (resting)(Change from Baseline to 10 weeks)
• Timed 25 feet walk test (T25FWT)(Change from Baseline to 10 weeks)
• MS impact scale (MSIS)(Change from Baseline to 10 weeks)
• Active Motor Threshold (aMT)(Change from Baseline to 10 weeks)
• 6-minute walk test (6MWT)(Change from Baseline to 10 weeks)
• Multiple Sclerosis Walking Scale (MSWS)(Change from Baseline to 10 weeks)
• Intracortical facilitation (ICF)(Change from Baseline to 10 weeks)
• EEG-EMG coherence (0-1)(Change from Baseline to 10 weeks)
• Modified fatigue impact scale (MFIS)(Change from Baseline to 10 weeks)
• Brief pain inventory (BPI)(Change from Baseline to 10 weeks)
• Accelerometry(Change from Baseline to 10 weeks)
• Patient determined disease steps (PDDS)(Change from Baseline to 10 weeks)
• Falls-efficacy scale - international (FES-1)(Change from Baseline to 10 weeks)
• Baecke physical activity(Change from Baseline to 10 weeks)