Current research pushes to advance therapeutic possibilities and understand underlying neural mechanisms for gait impairments in individuals with the disease.
REGULAR AEROBIC AND RESISTANCE TRAINING have been shown to increase cardiorespiratory fitness, enhance muscle strength and endurance, reduce fatigue, improve mood, and boost ability to perform daily tasks.1 Therefore, a large body of research within the field of multiple sclerosis (MS) aims to understand how exercise impacts overall brain health and progression of the disease. In 2020, the National Multiple Sclerosis Society released recommendations for exercise guidelines utilizing the Expanded Disability Status Scale and addressed barriers to participation for individuals with MS.2 However, despite these recommendations and recorded benefits, individuals with MS are much less likely to engage in physical activity than those without the disease.3,4 Therefore, our group is investigating how to improve mobility in those with MS, while identifying the neural mechanisms that serve as potential contributors to a lack of physical activity observed in individuals with MS.
Impaired walking ability is a common ailment in individuals with MS, with more than 50% requiring mobility assistance within 18 years of diagnosis.5 The majority of individuals with MS report significant asymmetries in strength and function between the legs, resulting in reduced coordination during gait. Previous research on those living with Parkinson disease or recovering from a stroke highlighted the association of this locomotive impairment with increased metabolic cost, postural instability, falls, and reduced quality of life.6-8 However, this limitation and its impacts have only recently begun to be adequately quantified in those with MS.9
Because of the individualization of the disease, there is a varying spectrum and pattern of mobility limitations within MS. However, it has been well documented that patients with MS typically walk slower, with a shorter stride and more prolonged double support phase than individuals without the disease.10-12 This is likely a compensation for deficits in balance and postural control.13 A systemic review by Coca-Tapia et al in 2021 analyzed several previous studies utilizing 3-dimensional motion capture to enhance understanding of the biomechanics within gait abnormalities in MS.14 The findings suggest that “people with MS have a decrease in speed and stride length, as well as an increase in double-stance intervals during gait. Likewise, it is common to observe a decrease in hip extension during the stance period, a decrease in knee flexion in the swing period, a decrease in ankle dorsiflexion in the initial contact and a decrease in ankle plantar flexion during the [preswing] phase.”14
The occurrence of these gait abnormalities can result in balance difficulties, joint discomfort, fatigue, and pain. Therefore, we must understand these mobility limitations as a potential barrier to participation in physical activity and exercise for individuals with MS (FIGURE 115).
Furthering our understanding of the underlying neurophysiology changes that accompany MS may be an effective strategy to provide a correlation to the known mobility and gait impairments in individuals with MS. A growing body of research is investigating the underlying neural mechanisms associated with mobility asymmetries in individuals with MS; although the exact pathophysiology is not well understood due to the unique and individualized pathology of the disease, recent findings suggest the altered and damaged structure of the corpus callosum may play a part in reduced coordination (FIGURE 2).9 The corpus callosum is the largest white matter fiber bundle in the human nervous system and consists of white matter tracts that connect the right and left hemispheres of the brain. Interhemispheric communication via the corpus callosum plays a pivotal role in the production of integrated motor behavior to generate appropriate and coordinated motor responses on both sides of the body.9
The 2 cortices are highly interconnected via the corpus callosum, allowing for interhemispheric transfer of information. For motor behaviors requiring precise temporal and spatial coordination between both sides of the body (eg, walking), movement of 1 limb has an overall inhibitory effect on the ipsilateral motor cortex.16,17 Reduced structural connectivity of the corpus callosum is common in individuals with MS, even in the absence of lesions within that structure,18,19 and a small but promising body of literature demonstrates individuals with MS also exhibit reduced interhemispheric inhibition between the primary motor cortices compared with age-matched controls.20 Moreover, reduced callosal structure and inhibitory capacity have been directly related to reduced, poorer manual control and greater motor-related disease severity in individuals with MS.21,22 Research in this field is investigating transcallosal structure as an integral neural mechanism underlying control of the lower limbs, which may identify callosal degradation as a key contributor to mobility declines in persons with MS.
Understanding the pathways and interconnectedness of the hemispheres is crucial for coordination as well as highlighting impairments in gait and balance for several neurodegenerative diseases.16,18,20 The current research investigating neural mechanisms occurring in individuals with MS provides specific direction toward rehabilitation strategies aimed at alleviating gait asymmetries.
In efforts to engage more individuals with MS in physical activity and exercise, we must place a priority on alleviating the unique barriers they face. Specifically, focusing on reducing gait asymmetry may help promote independence and increase quality of life of patients with MS.15 However, a multifaceted approach is necessary due to the intricate and complex underlying neural mechanisms responsible for coordination. Novel studies are pairing brain imaging and stimulation in combination with treadmill training and mobility metrics. The merging of these research fields allows for analysis of not only biomechanics of existing gait impairments, but also the neurophysiology to identify more targeted and specialized rehabilitation opportunities.
One of the emerging mobility tools being utilized is a split-belt treadmill where each belt is controlled independently. Previous studies utilizing this treadmill training have shown promising results in reducing gait asymmetry in those living with the effects of stroke23 or Parkinson disease.24 However, this tool has not been utilized for individuals with MS until recently. New studies are strategically pairing split-belt treadmill training with differing brain imaging and stimulation to highlight neural pathways that may be impaired, and they subsequently may hold the key to accelerating gait rehabilitation (FIGURE 3).25 We anticipate a breadth of deeper understanding regarding the neural mechanisms and therapeutic gait possibilities from these novel and ongoing studies.
With the potential of new and impactful findings from research pairing biomechanics and neurophysiology, the outlook for specialized rehabilitation protocols for individuals with MS is promising. Understanding not only the gait impairments but also the neural mechanisms underlying mobility challenges provides insight into the unique barriers faced by patients with MS. As stated, there has been insightful evidence for the benefits of exercise and physical activity for patients with neurodegenerative disease. However, there are several layers to the lack of exercise participation that we must recognize and advance our research toward alleviating. By tending to the mobility impairments and gait asymmetry prevalent in MS, we can begin to stratify individuals to appropriate rehabilitation paradigms. Further discernment of neurological pathways necessary for coordination of bilateral movements, along with stimulation efforts to amplify training effects, can provide more individualized therapeutic benefits for the patient. By utilizing a multidisciplinary approach to research the neural control of mobility in individuals with MS, we can work toward engaging more individuals in exercise as the barriers to participation are lifted.