Let’s Get Moving: A Multidisciplinary Approach to Gait Rehabilitation in Multiple Sclerosis

Publication
Article
NeurologyLiveFebruary 2023
Volume 6
Issue 1

Current research pushes to advance therapeutic possibilities and understand underlying neural mechanisms for gait impairments in individuals with the disease.

Jordan Acosta, MS, Graduate student, Health and Exercise Science, College of Health and Human Sciences, Colorado State University, Fort Collins, CO

Jordan Acosta, MS

Brett Fling, PhD, MS, Associate professor and director, Sensorimotor Neuroimaging Laboratory, Health and Exercise Science, College of Health and Human Sciences, Colorado State University, Fort Collins, CO

Brett Fling, PhD, MS

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.

Gait Asymmetry

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

(Click to enlarge)

FIGURE 1. Phases of the human gait cycle in neurotypical individuals

Adapted from Cicirelli et al, 2021.15

(Click to enlarge)

FIGURE 1. Phases of the human gait cycle in neurotypical individuals

Adapted from Cicirelli et al, 2021.15

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).

Neural Mechanisms

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

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FIGURE 2. Transcallosal Fiber Tract Degradation

Ongoing, novel research suggests the degradation of transcallosal fiber tract is a significant contributor to the increases in gait asymmetries in individuals with MS.

Adapted from Richmond and Fling, 2019.9

(Click to enlarge)

FIGURE 2. Transcallosal Fiber Tract Degradation

Ongoing, novel research suggests the degradation of transcallosal fiber tract is a significant contributor to the increases in gait asymmetries in individuals with MS.

Adapted from Richmond and Fling, 2019.9

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.

Multidisciplinary Rehabilitation Potential

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.

(Click to enlarge)

FIGURE 3. Transcranial Magnetic Stimulation and Split-belt Treadmill Training

Images taken at the Sensorimotor Neuroimaging Laboratory at Colorado State University, run by Brett Fling, PhD, MS. Participants with MS undergo (A) transcranial magnetic stimulation and (B) a split-belt treadmill training paradigm.

(Click to enlarge)

FIGURE 3. Transcranial Magnetic Stimulation and Split-belt Treadmill Training

Images taken at the Sensorimotor Neuroimaging Laboratory at Colorado State University, run by Brett Fling, PhD, MS. Participants with MS undergo (A) transcranial magnetic stimulation and (B) a split-belt treadmill training paradigm.

Moving Forward

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.

REFERENCES
  1. Bobryk P. Physical therapy approach for fatigue management in multiple sclerosis. NeurologyLive®. November 22, 2022. Accessed January 2, 2023. https://www.neurologylive.com/view/ physical-therapy-approach-for-fatigue-management-in-multiple-sclerosis
  2. Kalb R, Brown TR, Coote S, et al. Exercise and lifestyle physical activity recommendations for people with multiple sclerosis throughout the disease course. Mult Scler. 2020;26(12):1459-1469. doi:10.1177/1352458520915629
  3. Kinnett-Hopkins D, Adamson B, Rougeau K, Motl RW. People with MS are less physically active than healthy controls but as active as those with other chronic diseases: an updated meta-analysis. Mult Scler Relat Disord. 2017;13:38-43. doi:10.1016/j.msard.2017.01.016
  4. Motl RW, McAuley E, Snook EM. Physical activity and multiple sclerosis: a meta-analysis. Mult Scler. 2005;11(4):459-463. doi:10.1191/1352458505ms1188oa
  5. Confavreux C, Vukusic S, Moreau T, Adeleine P. Relapses and progression of disability in multiple sclerosis. N Engl J Med. 2000;343(20):1430-1438. doi:10.1056/NEJM200011163432001
  6. Platts MM, Rafferty D, Paul L. Metabolic cost of over ground gait in younger stroke patients and healthy controls. Med Sci Sports Exerc. 2006;38(6):1041-1046. doi:10.1249/01.mss.0000222829.34111.9c
  7. Stoquart G, Detrembleur C, Lejeune TM. The reasons why stroke patients expend so much energy to walk slowly. Gait Posture. 2012;36(3):409-413. doi:10.1016/j.gaitpost.2012.03.019
  8. Finley JM, Bastian AJ. Associations between foot placement asymmetries and metabolic cost of transport in hemiparetic gait. Neurorehabil Neural Repair. 2017;31(2):168-177. doi:10.1177/1545968316675428
  9. Richmond SB, Fling BW. Transcallosal control of bilateral actions. Exerc Sport Sci Rev. 2019;47(4):251-257. doi:10.1249/JES.0000000000000202
  10. Benedetti MG, Piperno R, Simoncini L, Bonato P, Tonini A, Giannini S. Gait abnormalities in minimally impaired multiple sclerosis patients. Mult Scler. 1999;5(5):363-368. doi:10.1177/135245859900500510
  11. Holden MK, Gill KM, Magliozzi MR, Nathan J, Piehl-Baker L. Clinical gait assessment in the neurologically impaired. Reliability and meaningfulness. Phys Ther. 1984;64(1):35-40. doi:10.1093/ptj/64.1.35
  12. Rodgers MM, Mulcare JA, King DL, Mathews T, Gupta SC, Glaser RM. Gait characteristics of individuals with multiple sclerosis before and after a 6-month aerobic training program. J Rehabil Res Dev. 1999;36(3):183-188.
  13. Syndulko K, Ke D, Ellison GW, Baumhefner RW, Myers LW, Tourtellotte WW. Comparative evaluations of neuroperformance and clinical outcome assessments in chronic progressive multiple sclerosis: I. reliability, validity and sensitivity to disease progression. Multiple Sclerosis Study Group. Mult Scler. 1996;2(3):142-156. doi:10.1177/135245859600200305
  14. Coca-Tapia M, Cuesta-Gómez A, Molina-Rueda F, Carratalá-Tejada M. Gait pattern in people with multiple sclerosis: a systematic review. Diagnostics (Basel). 2021;11(4):584. doi:10.3390/diagnostics11040584
  15. Cicirelli G, Impedovo D, Dentamaro V, Marani R, Pirlo G, D’Orazio TR. Human gait analysis in neurodegenerative diseases: a review. IEEE J Biomed Health Inform. 2022;26(1):229-242. doi:10.1109/JBHI.2021.3092875
  16. Sohn YH, Jung HY, Kaelin-Lang A, Hallett M. Excitability of the ipsilateral motor cortex during phasic voluntary hand movement. Exp Brain Res. 2003;148(2):176-185. doi:10.1007/s00221-002-1292-5
  17. Stinear CM, Byblow WD. Role of intracortical inhibition in selective hand muscle activation. J Neurophysiol. 2003;89(4):2014-2020. doi:10.1152/jn.00925.2002
  18. Fling BW, Seidler RD. Fundamental differences in callosal structure, neurophysiologic function, and bimanual control in young and older adults. Cereb Cortex. 2012;22(11):2643-2652. doi:10.1093/cercor/bhr349
  19. Wahl M, Hübers A, Lauterbach-Soon B, et al. Motor callosal disconnection in early relapsing-remitting multiple sclerosis. Hum Brain Mapp. 2011;32(6):846-855. doi:10.1002/hbm.21071
  20. Boroojerdi B, Hungs M, Mull M, Töpper R, Noth J. Interhemispheric inhibition in patients with multiple sclerosis. Electroencephalogr Clin Neurophysiol. 1998;109(3):230-237. doi:10.1016/s0924-980x(98)00013-7
  21. Bonzano L, Tacchino A, Roccatagliata L, Abbruzzese G, Mancardi GL, Bove M. Callosal contributions to simultaneous bimanual finger movements. J Neurosci. 2008;28(12):3227-3233. doi:10.1523/ JNEUROSCI.4076-07.2008
  22. Schmierer K, Irlbacher K, Grosse P, Röricht S, Meyer B-U. Correlates of disability in multiple sclerosis detected by transcranial magnetic stimulation. Neurology. 2002;59(8):1218-1224. doi:10.1212/wnl.59.8.1218
  23. Reisman DS, Wityk R, Silver K, Bastian AJ. Locomotor adaptation on a split-belt treadmill can improve walking symmetry post-stroke. Brain. 2007;130(pt 7):1861-1872. doi:10.1093/brain/awm035
  24. Fasano A, Schlenstedt C, Herzog J, et al. Split-belt locomotion in Parkinson’s disease links asymmetry, dyscoordination and sequence effect. Gait Posture. 2016;48:6-12. doi:10.1016/j.gaitpost.2016.04.020
  25. Nguemeni C, Hiew S, Kögler S, Homola GA, Volkmann J, Zeller D. Split-belt training but not cerebellar anodal tDCS improves stability control and reduces risk of fall in patients with multiple sclerosis. Brain Sci. 2021;12(1):63. doi:10.3390/brainsci12010063
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