Exercise and Gait Retraining in Persons with Multiple Sclerosis

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Barbara S. Giesser, MD, Clinical Professor of Neurology, David Geffen UCLA School of Medicine, Los Angeles, California

Multiple sclerosis (MS) is a disease that invariably affects the ability to walk and move in a majority of patients. The ability to move may be affected by numerous impairments, including weakness, imbalance, fatigue, spasticity, and environmental conditions. Standard physical therapy and other rehabilitative techniques may improve function in these areas to some extent, but is not always successful. Another complimentary approach to the treatment of these impairments is therapeutic exercise, which is often, but not always, incorporated into physical therapy sessions. Standard physical therapy and other rehabilitative techniques are designed to improve function, but can have limitations secondary to availability, insurance reimbursement and therapists’ knowledge of MS. Emerging evidence is showing the therapeutic benefits of a regular exercise program for people with MS.

Can Persons With MS Tolerate Exercise?
Until recently, there was concern that persons with MS might be unable to tolerate aerobic exercise regimens, primarily because of their susceptibility to heat-related worsening of symptoms and also fatigue. There are now evidence-based data, however, showing that not only can persons with MS tolerate standard aerobic exercise, but that they can benefit from it (Rietberg, Brooks, Uitdehaag, & Kwakkel, 2004).

Most studies of the benefits of physical therapy in persons with MS have focused primarily upon functional outcomes. In contrast, the studies of exercise in the MS population have addressed more specific questions. These include the effects of exercise in improving specific deficits such as muscle weakness and fatigue, improvement in fitness parameters, and mood and quality of life. Studies indicate that persons with MS can show improvement in all of these areas by using a variety of training and exercise protocols (Ponichtera-Mulcare 1993; Sutherland & Andersen, 2001;White & Dressendorfer, 2004; Ponichtera, Matthews, & Barett, 1997; Oken, et al. 2004).

Effects of Exercise
In 1996, the seminal study of Petajan and colleagues conducted a randomized controlled trial of aerobic exercise in patients with mild to moderate MS. The treatment group participated in 15 weeks of supervised aerobic training. Compared to the non-treated control group, they exhibited significant improvements in muscle strength, fitness, serum fats profile, bladder and bowel function, and quality of life. Overall disability scores, as measured by Expanded Disability Status Scale (EDSS), were unchanged (Petajan, Gappmaier, & White 1996). Studies that have examined effects of exercise and resistance training in improving muscle strength in persons with MS include the study of Kraft and his colleagues. They used a progressive resistance training regimen and demonstrated improved muscle strength in upper and lower extremities (Kraft, Alquist, Lateur, 1996). White and colleagues reported that an 8-week progressive lower limb resistance training protocol improved leg strength and stepping ability (White et al., 2004). DeBolt and McCubbin used lower body resistance training in a home-based design and found that leg extensor power increased, but there was no change in balance or overall mobility (De Bolt & McCubbin, 2004). Rodgers and her group reported that their 6-month aerobic training regimen had little effect on gait parameters in subjects with MS (Rodgers et al., 1999).

More recently, researchers in Finland examined the effects of a 6-month exercise training program in persons with mild to moderate MS and found significant improvements in muscle strength and walking speed compared to a control group (Romberg, Virtanen, & Ruutianen, 2004). Furthermore, a group of Italian researchers demonstrated that aerobic training on an exercycle for three sessions/week for 8 weeks improved walking distance and speed, as well as fitness parameters in patients with mild to moderate MS, when compared to a neurorehabilitation intervention (Rampello et al. 2007). In patients with MS with moderate disability, functional improvement as measured on a specific disability scale was demonstrated after a 12-week aerobic exercise program by Kileff & Ashburn (Kileff & Ashburn, 2005). Importantly, none of the studies listed above found any adverse effects of any of the training regimens (i.e., there were no increases in symptoms of deterioration in usual level of function). Even the 4-week study of aerobic training in persons with MS by Mostert et al., which showed benefits in fitness and fatigue parameters, demonstrated only a 6% incidence of symptom exacerbation (Mostert & Kesselreing, 2002).

While the mechanisms of exercise induced improvement in MS remain to be elucidated, there are some data that suggest that they may influence cellular and immune parameters. Exercise has been shown to increase the levels of brain-derived neurotrophic factor (BDNF) and other nerve growth factors in normal adult rats (Gomez-Panilla, Ying, Roy, Rafaella, Edgerton, 2002). In the animal model of MS, experimental allergic encephalomyelitis (EAE), regular exercise was shown to delay disease onset and duration in rats, compared to non-exercised controls (Gomez-Panilla, Ying, & Roy 1994). In persons with MS who participated in a standard aerobic exercise protocol, levels of BDNF were increased post exercise (Gold et al., 2003). These reports may have implications for exercise as a possible therapeutic or neuroprotective strategy for the underlying causes of nerve damage in MS, in addition to being a rehabilitative modality.

A large part of current rehabilitative strategies are to apply compensatory mechanisms to improve function. Ideally, more effective therapies could address and alter underlying impairment as well. Such therapies would exploit and/or enhance the nervous system’s capacity for plasticity and repair. One such approach is locomotor training (LT) using body weight support on a treadmill.

Locomotor Training
Walking is an effective exercise, but persons with inadequate leg strength and/or coordination can’t walk for distances needed for exercise. For these individuals, gait retraining is necessary, with one method being LT on a treadmill with body weight support. This is a new rehabilitative approach based on principles that promote the movement of the limbs and trunk to generate sensory information consistent with locomotion to improve the potential for the recovery of walking after neurologic injury (Barbeau, Wainberg, & Finch, 1987; Behrman & Harkema, 2000; Finch, Barbeau, & Arsenalut, 1991; Visinitin & Barbeau, 1989; Visintin & Barbeau, 1994). During step training the individual is suspended in a harness by an overhead support system over a treadmill. Body weight support (BWST)systems provide an environment in which one can facilitate balance control and manually or robotically assist trunk and leg movements during weight bearing stepping and standing. Locomotor training principles are followed to maximize task specific sensory stimulation that matches the movement patterns of walking.

An important emerging concept in retraining neurologically-impaired individuals to walk is the concept of task specificity. Rehabilitation paradigms in both animal and human studies indicate that functional outcomes improve when a specific task is repeatedly practiced, rather than non-specific interventions. An early study of patients with stroke demonstrated better functional gains in walking when task specific therapy was started early after injury, compared to traditional non-specific therapy interventions (Richards et al., 1993). This may explain why many of the studies of standard, non-task specific rehabilitative or exercise modalities in patients with MS may produce improvement in parameters such as muscle strength or fatigue, without producing functional gains in ambulation or measures of disability. LT emphasizes task specificity with respect to walking.

It has been shown that after severe spinal cord injury (SCI) individuals can generate standing and stepping patterns when provided with body weight support on a treadmill (BWST) and manual assistance (Harkema, Dobkin, & Edgerton, 2000). Many studies have demonstrated that LT using BWST improved the ability to walk in patients with SCI (Visinitin & Barbeau, 1989; Wernig & Muller, 1992; Wernig, Muller, Namassy, & Gagol, 1995; Barbeau, Danakas, & Arsenault 1993; Dobkin, Harkema, Requejo, & Edgerton, 1995; Protas, et al., 2001; Field-Fote, 2001).

Why Apply LT to an MS Population?
Patients with primarily spinal forms of MS clinically resemble individuals who have suffered an incomplete SCI in that both groups exhibit weakness in the extremities, spasticity, hyperreflexia, and loss of sensation, all of which can interfere with effective mobility. It is reasonable then to consider the application of therapeutic modalities that have been shown to benefit patients with SCI in terms of improving impairment and disability with respect to mobility to a selected MS population. The studies cited demonstrate the potential benefits of LT in the SCI population, but further randomized clinical trials are needed.

A pilot study conducted asked whether persons with MS could tolerate and would benefit from LT (Giesser, Beres Jones, Budovitch, Helihy, & Harkema, 2007). Four patients with MS and severe functional limitations in walking received an average of 40 sessions of locomotor training using manual LT facilitation. At the end of training, all subjects showed improvement in muscle strength, and 3 out of 4 subjects improved in balance, spasticity, endurance, and quality of life. All subjects tolerated the training well without incurring fatigue or interference with their usual daily activities. A larger trial funded by the National MS Society using a robot to provide the locomotor training and a resistive exercise group as a control, is currently in progress.

In addition to improvements at a functional level, exercise may have benefits at a tissue level as well, and may promote change in the brain. At least one study has reported that task specific training in persons with MS results in different brain activation patterns before and after training compared to controls, indicating the utility of fMRI in assessing cortical changes induced by rehabilitative intervention (Morgen et al., 2004).

In summary, a body of evidence accumulated over the past decade or two shows that persons with MS at various stages of disability can tolerate and benefit from exercise training as demonstrated by improvements at functional, neurological, tissue, and molecular levels.


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