Exercise-Based Interventions
Several systematic reviews have documented fitness, health and subjective well-being benefits of routine physical activity participation for adults with SCI (Neefkes-Zonneveld et al. 2015; Tomasone et al. 2013; van der Scheer et al. 2017; Martin-Ginis et al. 2009). Specifically, exercise guidelines for adults with SCI have been established to improve cardiorespiratory fitness and muscle strength (Martin-Ginis et al. 2018). However, no systematic reviews about the effects or benefits of physical activity or exercise for fatigue have been done on people with SCI. Although individualized and regular exercise therapy or physical activity and cognitive behavioral therapy are usually recommended for the management of fatigue in the general population (Rosenthal et al. 2008; Dukes et al. 2021).
Discussion
Exercise-based intervention studies that assessed fatigue outcomes in people with SCI included a moderate-intensity arm-crank home exercise program (Nightingale et al. 2018), a virtual reality exercise program (Jorjafaki et al. 2022), a hybrid (FES-leg cycling combined with arm ski ergometer) high-intensity interval training (HIIT) protocol (Vestergaard et al. 2022), a seated Tai Chi Chih program (Shem et al. 2016), and a modified Yoga program (Curtis et al. 2015).
Virtual Reality Exercise-based Interventions
The most recent RCT by Jorjafaki et al. (2022) divided 45 veterans with chronic paraplegia who were experiencing fatigue into an upper limb virtual reality exercise-based program (through virtual reality games), a reflexology program, or a control group (Jorjafaki et al. 2022). For the exercise condition, sessions lasted 50 min and were performed three times per week (Jorjafaki et al. 2022). After six weeks, both experimental interventions provided a significant effect on fatigue compared to the control condition, but without differences between the experimental interventions (Jorjafaki et al. 2022).
Although virtual reality is being studied extensively in other areas, few studies have assessed fatigue. One concurrent nested mixed-methods design with 11 participants with chronic SCI and pain showed that fatigue and pain were immediately reduced after one six-minute exercise test using arm ergometry if the session was performed with virtual reality than without virtual reality (Azurdia et al. 2022). In other clinical populations, such as patients with hemodialysis and end-stage renal failure, the prospective control group by Cho & Sohng (2014) assessed the effects of a virtual reality exercise program using Nintendo’s Wii Fit Plus for 40 minutes, three times a week for eight weeks. The experimental intervention was performed while waiting for dialyses and the control intervention consisted of receiving only the usual care (Cho & Sohng 2014). After the program intervention, only the experimental group showed a significant decrease in fatigue and a significant increase in physical fitness and body composition (Cho & Sohng 2014). Contrary to these positive results on fatigue, regarding patients with multiple sclerosis, the prospective cohort multicenter study by Saladino et al. (2023) did not observe differences in fatigue after a 12-week institutional virtual reality exergames program.
Home-Based Exercise Intervention at Moderate Intensity
The RCT of Nightingale et al. (2018) randomly divided 21 non-physically active participants with chronic paraplegia to receive a home-based exercise intervention with arm-crank or to maintain their habitual physical activity behavior. Sessions were performed four times a week for 45 minutes each at the participant’s homes, and the intensity was set to moderate intensity (60%-65% VO2 peak). After six weeks of the intervention, the change of the fatigue severity (measured by the FSS) was significantly different between groups, with a significant reduction in the intervention group, with a large effect: Cohen d (90% CI) = -0.99 (-1.75, -0.22); meanwhile global fatigue (measured by the VAS) did not significantly change between or within-groups (Nightingale et al. 2018). Significant positive results were also shown in terms of changes in health-related quality of life outcomes (e.g. physical component scores of the SF-36), exercise self-efficacy, physical activity, and fitness; favoring the intervention group with moderate to large effect sizes (d = 0.62-1.37) (Nightingale et al. 2018).
This RCT was also able to investigate the relationship between change scores in objective markers of moderate-to-vigorous physical activity and cardiorespiratory fitness with changes in indices of physical and psychological quality of life (Nightingale et al. 2018). It was revealed that both moderate-to-vigorous physical activity and cardiorespiratory fitness were significantly negatively associated with fatigue severity. Cardiorespiratory fitness was positively related to physical and mental component scores of health-related quality of life and global fatigue, and moderate-to-vigorous physical activity was positively associated with quality adjusted life years, but not with exercise self-efficacy (Nightingale et al. 2018). According to the authors, these relationships supported the argument that the intervention-induced changes in moderate-to-vigorous physical activity and cardiorespiratory fitness had a positive effect on participants’ physical and psychological quality of life. On the other hand, this study was the only one included in this chapter which provided the exercise program in a home environment (Nightingale et al. 2018). This should be of interest, especially considering that the lack of access to gym facilities and exercise equipment, as well as poor information and support, have been identified as key barriers to exercise for adults with SCI (Fekete & Rauch 2012; Stephens et al. 2012; Williams et al. 2014).
The results of the RCT by Nightingale et al. (2018) are in line with the recommendations of exercise prescription for patients with multiple sclerosis, where low to moderate-intensity exercise is recommended for the improvement of fatigue (Halabchi et al. 2017) and with the positive results of the implementation of a home exercise program in populations such as men with prostate cancer on androgen deprivation (Alibhai et al. 2024) or systemic sclerosis (Sari et al. 2024).
High-Intensity Exercise Interventions
One pre-post and feasibility study included eight participants with chronic paraplegia who performed a hybrid HIIT protocol, in the form of FES leg cycling combined with arm ski ergometer, three times per week (Vestergaard et al. 2022). After eight weeks of intervention, participants reported increased leisure time physical activity and health‐related quality of life, and reduced fatigue; however, the nature of this feasibility study did not support statistical analysis (Vestergaard et al. 2022).The study was deemed feasible because of high safety, acceptable attendance rate, and limited drop out (Vestergaard et al. 2022).
The recent systematic review and meta-analysis by Peters et al. (2021) has shown the benefits of HIIT for cardiovascular function (Peak Oxygen Uptake [VO2peak], standardized mean difference [SMD] = 0.81; 95% CI 0.23-1.39; P < 0.01 and Peak Power Output, SMD = 0.91; 95% CI 0.32-1.5; P < 0.01) in people with SCI (Peters et al. 2021). Additionally, different systematic reviews have shown that high-intensity exercise interventions could decrease fatigue in clinical populations such as cancer (Chen et al. 2023; Wang et al. 2023) or multiple sclerosis (Youssef et al. 2024). Further larger and higher quality studies need to be conducted with people with SCI to determine if this popular intervention has the same positive results in terms of fatigue.
Yoga and Tai Chi Exercise Interventions
Other pre-post studies conducted a modified yoga (Curtis et al. 2015) or a seated Tai Chi (Shem et al. 2016) program for people with chronic SCI. It should be noted that these two studies were the only ones that included participants with tetraplegia and paraplegia. Neither intervention revealed positive results for fatigue (Curtis et al. 2015; Shem et al. 2016).
Specifically for yoga, the results by Curtis et al. (2015) are contrary to those obtained in other systematic reviews, where positive effects on fatigue were shown in patients with cancer undergoing chemotherapy and/or radiotherapy (Ma et al. 2023), in patients with breast cancer (Hou et al. 2024), or in patients with multiple sclerosis (Shohani et al. 2020).
On the other hand, the findings by Shem et al. (2016) are not concurrent with to the systematic review and meta-analysis of the effects of this mind-body exercise for relieving fatigue (Xiang et al. 2017). In this review, Tai Chi was found to have improved fatigue more than conventional therapy (SMD: -0.45, 95% CI: -0.70, -0.20) overall, and have positive effects in cancer-related fatigue (SMD:-0.38, 95% CI: -0.65, -0.11); however, no significant difference was found in multiple sclerosis-related fatigue (SMD: -0.77, 95% CI: -1.76, 0.22) and age-related fatigue (SMD: -0.77, 95% CI: -1.78, 0.24). Overall, the effects of Tai Chi programs on fatigue are not sufficiently studied.
Relationship Between Fatigue and Physical Activity Level
It has been shown that RCTs assessing the impact of exercise on fatigue were generally effective, while a few non-RCTs demonstrated improved fatigue in people with SCI whereas others did not. A cross-sectional study of 49 people with SCI who used a manual wheelchair as their primary mode of mobility showed that greater physical activity was associated with fewer secondary complications including fatigue, pain, and depression (Tawashy et al. 2009). When surveying people with SCI about the association between exercise and fatigue, Hammell et al. (2009) found that opinions were divided, with some people with SCI believing that “exercise made you feel more fatigued” and some that believed “it made you less fatigued”. A previous systematic review and meta-analysis on factors associated with fatigue found that physical activity was inversely associated with fatigue, with small effect size, and high heterogeneity (r = 0.17; 95% CI, 0.28, 0.05; I2 = 75.5; P < 0.001); fatigue was also more often reported in people with SCI who ambulate and/or use their wheelchair less than 50% of the time (Onate-Figuérez et al. 2023). As previously detailed, several systematic reviews have documented fitness, health, quality of life, and subjective well-being benefits of routine physical activity participation for adults with SCI (Neefkes-Zonneveld et al. 2015; Tomasone et al. 2013; van der Scheer et al. 2017). It stands to reason that health, quality of life, and subjective well-being are antithetical to feelings of fatigue, but this has not been established in the literature.
Effects on Fatigue After Exercise Interventions in Other Populations
Overall, fatigue has been more frequently studied in multiple sclerosis than it has in SCI. In a systematic review and meta-analysis on the effectiveness of exercise on fatigue in people with multiple sclerosis, 26 studies were included and found a significant moderate effect of exercise on fatigue, though with significant heterogeneity between studies (SMD = ‐0.53, 95% CI, ‐0.73, ‐0.33, I2 > 58%, P < 0.01) (Heine et al. 2015). Exercise therapy has also been suggested to be beneficial for reducing fatigue in people with chronic fatigue syndrome (White et al. 2011), people with fibromyalgia (Estévez-López et al. 2021), people who have had a stroke (Zedlitz et al. 2012), and people with or recovering from cancer (Ahlberg et al. 2003).
Research evidence measuring the influence of exercise on fatigue is better established in the general population. In a meta-analysis of 81 studies, Wender et al. (2022) found that exercise decreased feelings of fatigue by a small effect size (g = −0.374; 95% CI, -0.521, -0.227) and increased feelings of energy by a small-to-moderate effect size (g = 0.415; 95% CI, 0.252, 0.578) (Wender et al. 2022). From 12 population-based studies comparing active versus sedentary adults, Puetz (2006) found an odds ratio of 0.61 (95% CI, 0.52, 0.72) between physical activity and a reduced risk of experiencing fatigue. In addition, two reviews state that individualized and regular exercise therapy or physical activity be recommended as part of the medical management of fatigue in the general population (Dukes et al. 2021; Rosenthal et al. 2008).
Conclusions
There is level 2 evidence (from one RCT: Jorjafaki et al. 2022) that 6 weeks of 50-min upper limb virtual reality exercise sessions, performed 3 times per week, decreases the fatigue severity (FSS) in veterans with paraplegia in a similar way to 6 weeks of 30-min reflexology massage sessions, performed 3 times per week, in comparison with a control condition.
There is level 2 evidence (from one RCT: Nightingale et al. 2018) that 6 weeks of 45-minute home-based, upper limb (arm-crank), and moderate-intensity exercise sessions, performed 4 times per week, significantly decreases the fatigue severity (FSS) with a large effect size (Cohen d = -0.99) and non-significantly decreases the fatigue (global fatigue) with a large effect size (Cohen d = 0.92), in comparison with lifestyle maintenance; in people with chronic SCI and physically inactive.
There is level 4 evidence (from one pre-post: Vestergaard et al. 2022) that an 8-week hybrid HIIT program using FES leg cycling and arm ski ergometer, performed 3 times per week, decreases fatigue (MFI-20) in people with chronic paraplegia.
There is level 4 evidence (from one pre-post: Shem et al. 2016) that a 12-week customized seated Tai Chi program (T’ai Chi Chih), performed once a week for 90 minutes each session, did not provide any change in the impact of fatigue (MFIS) in people with chronic SCI.
There is level 4 evidence (from one pre-post: Curtis et al. 2015) that an 8-week modified yoga program, performed once a week for 25-60 minutes each session, did not provide any change in the fatigue severity (FSS) in people with chronic SCI.
