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Specific Impairments
This section presents a review of studies of the effects of exercise on impairments specific to those with MS; control groups in these studies being those persons with MS who were randomized to a nonintervention group, e.g. waiting list, usual care or other control intervention.
Muscle Strength/Mobility/Spasticity
Numerous studies have demonstrated that exercise training can improve muscle strength in persons with MS. Protocols have included progressive resistance training (PRT), aerobic exercise (AE), combined AE and PRT, and other activities such as swimming and robotic-assisted treadmill training. Despite different subject populations and protocols, studies have consistently reported improvements in muscle strength after training. A review of PRT [Kjolhede et al. 2012] examined results from six RCTs of PRT and six non-controlled trials. The RCTs included subjects with expanded disability status scale (EDSS) scores ranging from 1.0 to 6.5, and duration and intensities of training ranging from 2 to 5 sessions/week over 3–20 weeks. Training modalities included free weights, resistance bands or weight machines.
Reviews of aerobic and other training modalities also report improvements in muscle strength. The seminal study of Petajan and colleagues was one of the first to report improvements in muscle strength in persons with MS after they were randomized to a protocol of arm and leg cycling 3 times per week for 15 weeks versus usual care [Petajan et al. 1996]. Improvement in muscle strength has also been reported with roboticassisted treadmill training [Beer et al. 2008], swimming [Gehlsen et al. 1984] and a combined AE plus PRT regimen [Konecny et al. 2010]. Sá has provided a comprehensive review of the physical (musculoskeletal) effects of exercise training in persons with MS [Sá, 2013].
Muscle strength has been reported to be an important determinant of walking speed in persons with MS [Thoumie et al. 2005]. The effects of AE and PRT on walking speed in RCTs have been somewhat less consistent than the effects on muscle strength noted above. At least one RCT of PRT [Dalgas et al. 2009] and one RCT of treadmill walking (Van den Berg et al. 2006] have reported improvement in walking speed; non controlled trials have also reported improvements [Motl and Pilutti, 2012].
A few studies have reported positive effects of exercise on reducing spasticity in persons with MS. These have included cycling [Sosoff et al. 2009], a group exercise intervention [Tarakci et al. 2013] and locomotor training [Giesser et al. 2007].
Fatigue
Fatigue is the most common symptom reported by person with MS, with an incidence of up to 90% in some studies. It is not solely a function of physical disability and may be the single most disabling symptom in an otherwise neurologically intact individual. Usual treatment measures include pharmacologic agents and energy conservation methods.
A review of the effects of exercise on fatigue in persons with MS has yielded somewhat heterogeneous results, with some studies demonstrating a benefit in improving fatigue, and other studies failing to show improvement. Improvement in fatigue has been reported in some trials of aerobic exercise [Petajan et al.1996; Rampello et al. 2007; Sabapathy et al. 2011], PRT [Dalgas et al. 2010], AE and PRT combined [Konecny et al. 2010] and other forms of activity such as sport (volleyball) [McCullagh et al. 2008], yoga [Oken et al. 2004] or aquatic exercise [Sutherland et al. 2001], to name a few. A meta-analysis of RCTs examining the effects of exercise training on fatigue found an overall small but significant benefit, with an effect size of 0.45 [Pilutti et al. 2013].
Importantly, no study has demonstrated a significant worsening of fatigue with any type of exercise, thus providing important reassurance for patients that they should be able to exercise safely without worsening their condition, other than possible temporary effects from overheating.
Mood
Depression may affect up to 50% of the MS population [Sadovnick et al. 1996] and can significantly impact other symptoms such as fatigue and pain, as well as negatively affecting cognition and quality of life. A recent Cochrane review found a small but significant effect of exercise on persons with depression (without MS) compared with waiting list or placebo [Cooney et al. 2013]. Petajan and colleagues performed one of the first studies to demonstrate that exercise could produce improvements in mood in person with MS [Petajan et al. 1996]. A recent review of the effects of exercise on depression in persons with MS reported heterogeneous results, with several studies using aerobic and PRT reporting positive effects on depression, and other trials failing to note improvement [Feinstein et al. 2013]. The authors note that none of these studies had depression as a primary outcome measure or used a clinician-based assessment of depression as an outcome measure, and suggest that further clarity is needed in this area. A more recent review of 13 RCTs of the effect of exercise on depressive symptoms in people with MS reported an effect size of 0.36 [Ensari et al. 2014].
Quality of Life
Health-related quality of life (HRQOL) has been reported to be reduced in persons with MS compared with those without MS and those with other chronic medical conditions [Benito-Leon et al. 2003]. A meta-analysis of studies of the effects of exercise on HRQOL in persons with MS concluded that, despite reports of individual studies reporting improved HRQOL with exercise, both with aerobic [Petajan et al. 1996; Romberg et al. 2004], PRT [Dalgas et al. 2010] and combined protocols [Dalgas et al. 2010], overall there was insufficient consistent evidence to prove definitively that exercise improved HRQOL in this patient population, as other studies of exercise did not show HRQOL improvement [Latimer-Cheung et al. 2013b].
Cognition
Exercise, primarily aerobic, has been reported to improve cognitive function in several patient populations, including Alzheimer's disease (AD), elderly people at risk for cognitive impairment and healthy older adults [Voss et al. 2013; Smith et al. 2010]. The literature on the effects of exercise in cognition in persons with MS is scant, although the animal literature consistently reports positive effects of exercise upon cognition [Van Praag et al. 2005; Cotman et al. 2007]. Improved physical fitness has been reported to correlate with improved cognitive function in persons with MS [Motl et al. 2011; Beier et al. 2014] and that cardiorespiratory fitness in persons with MS predicts neuronal plasticity [Prakash and Snook, 2007] and increased gray matter volume, better white matter integrity and improved performance on test of information processing speed [Prakash et al. 2010].
An early study employing a light intensity aerobic regimen or yoga failed to show improvement in performance on neurophysiologic tests [Oken, 2004]. However, a more recent RCT of an aerobic exercise intervention in persons with MS reported improved cognitive function in several neuropsychological domains in subjects who received the exercise intervention, compared with a waiting list control group [Briken et al. 2014]. A study using a computer/internet based intervention to increase physical activity behavior demonstrated a clinically significant increase in the Symbol Digit Modalities Test (SDMT) in a subset of subjects with mild disability at the end of the intervention while there was minimal change in this metric in a waiting list control group [Sandroff et al. 2014].
Neuroprotective Effects
Exercise has been shown to ameliorate the effects of trauma or disease to the central nervous system (CNS) in animal models of stroke [Hayes et al. 2008], spinal cord injury [Gomez-Pinilla et al. 2012], AD [Voss et al. 2013] and MS [Voss et al. 2013]. There is some evidence for neuroprotective effects of exercise in humans with MS, with a few trials of aerobic or aerobic plus resistance exercise training producing decreases in anti-inflammatory cytokines compared with non-exercised controls [Motl and Pilutti, 2012]. There is substantial evidence for increases in neurotrophins in response to exercise in the animal literature [Cotman et al. 2007]. One trial of aerobic exercise in persons with MS reported a transient increase in BDNF during an aerobic exercise regimen [Castellano and White, 2008]; another trial did not report significant increase in BDNF after exercise [Schultz et al. 2004]. More recently a trial comparing aquatic versus land exercise training in persons with MS reported that increases in BDNF were seen in the aquatic trained group [Bansi et al. 2013].
Exercise has been shown to increase synaptic density and growth in the hippocampus in the animal model of MS [Rossi et al. 2009]. One study in two people with MS reported a substantial increase in hippocampal volume in the subject randomized to an aerobic exercise program compared with a nonaerobic trained control [Leavitt et al. 2014].
Given that the primary mechanism of nerve damage in relapsing-remitting MS is inflammatory, if exercise has an anti-inflammatory effect through a combination of mechanisms (e.g. reducing inflammatory cytokines and reducing adipose tissue, which itself has been shown to produce inflammatory cytokines [Chan et al. 2013]), this would be a disease-modifying modality that appears to be well-tolerated by persons with MS and also cost effective. A review of exercise intervention studies that have used clinical outcome measures of disease progression or disability concluded that there are currently no data to date to establish a disease-modifying effect of exercise, but state that future studies and improved methodologies are necessary to answer this question [Dalgas and Stenager, 2012].
PART 3: Recommendations
http://activemsers.wssnoc.net/showthread.php?t=1854
This section presents a review of studies of the effects of exercise on impairments specific to those with MS; control groups in these studies being those persons with MS who were randomized to a nonintervention group, e.g. waiting list, usual care or other control intervention.
Muscle Strength/Mobility/Spasticity
Numerous studies have demonstrated that exercise training can improve muscle strength in persons with MS. Protocols have included progressive resistance training (PRT), aerobic exercise (AE), combined AE and PRT, and other activities such as swimming and robotic-assisted treadmill training. Despite different subject populations and protocols, studies have consistently reported improvements in muscle strength after training. A review of PRT [Kjolhede et al. 2012] examined results from six RCTs of PRT and six non-controlled trials. The RCTs included subjects with expanded disability status scale (EDSS) scores ranging from 1.0 to 6.5, and duration and intensities of training ranging from 2 to 5 sessions/week over 3–20 weeks. Training modalities included free weights, resistance bands or weight machines.
Reviews of aerobic and other training modalities also report improvements in muscle strength. The seminal study of Petajan and colleagues was one of the first to report improvements in muscle strength in persons with MS after they were randomized to a protocol of arm and leg cycling 3 times per week for 15 weeks versus usual care [Petajan et al. 1996]. Improvement in muscle strength has also been reported with roboticassisted treadmill training [Beer et al. 2008], swimming [Gehlsen et al. 1984] and a combined AE plus PRT regimen [Konecny et al. 2010]. Sá has provided a comprehensive review of the physical (musculoskeletal) effects of exercise training in persons with MS [Sá, 2013].
Muscle strength has been reported to be an important determinant of walking speed in persons with MS [Thoumie et al. 2005]. The effects of AE and PRT on walking speed in RCTs have been somewhat less consistent than the effects on muscle strength noted above. At least one RCT of PRT [Dalgas et al. 2009] and one RCT of treadmill walking (Van den Berg et al. 2006] have reported improvement in walking speed; non controlled trials have also reported improvements [Motl and Pilutti, 2012].
A few studies have reported positive effects of exercise on reducing spasticity in persons with MS. These have included cycling [Sosoff et al. 2009], a group exercise intervention [Tarakci et al. 2013] and locomotor training [Giesser et al. 2007].
Fatigue
Fatigue is the most common symptom reported by person with MS, with an incidence of up to 90% in some studies. It is not solely a function of physical disability and may be the single most disabling symptom in an otherwise neurologically intact individual. Usual treatment measures include pharmacologic agents and energy conservation methods.
A review of the effects of exercise on fatigue in persons with MS has yielded somewhat heterogeneous results, with some studies demonstrating a benefit in improving fatigue, and other studies failing to show improvement. Improvement in fatigue has been reported in some trials of aerobic exercise [Petajan et al.1996; Rampello et al. 2007; Sabapathy et al. 2011], PRT [Dalgas et al. 2010], AE and PRT combined [Konecny et al. 2010] and other forms of activity such as sport (volleyball) [McCullagh et al. 2008], yoga [Oken et al. 2004] or aquatic exercise [Sutherland et al. 2001], to name a few. A meta-analysis of RCTs examining the effects of exercise training on fatigue found an overall small but significant benefit, with an effect size of 0.45 [Pilutti et al. 2013].
Importantly, no study has demonstrated a significant worsening of fatigue with any type of exercise, thus providing important reassurance for patients that they should be able to exercise safely without worsening their condition, other than possible temporary effects from overheating.
Mood
Depression may affect up to 50% of the MS population [Sadovnick et al. 1996] and can significantly impact other symptoms such as fatigue and pain, as well as negatively affecting cognition and quality of life. A recent Cochrane review found a small but significant effect of exercise on persons with depression (without MS) compared with waiting list or placebo [Cooney et al. 2013]. Petajan and colleagues performed one of the first studies to demonstrate that exercise could produce improvements in mood in person with MS [Petajan et al. 1996]. A recent review of the effects of exercise on depression in persons with MS reported heterogeneous results, with several studies using aerobic and PRT reporting positive effects on depression, and other trials failing to note improvement [Feinstein et al. 2013]. The authors note that none of these studies had depression as a primary outcome measure or used a clinician-based assessment of depression as an outcome measure, and suggest that further clarity is needed in this area. A more recent review of 13 RCTs of the effect of exercise on depressive symptoms in people with MS reported an effect size of 0.36 [Ensari et al. 2014].
Quality of Life
Health-related quality of life (HRQOL) has been reported to be reduced in persons with MS compared with those without MS and those with other chronic medical conditions [Benito-Leon et al. 2003]. A meta-analysis of studies of the effects of exercise on HRQOL in persons with MS concluded that, despite reports of individual studies reporting improved HRQOL with exercise, both with aerobic [Petajan et al. 1996; Romberg et al. 2004], PRT [Dalgas et al. 2010] and combined protocols [Dalgas et al. 2010], overall there was insufficient consistent evidence to prove definitively that exercise improved HRQOL in this patient population, as other studies of exercise did not show HRQOL improvement [Latimer-Cheung et al. 2013b].
Cognition
Exercise, primarily aerobic, has been reported to improve cognitive function in several patient populations, including Alzheimer's disease (AD), elderly people at risk for cognitive impairment and healthy older adults [Voss et al. 2013; Smith et al. 2010]. The literature on the effects of exercise in cognition in persons with MS is scant, although the animal literature consistently reports positive effects of exercise upon cognition [Van Praag et al. 2005; Cotman et al. 2007]. Improved physical fitness has been reported to correlate with improved cognitive function in persons with MS [Motl et al. 2011; Beier et al. 2014] and that cardiorespiratory fitness in persons with MS predicts neuronal plasticity [Prakash and Snook, 2007] and increased gray matter volume, better white matter integrity and improved performance on test of information processing speed [Prakash et al. 2010].
An early study employing a light intensity aerobic regimen or yoga failed to show improvement in performance on neurophysiologic tests [Oken, 2004]. However, a more recent RCT of an aerobic exercise intervention in persons with MS reported improved cognitive function in several neuropsychological domains in subjects who received the exercise intervention, compared with a waiting list control group [Briken et al. 2014]. A study using a computer/internet based intervention to increase physical activity behavior demonstrated a clinically significant increase in the Symbol Digit Modalities Test (SDMT) in a subset of subjects with mild disability at the end of the intervention while there was minimal change in this metric in a waiting list control group [Sandroff et al. 2014].
Neuroprotective Effects
Exercise has been shown to ameliorate the effects of trauma or disease to the central nervous system (CNS) in animal models of stroke [Hayes et al. 2008], spinal cord injury [Gomez-Pinilla et al. 2012], AD [Voss et al. 2013] and MS [Voss et al. 2013]. There is some evidence for neuroprotective effects of exercise in humans with MS, with a few trials of aerobic or aerobic plus resistance exercise training producing decreases in anti-inflammatory cytokines compared with non-exercised controls [Motl and Pilutti, 2012]. There is substantial evidence for increases in neurotrophins in response to exercise in the animal literature [Cotman et al. 2007]. One trial of aerobic exercise in persons with MS reported a transient increase in BDNF during an aerobic exercise regimen [Castellano and White, 2008]; another trial did not report significant increase in BDNF after exercise [Schultz et al. 2004]. More recently a trial comparing aquatic versus land exercise training in persons with MS reported that increases in BDNF were seen in the aquatic trained group [Bansi et al. 2013].
Exercise has been shown to increase synaptic density and growth in the hippocampus in the animal model of MS [Rossi et al. 2009]. One study in two people with MS reported a substantial increase in hippocampal volume in the subject randomized to an aerobic exercise program compared with a nonaerobic trained control [Leavitt et al. 2014].
Given that the primary mechanism of nerve damage in relapsing-remitting MS is inflammatory, if exercise has an anti-inflammatory effect through a combination of mechanisms (e.g. reducing inflammatory cytokines and reducing adipose tissue, which itself has been shown to produce inflammatory cytokines [Chan et al. 2013]), this would be a disease-modifying modality that appears to be well-tolerated by persons with MS and also cost effective. A review of exercise intervention studies that have used clinical outcome measures of disease progression or disability concluded that there are currently no data to date to establish a disease-modifying effect of exercise, but state that future studies and improved methodologies are necessary to answer this question [Dalgas and Stenager, 2012].
PART 3: Recommendations
http://activemsers.wssnoc.net/showthread.php?t=1854