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Therapeutic Advances in Neurological Disorders
Barbara S. Giesser
Professor of Clinical Neurology, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA
From: Irwin Mortman (Autoimmune List)
Abstract and Introduction
For decades, persons with multiple sclerosis (MS) were counseled to avoid excessive physical activity and exercise because of concerns about worsening disease activity. Recent studies indicate that, not only can those with MS tolerate physical exercise, but that it is helpful in managing symptoms, preventing complications and comorbidities, and may possibly have neuroprotective actions. This article reviews previous studies on the effects of different exercise protocols in people with MS, and provides summaries of suggested exercise regimens that may be appropriate and beneficial for this patient population.
Introduction
As recently as a few decades ago, conventional wisdom held that persons with multiple sclerosis (MS) should avoid strenuous physical activity because of concerns that it might worsen their neurological status. This may have stemmed from the observation that most persons with MS may temporarily have exaggerated symptoms when they become overheated, e.g. as might happen with vigorous physical exertion. It is now becoming clear that this advice for those with MS not to be physically active was not only incorrect, but likely had potentially harmful consequences in terms of promoting deconditioning and contributing to comorbidities such as obesity, metabolic syndrome and osteoporosis, to name just a few.
Fortunately for people with MS and the healthcare professionals who treat them, there are now abundant data that demonstrate that physical activity is not only safe and well-tolerated for persons with MS, and has the same health benefits as it does for the general population, but additionally may be of value in alleviating some symptoms, preventing complications and possibly being neuroprotective. Obesity has been implicated as a risk factor for developing MS in adolescent girls [Langer-Gould et al. 2013] and other data suggest that those with MS with vascular comorbidities, such as hypertension and diabetes, have more disability and worse prognosis [Marrie and Harwell, 2013]. A recent review of 26 randomized, controlled trials (RCTs) of exercise training in persons with MS found a slightly decreased risk of relapse in the exercise group versus control (6.3% versus 4.6%) and no increase in risk for adverse events compared with the risk of adverse events for exercise training in a non-MS population [Pilutti et al. 2014]. Thus exercise may actually impact disease course in persons at risk for MS and after the disease develops, i.e. it might be potentially considered as a disease modifying therapy.
Unfortunately, persons with MS have been shown to be less physically active than healthy controls [Motl, 2014]. A survey of 417 persons with MS identified fatigue, impairment and lack of time as the top three barriers to exercise [Asano et al. 2013].
This paper reviews the data about exercise in the animal model of MS, experimental autoimmune encephalomyelitis (EAE), and then summarizes what has been observed about the effects of physical exercise on specific MS symptoms and impairments. Emerging data about the possible neuroprotective/neurorestorative properties of exercise are explored. Finally, current recommendations for appropriate exercise regimens for persons with MS are discussed.
The definition of exercise training is that of taken from Motl and Pilutti who defined it as 'planned, structured and repetitive physical activity undertaken over a prolonged period to maintain or improve physical fitness and functional capacity' [Motl and Pilutti, 2012]. This is to distinguish it from physical therapy, which may be defined as a structured set of exercises and strategies designed to overcome a specific deficit. The benefits of physical therapy for persons with MS are outside the scope of this review.
Exercise and EAE
EAE is the most studied animal model for MS and can be actively or passively induced in several rodent species. Disease severity is generally graded on a scale from 0 to 5, where '0' is asymptomatic, grades 1–4 indicate increasing degrees of motor deficit, and 5 is quadriplegic or moribund [Klaren et al. 2014]. The first study examining the effect of exercise in EAE used a forced running paradigm in rats beginning 1 day after disease induction. The exercised rats showed a significant delay in onset and decreased severity of disease compared with control (sedentary) rats [Le Page et al. 1994]. A follow-up study confirmed that exercise appeared to have maximal benefit when performed just after disease induction at high intensity, compared with exercise initiated before disease induction or after induction at variable speeds [Le Page et al. 1996].
More recent studies in murine EAE models have variably demonstrated benefits of exercise. Rossi and colleagues employed a voluntary exercise paradigm in mice and reported lower disease severity in both acute and chronic phases of EAE in mice with access to a running wheel, compared with mice without wheel access [Rossi et al. 2009]. Additionally, the exercised mice had less neural damage as assessed by electrophysiological responses, and increased dendritic spine density compared with controls. Another study used swimming exercise in mice as the exercise paradigm, where the exercised mice were made to swim 30 minutes/day for 5 days/week for 6 weeks. A control group of mice was placed in the water on a platform for the same time period. EAE was induced during the fifth week of training in both exercised and sedentary mice; a control group in each condition received sham injections. The EAE plus exercise mice showed decreased disease severity compared with controls [Bernardes et al. 2013]. The exercised mice showed increases in brain-derived neurotrophic factor (BDNF) and decreased demyelination compared with nonexercised mice with EAE, but cytokine patterns were not consistently different between the groups. Finally, a paradigm using forced treadmill walking in rats that were exercised for 10 days after induction of chronic EAE did not show any difference in clinical severity or levels of BDNF and tumor necrosis factor-α (TNF-α) between exercised and control rats, although the clinical disability score in both groups (1.0 = tail weakness) was low [Patel and White, 2013].
While the majority of this small number of studies suggest a beneficial effect of exercise on EAE, the study populations, types of exercise and timing of exercise all vary, and further research is needed in this area. For a complete review see the article by Klaren and colleagues [Klaren et al. 2014].
PART 2: Specific Impairments
http://activemsers.wssnoc.net/showthread.php?t=1853
Barbara S. Giesser
Professor of Clinical Neurology, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA
From: Irwin Mortman (Autoimmune List)
Abstract and Introduction
For decades, persons with multiple sclerosis (MS) were counseled to avoid excessive physical activity and exercise because of concerns about worsening disease activity. Recent studies indicate that, not only can those with MS tolerate physical exercise, but that it is helpful in managing symptoms, preventing complications and comorbidities, and may possibly have neuroprotective actions. This article reviews previous studies on the effects of different exercise protocols in people with MS, and provides summaries of suggested exercise regimens that may be appropriate and beneficial for this patient population.
Introduction
As recently as a few decades ago, conventional wisdom held that persons with multiple sclerosis (MS) should avoid strenuous physical activity because of concerns that it might worsen their neurological status. This may have stemmed from the observation that most persons with MS may temporarily have exaggerated symptoms when they become overheated, e.g. as might happen with vigorous physical exertion. It is now becoming clear that this advice for those with MS not to be physically active was not only incorrect, but likely had potentially harmful consequences in terms of promoting deconditioning and contributing to comorbidities such as obesity, metabolic syndrome and osteoporosis, to name just a few.
Fortunately for people with MS and the healthcare professionals who treat them, there are now abundant data that demonstrate that physical activity is not only safe and well-tolerated for persons with MS, and has the same health benefits as it does for the general population, but additionally may be of value in alleviating some symptoms, preventing complications and possibly being neuroprotective. Obesity has been implicated as a risk factor for developing MS in adolescent girls [Langer-Gould et al. 2013] and other data suggest that those with MS with vascular comorbidities, such as hypertension and diabetes, have more disability and worse prognosis [Marrie and Harwell, 2013]. A recent review of 26 randomized, controlled trials (RCTs) of exercise training in persons with MS found a slightly decreased risk of relapse in the exercise group versus control (6.3% versus 4.6%) and no increase in risk for adverse events compared with the risk of adverse events for exercise training in a non-MS population [Pilutti et al. 2014]. Thus exercise may actually impact disease course in persons at risk for MS and after the disease develops, i.e. it might be potentially considered as a disease modifying therapy.
Unfortunately, persons with MS have been shown to be less physically active than healthy controls [Motl, 2014]. A survey of 417 persons with MS identified fatigue, impairment and lack of time as the top three barriers to exercise [Asano et al. 2013].
This paper reviews the data about exercise in the animal model of MS, experimental autoimmune encephalomyelitis (EAE), and then summarizes what has been observed about the effects of physical exercise on specific MS symptoms and impairments. Emerging data about the possible neuroprotective/neurorestorative properties of exercise are explored. Finally, current recommendations for appropriate exercise regimens for persons with MS are discussed.
The definition of exercise training is that of taken from Motl and Pilutti who defined it as 'planned, structured and repetitive physical activity undertaken over a prolonged period to maintain or improve physical fitness and functional capacity' [Motl and Pilutti, 2012]. This is to distinguish it from physical therapy, which may be defined as a structured set of exercises and strategies designed to overcome a specific deficit. The benefits of physical therapy for persons with MS are outside the scope of this review.
Exercise and EAE
EAE is the most studied animal model for MS and can be actively or passively induced in several rodent species. Disease severity is generally graded on a scale from 0 to 5, where '0' is asymptomatic, grades 1–4 indicate increasing degrees of motor deficit, and 5 is quadriplegic or moribund [Klaren et al. 2014]. The first study examining the effect of exercise in EAE used a forced running paradigm in rats beginning 1 day after disease induction. The exercised rats showed a significant delay in onset and decreased severity of disease compared with control (sedentary) rats [Le Page et al. 1994]. A follow-up study confirmed that exercise appeared to have maximal benefit when performed just after disease induction at high intensity, compared with exercise initiated before disease induction or after induction at variable speeds [Le Page et al. 1996].
More recent studies in murine EAE models have variably demonstrated benefits of exercise. Rossi and colleagues employed a voluntary exercise paradigm in mice and reported lower disease severity in both acute and chronic phases of EAE in mice with access to a running wheel, compared with mice without wheel access [Rossi et al. 2009]. Additionally, the exercised mice had less neural damage as assessed by electrophysiological responses, and increased dendritic spine density compared with controls. Another study used swimming exercise in mice as the exercise paradigm, where the exercised mice were made to swim 30 minutes/day for 5 days/week for 6 weeks. A control group of mice was placed in the water on a platform for the same time period. EAE was induced during the fifth week of training in both exercised and sedentary mice; a control group in each condition received sham injections. The EAE plus exercise mice showed decreased disease severity compared with controls [Bernardes et al. 2013]. The exercised mice showed increases in brain-derived neurotrophic factor (BDNF) and decreased demyelination compared with nonexercised mice with EAE, but cytokine patterns were not consistently different between the groups. Finally, a paradigm using forced treadmill walking in rats that were exercised for 10 days after induction of chronic EAE did not show any difference in clinical severity or levels of BDNF and tumor necrosis factor-α (TNF-α) between exercised and control rats, although the clinical disability score in both groups (1.0 = tail weakness) was low [Patel and White, 2013].
While the majority of this small number of studies suggest a beneficial effect of exercise on EAE, the study populations, types of exercise and timing of exercise all vary, and further research is needed in this area. For a complete review see the article by Klaren and colleagues [Klaren et al. 2014].
PART 2: Specific Impairments
http://activemsers.wssnoc.net/showthread.php?t=1853