Lesley J. White

Exercise and Multiple Sclerosis

AbstractThe pathophysiology of multiple sclerosis (MS) is characterised by fatigue, motor weakness, spasticity, poor balance, heat sensitivity and mental depression. Also, MS symptoms may lead to physical inactivity associated with the development of secondary diseases. Persons with MS are thus challenged by their disability when attempting to pursue an active lifestyle compatible with health-related fitness. Although exercise prescription is gaining favour as a therapeutic strategy to minimise the loss of functional capacity in chronic diseases, it remains under-utilised as an intervention strategy in the MS population. However, a growing number of studies indicate that exercise in patients with mild-to-moderate MS provides similar fitness and psychological benefits as it does in healthy controls.We reviewed numerous studies describing the responses of selected MS patients to acute and chronic exercise compared with healthy controls. All training studies reported positive outcomes that outweighed potential adverse effects of the exercise intervention. Based on our review, this article highlights the role of exercise prescription in the multidisciplinary approach to MS disease management for improving and maintaining functional capacity. Despite the often unpredictable clinical course of MS, exercise programmes designed to increase cardiorespiratory fitness, muscle strength and mobility provide benefits that enhance lifestyle activity and quality of life while reducing risk of secondary disorders. Recommendations for the evaluation of cardiorespiratory fitness, muscle performance and flexibility are presented as well as basic guidelines for individualised exercise testing and training in MS. Special considerations for exercise, including medical management concerns, programme modifications and supervision, in the MS population are discussed.

Resistance training improves strength and functional capacity in persons with multiple sclerosis

The purpose of this study was to evaluate the effect of an eight-week progressive resistance training programme on lower extremity strength, ambulatory function, fatigue and self-reported disability in multiple sclerosis (MS) patients (mean disability score 3.79-0.8). Eight MS subjects volunteered for twice weekly training sessions. During the first two weeks, subjects completed one set of 8 -10 reps at 50% of maximal voluntary contraction (MVC) of knee flexion, knee extension and plantarflexion exercises. In subsequent sessions, the subjects completed one set of 10 -15 repetitions at 70% of MVC. The resistance was increased by 2 -5% when subjects completed 15 repetitions in consecutive sessions. Isometric strength of the quadriceps, hamstring, plantarflexor and dorsiflexor muscle groups was assessed before and after the training programme using an isokinetic dynamometer. Magnetic resonance images of the thigh were acquired before and after the exercise programme as were walking speed (25-ft), number of steps in 3 min, and self-reported fatigue and disability. Knee extension (7.4%), plantarflexion (52%) and stepping performance (8.7%) increased significantly (PB-0.05). Self-reported fatigue decreased (PB-0.05) and disability tended to decrease (P -0.07) following the training programme. MS patients are capable of making positive adaptations to resistance training that are associated with improved ambulation and decreased fatigue.

Exercise and brain health--implications for multiple sclerosis: Part 1--neuronal growth factors.

The benefits of regular exercise to promote general health and reduce the risk of hypokinetic diseases associated with sedentary lifestyles are well recognized. Recent studies suggest that exercise may enhance neurobiological processes that promote brain health in aging and disease. A current frontier in the neurodegenerative disorder multiple sclerosis (MS) concerns the role of physical activity for promoting brain health through protective, regenerative and adaptive neural processes. Research on neuromodulation, raises the possibility that regular physical activity may mediate favourable changes in disease factors and symptoms associated with MS, in part through changes in neuroactive proteins. Insulin-like growth factor-I appears to act as a neuroprotective agent and studies indicate that exercise could promote this factor in MS. Neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor likely play roles in neuronal survival and activity-dependent plasticity. Physical activity has also been shown to upregulate hippocampal BDNF, which may play a role in mood states, learning and memory to lessen the decline in cognitive function associated with MS. In addition, exercise may promote anti-oxidant defences and neurotrophic support that could attenuate CNS vulnerability to neuronal degeneration. Exercise exposure (preconditioning) may serve as a mechanism to enhance stress resistance and thereby may support neuronal survival under heightened stress conditions. Considering that axonal loss and cerebral atrophy occur early in the disease, exercise prescription in the acute stage could promote neuroprotection, neuroregeneration and neuroplasticity and reduce long-term disability. This review concludes with a proposed conceptual model to connect these promising links between exercise and brain health.

Cytokine responses to acute and chronic exercise in multiple sclerosis

Regular exercise reduces functional loss associated with multiple sclerosis (MS). However, the impact of exercise on inflammatory mediators associated with disease activity remains relatively unexplored. The purpose of this study was to determine whether ambulatory MS subjects would respond similarly to aerobic cycle training compared with matched controls on circulating immune variables, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Eleven MS and 11 non-MS control subjects (8 women and 3 men in both groups) matched in age, height, body mass, body fat, and peak O(2) uptake completed the study. Subjects completed 30 min of cycle ergometry at 60% of peak O(2) uptake, 3 day/wk for 8 wk. Plasma cytokine concentrations were determined before and after exercise at weeks 0, 4, and 8. MS and control subjects showed a similar cytokine responses to exercise. IL-6 at rest tended to decrease (P = 0.08) with training in both groups. Resting plasma TNF-alpha tended to be higher in MS compared with controls throughout the study (P = 0.08). MS subjects showed elevated resting TNF-alpha in MS at the end of the 8-wk program (P = 0.04), whereas resting TNF-alpha remained unchanged in controls (P > 0.05). Resting plasma IFN-gamma at rest was elevated in MS subjects (P = 0.008) and unchanged in controls at the end of the intervention (P > 0.05). The response of plasma IL-6, TNF-alpha, and IFN-gamma after a single bout of exercise was similar between MS and control subjects (P > 0.05). Additional research to understand the impact of exercise on immune variables in MS is warranted.

Cytokine responses to resistance training in people with multiple sclerosis

Abstract Exercise for individuals with multiple sclerosis (MS) has been shown to improve cardiovascular function, increase strength and endurance, and reduce fatigue. The impact of exercise on immune function in the disease, however, remains mostly unexplored. Ten female MS patients participated in an 8 week programme of twice-weekly progressive resistance training, with pre- and post-training assessment of serum concentrations of cytokines IL-2, IL-4, IL-6, IL-10, CRP, TNF-α and IFN-γ. After training, IL-4, IL-10, CRP and IFN-γ showed statistically reduced resting concentrations in blood, while TNF-α showed non-significant reductions and IL-2 and IL-6 remained unchanged. These results suggest that progressive resistance training may have an impact on cytokine concentrations in individuals with MS and should be confirmed in studies with stronger statistical power. The impact of these changes on overall immune function in MS and on disease status and prognosis remains to be determined.

Exercise and Brain Health - Implications for Multiple Sclerosis Part II - Immune Factors and Stress Hormones

Part I of this review addressed the possible modulatory role of exercise on neuronal growth factors to promote brain health in neurodegenerative diseases such as multiple sclerosis (MS), which is characterized by varied patterns of inflammation, demyelination and axonal loss. Part II presents evidence that supports the potential neuroprotective effect of exercise on the modulation of immune factors and stress hormones in MS. Many current therapies used to attenuate MS progression are mediated, at least in part, through alterations in the relative concentrations of pro- and anti-inflammatory cytokines. Exercise-induced alterations in local and systemic cytokine production may also benefit immune function in health and disease. Exercise immunomodulation appears to be mediated by a complex interaction of hormones, cytokines and neural factors that may favorably influence immune variables in MS. The promising interplay between exercise and brain health in MS deserves further investigation.

Effect of resistance training on risk of coronary artery disease in women with multiple sclerosis.

The effects of a lower‐extremity progressive resistance‐training program (PRT) on risk factors for coronary artery disease (CAD) were determined in patients with multiple sclerosis (MS). Twelve ambulatory women with MS (47.3±4.7 years; Expanded Disability Status Score (EDSS), 4.00±1.37) completed twice weekly lower‐body PRT for 8 weeks. Knee extensor and ankle flexor strength improved significantly (p<0.05) after training, and self‐reported fatigue decreased (p<0.05). Serum triglyceride concentrations decreased (p<0.05) but body‐weight and fatness, blood pressure, and serum glucose, total cholesterol and high‐density lipoprotein cholesterol were unchanged. However, the number of CAD risk factors that reached the clinical threshold for each subject declined after PRT, suggesting that resistance training can promote CAD risk reduction in ambulatory female MS subjects.

Early-phase neuroendocrine responses and strength adaptations following eccentric-enhanced resistance training.

Yarrow, JF, Borsa, PA, Borst, SE, Sitren, HS, Stevens, BR, White, LJ. Early-phase neuroendocrine responses and strength adaptations following eccentric-enhanced resistance training. J Strength Cond Res 22, 1205-1214, 2008-The purpose of this study was to evaluate the early-phase muscular performance adaptations to 5 weeks of traditional (TRAD) and eccentric-enhanced (ECC+) progressive resistance training and to compare the acute postexercise total testosterone (TT), bioavailable testosterone (BT), growth hormone (GH), and lactate responses in TRAD- and ECC+-trained individuals. Twenty-two previously untrained men (22.1 ± 0.8 years) completed 1 familiarization and 2 baseline bouts, 15 exercise bouts (i.e., 3 times per week for 5 weeks), and 2 postintervention testing bouts. Anthropometric and 1 repetition maximum (1RM) measurements (i.e., bench press and squat) were assessed during both baseline and postintervention testing. Following baseline testing, participants were randomized into TRAD (4 sets of 6 repetitions at 52.5% 1RM) or ECC+ (3 sets of 6 repetitions at 40% 1RM concentric and 100% 1RM eccentric) groups and completed the 5-week progressive resistance training protocols. During the final exercise bout, blood samples acquired at rest and following exercise were assessed for serum TT, BT, GH, and blood lactate. Both groups experienced similar increases in bench press (approximately 10%) and squat (approximately 22%) strength during the exercise intervention. At the conclusion of training, postexercise TT and BT concentrations increased (approximately 13% and 21%, respectively, p < 0.05) and GH concentrations increased (approximately 750-1200%, p < 0.05) acutely following exercise in both protocols. Postexercise lactate accumulation was similar between the TRAD (5.4 ± 0.4) and ECC+ (5.6 ± 0.4) groups; however, the ECC+ groups lactate concentrations were significantly lower than those of the TRAD group 30 to 60 minutes into recovery. In conclusion, TRAD training and ECC+ training appear to result in similar muscular strength adaptations and neuroendocrine responses, while postexercise lactate clearance is enhanced following ECC+ training.

Effect of 10-day forced treadmill training on neurotrophic factors in experimental autoimmune encephalomyelitis.

The impact of exercise on disease progression in multiple sclerosis (MS) is unclear. In the present study, we evaluated the clinical effects of forced wheel running on rats induced with experimental autoimmune encephalomyelitis (EAE), a model of MS. Female Lewis rats (n = 40) were randomly assigned to 1 of 4 groups prior to inoculation: EAE exercise (EAE-Ex), EAE sedentary (EAE-Sed), control exercise (Con-Ex), or control sedentary (Con-Sed). Exercise training was composed of forced treadmill running at increasing intensity across 10 consecutive days. No significant differences in clinical disability were observed in the EAE groups at the conclusion of this study. Furthermore, no significant differences in brain mass were observed across groups. Analysis of brain tissue proteins revealed that tumour necrosis factor-α (TNF-α) concentrations were higher in both EAE groups compared with the control groups (p < 0.05); however, no significant differences were seen between the EAE-Ex and EAE-Sed groups. The Con-Ex group had lower whole-brain TNF-α compared with the Con-Sed group (p < 0.05). Nerve growth factor concentrations were greater in the EAE-Ex animals compared with both control groups (p < 0.05 for both). No differences were seen in brain-derived neurotrophic factor. Our results indicate that aerobic exercise can modulate the proteins associated with disability in EAE; however, further research is required to understand the total impact of exercise on EAE disability and disease progression.

Effects of intermittent cycle exercise on intramyocellular lipid use and recovery.

The purpose of this investigation was to compare intramyocellular lipid (IMCL) changes in skeletal muscle in nine moderately trained subjects after 45 min of interval cycling and through 1 h of recovery. The exercise session was continous with alternating cycling intensity achieving 50 (3 min) and 110% (2 min) of ventilatory threshold. Spectra from the vastus lateralis were acquired before, immediately after, and 60 min following exercise using a 1.5 T Signa whole-body magnet (point-resolved spectroscopy sequence, echo time 60 ms, transverse relaxation time 2000 ms, 128 acquisitions, and 20 mm3 voxel). Immediately following exercise, IMCI concentration decreased 38% compared to pre-exercise levels (P<0.05). Fitness level and baseline IMCL were not correlated with changes in IMCL following exercise (P>0.05). In the 60-min recovery, IMCL was reduced 30% compared to baseline (P<0.05) and did not recover. In contrast, a nonexercising control group showed no change in IMCL. Our results suggest that IMCL decreased significantly following 45 min of interval cycling, with little recovery in the hour following.