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Rehabilitation Physiology Lab


Multiple Sclerosis

Recent Grants

NIDRR 2005-2008
Effects of Cooling and Fitness on Exercise Performance in Individuals with Multiple Sclerosis

Principal Investigator:
Nadine M. Fisher, Ed.D.
Co-Investigator:
Carl V. Granger, M.D.

Sponsor:
National Institute on Disability and Rehabilitation Research United States Department of Education

Multiple Sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system. The most common symptom of MS is a generalized sense of fatigue. Some distinguishing features of fatigue in MS are that it comes on easily, prevents sustained physical functioning, interferes with an individual’s responsibilities and role performance, and is worsened by heat. To manage fatigue, it has been suggested that individuals with MS should participate in aerobic exercise, plan for rest periods, improve sleep and avoid heat. The goals of this proposed research study are (1) to assess how work capacity (exercise) and fatigue are affected by different cooling strategies, and (2) to determine the effects of a 12-week aerobic exercise program on heat flux and changes in skin and core body temperature.

Sixty subjects with MS will be studied over the three-year period. The inclusion criteria are a definite diagnosis of MS made by a neurologist, an EDSS score of ( 6.0 (can walk with intermittent or constant unilateral support for 100 meters), a self-reported sensitivity to heat, ability to sustain low level intermittent cycling on a cycle ergometer for a minimum of 15 minutes, being agreeable to swallowing the temperature pill, and no contraindications for aerobic exercise. Subjects will be excluded if they have a neurological disorder other than MS or are wheelchair-bound. Statistics show that MS affects predominantly women (75%) between the ages of 35-64 who are unemployed due to their disease. We expect our population to reflect these statistics.

All 60 subjects will participate in Phase I of the study, i.e. assessing physiological changes during 4 cooling conditions. After completion of Phase 1, the subjects will be randomly assigned to an exercise without cooling (EX, n=20), exercise with cooling (CEX, n=20) or control group (C, n=20) for Phase II (a 12-week aerobic cycling exercise program). In Phase I, the 4 conditions are no cooling (NC) or control, active pre-cooling before exercise (PC), active cooling during exercise (CDE), and passive ad libitum cooling (ALC). The test protocol for Phase I is comprised of a medical exam and assessments of fatigue, perceived exertion, temperature (oral, tympanic, core and skin), functional performance, cardiovascular function, and psychomotor and neuropsychological function. For each subject, one cooling condition will be randomly selected each week over a 4 week period. For Phase II, a baseline maximal graded exercise test to assess cardiovascular function and measures of fatigue and temperature will be conducted prior to randomizing the subjects into the EX, CEX and C groups. The aerobic cycling program uses intermittent exercise of 1-hour duration, 3 days per week. Over 12 weeks, the exercise intensity progresses from 40-100% of the subject’s initial maximal oxygen consumption. The C group will receive bimonthly phone calls for social contact. After 12 weeks, all subjects will be retested using the same protocols.

Results will be analyzed at an alpha level of .05 using multivariate analysis of variance (MANOVA), step-down analysis, and post hoc analyses where appropriate. For Phase I, it is expected that exercise performance will increase during the cooling conditions, especially PC and CDE. For Phase II, it is expected that the aerobic exercise program will increase cardiovascular function and functional performance. Positive results of our study would lead to a better understanding of treatment (cooling) possibilities and exercise rehabilitation procedures available for individuals with MS.

NIDRR 2001-2006
Randomized Controlled Trial of Anti-Fatiguing Exercises to Improve Function in Individuals with Multiple Sclerosis

Principal Investigator:
Nadine M. Fisher, Ed.D.
Co-Investigator:
Carl V. Granger, M.D.
Participating Investigators:
Lawrence Jacobs, M.D.
Carol Brownscheidle, Ph.D.

Sponsor:
National Institute on Disability and Rehabilitation Research United States Department of Education

Multiple Sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system. The most common symptom of MS is a generalized sense of fatigue. Some distinguishing features of fatigue in MS are that it comes on easily, prevents sustained physical functioning, interferes with an individual's responsibilities and role performance, and is worsened by heat. To manage fatigue, it has been suggested that individuals with MS should participate in aerobic exercise, plan for rest periods, improve sleep and avoid heat. The goals of this proposed research study are (1) to assess how work capacity (exercise) and fatigue are affected by different cooling strategies, and (2) to determine the effects of a 12-week aerobic exercise program on heat flux and changes in skin and core body temperature.

Sixty subjects with MS will be studied over the three-year period. The inclusion criteria are a definite diagnosis of MS made by a neurologist, an EDSS score of 6.0 (can walk with intermittent or constant unilateral support for 100 meters), a self-reported sensitivity to heat, ability to sustain low level intermittent cycling on a cycle ergometer for a minimum of 15 minutes, being agreeable to swallowing the temperature pill, and no contraindications for aerobic exercise. Subjects will be excluded if they have a neurological disorder other than MS or are wheelchair-bound. Statistics show that MS affects predominantly women (75%) between the ages of 35-64 who are unemployed due to their disease. We expect our population to reflect these statistics.

All 60 subjects will participate in Phase I of the study, i.e. assessing physiological changes during 4 cooling conditions. After completion of Phase 1, the subjects will be randomly assigned to an exercise without cooling (EX, n=20), exercise with cooling (CEX, n=20) or control group (C, n=20) for Phase II (a 12-week aerobic cycling exercise program). In Phase I, the 4 conditions are no cooling (NC) or control, active pre-cooling before exercise (PC), active cooling during exercise (CDE), and passive ad libitum cooling (ALC). The test protocol for Phase I is comprised of a medical exam and assessments of fatigue, perceived exertion, temperature (oral, tympanic, core and skin), functional performance, cardiovascular function, and psychomotor and neuropsychological function. For each subject, one cooling condition will be randomly selected each week over a 4 week period. For Phase II, a baseline maximal graded exercise test to assess cardiovascular function and measures of fatigue and temperature will be conducted prior to randomizing the subjects into the EX, CEX and C groups. The aerobic cycling program uses intermittent exercise of 1-hour duration, 3 days per week. Over 12 weeks, the exercise intensity progresses from 40-100% of the subject's initial maximal oxygen consumption. The C group will receive bimonthly phone calls for social contact. After 12 weeks, all subjects will be retested using the same protocols.

Results will be analyzed at an alpha level of .05 using multivariate analysis of variance (MANOVA), step-down analysis, and post hoc analyses where appropriate. For Phase I, it is expected that exercise performance will increase during the cooling conditions, especially PC and CDE. For Phase II, it is expected that the aerobic exercise program will increase cardiovascular function and functional performance. Positive results of our study would lead to a better understanding of treatment (cooling) possibilities and exercise rehabilitation procedures available for individuals with MS.

PREVIOUS GRANTS

NM Fisher,CV Granger, L Jacobs, C Brownscheidle. Fatigue in Multiple Sclerosis. The John R. Oishei Foundation, $81,000, 2000-2002. (subcontract from Dr. Lawrence Jacobs (Principal Investigator).

NM Fisher, CV Granger, L Jacobs, C Brownscheidle. A Follow-Up Study of the Positive Effects of Anti-Fatiguing Exercise for Persons with Multiple Sclerosis. The Jacob and Valeria Langeloth Foundation, $88,279, 2000-2001.

Langeloth Foundation 2000-2001
A Follow-up Study of the Positive Effects of Anti-Fatiguing Exercise for Persons with Multiple Sclerosis

Principal Investigator:
Nadine M. Fisher, Ed.D.

No evidence exists that resistance exercises of an anti-fatiguing nature may help improve an MS patient's hysiological reserve, thereby resulting in less overall fatigue. We have shown in our last study funded by the Langeloth Foundation~hat we are able to improve fatigue levels after a 16-week supervised program of anti-fatiguing exercises. In order to determine if a 16-week program can have an impact on maintaining lower fatigue levels over time, thereby increasing a NIS patient's functional independence and ability to contribute to society, we need to know if physiological reserve can be maintained at a usable level. The current project is studying the long-term effects of the supervised exercise program and the feasibility and effectiveness of a home-based equivalent to our supervised program.

Langeloth Foundation 1999
Anti-Fatiguing Exercise for Persons with Multiple Sclerosis

Chronic fatigue and weakness are a significant problem for individuals with Multiple Sclerosis (MS). The fatigue experienced by these individuals is typically cognitive and physical, therefore having the potential to significantly impact on their abilities to perform normal (home, work and leisure) activities. Strength, endurance and contraction speed are also compromised as individuals become more sedentary. This disease and its accompanying fatigue and weakness have further deleterious effects due its onset at an early age. MS typically affects women from 30-50 years of age. For the above reasons, we proposed to study this population in order to determine their levels of fatigue during a typical workday and to study the potential to rehabilitate these individuals with a specific program of anti-fatiguing exercise. The major objectives of the study were (1) to assess workday fatigue and recovery and (2) to evaluate the effects of a 16-week rehabilitation program of anti-fatiguing resistance exercises in individuals with MS.

NM Fisher, CV Granger, L Jacobs, C Brownscheidle, K Wende. Anti-Fatiguing Exercise for Persons with Multiple Sclerosis. The Jacob and Valeria Langeloth Foundation, $77,895, 1999.

NM Fisher. Rehabilitation Research and Training Center on Functional Assessment and Evaluation of Rehabilitation Outcomes. National Institute of Disability and Rehabilitation Research, US Department of Education, $2,400,000, 1993-1998.

PUBLISHED ABSTRACTS

Fisher NM, JE Graham. Relationship of core temperature to physical activity and fatigue in MS. Neurology 66(5)Suppl 2:A238, 2006.

Objective: The purpose of this study was to measure changes in core temperature (Tc) over one and a half days of simulated work activity in individuals with and without Multiple Sclerosis (MS), and to relate these changes to self-reported fatigue.
Background: Fatigue is the most common complaint among individuals with MS. Moreover, ~70% of patients report heat sensitivity, i.e. symptoms worsen as body temperature increases. The relationship between rising temperature and diminishing function is related to small physiological increases in core temperature which are capable of inducing temporary conduction slowing or blocks in demyelinated axons.
Design/Methods: Participants included 48 MS (age=46.8±8.4 yrs, EDSS=3.6±2.0) and 12 control (C: age=48.1±11.7 yrs) individuals. Tc was recorded every 5min with a CorTemp telemetry unit. Fatigue (visual analog scale) was assessed before and immediately after exercise testing, which involved maximal muscle and cardiorespiratory function tests. Testing was conducted in the morning, afternoon, and following morning.
Results: Significant changes (p<.05) in temperature and fatigue were shown within both groups, but more so in MS, over time. There was a trend towards higher Tc in MS relative to C at all time points (MS: 37.10±0.45ºC vs. C: 36.95±0.35ºC). Fatigue was significantly higher in MS than C over time (MS: 2.18±2.4 to 5.80±2.7 cm. vs. C: 1.10±1.4 to 4.27±2.3 cm.). Perceived fatigue levels were not associated with increases in Tc.
Conclusions/Relevance: Heat sensitivity has long been the basis for advising MS patients to avoid physical activity. In the current study, temperature fluctuations in individuals with MS were similar to those without the disease; i.e., abnormal thermoregulation was not evident across the wide range of energy expenditures (sleep to maximum voluntary exercise) assessed in this study. The lack of correlation between fatigue and temperature suggests that fatigue is primarily governed by other pathophysiological processes in MS. Supported by: National Institute on Disability and Rehabilitation Research.

Graham JE, Fisher NM. Supervised resistance training improves muscular function in individuals with multiple sclerosis. Neurology 66(5)Suppl 2:A239, 2006.

OBJECTIVE: This study assessed the effectiveness of a supervised resistance exercise program versus two home-based protocols on muscle functioning and functional performance in patients with multiple sclerosis (MS).
BACKGROUND: MS is a chronic disease that frequently results in fatigue and disability. MS is associated with reductions in physical activity as well as muscular strength and endurance. Exercise is increasingly being emphasized in the self-management of MS.
METHODS: Seventy-three individuals with mild-moderate (EDSS < 6.5) MS (46.7+7.5yrs) and 20 non-MS controls (NC) (43.6+8.4yrs) participated in the study. Outcomes included measures of muscular strength, endurance, and contraction velocity for lower (quadriceps, hamstrings) and upper (biceps) extremities and mobility-based functional tasks (25ft and 6min walks, timed stair climb). Following baseline testing, the MS patients were randomly assigned to one of four groups for 12wks: supervised resistance exercise (SE) (3 times/wk in lab), home exercise (HE) (2-home, 1-lab/wk), functional training (FT) (2-home, 1-lab/wk), or control (MSC).
RESULTS: MS were significantly (p<.05) lower than NC on all tests except biceps muscle function. SE demonstrated significant improvements on biceps (60%), hamstrings (32%), and quadriceps strength (54%); quadriceps endurance (21%) and contraction velocity (32%) after training. HE also showed significant improvements in quadriceps contraction velocity (17%). MSC demonstrated decreases in strength and endurance for all muscle groups tested. SE showed the greatest improvements compared to the other groups in biceps contraction velocity and hamstrings endurance, FT demonstrated better improvement in 6min walk and stairs, and MSC showed the most improvement in 25ft walk time. Correlations between muscle function and mobility measures were low to moderate (range: 0.326–0.668).
CONCLUSIONS: The data suggest that a systematic progressive resistance training program (SE) is capable of not just slowing long-term muscle-function deficits in MS, but actually improving muscle function. Moreover, a structured supervised setting is more effective than home-based protocols.


Venkatraman JT, A Krishnan, NM Fisher. Effects of resistance exercise intervention on plasma cytokines and chemokines in MS patients. FASEB J 16(5):A1054,762.16, 2002.

MS is a complex disease of the central nervous system that is characterized by demyelination of nerves, inflammation and edema, and results in significant declines in physical and/or cognitive functioning. The pathogenesis of MS is complex and several studies implicate proinflammatory Th1 cytokines as disease promoting, whereas Th2 cells have anti-inflammatory effects. Chemotactic MCP-1, RANTES and IL-8, expressed locally in response to inflammation, act in concert with cytokines in the recruitment of inflammatory cells into disease areas. The present study investigated the effects of a resistance exercise program on immunological aspects of MS. Blood was collected at baseline (Pre-exercise) and following 16 wks (Post-exercise) of an anti-fatiguing training program in 13 MS patients, ages 32-64 yrs. The levels of proinflammatory cytokines, TNF-alpha and IL-1beta, decreased following 16 wks of the resistance exercise program. Levels of IL-6 (p<0.001) and IL-4 (p<0.05) significantly increased in Post- Exercise MS patients. In addition, RANTES levels in plasma increased (p<0.05), while MCP-1 levels (p<0.05) significantly decreased in MS patients. Significant positive correlations between IL-2 and IFN-y (p<0.0001) and IL-8 and IL-6 (p<0.0001) were observed in MS patients. Resistance exercise may possibly induce changes in systemic immune function by lowering levels of cytokines and chemokines and subsequently, by modulating inflammation, and decreasing fatigue and improving physical performance. Exercise may alter immune function directly or indirectly through modifying stress and neuroendocrine factors that may play a role in maintaining optimal immune status in patients during times of illness. (Research supported by The Jacob & Valeria Langeloth Foundation).

Fisher NM, J Lenox, CV Granger, L Jacobs, C Brownsheidle.
Effects of an anti-fatiguing exercise program on fatigue and physiological function in patients with multiple sclerosis
. Neurology 54(7)Suppl 3:A338, 2000.

This study measured the effects of a simulated workday and overnight recovery on total, mental and physical fatigue, physiologic capacity and functional performance in patients with multiple sclerosis (MS). The efficacy and effects of an anti-fatiguing resistance exercise program on these parameters was also evaluated. MS is a common, chronic and debilitating disease with long term health consequences. The most debilitating symptom is the lingering fatigue that follows activity and limits function. Little data are available to quantify this fatigue or examine the physiological mechanism behind it. Physical activity increases fatigue and therefore exercise therapy has been overlooked as a treatment. We developed a program of resistance exercises, individually prescribed, to avoid fatigue while improving physiological capacity. This exercise program had not been tested previously in patients with MS. A pre-post-test repeated measures design was used with 16 patients (age=43+9yrs, weight=71+16kg) with confirmed MS (MRI). All subjects had EDSS scores of <6.5 and could ambulate a minimum of 50 ft. Tests were conducted in the morning, after a simulated workday, and the next morning, prior to and after the exercise program. Fatigue (total, mental, physical, force-time index), upper and lower body muscular strength, endurance, speed, and functional performance were measured in each test session. Data for each parameter were examined by Analysis of Variance for Repeated Measures (p<0.5). Subjects participated in the 16-week progressive anti-fatiguing resistance exercise program 3 days per week, 1 hour per day. All subjects completed all aspects of the study. They had increased fatigue at the end of the simulated workday (70%-108%), which remained until the next day (46%-76%). After the exercise program, the subjects were not fatigued at the end of the simulated workday or the next morning (residual). Maximal aerobic power, muscular strength, endurance, speed and functional performance were below control levels, but increased significantly after the anti-fatiguing exercise program by 16%, 42-75%, 43-97%, 192% and 8-14%, respectively. Patients with MS have reduced functional performance due to increased fatigue, which is secondary to the reductions in aerobic and muscular capacity. A simulated day's work increased fatigue and depressed physiological performance. These changes were still evident after a night's rest, suggesting a residual effect of a day's work on both fatigue and physiological variables. The patients enthusiastically completed the anti-fatiguing resistance exercises without exacerbation. The exercise program improved all physiological variables, led to reduced fatigue during the workday, eliminated the residual fatigue and improved functional performance. This anti-fatiguing resistance exercise program was beneficial to patients with MS and could serve to increase individual productivity and thus, could reduce disability and its associated costs in these patients.