Physical Activity in Neuromuscular Disease

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Physical Activity in Neuromuscular Disease
Craig M. McDonald, MD, Assoc. ProfessorDepartment
s of PMR and PediatricsUC Davis School of
Medicine cmmcdonald_at_ucdavis.edu Director RRTC
in Neuromuscular Diseases, UCDMC Neuromuscular
Disease Clinic, and UCDMC Pediatric
Rehabilitation Program Presented at NIDRR
Rehabilitation Research and Training Center in
Neuromuscular Diseases Roundtable 2001 Role of
Physical Activity and Exercise Training in
Progressive Neuromuscular Diseases. Sept. 30,
Oct. 1-3, 2001, San Diego, CA.
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Hereditary and Acquired Neuromuscular Diseases

• Definition Peripheral disorders of the nervous
  system affecting anterior horn cells, peripheral
  nerves, neuromuscular junction, and muscle.
• More than 300 neuromuscular diseases (NMD over
  250 distinct genes)
• Prevalence of the most common NMD is
  approximately 400,000
• Overall prevalence is greater than 4 millionin
  the U.S.

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Enhance Quality of Life in Persons with
Neuromuscular Disease
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Quality of Life According toConsumers with NMD

• Comprehensive Quality of Life Survey of target
  population (n 811) reported problems that
  reduce quality of life
• Weakness
• Difficulty getting exercise
• Fatigue / poor endurance
• Problems with weight
• Respiratory / sleep problems
• Pain

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Limitations in Physical Activity in NMD from
SF-36 (n 811)
Recalculated from physical activity data from
the SF-36 survey conducted by Abresch et al., Am
J Hospice and Palliative Care 200219(1)39-48.
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Physical Activity in NMD

• Impact of reduced physical activity on health and
  fitness
• Methodologic issues relating to assessment of
  physical activity
• Determinants of physical activity(in DMD)

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Goals of Physical Activity Exercise in NMD

• Increased cardiopulmonary endurance
• Increased lean mass, decreased fat mass
• Increased muscle strength endurance
• Improved flexibility
• Improved health outcomes
• Psychosocial benefits

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Benefits of Physical Activity in the Able-Bodied

• Prevention and control of
• Coronary artery disease
• Hypertension
• NIDDM
• Osteoporosis
• Obesity
• Mental health

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Persons with NMD are Sedentary and Deconditioned

• Lower work capacity / peak VO2
• Reduced resting energy expenditure
• Body composition changes
• Decreased muscle strength and endurance

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Age-Related Changes Observed in Sedentary Subjects

• Greater
• age-related decline in VO2 max
• decrease in muscle mass (sarcopenia)
• increase in body fat
• decrease in strength
• reduction in walking speed in those with weak
  knee extension

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Reduced Exercise Performance in NMD Disuse or
Disease?
Reduced functional muscle mass
(Disease) Reduced physical activity Disuse
atrophy To the extent that reduced exercise
performance is due to the effects of detraining
from a sedentary existence, endurance exercise
may be helpful in reversing the negative effects
of the deconditioned state. (Neufer 1989)
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Objective Assessment of Physical Activity
Current Methods

• Diary/self-report
• Doubly labeled water (total energy expenditure)
• Standard pedometry
• Accelerometers
• Long-term heart rate monitoring (with HR-VO2
  calibration)

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Goals for the Quantitative Assessment of
Physical Activity

• When is a subject active/sedentary duringa day ?
• What is the magnitude of peak activity?
• What is the average total daily physical activity
  over extended sampling time?
• What is the mean proportion of time spent at
  defined physical activity intensities?
• Unobtrusive monitoring in community.

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Physical Activity Assessment Heart Rate
Monitoring
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Physical Activity in Slowly Progressive NMD
(McCrory 1998)

• n 26 (MMD, HMSN-1, Limb Girdle Dystrophy, FSHD,
  BMD, SMA III
• Community heart rate monitoring
• TEE REE ACTEE

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Physical Activity in Slowly Progressive NMD
(McCrory 1998)
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Physical Activity in Slowly Progressive NMD
(McCrory 1998)

• NMD subjects reported spending less time
  exercising than controls
• NMD exercise at light level, controls at
  moderate level
• Body fat in NMD subjects inversely related to
  minutes active and fat-free mass

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Step Activity Monitor (PRS, Seattle, WA)
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Step Activity Monitor (PRS, Seattle, WA)
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Accuracy of the SAM
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Step Activity Monitor (PRS, Seattle, WA)
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(No Transcript)
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Total Daily Steps in Able-Bodied Control Children
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Step Activity Able-Bodied Obese vs. Controls
(children ages 6-10)
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Determinants of Physical Activity

• Medical Rehabilitation Model(NCMRR)
• Pathophysiology
• Impairment
• Functional limitation
• Disability
• Societal limitation

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Natural History of Duchenne Muscular Dystrophy
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DMD/BMD Gene
XP 21 locus 2.4 million base pairs Exons 1 -
79 Hotspots Exons 3 - 19
Exons 42 - 60
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Pathophysiology
Defined Interruption of or interference with
normal physiological and developmental processes
or structures. Example Absence of dystrophin
leads to progressive loss of functional muscle
fibers in DMD.
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Dystrophin Complex
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Dystrophin
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Pathophysiology of Duchenne Muscular
Dystrophy
Gene abnormality at xp 21 Absence of
dystrophin Susceptibility of sarcolemmal
membrane to mechanical injury Muscle fiber
injury and degeneration Cycles of degeneration
and regeneration Cell death (replacement by fat
connective tissue)
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Muscular Dystrophy Muscle Biopsy Findings

• Histology
• Normal fibers
• Hypertrophy of fibers
• Degeneration of fibers
• Atrophy of fibers
• Regeneration of fibers
• Connective tissue/fatty infiltration

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Muscle Biopsy 3-yr-old boy, normal fiber
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Muscle Biopsy 3-yr-old, DMD fiber
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Muscle Biopsy 8-yr-old, DMD fiber
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Muscle Biopsy 19-yr-old, DMD fiber, postmortem
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Biceps Muscle Biopsy 19-yr-old, DMD fiber,
postmortem
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Gastrocnemius Muscle 19-yr-old, DMD fiber,
postmortem
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DEXA
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DEXA Scan of 17-yr-old Male with DMD

• Validity measure of body composition
• Test-retest reliability 0.998
• Applicable to severe NMD with myogenic atrophy
• Scoliosis and contractures

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Body Composition in DMD
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Mean Lean Tissue Mass in DMD
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Body Fat and Physical Activity in DMD

• Correlation between body fat by DEXA and
  total steps per day by SAM -0.61.

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Impairment

• Defined Loss or abnormality of cognitive,
  emotional, physiological, or anatomical structure
  or function, including all losses or
  abnormalities, not just those attributable to the
  initial pathophysiology.
• Example Decreased strength in DMD due to loss
  of muscle fiber, impaired contractility, and/or
  disuse weakness.

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Quantitative Strength Testing in DMD
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Quantitative Strength Testing in DMD
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Strength per Lean Tissue Ratio in DMD
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Impairment Predicts Functional Limitation

• Correlation between knee extension strength and
  walking speed in DMD 0.70.
• Walking speed predicts time to wheelchair
  (McDonald, 1995).

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Functional Limitation Leads to Further
Impairment

• Transition to sedentary existence in wheelchair
  leads to contractures in DMD.
• Short periods of bed rest result in significant
  loss of strength and function in DMD.

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Ankle Plantarflexion Contractures in DMD
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Knee Contractures in DMD
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Hip Flexion Contractures in DMD
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Static Positioning Leads to Contractures in DMD
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Elbow Flexion Contractures in DMD
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Static Positioning Leads to Contractures in DMD
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Impairments that Reduce Physical Activity in DMD

• Weakness (due to dystrophinopathy and disuse)
• Fatigue
• Cardiopulmonary involvement
• Contractures
• Excessive weight gain

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Weight Management inNeuromuscular Disease

• Obesity (sedentary)
• Cacchexia (end-stage)

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Weight Gain in DMD
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Functional Limitation

• Defined Restriction or lack of ability to
  perform an action in the manner or within a range
  consistent with the purpose of an organ or organ
  system.
• Example Decreased velocity of ambulation,
  decreased distance achieved per unit time,
  metabolically inefficient ambulation in DMD.

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Velocity of Locomotion in DMD
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Percent Individuals Who Walked Distance in Ten
Minutes
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Energy Cost of Locomotion with COSMED K4b2
Validity Test-retest reliability
0.94 Functionally relevant measure of economy of
actual locomotion
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Energy Expenditure During Wheelchair Propulsion
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Economy of Movement Able-Bodied Obese vs.
Controls
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O2 Cost During Walking and Sprinting
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Walking O2 Cost vs. Velocity
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Heart Rate in DMD During 100-Meter Sprint
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Sprinting VO2 vs. Distance Traveled 100-meter
Sprint
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VO2 per Gram Lean (DEXA)
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Sprinting O2 Cost vs. Velocity
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Disability

• Defined Inability or limitation in performing
  tasks, activities, and roles to levels expected
  within physical and social contexts.
• Example Inability to exercise, decreased daily
  physical activity in the community in DMD.

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Step Activity Monitor (24 Hour) Able-Bodied
Control
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Step Activity Monitor (24 Hour) Duchenne
Muscular Dystrophy
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Step Activity in DMD vs. Controls
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Quantitative Physical Activity in DMD
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Societal Limitation

• Defined Restriction, attributable to social
  policy or barriers (structural or attitudinal)
  which limits fulfillment of roles or denies
  access to services and opportunities that are
  associated with full participation in society.
• Example Teenager in power wheelchair with DMD
  does not participate in PE adaptive PE not
  available or is poorly developed.

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Future Needs Scientifically Based
Recommendations Concerning Optimal Exercise
Guidelines

• Disease-specific recommendations relating to
  types of exercise that can be safely performed.

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Future Needs Scientifically Based
Recommendations Concerning Optimal Exercise
Guidelines

• Disease-specific recommendations relating to
  types of exercise that can be safely performed.
• Recommendations regarding the minimum frequency,
  amount, and duration of exercise required for
  beneficial health effects.

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Future Needs Scientifically Based
Recommendations Concerning Optimal Exercise
Guidelines

• Disease-specific recommendations relating to
  types of exercise that can be safely performed.
• Recommendations regarding the minimum frequency,
  amount, and duration of exercise required for
  beneficial health effects.
• Development of novel approaches to enhance levels
  of physical activity in persons with varied
  severities of impairment due to NMD.
• This work was supported by the National
  Institute on Disability and Rehabilitation
  Research Grant HB133B980008 and a grant from the
  National Institutes of Health RO1 HD35714.