Exercise Therapy
In
Neuromuscular Disease
05/10/2013
Maryam Tahmasbi Sohi, MD
Fellow in Neuromuscular Medicine
Department of Neurology
University of Kansas Medical Center
Objectives
• Overview of different types of exercise
• Physiologic responses to exercise
• Review of available literature for specific
neuromuscular disorders
• Recommendations
• Will not cover pulmonary rehabilitation
Different Types of Exercise
Flexibility Training
•
•
•
•
Involves stretching and range of motion
Reduces pain
Reduces spasticity
Increases joint
blood flow and
lubrication
• Prevents contractures
Aerobic Exercise
•
•
•
•
•
Prolonged low-resistance
Dynamic activity
Large muscle groups
Cardiopulmonary effects
American College of Sport Medicine (ACSM)
recommendation:
– 30 minutes at 55%-90% of maximum heart rate
or
– 40-85% of maximum oxygen uptake (VO2 max)
– 4 days a week
Aerobic Exercise-Benefits
•
•
•
•
Improves functional exercise capacity
Decreased psychological stress
Improves quality of life
Prevents secondary disease (DM, HTN,
CAD)
• Improves sleep
• Helps maintain bone density if performed in a
weight bearing manner
• Produces greater independence with ADLs in
elderly population
Maximal Aerobic Capacity
(VO2 Max)
• Maximum capacity of an individual's body to
transport and use oxygen during incremental
exercise
• Reflects the physical fitness of the individual
• L/min or mL/kg/min
• Graded exercise test while
measuring ventilation, O2
and CO2
• O2 consumption remains
unchanged despite an
increase in workload
Static
Strengthening
Exercise
Isometric
Eccentric
Isotonic
Concentric
Dynamic
Isokinetic
Static
Strengthening
Exercise
Isometric
Eccentric
Isotonic
Concentric
Dynamic
Isokinetic
Isometric Exercise
• No change in muscle length
• No visible joint movement
• Primary use is for rehabilitation of joints
with limited ROM due to injury
or post op
• Only increases strength
within a limited range of
motion (ROM)
Static
Strengthening
Exercise
Isometric
Eccentric
Isotonic
Concentric
Dynamic
Isokinetic
Isokinetic Exercise
• Constant speed
• Variable resistance
throughout the range of
motion
• Lower chance of injury
• Athletic training for
strengthening throughout
the required ROM
Nautilus- Upright Exercise Bike
Static
Strengthening
Exercise
Isometric
Eccentric
Isotonic
Concentric
Dynamic
Isokinetic
Concentric Contraction
• Muscle shortens to generate force
• Force generated is sufficient to overcome the
resistance
Eccentric Contraction
• Muscle fibers lengthen
• Force generated is insufficient to overcome
the external load on the muscle
• Mean of decelerating a body part or object,
or lowering a load gently rather than letting
it drop
• Negative training
Sarcomere
Delayed-Onset Muscle Soreness
(DOMS)
• Muscular discomfort and pain
• 24±48 h after strenuous exercise
• Proximal and distal muscle tendon junctions spreading
throughout the entire muscle
• Directly associated with the eccentric exercise (Asmussen
1952, 1956)
• Objective findings:
– Strength loss
– Reduced range of motion
– Elevated serum creatine kinase (CK)
DOMS
• Z disk is the most
vulnerable structure
• Type II fiber- biased
damage (Lieber & FrideÂn
1988)
• Loss of desmin,
inflammatory changes
and necrosis in animals
• Older men are not as
susceptible (Lavender and
Nosaka; 2006)
Physiologic Response to Exercise
• Neural adaptation:
– Accounts for early strength gain with training
programs (2 weeks)
– Increase in muscle strength without noticeable
hypertrophy
• Muscular Adaptation:
– 6-8 weeks to develop
– Increase in muscle cross-sectional area (muscle
hypertrophy) in response to resistive exercise
– Fast twitch (type II) fibers more than type I
Cross-transference
• Strength gain in the opposite, untrained
limb following unilateral resistance training
• Due to neural adaptation
• Improves the strength of a unmovable
injured limb or during post surgical period
• Implication in research:
– Cannot use the opposite limb as control
– 7.8-10% improvement in strength of the
untrained limb (Meta-analysis study)
Neuromuscular Disease Spectrum
• Motor neuron disease
(ALS, polio)
• Nerve roots or
peripheral nerves
• Neuromuscular junction
transmission (MG,
LEMS)
• Myofiber
– Acquired (IBM, DM, PM)
– Congenital (MD,
BMD,DM, Mitochondrial)
Questions to answer
Safe?
Beneficial?
Studies in NMDs
• Limited number of studies
• Methodological limitations
– Lack of good controlled studies due to the rarity of NMDs
– Grouped subjects with different NMDs with different
disease type, severity, and rate of progression
– Little uniformity regarding the type of exercise
interventions (aerobic, strengthening, or combinations of
exercise regimens),duration of exercise, intensity of
exercise therapy, and initial state of physical activity and
fitness
– Lack of clearly identified primary and secondary
outcome measures
• Strength, endurance, fatigue, cardiopulmonary function,
functional ability, activities of daily living, anxiety, depression,
wellbeing, and pain
Muscular Dystrophies
• Heterogeneous group of
hereditary muscle
diseases
• Progressive muscle
weakness
• Muscle fiber damage,
inflammation, necrosis,
and regeneration
• Defects in sarcolemmal
and extracellular matrix
proteins, essential in
maintaining the
cytoskeletal framework of
the muscle fiber during
muscle contraction
DMD
BMD
Incidence
1 in 3,500
1 in 30,000
Age of Onset
3 to 5 yrs
> 7 yrs
Dystrophin
Mutation
CK
Frameshift Mutation
In-frame Mutation
Presentation
Very high (5,000 to 20,000)
Proximal > Distal
Symmetric Legs & Arms
Calf Hypertrophy
Failure to Walk 9 - 13 years
Cause of death
16-80 years
Respiratory failure
Cardiac
Strengthening Exercise
• Studies in dystrophin-deficient mdx mice
have shown that dystrophic muscle is more
susceptible to contraction-induced muscle
damage compared to healthy mice
• Available randomized control trials are small
in size, with inconsistent methodologies and
conflicting results
• General consensus is that high resistance
strengthening exercises are contraindicated
in patients with dystrophinopathy
Unstable sarcolemma makes the
muscle susceptible to mechanical
stress , muscle fiber necrosis, fiber
loss, and replacement with fibrotic
tissue
Disruption of dystrophin down regulates
nitric oxide synthase (nNOS), which
leads to disregulation of blood flow to
the muscle and functional muscle
ischemia
Tadalafil-Muscle Ischemia-BMD
“Tadalafil Alleviates Muscle Ischemia in
Patients With Becker Muscular Dystrophy”
• Randomized placebo-controlled crossover
trial
• Tadalafil (phosphodiesterase 5A inhibitor)
• Functional muscle ischemia is alleviated and
normal blood flow regulation is fully restored
in the muscles of men with BMD
• There were no adverse events or side effects
Martin et al 2012
Endurance Training and BMD
Method:
• Eleven patients with BMD and seven healthy subjects
• All patients were ambulant
• Onset of symptoms at age 8 ± 2years
• Asymptomatic cardiomyopathy (LVEF):35–45% in 3
patients
• Forced vital capacity (FVC) was on average decreased
by 14±2% (within normal limits)
Primary Outcomes: VO2max, Plasma Ck, and self report
questionnaire
Intervention: Cycled 50, 30min sessions at 65% of their
VO2max over 12 weeks, and six patients continued cycling
for 1 year
Sveen et al 2008
Endurance Training and BMD
Results:
– Improved VO2max by 47± 11% in patients (P0.005)
– Weekly CK levels did not increase with training
– No change in the number of central nuclei, necrotic and
regenerating fibers
– Strength in muscles involved in cycle exercise (knee
extension, and dorsi- and plantar-flexion) increased
significantly by 13-40%.
– Cardiac pump function, measured by echocardiography, did
not change with training
– All improvements and safety markers were maintained after 1
year of training
Conclusion:
– Moderate endurance training is safe to increase exercise
performance and daily function in patients with BMD
Sveen et al 2008
High Intensity Endurance Training
“Creatine kinase response to high-intensity
aerobic exercise in adult-onset muscular
dystrophy”
Method:
• Fourteen patients with muscular dystrophy (BMD: 5, FSHD:
5 , LGMD2-I and LGMD2-A: 4 )
• Eight healthy subjects
• 5 cycling tests at 65, 75, 85 and 95 % of VO2 max
• Heart rate and oxygen consumption were measured during
tests
• Plasma CK was measured before, immediately after, and
24 hours after exercise
Anderson et al 2013
High Intensity Endurance Training
Results:
• Plasma CK increased after all exercise tests in
all patients
• In persons affected by LGMD2A, LGMD2I, and
FSHD, plasma CK declined to the pre-exercise
level 24 hours after exercise
• Plasma CK remained elevated 24 hours after
exercise in persons with BMD (only after the
95% of VO2max test)
• The subjects never scored higher than 3.5 on
the leg pain VAS (immediately after exercise)
Anderson et al 2013
High Intensity Endurance Training
Conclusion:
• High-intensity aerobic exercise is generally
well-tolerated in persons with LGMD2 and
FSHD
• Patients with BMD may be more prone to
exercise induced damage
• Closer supervision of training is warranted
if high-intensity exercise is implemented
Anderson et al 2013
Idiopathic Inflammatory Myopathies
(IIM)
• Heterogeneous group of rare disorders that present
with acute, subacute, or chronic muscle weakness
• Overlapping clinical manifestations
• Divergent from the histopathological and
pathogenetic standpoints
• Generally respond well to immunosuppressive
therapy
• Inclusion body myositis (IBM), the most common
IIM in the elderly, is clinically, histopathologically
and pathogenetically distinct
• IBM is refractory to all currently available therapies
Exercise and IIM
• Studies in active and chronic disease phase
have been reported
• All demonstrated the safety and efficacy of
exercise
• Neuromuscular specialists usually wait for the
first two to three months for strength and CK to
start responding to pharmacotherapy before
starting the strengthening exercise program
• Early mobilization is important to prevent
flexion contractures
Dimachkie 2011
Exercise and IBM
(Arnardottir et al, 2003):
• A home exercise program, five days a week for 12 weeks,
was found to be safe in seven patients. There was no
strength deterioration, no change in serum CK, and no
increased in muscle inflammation on biopsy
(Johnson et al., 2009):
• Aerobic exercise program using a stationary cycle
ergometer at 80% of the initial maximum heart rate (for two
minutes less than the total time achieved during maximal
aerobic test) combined with resistance isometric and
isotonic exercises of the upper and lower limbs in a group of
seven IBM cases. Besides demonstrating it to be safe, they
found this exercise routine to improve aerobic capacity and
muscle strength.
Dimachkie 2011
Mitochondrial Myopathy
•
•
•
•
Heterogeneous group of metabolic muscle disorders
Mutation in either nuclear or mitochondrial DNA (mtDNA)
Brain and skeletal muscles are particularly susceptible
Single-organ to multisystem disorders (muscle weakness
or exercise intolerance, arrhythmia, dementia, movement
disorders, stroke-like episodes, deafness, blindness,
ophthalmoplegia, and seizures)
• Heteroplasty: mtDNA mutations coexist with wild-type
mtDNA (Mild phenotypes have higher proportions of
wild-type mtDNA)
• Mature muscle cells have a high degree of mtDNA
mutations, whereas the level of mutations is low or
undetectable in satellite cells
Exercise in MT-Myopathy
• Resistance exercise serves as stimulus for
satellite-cell induction within skeletal muscle,
lowering the level of mutant mtDNA and
improving oxidative capacity (Murphy et al 2008)
• The beneficial effects of endurance training
have been reported in 8 published reports,
with no adverse effects
• Hypothesized to induce mitochondrial
biogenesis and capacity for oxidative
phosphorylation  improve function
Amyotrophic Lateral Sclerosis
(ALS)
• Progressive degenerative disease of the upper
and lower motor neuron
• Majority of cases are sporadic (90%)
• Hereditary defect in the superoxide dismutase
(SOD) gene (20%)
• Studies of exercise on SOD deficient mice suggest
that endurance exercise training at moderate
intensities slows disease progression, and
increases lifespan
• High-intensity exercise showed no improvement or
hastened symptoms and death
Exercise and ALS
• Twenty-five patients were randomized to
receive a moderate daily exercise
program (n=14) or control (n=11)
• Outcome measures at baseline and after
3, 6, 9 and 12 months
–
–
–
–
–
Manual muscle strength testing
Ashworth spasticity scale
ALS functional rating scale (ALSFRS)
Visual analog scale for pain
Quality-of-life scale (SF-36)
Drory et al 2001
Exercise and ALS
• At 3 months, patients who performed regular
exercise showed less deterioration on FRS
and Ashworth scales, but not on other
parameters
• At 6 months, there was no significant
difference between groups, although a trend
towards less deterioration in the treated
group on most scales was observed
• At 9 and 12 months, there were too few
patients in each group for statistical
evaluation
Exercise and ALS
Method:
27 patients with a diagnosis of ALS, FVCof ≥90% predicted,
and ALS Functional Rating Scale (ALSFRS) score of 30 or
greater were randomly assigned to a resistance exercise
group (n=13) or to a usual care group (n=14)
Results:
- Eight resistance exercise subjects and 10 usual care
subjects completed the trial
- At 6 months, the resistance exercise group had significantly
higher ALSFRS and SF-36 scores
- No adverse events
- Less decline in leg strength measured by MVIC
Bello- Haas et al 2007
Post Polio Syndrome
• Affects individuals who had a confirmed case
of polio with a partial or fairly complete
neurological and functional recovery after the
acute episode
• At least 15 years of neurological and
functional stability
• Presenting with gradual or abrupt onset of
new muscle weakness, muscle atrophy,
muscle pain, and fatigue
• Persists for more than 1 year
Exercise in PPS
• European Federation of Neurological Society
(ENFS) task force determined that both
aerobic training and progressive resistance
exercise training can benefit individuals with
PPS (2006)
• Systematic analysis by Cup et al in 2008
determined that there is insufficient evidence
to assess the effectiveness of muscle
strengthening exercises, aerobic exercises, or
a combination of these exercises in
individuals with PPS
Abresch et al 2009
Class Remote
Recent
Exam *
Weakness Weakness
EMG/NCS**
I
No
No
Normal
Normal
II
No
No
Normal
Chronic denervation
III
Residual
No
Abnormal
Chronic ± Active
denervation
IV
Residual
Yes
Abnormal
V
Residual
yes
Abnormal
Chronic ± Active
denervation
↓insertional activity
Chronic ± Active
denervation
*: Visible atrophy, Manual muscle testing, DTRs, sensation
**: biceps, triceps, and FDI in UE and Med gastroc, TA, and Quad in LE
Halstead et al 2010
Class Remote
Recent
Exam *
Weakness Weakness
EMG/NCS**
I
No
No
Normal
Normal
II
No
No
Normal
Chronic denervation
III
Residual
No
Abnormal Chronic ± Active
denervation
IV
Residual
Yes
V
Residual
yes
Abnormal Chronic ± Active
denervation
Abnormal ↓insertional activity
Chronic ± Active
denervation
*: Visible atrophy, Manual muscle testing, DTRs, sensation
**: biceps, triceps, and FDI in UE and Med gastroc, TA, and Quad in LE
Proposed Exercise in PPS
• Class 1:
– Moderate intensity: 60-80% maximal HR
– Duration: 15-30 min
– Frequency: 3-5/week
Examples:
• Swimming 25-35 yards/min
• Walking 5-6 mph
• Bicycle riding 12-14 mph
Halstead et al 2010
Class Remote
Recent
Exam *
Weakness Weakness
EMG/NCS**
I
No
No
Normal
Normal
II
No
No
Normal
Chronic denervation
III
Residual
No
Abnormal Chronic ± Active
denervation
IV
Residual
Yes
V
Residual
yes
Abnormal Chronic ± Active
denervation
Abnormal ↓insertional activity
Chronic ± Active
denervation
*: Visible atrophy, Manual muscle testing, DTRs, sensation
**: biceps, triceps, and FDI in UE and Med gastroc, TA, and Quad in LE
Proposed Exercise in PPS
• Class II:
– Moderate intensity: 60-80% maximal HR
– Duration: 15-30 min
– Frequency: 3-4/week on alternate days
– Pacing: perform 4-5 min, rest 1 min
*Decrease if pain, fatigue or new weakness
Halstead et al 2010
Class Remote
Recent
Exam *
Weakness Weakness
EMG/NCS**
I
No
No
Normal
Normal
II
No
No
Normal
Chronic denervation
III
Residual
No
Abnormal Chronic ± Active
denervation
IV
Residual
Yes
V
Residual
yes
Abnormal Chronic ± Active
denervation
Abnormal ↓insertional activity
Chronic ± Active
denervation
*: Visible atrophy, Manual muscle testing, DTRs, sensation
**: biceps, triceps, and FDI in UE and Med gastroc, TA, and Quad in LE
Proposed Exercise in PPS
• Class III:
– Low intensity: 40-60% of max HR
– Duration: 15-20 min
– Frequency: 3-4/week
– Pacing: Resting 1 min/2-3 min of activity
*modify if new weakness, pain or fatigue
Halstead et al 2010
Class Remote
Recent
Exam *
Weakness Weakness
EMG/NCS**
I
No
No
Normal
Normal
II
No
No
Normal
Chronic denervation
III
Residual
No
Abnormal Chronic ± Active
denervation
IV
Residual
Yes
V
Residual
yes
Abnormal Chronic ± Active
denervation
Abnormal ↓insertional activity
Chronic ± Active
denervation
*: Visible atrophy, Manual muscle testing, DTRs, sensation
**: biceps, triceps, and FDI in UE and Med gastroc, TA, and Quad in LE
Proposed Exercise in PPS
• Class IV:
– Trial of rest to exclude overuse weakness
– Daily active/passive stretching program
– No cardiopulmonary aerobic exercise
– If overuse is excluded, trial of monitored, nonfatiguing, progressive resistive exercise
program
– If overuse weakness, modify activity, use
bracing, scooter, etc.
Halstead et al 2010
Class Remote
Weakness
Recent
Exam *
Weakness
EMG/NCS**
I
No
No
Normal
Normal
II
No
No
Normal
Chronic denervation
III
Residual
No
Abnormal Chronic ± Active
denervation
IV
Residual
Yes
V
Residual
yes
Abnormal Chronic ± Active
denervation
Abnormal ↓insertional activity
Chronic ± Active
denervation
*: Visible atrophy, Manual muscle testing, DTRs, sensation
**: biceps, triceps, and FDI in UE and Med gastroc, TA, and Quad in LE
Proposed Exercise in PPS
• Class V:
– Performing activities of daily living
– Bracing and/or wheelchair usually needed
Halstead et al 2010
Diabetic Neuropathy
• Pilot study
• Seventeen subjects (8 males/9 females; age 58.4±5.98;
duration of diabetes 12.4±12.2 years)
• 10- week supervised, moderately intense aerobic and
resistance exercise program
• Outcome measures:
– Pain (visual analog scale)
– Michigan Neuropathy Screening Instrument (MNSI)
– Intraepidermal nerve fiber (IENF) density and branching
RESULTS:
• Significant reductions in pain, neuropathic symptoms, and
increased intraepidermal nerve fiber branching from a
proximal skin biopsy
Pasnoor et al 2012
Conclusion
1. Individuals with NMDs should adopt an
active lifestyle for its physical and
psychological benefits
2. Stretching and range-of-motion exercises
may be helpful in decreasing the discomfort
due to the limited joint mobility
3. Moderate resistance exercise should be
given to patients with antigravity strength or
better to maintain strength
Abresch et al 2012
Conclusion
4. Moderate aerobic exercise should be given
to prevent deconditioning and loss of
cardiopulmonary fitness
5. High-intensity exercises relative to an
individual’s strength should be avoided
6. The intensity and frequency of exercise
should be tailored to individual's level of
physical fitness and need
7. The effects of exercise should be closely
monitored
Abresch et al 2012
What to Tell Patients?
•
•
•
•
•
Moderate:
40-60% VO2 Max or 60%of maximum HR
Walking as fast as 100 steps per minute
Breathing quickens, but not out of breath
Develop a light sweat after about 10
minutes of activity
• Can carry on a conversation, but you can't
sing
What to Tell Patients?
Vigorous exercise intensity
• Breathing is deep and rapid
• Develop a sweat after a few minutes of
activity
• Cannot say more than a few words without
pausing for breath
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exercise program on muscle function,histopathology and
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neuromuscular disease to occupational therapy, physical therapy
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•
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• FrideÂn, J. & Lieber, R.L. 1998. Segmental muscle ®ber
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165±171
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Thank You