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29 Cards in this Set
- Front
- Back
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Duchenne Muscular Dystrophy (DMD)
Most common of the human muscular dystrophies –___ recessive disorder –GeneXp21: discovered 1982-60% deletion and 40% spontaneous mutation –Absence of large muscle protein: ___-discovered 1987 –Skeletal and Cardiac Muscle –Affects 1/3500 males –100% LETHAL |
X-linked
Dystrophin |
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Dystrophin is found on the ___ surface of muscle cell membranes
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cytoplasmic
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___ is the Key building block to muscle fibers
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Dystrophin
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Function of dystrophin: to stabilize the ___
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plasma membrane
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dystrophin provides mechanical reinforcement to the ___ ->protecting the membrane from stresses developed during muscle contraction
•Mechanical stress vs# of activations •Repeated contractions and relaxations |
sarcolemma
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Diagnosis of DMD
Blood tests: elevated ___ levels > ___ (nl=200) |
CK
5000 |
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Diagnosis of DMD
Muscle ___: necrosis and regeneration,variation in muscle fiber size, increased ___ fibers, increased ___, fat infiltration, increased # ___ |
biopsy
type I connective tissue macrophages |
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Diagnosis of DMD
Clinical signs: ___ sign, weakness, coordination problems, clumsiness, enlarged ___ |
gowers
calf’s |
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Monitoring Muscle Damage
Muscle Biopsy & Histology ___ Tissue Representation Biopsy is Invasive |
Limited
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Disease Progression
Missing Dystrophin or DAG = Decreased ___ Stability Damage to Sarcolemma Satellite Cells Fuse and Repair Fibers Cell Signaling |
Sarcolemmal
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Damage
•Mechanically induced damage: eccentric, concentric, isometric contractions –Produce micro lesions-> loss of ___homeostasis, and cell death |
Ca2+
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Damage
Downstream events: –Altered regeneration, inflammation, impaired ___ adaptation (lack of O2), and ___ |
vascular
fibrosis |
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___ provides a noninvasive and sensitive method to monitor changes in
dystrophic muscle fiber structure and integrity |
MRI
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Progress ___ muscles to smaller muscles, ___ before UE, proximal muscles first weakness then distal muscles
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large
LE |
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DMD Progression
• ___ muscles are the first to show weakness • Muscle weakness leads to changes in ___ and difficulty with daily activities (Sussman, 2002) • Wheelchair required by early to mid-teens • Shortened life expectancy: early to mid-20s |
Proximal
posture |
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Weakness
Pseudo-hypertrophy Postural changes Impaired mobility - ___ Sign |
Gower's sign
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Muscular Dystrophy - Therapeutic Approaches
Cell Therapy Gene Therapy Pharmaceutics |
ok
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Current Therapies
•___ gene delivery •Correction of mutant dystrophin(RNA/DNA) •Cell based therapies-delivery of normal cells to dystrophic muscle |
Dystrophin
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Molecular, Cellular, Pharmacological Therapies
•Correcting the molecular defect •Promoting muscle cell survival |
ok
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Pharmacological Approaches
•Allupurinol, vitamin E, selenium, growth hormone->___ |
ineffective
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Pharmacological Approaches
•Up-regulation of dystrophin-related protein ___->different locations on the sarcolemma |
utrophin
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Pharmacological Approaches
•Antibiotics-Stop codon within the coding sequence, misreading of RNA code->made a difference but can’t restore all of dystrophin |
ok
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Pharmacological Approaches
•Myostatin and ___->effecting satellite cell function between basal lamina and sarcolemma |
glucocorticoids
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Research at University of Florida MRI Studies
•To develop magnetic resonance as a ___ of disease progression in boys with Duchenne Muscular Dystrophy •Natural History •PTC Therapeutics •Multi-center trials |
biomarker
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Disease Progression/Pathology
Why MRI/MRS? Noninvasive/nondestructive • Detailed information • Quantitative • Sensitive • MRI – Cross-sectional area (CSA) – Qualitative fatty infiltration – Contractile area • MRS – Quantification of intramuscular lipids |
ok
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Disease Progression/Pathology
Strength • Weakness becomes more evident with increasing age • Lower extremities ___ than upper extremities • ___ weaker than distal • MMT’s inferior to quantitative tests |
weaker
Proximal |
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Gait
Preliminary Data Spatiotemporal Parameters Stride and step lengths were ___ in DMD subjects (p < 0.05) -Trend for ___ base of support and slower gait velocity (p < 0.09) |
shorter
greater |
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Clinical Interventions
• Preserving ROM – Not over stretching – ___ for decreasing impact/progression of contractures • Balance: ankle strategy, trunk reactions • Respiratory care – Assistive cough, positioning, CPT • Swimming, Hippotherapy |
Orthoses
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Rehabilitation
(Grange & Call, 2007) •No sufficient data in the literature to justify a sound exercise prescription for DMD |
ok
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