Muscular Dystrophy and other Myopathies

Congenital Myopathies

• Affect both boys and girls • Apparent at birth or before age 2 • Hypotonic (floppy) or weak infant • Slow/rapid; mild/severe impairment - Usually non‐progressive or slowly progressive • Unusual morphological changes in muscle fibers

Metabolic Myopathies McArdle's Disease

• Affects about 1 in 100,000 people in the United States. • Myophosphorylase deficiency - No ATP for muscles to generate movemnt • Autosomal recessive • Cramps and muscular stiffness on exertion • Myoglobinuria may occur in 50% of cases • No specific treatment • Avoid sudden strenuous exercise

Metabolic Myopathies Pompe's Disease

• Affects about 1 in 40,000 people in the United States. • Infantile‐onset acid maltase deficiency • Autosomal recessive • Generalized progressive weakness • Death usually from cardio‐respiratory failure before age 2 • Childhood‐onset and adult‐onset forms are less severe than infantile form

Duchenne Muscular Dystrophy

• Affects ~ 1 in 3500 live male births • X‐linked disease • Boys usually present below age 5 with proximal weakness • 50% of cases are sporadic • Waddling gait • Difficulty getting up from the floor (Gower's maneuver) • Difficulty with climbing stairs • Enlarged calves (pseudo‐hypertrophy) • Elevated creatine kinase • Loss of ambulation between 8 and 12 years • Usually die in late teens or early 20s from respiratory insufficiency or pneumonia

Polymyositis Dermatomyositis

• Chronic inflammatory infiltrate • Variation in fiber size • Perifascicular atrophy

Central Core Disease

• Common congenital myopathy • Autosomal dominant • Delay in achieving motor milestones (walking) • Mild non‐ progressive weakness of proximal limb musculature • Central area in muscle fibers that lacks oxidative enzymes • Affects type 1 (slow twitch) muscle fibers • Strong association with susceptibility to malignant hyperthermia (a fast rise in body temperature and severe muscle contractions when someone with the disease gets general anesthesia)

Inherited Myopathy

• Congenital and later onset in childhood or adulthood • Muscular dystrophies (progressive) • Congenital myopathies • Mitochondrial myopathies • Metabolic myopathies

Channelopathies

• Diseases caused by disturbed function of ion channel subunits or the proteins that regulate them • Malignant hyperthermia • Myotonia congenita • muscles cannot relax normally • Hyperkalemic periodic paralysis • Hypokalemic periodic paralysis

Metabolic Myopathies

• Glycogen storage diseases (GSD) - caused by mutations in genes controlling enzymes that metabolize glycogen and glucose (blood sugar); - Pompe's Disease, Andersen's and Cori's diseases - McArdle's Disease • Corticosteroid Myopathy • Fatty acid oxidation defects (FAOD) • Fatty acid transport defects • Myoadenylate deaminase deficiency • .........

Acquired

• Inflammatory myopathies • Toxic myopathies • Associated with systemic conditions

Etiology

• Inherited (such as the muscular dystrophies) or acquired (such as common muscle cramps) • Genetic abnormalities, toxins, inflammation, infection, and hormonal and electrolyte imbalances

Myotonic dystrophy

• Most common form of muscular dystrophy that begins in adulthood Weakness and wasting (shrinking) of voluntary muscles in the face, neck and lower arms and legs are common in type 1 myotonic muscular dystrophy. Muscles between the ribs and those of the diaphragm, which moves up and down to allow inhalation and exhalation of air, also can be weakened.

Mitochondrial Myopathies

caused by genetic abnormalities in mitochondria, cellular structures that control energy ❑ May develop symptoms later in life ❑ Increased numbers of abnormally formed mitochondria in muscle ❑ Maternal inheritance

Myasthenia Gravis

• Neuromuscular transmission disorder • Fluctuating weakness, principally abnormal fatiguability after repeated activity • Improvement after rest • More common in females (20s‐30s) or older man (60s70s) • Circulating antibodies to acetylcholine receptors • Leads to lysis of postsynaptic membranes • Inhibits acetylcholinesterase

Specific Concerns

• Overuse weakness • Resistance exercise in rapidly progressive myopathies (various outcomes depending on the stages of progression) • Resistance exercise in slowly progressive myopathies - improve the strength (rather than slow down the pace of disease progression) • Resistance exercise in inflammatory myopathies - gentle rom (traditional view) - resistance training and general conditioning are safe (if the condition is controlled by medication) • Respiratory muscle training • Aerobic training

Symptoms of Myopathies

• Progressive muscle weakness - Structural myopathies • Episodic fatigability - Metabolic myopathies • Often starts with proximal muscles that eventually spreads more distally with the exceptions: fascioscapulohumeral dystrophy (FSHD), distal myopathies, myotonic muscular dystrophy • Fat metabolism, mitochondrial cytopathies‐ impairment seen in endurance‐type activities • Glycogen storage disease‐ impairment seen in higherintensity muscle contraction

General issues in exercise

• Screening the evidence of cardiac conduction defects and cardiomyopathy (myotonic dystrophy, DMD) • higher number of repetitions and lower percentage (40‐50%) of 1‐RM in the first week (no more than 3 sets of 10 reps) • one muscle group be exercised with resistance training no more frequently than every 48 hours • delay training or prescribe gentle stretching exercise to a recently diagnosed inflammatory myopathy patient. (until the condition is controlled)

Duchenne Muscular Dystrophy Pathology

• Variation in fiber size with large rounded fibers • Marked endomysial fibrosis • Some regeneration • Eventually muscle replaced by fat and fibrous tissue

Myopathic Pathology

• Wide variation in fiber size • Degeneration and regeneration • Inflammation • Central nuclei • Fibrosis • Architectural changes

Polymyositis and Dermatomyositis

• can occur at any age (more often in mid childhood or 20s) • Pain and aching in muscles • Proximal weakness • More common in females • Elevated creatinine kinase • Facial rash in dermatomyositis • Respond to steroids

The goals of exercise

• maintenance of maximal muscle mass and strength within the limitations imposed by the disease process • prevention or slowing of secondary complications, including disuse weakness and atrophy as well as the development of contracture that lead to the premature loss of ambulation and functional independence

Myopathies

Neuromuscular disorders in which the primary symptom is muscle weakness due to dysfunction of skeletal muscle fiber.