Approach to myopathies

1. APPROACH TO MYOPATHIES

2. CLINICAL FEATURES
 Proximal, symmetric limb weakness (arms or legs)
 Normal sensations
 Preserved reflexes
 Muscles are normal in size , without atrophy and fasciculations
 Muscle pain or discomfort with palpation ( myalgia )
 Muscle stiffness or cramps
 Fatigue
 Myoglobinuria

3. LABORATORY EVALUATION
 Serum Enzymes - CK is the preferred muscle enzyme to measure in the evaluation of
myopathies
 Electrodiagnostic Studies - EMG, repetitive nerve stimulation, and nerve conduction studies are
essential methods for evaluation
 DNA Analysis
 Forearm Exercise Test – Metabolic myopathies
 Muscle Biopsy - usually obtained from a quadriceps or biceps brachii muscle

4. MUSCULAR DYSTROPHIES
 Inherited disorders with progressive muscle destruction, and may be associated with cardiac
and/or respiratory involvement
 Myotonic dystrophy is the most common

5. MYOTONIC DYSTROPHY
 Myotonia - prolonged muscle contraction followed by slow muscle relaxation
 typical "hatchet-faced" appearance due to temporalis, masseter, and facial muscle atrophy
and weakness
 Frontal baldness is also characteristic
 Myotonia, which usually appears by age 5 years
 Cardiac disturbances occur commonly, ECG abnormalities include first-degree heart block
and more extensive conduction system involvement, Complete heart block and sudden death
can occur
 Other associated features include intellectual impairment, hypersomnia, posterior subcapsular
cataracts, gonadal atrophy, insulin resistance, and decreased esophageal and colonic
motility

7. DUCHENNE'S MUSCULAR DYSTROPHY
 incidence of 30 per 100,000 live-born males
 becomes apparent between ages 3 and 5 years
 On getting up from the floor, the patient uses his hands to climb up himself - Gowers' manoeuvre
 By age 12 years, most patients are wheelchair dependent
 By age 16–18 years, patients are predisposed to serious respiratory failure, sometimes fatal
pulmonary infections
 presence of a cardiomyopathy in almost all patients
 Intellectual impairment is common
 diagnosis can be made by Western blot analysis of muscle biopsy specimens
 prednisone in a dose of 0.75 mg/kg per day, significantly slow progression for up to 3 years

9. BECKER'S MUSCULAR DYSTROPHY
 less severe form
 incidence of about 3 per 100,000 live-born males.
 Hypertrophy of muscles, particularly in the calves, is an early and prominent finding
 Onset is between ages 5 and 15 years
 reduced life expectancy, but most survive into the fourth or fifth decade.
 Mental retardation may occur
 Cardiac involvement occurs and may result in heart failure
 Diagnosis requires Western blot analysis of muscle biopsy

10. LIMB-GIRDLE MUSCULAR DYSTROPHY
 Classification is based on autosomal dominant (LGMD1) and autosomal recessive (LGMD2)
inheritance
 Both males and females are affected
 onset ranging from late in the first decade to the fourth decade
 typically manifest with progressive weakness of pelvic and shoulder girdle musculature
 Respiratory insufficiency from weakness of the diaphragm may occur, as may cardiomyopathy

11. OTHERS
 Emery-Dreifuss Muscular Dystrophy
 Congenital Muscular Dystrophy
 Facioscapulohumeral (FSH) Muscular Dystrophy
 Oculopharyngeal Dystrophy

12. METABOLIC MYOPATHIES
 disorders that interfere with the biochemical pathways that maintain the energy supply to
muscles

14. CHANNELOPATHIES

15. HYPOKALEMIC PERIODIC PARALYSIS (HYPOKPP)
 Onset occurs at adolescence
 Attacks are often provoked by meals high in carbohydrates or sodium
 Ocular and bulbar muscles are less likely to be affected, Respiratory muscles are usually spared
 Weakness may take as long as 24 hours to resolve
 low serum potassium level during an attack establishes the diagnosis
 acute paralysis improves after the administration of potassium, Oral should be given every 30
minutes
 low-carbohydrate, low-sodium diet
 Prophylactic administration of acetazolamide (125–1000 mg/d in divided doses) reduces or
may abolish attacks

17. HYPOTHYROIDISM
 frequent muscle complaints, and proximal muscle weakness occurs in about one-third
 Muscle cramps, pain, and stiffness are common
 Some patients have enlarged muscles
 Features of slow muscle contraction and relaxation occur in 25% of patients
 the relaxation phase of muscle stretch reflexes is characteristically prolonged and best
observed at the ankle or biceps brachii reflexes

18. HYPERTHYROIDISM
 proximal muscle weakness and atrophy on examination
 Activity of deep tendon reflexes may be enhanced
 Bulbar, respiratory, and even esophageal muscles may occasionally be affected, causing
dysphagia, dysphonia, and aspiration
 Other neuromuscular disorders occur in association - acquired hypokalemic periodic paralysis,
myasthenia gravis, and Graves' ophthalmopathy

19. MYOPATHY FROM LIPID-LOWERING AGENTS
 All classes of lipid-lowering agents have been implicated in muscle toxicity, including fibrates,
statins, niacin, and ezetimibe
 Myalgia, malaise, and muscle tenderness are the most common manifestations
 Varying degrees of muscle necrosis are seen, and in severe reactions rhabdomyolysis and
myoglobinuria occur
 Elevated serum CK is an important indication of toxicity
 Severe myalgias, muscle weakness, significant elevations in serum CK (>three times baseline),
and myoglobinuria are indications for stopping the drug

20. GLUCOCORTICOID-RELATED MYOPATHIES
 occurs with chronic treatment or as "acute quadriplegic" myopathy secondary to high-dose IV
glucocorticoid use
 chronic use of prednisone at a daily dose of 30 mg/d is most often associated with toxicity
 fluorinated glucocorticoids (triamcinolone, betamethasone, dexamethasone) appear to be at
especially high risk for myopathy
 serum CK is usually normal
 critical illness myopathy - high-dose IV glucocorticoids for status asthmaticus, chronic
obstructive pulmonary disease, organ transplantation, or other indications may develop severe
generalized weakness, can also occur in the setting of sepsis
 use of glucocorticoids in combination with nondepolarizing neuromuscular blocking agents
potentiate this complication

21. INFLAMMATORY MYOPATHIES
 largest group of acquired and potentially treatable causes of skeletal muscle weakness
 classified into three major groups: polymyositis (PM), dermatomyositis (DM), and inclusion body
myositis (IBM)
 present as progressive and symmetric muscle weakness
 except for IBM, which can have an asymmetric pattern
 Ocular muscles are spared, even in advanced, untreated cases
 Facial muscles are unaffected in PM and DM, but mild facial muscle weakness is common in
patientswith IBM
 They can occur in isolation or in association with other autoimmune diseases, such as SLE,
systemic sclerosis and Sjögren’s syndrome

22. DERMATOMYOSITIS
 DM affects both children and adults and women more often than men
 characteristic rash accompanying, or more often preceding, muscle weakness
 heliotrope rash - blue-purple discoloration on the upper eyelids with edema
 Gottron's sign - erythema of the knuckles with a raised violaceous scaly eruption
 erythematous rash can also occur on other body surfaces, including the knees, elbows,
malleoli, neck and anterior chest (often in a V sign), or back and shoulders (shawl sign), worsen
after sun exposure
 Dilated capillary loops at the base of the fingernails are also characteristic
 mechanic's hands - palmar areas of the fingers may become rough and cracked, with
irregular, "dirty" horizontal lines
 muscle biopsy - significant perivascular and perimysial inflammation and perifascicular atrophy
is seen

24. POLYMYOSITIS

25. INCLUSION BODY MYOSITIS
 most likely to affect persons aged >50 years
 three times more frequent in men than in women
 Weakness and atrophy of the distal muscles, especially foot extensors and deep finger flexors
 Dysphagia is common, occurring in up to 60% of IBM
 20% of cases, IBM is associated with systemic autoimmune or connective tissue diseases

26. EXTRAMUSCULAR MANIFESTATIONS
 Systemic symptoms, such as fever, malaise, weight loss, arthralgia, and Raynaud's
phenomenon
 Dysphagia and gastrointestinal symptoms, due to involvement of oropharyngeal striated
muscles and upper esophagus, especially in DM and IBM
 Cardiac disturbances, including atrioventricular conduction defects, tachyarrhythmias, dilated
cardiomyopathy, a low ejection fraction, and congestive heart failure
 Pulmonary dysfunction, due to weakness of the thoracic muscles, interstitial lung disease
 Subcutaneous calcifications, in DM

27. ASSOCIATION WITH MALIGNANCIES
 incidence of malignant conditions appears to be specifically increased only in patients with
DM and not in those with PM or IBM
 most common tumors associated with DM are ovarian cancer, breast cancer, melanoma,
colon cancer, and non-Hodgkin lymphoma
 Screening for underlying malignancy should be undertaken routinely, and should include CT of
chest/ abdomen/pelvis, upper and lower gastrointestinal endoscopy, and mammography in
women

28. DIAGNOSIS
 The most sensitive enzyme is CK, level usually parallels disease activity
 Muscle biopsy - most sensitive and specific test for establishing the diagnosis of inflammatory
myopathy

30. MANAGEMENT
 Oral corticosteroids (prednisolone 1 mg/kg daily) are the mainstay of initial treatment
 high-dose intravenous methylprednisolone (1 g/day for 3 days) may be required in patients
with respiratory or pharyngeal weakness
 many need additional immunosuppressive therapy.
 MMF, Azathioprine and methotrexate are the agents of first choice