APPROACH TO MYOPATHIES

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

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

MUSCULAR DYSTROPHIES

Inherited disorders with progressive muscle destruction, and may be associated with cardiac

and/or respiratory involvement

Myotonic dystrophy is the most common

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

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

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

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

OTHERS

Emery-Dreifuss Muscular Dystrophy

Congenital Muscular Dystrophy

Facioscapulohumeral (FSH) Muscular Dystrophy

Oculopharyngeal Dystrophy

METABOLIC MYOPATHIES

disorders that interfere with the biochemical pathways that maintain the energy supply to

muscles

CHANNELOPATHIES

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

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

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

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

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

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

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

POLYMYOSITIS

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

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

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

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

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