DISEASES OF MUSCLE

Voluntary muscle is subject to a range of hereditary and acquired disorders affecting either its structure, or the biochemical processes which convert the chemical energy derived from cell metabolism into mechanical energy in a controlled manner. These disorders present in a limited number of ways, most commonly a symmetrical weakness of the large, power-generating proximal muscles (proximal myopathy). This weakness may be fixed or periodic. Other symptoms and signs of muscle disease include myotonia (an abnormality of muscle relaxation) and muscle pain.

Diagnosis depends upon consideration of the clinical picture along with the results of EMG studies and muscle biopsy. In some inherited muscular diseases, diagnosis can be made by identifying the presence of a specific genetic abnormality.

Muscular dystrophies Muscular dystrophies are inherited myopathies characterized by progressive muscle weakness and degeneration and subsequent replacement by fibrous and fatty connective tissue. Historically, muscular dystrophies were categorized by their distribution of weakness, age at onset, and inheritance pattern

Myotonic dystrophy is an autosomal dominant multisystem disorder that affects skeletal, cardiac, and smooth muscle and other organs, including the eyes, the endocrine system, and the brain. This is the most prevalent muscular dystrophy, with an incidence of 13.5 per 100,000 live births. Myotonic dystrophy can occur at any age, with the usual onset of symptoms in the late second or third decade

Typical patients exhibit facial weakness with temporalis muscle wasting, frontal balding, ptosis, and neck flexor weakness. Extremity weakness usually begins distally and progresses slowly to affect the proximal limb-girdle muscles. Percussion myotonia can be elicited on examination in most cases, especially in thenar and wrist extensor muscles.

Associated manifestations include cataracts, testicular atrophy and impotence, intellectual impairment, and hypersomnia associated with both central and obstructive sleep apnea. Respiratory muscle weakness may be severe, with impairment of ventilatory drive. Cardiac conduction defects are common and can produce sudden death. Pacemakers may be necessary, and annual electrocardiograms are recommended. Chronic hypoxia can lead to cor pulmonale

Duchenne dystrophy is present at birth, but the disorder usually becomes apparent between ages 3 and 5. The boys fall frequently and have difficulty keeping up with friends when playing. Running, jumping, and hopping are invariably abnormal. By age 5, muscle weakness is obvious by muscle testing. On getting up from the floor, the patient uses his hands to climb up himself [Gowers' maneuver

Becker Muscular Dystrophy This less severe form of X-linked recessive muscular dystrophy results from allelic defects of the same gene responsible for Duchenne dystrophy. Becker muscular dystrophy is ~10 times less frequent than Duchenne, with an incidence of about 3 per 100,000 live-born males.

Most patients with Becker dystrophy first experience difficulties between ages 5 and 15 years, although onset in the third or fourth decade or even later can occur. By definition, patients with Becker dystrophy walk beyond age 15, while patients with Duchenne dystrophy are typically in a wheelchair by the age of 12. Patients with Becker dystrophy have a reduced life expectancy, but most survive into the fourth or fifth decade. Mental retardation may occur in Becker dystrophy, but it is not as common as in Duchenne. Cardiac involvement occurs in Becker dystrophy and may result in heart failure; some patients manifest with only heart failure. Other less common presentations are asymptomatic hyper-CK-emia, myalgias without weakness, and myoglobinuria

CHANNELOPATHIES Inherited abnormalities of the sodium, calcium and chloride ion channels in striated muscle produce various syndromes of familial periodic paralysis, myotonia and malignant hyperthermia which can be recognised by their clinical characteristics, provocation by exercise or eating, and associated changes in serum potassium concentration

hypokalemic periodic paralysis The majority of cases of hypokalemic periodic paralysis are caused by mutations in the muscle calcium channel. Attacks begin by adolescence and are triggered by exercise, sleep, stress, or meals rich in carbohydrates and sodium. Attacks last from 3 to 24 hours. A vague prodrome of stiffness or heaviness in the legs can occur, and, if the patient performs mild exercise, a full-blown attack may be aborted. Ocular, bulbar, and respiratory muscles are rarely involved.

Early in the disease, patients have normal interattack examinations except for eyelid myotonia (about 50%). Later, attack frequency can lessen, but many patients have proximal weakness. Preventive measures include a low-carbohydrate, low-sodium diet and drugs such as acetazolamide or dichlorphenamide. Acute attacks are treated with oral potassium

ACQUIRED MYOPATHIES Muscle weakness may be caused by a range of metabolic, endocrine, toxic or inflammatory disorders Disorders affecting the muscles' structural integrity can be distinguished by EMG from those caused by metabolic derangement. In metabolic disorders, weakness is often acute and generalised, while a proximal myopathy predominantly affecting the pelvic girdle is a feature of some endocrine disorders. This may develop without other manifestations of hormonal disturbance

CAUSES OF ACQUIRED PROXIMAL MYOPATHY Inflammatory) Polymyositis Dermatomyositis Endocrine and metabolic Hypothyroidism Hyperthyroidism Acromegaly Cushing's syndrome (including iatrogenic) Addison's disease Conn's syndrome Osteomalacia

Hypokalaemia (liquorice, diuretic and purgative abuse) Hypercalcaemia (disseminated bony metastases) Toxic Alcohol (chronic and acute syndromes) Vitamin E Organophosphates

Drugs Corticosteroids (especially fluorinated ) Chloroquine Amiodarone β-blockers Statins Clofibrate Ciclosporin Vincristine Zidovudine Opiates ε-aminocaproic acid Paraneoplastic