Disorders Of Skeletal Muscle 1m534n

Disorders of Skeletal Muscle

Department of Neurology

Anatomy Skeletal muscle is made up of large numbers of multinucleated muscle fibers, which have an outer membrane and cytoplasm and in which lie the contractile components of the muscle. The fibers are separated by connective tissue and arranged in bundles. Each fasciculus has a connective tissue sheath. The muscle is made up of a number of fasciculi bound togather and surrounded by a connective tissue sheath. There aer two broad types of muscle fiber, which are functionally different:

 Type 1---rich in myoglobulin, with low metabolism, and low in sarcoplasm.  Type2---low in myoglobin, with high mitabolism and little sarcoplasm.

Clinical features of muscle disease

Muscle has rather uniform structure and function and thus diseases of muscle from a variety of cause can produce similar clinical features. The general features of muscle disease will therefore be discussed prior to discussion of the most common and important specific diseases.

Weakness Weakness of muscles is a characteristic finding in myopathies. Each muscle disease exhibits a particular pattern of involvement, which is an important diagnostic clue. Careful examination of all muscle groups is important to classify a myapathy, and to differentiate it from a neuropathy or central nervous system discorder.

Changes in muscle contractility Myotonia—persistence of contraction, often for several seconds, during attempted relaxation—is found in myotonic dystrophy, paramyotonia congenita, hyperkalaemic penodic paralysis, and congenital myatonia. On electromyography, the characterristic findings consist of rhythmic discharges. This phenomenon may also be elicited by a sharp tap on the muscle belly. Myotonin must be differentiated from neuromyotonia, which is derived from nerve abnormality.

Change in muscle tone

There may be a loss of tone secondary to disease of muscle.

Changes in muscle bulk Atrophy result with muscular dystrophies or is caused by a lower motor neuron lesion. Enlargement of muscle may be result of overactivity or an early sign in certain dystrophies, caused by infiltration of fat, exacerbating the weakness.

Pain

Pain is a rare complaint in primary muscle disease except in deficiencies of certain enzymes of glycolytic or fat pathways or when the disease involves blood vessels within the muscle.

Family history Many muscle diseases are inherited an therefore a full family history is essential. Inherited muscles diseases include: X-linked—Duchenne muscular dystrophy, Becker’s muscular dystrophy, Emery-Dreifuss dystrophy. Autosomal domiant—facio-scapulo-humeral dystrophy, scapuloperoneal dysprothy, myotonic dystrophy. Autosomal recessive---limb-gride dystrophy, all deficiencies of enzymes of glycolytic and lipid metabolism.

Investigation of muscle disease The diagnosis may be possible from the clinical features in some causes of muscle disease. Additionally, helpful test include: Serum creatine phosphokinase (K) , this is often highly raised in many dystrophies and in inflammatory muscle disorders. EMG---needle examination will reveal myopathic units. There may be evidence of myotonic discharges in myotonias.

Muscle biopsy----this can yield information about fibre bype, inflammation, and dystrophic and histo-chemical changes. Electron microscopy is sometimes required.

Hereditary myopathies

Muscular dystrophies: Duchenne muscular dystrophy Becker’s muscular dystrophy

Duchenne muscular dystrophy

Duchenne musclar dystrophy is an X-linked recessive condition caused by an absent of dystrophin, occurring in 20-30/1000000 liveborn males. It attacks skeletal and cardiac muscle.

Clinical feature

With Duchenne muscular dystrophy, there is no abnormality at birth, but the condition is apparent by the fourth year. The boy is usually wheelchairbound by 10 years old, and death is usual by the age of 20, from respiratory failure or cardiomyopathy.

There is initially proxiaml muscle weakness with pseudohypertrophy of the calves. The weakness then spreads. When rising to an erect position, there is a characteristic manoeuver in which the patient has to climb his legs with his hands------Gower’s sign

Diagnosis

The diagnosis of Duchenne muscular dystrophy is often made clinically. However, the CK is grossly elevated often more than 10000U/L. The EMG is myopathic, and muscle biopsy shows fatty infiltration and absence of staining for dystrophin.

Management

There is no cure for Duchenne muscular dystrophy, so the management is ive. Steroids may provide short-term improvement. Genetic counselling is important-in carrier females, the CK is often raised and the EMG may be myopathic, although there are no clinical signs. There is also an accurate and rapid DNA prode available, so accurate carrier and prenatal diagnosis can be made and acted upon.

Becker’s muscular dystrophy

Becker’s muscular dystrophy is also an X-linked recessive condition, with similar characteristic to Duchenne muscular dystrophy, but it has a much milder cause. Dystrophin is altered rather than absent.

Clinical feature

The symptoms of Becker’s muscular dystrophy begin in the first decade, although often are not noticed until later. Boys continue to walk into their teens and early adult life. Cramps associated with exercise are common. Cardiomopathy can be worse than the weakness.

Hypokalaemic periodic paralysis Hypokalaemic periodic paralysis is an autosomal dominant condition that results in abnormalities of Ltype calcium channels. It becomes apparent between 10 and 20 years of age and may remit after 35 years of age. Attacks of generalized weakness develop after a heavy carbohydrate meal or after a period of rest following strenuous exertion.

During an attack, the serum potassium falts to below 3mmol/L. Attacks may last from 4 to 24 hours. The weakness responds to treatment with potassium chloride. The condition is rarely fatal, as the diaphragm and respiratory muscles tend to be spared. Similar weakness with hypokalaemian may occur in thyrotoxicosis.

Acquired myopathies Polymyositis and dermatomyositis Polymyositis and dermatomyositis are conditions in which there is inflammation within the muscle. There may be associated connective tissue disease (25%) or underlying carcinoma (10%), especially if skin changes are present .

Clinical feature

Polymyositis and dematomyositis usually present in the fourth to fifth decade, with women more commonly affected than men. Proximal muscle weakness is the cardinal symptom. Pain and tenderness of muscles occurs in less than half the patients.

The associated skin changes include:  Macular erythema on the face---especially in the periorbital area, where it is heliotrope in colour.  Erythematous plaques over the dorsal aspects of the fingers,  Nail-fold haemorrhages  Photosensitivity

As the disease progresses, there may be widespread wasting and weakness, with bulbar dysfunction and respiratory muscle weakness.

Investigation Investigations for polymyositis and dermatomyositis include the following ESR----raised CK---usually raised EMG---myapathic picture but may include fibrillations

 Muscle biospy----muscle fibre necrosis with inflammatory infiltrate  Autoantibodies ---present in up to 25% of patients.  Investigation for underlying carcinoma

Treatment

Corticosteroids and other immunosupressive drugs reduce the symptoms in about 75% of cases that not associated with malignancy. Removal of an associated tumour may cause complete remission.

There is full recovery in about 10% of patients. The remainder have varying degrees of disability , and the disease may become inactive after a few years. When associated with connective tissue disease, the prognosis is linked to the course of this disease.