Muscle disease

Published on 10/04/2015 by admin

Filed under Neurology

Last modified 10/04/2015

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Muscle disease

Primary muscle disease is relatively uncommon (prevalence 12 per 100 000) and may be inherited or acquired. This is an area in neurology where the recent rapid developments in molecular genetics are providing new insights into the molecular basis of muscle disease. This is also leading to developments in the classification of muscle disease, for example the channelopathies.

Inherited diseases include the following:

image Progressive muscular dystrophies causing progressive weakness. The patterns of inheritance, age of onset, patterns of muscular involvement and prognoses differ according to type.
image Metabolic myopathies may produce progressive deficits, e.g. most mitochondrial myopathies, or intermittent, particularly exertional symptoms, e.g. McArdle’s disease.
image Non-progressive congenital myopathies present at various ages and may be mild to severe. Examples include central core, myotubular and nemaline myopathies. All are rare.
image Myotonic syndromes are characterized by impaired muscle relaxation after contraction, sometimes with muscle weakness.
image Syndromes of episodic weakness or periodic paralysis due to disorders of ion channels in the muscle membranes.

Muscular dystrophies

The most common inherited muscle disease is X-linked recessive Duchenne muscular dystrophy (DMD), which affects 1 in 3300 live male births. Thirty per cent of female carriers may be mildly to moderately affected. In DMD, there is absence of dystrophin, a protein involved in linking the sarcolemma with actin molecules involved in contraction. This is thought to cause breaks in the membrane during muscle contraction. In Becker muscular dystrophy (BMD), dystrophin is present but abnormal.

Boys with DMD develop weakness of the lower limb girdle by the age of 3–6 years. They adopt the Gower manoeuvre to rise from lying (Fig. 1). Weakness then spreads to other muscle groups in the legs and arms. There may be characteristic rubbery enlargement (pseudohypertrophy) of the calf muscles and 30% have a low IQ. Untreated, most are wheelchair-bound by the age of 12 years and die from respiratory complications by the age of 25 years.

image

Fig. 1 Gower’s manoeuvre.

Investigations include muscle creatine kinase (CK), which is highly elevated, and muscle biopsy, which shows no fibres staining for dystrophin. An ECG is often abnormal. Treatment is supportive, especially prevention of complications, including respiratory infection and contractures. Steroids may slow the progression and respiratory support can prolong survival. Genetic treatments and stem cell implants have yet to provide benefit. BMD follows a milder course with an onset at age 5–45 years; there is also calf pseudohypertrophy and a highly elevated CK, 20–200 times normal. Other dystrophies are described in Table 1; some have been identified as affecting proteins closely linked with dystrophin.

Table 1 Patterns of muscular dystrophies

image

Metabolic myopathies

These rare disorders may affect carbohydrate or lipid metabolism. The enzyme defects can often be identified on muscle biopsy but these may require specialized studies. Three types of symptom occur:

1. Cramps and muscle fatigue, particularly related to exertion: some during exertion, others following. In severe episodes, there may be myoglobinuria, which can lead to renal failure. McArdle’s disease (myophosphorylase deficiency) and carnitine palmityl transferase deficiency can present this way.
2. Generalized, particularly proximal weakness that is slowly progressive. Acid maltase deficiency and mitochondrial myopathies can present this way, the latter with external ocular muscle weakness.
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