This is a rare non-metastatic manifestation of small-cell carcinoma of the bronchus. There is defective acetylcholine release at the neuromuscular junction. Proximal muscle weakness, sometimes involving the ocular and bulbar muscles, is found, with absent reflexes. Weakness tends to improve after muscular contraction (unlike myasthenia gravis).
Other myasthenic syndromes Other rare myasthenic syndromes occur, for example congenital myasthenia.
These are progressive, genetically determined disorders of skeletal and sometimes cardiac muscle. Duchenne muscular dystrophy (DMD) This is inherited as an X-linked recessive disorder, but one-third of cases arise by spontaneous mutation. It ccurs in 1 in 3000 male infants. Recently the DMD locus has been localized to the Xp21 regio of the X chromosome and the disease is characterized by the absence of the gene product-the protein dystrophin, which is a rod-shaped cytoskeletal protein found in muscle. DMD is usually obvious by the fourth year, and causes death by the age of 20 years.
The boy has difficulty in running and in rising to an erect position, when he has to ‘climb up his legs with his hands’ (Cowers’ sign).
There is initially a proximal limb weakness with pseudohypertrophy of the calves. The myocardium is affected. The boy becomes severely disabled by 10 years.
The diagnosis is often made on clinical grounds alone. The creatine phosphokinase is grossly elevated (100- 200 times the normal level). Muscle biopsy shows characteristic variation in fibre size, fibre necrosis, regeneration and replacement by fat, and on immunochemical stainingan absence of dystrophin. The electromyogram shows a myopat ic pattern.
There is no curative treatment. Passive physiotherapy helps to prevent contractures in the later stages of the disease. A trial of prednisolone therapy has shown a short-term improvement in muscle strength and
A female with an affected brother has a 50% chance of carrying the gene. In carrier females, 70% have a raised creatine phosphokinase level and the remainder usually have electro myographic abnormalities or changes on biopsy. Accurate carrier and prenatal diagnosis can be made using cDNA probes that are co-inherited with the DMD locus.
Genetic advice explaining the inheritance of the condition and counselling about abortion should be given. Determination of the fetal sex by amniocentesis and selective abortion of a male fetus is sometimes carried out. Many proven carrier females choose not to have offspring.
Limb girdle and facio-scapulohumeral dystrophy
These milder dystrophies are summarized in Table 18.58. There are many other varieties of muscular dystrophy.
These conditions are characterized by myotonia, i.e. continued muscle contraction after the cessation of voluntary effort. The electromyogram is characteristic (see p. 951). The myotonias are important because patients tolerate general anaesthetics poorly. The commonest two of theserare conditions are mentioned below. Dystrophia myotonica Myotonia congenita (Thomsen’s disease)
This is an autosomal dominant disorder. An isolated myotonia, usually mild, occurs in childhood and persists throughout life. The myotonia is accentuated by rest and by cold. Diffuse muscle hypertrophy occurs and the patient appears to have well-developed muscles. PERIODIC PARALYSES These are rare membrane disorders characterized by intermittent flaccid muscle wealcness and alterations in serum potassium.
Hypokalaemic periodic paralysis This condition, usually inherited as an autosomal dominant trait, is characterized by generalized wealcness (including the speech and bulbar muscles) that often starts after a heavy carbohydrate meal or after a period of rest after exertion. Attacks last for several hours. It is often first noted in the teenage years and tends to remit after the age of 35 years. The serum potassium is usually below 3.0 mmol litre ” in an attack. The wealcness responds to the administration of potassium chloride. Similar wealcness also occurs in hypokalaemia due to diuretics, and may occur during thyrotoxicosis.
Hyperkalaemic periodic paralysis
This condition, usually inherited as an autosomal dominant trait, is characterized by sudden attacks of wealcness that are sometimes precipitated by exercise. Attacks start in childhood and tend to remit after the age of 20 years. They last from 30 min to 2 hours. Myotonia may occur. The serum potassium is raised.The attacks are terminated by intravenous calcium gluconate or chloride.
A very rare normokalaemic, sodium-responsive periodic paralysis also occurs.
SPECIFIC METABOLIC MYOPATHIES
This is a large group of rare, genetically determined muscle diseases. Two of these diseases will be mentioned here.
Myophosphorylase deficiency (McArdle’s syndrome)
This is an autosomal recessive disorder in which there isa lack of skeletal muscle myophosphorylase. The disorder causes easy fatiguability and severe cram on exercise, with myoglobinuria. There is no rise in venous lactate during ischaemic exercise; this forms the basis of a test for the condition. Malignant hyperpyrexia Widespread skeletal muscle rigidity and hyperpyrexia developing as a sequel to general anaesthesia is due to a genetic defect in the calcium release channel of the sarcoplasmic reticulum. Sudden death during or after anaesthesia may occur in this rare condition, which is some times inherited as an autosomal dominant trait. Dantrolene is useful in controlling the rigidity.