Syndromes of the Neuromuscular Junction and Muscle

Myasthenia

Abnormal fatigability of striated muscle is the cardinal manifestation of disorders of the neuromuscular junction. Exercise-dependent weakness often affects the extraocular muscles first, causing ptosis or diplopia, as the motor units of these muscles contain only a small number of muscle fibers. Patients with generalized myasthenia also suffer from dysphagia and exercise-depend- ent, mainly proximal weakness of skeletal muscle. The most common cause of the myasthenic syndrome is myasthenia gravis (older term: myasthenia gravis pseudoparalytica), an autoimmune disease in which the body forms antibodies against the acetylcholine receptors of the motor end plate. Too few receptors are left for adequate signal transmission, so that the muscles can no longer be sufficiently excited by the nerves that innervate them. The electromyographic correlate is a diminution in size (“decrement”) of the muscle action potential on repetitive electrical stimulation of an affected muscle. Myasthenia gravis is diagnosed on the basis of the typical clinical manifestations, the electromyographic decrement, the demonstration of circulating antibodies to the acetylcholine receptor, and the improvement of weakness upon administration of a short-acting acetylcholinesterase inhibitor, such as edrophonium chloride. The disorder can be treated effectively with longer-acting acetylcholinesterase inhibitors, immune suppression, and additionally (in some younger patients) thymectomy.

Myopathy

In contrast to myasthenia, the myopathies (primary disorders of muscle) generally cause slowly progressive, non-exercise-dependent weakness. Myopathic muscle atrophy is less severe than neurogenic muscle atrophy and is partially concealed by fatty replacement of muscle tissue (liposis, also called lipomatosis), so that there may be a discrepancy between the normal or pseudohypertrophic appearance of muscle and the actual degree of weakness. There are no sensory or autonomic deficits, nor are there fasciculations, which would imply a neurogenic lesion. Myalgia and muscle spasms are more common in metabolic than in congenital myopathies.

The many types of myopathy include the muscular dystrophies (X-linked recessive, autosomal dominant, and recessive), metabolic myopathies, myotonic dystrophies (with additional manifestations such as cataract, frontal baldness, and other systemic abnormalities, as in Steinert­Batten­Curschmann dystrophy), and myositides. A systematic discussion of these diseases would be bey-

Baehr, Duus' Topical Diagnosis in Neurology © 2005 Thieme

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