For those interested in muscle diseases

Disorders affecting the neuromuscular junction

The neuromuscular junction is a chemical synapse that transmits an electrical impulse from the peripheral nerve ending to a muscle fiber. Acetylcholine released at the nerve ending binds to its receptors located on the surface of the muscle fibers and initiates the excitation-contraction coupling process via release of calcium ions from the sarcoplasmic reticulum followed by myofibril contraction.

Autoantibodies that disrupt this process lead to the following disorders:

a. Myasthenia gravis

Muscle weakness and rapid fatigability are the hallmarks of myasthenia gravis. The eye muscles are commonly affected leading to double vision and drooping of the eyelids. Muscle fatigability also causes difficulties in chewing, swallowing, and walking. Head drop secondary to weakness of neck muscles may occur in a few cases. Disease progression can lead to life-threatening respiratory failure. A characteristic of myasthenia gravis is the diurnal and day-to-day variations in muscle strength and disease severity; this condition typically improves with rest and worsens in the evening.

Myasthenia gravis is an autoimmune disease caused by the development of autoantibodies against the nicotinic postsynaptic acetylcholine receptors (receptors on the muscle fiber side of the neuromuscular junction). A small number of patients show other antibodies including the MuSK antibody. Diagnosis is based on the detection of these antibodies and electrophysiological tests, which confirm easy muscle fatigability. Examination of the thymus is important because thymoma and thymus hypertrophy are often present in this condition.

Treatment is primarily aimed at immunological therapy against the autoantibodies. Plasma exchange and immunoglobulin administration are often useful in addition to the administration of corticosteroids and other drugs. Thymectomy is needed for patients with thymoma and may benefit some others as well.

b. Lambert-Eaton myasthenic syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is caused by the action of an autoantibody that blocks the secretion of acetylcholine from nerve terminals. Symptoms of LEMS are largely similar to myasthenia gravis except tendon reflexes are often suppressed in patients with LEMS and ocular symptoms are less common. A mild response to electrical stimulation and other electrophysiological features can distinguish between LEMS and myasthenia gravis. LEMS is often associated with malignant neoplasms, particularly small cell carcinoma of the lung. Therefore, it is an important factor that determines a patient’s prognosis.

c. Congenital myasthenia
Mutations in the genes encoding proteins that constitute acetylcholine receptors and related structures can cause myasthenia or myopathies associated with myasthenic symptoms, although these are rare conditions.

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